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Mesothelin-targeted CD40 agonistic multispecific antibody constructs for the treatment of solid tumors
Filed
2024-01-19
Issued
2026-04-28
Expires
2044-01-19
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Claims
20
Drawings
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Abstract
The present invention relates to a human agonistic CD40 multispecific antibody construct for treatment of solid tumors by engineering a molecule that specifically targets the CD40 pathway on tumor-associated APCs, without systemic CD40 activation.
Claims (20)
- 11. A multispecific antibody construct comprising: (i) a first antibody comprising two light chains and two heavy chains, wherein (a) the light chains comprise a first variable region (VL1) and a light chain constant region (CL); (b) the heavy chains comprise a first heavy variable region (VH1) and CH1, hinge, CH2, and CH3 regions; and (c) the heavy chains comprise at least one amino acid substitution that results in a reduced binding affinity of the heavy chain for Fc gamma RI receptor as compared with an unsubstituted heavy chain; and (ii) a scFv comprising a second light chain variable region (VL2) and a second heavy chain variable region (VH2) of a second antibody, wherein the VL2 and the VH2 are connected via a first peptide linker, wherein the scFv is fused at its amino terminus to the carboxyl terminus of each of the heavy chains through a second peptide linker such that a heavy chain fusion protein is formed; and wherein the first antibody specifically binds to and agonizes human CD40 comprising the amino acid sequence of SEQ ID NO:1, and the scFv specifically binds to human mesothelin (MSLN) comprising the amino acid sequence of SEQ ID NO:2; and wherein: i) the VL1 and VH1 are selected from the group consisting of: a) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 58, 59, and 60, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 136, 137, and 138, respectively; b) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 64, 65, and 66, respectively; and a VH1 comprising aCDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 142, 143, and 144, respectively; c) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 70, 71, and 72, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 148, 149, and 150, respectively; d) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 76, 77, and 78, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 154, 155, and 156, respectively; e) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 82, 83, and 84, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 160, 161, and 162, respectively; f) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 88, 89, and 90, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 166, 167, and 168, respectively; g) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 94, 95, and 96, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 172, 173, and 174, respectively; h) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 100, 101, and 102, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 178, 179, and 180, respectively; i) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 106, 107, and 108, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 184, 185, and 186, respectively; j) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 112, 113, and 114, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 190, 191, and 192, respectively; k) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 118, 119, and 120, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 196, 197, and 198, respectively; l) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 124, 125, and 126, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 202, 203, and 204, respectively; and m) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 130, 131, and 132, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 208, 209, and 210, respectively; and n) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 100, 101, and amino acids 91 to 101 of SEQ ID NO: 370, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 178, 179, and 180, respectively; and ii) the VL2 and VH2 are selected from the group consisting of: a) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 230, 231, and 232, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 254, 255, and 256, respectively; b) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 236, 237, and 238, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 260, 261, and 262, respectively; c) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 242, 243, and 244, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 266, 267, and 268, respectively; and d) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 248, 249, and 250, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 272, 273, and 274, respectively.
Description (75,837 words)
CROSS REFERENCE TO RELATED APPLICATIONS
This patent application is a divisional application of U.S. application Ser. No. 17/127,629, filed Dec. 18, 2020, which claims the benefit of U.S. provisional application No. 62/951,408, filed Dec. 20, 2019. The complete contents of foregoing applications are incorporated herein by reference in their entirety for all purposes.
The present application is being filed along with a sequence listing in electronic format. The sequence listing is provided as a file entitled A-2428-US03-DIV_Seq Listing, created Jan. 19, 2024, 2020, which is 1,670,896 bytes in size. The information in the electronic format of the sequence listing is incorporated herein by reference in its entirety.
FIELD OF THE INVENTION
The present invention relates to the field of oncology, specifically cancer immunotherapy. The invention relates to a human agonistic CD40 antibody by engineering a molecule that specifically targets the CD40 pathway on tumor-associated APCs, without systemic CD40 activation.
BACKGROUND OF THE INVENTION
Treating cancer patients who do not respond to immune checkpoint inhibitors, such as anti-PD1, represent both the primary challenge and an exciting opportunity in the quickly changing landscape of immunotherapy. A major determinant of response to PD1 blockade in solid tumors is the degree of pre-treatment tumor-associated T cell infiltration, with patients having poorly infiltrated, ‘cold’ tumors showing minimum clinical benefit. While clinical data are still emerging, the clinical activity of other T cell-targeted immunotherapies beyond PD1 blockade, such as solid tumor BiTE® antibody constructs or CAR-T approaches, may also be limited in ‘cold’ tumors. Combining T cell-targeted approaches with new classes of therapeutics capable of enhancing T-cell infiltration into solid tumors may be critical for maximizing the number of patients benefiting from immunotherapy.
CD40 is a member of the TNF receptor (TNFR) superfamily that is preferentially expressed by antigen presenting cells (APCs), such as dendritic cells, B cells and macrophages. Interaction with its trimeric ligand on activated T helper cells results in APC activation that includes upregulation of cytokines/chemokines (such as interleukin-12 [IL-12] and CxCL10), proteins involved in antigen-presentation (such as MHC class I and II ligands), T cell costimulatory ligands (such as CD80 and CD86), and array of other immune modulatory factors (i.e., adhesion molecules and other TNFRs). These “licensed” APCs can then trigger a cascade of events leading to induction of robust adaptive immune responses.
Therapeutics capable of activating CD40 signaling have the potential to inflame solid tumors through their ability to enhance generation of anti-tumor T cells and enhance T cell recruitment directly into the tumor lesion. Preclinical studies with anti-CD40 agonists suggest that triggering CD40 with crosslinking antibodies on APCs can substitute for CD4 T cell help to license APCs and facilitate the activation as well as expansion of CD8 effector T cells. In addition, CD40-activated macrophages may also exert direct tumoricidal functions. These anti-CD40 agonist antibodies have been demonstrated to be efficacious in multiple syngeneic tumor models alone or in combination with other therapies. Based on these pre-clinical studies several CD40 agonistic antibodies are under investigation in phase I/II clinical trials of solid tumor patients. To date, these monoclonal anti-CD40 antibodies have shown some signs of clinical activity, but are often associated with immune-related adverse effects, such as cytokine release syndrome and evidence of liver damage. These toxicities limit the dose of CD40 agonist that can be delivered, and thus may result in insufficient activation of the CD40 pathway in tumor-associated APC population, negatively impacting the efficacy of this therapeutic approach. Therapeutics capable of localizing activation of CD40 signaling in tumor tissue may improve anti-tumor effects while limiting systemic toxicities.
In order to achieve tumor localization, an agonistic multispecific antibody construct that binds both CD40 and a tumor-associated antigen (TAA), mesothelin (MSLN), was designed. Robust agonist activity of this multispecific antibody construct on CD40-expressing APCs is entirely dependent on the presence of neighboring MSLN-expressing cells. The multispecific antibody construct was specifically engineered to lack CD40 agonist activity upon binding to CD40 in the absence of MSLN-expressing cells. In addition, introduction of mutations into the IgG Fc domain limits binding to Fc receptors, thus preventing Fc receptor-mediated CD40 agonist activity. Thus, the MSLN-dependent CD40 agonist multispecific antibody construct described herein has the potential to drive robust CD40-mediated activation of APCs in a manner that is confined primarily to tumor tissue, thus minimizing induction of systemic toxicities.
SUMMARY OF THE INVENTION
The present invention is directed to a multispecific antibody construct comprising:
(i) a first antibody comprising two light chains and two heavy chains, wherein
the light chains comprise a first variable region (VL1) and a light chain constant region (CL);
the heavy chains comprise a first heavy variable region (VH1) and CH1, hinge, CH2, and CH3 regions;
the heavy chains comprise at least one amino acid substitution that results in a reduced binding affinity of the heavy chain for human Fc gamma RI receptor as compared with an unsubstituted heavy chain; and
(ii) a scFv comprising a second light chain variable region (VL2) and a second heavy chain variable region (VH2) of a second antibody, wherein the VL2 and the VH2 are connected via a first peptide linker,
wherein the scFv is fused at its amino terminus to the carboxyl terminus of each of the heavy chains through a second peptide linker such that a heavy chain fusion protein is formed; and
wherein the first antibody specifically binds to and agonizes human CD40 (SEQ ID NO: 1) and the scFv specifically binds to human mesothelin (MSLN) (SEQ ID NO: 2).
In one embodiment, the multispecific antibody construct specifically agonizes CD40 in a MSLN-dependent fashion.
In one embodiment, the multispecific antibody construct comprises mutations limiting Fc receptor binding and thus decreases Fc receptor-dependent CD40 agonism.
In one embodiment, the two light chains are identical and the two heavy chain fusion proteins are identical.
In one embodiment, the heavy chain comprises an amino acid substitution selected from the group consisting of:
(i) N297G or N297A;
(ii) L234A and L235A; and
(iii) R292C and V302C;
wherein the amino acid numbering is EU numbering according to Kabat.
In one embodiment, the heavy chain comprises N297G, R292C, and V302C mutations, wherein the amino acid numbering is EU numbering according to Kabat.
In one embodiment, the VL1 comprises a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of:
SEQ ID NOs: 58, 59, and 60, respectively;
SEQ ID NOs: 64, 65, and 66, respectively;
SEQ ID NOs: 70, 71, and 72, respectively;
SEQ ID NOs: 76, 77, and 78, respectively;
SEQ ID NOs: 82, 83, and 84, respectively;
SEQ ID NOs: 88, 89, and 90, respectively;
SEQ ID NOs: 94, 95, and 96, respectively;
SEQ ID NOs: 100, 101, and 102, respectively;
SEQ ID NOs: 106, 107, and 108, respectively;
SEQ ID NOs: 112, 113, and 114, respectively;
SEQ ID NOs: 118, 119, and 120, respectively;
SEQ ID NOs: 124, 125, and 126, respectively; and
SEQ ID NOs: 130, 131, and 132, respectively;
the VH1 comprises a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of:
SEQ ID NOs: 136, 137, and 138, respectively;
SEQ ID NOs: 142, 143, and 144, respectively;
SEQ ID NOs: 148, 149, and 150, respectively;
SEQ ID NOs: 154, 155, and 156, respectively;
SEQ ID NOs: 160, 161, and 162, respectively;
SEQ ID NOs: 166, 167, and 168, respectively;
SEQ ID NOs: 172, 173, and 174, respectively;
SEQ ID NOs: 178, 179, and 180, respectively;
SEQ ID NOs: 184, 185, and 186, respectively;
SEQ ID NOs: 190, 191, and 192, respectively;
SEQ ID NOs: 196, 197, and 198, respectively;
SEQ ID NOs: 202, 203, and 204, respectively; and
SEQ ID NOs: 208, 209, and 210, respectively;
the VL2 comprises a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of:
SEQ ID NOs: 230, 231, and 232, respectively;
SEQ ID NOs: 236, 237, and 238, respectively;
SEQ ID NOs: 242, 243, and 244, respectively; and
SEQ ID NOs: 248, 249, and 250, respectively;
and the VH2 comprises a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of:
SEQ ID NOs: 254, 255, and 256, respectively;
SEQ ID NOs: 260, 261, and 262, respectively;
SEQ ID NOs: 266, 267, and 268, respectively; and
SEQ ID NOs: 272, 273, and 274, respectively.
In one embodiment, 1) the VL1 and VH1 are selected from the group consisting of:
a) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 58, 59, and 60, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 136, 137, and 138, respectively;
b) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 64, 65, and 66, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 142, 143, and 144, respectively;
c) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 70, 71, and 72, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 148, 149, and 150, respectively;
d) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 76, 77, and 6780, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 154, 155, and 156, respectively;
e) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 82, 83, and 84, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 160, 161, and 162, respectively;
f) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 88, 89, and 90, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 166, 167, and 168, respectively;
g) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 94, 95, and 96, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 172, 173, and 174, respectively;
h) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 100, 101, and 102, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 178, 179, and 180, respectively;
i) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 106, 107, and 108, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 184, 185, and 186, respectively;
j) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 112, 113, and 114, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 190, 191, and 192, respectively;
k) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 118, 119, and 120, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 196, 197, and 198, respectively;
l) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 124, 125, and 126, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 202, 203, and 204, respectively; and
m) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 130, 131, and 132, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 208, 209, and 210, respectively;
and
2) the VL2 and VH2 are selected from the group consisting of:
a) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 230, 231, and 232, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 254, 255, and 256, respectively;
b) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 236, 237, and 238, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 260, 261, and 262, respectively;
c) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 242, 243, and 244, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 266, 267, and 268, respectively; and
d) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 248, 249, and 250, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 272, 273, and 274, respectively.
In one embodiment, the VL1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53;
the VH1 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, and 54;
the VL2 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 213, 217, 221, and 225;
the VH2 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 214, 218, 222, and 226.
In one embodiment,
1) the VL1 and VH1 are selected from the group consisting of:
a) a VL1 comprising SEQ ID NO: 5 and a VH1 comprising SEQ ID NO: 6;
b) a VL1 comprising SEQ ID NO: 9 and a VH1 comprising SEQ ID NO: 10;
c) a VL1 comprising SEQ ID NO: 13 and a VH1 comprising SEQ ID NO: 14;
d) a VL1 comprising SEQ ID NO: 17 and a VH1 comprising SEQ ID NO: 18;
e) a VL1 comprising SEQ ID NO: 21 and a VH1 comprising SEQ ID NO: 22;
f) a VL1 comprising SEQ ID NO: 25 and a VH1 comprising SEQ ID NO: 26;
g) a VL1 comprising SEQ ID NO: 29 and a VH1 comprising SEQ ID NO: 30;
h) a VL1 comprising SEQ ID NO: 33 and a VH1 comprising SEQ ID NO: 34;
i) a VL1 comprising SEQ ID NO: 37 and a VH1 comprising SEQ ID NO: 38;
j) a VL1 comprising SEQ ID NO: 41 and a VH1 comprising SEQ ID NO: 42;
k) a VL1 comprising SEQ ID NO: 45 and a VH1 comprising SEQ ID NO: 46;
l) a VL1 comprising SEQ ID NO: 49 and a VH1 comprising SEQ ID NO: 50; and
m) a VL1 comprising SEQ ID NO: 53 and a VH1 comprising SEQ ID NO: 54;
and
2) the VL2 and VH2 are selected from the group consisting of:
a) a VL2 comprising SEQ ID NO: 213 and a VH2 comprising SEQ ID NO: 214;
b) a VL2 comprising SEQ ID NO: 217 and a VH2 comprising SEQ ID NO: 218;
c) a VL2 comprising SEQ ID NO: 221 and a VH2 comprising SEQ ID NO: 222; and
d) a VL2 comprising SEQ ID NO: 225 and a VH2 comprising SEQ ID NO: 226.
In one embodiment, the CL of the light chain is selected from the group consisting of SEQ ID NO: 883 and SEQ ID NO: 884.
In one embodiment, the CH1-hinge-CH2-CH3 of the heavy chain is selected from the group consisting of SEQ ID NO: 885 and SEQ ID NO: 886.
In one embodiment, the first peptide linker is selected from the group consisting of SEQ ID NOs: 888-893.
In one embodiment, the second peptide linker is selected from the group consisting of SEQ ID NOs: 887-893.
In one embodiment, the first peptide linker comprises SEQ ID NO: 889 and the second peptide linker comprises SEQ ID NO: 887.
In one embodiment,
the light chain comprises a sequence selected from the group consisting of SEQ ID NOs: 286, 290, 294, 298, 302, 306, 310, 314, 318, 322, 326, 330, 336, 342, 346, 350, 354, 358, 362, 366, 370, 374, and 378; and
the heavy chain fusion protein comprises a sequence selected from the group consisting of SEQ ID Nos: 285, 289, 293, 297, 301, 305, 309, 313, 317, 321, 325, 329, 333, 337, 341, 345, 349, 353, 357, 361, 365, 369, 373, and 377.
In one embodiment, the light chain and the heavy chain fusion protein comprise polypeptides comprising amino acid sequences selected from the group consisting of:
SEQ ID NO: 286 and SEQ ID NO: 285, respectively;
SEQ ID NO: 290 and SEQ ID NO: 289, respectively;
SEQ ID NO: 294 and SEQ ID NO: 293, respectively;
SEQ ID NO: 298 and SEQ ID NO: 297, respectively;
SEQ ID NO: 302 and SEQ ID NO: 301, respectively;
SEQ ID NO: 306 and SEQ ID NO: 305, respectively;
SEQ ID NO: 310 and SEQ ID NO: 309, respectively;
SEQ ID NO: 314 and SEQ ID NO: 313, respectively;
SEQ ID NO: 318 and SEQ ID NO: 317, respectively;
SEQ ID NO: 322 and SEQ ID NO: 321, respectively;
SEQ ID NO: 326 and SEQ ID NO: 325, respectively;
SEQ ID NO: 330 and SEQ ID NO: 329, respectively;
SEQ ID NO: 334 and SEQ ID NO: 333, respectively;
SEQ ID NO: 338 and SEQ ID NO: 337, respectively;
SEQ ID NO: 342 and SEQ ID NO: 341, respectively;
SEQ ID NO: 346 and SEQ ID NO: 345, respectively;
SEQ ID NO: 350 and SEQ ID NO: 349, respectively;
SEQ ID NO: 354 and SEQ ID NO: 353, respectively;
SEQ ID NO: 358 and SEQ ID NO: 357, respectively;
SEQ ID NO: 362 and SEQ ID NO: 361, respectively;
SEQ ID NO: 366 and SEQ ID NO: 365, respectively;
SEQ ID NO: 370 and SEQ ID NO: 369, respectively;
SEQ ID NO: 374 and SEQ ID NO: 373, respectively; and
SEQ ID NO: 378 and SEQ ID NO: 377, respectively.
In one aspect, the present invention is directed to a polynucleotide encoding the light chain of the antibody construct of the present invention.
In one aspect, the present invention is directed to a polynucleotide encoding the heavy chain fusion protein of the antibody construct of the present invention.
In one aspect, the present invention is directed to a vector comprising the polynucleotide encoding the light chain of the antibody construct, the polynucleotide encoding the heavy chain of the antibody construct, or both.
In one aspect, the present invention is directed to a host cell transformed or transfected with the vector or the polynucleotide encoding the light chain of the antibody construct and the polynucleotide encoding the heavy chain of the antibody construct.
In one aspect, the present invention is directed to a process for producing the antibody construct of the present invention, the process comprising culturing a host cell comprising a polynucleotide encoding the light chain and also comprising a polynucleotide encoding the heavy chain fusion protein under conditions allowing the expression of the antibody construct, and recovering the produced antibody construct from the culture.
In one aspect, the present invention is directed to a pharmaceutical composition comprising the antibody construct according to the present invention and a carrier, stabilizer, excipient, diluent, solubilizer, surfactant, emulsifier, preservative or adjuvant.
In one aspect, the present invention is directed to a method for treating or ameliorating a solid tumor disease or a metastatic cancer disease, comprising the step of administering to a subject in need thereof an effective amount of the antibody construct according to the present invention.
In one embodiment, the solid tumor disease is selected from the group consisting of: ovarian cancer, pancreatic cancer, mesothelioma, lung cancer, gastric cancer and triple negative breast cancer disease or a metastatic cancer disease derived from any of the foregoing.
In one aspect, the present invention is directed to a kit comprising the antibody construct according to the present invention and, optionally, directions for use.
In one aspect, the present invention is directed to a multispecific antibody construct comprising:
(i) a first antibody comprising two light chains and two heavy chains, wherein
the light chains comprise a first variable region (VL1) and a light chain constant region (CL);
the heavy chains comprise a first heavy variable region (VH1) and CH1, hinge, CH2, and CH3 regions;
the heavy chains comprise at least one amino acid substitution that results in a reduced binding affinity of the heavy chain for human Fc gamma RI receptor as compared with an unsubstituted heavy chain; and
(ii) a scFv comprising a second light chain variable region (VL2) and a second heavy chain variable region (VH2) of a second antibody, wherein the VL2 and the VH2 are connected via a first peptide linker,
wherein the scFv is fused at its amino terminus to the carboxyl terminus of each of the heavy chains through a second peptide linker such that a heavy chain fusion protein is formed; and
wherein the first antibody specifically binds to human mesothelin (MSLN) (SEQ ID NO: 2) and the scFv specifically binds to and agonizes human CD40 (SEQ ID NO: 1).
In one embodiment, the multispecific antibody construct specifically agonizes CD40 in a MSLN-dependent fashion.
In one embodiment, the multispecific antibody construct comprises mutations limiting Fc receptor binding and thus decreases Fc receptor-dependent CD40 agonism.
In one embodiment, the two light chains are identical and the two heavy chain fusion proteins are identical.
In one embodiment, the heavy chain comprises an amino acid substitution selected from the group consisting of:
(i) N297G or N297A;
(ii) L234A and L235A; and
(iii) R292C and V302C;
wherein the amino acid numbering is EU numbering according to Kabat.
In one embodiment, the heavy chain comprises N297G, R292C, and V302C mutations, wherein the amino acid numbering is EU numbering according to Kabat.
In one embodiment:
the VL1 comprises a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of:
SEQ ID NOs: 230, 231, and 232, respectively;
SEQ ID NOs: 236, 237, and 238, respectively;
SEQ ID NOs: 242, 243, and 244, respectively; and
SEQ ID NOs: 248, 249, and 250, respectively;
the VH1 comprises a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of:
SEQ ID NOs: 254, 255, and 256, respectively;
SEQ ID NOs: 260, 261, and 262, respectively;
SEQ ID NOs: 266, 267, and 268, respectively; and
SEQ ID NOs: 272, 273, and 274, respectively;
the VL2 comprises a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of:
SEQ ID NOs: 58, 59, and 60, respectively;
SEQ ID NOs: 64, 65, and 66, respectively;
SEQ ID NOs: 70, 71, and 72, respectively;
SEQ ID NOs: 76, 77, and 78, respectively;
SEQ ID NOs: 82, 83, and 84, respectively;
SEQ ID NOs: 88, 89, and 90, respectively;
SEQ ID NOs: 94, 95, and 96, respectively;
SEQ ID NOs: 100, 101, and 102, respectively;
SEQ ID NOs: 106, 107, and 108, respectively;
SEQ ID NOs: 112, 113, and 114, respectively;
SEQ ID NOs: 118, 119, and 120, respectively;
SEQ ID NOs: 124, 125, and 126, respectively; and
SEQ ID NOs: 130, 131, and 132, respectively;
and
the VH2 comprises a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of:
SEQ ID NOs: 136, 137, and 138, respectively;
SEQ ID NOs: 142, 143, and 144, respectively;
SEQ ID NOs: 148, 149, and 150, respectively;
SEQ ID NOs: 154, 155, and 156, respectively;
SEQ ID NOs: 160, 161, and 162, respectively;
SEQ ID NOs: 166, 167, and 168, respectively;
SEQ ID NOs: 172, 173, and 174, respectively;
SEQ ID NOs: 178, 179, and 180, respectively;
SEQ ID NOs: 184, 185, and 186, respectively;
SEQ ID NOs: 190, 191, and 192, respectively;
SEQ ID NOs: 196, 197, and 198, respectively;
SEQ ID NOs: 202, 203, and 204, respectively; and
SEQ ID NOs: 208, 209, and 210, respectively.
In one embodiment,
1) the VL1 and VH1 are selected from the group consisting of:
a) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 230, 231, and 232, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 254, 255, and 256, respectively;
b) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 236, 237, and 238, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 260, 261, and 262, respectively;
c) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 242, 243, and 244, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 266, 267, and 268, respectively; and
d) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 248, 249, and 250, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 272, 273, and 274, respectively;
and
2) the VL2 and VH2 are selected from the group consisting of:
a) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 58, 59, and 60, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 136, 137, and 138, respectively;
b) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 64, 65, and 66, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 142, 143, and 144, respectively;
c) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 70, 71, and 72, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 148, 149, and 150, respectively;
d) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 76, 77, and 6780, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 154, 155, and 156, respectively;
e) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 82, 83, and 84, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 160, 161, and 162, respectively;
f) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 88, 89, and 90, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 166, 167, and 168, respectively;
g) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 94, 95, and 96, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 172, 173, and 174, respectively;
h) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 100, 101, and 102, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 178, 179, and 180, respectively;
i) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 106, 107, and 108, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 184, 185, and 186, respectively;
j) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 112, 113, and 114, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 190, 191, and 192, respectively;
k) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 118, 119, and 120, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 196, 197, and 198, respectively;
l) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 124, 125, and 126, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 202, 203, and 204, respectively; and
m) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 130, 131, and 132, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 208, 209, and 210, respectively.
In one embodiment:
the VL1 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 213, 217, 221, and 225;
the VH1 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 214, 218, 222, and 226;
the VL2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53; and
the VH2 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, and 54.
In one embodiment:
1) the VL1 and VH1 are selected from the group consisting of:
a) a VL1 comprising SEQ ID NO: 213 and a VH1 comprising SEQ ID NO: 214;
b) a VL1 comprising SEQ ID NO: 217 and a VH1 comprising SEQ ID NO: 218;
c) a VL1 comprising SEQ ID NO: 221 and a VH1 comprising SEQ ID NO: 222; and
d) a VL1 comprising SEQ ID NO: 225 and a VH1 comprising SEQ ID NO: 226;
and
2) the VL2 and VH2 are selected from the group consisting of:
a) a VL2 comprising SEQ ID NO: 5 and a VH2 comprising SEQ ID NO: 6;
b) a VL2 comprising SEQ ID NO: 9 and a VH2 comprising SEQ ID NO: 10;
c) a VL2 comprising SEQ ID NO: 13 and a VH2 comprising SEQ ID NO: 14;
d) a VL2 comprising SEQ ID NO: 17 and a VH2 comprising SEQ ID NO: 18;
e) a VL2 comprising SEQ ID NO: 21 and a VH2 comprising SEQ ID NO: 22;
f) a VL2 comprising SEQ ID NO: 25 and a VH2 comprising SEQ ID NO: 26;
g) a VL2 comprising SEQ ID NO: 29 and a VH2 comprising SEQ ID NO: 30;
h) a VL2 comprising SEQ ID NO: 33 and a VH2 comprising SEQ ID NO: 34;
i) a VL2 comprising SEQ ID NO: 37 and a VH2 comprising SEQ ID NO: 38;
j) a VL2 comprising SEQ ID NO: 41 and a VH2 comprising SEQ ID NO: 42;
k) a VL2 comprising SEQ ID NO: 45 and a VH2 comprising SEQ ID NO: 46;
l) a VL2 comprising SEQ ID NO: 49 and a VH2 comprising SEQ ID NO: 50; and
m) a VL2 comprising SEQ ID NO: 53 and a VH2 comprising SEQ ID NO: 54.
In one embodiment, the CL of the light chain is selected from the group consisting of SEQ ID NO: 883 and SEQ ID NO: 884.
In one embodiment, the CH1-hinge-CH2-CH3 of the heavy chain is selected from the group consisting of SEQ ID NO: 885 and SEQ ID NO: 886.
In one embodiment, the first peptide linker is selected from the group consisting of SEQ ID NOs: 888-893.
In one embodiment, the second peptide linker is selected from the group consisting of SEQ ID NOs: 887-893.
In one embodiment, the first peptide linker comprises SEQ ID NO: 889 and the second peptide linker comprises SEQ ID NO: 887.
In one embodiment,
the light chain comprises a sequence selected from the group consisting of SEQ ID NOs: 382, 386, 390, 394, 398, 402, 406, 410, 414, 418, 422, 426, 430, 434, 438, 442, 446, and 450; and
the heavy chain fusion protein comprises a sequence selected from the group consisting of SEQ ID NOs: 381, 385, 389, 393, 397, 401, 405, 409, 413, 417, 421, 425, 429, 433, 437, 441, 445, and 449.
In one embodiment, the light chain and the heavy chain fusion protein comprise polypeptides comprising amino acid sequences selected from the group consisting of:
SEQ ID NO: 382 and SEQ ID NO: 381, respectively;
SEQ ID NO: 386 and SEQ ID NO: 385, respectively;
SEQ ID NO: 390 and SEQ ID NO: 389, respectively;
SEQ ID NO: 394 and SEQ ID NO: 393, respectively;
SEQ ID NO: 398 and SEQ ID NO: 397, respectively;
SEQ ID NO: 402 and SEQ ID NO: 401, respectively;
SEQ ID NO: 406 and SEQ ID NO: 405, respectively;
SEQ ID NO: 410 and SEQ ID NO: 409, respectively;
SEQ ID NO: 414 and SEQ ID NO: 413, respectively;
SEQ ID NO: 418 and SEQ ID NO: 417, respectively;
SEQ ID NO: 422 and SEQ ID NO: 421, respectively;
SEQ ID NO: 426 and SEQ ID NO: 425, respectively;
SEQ ID NO: 430 and SEQ ID NO: 429, respectively;
SEQ ID NO: 434 and SEQ ID NO: 433, respectively;
SEQ ID NO: 438 and SEQ ID NO: 437, respectively;
SEQ ID NO: 442 and SEQ ID NO: 441, respectively;
SEQ ID NO: 446 and SEQ ID NO: 445, respectively; and
SEQ ID NO: 450 and SEQ ID NO: 449, respectively.
In one aspect, the present invention is directed to a multispecific antibody construct comprising:
a) two identical heavy chain fusion proteins each comprising a first heavy chain variable region (VH1) and a first CH1 domain, wherein the first CH1 domain is linked to a hinge-CH2-CH3 polypeptide, and wherein the hinge-CH2-CH3 polypeptide is linked to a second heavy chain variable region (VH2), wherein the VH2 is linked to a second CH1 domain; wherein
i) the VH1 or first CH1 domain comprises at least one amino acid substitution to introduce a positively charged amino acid at a residue selected from the group consisting of positions 39, 44, and 183 using EU numbering; and
ii) the VH2 or second CH1 domain comprises at least one amino acid substitution to introduce a negatively charged amino acid at a residue selected from the group consisting of a residue that corresponds to positions 39, 44, and 183 using EU numbering; and
b) a second polypeptide comprising a first light chain, wherein the first light chain comprises a first light chain variable region (VL1) and a first CL region; and wherein the VL1 or first CL domain comprises at least one amino acid substitution to introduce a negatively charged amino acid at a residue selected from the group consisting of positions 38, 100, and 176 using EU numbering; and
c) a third polypeptide comprising a second light chain, wherein the second light chain comprises a second light chain variable region (VL2) and a second CL region; and wherein the VL2 or second CL domain comprises at least one amino acid substitution to introduce a positively charged amino acid at a residue selected from the group consisting of positions 38, 100, and 176 using EU numbering;
wherein the VH1 and VL1 interact to bind a first antigen and wherein the VH2 and VL2 interact to bind a second antigen;
wherein:
the first antigen is human CD40 (SEQ ID NO: 1) and the second antigen is human mesothelin (“MSLN”; SEQ ID NO: 2); or
the first antigen is human MSLN (SEQ ID NO: 2) and the second antigen is human CD40 (SEQ ID NO: 1).
In one aspect, the present invention is directed to a multispecific antibody construct comprising:
a) two identical heavy chain fusion proteins each comprising a first heavy chain variable region (VH1) and a first CH1 domain, wherein the first CH1 domain is linked to a hinge-CH2-CH3 polypeptide, and wherein the hinge-CH2-CH3 polypeptide is linked to a second heavy chain variable region (VH2), wherein the VH2 is linked to a second CH1 domain; wherein
i) the VH1 or first CH1 domain comprises at least one amino acid substitution to introduce a negatively charged amino acid at a residue selected from the group consisting of positions 39, 44, and 183 using EU numbering; and
ii) the VH2 or second CH1 domain comprises at least one amino acid substitution to introduce a positively charged amino acid at a residue selected from the group consisting of a residue that corresponds to positions 39, 44, and 183 using EU numbering; and
b) a second polypeptide comprising a first light chain, wherein the first light chain comprises a first light chain variable region (VL1) and a first CL region; and wherein the VL1 or first CL domain comprises at least one amino acid substitution to introduce a positively charged amino acid at a residue selected from the group consisting of positions 38, 100, and 176 using EU numbering; and
c) a third polypeptide comprising a second light chain, wherein the second light chain comprises a second light chain variable region (VL2) and a second CL region; and wherein the VL2 or second CL domain comprises at least one amino acid substitution to introduce a negatively charged amino acid at a residue selected from the group consisting of positions 38, 100, and 176 using EU numbering;
wherein the VH1 and VL1 interact to bind a first antigen and wherein the VH2 and VL2 interact to bind a second antigen;
wherein:
the first antigen is human CD40 (SEQ ID NO: 1) and the second antigen is human mesothelin (“MSLN”; SEQ ID NO: 2); or
the first antigen is human MSLN (SEQ ID NO: 2) and the second antigen is human CD40 (SEQ ID NO: 1).
In one embodiment, the hinge-CH2-CH3 polypeptide is linked to the VH2 via a peptide linker.
In one embodiment, the peptide linker comprises a sequence selected from the group consisting of (Gly3Ser)2 (SEQ ID NO: 916), (Gly4Ser)2 (SEQ ID NO: 888), (Gly3Ser)3 (SEQ ID NO: 917), (Gly4Ser)3 (SEQ ID NO: 889), (Gly3Ser)4 (SEQ ID NO: 918), (Gly4Ser)4 (SEQ ID NO: 890), (Gly3Ser)5 (SEQ ID NO: 919), (Gly4Ser)5 (SEQ ID NO: 920), (Gly3Ser)6 (SEQ ID NO: 921), and (Gly4Ser)6 (SEQ ID NO: 922).
In one embodiment,
a) the VH1 or first CH1 domain comprises a mutation selected from the group consisting of Q39K, G44K, and S183K using EU numbering;
b) the VH2 or second CH1 domain comprises a mutation selected from the group consisting of Q39E, G44E, and S183E using EU numbering;
c) the VL1 or first CL domain comprises a mutation selected from the group consisting of Q38E, G100E, and S176E using EU numbering; and
d) the VL2 or second CL domain comprises a mutation selected from the group consisting of Q38K, G100K, and S176K using EU numbering.
In one embodiment,
a) the first CH1 domain comprises a S183K mutation using EU numbering;
b) the second CH1 domain comprises a S183E mutation using EU numbering;
c) the first CL domain comprises a S176E mutation using EU numbering; and
d) the second CL domain comprises a S176K mutation using EU numbering.
In one embodiment,
a) the VH1 comprises a Q39K mutation and the first CH1 domain comprises a S183K mutation using EU numbering;
b) the VH2 comprises a Q39E mutation and the second CH1 domain comprises a S183E mutation using EU numbering;
c) the VL1 comprises a Q38E mutation and the first CL domain comprises a S176E mutation using EU numbering; and
d) the VL2 comprises a Q38K mutation and the second CL domain comprises a S176K mutation using EU numbering.
In one embodiment,
a) the first CH1 domain comprises G44K and S183K mutations using EU numbering;
b) the second CH1 domain comprises G44E and S183E mutations using EU numbering;
c) the first CL domain comprises G100E and S176E mutations using EU numbering; and
d) the second CL domain comprises G100K and S176K mutations using EU numbering.
In one embodiment,
a) the VH1 or first CH1 domain comprises a mutation selected from the group consisting of Q39E, G44E, and S183E using EU numbering;
b) the VH2 or second CH1 domain comprises a mutation selected from the group consisting of Q39K, G44K, and S183K using EU numbering;
c) the VL1 or first CL domain comprises a mutation selected from the group consisting of Q38K, G100K, and S176K using EU numbering; and
d) the VL2 or second CL domain comprises a mutation selected from the group consisting of Q38E, G100E, and S176E using EU numbering.
In one embodiment,
a) the first CH1 domain comprises a S183E mutation using EU numbering;
b) the second CH1 domain comprises a S183K mutation using EU numbering;
c) the first CL domain comprises a S176K mutation using EU numbering; and
d) the second CL domain comprises a S176E mutation using EU numbering.
In one embodiment,
a) the VH1 comprises a Q39E mutation and the first CH1 domain comprises a S183E mutation using EU numbering;
b) the VH2 comprises a Q39K mutation and the second CH1 domain comprises a S183K mutation using EU numbering;
c) the VL1 comprises a Q38K mutation and the first CL domain comprises a S176K mutation using EU numbering; and
d) the VL2 comprises a Q38E mutation and the second CL domain comprises a S176E mutation using EU numbering.
In one embodiment,
a) the first CH1 domain comprises G44E and S183E mutations using EU numbering;
b) the second CH1 domain comprises G44Kand S183K mutations using EU numbering;
c) the first CL domain comprises G100K and S176K mutations using EU numbering; and
d) the second CL domain comprises G100E and S176E mutations using EU numbering.
In one embodiment, the hinge-CH2-CH3 polypeptide comprises an amino acid substitution selected from the group consisting of:
(i) N297G or N297A;
(ii) L234A and L235A; and
(iii) R292C and V302C;
wherein the amino acid numbering is EU numbering according to Kabat.
In one embodiment, the hinge-CH2-CH3 polypeptide comprises N297G, R292C, and V302C mutations, wherein the amino acid numbering is EU numbering according to Kabat.
In one embodiment, the first antigen is human CD40 (SEQ ID NO: 1) and the second antigen is human MSLN (SEQ ID NO: 2); and
the VL1 comprises a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of:
SEQ ID NOs: 58, 59, and 60, respectively;
SEQ ID NOs: 64, 65, and 66, respectively;
SEQ ID NOs: 70, 71, and 72, respectively;
SEQ ID NOs: 76, 77, and 78, respectively;
SEQ ID NOs: 82, 83, and 84, respectively;
SEQ ID NOs: 88, 89, and 90, respectively;
SEQ ID NOs: 94, 95, and 96, respectively;
SEQ ID NOs: 100, 101, and 102, respectively;
SEQ ID NOs: 106, 107, and 108, respectively;
SEQ ID NOs: 112, 113, and 114, respectively;
SEQ ID NOs: 118, 119, and 120, respectively;
SEQ ID NOs: 124, 125, and 126, respectively; and
SEQ ID NOs: 130, 131, and 132, respectively;
the VH1 comprises a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of:
SEQ ID NOs: 136, 137, and 138, respectively;
SEQ ID NOs: 142, 143, and 144, respectively;
SEQ ID NOs: 148, 149, and 150, respectively;
SEQ ID NOs: 154, 155, and 156, respectively;
SEQ ID NOs: 160, 161, and 162, respectively;
SEQ ID NOs: 166, 167, and 168, respectively;
SEQ ID NOs: 172, 173, and 174, respectively;
SEQ ID NOs: 178, 179, and 180, respectively;
SEQ ID NOs: 184, 185, and 186, respectively;
SEQ ID NOs: 190, 191, and 192, respectively;
SEQ ID NOs: 196, 197, and 198, respectively;
SEQ ID NOs: 202, 203, and 204, respectively; and
SEQ ID NOs: 208, 209, and 210, respectively;
the VL2 comprises a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of:
SEQ ID NOs: 230, 231, and 232, respectively;
SEQ ID NOs: 236, 237, and 238, respectively;
SEQ ID NOs: 242, 243, and 244, respectively; and
SEQ ID NOs: 248, 249, and 250, respectively;
and the VH2 comprises a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of:
SEQ ID NOs: 254, 255, and 256, respectively;
SEQ ID NOs: 260, 261, and 262, respectively;
SEQ ID NOs: 266, 267, and 268, respectively; and
SEQ ID NOs: 272, 273, and 274, respectively.
In one embodiment, the first antigen is human CD40 (SEQ ID NO: 1) and the second antigen is human MSLN (SEQ ID NO:2), wherein
1) the VL1 and VH1 are selected from the group consisting of:
a) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 58, 59, and 60, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 136, 137, and 138, respectively;
b) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 64, 65, and 66, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 142, 143, and 144, respectively;
c) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 70, 71, and 72, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 148, 149, and 150, respectively;
d) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 76, 77, and 6780, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 154, 155, and 156, respectively;
e) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 82, 83, and 84, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 160, 161, and 162, respectively;
f) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 88, 89, and 90, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 166, 167, and 168, respectively;
g) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 94, 95, and 96, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 172, 173, and 174, respectively;
h) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 100, 101, and 102, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 178, 179, and 180, respectively;
i) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 106, 107, and 108, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 184, 185, and 186, respectively;
j) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 112, 113, and 114, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 190, 191, and 192, respectively;
k) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 118, 119, and 120, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 196, 197, and 198, respectively;
l) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 124, 125, and 126, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 202, 203, and 204, respectively; and
m) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 130, 131, and 132, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 208, 209, and 210, respectively;
and
2) the VL2 and VH2 are selected from the group consisting of:
a) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 230, 231, and 232, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 254, 255, and 256, respectively;
b) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 236, 237, and 238, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 260, 261, and 262, respectively;
c) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 242, 243, and 244, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 266, 267, and 268, respectively; and
d) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 248, 249, and 250, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 272, 273, and 274, respectively.
In one embodiment:
the VL1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53;
the VH1 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, and 54;
the VL2 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 213, 217, 221, and 225;
the VH2 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 214, 218, 222, and 226.
In one embodiment:
1) the VL1 and VH1 are selected from the group consisting of:
a) a VL1 comprising SEQ ID NO: 5 and a VH1 comprising SEQ ID NO: 6;
b) a VL1 comprising SEQ ID NO: 9 and a VH1 comprising SEQ ID NO: 10;
c) a VL1 comprising SEQ ID NO: 13 and a VH1 comprising SEQ ID NO: 14;
d) a VL1 comprising SEQ ID NO: 17 and a VH1 comprising SEQ ID NO: 18;
e) a VL1 comprising SEQ ID NO: 21 and a VH1 comprising SEQ ID NO: 22;
f) a VL1 comprising SEQ ID NO: 25 and a VH1 comprising SEQ ID NO: 26;
g) a VL1 comprising SEQ ID NO: 29 and a VH1 comprising SEQ ID NO: 30;
h) a VL1 comprising SEQ ID NO: 33 and a VH1 comprising SEQ ID NO: 34;
i) a VL1 comprising SEQ ID NO: 37 and a VH1 comprising SEQ ID NO: 38;
j) a VL1 comprising SEQ ID NO: 41 and a VH1 comprising SEQ ID NO: 42;
k) a VL1 comprising SEQ ID NO: 45 and a VH1 comprising SEQ ID NO: 46;
l) a VL1 comprising SEQ ID NO: 49 and a VH1 comprising SEQ ID NO: 50; and
m) a VL1 comprising SEQ ID NO: 53 and a VH1 comprising SEQ ID NO: 54;
and
2) the VL2 and VH2 are selected from the group consisting of:
a) a VL2 comprising SEQ ID NO: 213 and a VH2 comprising SEQ ID NO: 214;
b) a VL2 comprising SEQ ID NO: 217 and a VH2 comprising SEQ ID NO: 218;
c) a VL2 comprising SEQ ID NO: 221 and a VH2 comprising SEQ ID NO: 222; and
d) a VL2 comprising SEQ ID NO: 225 and a VH2 comprising SEQ ID NO: 226.
In one aspect, the present invention is directed to a polynucleotide encoding the first light chain of the antibody construct.
In one aspect, the present invention is directed to a polynucleotide encoding the second light chain of the antibody construct.
In one aspect, the present invention is directed to a polynucleotide encoding the heavy chain fusion protein of the antibody construct.
In one aspect, the present invention is directed to a vector comprising:
a) the polynucleotide encoding the first light chain of the antibody construct,
b) the polynucleotide encoding the second light chain of the antibody construct,
c) the polynucleotide encoding the heavy chain fusion protein of the antibody construct, or
d) any combination of a), b), and c).
In one aspect, the present invention is directed to a host cell transformed or transfected with the vector or polynucleotide according to the present invention.
In one aspect, the present invention is directed to a process for producing the antibody construct according to the present invention, the process comprising culturing a host cell comprising a polynucleotide encoding the first light chain, a polynucleotide encoding the second light chain and a polynucleotide encoding the heavy chain fusion protein under conditions allowing the expression of the antibody construct, and recovering the produced antibody construct from the culture.
In one aspect, the present invention is directed to a pharmaceutical composition comprising the antibody construct according to the present invention and a carrier, stabilizer, excipient, diluent, solubilizer, surfactant, emulsifier, preservative or adjuvant.
In one aspect, the present invention is directed to a method for treating or ameliorating a solid tumor disease or a metastatic cancer disease, comprising the step of administering to a subject in need thereof an effective amount of the antibody construct according to the present invention.
In one embodiment, the solid tumor disease is selected from the group consisting of: ovarian cancer, pancreatic cancer, mesothelioma, lung cancer, gastric cancer and triple negative breast cancer disease or a metastatic cancer disease derived from any of the foregoing.
In one aspect, the present invention is directed to a kit comprising the antibody construct according to the present invention and, optionally, directions for use.
In one embodiment, the first antigen is human MSLN (SEQ ID NO: 2) and the second antigen is human CD40 (SEQ ID NO: 1); wherein:
the VL1 comprises a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of:
SEQ ID NOs: 230, 231, and 232, respectively;
SEQ ID NOs: 236, 237, and 238, respectively;
SEQ ID NOs: 242, 243, and 244, respectively; and
SEQ ID NOs: 248, 249, and 250, respectively;
the VH1 comprises a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of:
SEQ ID NOs: 254, 255, and 256, respectively;
SEQ ID NOs: 260, 261, and 262, respectively;
SEQ ID NOs: 266, 267, and 268, respectively; and
SEQ ID NOs: 272, 273, and 274, respectively;
the VL2 comprises a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of:
SEQ ID NOs: 58, 59, and 60, respectively;
SEQ ID NOs: 64, 65, and 66, respectively;
SEQ ID NOs: 70, 71, and 72, respectively;
SEQ ID NOs: 76, 77, and 78, respectively;
SEQ ID NOs: 82, 83, and 84, respectively;
SEQ ID NOs: 88, 89, and 90, respectively;
SEQ ID NOs: 94, 95, and 96, respectively;
SEQ ID NOs: 100, 101, and 102, respectively;
SEQ ID NOs: 106, 107, and 108, respectively;
SEQ ID NOs: 112, 113, and 114, respectively;
SEQ ID NOs: 118, 119, and 120, respectively;
SEQ ID NOs: 124, 125, and 126, respectively; and
SEQ ID NOs: 130, 131, and 132, respectively;
and
the VH2 comprises a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of:
SEQ ID NOs: 136, 137, and 138, respectively;
SEQ ID NOs: 142, 143, and 144, respectively;
SEQ ID NOs: 148, 149, and 150, respectively;
SEQ ID NOs: 154, 155, and 156, respectively;
SEQ ID NOs: 160, 161, and 162, respectively;
SEQ ID NOs: 166, 167, and 168, respectively;
SEQ ID NOs: 172, 173, and 174, respectively;
SEQ ID NOs: 178, 179, and 180, respectively;
SEQ ID NOs: 184, 185, and 186, respectively;
SEQ ID NOs: 190, 191, and 192, respectively;
SEQ ID NOs: 196, 197, and 198, respectively;
SEQ ID NOs: 202, 203, and 204, respectively; and
SEQ ID NOs: 208, 209, and 210, respectively.
In one embodiment,
1) the VL1 and VH1 are selected from the group consisting of:
a) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 230, 231, and 232, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 254, 255, and 256, respectively;
b) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 236, 237, and 238, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 260, 261, and 262, respectively;
c) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 242, 243, and 244, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 266, 267, and 268, respectively; and
d) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 248, 249, and 250, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 272, 273, and 274, respectively;
and
2) the VL2 and VH2 are selected from the group consisting of:
a) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 58, 59, and 60, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 136, 137, and 138, respectively;
b) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 64, 65, and 66, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 142, 143, and 144, respectively;
c) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 70, 71, and 72, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 148, 149, and 150, respectively;
d) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 76, 77, and 6780, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 154, 155, and 156, respectively;
e) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 82, 83, and 84, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 160, 161, and 162, respectively;
f) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 88, 89, and 90, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 166, 167, and 168, respectively;
g) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 94, 95, and 96, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 172, 173, and 174, respectively;
h) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 100, 101, and 102, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 178, 179, and 180, respectively;
i) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 106, 107, and 108, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 184, 185, and 186, respectively;
j) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 112, 113, and 114, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 190, 191, and 192, respectively;
k) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 118, 119, and 120, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 196, 197, and 198, respectively;
l) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 124, 125, and 126, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 202, 203, and 204, respectively; and
m) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 130, 131, and 132, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 208, 209, and 210, respectively.
In one embodiment,
the VL1 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 213, 217, 221, and 225;
the VH1 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 214, 218, 222, and 226;
the VL2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53; and
the VH2 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, and 54.
In one embodiment,
1) the VL1 and VH1 are selected from the group consisting of:
a) a VL1 comprising SEQ ID NO: 213 and a VH1 comprising SEQ ID NO: 214;
b) a VL1 comprising SEQ ID NO: 217 and a VH1 comprising SEQ ID NO: 218;
c) a VL1 comprising SEQ ID NO: 221 and a VH1 comprising SEQ ID NO: 222; and
d) a VL1 comprising SEQ ID NO: 225 and a VH1 comprising SEQ ID NO: 226;
and
2) the VL2 and VH2 are selected from the group consisting of:
a) a VL2 comprising SEQ ID NO: 5 and a VH2 comprising SEQ ID NO: 6;
b) a VL2 comprising SEQ ID NO: 9 and a VH2 comprising SEQ ID NO: 10;
c) a VL2 comprising SEQ ID NO: 13 and a VH2 comprising SEQ ID NO: 14;
d) a VL2 comprising SEQ ID NO: 17 and a VH2 comprising SEQ ID NO: 18;
e) a VL2 comprising SEQ ID NO: 21 and a VH2 comprising SEQ ID NO: 22;
f) a VL2 comprising SEQ ID NO: 25 and a VH2 comprising SEQ ID NO: 26;
g) a VL2 comprising SEQ ID NO: 29 and a VH2 comprising SEQ ID NO: 30;
h) a VL2 comprising SEQ ID NO: 33 and a VH2 comprising SEQ ID NO: 34;
i) a VL2 comprising SEQ ID NO: 37 and a VH2 comprising SEQ ID NO: 38;
j) a VL2 comprising SEQ ID NO: 41 and a VH2 comprising SEQ ID NO: 42;
k) a VL2 comprising SEQ ID NO: 45 and a VH2 comprising SEQ ID NO: 46;
l) a VL2 comprising SEQ ID NO: 49 and a VH2 comprising SEQ ID NO: 50; and
m) a VL2 comprising SEQ ID NO: 53 and a VH2 comprising SEQ ID NO: 54.
In one aspect, the present invention is directed to an antigen binding protein that specifically binds and agonizes human CD40 (SEQ ID NO: 1), the antigen binding protein comprising a light chain variable region (VL) and a heavy chain variable region (VH), wherein:
the VL comprises a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of:
SEQ ID NOs: 58, 59, and 60, respectively;
SEQ ID NOs: 64, 65, and 66, respectively;
SEQ ID NOs: 70, 71, and 72, respectively;
SEQ ID NOs: 76, 77, and 78, respectively;
SEQ ID NOs: 82, 83, and 84, respectively;
SEQ ID NOs: 88, 89, and 90, respectively;
SEQ ID NOs: 94, 95, and 96, respectively;
SEQ ID NOs: 100, 101, and 102, respectively;
SEQ ID NOs: 106, 107, and 108, respectively;
SEQ ID NOs: 112, 113, and 114, respectively;
SEQ ID NOs: 118, 119, and 120, respectively;
SEQ ID NOs: 124, 125, and 126, respectively; and
SEQ ID NOs: 130, 131, and 132, respectively;
and
the VH comprises a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of:
SEQ ID NOs: 136, 137, and 138, respectively;
SEQ ID NOs: 142, 143, and 144, respectively;
SEQ ID NOs: 148, 149, and 150, respectively;
SEQ ID NOs: 154, 155, and 156, respectively;
SEQ ID NOs: 160, 161, and 162, respectively;
SEQ ID NOs: 166, 167, and 168, respectively;
SEQ ID NOs: 172, 173, and 174, respectively;
SEQ ID NOs: 178, 179, and 180, respectively;
SEQ ID NOs: 184, 185, and 186, respectively;
SEQ ID NOs: 190, 191, and 192, respectively;
SEQ ID NOs: 196, 197, and 198, respectively;
SEQ ID NOs: 202, 203, and 204, respectively; and
SEQ ID NOs: 208, 209, and 210, respectively.
In one embodiment, the multispecific antibody construct comprises mutations limiting Fc receptor binding and thus decreases Fc receptor-dependent CD40 agonism.
In one embodiment,
the VL and VH are selected from the group consisting of:
a) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 58, 59, and 60, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 136, 137, and 138, respectively;
b) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 64, 65, and 66, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 142, 143, and 144, respectively;
c) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 70, 71, and 72, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 148, 149, and 150, respectively;
d) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 76, 77, and 6780, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 154, 155, and 156, respectively;
e) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 82, 83, and 84, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 160, 161, and 162, respectively;
f) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 88, 89, and 90, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 166, 167, and 168, respectively;
g) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 94, 95, and 96, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 172, 173, and 174, respectively;
h) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 100, 101, and 102, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 178, 179, and 180, respectively;
i) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 106, 107, and 108, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 184, 185, and 186, respectively;
j) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 112, 113, and 114, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 190, 191, and 192, respectively;
k) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 118, 119, and 120, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 196, 197, and 198, respectively;
l) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 124, 125, and 126, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 202, 203, and 204, respectively; and
m) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 130, 131, and 132, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 208, 209, and 210, respectively.
In one embodiment,
the VL comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53; and
the VH comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, and 54.
In one embodiment,
the VL and VH are selected from the group consisting of:
a) a VL comprising SEQ ID NO: 5 and a VH comprising SEQ ID NO: 6;
b) a VL comprising SEQ ID NO: 9 and a VH comprising SEQ ID NO: 10;
c) a VL comprising SEQ ID NO: 13 and a VH comprising SEQ ID NO: 14;
d) a VL comprising SEQ ID NO: 17 and a VH comprising SEQ ID NO: 18;
e) a VL comprising SEQ ID NO: 21 and a VH comprising SEQ ID NO: 22;
f) a VL comprising SEQ ID NO: 25 and a VH comprising SEQ ID NO: 26;
g) a VL comprising SEQ ID NO: 29 and a VH comprising SEQ ID NO: 30;
h) a VL comprising SEQ ID NO: 33 and a VH comprising SEQ ID NO: 34;
i) a VL comprising SEQ ID NO: 37 and a VH comprising SEQ ID NO: 38;
j) a VL comprising SEQ ID NO: 41 and a VH comprising SEQ ID NO: 42;
k) a VL comprising SEQ ID NO: 45 and a VH comprising SEQ ID NO: 46;
l) a VL comprising SEQ ID NO: 49 and a VH comprising SEQ ID NO: 50; and
m) a VL comprising SEQ ID NO: 53 and a VH comprising SEQ ID NO: 54.
In one embodiment, the heavy chain comprises an amino acid substitution selected from the group consisting of:
(i) N297G or N297A;
(ii) L234A and L235A; and
(iii) R292C and V302C;
wherein the amino acid numbering is EU numbering according to Kabat.
In one embodiment, the heavy chain comprises N297G, R292C, and V302C mutations, wherein the amino acid numbering is EU numbering according to Kabat.
In one embodiment, the antigen binding protein further comprises a light chain CL polypeptide linked to the VL, wherein the CL polypeptide is selected from the group consisting of SEQ ID NO: 883 and SEQ ID NO: 884.
In one embodiment, the antigen binding protein further comprises a heavy chain CH1-hinge-CH2-CH3 polypeptide wherein the CH1-hinge-CH2-CH3 polypeptide is selected from the group consisting of SEQ ID NO: 885 and SEQ ID NO: 886.
In one embodiment, the antigen binding protein further comprises a second antigen binding portion that specifically binds a second antigen.
In one embodiment, the second antigen is a tumor associated antigen (TAA).
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1A-1D depict on cell binding of anti-MSLN antibodies to CHO cells expressing human MSLN.
FIGS. 2A-2B depict Activity of anti-CD40 antibodies with and without crosslinking in human B cell assay.
FIGS. 3A-3B depict Bivalent bispecific antibody formats.
FIG. 4 depicts Generation of cell lines expressing varying levels of MSLN.
FIG. 5 depicts Pharmacokinetic properties and stability of anti-CD40xMSLN bispecific molecules in mouse.
FIGS. 6A-6D depict Generation of MC38-human EPCAM and B16F10-human EPCAM expressing cell line.
FIGS. 7A-7B depict Activity of mouse surrogate anti-CD40xhuman EPCAM bispecific molecule.
FIGS. 8A-8B depict Mouse surrogate anti-CD40xhuman EPCAM bispecific molecule has tumor-localized, TAA-mediated X-linking-dependent activity in vivo.
FIG. 9 depicts Mouse surrogate anti-CD40xhuman EPCAM bispecific molecule enhances CD8+ T cell anti-tumor responses.
FIGS. 10A-10B depict Mouse surrogate anti-CD40xhuman EPCAM bispecific molecule has tumor-localized, TAA-mediated X-linking-dependent activity in vivo.
FIGS. 11A-11C depict Mouse surrogate anti-CD40xhuman EPCAM bispecific molecule does not increase levels of systemic cytokines or increase liver inflammation.
FIGS. 12A-12B depict Mouse surrogate anti-CD40xhuman EPCAM bispecific molecule induces regression of established MC38-human EPCAM tumors alone and in combination with PD1/PDL1 blockade.
FIG. 13 depicts Mouse surrogate anti-CD40xhuman EPCAM bispecific molecule induces long-lasting immune memory that protects against tumor re-challenge.
DETAILED DESCRIPTION
Unless otherwise indicated, the term “at least” preceding a series of elements is to be understood to refer to every element in the series. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the present invention.
The term “and/or” wherever used herein includes the meaning of “and”, “or” and “all or any other combination of the elements connected by said term”.
The term “about” or “approximately” as used herein means within +20%, preferably within +15%, more preferably within +10%, and most preferably within +5% of a given value or range.
Throughout this specification and the claims which follow, unless the context requires otherwise, the word “comprise”, and variations such as “comprises” and “comprising”, will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integer or step. When used herein the term “comprising” can be substituted with the term “containing” or “including” or sometimes when used herein with the term “having”.
When used herein “consisting of” excludes any element, step, or ingredient not specified in the claim element. When used herein, “consisting essentially of” does not exclude materials or steps that do not materially affect the basic and novel characteristics of the claim.
In each instance herein any of the terms “comprising”, “consisting essentially of” and “consisting of” may be replaced with either of the other two terms.
As used herein, the term “antigen binding protein” refers to a protein that specifically binds to one or more target antigens. An antigen binding protein can include an antibody and functional fragments thereof. A “functional antibody fragment” is a portion of an antibody that lacks at least some of the amino acids present in a full-length heavy chain and/or light chain, but which is still capable of specifically binding to an antigen. A functional antibody fragment includes, but is not limited to, a Fab fragment, a Fab′ fragment, a F(ab′)2 fragment, a Fv fragment, a Fd fragment, and a complementarity determining region (CDR) fragment, and can be derived from any mammalian source, such as human, mouse, rat, rabbit, or camelid. Functional antibody fragments may compete for binding of a target antigen with an intact antibody and the fragments may be produced by the modification of intact antibodies (e.g. enzymatic or chemical cleavage) or synthesized de novo using recombinant DNA technologies or peptide synthesis.
The term “antibody construct” refers to a molecule in which the structure and/or function is/are based on the structure and/or function of an antibody, e.g., of a full-length or whole immunoglobulin molecule. An antibody construct is hence capable of binding to its specific target or antigen. Furthermore, an antibody construct according to the invention comprises the minimum structural requirements of an antibody which allow for the target binding. This minimum requirement may e.g. be defined by the presence of at least the three light chain CDRs (i.e. CDR1, CDR2 and CDR3 of the VL region) and/or the three heavy chain CDRs (i.e. CDR1, CDR2 and CDR3 of the VH region), preferably of all six CDRs. The antibodies on which the constructs according to the invention are based include for example monoclonal, recombinant, chimeric, deimmunized, humanized and human antibodies.
In certain embodiments, the antigen binding proteins of the invention comprise antibodies. As used herein, the term “antibody” refers to a tetrameric immunoglobulin protein comprising two light chain polypeptides (about 25 kDa each) and two heavy chain polypeptides (about 50-70 kDa each). The term “light chain” or “immunoglobulin light chain” refers to a polypeptide comprising, from amino terminus to carboxyl terminus, a single immunoglobulin light chain variable region (VL) and a single immunoglobulin light chain constant domain (CL). The immunoglobulin light chain constant domain (CL) can be kappa (κ) or lambda (λ). The term “heavy chain” or “immunoglobulin heavy chain” refers to a polypeptide comprising, from amino terminus to carboxyl terminus, a single immunoglobulin heavy chain variable region (VH), an immunoglobulin heavy chain constant domain 1 (CH1), an immunoglobulin hinge region, an immunoglobulin heavy chain constant domain 2 (CH2), an immunoglobulin heavy chain constant domain 3 (CH3), and optionally an immunoglobulin heavy chain constant domain 4 (CH4). Heavy chains are classified as mu (μ), delta (Δ), gamma (γ), alpha (α), and epsilon (ε), and define the antibody's isotype as IgM, IgD, IgG, IgA, and IgE, respectively. The IgG-class and IgA-class antibodies are further divided into subclasses, namely, IgG1, IgG2, IgG3, and IgG4, and IgAQ1 and IgA2, respectively. The heavy chains in IgG, IgA, and IgD antibodies have three domains (CH1, CH2, and CH3), whereas the heavy chains in IgM and IgE antibodies have four domains (CH1, CH2, CH3, and CH4). The immunoglobulin heavy chain constant domains can be from any immunoglobulin isotype, including subtypes. The antibody chains are linked together via inter-polypeptide disulfide bonds between the CL domain and the CH1 domain (i.e. between the light and heavy chain) and between the hinge regions of the antibody heavy chains.
In a human antibody, CH1 means a region having the amino acid sequence at positions 118 to 215 of the EU index. A highly flexible amino acid region called a “hinge region” exists between CH1 and CH2. CH2 represents a region having the amino acid sequence at positions 231 to 340 of the EU index, and CH3 represents a region having the amino acid sequence at positions 341 to 446 of the EU index.
“CL” represents a constant region of a light chain. In the case of a κ chain of a human antibody, CL represents a region having the amino acid sequence at positions 108 to 214 of the EU index. In a λ chain, CL represents a region having the amino acid sequence at positions 108 to 215.
Both the EU index as in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD (1991) and AHo numbering schemes (Honegger A. and Phickthun A. J Mol Biol. 2001 Jun. 8; 309(3):657-70) can be used in the present invention. Amino acid positions and complementarity determining regions (CDRs) and framework regions (FR) of a given antibody may be identified using either system. For example, EU heavy chain positions of 39, 44, 183, 356, 357, 360, 370, 392, 399, and 409 are equivalent to AHo heavy chain positions 46, 51, 230, 484, 485, 491, 501, 528, 535, and 551, respectively.
In one aspect, the present invention is directed to an antigen binding protein that specifically binds and agonizes human CD40 (SEQ ID NO: 1), the antigen binding protein comprising a light chain variable region (VL) and a heavy chain variable region (VH), wherein:
the VL comprises a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of:
SEQ ID NOs: 58, 59, and 60, respectively;
SEQ ID NOs: 64, 65, and 66, respectively;
SEQ ID NOs: 70, 71, and 72, respectively;
SEQ ID NOs: 76, 77, and 78, respectively;
SEQ ID NOs: 82, 83, and 84, respectively;
SEQ ID NOs: 88, 89, and 90, respectively;
SEQ ID NOs: 94, 95, and 96, respectively;
SEQ ID NOs: 100, 101, and 102, respectively;
SEQ ID NOs: 106, 107, and 108, respectively;
SEQ ID NOs: 112, 113, and 114, respectively;
SEQ ID NOs: 118, 119, and 120, respectively;
SEQ ID NOs: 124, 125, and 126, respectively; and
SEQ ID NOs: 130, 131, and 132, respectively;
and
the VH comprises a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of:
SEQ ID NOs: 136, 137, and 138, respectively;
SEQ ID NOs: 142, 143, and 144, respectively;
SEQ ID NOs: 148, 149, and 150, respectively;
SEQ ID NOs: 154, 155, and 156, respectively;
SEQ ID NOs: 160, 161, and 162, respectively;
SEQ ID NOs: 166, 167, and 168, respectively;
SEQ ID NOs: 172, 173, and 174, respectively;
SEQ ID NOs: 178, 179, and 180, respectively;
SEQ ID NOs: 184, 185, and 186, respectively;
SEQ ID NOs: 190, 191, and 192, respectively;
SEQ ID NOs: 196, 197, and 198, respectively;
SEQ ID NOs: 202, 203, and 204, respectively; and
SEQ ID NOs: 208, 209, and 210, respectively.
In one embodiment,
the VL and VH are selected from the group consisting of:
a) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 58, 59, and 60, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 136, 137, and 138, respectively;
b) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 64, 65, and 66, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 142, 143, and 144, respectively;
c) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 70, 71, and 72, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 148, 149, and 150, respectively;
d) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 76, 77, and 6780, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 154, 155, and 156, respectively;
e) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 82, 83, and 84, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 160, 161, and 162, respectively;
f) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 88, 89, and 90, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 166, 167, and 168, respectively;
g) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 94, 95, and 96, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 172, 173, and 174, respectively;
h) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 100, 101, and 102, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 178, 179, and 180, respectively;
i) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 106, 107, and 108, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 184, 185, and 186, respectively;
j) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 112, 113, and 114, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 190, 191, and 192, respectively;
k) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 118, 119, and 120, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 196, 197, and 198, respectively;
l) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 124, 125, and 126, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 202, 203, and 204, respectively; and
m) a VL comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 130, 131, and 132, respectively; and a VH comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 208, 209, and 210, respectively.
In one embodiment,
the VL comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53; and
the VH comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, and 54.
In one embodiment,
the VL and VH are selected from the group consisting of:
a) a VL comprising SEQ ID NO: 5 and a VH comprising SEQ ID NO: 6;
b) a VL comprising SEQ ID NO: 9 and a VH comprising SEQ ID NO: 10;
c) a VL comprising SEQ ID NO: 13 and a VH comprising SEQ ID NO: 14;
d) a VL comprising SEQ ID NO: 17 and a VH comprising SEQ ID NO: 18;
e) a VL comprising SEQ ID NO: 21 and a VH comprising SEQ ID NO: 22;
f) a VL comprising SEQ ID NO: 25 and a VH comprising SEQ ID NO: 26;
g) a VL comprising SEQ ID NO: 29 and a VH comprising SEQ ID NO: 30;
h) a VL comprising SEQ ID NO: 33 and a VH comprising SEQ ID NO: 34;
i) a VL comprising SEQ ID NO: 37 and a VH comprising SEQ ID NO: 38;
j) a VL comprising SEQ ID NO: 41 and a VH comprising SEQ ID NO: 42;
k) a VL comprising SEQ ID NO: 45 and a VH comprising SEQ ID NO: 46;
l) a VL comprising SEQ ID NO: 49 and a VH comprising SEQ ID NO: 50; and
m) a VL comprising SEQ ID NO: 53 and a VH comprising SEQ ID NO: 54.
In one embodiment, the antigen binding protein further comprises a second antigen binding portion that specifically binds a second antigen.
In one embodiment, the second antigen is a tumor associated antigen (TAA).
“Antibody constructs” according to the invention are fragments of full-length antibodies, such as VH, VHH, VL, (s)dAb, Fv, Fd, Fab, Fab′, F(ab′)2 or “r IgG” (“half antibody”). Antibody constructs according to the invention may also be modified fragments of antibodies, also called antibody variants, such as scFv, di-scFv or bi(s)-scFv, scFv-Fc, scFv-zipper, scFab, Fab2, Fab3, diabodies, single chain diabodies, tandem diabodies (Tandab's), tandem di-scFv, tandem tri-scFv, “minibodies” exemplified by a structure which is as follows: (VH-VL-CH3)2, (scFv-CH3)2, ((scFv)2-CH3+CH3), ((scFv)2-CH3) or (scFv-CH3-scFv)2, multibodies such as triabodies or tetrabodies, and single domain antibodies such as nanobodies or single variable domain antibodies comprising merely one variable domain, which might be VHH, VH or VL, that specifically bind an antigen or epitope independently of other V regions or domains. Also, included within the definition of “antibody construct” are multispecific molecules that incorporate multiple types of antibodies and antibody constructs, for example, IgG-scFv which comprises a scFv linked to an IgG or an IgG-Fab, which comprises a Fab fragment linked to an IgG. In one embodiment, a scFv linked to an immunoglobulin heavy chain is called “a heavy chain fusion protein”. In another embodiment, a VH-CH1 polypeptide linked to an immunoglobulin heavy chain is called “a heavy chain fusion protein”.
A “binding domain”, or “antigen binding domain”, may typically comprise an antibody light chain variable region (VL) and an antibody heavy chain variable region (VH); however, it does not have to comprise both. Fd fragments, for example, have two VH regions and often retain some antigen-binding function of the intact antigen-binding domain. Additional examples for the format of antibody fragments, antibody variants or binding domains include (1) a Fab fragment, a monovalent fragment having the VL, VH, CL and CH1 domains; (2) a F(ab′)2 fragment, a bivalent fragment having two Fab fragments linked by a disulfide bridge at the hinge region; (3) an Fd fragment having the two VH and CH1 domains; (4) an Fv fragment having the VL and VH domains of a single arm of an antibody, (5) a dAb fragment (Ward et al., (1989) Nature 341:544-546), which has a VH domain; (6) an isolated complementarity determining region (CDR), and (7) a single chain Fv (scFv), the latter being preferred (for example, derived from an scFV-library). Examples for embodiments of antibody constructs according to the invention are e.g. described in WO 00/006605, WO 2005/040220, WO 2008/1 19567, WO 2010/037838, WO 2013/026837, WO 2013/026833, US 2014/0308285, US 2014/0302037, W 02014/144722, WO 2014/151910, and WO 2015/048272.
Furthermore, the definition of the term “antibody construct” includes monovalent, bivalent and polyvalent/multivalent constructs and, thus, monospecific constructs, specifically binding to only one antigenic structure, as well as bispecific and multispecific constructs, which specifically bind more than one antigenic structure, e.g. two, three or more, through distinct binding domains.
Moreover, the definition of the term “antibody construct” includes molecules consisting of only one polypeptide chain as well as molecules consisting of more than one polypeptide chain, which chains can be either identical (homodimers, homotrimers or homo oligomers) or different (heterodimer, heterotrimer or heterooligomer). Examples for the above identified antibodies and variants or derivatives thereof are described inter alia in Harlow and Lane, Antibodies a laboratory manual, CSHL Press (1988) and Using Antibodies: a laboratory manual, CSHL Press (1999), Kontermann and Dubel, Antibody Engineering, Springer, 2nd ed. 2010 and Little, Recombinant Antibodies for Immunotherapy, Cambridge University Press 2009.
The antibody constructs of the present invention are preferably “in vitro generated antibody constructs”. This term refers to an antibody construct according to the above definition where all or part of the variable region (e.g., at least one CDR) is generated in a non-immune cell selection, e.g., an in vitro phage display, protein chip or any other method in which candidate sequences can be tested for their ability to bind to an antigen. This term thus preferably excludes sequences generated solely by genomic rearrangement in an immune cell in an animal. A “recombinant antibody” is an antibody made through the use of recombinant DNA technology or genetic engineering.
In one aspect, the present invention is directed to a multispecific antibody construct comprising:
(i) a first antibody comprising two light chains and two heavy chains, wherein
the light chains comprise a first variable region (VL1) and a light chain constant region (CL);
the heavy chains comprise a first heavy variable region (VH1) and CH1, hinge, CH2, and CH3 regions;
the heavy chains comprise at least one amino acid substitution that results in a reduced binding affinity of the heavy chain for human Fc gamma RI receptor as compared with an unsubstituted heavy chain; and
(ii) a scFv comprising a second light chain variable region (VL2) and a second heavy chain variable region (VH2) of a second antibody, wherein the VL2 and the VH2 are connected via a first peptide linker,
wherein the scFv is fused at its amino terminus to the carboxyl terminus of each of the heavy chains through a second peptide linker such that a heavy chain fusion protein is formed; and
wherein the first antibody specifically binds to and agonizes human CD40 (SEQ ID NO: 1) and the scFv specifically binds to human mesothelin (MSLN) (SEQ ID NO: 2).
In one embodiment, the multispecific antibody construct specifically agonizes CD40 in a MSLN-dependent fashion.
In one embodiment, the multispecific antibody construct comprises mutations limiting Fc receptor binding and thus decreases Fc receptor-dependent CD40 agonism.
In one embodiment, the two light chains are identical and the two heavy chain fusion proteins are identical.
In one embodiment, the VL1 comprises a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of:
SEQ ID NOs: 58, 59, and 60, respectively;
SEQ ID NOs: 64, 65, and 66, respectively;
SEQ ID NOs: 70, 71, and 72, respectively;
SEQ ID NOs: 76, 77, and 78, respectively;
SEQ ID NOs: 82, 83, and 84, respectively;
SEQ ID NOs: 88, 89, and 90, respectively;
SEQ ID NOs: 94, 95, and 96, respectively;
SEQ ID NOs: 100, 101, and 102, respectively;
SEQ ID NOs: 106, 107, and 108, respectively;
SEQ ID NOs: 112, 113, and 114, respectively;
SEQ ID NOs: 118, 119, and 120, respectively;
SEQ ID NOs: 124, 125, and 126, respectively; and
SEQ ID NOs: 130, 131, and 132, respectively;
the VH1 comprises a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of:
SEQ ID NOs: 136, 137, and 138, respectively;
SEQ ID NOs: 142, 143, and 144, respectively;
SEQ ID NOs: 148, 149, and 150, respectively;
SEQ ID NOs: 154, 155, and 156, respectively;
SEQ ID NOs: 160, 161, and 162, respectively;
SEQ ID NOs: 166, 167, and 168, respectively;
SEQ ID NOs: 172, 173, and 174, respectively;
SEQ ID NOs: 178, 179, and 180, respectively;
SEQ ID NOs: 184, 185, and 186, respectively;
SEQ ID NOs: 190, 191, and 192, respectively;
SEQ ID NOs: 196, 197, and 198, respectively;
SEQ ID NOs: 202, 203, and 204, respectively; and
SEQ ID NOs: 208, 209, and 210, respectively;
the VL2 comprises a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of:
SEQ ID NOs: 230, 231, and 232, respectively;
SEQ ID NOs: 236, 237, and 238, respectively;
SEQ ID NOs: 242, 243, and 244, respectively; and
SEQ ID NOs: 248, 249, and 250, respectively;
and the VH2 comprises a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of:
SEQ ID NOs: 254, 255, and 256, respectively;
SEQ ID NOs: 260, 261, and 262, respectively;
SEQ ID NOs: 266, 267, and 268, respectively; and
SEQ ID NOs: 272, 273, and 274, respectively.
In one embodiment, 1) the VL1 and VH1 are selected from the group consisting of:
a) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 58, 59, and 60, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 136, 137, and 138, respectively;
b) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 64, 65, and 66, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 142, 143, and 144, respectively;
c) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 70, 71, and 72, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 148, 149, and 150, respectively;
d) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 76, 77, and 6780, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 154, 155, and 156, respectively;
e) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 82, 83, and 84, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 160, 161, and 162, respectively;
f) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 88, 89, and 90, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 166, 167, and 168, respectively;
g) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 94, 95, and 96, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 172, 173, and 174, respectively;
h) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 100, 101, and 102, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 178, 179, and 180, respectively;
i) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 106, 107, and 108, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 184, 185, and 186, respectively;
j) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 112, 113, and 114, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 190, 191, and 192, respectively;
k) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 118, 119, and 120, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 196, 197, and 198, respectively;
l) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 124, 125, and 126, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 202, 203, and 204, respectively; and
m) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 130, 131, and 132, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 208, 209, and 210, respectively;
and
2) the VL2 and VH2 are selected from the group consisting of:
a) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 230, 231, and 232, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 254, 255, and 256, respectively;
b) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 236, 237, and 238, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 260, 261, and 262, respectively;
c) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 242, 243, and 244, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 266, 267, and 268, respectively; and
d) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 248, 249, and 250, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 272, 273, and 274, respectively.
In one embodiment, the VL1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53;
the VH1 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, and 54;
the VL2 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 213, 217, 221, and 225;
the VH2 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 214, 218, 222, and 226.
In one embodiment,
1) the VL1 and VH1 are selected from the group consisting of:
a) a VL1 comprising SEQ ID NO: 5 and a VH1 comprising SEQ ID NO: 6;
b) a VL1 comprising SEQ ID NO: 9 and a VH1 comprising SEQ ID NO: 10;
c) a VL1 comprising SEQ ID NO: 13 and a VH1 comprising SEQ ID NO: 14;
d) a VL1 comprising SEQ ID NO: 17 and a VH1 comprising SEQ ID NO: 18;
e) a VL1 comprising SEQ ID NO: 21 and a VH1 comprising SEQ ID NO: 22;
f) a VL1 comprising SEQ ID NO: 25 and a VH1 comprising SEQ ID NO: 26;
g) a VL1 comprising SEQ ID NO: 29 and a VH1 comprising SEQ ID NO: 30;
h) a VL1 comprising SEQ ID NO: 33 and a VH1 comprising SEQ ID NO: 34;
i) a VL1 comprising SEQ ID NO: 37 and a VH1 comprising SEQ ID NO: 38;
j) a VL1 comprising SEQ ID NO: 41 and a VH1 comprising SEQ ID NO: 42;
k) a VL1 comprising SEQ ID NO: 45 and a VH1 comprising SEQ ID NO: 46;
l) a VL1 comprising SEQ ID NO: 49 and a VH1 comprising SEQ ID NO: 50; and
m) a VL1 comprising SEQ ID NO: 53 and a VH1 comprising SEQ ID NO: 54;
and
2) the VL2 and VH2 are selected from the group consisting of:
a) a VL2 comprising SEQ ID NO: 213 and a VH2 comprising SEQ ID NO: 214;
b) a VL2 comprising SEQ ID NO: 217 and a VH2 comprising SEQ ID NO: 218;
c) a VL2 comprising SEQ ID NO: 221 and a VH2 comprising SEQ ID NO: 222; and
d) a VL2 comprising SEQ ID NO: 225 and a VH2 comprising SEQ ID NO: 226.
In one embodiment,
the light chain comprises a sequence selected from the group consisting of SEQ ID NOs: 286, 290, 294, 298, 302, 306, 310, 314, 318, 322, 326, 330, 336, 342, 346, 350, 354, 358, 362, 366, 370, 374, and 378; and
the heavy chain fusion protein comprises a sequence selected from the group consisting of SEQ ID Nos: 285, 289, 293, 297, 301, 305, 309, 313, 317, 321, 325, 329, 333, 337, 341, 345, 349, 353, 357, 361, 365, 369, 373, and 377.
In one embodiment, the light chain and the heavy chain fusion protein comprise polypeptides comprising amino acid sequences selected from the group consisting of:
SEQ ID NO: 286 and SEQ ID NO: 285, respectively;
SEQ ID NO: 290 and SEQ ID NO: 289, respectively;
SEQ ID NO: 294 and SEQ ID NO: 293, respectively;
SEQ ID NO: 298 and SEQ ID NO: 297, respectively;
SEQ ID NO: 302 and SEQ ID NO: 301, respectively;
SEQ ID NO: 306 and SEQ ID NO: 305, respectively;
SEQ ID NO: 310 and SEQ ID NO: 309, respectively;
SEQ ID NO: 314 and SEQ ID NO: 313, respectively;
SEQ ID NO: 318 and SEQ ID NO: 317, respectively;
SEQ ID NO: 322 and SEQ ID NO: 321, respectively;
SEQ ID NO: 326 and SEQ ID NO: 325, respectively;
SEQ ID NO: 330 and SEQ ID NO: 329, respectively;
SEQ ID NO: 334 and SEQ ID NO: 333, respectively;
SEQ ID NO: 338 and SEQ ID NO: 337, respectively;
SEQ ID NO: 342 and SEQ ID NO: 341, respectively;
SEQ ID NO: 346 and SEQ ID NO: 345, respectively;
SEQ ID NO: 350 and SEQ ID NO: 349, respectively;
SEQ ID NO: 354 and SEQ ID NO: 353, respectively;
SEQ ID NO: 358 and SEQ ID NO: 357, respectively;
SEQ ID NO: 362 and SEQ ID NO: 361, respectively;
SEQ ID NO: 366 and SEQ ID NO: 365, respectively;
SEQ ID NO: 370 and SEQ ID NO: 369, respectively;
SEQ ID NO: 374 and SEQ ID NO: 373, respectively; and
SEQ ID NO: 378 and SEQ ID NO: 377, respectively.
In another aspect, the present invention is directed to a multispecific antibody construct comprising:
(i) a first antibody comprising two light chains and two heavy chains, wherein
the light chains comprise a first variable region (VL1) and a light chain constant region (CL);
the heavy chains comprise a first heavy variable region (VH1) and CH1, hinge, CH2, and CH3 regions;
the heavy chains comprise at least one amino acid substitution that results in a reduced binding affinity of the heavy chain for human Fc gamma RI receptor as compared with an unsubstituted heavy chain; and
(ii) a scFv comprising a second light chain variable region (VL2) and a second heavy chain variable region (VH2) of a second antibody, wherein the VL2 and the VH2 are connected via a first peptide linker,
wherein the scFv is fused at its amino terminus to the carboxyl terminus of each of the heavy chains through a second peptide linker such that a heavy chain fusion protein is formed; and
wherein the first antibody specifically binds to human mesothelin (MSLN) (SEQ ID NO: 2) and the scFv specifically binds to and agonizes human CD40 (SEQ ID NO: 1).
In one embodiment, the multispecific antibody construct specifically agonizes CD40 in a MSLN-dependent fashion.
In one embodiment, the multispecific antibody construct comprises mutations limiting Fc receptor binding and thus decreases Fc receptor-dependent CD40 agonism.
In one embodiment, the two light chains are identical and the two heavy chain fusion proteins are identical.
In one embodiment:
the VL1 comprises a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of:
SEQ ID NOs: 230, 231, and 232, respectively;
SEQ ID NOs: 236, 237, and 238, respectively;
SEQ ID NOs: 242, 243, and 244, respectively; and
SEQ ID NOs: 248, 249, and 250, respectively;
the VH1 comprises a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of:
SEQ ID NOs: 254, 255, and 256, respectively;
SEQ ID NOs: 260, 261, and 262, respectively;
SEQ ID NOs: 266, 267, and 268, respectively; and
SEQ ID NOs: 272, 273, and 274, respectively;
the VL2 comprises a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of:
SEQ ID NOs: 58, 59, and 60, respectively;
SEQ ID NOs: 64, 65, and 66, respectively;
SEQ ID NOs: 70, 71, and 72, respectively;
SEQ ID NOs: 76, 77, and 78, respectively;
SEQ ID NOs: 82, 83, and 84, respectively;
SEQ ID NOs: 88, 89, and 90, respectively;
SEQ ID NOs: 94, 95, and 96, respectively;
SEQ ID NOs: 100, 101, and 102, respectively;
SEQ ID NOs: 106, 107, and 108, respectively;
SEQ ID NOs: 112, 113, and 114, respectively;
SEQ ID NOs: 118, 119, and 120, respectively;
SEQ ID NOs: 124, 125, and 126, respectively; and
SEQ ID NOs: 130, 131, and 132, respectively;
and
the VH2 comprises a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of:
SEQ ID NOs: 136, 137, and 138, respectively;
SEQ ID NOs: 142, 143, and 144, respectively;
SEQ ID NOs: 148, 149, and 150, respectively;
SEQ ID NOs: 154, 155, and 156, respectively;
SEQ ID NOs: 160, 161, and 162, respectively;
SEQ ID NOs: 166, 167, and 168, respectively;
SEQ ID NOs: 172, 173, and 174, respectively;
SEQ ID NOs: 178, 179, and 180, respectively;
SEQ ID NOs: 184, 185, and 186, respectively;
SEQ ID NOs: 190, 191, and 192, respectively;
SEQ ID NOs: 196, 197, and 198, respectively;
SEQ ID NOs: 202, 203, and 204, respectively; and
SEQ ID NOs: 208, 209, and 210, respectively.
In one embodiment,
1) the VL1 and VH1 are selected from the group consisting of:
a) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 230, 231, and 232, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 254, 255, and 256, respectively;
b) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 236, 237, and 238, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 260, 261, and 262, respectively;
c) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 242, 243, and 244, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 266, 267, and 268, respectively; and
d) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 248, 249, and 250, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 272, 273, and 274, respectively;
and
2) the VL2 and VH2 are selected from the group consisting of:
a) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 58, 59, and 60, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 136, 137, and 138, respectively;
b) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 64, 65, and 66, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 142, 143, and 144, respectively;
c) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 70, 71, and 72, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 148, 149, and 150, respectively;
d) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 76, 77, and 6780, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 154, 155, and 156, respectively;
e) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 82, 83, and 84, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 160, 161, and 162, respectively;
f) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 88, 89, and 90, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 166, 167, and 168, respectively;
g) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 94, 95, and 96, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 172, 173, and 174, respectively;
h) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 100, 101, and 102, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 178, 179, and 180, respectively;
i) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 106, 107, and 108, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 184, 185, and 186, respectively;
j) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 112, 113, and 114, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 190, 191, and 192, respectively;
k) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 118, 119, and 120, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 196, 197, and 198, respectively;
l) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 124, 125, and 126, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 202, 203, and 204, respectively; and
m) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 130, 131, and 132, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 208, 209, and 210, respectively.
In one embodiment:
the VL1 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 213, 217, 221, and 225;
the VH1 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 214, 218, 222, and 226;
the VL2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53; and
the VH2 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, and 54.
In one embodiment:
1) the VL1 and VH1 are selected from the group consisting of:
a) a VL1 comprising SEQ ID NO: 213 and a VH1 comprising SEQ ID NO: 214;
b) a VL1 comprising SEQ ID NO: 217 and a VH1 comprising SEQ ID NO: 218;
c) a VL1 comprising SEQ ID NO: 221 and a VH1 comprising SEQ ID NO: 222; and
d) a VL1 comprising SEQ ID NO: 225 and a VH1 comprising SEQ ID NO: 226;
and
2) the VL2 and VH2 are selected from the group consisting of:
a) a VL2 comprising SEQ ID NO: 5 and a VH2 comprising SEQ ID NO: 6;
b) a VL2 comprising SEQ ID NO: 9 and a VH2 comprising SEQ ID NO: 10;
c) a VL2 comprising SEQ ID NO: 13 and a VH2 comprising SEQ ID NO: 14;
d) a VL2 comprising SEQ ID NO: 17 and a VH2 comprising SEQ ID NO: 18;
e) a VL2 comprising SEQ ID NO: 21 and a VH2 comprising SEQ ID NO: 22;
f) a VL2 comprising SEQ ID NO: 25 and a VH2 comprising SEQ ID NO: 26;
g) a VL2 comprising SEQ ID NO: 29 and a VH2 comprising SEQ ID NO: 30;
h) a VL2 comprising SEQ ID NO: 33 and a VH2 comprising SEQ ID NO: 34;
i) a VL2 comprising SEQ ID NO: 37 and a VH2 comprising SEQ ID NO: 38;
j) a VL2 comprising SEQ ID NO: 41 and a VH2 comprising SEQ ID NO: 42;
k) a VL2 comprising SEQ ID NO: 45 and a VH2 comprising SEQ ID NO: 46;
l) a VL2 comprising SEQ ID NO: 49 and a VH2 comprising SEQ ID NO: 50; and
m) a VL2 comprising SEQ ID NO: 53 and a VH2 comprising SEQ ID NO: 54.
In one embodiment, the CL of the light chain is selected from the group consisting of SEQ ID NO: 883 and SEQ ID NO: 884.
In one embodiment, the CH1-hinge-CH2-CH3 of the heavy chain is selected from the group consisting of SEQ ID NO: 885 and SEQ ID NO: 886.
In one embodiment, the first peptide linker is selected from the group consisting of SEQ ID NOs: 888-893.
In one embodiment, the second peptide linker is selected from the group consisting of SEQ ID NOs: 887-893.
In one embodiment, the first peptide linker comprises SEQ ID NO: 889 and the second peptide linker comprises SEQ ID NO: 887.
In one embodiment,
the light chain comprises a sequence selected from the group consisting of SEQ ID NOs: 382, 386, 390, 394, 398, 402, 406, 410, 414, 418, 422, 426, 430, 434, 438, 442, 446, and 450; and
the heavy chain fusion protein comprises a sequence selected from the group consisting of SEQ ID NOs: 381, 385, 389, 393, 397, 401, 405, 409, 413, 417, 421, 425, 429, 433, 437, 441, 445, and 449.
In one embodiment, the light chain and the heavy chain fusion protein comprise polypeptides comprising amino acid sequences selected from the group consisting of:
SEQ ID NO: 382 and SEQ ID NO: 381, respectively;
SEQ ID NO: 386 and SEQ ID NO: 385, respectively;
SEQ ID NO: 390 and SEQ ID NO: 389, respectively;
SEQ ID NO: 394 and SEQ ID NO: 393, respectively;
SEQ ID NO: 398 and SEQ ID NO: 397, respectively;
SEQ ID NO: 402 and SEQ ID NO: 401, respectively;
SEQ ID NO: 406 and SEQ ID NO: 405, respectively;
SEQ ID NO: 410 and SEQ ID NO: 409, respectively;
SEQ ID NO: 414 and SEQ ID NO: 413, respectively;
SEQ ID NO: 418 and SEQ ID NO: 417, respectively;
SEQ ID NO: 422 and SEQ ID NO: 421, respectively;
SEQ ID NO: 426 and SEQ ID NO: 425, respectively;
SEQ ID NO: 430 and SEQ ID NO: 429, respectively;
SEQ ID NO: 434 and SEQ ID NO: 433, respectively;
SEQ ID NO: 438 and SEQ ID NO: 437, respectively;
SEQ ID NO: 442 and SEQ ID NO: 441, respectively;
SEQ ID NO: 446 and SEQ ID NO: 445, respectively; and
SEQ ID NO: 450 and SEQ ID NO: 449, respectively.
In one embodiment, the CL of the light chain is selected from the group consisting of SEQ ID NO: 883 and SEQ ID NO: 884.
In one embodiment, the CH1-hinge-CH2-CH3 of the heavy chain is selected from the group consisting of SEQ ID NO: 885 and SEQ ID NO: 886.
In one embodiment, the first peptide linker is selected from the group consisting of SEQ ID NOs: 888-893.
In one embodiment, the second peptide linker is selected from the group consisting of SEQ ID NOs: 887-893.
In one embodiment, the first peptide linker comprises SEQ ID NO: 889 and the second peptide linker comprises SEQ ID NO: 887.
The term “monoclonal antibody” (mAb) or monoclonal antibody construct as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations and/or post-translation modifications (e.g., isomerizations, amidations) that may be present in minor amounts. Monoclonal antibodies are highly specific, being directed against a single antigenic site or determinant on the antigen, in contrast to conventional (polyclonal) antibody preparations which typically include different antibodies directed against different determinants (or epitopes). In addition to their specificity, the monoclonal antibodies are advantageous in that they are synthesized by the hybridoma culture, hence uncontaminated by other immunoglobulins. The modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method.
For the preparation of monoclonal antibodies, any technique providing antibodies produced by continuous cell line cultures can be used. For example, monoclonal antibodies to be used may be made by the hybridoma method first described by Koehler et al., Nature, 256: 495 (1975), or may be made by recombinant DNA methods (see, e.g., U.S. Pat. No. 4,816,567). Examples for further techniques to produce human monoclonal antibodies include the trioma technique, the human B-cell hybridoma technique (Kozbor, Immunology Today 4 (1983), 72) and the EBV-hybridoma technique (Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc. (1985), 77-96).
Hybridomas can then be screened using standard methods, such as enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (BIACORETM) analysis, to identify one or more hybridomas that produce an antibody that specifically binds with a specified antigen. Any form of the relevant antigen may be used as the immunogen, e.g., recombinant antigen, naturally occurring forms, any variants or fragments thereof, as well as an antigenic peptide thereof. Surface plasmon resonance as employed in the BIAcore system can be used to increase the efficiency of phage antibodies which bind to an epitope of a target antigen, such as MSLN or CD40 (Schier, Human Antibodies Hybridomas 7 (1996), 97-105; Malmborg, J. Immunol. Methods 183 (1995), 7-13).
Another exemplary method of making monoclonal antibodies includes screening protein expression libraries, e.g., phage display or ribosome display libraries. Phage display is described, for example, in Ladner et al., U.S. Pat. No. 5,223,409; Smith (1985) Science 228:1315-1317, Clackson et al., Nature, 352: 624-628 (1991) and Marks et al., J. Mol. Biol., 222: 581-597 (1991).
In addition to the use of display libraries, the relevant antigen can be used to immunize a non-human animal, e.g., a rodent (such as a mouse, hamster, rabbit or rat). In one embodiment, the non-human animal includes at least a part of a human immunoglobulin gene. For example, it is possible to engineer mouse strains deficient in mouse antibody production with large fragments of the human Ig (immunoglobulin) loci. Using the hybridoma technology, antigen-specific monoclonal antibodies derived from the genes with the desired specificity may be produced and selected. See, e.g., XENOMOUSETM, Green et al. (1994) Nature Genetics 7:13-21, US 2003-0070185, WO 96/34096, and WO 96/33735.
A monoclonal antibody can also be obtained from a non-human animal, and then modified, e.g., humanized, deimmunized, rendered chimeric etc., using recombinant DNA techniques known in the art. Examples of modified antibody constructs include humanized variants of non-human antibodies, “affinity matured” antibodies (see, e.g. Hawkins et al. J. Mol. Biol. 254, 889-896 (1992) and Lowman et al., Biochemistry 30, 10832-10837 (1991)) and antibody mutants with altered effector function(s) (see, e.g., U.S. Pat. No. 5,648,260, Kontermann and Dubel (2010), loc. cit. and Little (2009), loc. cit).
In immunology, affinity maturation is the process by which B cells produce antibodies with increased affinity for antigen during the course of an immune response. With repeated exposures to the same antigen, a host will produce antibodies of successively greater affinities. Like the natural prototype, the in vitro affinity maturation is based on the principles of mutation and selection. The in vitro affinity maturation has successfully been used to optimize antibodies, antibody constructs, and antibody fragments. Random mutations inside the CDRs are introduced using radiation, chemical mutagens or error-prone PCR. In addition, the genetical diversity can be increased by chain shuffling.
Two or three rounds of mutation and selection using display methods like phage display usually results in antibody fragments with affinities in the low nanomolar range.
A preferred type of an amino acid substitutional variation of the antibody constructs involves substituting one or more hypervariable region residues of a parent antibody (e. g. a humanized or human antibody). Generally, the resulting variant(s) selected for further development will have improved biological properties relative to the parent antibody from which they are generated. A convenient way for generating such substitutional variants involves affinity maturation using phage display. Briefly, several hypervariable region sites (e. g. 6-7 sites) are mutated to generate all possible amino acid substitutions at each site. The antibody variants thus generated are displayed in a monovalent fashion from filamentous phage particles as fusions to the gene III product of M13 packaged within each particle. The phage-displayed variants are then screened for their biological activity (e. g. binding affinity) as herein disclosed. In order to identify candidate hypervariable region sites for modification, alanine scanning mutagenesis can be performed to identify hypervariable region residues contributing significantly to antigen binding. Alternatively, or additionally, it may be beneficial to analyze a crystal structure of the antigen-antibody complex to identify contact points between the binding domain and, e.g., human MSLN. Such contact residues and neighboring residues are candidates for substitution according to the techniques elaborated herein. Once such variants are generated, the panel of variants is subjected to screening as described herein and antibodies with superior properties in one or more relevant assays may be selected for further development.
The monoclonal antibodies and antibody constructs of the present invention specifically include “chimeric” antibodies (immunoglobulins) in which a portion of the heavy and/or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is/are identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit the desired biological activity (U.S. Pat. No. 4,816,567; Morrison et al., Proc. Natl. Acad. Sci. USA, 81: 6851-6855 (1984)). Chimeric antibodies of interest herein include “primitized” antibodies comprising variable domain antigen-binding sequences derived from a non-human primate (e.g., Old World Monkey, Ape etc.) and human constant region sequences. A variety of approaches for making chimeric antibodies have been described. See e.g., Morrison et al., Proc. Natl. Acad. ScL U.S.A. 81:6851, 1985; Takeda et al., Nature 314:452, 1985, Cabilly et al., U.S. Pat. No. 4,816,567; Boss et al., U.S. Pat. No. 4,816,397; Tanaguchi et al., EP 0171496; EP 0173494; and GB 2177096.
An antibody, antibody construct, antibody fragment or antibody variant may also be modified by specific deletion of human T cell epitopes (a method called “deimmunization”) by the methods disclosed for example in WO 98/52976 or WO 00/34317. Briefly, the heavy and light chain variable domains of an antibody can be analyzed for peptides that bind to MHC class II; these peptides represent potential T cell epitopes (as defined in WO 98/52976 and WO 00/34317). For detection of potential T cell epitopes, a computer modeling approach termed “peptide threading” can be applied, and in addition a database of human MHC class II binding peptides can be searched for motifs present in the VH and VL sequences, as described in WO 98/52976 and WO 00/34317. These motifs bind to any of the 18 major MHC class II DR allotypes, and thus constitute potential T cell epitopes. Potential T cell epitopes detected can be eliminated by substituting small numbers of amino acid residues in the variable domains, or preferably, by single amino acid substitutions. Typically, conservative substitutions are made. Often, but not exclusively, an amino acid common to a position in human germline antibody sequences may be used. Human germline sequences are disclosed e.g. in Tomlinson, et al. (1992) J. Mol. Biol. 227:776-798; Cook, G. P. et al. (1995) Immunol. Today Vol. 16 (5): 237-242; and Tomlinson et al. (1995) EMBO J. 14: 14:4628-4638. The V BASE directory provides a comprehensive directory of human immunoglobulin variable region sequences (compiled by Tomlinson, LA. et al. MRC Centre for Protein Engineering, Cambridge, UK). These sequences can be used as a source of human sequence, e.g., for framework regions and CDRs. Consensus human framework regions can also be used, for example as described in U.S. Pat. No. 6,300,064.
“Humanized” antibodies, antibody constructs, variants or fragments thereof (such as Fv, Fab, Fab′, F(ab′)2 or other antigen-binding subsequences of antibodies) are antibodies or immunoglobulins of mostly human sequences, which contain (a) minimal sequence(s) derived from non-human immunoglobulin. For the most part, humanized antibodies are human immunoglobulins (recipient antibody) in which residues from a hypervariable region (also CDR) of the recipient are replaced by residues from a hypervariable region of a non-human (e.g., rodent) species (donor antibody) such as mouse, rat, hamster or rabbit having the desired specificity, affinity, and capacity. In some instances, Fv framework region (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, “humanized antibodies” as used herein may also comprise residues which are found neither in the recipient antibody nor the donor antibody. These modifications are made to further refine and optimize antibody performance. The humanized antibody may also comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. For further details, see Jones et al., Nature, 321: 522-525 (1986); Reichmann et al., Nature, 332: 323-329 (1988); and Presta, Curr. Op. Struct. Biol., 2: 593-596 (1992).
Humanized antibodies or fragments thereof can be generated by replacing sequences of the Fv variable domain that are not directly involved in antigen binding with equivalent sequences from human Fv variable domains. Exemplary methods for generating humanized antibodies or fragments thereof are provided by Morrison (1985) Science 229:1202-1207; by Oi et al. (1986) BioTechniques 4:214; and by U.S. Pat. Nos. 5,585,089; 5,693,761; 5,693,762; 5,859,205; and 6,407,213. Those methods include isolating, manipulating, and expressing the nucleic acid sequences that encode all or part of immunoglobulin Fv variable domains from at least one of a heavy or light chain. Such nucleic acids may be obtained from a hybridoma producing an antibody against a predetermined target, as described above, as well as from other sources. The recombinant DNA encoding the humanized antibody molecule can then be cloned into an appropriate expression vector.
Humanized antibodies may also be produced using transgenic animals such as mice that express human heavy and light chain genes, but are incapable of expressing the endogenous mouse immunoglobulin heavy and light chain genes. Winter describes an exemplary CDR grafting method that may be used to prepare the humanized antibodies described herein (U.S. Pat. No. 5,225,539). All of the CDRs of a particular human antibody may be replaced with at least a portion of a non-human CDR, or only some of the CDRs may be replaced with non-human CDRs. It is only necessary to replace the number of CDRs required for binding of the humanized antibody to a predetermined antigen.
A humanized antibody can be optimized by the introduction of conservative substitutions, consensus sequence substitutions, germline substitutions and/or back mutations. Such altered immunoglobulin molecules can be made by any of several techniques known in the art, (e.g., Teng et al., Proc. Natl. Acad. Sci. U.S.A., 80: 7308-7312, 1983; Kozbor et al., Immunology Today, 4: 7279, 1983; Olsson et ai, Meth. Enzymol., 92: 3-16, 1982, and EP 239 400).
The term “human antibody”, “human antibody construct” and “human binding domain” includes antibodies, antibody constructs and binding domains having antibody regions such as variable and constant regions or domains which correspond substantially to human germline immunoglobulin sequences known in the art, including, for example, those described by Kabat et al. (1991) (loc. cit.). The human antibodies, antibody constructs or binding domains of the invention may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo), for example in the CDRs, and in particular, in CDR3. The human antibodies, antibody constructs or binding domains can have at least one, two, three, four, five, or more positions replaced with an amino acid residue that is not encoded by the human germline immunoglobulin sequence. The definition of human antibodies, antibody constructs and binding domains as used herein also contemplates fully human antibodies, which include only non-artificially and/or genetically altered human sequences of antibodies as those can be derived by using technologies or systems such as the Xenomouse.
In some embodiments, the antibody constructs of the invention are “isolated” or “substantially pure” antibody constructs. “Isolated” or “substantially pure”, when used to describe the antibody constructs disclosed herein, means an antibody construct that has been identified, separated and/or recovered from a component of its production environment. Preferably, the antibody construct is free or substantially free of association with all other components from its production environment.
Contaminant components of its production environment, such as that resulting from recombinant transfected cells, are materials that would typically interfere with diagnostic or therapeutic uses for the polypeptide, and may include enzymes, hormones, and other proteinaceous or non-proteinaceous solutes. The antibody constructs may e.g constitute at least about 5%, or at least about 50% by weight of the total protein in a given sample. It is understood that the isolated protein may constitute from 5% to 99.9% by weight of the total protein content, depending on the circumstances. The polypeptide may be made at a significantly higher concentration through the use of an inducible promoter or high expression promoter, such that it is made at increased concentration levels. The definition includes the production of an antibody construct in a wide variety of organisms and/or host cells that are known in the art. In preferred embodiments, the antibody construct will be purified (1) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (2) to homogeneity by SDS-PAGE under non-reducing or reducing conditions using Coomassie blue or, preferably, silver stain. Ordinarily, however, an isolated antibody construct will be prepared by at least one purification step.
The term “binding domain” characterizes in connection with the present invention a domain which (specifically) binds to/interacts with/recognizes a given target epitope or a given target site on the target molecules (antigens), here: MSLN and CD40, respectively. The structure and function of the one binding domain (recognizing MSLN), and preferably also the structure and/or function of another binding domain (recognizing CD40), is/are based on the structure and/or function of an antibody, e.g. of a full-length or whole immunoglobulin molecule. According to the invention, the binding domains are characterized by the presence of three light chain CDRs (i.e. CDRL1, CDRL2 and CDRL3 of the VL region) and/or three heavy chain CDRs (i.e. CDRH1, CDRH2 and CDRH3 of the VH region). It is envisaged that the binding domains are produced by or obtainable by phage-display or library screening methods rather than by grafting CDR sequences from a pre-existing (monoclonal) antibody into a scaffold. According to the present invention, binding domains are in the form of one or more polypeptides. Such polypeptides may include proteinaceous parts and non-proteinaceous parts (e.g. chemical linkers or chemical cross-linking agents such as glutaraldehyde).
Proteins (including fragments thereof, preferably biologically active fragments, and peptides, usually having less than 30 amino acids) comprise two or more amino acids coupled to each other via a covalent peptide bond (resulting in a chain of amino acids). The term “polypeptide” as used herein describes a group of molecules, which usually consist of more than 30 amino acids. Polypeptides may further form multimers such as dimers, trimers and higher oligomers, i.e., consisting of more than one polypeptide molecule. Polypeptide molecules forming such dimers, trimers etc. may be identical or non-identical. The corresponding higher order structures of such multimers are, consequently, termed homo- or heterodimers, homo- or heterotrimers etc. An example for a hereteromultimer is an antibody molecule, which, in its naturally occurring form, consists of two identical light polypeptide chains and two identical heavy polypeptide chains. The terms “peptide”, “polypeptide” and “protein” also refer to naturally modified peptides/polypeptides/proteins wherein the modification is effected e.g. by post-translational modifications like glycosylation, acetylation, phosphorylation and the like. A “peptide”, “polypeptide” or “protein” when referred to herein may also be chemically modified such as pegylated. Such modifications are well known in the art and described herein below.
Preferably the binding domain which binds to MSLN and/or the binding domain which binds to CD40 is/are human binding domains. Antibodies and antibody constructs comprising at least one human binding domain avoid some of the problems associated with antibodies or antibody constructs that possess non-human such as rodent (e.g. murine, rat, hamster or rabbit) variable and/or constant regions. The presence of such rodent derived proteins can lead to the rapid clearance of the antibodies or antibody constructs or can lead to the generation of an immune response against the antibody or antibody construct by a patient. In order to avoid the use of rodent derived antibodies or antibody constructs, human or fully human antibodies/antibody constructs can be generated through the introduction of human antibody function into a rodent so that the rodent produces fully human antibodies.
The ability to clone and reconstruct megabase-sized human loci in YACs and to introduce them into the mouse germline provides a powerful approach to elucidating the functional components of very large or crudely mapped loci as well as generating useful models of human disease.
Furthermore, the use of such technology for substitution of mouse loci with their human equivalents could provide unique insights into the expression and regulation of human gene products during development, their communication with other systems, and their involvement in disease induction and progression.
An important practical application of such a strategy is the “humanization” of the mouse humoral immune system. Introduction of human immunoglobulin (Ig) loci into mice in which the endogenous Ig genes have been inactivated offers the opportunity to study the mechanisms underlying programmed expression and assembly of antibodies as well as their role in B-cell development.
Furthermore, such a strategy could provide an ideal source for production of fully human monoclonal antibodies (mAbs)—an important milestone towards fulfilling the promise of antibody therapy in human disease. Fully human antibodies or antibody constructs are expected to minimize the immunogenic and allergic responses intrinsic to mouse or mouse-derivatized mAbs and thus to increase the efficacy and safety of the administered antibodies/antibody constructs. The use of fully human antibodies or antibody constructs can be expected to provide a substantial advantage in the treatment of chronic and recurring human diseases, such as inflammation, autoimmunity, and cancer, which require repeated compound administrations.
One approach towards this goal was to engineer mouse strains deficient in mouse antibody production with large fragments of the human Ig loci in anticipation that such mice would produce a large repertoire of human antibodies in the absence of mouse antibodies. Large human Ig fragments would preserve the large variable gene diversity as well as the proper regulation of antibody production and expression. By exploiting the mouse machinery for antibody diversification and selection and the lack of immunological tolerance to human proteins, the reproduced human antibody repertoire in these mouse strains should yield high affinity antibodies against any antigen of interest, including human antigens. Using the hybridoma technology, antigen-specific human mAbs with the desired specificity could be readily produced and selected. This general strategy was demonstrated in connection with the generation of the first XenoMouse mouse strains (see Green et al. Nature Genetics 7:13-21 (1994)). The XenoMouse strains were engineered with yeast artificial chromosomes (YACs) containing 245 kb and 190 kb-sized germline configuration fragments of the human heavy chain locus and kappa light chain locus, respectively, which contained core variable and constant region sequences. The human Ig containing YACs proved to be compatible with the mouse system for both rearrangement and expression of antibodies and were capable of substituting for the inactivated mouse Ig genes. This was demonstrated by their ability to induce B cell development, to produce an adult-like human repertoire of fully human antibodies, and to generate antigen-specific human mAbs.
These results also suggested that introduction of larger portions of the human Ig loci containing greater numbers of V genes, additional regulatory elements, and human Ig constant regions might recapitulate substantially the full repertoire that is characteristic of the human humoral response to infection and immunization. The work of Green et al. was recently extended to the introduction of greater than approximately 80% of the human antibody repertoire through introduction of megabase sized, germline configuration YAC fragments of the human heavy chain loci and kappa light chain loci, respectively. See Mendez et al. Nature Genetics 15:146-156 (1997) and U.S. patent application Ser. No. 08/759,620.
The production of the XenoMouse mice is further discussed and delineated in U.S. patent application Ser. No. 07/466,008, Ser. No. 07/610,515, Ser. No. 07/919,297, Ser. No. 07/922,649, Ser. No. 08/031,801, Ser. No. 08/112,848, Ser. No. 08/234,145, Ser. No. 08/376,279, Ser. No. 08/430,938, Ser. No. 08/464,584, Ser. No. 08/464,582, Ser. No. 08/463,191, Ser. No. 08/462,837, Ser. No. 08/486,853, Ser. No. 08/486,857, Ser. No. 08/486,859, Ser. No. 08/462,513, Ser. No. 08/724,752, and Ser. No. 08/759,620; and U.S. Pat. Nos. 6,162,963; 6,150,584; 6,114,598; 6,075,181, and 5,939,598 and Japanese Patent Nos. 3 068 180 B2, 3 068 506 B2, and 3 068 507 B2. See also Mendez et al. Nature Genetics 15:146-156 (1997) and Green and Jakobovits J. Exp. Med. 188:483-495 (1998), EP 0 463 151 B1, WO 94/02602, WO 96/34096, WO 98/24893, WO 00/76310, and WO 03/47336.
In an alternative approach, others, including GenPharm International, Inc., have utilized a “minilocus” approach. In the minilocus approach, an exogenous Ig locus is mimicked through the inclusion of pieces (individual genes) from the Ig locus. Thus, one or more VH genes, one or more DH genes, one or more JH genes, a mu constant region, and a second constant region (preferably a gamma constant region) are formed into a construct for insertion into an animal. This approach is described in U.S. Pat. No. 5,545,807 to Surani et al. and U.S. Pat. Nos. 5,545,806; 5,625,825; 5,625,126; 5,633,425; 5,661,016; 5,770,429; 5,789,650; 5,814,318; 5,877,397; 5,874,299; and 6,255,458 each to Lonberg and Kay, U.S. Pat. Nos. 5,591,669 and 6,023,010 to Krimpenfort and Berns, U.S. Pat. Nos. 5,612,205; 5,721,367; and U.S. Pat. No. 5,789,215 to Berns et al., and U.S. Pat. No. 5,643,763 to Choi and Dunn, and GenPharm International U.S. patent application Ser. No. 07/574,748, Ser. No. 07/575,962, Ser. No. 07/810,279, Ser. No. 07/853,408, Ser. No. 07/904,068, Ser. No. 07/990,860, Ser. No. 08/053,131, Ser. No. 08/096,762, Ser. No. 08/155,301, Ser. No. 08/161,739, Ser. No. 08/165,699, Ser. No. 08/209,741. See also EP 0 546 073 B1, WO 92/03918, WO 92/22645, WO 92/22647, WO 92/22670, WO 93/12227, WO 94/00569, WO 94/25585, WO 96/14436, WO 97/13852, and WO 98/24884 and U.S. Pat. No. 5,981,175. See further Taylor et al. (1992), Chen et al. (1993), Tuaillon et al. (1993), Choi et al. (1993), Lonberg et al. (1994), Taylor et al. (1994), and Tuaillon et al. (1995), Fishwild et al. (1996).
Kirin has also demonstrated the generation of human antibodies from mice in which, through microcell fusion, large pieces of chromosomes, or entire chromosomes, have been introduced. See European Patent Application Nos. 773 288 and 843 961. Xenerex Biosciences is developing a technology for the potential generation of human antibodies. In this technology, SCID mice are reconstituted with human lymphatic cells, e.g., B and/or T cells. Mice are then immunized with an antigen and can generate an immune response against the antigen. See U.S. Pat. Nos. 5,476,996; 5,698,767; and 5,958,765.
Human anti-mouse antibody (HAMA) responses have led the industry to prepare chimeric or otherwise humanized antibodies. It is however expected that certain human anti-chimeric antibody (HACA) responses will be observed, particularly in chronic or multi-dose utilizations of the antibody.
Thus, it would be desirable to provide antibody constructs comprising a human binding domain against MSLN and a human binding domain against CD40 in order to vitiate concerns and/or effects of HAMA or HACA response.
The terms “(specifically) binds to”, (specifically) recognizes”, “is (specifically) directed to”, and “(specifically) reacts with” mean in accordance with this invention that a binding domain interacts or specifically interacts with a given epitope or a given target site on the target molecules (antigens), here: MSLN and CD40, respectively.
The term “epitope” refers to a site on an antigen to which a binding domain, such as an antibody or immunoglobulin, or a derivative, fragment or variant of an antibody or an immunoglobulin, specifically binds. An “epitope” is antigenic and thus the term epitope is sometimes also referred to herein as “antigenic structure” or “antigenic determinant”. Thus, the binding domain is an “antigen interaction site”. Said binding/interaction is also understood to define a “specific recognition”.
“Epitopes” can be formed both by contiguous amino acids or non-contiguous amino acids juxtaposed by tertiary folding of a protein. A “linear epitope” is an epitope where an amino acid primary sequence comprises the recognized epitope. A linear epitope typically includes at least 3 or at least 4, and more usually, at least 5 or at least 6 or at least 7, for example, about 8 to about 10 amino acids in a unique sequence.
A “conformational epitope”, in contrast to a linear epitope, is an epitope wherein the primary sequence of the amino acids comprising the epitope is not the sole defining component of the epitope recognized (e.g., an epitope wherein the primary sequence of amino acids is not necessarily recognized by the binding domain). Typically a conformational epitope comprises an increased number of amino acids relative to a linear epitope. With regard to recognition of conformational epitopes, the binding domain recognizes a three-dimensional structure of the antigen, preferably a peptide or protein or fragment thereof (in the context of the present invention, the antigenic structure for one of the binding domains is comprised within the MSLN protein). For example, when a protein molecule folds to form a three-dimensional structure, certain amino acids and/or the polypeptide backbone forming the conformational epitope become juxtaposed enabling the antibody to recognize the epitope. Methods of determining the conformation of epitopes include, but are not limited to, x-ray crystallography, two-dimensional nuclear magnetic resonance (2D-NMR) spectroscopy and site-directed spin labelling and electron paramagnetic resonance (EPR) spectroscopy.
A method for epitope mapping is described in the following: When a region (a contiguous amino acid stretch) in the human MSLN protein is exchanged/replaced with its corresponding region of a non-human and non-primate MSLN antigen (e.g., mouse MSLN, but others like chicken, rat, hamster, rabbit etc. might also be conceivable), a decrease in the binding of the binding domain is expected to occur, unless the binding domain is cross-reactive for the non-human, non-primate MSLN used. Said decrease is preferably at least 10%, 20%, 30%, 40%, or 50%; more preferably at least 60%, 70%, or 80%, and most preferably 90%, 95% or even 100% in comparison to the binding to the respective region in the human MSLN protein, whereby binding to the respective region in the human MSLN protein is set to be 100%. It is envisaged that the aforementioned human MSLN/non-human MSLN chimeras are expressed in CHO cells. The human MSLN/non-human MSLN chimeras may also be fused with a transmembrane domain and/or cytoplasmic domain of a different membrane-bound protein such as EpCAM, although such technique was not necessary for the method described in Examples 1 and 2.
In an alternative or additional method for epitope mapping, several truncated versions of the human MSLN extracellular domain can be generated in order to determine a specific region that is recognized by a binding domain. In these truncated versions, the different extracellular MSLN domains/sub-domains or regions are stepwise deleted, starting from the N-terminus. The truncated MSLN versions that may be expressed in CHO cells. It is also envisaged that the truncated MSLN versions may be fused with a transmembrane domain and/or cytoplasmic domain of a different membrane-bound protein such as EpCAM. It is also envisaged that the truncated MSLN versions may encompass a signal peptide domain at their N-terminus, for example a signal peptide derived from mouse IgG heavy chain signal peptide. It is furtherore envisaged that the truncated MSLN versions may encompass a v5 domain at their N-terminus (following the signal peptide) which allows verifying their correct expression on the cell surface. A decrease or a loss of binding is expected to occur with those truncated MSLN versions which do not encompass any more the MSLN region that is recognized by the binding domain. The decrease of binding is preferably at least 10%, 20%, 30%, 40%, 50%; more preferably at least 60%, 70%, 80%, and most preferably 90%, 95% or even 100%, whereby binding to the entire human MSLN protein (or its extracellular region or domain) is set to be 100%.
A further method to determine the contribution of a specific residue of a target antigen to the recognition by a antibody construct or binding domain is alanine scanning (see e.g. Morrison K L & Weiss G A. Cur Opin Chem Biol. 2001 June; 5(3):302-7), where each residue to be analyzed is replaced by alanine, e.g. via site-directed mutagenesis. Alanine is used because of its non-bulky, chemically inert, methyl functional group that nevertheless mimics the secondary structure references that many of the other amino acids possess. Sometimes bulky amino acids such as valine or leucine can be used in cases where conservation of the size of mutated residues is desired. Alanine scanning is a mature technology which has been used for a long period of time.
The interaction between the binding domain and the epitope or the region comprising the epitope implies that a binding domain exhibits appreciable affinity for the epitope/the region comprising the epitope on a particular protein or antigen (here: MSLN and CD40, respectively) and, generally, does not exhibit significant reactivity with proteins or antigens other than MSLN or CD40. “Appreciable affinity” includes binding with an affinity of about 10−6 M (KD) or stronger. Preferably, binding is considered specific when the binding affinity is about 10−42 to 10-8 M, 10−42 to 10−9 M, 10−12 to 10−10 M, 10−11 to 10−8 M, preferably of about 10−11 to 10−9 M. Whether a binding domain specifically reacts with or binds to a target can be tested readily by, inter alia, comparing the reaction of said binding domain with a target protein or antigen with the reaction of said binding domain with proteins or antigens other than MSLN or CD40. Preferably, a binding domain of the invention does not essentially or substantially bind to proteins or antigens other than MSLN or CD40 (e.g., one binding domain is not capable of binding to proteins other than MSLN and the other binding domain is not capable of binding to proteins other than CD40).
The term “does not essentially/substantially bind” or “is not capable of binding” means that a binding domain of the present invention does not bind a protein or antigen other than MSLN or CD40, i.e., does not show reactivity of more than 30%, preferably not more than 20%, more preferably not more than 10%, particularly preferably not more than 9%, 8%, 7%, 6% or 5% with proteins or antigens other than MSLN or CD40, whereby binding to MSLN or CD40, respectively, is set to be 100%.
Specific binding is believed to be effected by specific motifs in the amino acid sequence of the binding domain and the antigen. Thus, binding is achieved as a result of their primary, secondary and/or tertiary structure as well as the result of secondary modifications of said structures. The specific interaction of the antigen-interaction-site with its specific antigen may result in a simple binding of said site to the antigen. Moreover, the specific interaction of the antigen-interaction-site with its specific antigen may alternatively or additionally result in the initiation of a signal, e.g. due to the induction of a change of the conformation of the antigen, an oligomerization of the antigen, etc.
The Fc region of an antibody interacts with a number of Fc receptors and ligands, imparting an array of important functional capabilities referred to as effector functions. For IgG the Fc region comprises Ig domains CH2 and CH3. An important family of Fc receptors for the IgG isotype are the Fc gamma receptors (FcγRs). These receptors mediate communication between antibodies and the cellular arm of the immune system. In humans this protein family includes FcγRI (CD64), including isoforms FcγRIa, FcγRIb, and FcγRIc; FcγRII (CD32), including isoforms FcγRIIa (including allotypes H131 and R131), FcγRIIb (including FcγRIIb-1 and FcγRIIb-2), and FcγRIIc; and FcγRIII (CD16), including isoforms FcγRIIIa (including allotypes V158 and F158) and FcγRIIIb (including allotypes FcγRIIIb-NA1 and FcγRIIIb-NA2) (Jefferis et al., 2002, Immunol Lett 82:57-65). These receptors typically have an extracellular domain that mediates binding to Fc, a membrane spanning region, and an intracellular domain that may mediate some signaling event within the cell. These receptors are expressed in a variety of immune cells including monocytes, macrophages, neutrophils, dendritic cells, eosinophils, mast cells, platelets, B cells, large granular lymphocytes, Langerhans' cells, natural killer (NK) cells, and γδ T cells. Formation of the Fc/FcγR complex recruits these effector cells to sites of bound antigen, typically resulting in signaling events within the cells and important subsequent immune responses such as release of inflammation mediators, B cell activation, endocytosis, phagocytosis, and cytotoxic attack. The ability to mediate cytotoxic and phagocytic effector functions is a potential mechanism by which antibodies destroy targeted cells. The cell-mediated reaction wherein nonspecific cytotoxic cells that express FcγRs recognize bound antibody on a target cell and subsequently cause lysis of the target cell is referred to as antibody dependent cell-mediated cytotoxicity (ADCC). The cell-mediated reaction wherein nonspecific cytotoxic cells that express FcγRs recognize bound antibody on a target cell and subsequently cause phagocytosis of the target cell is referred to as antibody dependent cell-mediated phagocytosis (ADCP).
The different IgG subclasses have different affinities for the FcγRs, with lgG1 and lgG3 typically binding substantially better to the receptors than lgG2 and lgG4. All FcγRs bind the same region on IgG Fc, yet with different affinities: the high affinity binder FcγRI has a Kd for lgG1 of 10-8 M-1, whereas the low affinity receptors FcγRII and FcγRIII generally bind at 10−6 and 10−5 respectively.
By “Fc gamma receptor” or “FcγR” as used herein is meant any member of the family of proteins that bind the IgG antibody Fc region and are substantially encoded by the FcγR genes. In humans this family includes but is not limited to FcγRI (CD64), including isoforms FcγRIa, FcγRIb, and FcγRIc; FcγRII (CD32), including isoforms FcγRIIa (including allotypes H131 and R131), FcγRIIb (including FcγRIIb-1 and FcγRIIb-2), and FcγRIIc; and FcγRIII (CD16), including isoforms FcγRIIIa (including allotypes V158 and F158) and FcγRIIIb (including allotypes FcγRIIIb-NA1 and FcγRIIIb-NA2) (Jefferis et al., 2002, Immunol Lett 82:57-65), as well as any undiscovered human FcγRs or FcγR isoforms or allotypes. An FcγR may be from any organism, including but not limited to humans, mice, rats, rabbits, and monkeys. Mouse FcγRs include but are not limited to FcγRI (CD64), FcγRII (CD32), FcγRIII (CD16), and FcγRIII-2 (CD16-2), as well as any undiscovered mouse FcγRs or FcγR isoforms or allotypes.
Binding to FcγRs can be performed directly by determining the affinity of an antibody for the FcγR. Or binding can be determined indirectly by measuring cytokine release in a cell-based assay.
To facilitate the association of a particular heavy chain with its cognate light chain, both the heavy and light chains may contain complimentary amino acid substitutions. As used herein, “complimentary amino acid substitutions” refer to a substitution to a positively-charged amino acid in one chain paired with a negatively-charged amino acid substitution in the other chain. For example, in some embodiments, the heavy chain comprises at least one amino acid substitution to introduce a charged amino acid and the corresponding light chain comprises at least one amino acid substitution to introduce a charged amino acid, wherein the charged amino acid introduced into the heavy chain has the opposite charge of the amino acid introduced into the light chain. In certain embodiments, one or more positively-charged residues (e.g., lysine, histidine or arginine) can be introduced into a first light chain (LC1) and one or more negatively-charged residues (e.g., aspartic acid or glutamic acid) can be introduced into the companion heavy chain (HC1) at the binding interface of LC1/HC1, whereas one or more negatively-charged residues (e.g., aspartic acid or glutamic acid) can be introduced into a second light chain (LC2) and one or more positively-charged residues (e.g., lysine, histidine or arginine) can be introduced into the companion heavy chain (HC2) at the binding interface of LC2/HC2. The electrostatic interactions will direct the LC1 to pair with HC1 and LC2 to pair with HC2, as the opposite charged residues (polarity) at the interface attract. The heavy/light chain pairs having the same charged residues (polarity) at an interface (e.g. LC1/HC2 and LC2/HC1) will repel, resulting in suppression of the unwanted HC/LC pairings.
In these and other embodiments, the CH1 domain of the heavy chain or the CL domain of the light chain comprises an amino acid sequence differing from wild-type IgG amino acid sequence such that one or more positively-charged amino acids in wild-type IgG amino acid sequence is replaced with one or more negatively-charged amino acids. Alternatively, the CH1 domain of the heavy chain or the CL domain of the light chain comprises an amino acid sequence differing from wild-type IgG amino acid sequence such that one or more negatively-charged amino acids in wild-type IgG amino acid sequence is replaced with one or more positively-charged amino acids. In some embodiments, one or more amino acids in the CH1 domain of the first and/or second heavy chain in the multispecific antibody construct at an EU position selected from F126, P127, L128, A141, L145, K147, D148, H168, F170, P171, V173, Q175, S176, S183, V185 and K213 is replaced with a charged amino acid. In certain embodiments, a heavy chain residue for substitution with a negatively- or positively-charged amino acid is S183 (EU numbering system). In some embodiments, S183 is substituted with a positively-charged amino acid. In alternative embodiments, S183 is substituted with a negatively-charged amino acid. For instance, in one embodiment, S183 is substituted with a negatively-charged amino acid (e.g. S183E) in the first heavy chain, and S183 is substituted with a positively-charged amino acid (e.g. S183K) in the second heavy chain.
In embodiments in which the light chain is a kappa light chain, one or more amino acids in the CL domain of the first and/or second light chain in the multimeric antibody construct at a position (EU numbering in a kappa light chain) selected from F116, F118, S121, D122, E123, Q124, S131, V133, L135, N137, N138, Q160, S162, T164, S174 and S176 is replaced with a charged amino acid. In embodiments in which the light chain is a lambda light chain, one or more amino acids in the CL domain of the first and/or second light chain in the multispecific antibody construct at a position (EU numbering in a lambda chain) selected from T116, F118, S121, E123, E124, K129, T131, V133, L135, S137, E160, T162, S165, Q167, A174, S176 and Y178 is replaced with a charged amino acid. In some embodiments, a residue for substitution with a negatively- or positively-charged amino acid is S176 (EU numbering system) of the CL domain of either a kappa or lambda light chain. In certain embodiments, S176 of the CL domain is replaced with a positively-charged amino acid. In alternative embodiments, S176 of the CL domain is replaced with a negatively-charged amino acid. In one embodiment, S176 is substituted with a positively-charged amino acid (e.g. S176K) in the first light chain, and S176 is substituted with a negatively-charged amino acid (e.g. S176E) in the second light chain.
In addition to or as an alternative to the complimentary amino acid substitutions in the CH1 and CL domains, the variable regions of the light and heavy chains in the multispecific antibody construct may contain one or more complimentary amino acid substitutions to introduce charged amino acids. For instance, in some embodiments, the VH region of the heavy chain or the VL region of the light chain of a multispecific antibody construct comprises an amino acid sequence differing from wild-type IgG amino acid sequence such that one or more positively-charged amino acids in wild-type IgG amino acid sequence is replaced with one or more negatively-charged amino acids.
Alternatively, the VH region of the heavy chain or the VL region of the light chain comprises an amino acid sequence differing from wild-type IgG amino acid sequence such that one or more negatively-charged amino acids in wild-type IgG amino acid sequence is replaced with one or more positively-charged amino acids.
V region interface residues (i.e., amino acid residues that mediate assembly of the VH and VL regions) within the VH region include EU positions 1, 3, 35, 37, 39, 43, 44, 45, 46, 47, 50, 59, 89, 91, and 93. One or more of these interface residues in the VH region can be substituted with a charged (positively- or negatively-charged) amino acid. In certain embodiments, the amino acid at EU position 39 in the VH region of the first and/or second heavy chain is substituted for a positively-charged amino acid, e.g., lysine. In alternative embodiments, the amino acid at EU position 39 in the VH region of the first and/or second heavy chain is substituted for a negatively-charged amino acid, e.g., glutamic acid. In some embodiments, the amino acid at EU position 39 in the VH region of the first heavy chain is substituted for a negatively-charged amino acid (e.g. G39E), and the amino acid at EU position 39 in the VH region of the second heavy chain is substituted for a positively-charged amino acid (e.g. G39K). In some embodiments, the amino acid at EU position 44 in the VH region of the first and/or second heavy chain is substituted for a positively-charged amino acid, e.g., lysine. In alternative embodiments, the amino acid at EU position 44 in the VH region of the first and/or second heavy chain is substituted for a negatively-charged amino acid, e.g., glutamic acid. In certain embodiments, the amino acid at EU position 44 in the VH region of the first heavy chain is substituted for a negatively-charged amino acid (e.g. G44E), and the amino acid at EU position 44 in the VH region of the second heavy chain is substituted for a positively-charged amino acid (e.g. G44K).
V region interface residues (i.e., amino acid residues that mediate assembly of the VH and VL regions) within the VL region include EU positions 32, 34, 35, 36, 38, 41, 42, 43, 44, 45, 46, 48, 49, 50, 51, 53, 54, 55, 56, 57, 58, 85, 87, 89, 90, 91, and 100. One or more interface residues in the VL region can be substituted with a charged amino acid, preferably an amino acid that has an opposite charge to those introduced into the VH region of the cognate heavy chain. In some embodiments, the amino acid at EU position 100 in the VL region of the first and/or second light chain is substituted for a positively-charged amino acid, e.g., lysine. In alternative embodiments, the amino acid at EU position 100 in the VL region of the first and/or second light chain is substituted for a negative-charged amino acid, e.g., glutamic acid. In certain embodiments, the amino acid at EU position 100 in the VL region of the first light chain is substituted for a positively-charged amino acid (e.g. G100K), and the amino acid at EU position 100 in the VL region of the second light chain is substituted for a negatively-charged amino acid (e.g. G100E).
Any of the constant domains can be modified to contain one or more of the charge pair mutations described above to facilitate correct assembly of a multispecific antibody construct.
As used herein, the term “Fc region” refers to the C-terminal region of an immunoglobulin heavy chain which may be generated by papain digestion of an intact antibody. The Fc region of an immunoglobulin generally comprises two constant domains, a CH2 domain and a CH3 domain, and optionally comprises a CH4 domain. In certain embodiments, the Fc region is an Fc region from an IgG1, IgG2, IgG3, or IgG4 immunoglobulin. In some embodiments, the Fc region comprises CH2 and CH3 domains from a human IgG1 or human IgG2 immunoglobulin. The Fc region may retain effector function, such as Clq binding, complement dependent cytotoxicity (CDC), Fc receptor binding, antibody-dependent cell-mediated cytotoxicity (ADCC), and phagocytosis. In other embodiments, the Fc region may be modified to reduce or eliminate effector function as described in further detail herein.
The heavy chain constant regions or the Fc regions of the multispecific antibody constructs described herein may comprise one or more amino acid substitutions that affect the glycosylation and/or effector function of the antigen binding protein. One of the functions of the Fc region of an immunoglobulin is to communicate to the immune system when the immunoglobulin binds its target. This is commonly referred to as “effector function.” Communication leads to antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and/or complement dependent cytotoxicity (CDC). ADCC and ADCP are mediated through the binding of the Fc region to Fc receptors on the surface of cells of the immune system. CDC is mediated through the binding of the Fc with proteins of the complement system, e.g., Clq. In some embodiments, the multispecific antibody constructs of the invention comprise one or more amino acid substitutions in the constant region to enhance effector function, including ADCC activity, CDC activity, ADCP activity, and/or the clearance or half-life of the antigen binding protein. Exemplary amino acid substitutions (EU numbering) that can enhance effector function include, but are not limited to, E233L, L234I, L234Y, L235S, G236A, S239D, F243L, F243V, P247I, D280H, K290S, K290E, K290N, K290Y, R292P, E294L, Y296W, S298A, S298D, S298V, S298G, S298T, T299A, Y300L, V305I, Q311M, K326A, K326E, K326W, A330S, A330L, A330M, A330F, I332E, D333A, E333S, E333A, K334A, K334V, A339D, A339Q, P396L, or combinations of any of the foregoing.
In other embodiments, the multispecific antibody constructs of the invention comprise one or more amino acid substitutions in the constant region to reduce effector function. Exemplary amino acid substitutions (EU numbering) that can reduce effector function include, but are not limited to, C220S, C226S, C229S, E233P, L234A, L234V, V234A, L234F, L235A, L235E, G237A, P238S, S267E, H268Q, N297A, N297G, V309L, E318A, L328F, A330S, A33iS, P331S or combinations of any of the foregoing.
Glycosylation can contribute to the effector function of antibodies, particularly IgG1 antibodies. Thus, in some embodiments, the multispecific antibody constructs of the invention may comprise one or more amino acid substitutions that affect the level or type of glycosylation of the binding proteins. Glycosylation of polypeptides is typically either N-linked or O-linked. N-linked refers to the attachment of the carbohydrate moiety to the side chain of an asparagine residue. The tri-peptide sequences asparagine-X-serine and asparagine-X-threonine, where X is any amino acid except proline, are the recognition sequences for enzymatic attachment of the carbohydrate moiety to the asparagine side chain. Thus, the presence of either of these tri-peptide sequences in a polypeptide creates a potential glycosylation site. O-linked glycosylation refers to the attachment of one of the sugars N-acetylgalactosamine, galactose, or xylose, to a hydroxyamino acid, most commonly serine or threonine, although 5-hydroxyproline or 5-hydroxylysine may also be used.
In certain embodiments, glycosylation of the multispecific antibody constructs described herein is increased by adding one or more glycosylation sites, e.g., to the Fc region of the binding protein. Addition of glycosylation sites to the antigen binding protein can be conveniently accomplished by altering the amino acid sequence such that it contains one or more of the above-described tri-peptide sequences (for N-linked glycosylation sites). The alteration may also be made by the addition of, or substitution by, one or more serine or threonine residues to the starting sequence (for O-linked glycosylation sites). For ease, the antigen binding protein amino acid sequence may be altered through changes at the DNA level, particularly by mutating the DNA encoding the target polypeptide at preselected bases such that codons are generated that will translate into the desired amino acids.
The invention also encompasses production of multispecific antibody construct molecules with altered carbohydrate structure resulting in altered effector activity, including antigen binding proteins with absent or reduced fucosylation that exhibit improved ADCC activity. Various methods are known in the art to reduce or eliminate fucosylation. For example, ADCC effector activity is mediated by binding of the antibody molecule to the FcγRIII receptor, which has been shown to be dependent on the carbohydrate structure of the N-linked glycosylation at the N297 residue of the CH2 domain. Non-fucosylated antibodies bind this receptor with increased affinity and trigger FcγRIII-mediated effector functions more efficiently than native, fucosylated antibodies. For example, recombinant production of non-fucosylated antibody in CHO cells in which the alpha-1,6-fucosyl transferase enzyme has been knocked out results in antibody with 100-fold increased ADCC activity (see Yamane-Ohnuki et al., Biotechnol Bioeng. 87(5):614-22, 2004). Similar effects can be accomplished through decreasing the activity of alpha-1,6-fucosyl transferase enzyme or other enzymes in the fucosylation pathway, e.g., through siRNA or antisense RNA treatment, engineering cell lines to knockout the enzyme(s), or culturing with selective glycosylation inhibitors (see Rothman et al., Mol Immunol. 26(12):1113-23, 1989). Some host cell strains, e.g. Lec13 or rat hybridoma YB2/0 cell line naturally produce antibodies with lower fucosylation levels (see Shields et al., J Biol Chem. 277(30):26733-40, 2002 and Shinkawa et al., J Biol Chem. 278(5):3466-73, 2003). An increase in the level of bisected carbohydrate, e.g. through recombinantly producing antibody in cells that overexpress GnTIII enzyme, has also been determined to increase ADCC activity (see Umana et al., Nat Biotechnol. 17(2):176-80, 1999).
In other embodiments, glycosylation of the multispecific antibody constructs described herein is decreased or eliminated by removing one or more glycosylation sites, e.g., from the Fc region of the binding protein. Amino acid substitutions that eliminate or alter N-linked glycosylation sites can reduce or eliminate N-linked glycosylation of the antigen binding protein. In certain embodiments, the multispecific antibody constructs described herein comprise a mutation at position N297 (EU numbering), such as N297Q, N297A, or N297G. In certain embodiments, the multispecific antibody constructs described herein comprise a mutation at positions L234 and L235 (EU numbering), such as L234A and L235A. In one particular embodiment, the multispecific antibody constructs of the invention comprise a Fc region from a human IgG1 antibody with a N297G mutation. To improve the stability of molecules comprising a N297 mutation, the Fc region of the molecules may be further engineered. For instance, in some embodiments, one or more amino acids in the Fc region are substituted with cysteine to promote disulfide bond formation in the dimeric state. Residues corresponding to V259, A287, R292, V302, L306, V323, or 1332 (EU numbering) of an IgG1 Fc region may thus be substituted with cysteine. In one embodiment, specific pairs of residues are substituted with cysteine such that they preferentially form a disulfide bond with each other, thus limiting or preventing disulfide bond scrambling. In certain embodiments pairs include, but are not limited to, A287C and L306C, V259C and L306C, R292C and V302C, and V323C and I332C. In particular embodiments, the multispecific antibody constructs described herein comprise a Fc region from a human IgG1 antibody with mutations at R292C and V302C. In such embodiments, the Fc region may also comprise a N297G mutation.
In one embodiment, the heavy chain comprises an amino acid substitution selected from the group consisting of:
(i) N297G or N297A;
(ii) L234A and L235A; and
(iii) R292C and V302C;
wherein the amino acid numbering is EU numbering according to Kabat.
In one embodiment, the heavy chain comprises N297G, R292C, and V302C mutations, wherein the amino acid numbering is EU numbering according to Kabat.
Modifications of the multispecific antibody constructs of the invention to increase serum half-life also may desirable, for example, by incorporation of or addition of a salvage receptor binding epitope (e.g., by mutation of the appropriate region or by incorporating the epitope into a peptide tag that is then fused to the antigen binding protein at either end or in the middle, e.g., by DNA or peptide synthesis; see, e.g., WO96/32478) or adding molecules such as PEG or other water soluble polymers, including polysaccharide polymers. The salvage receptor binding epitope preferably constitutes a region wherein any one or more amino acid residues from one or two loops of a Fc region are transferred to an analogous position in the antigen binding protein. In one embodiment, three or more residues from one or two loops of the Fc region are transferred. In one embodiment, the epitope is taken from the CH2 domain of the Fc region (e.g., an IgG Fc region) and transferred to the CH1, CH3, or VH region, or more than one such region, of the antigen binding protein. Alternatively, the epitope is taken from the CH2 domain of the Fc region and transferred to the CL region or VL region, or both, of the antigen binding protein. See International applications WO 97/34631 and WO 96/32478 for a description of Fc variants and their interaction with the salvage receptor.
In certain embodiments of the multispecific antibody construct of the invention, the binding domain positioned at the amino terminus of the Fc region (i.e. the amino-terminal binding domain) is a Fab fragment fused to the amino terminus of the Fc region through a peptide linker described herein or through an immunoglobulin hinge region. An “immunoglobulin hinge region” refers to the amino acid sequence connecting the CH1 domain and the CH2 domain of an immunoglobulin heavy chain. The hinge region of human IgG1 is generally defined as the amino acid sequence from about Glu216 or about Cys226, to about Pro230. Hinge regions of other IgG isotypes may be aligned with the IgG1 sequence by placing the first and last cysteine residues forming inter-heavy chain disulfide bonds in the same positions and are determinable to those of skill in the art. In some embodiments, the amino-terminal binding domain is joined to the amino terminus of the Fc region through a human IgG1 hinge region. In other embodiments, the amino-terminal binding domain is joined to the amino terminus of the Fc region through a human IgG2 hinge region. In one embodiment, the amino-terminal binding domain (e.g. Fab fragment) is fused to the Fc region through the carboxyl terminus of the CH1 region of the Fab.
In some embodiments of the heavy chain fusion proteins of the invention, the binding domain positioned at the carboxyl terminus of the Fc region (i.e. the carboxyl-terminal binding domain) is a Fab fragment. In such embodiments, the Fab is fused or otherwise connected to the carboxyl terminus of the Fc region (e.g. the carboxyl terminus of the CH3 domain) through a peptide linker through the amino terminus of the VH region of the Fab fragment. Thus, in one embodiment, the Fab is fused to an Fc region through the amino terminus of the VH region of the Fab such that the resulting fusion protein comprises, from N-terminus to C-terminus, a CH2 domain, a CH3 domain, a peptide linker, a VH region, and a CH1 region.
The peptide linker joining the Fc region to the carboxyl-terminal Fab can be any of the peptide linkers described herein. In particular embodiments, the peptide linker joining the Fc region to the carboxyl-terminal Fab fragment is at least 5 amino acids in length. In other embodiments, the peptide linker joining the Fc region to the carboxyl-terminal Fab fragment is at least 8 amino acids in length. Particularly suitable peptide linkers for joining the Fc region to the carboxyl-terminal Fab fragment are glycine-serine linkers, such as (GlyxSer)n where x=3 or 4 and n=2, 3, 4, 5 or 6 (SEQ ID NO: 923). In one embodiment, the peptide linker connecting the Fc region to the carboxyl-terminal Fab fragment is a L10 (G4S)2 linker (SEQ ID NO: 888). In another embodiment, the peptide linker connecting the Fc region to the carboxyl-terminal Fab fragment is a L9 or G3SG4S linker (SEQ ID NO: 924).
In some embodiments of the antigen binding proteins of the invention in which the carboxyl-terminal binding domain is a Fab fragment, the binding domain positioned at the amino terminus of the Fc region (i.e. the amino-terminal binding domain) is also a Fab fragment. The amino-terminal Fab fragment can be fused to the amino terminus of the Fc region through a peptide linker or an immunoglobulin hinge region described herein. In some embodiments, the amino-terminal Fab fragment is joined to the amino terminus of the Fc region through a human IgG1 hinge region. In other embodiments, the amino-terminal Fab fragment is joined to the amino terminus of the Fc region through a human IgG2 hinge region. In one embodiment, the amino-terminal Fab fragment is fused to the Fc region through the carboxyl terminus of the CH1 region of the Fab.
In some embodiments, the multispecific antibody construct of the invention comprises a first antibody that specifically binds to a first target where one polypeptide chain (e.g. the heavy chain (VH2-CH1)) of a Fab fragment from a second antibody that specifically binds to a second target is fused to the carboxyl terminus of the heavy chain of the first antibody. The multispecific antibody construct in such embodiments also comprises a polypeptide chain containing the other half of the Fab fragment from the second antibody (e.g., the light chain (VL2-CL)). This format is referred to herein as the “IgG-Fab” format, and one embodiment of this type of molecule is shown schematically in FIG. 1. Thus, in certain embodiments, the present invention includes a bispecific, multivalent antigen binding protein comprising: (i) a light chain from a first antibody, (ii) a heavy chain from the first antibody, wherein the heavy chain is fused at its carboxyl terminus through a peptide linker to a first polypeptide comprising VH-CH1 domains of a second antibody to form a modified heavy chain, and (iii) a second polypeptide comprising VL-CL domains of the second antibody. When dimerized, the multispecific antibody construct is a homohexamer comprising two modified heavy chains, two light chains from the first antibody, and two polypeptide chains containing the other half of the Fab fragment from the second antibody (the Fd fragment). In one embodiment, the first polypeptide, which is fused to the carboxyl terminus of the heavy chain, comprises VH and CH1 domains from the second antibody, and the second polypeptide comprises VL and CL domains from the second antibody.
Charge pair mutations or complimentary amino acid substitutions as described herein can be introduced into the Fab regions of the first antibody (Fab 1) or second antibody (Fab 2) to promote correct heavy chain-light chain pairing. For instance, in some embodiments, the amino acid at EU position 38 of the VL domain in Fab 1 is replaced with a negatively-charged amino acid (e.g. glutamic acid) and the amino acid at EU position 39 of the VH domain in Fab 1 is replaced with a positively-charged amino acid (e.g. lysine). In other embodiments, the amino acid at EU position 38 of the VL domain in Fab 1 is replaced with a positively-charged amino acid (e.g. lysine) and the amino acid at EU position 39 of the VH domain in Fab 1 is replaced with a negatively-charged amino acid (e.g. glutamic acid). In certain embodiments, the amino acid at EU position 38 of the VL domain in Fab 2 is replaced with a negatively-charged amino acid (e.g. glutamic acid) and the amino acid at EU position 39 of the VH domain in Fab 2 is replaced with a positively-charged amino acid (e.g. lysine). In other embodiments, the amino acid at EU position 38 of the VL domain in Fab 2 is replaced with a positively-charged amino acid (e.g. lysine) and the amino acid at EU position 39 of the VH domain in Fab 2 is replaced with a negatively-charged amino acid (e.g. glutamic acid).
In embodiments in which the VH-CH1 region (i.e. Fd fragment) from the second antibody is fused to the heavy chain of the first antibody, the heavy chain from the first antibody comprises a S183E mutation (EU numbering), the light chain from the first antibody comprises a S176K mutation (EU numbering), the light chain from the second antibody comprises a S176E mutation (EU numbering), and the Fd region from the second antibody (which is fused to the C-terminus of the heavy chain from the first antibody) comprises a S183K mutation (EU numbering). In other embodiments, the heavy chain from the first antibody comprises a G44E mutation (EU) and S183E mutation (EU numbering), the light chain from the first antibody comprises a G100K mutation (EU) and S176K mutation (EU numbering), the light chain from the second antibody comprises a G100E mutation (EU) and S176E mutation (EU numbering), and the Fd region from the second antibody (which is fused to the C-terminus of the heavy chain from the first antibody) comprises a G44K mutation (EU) and S183K mutation (EU numbering). The charges in the foregoing examples may be reversed so long as the charge on the corresponding light or heavy chain is also reversed so that the correct heavy/light chain pairs have opposite charges.
“Corresponds to” as it pertains to the VH2 and second CH1 domain means that the amino acid residues of the VH2 and second CH1 domain are counted from the C-terminus of the first heavy chain if there is no linker. If there is a peptide linker, the amino acid residues of the VH2 and second CH1 domain are counted from the C-terminus of the peptide linker. In neither case are the amino acid residues counted from the N-terminus of the first heavy chain. Rather, for the VH2 and second CH1 domain, counting begins at the first amino acid residue of the VH2 domain. The counting of amino acid residues is performed using the EU or AHo convention.
In certain embodiments: a) the VH1 comprises a Q39E mutation and the first CH1 domain comprises a S183K mutation using EU numbering; b) the VH2 comprises a Q39K mutation and the second CH1 domain comprises a S183E mutation using EU numbering; c) the VL1 comprises a Q38K mutation and the first CL domain comprises a S176E mutation using EU numbering; and d) the VL2 comprises a Q38E mutation and the second CL domain comprises a S176K mutation using EU numbering.
In certain embodiments: a) the first CH1 domain comprises G44E and S183K mutations using EU numbering; b) the second CH1 domain comprises G44K and S183E mutations using EU numbering; c) the first CL domain comprises G100K and S176E mutations using EU numbering; and d) the second CL domain comprises G100E and S176K mutations using EU numbering.
In certain embodiments: a) the VH1 comprises a Q39K mutation and the first CH1 domain comprises a S183E mutation using EU numbering; b) the VH2 comprises a Q39E mutation and the second CH1 domain comprises a S183K mutation using EU numbering; c) the VL1 comprises a Q38E mutation and the first CL domain comprises a S176K mutation using EU numbering; and d) the VL2 comprises a Q38K mutation and the second CL domain comprises a S176E mutation using EU numbering.
In certain embodiments: a) the first CH1 domain comprises G44K and S183E mutations using EU numbering; b) the second CH1 domain comprises G44E and S183K mutations using EU numbering; c) the first CL domain comprises G100E and S176K mutations using EU numbering; and d) the second CL domain comprises G100K and S176E mutations using EU numbering.
In certain embodiments the first heavy chain is fused to the VH2 via a peptide linker. In certain embodiments the peptide linker comprises a sequence selected from the group consisting of (Gly3Ser)2 (SEQ ID NO: 916), (Gly4Ser)2 (SEQ ID NO: 888), (Gly3Ser)3 (SEQ ID NO: 917), (Gly4Ser)3 (SEQ ID NO: 889), (Gly3Ser)4 (SEQ ID NO: 918), (Gly4Ser)4 (SEQ ID NO: 890), (Gly3Ser)5 (SEQ ID NO: 919), (Gly4Ser)5 (SEQ ID NO: 920), (Gly3Ser)6 (SEQ ID NO: 921), and (Gly4Ser)6 (SEQ ID NO: 922). These sequences can also be written as GGGSGGGS (SEQ ID NO: 916), GGGGSGGGGS (SEQ ID NO: 888), GGGSGGGSGGGS (SEQ ID NO: 917), GGGGSGGGGSGGGGS (SEQ ID NO: 889), GGGSGGGSGGGSGGGS (SEQ ID NO: 918), GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 890), GGGSGGGSGGGSGGGSGGGS (SEQ ID NO: 919), GGGGSGGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 920), GGGSGGGSGGGSGGGSGGGSGGGS (SEQ ID NO: 921), and GGGGSGGGGSGGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 922).
Additionally or alternatively, correct heavy-light chain pairing may be facilitated by swapping the CH1 and CL domains in the carboxyl-terminal Fab binding domain. By way of example, the first polypeptide, which is fused to the carboxyl terminus of the heavy chain, may comprise a VL domain and CH1 domain from the second antibody, and the second polypeptide may comprise a VH domain and CL domain from the second antibody. In another embodiment, the first polypeptide, which is fused to the carboxyl terminus of the heavy chain, may comprise a VH domain and a CL domain from the second antibody, and the second polypeptide may comprise a VL domain and CH1 domain from the second antibody.
In another aspect, the present invention is directed to a multispecific antibody construct comprising:
a) two identical heavy chain fusion proteins each comprising a first heavy chain variable region (VH1) and a first CH1 domain, wherein the first CH1 domain is linked to a hinge-CH2-CH3 polypeptide, and wherein the hinge-CH2-CH3 polypeptide is linked to a second heavy chain variable region (VH2), wherein the VH2 is linked to a second CH1 domain; wherein
i) the VH1 or first CH1 domain comprises at least one amino acid substitution to introduce a positively charged amino acid at a residue selected from the group consisting of positions 39, 44, and 183 using EU numbering; and
ii) the VH2 or second CH1 domain comprises at least one amino acid substitution to introduce a negatively charged amino acid at a residue selected from the group consisting of a residue that corresponds to positions 39, 44, and 183 using EU numbering; and
b) a second polypeptide comprising a first light chain, wherein the first light chain comprises a first light chain variable region (VL1) and a first CL region; and wherein the VL1 or first CL domain comprises at least one amino acid substitution to introduce a negatively charged amino acid at a residue selected from the group consisting of positions 38, 100, and 176 using EU numbering; and
c) a third polypeptide comprising a second light chain, wherein the second light chain comprises a second light chain variable region (VL2) and a second CL region; and wherein the VL2 or second CL domain comprises at least one amino acid substitution to introduce a positively charged amino acid at a residue selected from the group consisting of positions 38, 100, and 176 using EU numbering;
wherein the VH1 and VL1 interact to bind a first antigen and wherein the VH2 and VL2 interact to bind a second antigen;
wherein:
the first antigen is human CD40 (SEQ ID NO: 1) and the second antigen is human mesothelin (“MSLN”; SEQ ID NO: 2); or
the first antigen is human MSLN (SEQ ID NO: 2) and the second antigen is human CD40 (SEQ ID NO: 1).
In one aspect, the present invention is directed to a multispecific antibody construct comprising:
a) two identical heavy chain fusion proteins each comprising a first heavy chain variable region (VH1) and a first CH1 domain, wherein the first CH1 domain is linked to a hinge-CH2-CH3 polypeptide, and wherein the hinge-CH2-CH3 polypeptide is linked to a second heavy chain variable region (VH2), wherein the VH2 is linked to a second CH1 domain; wherein
i) the VH1 or first CH1 domain comprises at least one amino acid substitution to introduce a negatively charged amino acid at a residue selected from the group consisting of positions 39, 44, and 183 using EU numbering; and
ii) the VH2 or second CH1 domain comprises at least one amino acid substitution to introduce a positively charged amino acid at a residue selected from the group consisting of a residue that corresponds to positions 39, 44, and 183 using EU numbering; and
b) a second polypeptide comprising a first light chain, wherein the first light chain comprises a first light chain variable region (VL1) and a first CL region; and wherein the VL1 or first CL domain comprises at least one amino acid substitution to introduce a positively charged amino acid at a residue selected from the group consisting of positions 38, 100, and 176 using EU numbering; and
c) a third polypeptide comprising a second light chain, wherein the second light chain comprises a second light chain variable region (VL2) and a second CL region; and wherein the VL2 or second CL domain comprises at least one amino acid substitution to introduce a negatively charged amino acid at a residue selected from the group consisting of positions 38, 100, and 176 using EU numbering;
wherein the VH1 and VL1 interact to bind a first antigen and wherein the VH2 and VL2 interact to bind a second antigen;
wherein:
the first antigen is human CD40 (SEQ ID NO: 1) and the second antigen is human mesothelin (“MSLN”; SEQ ID NO: 2); or
the first antigen is human MSLN (SEQ ID NO: 2) and the second antigen is human CD40 (SEQ ID NO: 1).
In one embodiment, the hinge-CH2-CH3 polypeptide is linked to the VH2 via a peptide linker.
In one embodiment, the peptide linker comprises a sequence selected from the group consisting of (Gly3Ser)2 (SEQ ID NO: 916), (Gly4Ser)2 (SEQ ID NO: 888), (Gly3Ser)3 (SEQ ID NO: 917), (Gly4Ser)3 (SEQ ID NO: 889), (Gly3Ser)4 (SEQ ID NO: 918), (Gly4Ser)4 (SEQ ID NO: 890), (Gly3Ser)5 (SEQ ID NO: 919), (Gly4Ser)5 (SEQ ID NO: 920), (Gly3Ser)6 (SEQ ID NO: 921), and (Gly4Ser)6 (SEQ ID NO: 922).
In one embodiment,
a) the VH1 or first CH1 domain comprises a mutation selected from the group consisting of Q39K, G44K, and S183K using EU numbering;
b) the VH2 or second CH1 domain comprises a mutation selected from the group consisting of Q39E, G44E, and S183E using EU numbering;
c) the VL1 or first CL domain comprises a mutation selected from the group consisting of Q38E, G100E, and S176E using EU numbering; and
d) the VL2 or second CL domain comprises a mutation selected from the group consisting of Q38K, G100K, and S176K using EU numbering.
In one embodiment,
a) the first CH1 domain comprises a S183K mutation using EU numbering;
b) the second CH1 domain comprises a S183E mutation using EU numbering;
c) the first CL domain comprises a S176E mutation using EU numbering; and
d) the second CL domain comprises a S176K mutation using EU numbering.
In one embodiment,
a) the VH1 comprises a Q39K mutation and the first CH1 domain comprises a S183K mutation using EU numbering;
b) the VH2 comprises a Q39E mutation and the second CH1 domain comprises a S183E mutation using EU numbering;
c) the VL1 comprises a Q38E mutation and the first CL domain comprises a S176E mutation using EU numbering; and
d) the VL2 comprises a Q38K mutation and the second CL domain comprises a S176K mutation using EU numbering.
In one embodiment,
a) the first CH1 domain comprises G44K and S183K mutations using EU numbering;
b) the second CH1 domain comprises G44E and S183E mutations using EU numbering;
c) the first CL domain comprises G100E and S176E mutations using EU numbering; and
d) the second CL domain comprises G100K and S176K mutations using EU numbering.
In one embodiment,
a) the VH1 or first CH1 domain comprises a mutation selected from the group consisting of Q39E, G44E, and S183E using EU numbering;
b) the VH2 or second CH1 domain comprises a mutation selected from the group consisting of Q39K, G44K, and S183K using EU numbering;
c) the VL1 or first CL domain comprises a mutation selected from the group consisting of Q38K, G100K, and S176K using EU numbering; and
d) the VL2 or second CL domain comprises a mutation selected from the group consisting of Q38E, G100E, and S176E using EU numbering.
In one embodiment,
a) the first CH1 domain comprises a S183E mutation using EU numbering;
b) the second CH1 domain comprises a S183K mutation using EU numbering;
c) the first CL domain comprises a S176K mutation using EU numbering; and
d) the second CL domain comprises a S176E mutation using EU numbering.
In one embodiment,
a) the VH1 comprises a Q39E mutation and the first CH1 domain comprises a S183E mutation using EU numbering;
b) the VH2 comprises a Q39K mutation and the second CH1 domain comprises a S183K mutation using EU numbering;
c) the VL1 comprises a Q38K mutation and the first CL domain comprises a S176K mutation using EU numbering; and
d) the VL2 comprises a Q38E mutation and the second CL domain comprises a S176E mutation using EU numbering.
In one embodiment,
a) the first CH1 domain comprises G44E and S183E mutations using EU numbering;
b) the second CH1 domain comprises G44K and S183K mutations using EU numbering;
c) the first CL domain comprises G100K and S176K mutations using EU numbering; and
d) the second CL domain comprises G100E and S176E mutations using EU numbering.
In one embodiment, the hinge-CH2-CH3 polypeptide comprises an amino acid substitution selected from the group consisting of:
(i) N297G or N297A;
(ii) L234A and L235A; and
(iii) R292C and V302C;
wherein the amino acid numbering is EU numbering according to Kabat.
In one embodiment, the hinge-CH2-CH3 polypeptide comprises N297G, R292C, and V302C mutations, wherein the amino acid numbering is EU numbering according to Kabat.
In one embodiment, the first antigen is human CD40 (SEQ ID NO: 1) and the second antigen is human MSLN (SEQ ID NO: 2); and
the VL1 comprises a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of:
SEQ ID NOs: 58, 59, and 60, respectively;
SEQ ID NOs: 64, 65, and 66, respectively;
SEQ ID NOs: 70, 71, and 72, respectively;
SEQ ID NOs: 76, 77, and 78, respectively;
SEQ ID NOs: 82, 83, and 84, respectively;
SEQ ID NOs: 88, 89, and 90, respectively;
SEQ ID NOs: 94, 95, and 96, respectively;
SEQ ID NOs: 100, 101, and 102, respectively;
SEQ ID NOs: 106, 107, and 108, respectively;
SEQ ID NOs: 112, 113, and 114, respectively;
SEQ ID NOs: 118, 119, and 120, respectively;
SEQ ID NOs: 124, 125, and 126, respectively; and
SEQ ID NOs: 130, 131, and 132, respectively;
the VH1 comprises a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of:
SEQ ID NOs: 136, 137, and 138, respectively;
SEQ ID NOs: 142, 143, and 144, respectively;
SEQ ID NOs: 148, 149, and 150, respectively;
SEQ ID NOs: 154, 155, and 156, respectively;
SEQ ID NOs: 160, 161, and 162, respectively;
SEQ ID NOs: 166, 167, and 168, respectively;
SEQ ID NOs: 172, 173, and 174, respectively;
SEQ ID NOs: 178, 179, and 180, respectively;
SEQ ID NOs: 184, 185, and 186, respectively;
SEQ ID NOs: 190, 191, and 192, respectively;
SEQ ID NOs: 196, 197, and 198, respectively;
SEQ ID NOs: 202, 203, and 204, respectively; and
SEQ ID NOs: 208, 209, and 210, respectively;
the VL2 comprises a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of:
SEQ ID NOs: 230, 231, and 232, respectively;
SEQ ID NOs: 236, 237, and 238, respectively;
SEQ ID NOs: 242, 243, and 244, respectively; and
SEQ ID NOs: 248, 249, and 250, respectively;
and the VH2 comprises a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of:
SEQ ID NOs: 254, 255, and 256, respectively;
SEQ ID NOs: 260, 261, and 262, respectively;
SEQ ID NOs: 266, 267, and 268, respectively; and
SEQ ID NOs: 272, 273, and 274, respectively.
In one embodiment, the first antigen is human CD40 (SEQ ID NO: 1) and the second antigen is human MSLN (SEQ ID NO:2), wherein
1) the VL1 and VH1 are selected from the group consisting of:
a) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 58, 59, and 60, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 136, 137, and 138, respectively;
b) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 64, 65, and 66, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 142, 143, and 144, respectively;
c) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 70, 71, and 72, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 148, 149, and 150, respectively;
d) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 76, 77, and 6780, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 154, 155, and 156, respectively;
e) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 82, 83, and 84, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 160, 161, and 162, respectively;
f) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 88, 89, and 90, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 166, 167, and 168, respectively;
g) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 94, 95, and 96, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 172, 173, and 174, respectively;
h) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 100, 101, and 102, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 178, 179, and 180, respectively;
i) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 106, 107, and 108, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 184, 185, and 186, respectively;
j) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 112, 113, and 114, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 190, 191, and 192, respectively;
k) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 118, 119, and 120, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 196, 197, and 198, respectively;
l) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 124, 125, and 126, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 202, 203, and 204, respectively; and
m) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 130, 131, and 132, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 208, 209, and 210, respectively;
and
2) the VL2 and VH2 are selected from the group consisting of:
a) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 230, 231, and 232, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 254, 255, and 256, respectively;
b) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 236, 237, and 238, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 260, 261, and 262, respectively;
c) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 242, 243, and 244, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 266, 267, and 268, respectively; and
d) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 248, 249, and 250, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 272, 273, and 274, respectively.
In one embodiment:
the VL1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53;
the VH1 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, and 54;
the VL2 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 213, 217, 221, and 225;
the VH2 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 214, 218, 222, and 226.
In one embodiment:
1) the VL1 and VH1 are selected from the group consisting of:
a) a VL1 comprising SEQ ID NO: 5 and a VH1 comprising SEQ ID NO: 6;
b) a VL1 comprising SEQ ID NO: 9 and a VH1 comprising SEQ ID NO: 10;
c) a VL1 comprising SEQ ID NO: 13 and a VH1 comprising SEQ ID NO: 14;
d) a VL1 comprising SEQ ID NO: 17 and a VH1 comprising SEQ ID NO: 18;
e) a VL1 comprising SEQ ID NO: 21 and a VH1 comprising SEQ ID NO: 22;
f) a VL1 comprising SEQ ID NO: 25 and a VH1 comprising SEQ ID NO: 26;
g) a VL1 comprising SEQ ID NO: 29 and a VH1 comprising SEQ ID NO: 30;
h) a VL1 comprising SEQ ID NO: 33 and a VH1 comprising SEQ ID NO: 34;
i) a VL1 comprising SEQ ID NO: 37 and a VH1 comprising SEQ ID NO: 38;
j) a VL1 comprising SEQ ID NO: 41 and a VH1 comprising SEQ ID NO: 42;
k) a VL1 comprising SEQ ID NO: 45 and a VH1 comprising SEQ ID NO: 46;
l) a VL1 comprising SEQ ID NO: 49 and a VH1 comprising SEQ ID NO: 50; and
m) a VL1 comprising SEQ ID NO: 53 and a VH1 comprising SEQ ID NO: 54;
and
2) the VL2 and VH2 are selected from the group consisting of:
a) a VL2 comprising SEQ ID NO: 213 and a VH2 comprising SEQ ID NO: 214;
b) a VL2 comprising SEQ ID NO: 217 and a VH2 comprising SEQ ID NO: 218;
c) a VL2 comprising SEQ ID NO: 221 and a VH2 comprising SEQ ID NO: 222; and
d) a VL2 comprising SEQ ID NO: 225 and a VH2 comprising SEQ ID NO: 226.
In one embodiment, the first antigen is human MSLN (SEQ ID NO: 2) and the second antigen is human CD40 (SEQ ID NO: 1); wherein:
the VL1 comprises a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of:
SEQ ID NOs: 230, 231, and 232, respectively;
SEQ ID NOs: 236, 237, and 238, respectively;
SEQ ID NOs: 242, 243, and 244, respectively; and
SEQ ID NOs: 248, 249, and 250, respectively;
the VH1 comprises a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of:
SEQ ID NOs: 254, 255, and 256, respectively;
SEQ ID NOs: 260, 261, and 262, respectively;
SEQ ID NOs: 266, 267, and 268, respectively; and
SEQ ID NOs: 272, 273, and 274, respectively;
the VL2 comprises a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of:
SEQ ID NOs: 58, 59, and 60, respectively;
SEQ ID NOs: 64, 65, and 66, respectively;
SEQ ID NOs: 70, 71, and 72, respectively;
SEQ ID NOs: 76, 77, and 78, respectively;
SEQ ID NOs: 82, 83, and 84, respectively;
SEQ ID NOs: 88, 89, and 90, respectively;
SEQ ID NOs: 94, 95, and 96, respectively;
SEQ ID NOs: 100, 101, and 102, respectively;
SEQ ID NOs: 106, 107, and 108, respectively;
SEQ ID NOs: 112, 113, and 114, respectively;
SEQ ID NOs: 118, 119, and 120, respectively;
SEQ ID NOs: 124, 125, and 126, respectively; and
SEQ ID NOs: 130, 131, and 132, respectively;
and
the VH2 comprises a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of:
SEQ ID NOs: 136, 137, and 138, respectively;
SEQ ID NOs: 142, 143, and 144, respectively;
SEQ ID NOs: 148, 149, and 150, respectively;
SEQ ID NOs: 154, 155, and 156, respectively;
SEQ ID NOs: 160, 161, and 162, respectively;
SEQ ID NOs: 166, 167, and 168, respectively;
SEQ ID NOs: 172, 173, and 174, respectively;
SEQ ID NOs: 178, 179, and 180, respectively;
SEQ ID NOs: 184, 185, and 186, respectively;
SEQ ID NOs: 190, 191, and 192, respectively;
SEQ ID NOs: 196, 197, and 198, respectively;
SEQ ID NOs: 202, 203, and 204, respectively; and
SEQ ID NOs: 208, 209, and 210, respectively.
In one embodiment,
1) the VL1 and VH1 are selected from the group consisting of:
a) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 230, 231, and 232, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 254, 255, and 256, respectively;
b) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 236, 237, and 238, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 260, 261, and 262, respectively;
c) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 242, 243, and 244, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 266, 267, and 268, respectively; and
d) a VL1 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 248, 249, and 250, respectively; and a VH1 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 272, 273, and 274, respectively;
and
2) the VL2 and VH2 are selected from the group consisting of:
a) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 58, 59, and 60, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 136, 137, and 138, respectively;
b) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 64, 65, and 66, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 142, 143, and 144, respectively;
c) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 70, 71, and 72, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 148, 149, and 150, respectively;
d) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 76, 77, and 6780, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 154, 155, and 156, respectively;
e) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 82, 83, and 84, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 160, 161, and 162, respectively;
f) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 88, 89, and 90, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 166, 167, and 168, respectively;
g) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 94, 95, and 96, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 172, 173, and 174, respectively;
h) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 100, 101, and 102, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 178, 179, and 180, respectively;
i) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 106, 107, and 108, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 184, 185, and 186, respectively;
j) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 112, 113, and 114, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 190, 191, and 192, respectively;
k) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 118, 119, and 120, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 196, 197, and 198, respectively;
l) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 124, 125, and 126, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 202, 203, and 204, respectively; and
m) a VL2 comprising a CDRL1, a CDRL2, and a CDRL3 selected from the group consisting of SEQ ID NOs: 130, 131, and 132, respectively; and a VH2 comprising a CDRH1, a CDRH2, and a CDRH3 selected from the group consisting of SEQ ID NOs: 208, 209, and 210, respectively.
In one embodiment,
the VL1 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 213, 217, 221, and 225;
the VH1 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 214, 218, 222, and 226;
the VL2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53; and
the VH2 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, and 54.
In one embodiment,
1) the VL1 and VH1 are selected from the group consisting of:
a) a VL1 comprising SEQ ID NO: 213 and a VH1 comprising SEQ ID NO: 214;
b) a VL1 comprising SEQ ID NO: 217 and a VH1 comprising SEQ ID NO: 218;
c) a VL1 comprising SEQ ID NO: 221 and a VH1 comprising SEQ ID NO: 222; and
d) a VL1 comprising SEQ ID NO: 225 and a VH1 comprising SEQ ID NO: 226;
and
2) the VL2 and VH2 are selected from the group consisting of:
a) a VL2 comprising SEQ ID NO: 5 and a VH2 comprising SEQ ID NO: 6;
b) a VL2 comprising SEQ ID NO: 9 and a VH2 comprising SEQ ID NO: 10;
c) a VL2 comprising SEQ ID NO: 13 and a VH2 comprising SEQ ID NO: 14;
d) a VL2 comprising SEQ ID NO: 17 and a VH2 comprising SEQ ID NO: 18;
e) a VL2 comprising SEQ ID NO: 21 and a VH2 comprising SEQ ID NO: 22;
f) a VL2 comprising SEQ ID NO: 25 and a VH2 comprising SEQ ID NO: 26;
g) a VL2 comprising SEQ ID NO: 29 and a VH2 comprising SEQ ID NO: 30;
h) a VL2 comprising SEQ ID NO: 33 and a VH2 comprising SEQ ID NO: 34;
i) a VL2 comprising SEQ ID NO: 37 and a VH2 comprising SEQ ID NO: 38;
j) a VL2 comprising SEQ ID NO: 41 and a VH2 comprising SEQ ID NO: 42;
k) a VL2 comprising SEQ ID NO: 45 and a VH2 comprising SEQ ID NO: 46;
l) a VL2 comprising SEQ ID NO: 49 and a VH2 comprising SEQ ID NO: 50; and
m) a VL2 comprising SEQ ID NO: 53 and a VH2 comprising SEQ ID NO: 54.
The present invention includes one or more isolated nucleic acids encoding the multispecific antibody constructs and components thereof described herein. Nucleic acid molecules of the invention include DNA and RNA in both single-stranded and double-stranded form, as well as the corresponding complementary sequences. DNA includes, for example, cDNA, genomic DNA, chemically synthesized DNA, DNA amplified by PCR, and combinations thereof. The nucleic acid molecules of the invention include full-length genes or cDNA molecules as well as a combination of fragments thereof. In one embodiment, the nucleic acids of the invention are derived from human sources, but the invention includes those derived from non-human species, as well.
An “isolated nucleic acid,” which is used interchangeably herein with “isolated polynucleotide,” is a nucleic acid that has been separated from adjacent genetic sequences present in the genome of the organism from which the nucleic acid was isolated, in the case of nucleic acids isolated from naturally-occurring sources. In the case of nucleic acids synthesized enzymatically from a template or chemically, such as PCR products, cDNA molecules, or oligonucleotides for example, it is understood that the nucleic acids resulting from such processes are isolated nucleic acids. An isolated nucleic acid molecule refers to a nucleic acid molecule in the form of a separate fragment or as a component of a larger nucleic acid construct. In one embodiment, the nucleic acids are substantially free from contaminating endogenous material. The nucleic acid molecule has been derived from DNA or RNA isolated at least once in substantially pure form and in a quantity or concentration enabling identification, manipulation, and recovery of its component nucleotide sequences by standard biochemical methods (such as those outlined in Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor, NY (1989)). Such sequences are provided and/or constructed in the form of an open reading frame uninterrupted by internal non-translated sequences, or introns, that are typically present in eukaryotic genes. Sequences of non-translated DNA can be present 5′ or 3′ from an open reading frame, where the same do not interfere with manipulation or expression of the coding region. Unless specified otherwise, the left-hand end of any single-stranded polynucleotide sequence discussed herein is the 5′ end; the left-hand direction of double-stranded polynucleotide sequences is referred to as the 5′ direction. The direction of 5′ to 3′ production of nascent RNA transcripts is referred to as the transcription direction; sequence regions on the DNA strand having the same sequence as the RNA transcript that are 5′ to the 5′ end of the RNA transcript are referred to as “upstream sequences;” sequence regions on the DNA strand having the same sequence as the RNA transcript that are 3′ to the 3′ end of the RNA transcript are referred to as “downstream sequences.”
In one aspect, the present invention is directed to a polynucleotide encoding the light chain of the antibody construct of the present invention.
In one aspect, the present invention is directed to a polynucleotide encoding the heavy chain fusion protein of the antibody construct of the present invention.
In one aspect, the present invention is directed to a vector comprising the polynucleotide encoding the light chain of the antibody construct, the polynucleotide encoding the heavy chain of the antibody construct, or both.
In one aspect, the present invention is directed to a host cell transformed or transfected with the vector or the polynucleotide encoding the light chain of the antibody construct and the polynucleotide encoding the heavy chain of the antibody construct.
In one aspect, the present invention is directed to a process for producing the antibody construct of the present invention, the process comprising culturing a host cell comprising a polynucleotide encoding the light chain and also comprising a polynucleotide encoding the heavy chain fusion protein under conditions allowing the expression of the antibody construct, and recovering the produced antibody construct from the culture.
Variants of the antigen binding proteins described herein can be prepared by site-specific mutagenesis of nucleotides in the DNA encoding the polypeptide, using cassette or PCR mutagenesis or other techniques well known in the art, to produce DNA encoding the variant, and thereafter expressing the recombinant DNA in cell culture as outlined herein. However, antigen binding proteins comprising variant CDRs having up to about 100-150 residues may be prepared by in vitro synthesis using established techniques. The variants typically exhibit the same qualitative biological activity as the naturally occurring analogue, e.g., binding to antigen. Such variants include, for example, deletions and/or insertions and/or substitutions of residues within the amino acid sequences of the antigen binding proteins. Any combination of deletion, insertion, and substitution is made to arrive at the final construct, provided that the final construct possesses the desired characteristics. The amino acid changes also may alter post-translational processes of the antigen binding protein, such as changing the number or position of glycosylation sites. In certain embodiments, antigen binding protein variants are prepared with the intent to modify those amino acid residues which are directly involved in epitope binding. In other embodiments, modification of residues which are not directly involved in epitope binding or residues not involved in epitope binding in any way, is desirable, for purposes discussed herein. Mutagenesis within any of the CDR regions and/or framework regions is contemplated. Covariance analysis techniques can be employed by the skilled artisan to design useful modifications in the amino acid sequence of the antigen binding protein. See, e.g., Choulier, et al., Proteins 41:475-484, 2000; Demarest et al., J. Mol. Biol. 335:41-48, 2004; Hugo et al., Protein Engineering 16(5):381-86, 2003; Aurora et al., US Patent Publication No. 2008/0318207 A1; Glaser et al., US Patent Publication No. 2009/0048122 A1; Urech et al., WO 2008/110348 A1; Borras et al., WO 2009/000099 A2. Such modifications determined by covariance analysis can improve potency, pharmacokinetic, pharmacodynamic, and/or manufacturability characteristics of an antigen binding protein.
The nucleic acid sequences of the present invention. As will be appreciated by those in the art, due to the degeneracy of the genetic code, an extremely large number of nucleic acids may be made, all of which encode the CDRs (and heavy and light chains or other components of the antigen binding proteins described herein) of the invention. Thus, having identified a particular amino acid sequence, those skilled in the art could make any number of different nucleic acids, by simply modifying the sequence of one or more codons in a way which does not change the amino acid sequence of the encoded protein.
The present invention also includes vectors comprising one or more nucleic acids encoding one or more components of the multispecific antibody constructs of the invention (e.g. variable regions, light chains, heavy chains, modified heavy chains, and Fd fragments). The term “vector” refers to any molecule or entity (e.g., nucleic acid, plasmid, bacteriophage or virus) used to transfer protein coding information into a host cell. Examples of vectors include, but are not limited to, plasmids, viral vectors, non-episomal mammalian vectors and expression vectors, for example, recombinant expression vectors. The term “expression vector” or “expression construct” as used herein refers to a recombinant DNA molecule containing a desired coding sequence and appropriate nucleic acid control sequences necessary for the expression of the operably linked coding sequence in a particular host cell. An expression vector can include, but is not limited to, sequences that affect or control transcription, translation, and, if introns are present, affect RNA splicing of a coding region operably linked thereto. Nucleic acid sequences necessary for expression in prokaryotes include a promoter, optionally an operator sequence, a ribosome binding site and possibly other sequences.
Eukaryotic cells are known to utilize promoters, enhancers, and termination and polyadenylation signals. A secretory signal peptide sequence can also, optionally, be encoded by the expression vector, operably linked to the coding sequence of interest, so that the expressed polypeptide can be secreted by the recombinant host cell, for more facile isolation of the polypeptide of interest from the cell, if desired. For instance, in some embodiments, signal peptide sequences may be appended/fused to the amino terminus of any of the polypeptides sequences of the present invention. In certain embodiments, a signal peptide having the amino acid sequence of MDMRVPAQLLGLLLLWLRGARC (SEQ ID NO: 894) is fused to the amino terminus of any of the polypeptide sequences of the present invention. In other embodiments, a signal peptide having the amino acid sequence of MAWALLLLTLLTQGTGSWA (SEQ ID NO: 895) is fused to the amino terminus of any of the polypeptide sequences of the present invention. In still other embodiments, a signal peptide having the amino acid sequence of MTCSPLLLTLLIHCTGSWA (SEQ ID NO: 896) is fused to the amino terminus of any of the polypeptide sequences of the present invention. Other suitable signal peptide sequences that can be fused to the amino terminus of the polypeptide sequences described herein include: MEAPAQLLFLLLLWLPDTTG (SEQ ID NO: 897), MEWTWRVLFLVAAATGAHS (SEQ ID NO: 898), METPAQLLFLLLLWLPDTTG (SEQ ID NO: 899), METPAQLLFLLLLWLPDTTG (SEQ ID NO: 900), MKHLWFFLLLVAAPRWVLS (SEQ ID NO: 901), and MEWSWVFLFFLSVTTGVHS (SEQ ID NO: 902). Other signal peptides are known to those of skill in the art and may be fused to any of the polypeptide chains of the present invention, for example, to facilitate or optimize expression in particular host cells.
Typically, expression vectors used in the host cells to produce the bispecific antigen proteins of the invention will contain sequences for plasmid maintenance and for cloning and expression of exogenous nucleotide sequences encoding the components of the multispecific antibody constructs. Such sequences, collectively referred to as “flanking sequences,” in certain embodiments will typically include one or more of the following nucleotide sequences: a promoter, one or more enhancer sequences, an origin of replication, a transcriptional termination sequence, a complete intron sequence containing a donor and acceptor splice site, a sequence encoding a leader sequence for polypeptide secretion, a ribosome binding site, a polyadenylation sequence, a polylinker region for inserting the nucleic acid encoding the polypeptide to be expressed, and a selectable marker element.
Each of these sequences is discussed below.
Optionally, the vector may contain a “tag”-encoding sequence, i.e., an oligonucleotide molecule located at the 5′ or 3′ end of the polypeptide coding sequence; the oligonucleotide tag sequence encodes polyHis (such as hexaHis (SEQ ID NO: 925)), FLAG, HA (hemaglutinin influenza virus), myc, or another “tag” molecule for which commercially available antibodies exist. This tag is typically fused to the polypeptide upon expression of the polypeptide, and can serve as a means for affinity purification or detection of the polypeptide from the host cell. Affinity purification can be accomplished, for example, by column chromatography using antibodies against the tag as an affinity matrix. Optionally, the tag can subsequently be removed from the purified polypeptide by various means such as using certain peptidases for cleavage.
Flanking sequences may be homologous (i.e., from the same species and/or strain as the host cell), heterologous (i.e., from a species other than the host cell species or strain), hybrid (i.e., a combination of flanking sequences from more than one source), synthetic or native. As such, the source of a flanking sequence may be any prokaryotic or eukaryotic organism, any vertebrate or invertebrate organism, or any plant, provided that the flanking sequence is functional in, and can be activated by, the host cell machinery.
Flanking sequences useful in the vectors of this invention may be obtained by any of several methods well known in the art. Typically, flanking sequences useful herein will have been previously identified by mapping and/or by restriction endonuclease digestion and can thus be isolated from the proper tissue source using the appropriate restriction endonucleases. In some cases, the full nucleotide sequence of a flanking sequence may be known. Here, the flanking sequence may be synthesized using routine methods for nucleic acid synthesis or cloning.
Whether all or only a portion of the flanking sequence is known, it may be obtained using polymerase chain reaction (PCR) and/or by screening a genomic library with a suitable probe such as an oligonucleotide and/or flanking sequence fragment from the same or another species. Where the flanking sequence is not known, a fragment of DNA containing a flanking sequence may be isolated from a larger piece of DNA that may contain, for example, a coding sequence or even another gene or genes. Isolation may be accomplished by restriction endonuclease digestion to produce the proper DNA fragment followed by isolation using agarose gel purification, Qiagen® column chromatography (Chatsworth, CA), or other methods known to the skilled artisan. The selection of suitable enzymes to accomplish this purpose will be readily apparent to one of ordinary skill in the art.
An origin of replication is typically a part of those prokaryotic expression vectors purchased commercially, and the origin aids in the amplification of the vector in a host cell. If the vector of choice does not contain an origin of replication site, one may be chemically synthesized based on a known sequence, and ligated into the vector. For example, the origin of replication from the plasmid pBR322 (New England Biolabs, Beverly, MA) is suitable for most gram-negative bacteria, and various viral origins (e.g., SV40, polyoma, adenovirus, vesicular stomatitus virus (VSV), or papillomaviruses such as HPV or BPV) are useful for cloning vectors in mammalian cells. Generally, the origin of replication component is not needed for mammalian expression vectors (for example, the SV40 origin is often used only because it also contains the virus early promoter).
A transcription termination sequence is typically located 3′ to the end of a polypeptide coding region and serves to terminate transcription. Usually, a transcription termination sequence in prokaryotic cells is a G-C rich fragment followed by a poly-T sequence. While the sequence is easily cloned from a library or even purchased commercially as part of a vector, it can also be readily synthesized using known methods for nucleic acid synthesis.
A selectable marker gene encodes a protein necessary for the survival and growth of a host cell grown in a selective culture medium. Typical selection marker genes encode proteins that (a) confer resistance to antibiotics or other toxins, e.g., ampicillin, tetracycline, or kanamycin for prokaryotic host cells; (b) complement auxotrophic deficiencies of the cell; or (c) supply critical nutrients not available from complex or defined media. Specific selectable markers are the kanamycin resistance gene, the ampicillin resistance gene, and the tetracycline resistance gene. Advantageously, a neomycin resistance gene may also be used for selection in both prokaryotic and eukaryotic host cells.
Other selectable genes may be used to amplify the gene that will be expressed. Amplification is the process wherein genes that are required for production of a protein critical for growth or cell survival are reiterated in tandem within the chromosomes of successive generations of recombinant cells. Examples of suitable selectable markers for mammalian cells include dihydrofolate reductase (DHFR) and promoterless thymidine kinase genes. Mammalian cell transformants are placed under selection pressure wherein only the transformants are uniquely adapted to survive by virtue of the selectable gene present in the vector. Selection pressure is imposed by culturing the transformed cells under conditions in which the concentration of selection agent in the medium is successively increased, thereby leading to the amplification of both the selectable gene and the DNA that encodes another gene, such as one or more components of the multispecific antibody constructs described herein. As a result, increased quantities of a polypeptide are synthesized from the amplified DNA.
A ribosome-binding site is usually necessary for translation initiation of mRNA and is characterized by a Shine-Dalgarno sequence (prokaryotes) or a Kozak sequence (eukaryotes). The element is typically located 3′ to the promoter and 5′ to the coding sequence of the polypeptide to be expressed. In certain embodiments, one or more coding regions may be operably linked to an internal ribosome binding site (IRES), allowing translation of two open reading frames from a single RNA transcript.
In some cases, such as where glycosylation is desired in a eukaryotic host cell expression system, one may manipulate the various pre- or prosequences to improve glycosylation or yield. For example, one may alter the peptidase cleavage site of a particular signal peptide, or add prosequences, which also may affect glycosylation. The final protein product may have, in the −1 position (relative to the first amino acid of the mature protein) one or more additional amino acids incident to expression, which may not have been totally removed. For example, the final protein product may have one or two amino acid residues found in the peptidase cleavage site, attached to the amino-terminus.
Alternatively, use of some enzyme cleavage sites may result in a slightly truncated form of the desired polypeptide, if the enzyme cuts at such area within the mature polypeptide.
Expression and cloning vectors of the invention will typically contain a promoter that is recognized by the host organism and operably linked to the molecule encoding the polypeptide. The term “operably linked” as used herein refers to the linkage of two or more nucleic acid sequences in such a manner that a nucleic acid molecule capable of directing the transcription of a given gene and/or the synthesis of a desired protein molecule is produced. For example, a control sequence in a vector that is “operably linked” to a protein coding sequence is ligated thereto so that expression of the protein coding sequence is achieved under conditions compatible with the transcriptional activity of the control sequences. More specifically, a promoter and/or enhancer sequence, including any combination of cis-acting transcriptional control elements is operably linked to a coding sequence if it stimulates or modulates the transcription of the coding sequence in an appropriate host cell or other expression system.
Promoters are untranscribed sequences located upstream (i.e., 5′) to the start codon of a structural gene (generally within about 100 to 1000 bp) that control transcription of the structural gene. Promoters are conventionally grouped into one of two classes: inducible promoters and constitutive promoters. Inducible promoters initiate increased levels of transcription from DNA under their control in response to some change in culture conditions, such as the presence or absence of a nutrient or a change in temperature. Constitutive promoters, on the other hand, uniformly transcribe a gene to which they are operably linked, that is, with little or no control over gene expression. A large number of promoters, recognized by a variety of potential host cells, are well known. A suitable promoter is operably linked to the DNA encoding e.g., heavy chain, light chain, modified heavy chain, or other component of the multispecific antibody constructs of the invention, by removing the promoter from the source DNA by restriction enzyme digestion and inserting the desired promoter sequence into the vector.
Suitable promoters for use with yeast hosts are also well known in the art. Yeast enhancers are advantageously used with yeast promoters. Suitable promoters for use with mammalian host cells are well known and include, but are not limited to, those obtained from the genomes of viruses such as polyoma virus, fowlpox virus, adenovirus (such as Adenovirus 2), bovine papilloma virus, avian sarcoma virus, cytomegalovirus, retroviruses, hepatitis-B virus and Simian Virus 40 (SV40). Other suitable mammalian promoters include heterologous mammalian promoters, for example, heat-shock promoters and the actin promoter.
Additional promoters which may be of interest include, but are not limited to: SV40 early promoter (Benoist and Chambon, 1981, Nature 290:304-310); CMV promoter (Thornsen et al., 1984, Proc. Natl. Acad. U.S.A. 81:659-663); the promoter contained in the 3′ long terminal repeat of Rous sarcoma virus (Yamamoto et al., 1980, Cell 22:787-797); herpes thymidine kinase promoter (Wagner et al., 1981, Proc. Natl. Acad. Sci. U.S.A. 78: 1444-1445); promoter and regulatory sequences from the metallothionine gene Prinster et al., 1982, Nature 296:39-42); and prokaryotic promoters such as the beta-lactamase promoter (Villa-Kamaroff et al., 1978, Proc. Natl. Acad. Sci. U.S.A. 75:3727-3731); or the tac promoter (DeBoer et al., 1983, Proc. Natl. Acad. Sci. U.S.A. 80:21-25). Also of interest are the following animal transcriptional control regions, which exhibit tissue specificity and have been utilized in transgenic animals: the elastase I gene control region that is active in pancreatic acinar cells (Swift et al., 1984, Cell 38:639-646; Ornitz et al., 1986, Cold Spring Harbor Symp. Quant. Biol. 50:399-409; MacDonald, 1987, Hepatology 7:425-515); the insulin gene control region that is active in pancreatic beta cells (Hanahan, 1985, Nature 315: 115-122); the immunoglobulin gene control region that is active in lymphoid cells (Grosschedl et al., 1984, Cell 38:647-658; Adames et al., 1985, Nature 318:533-538; Alexander et al., 1987, Mol. Cell. Biol. 7: 1436-1444); the mouse mammary tumor virus control region that is active in testicular, breast, lymphoid and mast cells (Leder et al., 1986, Cell 45:485-495); the albumin gene control region that is active in liver (Pinkert et al., 1987, Genes and Devel. 1:268-276); the alpha-feto-protein gene control region that is active in liver (Krumlauf et al., 1985, Mol. Cell. Biol. 5: 1639-1648; Hammer et al., 1987, Science 253:53-58); the alpha 1-antitrypsin gene control region that is active in liver (Kelsey et al., 1987, Genes and Devel. 1: 161-171); the beta-globin gene control region that is active in myeloid cells (Mogram et al, 1985, Nature 315:338-340; Kollias et al, 1986, Cell 46:89-94); the myelin basic protein gene control region that is active in oligodendrocyte cells in the brain (Readhead et al., 1987, Cell 48:703-712); the myosin light chain-2 gene control region that is active in skeletal muscle (Sani, 1985, Nature 314:283-286); and the gonadotropic releasing hormone gene control region that is active in the hypothalamus (Mason et al., 1986, Science 234: 1372-1378).
An enhancer sequence may be inserted into the vector to increase transcription of DNA encoding a component of the multispecific antibody constructs (e.g., light chain, heavy chain, modified heavy chain, Fd fragment) by higher eukaryotes. Enhancers are cis-acting elements of DNA, usually about 10−300 bp in length, that act on the promoter to increase transcription. Enhancers are relatively orientation and position independent, having been found at positions both 5′ and 3′ to the transcription unit. Several enhancer sequences available from mammalian genes are known (e.g., globin, elastase, albumin, alpha-feto-protein and insulin). Typically, however, an enhancer from a virus is used. The SV40 enhancer, the cytomegalovirus early promoter enhancer, the polyoma enhancer, and adenovirus enhancers known in the art are exemplary enhancing elements for the activation of eukaryotic promoters. While an enhancer may be positioned in the vector either 5′ or 3′ to a coding sequence, it is typically located at a site 5′ from the promoter. A sequence encoding an appropriate native or heterologous signal sequence (leader sequence or signal peptide) can be incorporated into an expression vector, to promote extracellular secretion of the antibody. The choice of signal peptide or leader depends on the type of host cells in which the antibody is to be produced, and a heterologous signal sequence can replace the native signal sequence. Examples of signal peptides are described above. Other signal peptides that are functional in mammalian host cells include the signal sequence for interleukin-7 (IL-7) described in U.S. Pat. No. 4,965,195; the signal sequence for interleukin-2 receptor described in Cosman et al., 1984, Nature 312:768; the interleukin-4 receptor signal peptide described in EP Patent No. 0367 566; the type I interleukin-1 receptor signal peptide described in U.S. Pat. No. 4,968,607; the type II interleukin-1 receptor signal peptide described in EP Patent No. 0 460 846.
The expression vectors that are provided may be constructed from a starting vector such as a commercially available vector. Such vectors may or may not contain all of the desired flanking sequences. Where one or more of the flanking sequences described herein are not already present in the vector, they may be individually obtained and ligated into the vector. Methods used for obtaining each of the flanking sequences are well known to one skilled in the art. The expression vectors can be introduced into host cells to thereby produce proteins, including fusion proteins, encoded by nucleic acids as described herein.
In certain embodiments, nucleic acids encoding the different components of the multispecific antibody constructs of the invention may be inserted into the same expression vector. For instance, the nucleic acid encoding an anti-first target antigen light chain can be cloned into the same vector as the nucleic acid encoding an anti-first target antigen heavy chain. In such embodiments, the two nucleic acids may be separated by an internal ribosome entry site (IRES) and under the control of a single promoter such that the light chain and heavy chain are expressed from the same mRNA transcript. Alternatively, the two nucleic acids may be under the control of two separate promoters such that the light chain and heavy chain are expressed from two separate mRNA transcripts. In some embodiments, nucleic acids encoding the anti-first target antigen light chain and heavy chain are cloned into one expression vector and the nucleic acids encoding the anti-second target antigen light chain and heavy chain are cloned into a second expression vector.
Similarly, for IgG-Fab multispecific antibody constructs, nucleic acids encoding each of the three components may be cloned into the same expression vector. In some embodiments, the nucleic acid encoding the light chain of the IgG-Fab molecule and the nucleic acid encoding the second polypeptide (which comprises the other half of the C-terminal Fab domain) are cloned into one expression vector, whereas the nucleic acid encoding the modified heavy chain (fusion protein comprising a heavy chain and half of a Fab domain) is cloned into a second expression vector. In certain embodiments, all components of the multispecific antibody constructs described herein are expressed from the same host cell population. For example, even if one or more components is cloned into a separate expression vector, the host cell is co-transfected with both expression vectors such that one cell produces all components of the multispecific antibody constructs.
After the vector has been constructed and the one or more nucleic acid molecules encoding the components of the multispecific antibody constructs described herein has been inserted into the proper site(s) of the vector or vectors, the completed vector(s) may be inserted into a suitable host cell for amplification and/or polypeptide expression. Thus, the present invention encompasses an isolated host cell comprising one or more expression vectors encoding the components of the multispecific antibody constructs. The term “host cell” as used herein refers to a cell that has been transformed, or is capable of being transformed, with a nucleic acid and thereby expresses a gene of interest. The term includes the progeny of the parent cell, whether or not the progeny is identical in morphology or in genetic make-up to the original parent cell, so long as the gene of interest is present. A host cell that comprises an isolated nucleic acid of the invention, in one embodiment operably linked to at least one expression control sequence (e.g. promoter or enhancer), is a “recombinant host cell.”
The transformation of an expression vector for an antigen binding protein into a selected host cell may be accomplished by well-known methods including transfection, infection, calcium phosphate co-precipitation, electroporation, microinjection, lipofection, DEAE-dextran mediated transfection, or other known techniques. The method selected will in part be a function of the type of host cell to be used. These methods and other suitable methods are well known to the skilled artisan, and are set forth, for example, in Sambrook et al., 2001, supra.
A host cell, when cultured under appropriate conditions, synthesizes an antigen binding protein that can subsequently be collected from the culture medium (if the host cell secretes it into the medium) or directly from the host cell producing it (if it is not secreted). The selection of an appropriate host cell will depend upon various factors, such as desired expression levels, polypeptide modifications that are desirable or necessary for activity (such as glycosylation or phosphorylation) and ease of folding into a biologically active molecule.
Exemplary host cells include prokaryote, yeast, or higher eukaryote cells. Prokaryotic host cells include eubacteria, such as Gram-negative or Gram-positive organisms, for example, Enterobacteriaceae such as Escherichia, e.g., E. coli, Enterobacter, Erwinia, Klebsiella, Proteus, Salmonella, e.g., Salmonella typhimurium, Serratia, e.g., Serratia marcescans, and Shigella, as well as Bacillus, such as B. subtilis and B. licheniformis, Pseudomonas, and Streptomyces. Eukaryotic microbes such as filamentous fungi or yeast are suitable cloning or expression hosts for recombinant polypeptides. Saccharomyces cerevisiae, or common baker's yeast, is the most commonly used among lower eukaryotic host microorganisms. However, a number of other genera, species, and strains are commonly available and useful herein, such as Pichia, e.g. P. pastoris, Schizosaccharomyces pombe; Kluyveromyces, Yarrowia; Candida; Trichoderma reesia; Neurospora crassa; Schwanniomyces, such as Schwanniomyces occidentalis; and filamentous fungi, such as, e.g., Neurospora, Penicillium, Tolypocladium, and Aspergillus hosts such as A. nidulans and A. niger.
Host cells for the expression of glycosylated antigen binding proteins can be derived from multicellular organisms. Examples of invertebrate cells include plant and insect cells. Numerous baculoviral strains and variants and corresponding permissive insect host cells from hosts such as Spodoptera frugiperda (caterpillar), Aedes aegypti (mosquito), Aedes albopictus (mosquito), Drosophila melanogaster (fruitfly), and Bombyx mori have been identified. A variety of viral strains for transfection of such cells are publicly available, e.g., the L-1 variant of Autographa californica NPV and the Bm-5 strain of Bombyx mori NPV.
Vertebrate host cells are also suitable hosts, and recombinant production of antigen binding proteins from such cells has become routine procedure. Mammalian cell lines available as hosts for expression are well known in the art and include, but are not limited to, immortalized cell lines available from the American Type Culture Collection (ATCC), including but not limited to Chinese hamster ovary (CHO) cells, including CHOKI cells (ATCC CCL61), DXB-11, DG-44, and Chinese hamster ovary cells/-DHFR (CHO, Urlaub et al., Proc. Natl. Acad. Sci. USA 77: 4216, 1980); monkey kidney CV1 line transformed by SV40 (COS-7, ATCC CRL 1651); human embryonic kidney line (293 or 293 cells subcloned for growth in suspension culture, (Graham et al., J. Gen Virol. 36: 59, 1977); baby hamster kidney cells (BHK, ATCC CCL 10); mouse sertoli cells (TM4, Mather, Biol. Reprod. 23: 243-251, 1980); monkey kidney cells (CV1 ATCC CCL 70); African green monkey kidney cells (VERO-76, ATCC CRL-1587); human cervical carcinoma cells (HELA, ATCC CCL 2); canine kidney cells (MDCK, ATCC CCL 34); buffalo rat liver cells (BRL 3A, ATCC CRL 1442); human lung cells (W138, ATCC CCL 75); human hepatoma cells (Hep G2, HB 8065); mouse mammary tumor (MMT 060562, ATCC CCL51); TRI cells (Mather et al., Annals N.Y Acad. Sci. 383: 44-68, 1982); MRC 5 cells or FS4 cells; mammalian myeloma cells, and a number of other cell lines. In certain embodiments, cell lines may be selected through determining which cell lines have high expression levels and constitutively produce multispecific antibody constructs of the present invention. In another embodiment, a cell line from the B cell lineage that does not make its own antibody but has a capacity to make and secrete a heterologous antibody can be selected. CHO cells are host cells in some embodiments for expressing the multispecific antibody constructs of the invention.
Host cells are transformed or transfected with the above-described nucleic acids or vectors for production of multispecific antibody constructs and are cultured in conventional nutrient media modified as appropriate for inducing promoters, selecting transformants, or amplifying the genes encoding the desired sequences. In addition, novel vectors and transfected cell lines with multiple copies of transcription units separated by a selective marker are particularly useful for the expression of antigen binding proteins. Thus, the present invention also provides a method for preparing a multispecific antibody construct described herein comprising culturing a host cell comprising one or more expression vectors described herein in a culture medium under conditions permitting expression of the multispecific antibody construct encoded by the one or more expression vectors; and recovering the multispecific antibody construct from the culture medium.
The host cells used to produce the antigen binding proteins of the invention may be cultured in a variety of media. Commercially available media such as Ham's F10 (Sigma), Minimal Essential Medium ((MEM), (Sigma), RPMI-1640 (Sigma), and Dulbecco's Modified Eagle's Medium ((DMEM), Sigma) are suitable for culturing the host cells. In addition, any of the media described in Ham et al., Meth. Enz. 58: 44, 1979; Barnes et al., Anal. Biochem. 102: 255, 1980; U.S. Pat. Nos. 4,767,704; 4,657,866; 4,927,762; 4,560,655; or 5,122,469; WO90103430; WO 87/00195; or U.S. Patent Re. No. 30,985 may be used as culture media for the host cells. Any of these media may be supplemented as necessary with hormones and/or other growth factors (such as insulin, transferrin, or epidermal growth factor), salts (such as sodium chloride, calcium, magnesium, and phosphate), buffers (such as HEPES), nucleotides (such as adenosine and thymidine), antibiotics (such as Gentamycin™ drug), trace elements (defined as inorganic compounds usually present at final concentrations in the micromolar range), and glucose or an equivalent energy source. Any other necessary supplements may also be included at appropriate concentrations that would be known to those skilled in the art. The culture conditions, such as temperature, pH, and the like, are those previously used with the host cell selected for expression, and will be apparent to the ordinarily skilled artisan.
Upon culturing the host cells, the multispecific antibody construct can be produced intracellularly, in the periplasmic space, or directly secreted into the medium. If the antigen binding protein is produced intracellularly, as a first step, the particulate debris, either host cells or lysed fragments, is removed, for example, by centrifugation or ultrafiltration. The bispecifc antigen binding protein can be purified using, for example, hydroxyapatite chromatography, cation or anion exchange chromatography, or affinity chromatography, using the antigen(s) of interest or protein A or protein G as an affinity ligand. Protein A can be used to purify proteins that include polypeptides that are based on human γ1, γ2, or γ4 heavy chains (Lindmark et al., J. Immunol. Meth. 62: 1-13, 1983). Protein G is recommended for all mouse isotypes and for human γ3 (Guss et al., EMBO J. 5: 15671575, 1986). The matrix to which the affinity ligand is attached is most often agarose, but other matrices are available. Mechanically stable matrices such as controlled pore glass or poly(styrenedivinyl)benzene allow for faster flow rates and shorter processing times than can be achieved with agarose. Where the protein comprises a CH3 domain, the Bakerbond ABX™ resin (J. T. Baker, Phillipsburg, N.J.) is useful for purification. Other techniques for protein purification such as ethanol precipitation, Reverse Phase HPLC, chromatofocusing, SDS-PAGE, and ammonium sulfate precipitation are also possible depending on the particular multispecific antibody construct to be recovered.
The multispecific antibody constructs of the invention are useful for detecting target antigen(s) in biological samples and identification of cells or tissues that express the target antigen(s). The multispecific antibody constructs described herein can be used for diagnostic purposes to detect, diagnose, or monitor diseases and/or conditions associated with the target antigen(s). Also provided are methods for the detection of the presence of the target antigen(s) in a sample using classical immunohistological methods known to those of skill in the art (e.g., Tijssen, 1993, Practice and Theory of Enzyme Immunoassays, Vol 15 (Eds R. H. Burdon and P. H. van Knippenberg, Elsevier, Amsterdam); Zola, 1987, Monoclonal Antibodies: A Manual of Techniques, pp. 147-158 (CRC Press, Inc.); Jalkanen et al., 1985, J. Cell. Biol. 101:976-985; Jalkanen et al., 1987, J. Cell Biol. 105:3087-3096). The detection of either target can be performed in vivo or in vitro.
One embodiment provides the multispecific antibody construct of the invention or the multispecific antibody construct produced according to the process of the invention for use in the prevention, treatment or amelioration of a tumor or cancer disease or of a metastatic cancer disease.
According to a preferred embodiment of the invention said tumor or cancer disease is a solid tumor disease.
The formulations described herein are useful as pharmaceutical compositions in the treatment, amelioration and/or prevention of the pathological medical condition as described herein in a patient in need thereof. The term “treatment” refers to both therapeutic treatment and prophylactic or preventative measures. Treatment includes the application or administration of the formulation to the body, an isolated tissue, or cell from a patient who has a disease/disorder, a symptom of a disease/disorder, or a predisposition toward a disease/disorder, with the purpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve, or affect the disease, the symptom of the disease, or the predisposition toward the disease.
The term “amelioration” as used herein refers to any improvement of the disease state of a patient having a tumor or cancer or a metastatic cancer as specified herein below, by the administration of an multispecific antibody construct according to the invention to a subject in need thereof. Such an improvement may also be seen as a slowing or stopping of the p progression of the tumor or cancer or metastatic cancer of the patient. The term “prevention” as used herein means the avoidance of the occurrence or re-occurrence of a patient having a tumor or cancer or a metastatic cancer as specified herein below, by the administration of an multispecific antibody construct according to the invention to a subject in need thereof.
The term “disease” refers to any condition that would benefit from treatment with the multispecific antibody construct or the pharmaceutic composition described herein. This includes chronic and acute disorders or diseases including those pathological conditions that predispose the mammal to the disease in question. A “neoplasm” is is an abnormal growth of tissue, usually but not always forming a mass. When also forming a mass, it is commonly referred to as a “tumor”. Neoplasms or tumors or can be benign, potentially malignant (pre-cancerous), or malignant. Malignant neoplasms are commonly called cancer. They usually invade and destroy the surrounding tissue and may form metastases, i.e., they spread to other parts, tissues or organs of the body. Hence, the term “metatstatic cancer” encompasses metastases to other tissues or organs than the one of the original tumor. Lymphomas and leukemias are lymphoid neoplasms. For the purposes of the present invention, they are also encompassed by the terms “tumor” or “cancer”.
In a preferred embodiment of the invention, the tumor or cancer disease is a solid tumor disease and the metastatic cancer disease can be derived from any of the foregoing.
Preferred tumor or cancer diseases in conneetion with this invention are selected from a group consisting of breast cancer, Carcinoid, cervical cancer, colorectal cancer, endometrial cancer, gastric cancer, head and neck cancer, mesothelioma, liver cancer, lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, skin cancer, renal cancer and stomach cancer. More prefereably, the tumor or cancer disease, which is prefereably a solid tumor disease, can be selected from the group consisting of ovarian cancer, pancreatic cancer, mesothelioma, lung cancer, gastric cancer and triple negative breast cancer. The metastatic cancer disease can be derived from any of the foregoing.
The invention also provides a method for the treatment or amelioration of tumor or cancer disease or a metastatic cancer disease, comprising the step of administering to a subject in need thereof the multispecific antibody construct of the invention or the multispecific antibody construct produced according to the process of the invention.
The terms “subject in need” or those “in need of treatment” includes those already with the disorder, as well as those in which the disorder is to be prevented. The subject in need or “patient” includes human and other mammalian subjects that receive either prophylactic or therapeutic treatment.
The multispecific antibody construct of the invention will generally be designed for specific routes and methods of administration, for specific dosages and frequencies of administration, for specific treatments of specific diseases, with ranges of bio-availability and persistence, among other things. The materials of the composition are preferably formulated in concentrations that are acceptable for the site of administration.
Formulations and compositions thus may be designed in accordance with the invention for delivery by any suitable route of administration. In the context of the present invention, the routes of administration include, but are not limited to
topical routes (such as epicutaneous, inhalational, nasal, opthalmic, auricular/aural, vaginal, mucosal);
enteral routes (such as oral, gastrointestinal, sublingual, sublabial, buccal, rectal); and
parenteral routes (such as intravenous, intraarterial, intraosseous, intramuscular, intracerebral, intracerebroventricular, epidural, intrathecal, subcutaneous, intraperitoneal, extra-amniotic, intraarticular, intracardiac, intradermal, intralesional, intrauterine, intravesical, intravitreal, transdermal, intranasal, transmucosal, intrasynovial, intraluminal).
The pharmaceutical compositions and the multispecific antibody construct of this invention are particularly useful for parenteral administration, e.g., subcutaneous or intravenous delivery, for example by injection such as bolus injection, or by infusion such as continuous infusion.
Pharmaceutical compositions may be administered using a medical device. Examples of medical devices for administering pharmaceutical compositions are described in U.S. Pat. Nos. 4,475,196; 4,439,196; 4,447,224; 4,447, 233; 4,486,194; 4,487,603; 4,596,556; 4,790,824; 4,941,880; 5,064,413; 5,312,335; 5,312,335; 5,383,851; and 5,399,163.
In particular, the present invention provides for an uninterrupted administration of the suitable composition. As a non-limiting example, uninterrupted or substantially uninterrupted, i.e. continuous administration may be realized by a small pump system worn by the patient for metering the influx of therapeutic agent into the body of the patient. The pharmaceutical composition comprising the multispecific antibody construct of the invention can be administered by using said pump systems.
Such pump systems are generally known in the art, and commonly rely on periodic exchange of cartridges containing the therapeutic agent to be infused. When exchanging the cartridge in such a pump system, a temporary interruption of the otherwise uninterrupted flow of therapeutic agent into the body of the patient may ensue. In such a case, the phase of administration prior to cartridge replacement and the phase of administration following cartridge replacement would still be considered within the meaning of the pharmaceutical means and methods of the invention together make up one “uninterrupted administration” of such therapeutic agent.
The continuous or uninterrupted administration of the multispecific antibody constructs of the invention may be intravenous or subcutaneous by way of a fluid delivery device or small pump system including a fluid driving mechanism for driving fluid out of a reservoir and an actuating mechanism for actuating the driving mechanism. Pump systems for subcutaneous administration may include a needle or a cannula for penetrating the skin of a patient and delivering the suitable composition into the patient's body. Said pump systems may be directly fixed or attached to the skin of the patient independently of a vein, artery or blood vessel, thereby allowing a direct contact between the pump system and the skin of the patient. The pump system can be attached to the skin of the patient for 24 hours up to several days. The pump system may be of small size with a reservoir for small volumes. As a non-limiting example, the volume of the reservoir for the suitable pharmaceutical composition to be administered can be between 0.1 and 50 ml.
The continuous administration may also be transdermal by way of a patch worn on the skin and replaced at intervals. One of skill in the art is aware of patch systems for drug delivery suitable for this purpose. It is of note that transdermal administration is especially amenable to uninterrupted administration, as exchange of a first exhausted patch can advantageously be accomplished simultaneously with the placement of a new, second patch, for example on the surface of the skin immediately adjacent to the first exhausted patch and immediately prior to removal of the first exhausted patch. Issues of flow interruption or power cell failure do not arise.
If the pharmaceutical composition has been lyophilized, the lyophilized material is first reconstituted in an appropriate liquid prior to administration. The lyophilized material may be reconstituted in, e.g., bacteriostatic water for injection (BWFI), physiological saline, phosphate buffered saline (PBS), or the same formulation the protein had been in prior to lyophilization.
The compositions of the present invention can be administered to the subject at a suitable dose which can be determined e.g. by dose escalating studies by administration of increasing doses of the multispecific antibody construct of the invention exhibiting cross-species specificity described herein to non-chimpanzee primates, for instance macaques. As set forth above, the multispecific antibody construct of the invention exhibiting cross-species specificity described herein can be advantageously used in identical form in preclinical testing in non-chimpanzee primates and as drug in humans. The dosage regimen will be determined by the attending physician and clinical factors. As is well known in the medical arts, dosages for any one patient depend upon many factors, including the patient's size, body surface area, age, the particular compound to be administered, sex, time and route of administration, general health, and other drugs being administered concurrently.
The term “effective dose” or “effective dosage” is defined as an amount sufficient to achieve or at least partially achieve the desired effect. The term “therapeutically effective dose” is defined as an amount sufficient to cure or at least partially arrest the disease and its complications in a patient already suffering from the disease. Amounts or doses effective for this use will depend on the condition to be treated (the indication), the delivered multispecific antibody construct, the therapeutic context and objectives, the severity of the disease, prior therapy, the patient's clinical history and response to the therapeutic agent, the route of administration, the size (body weight, body surface or organ size) and/or condition (the age and general health) of the patient, and the general state of the patient's own immune system. The proper dose can be adjusted according to the judgment of the attending physician such that it can be administered to the patient once or over a series of administrations, and in order to obtain the optimal therapeutic effect.
A therapeutic effective amount of an multispecific antibody construct of the invention preferably results in a decrease in severity of disease symptoms, an increase in frequency or duration of disease symptom-free periods or a prevention of impairment or disability due to the disease affliction. For treating MSLN-expressing tumors, a therapeutically effective amount of the multispecific antibody construct of the invention, e.g. an anti-MSLN/anti-CD40 multispecific antibody construct, preferably inhibits cell growth or tumor growth by at least about 20%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90% relative to untreated patients. The ability of a compound to inhibit tumor growth may be evaluated in an animal model predictive of efficacy in human tumors.
The pharmaceutical composition can be administered as a sole therapeutic or in combination with additional therapies such as anti-cancer therapies as needed, e.g. other proteinaceous and non-proteinaceous drugs. These drugs may be administered simultaneously with the composition comprising the multispecific antibody construct of the invention as defined herein or separately before or after administration of said multispecific antibody construct in timely defined intervals and doses.
The term “effective and non-toxic dose” as used herein refers to a tolerable dose of an inventive multispecific antibody construct which is high enough to cause depletion of pathologic cells, tumor elimination, tumor shrinkage or stabilization of disease without or essentially without major toxic effects. Such effective and non-toxic doses may be determined e.g. by dose escalation studies described in the art and should be below the dose inducing severe adverse side events (dose limiting toxicity, DLT).
The term “toxicity” as used herein refers to the toxic effects of a drug manifested in adverse events or severe adverse events. These side events might refer to a lack of tolerability of the drug in general and/or a lack of local tolerance after administration. Toxicity could also include teratogenic or carcinogenic effects caused by the drug.
The term “safety”, “in vivo safety” or “tolerability” as used herein defines the administration of a drug without inducing severe adverse events directly after administration (local tolerance) and during a longer period of application of the drug. “Safety”, “in vivo safety” or “tolerability” can be evaluated e.g. at regular intervals during the treatment and follow-up period. Measurements include clinical evaluation, e.g. organ manifestations, and screening of laboratory abnormalities. Clinical evaluation may be carried out and deviations to normal findings recorded/coded according to NCI-CTC and/or MedDRA standards. Organ manifestations may include criteria such as allergy/immunology, blood/bone marrow, cardiac arrhythmia, coagulation and the like, as set forth e.g. in the Common Terminology Criteria for adverse events v3.0 (CTCAE). Laboratory parameters which may be tested include for instance hematology, clinical chemistry, coagulation profile and urine analysis and examination of other body fluids such as serum, plasma, lymphoid or spinal fluid, liquor and the like. Safety can thus be assessed e.g. by physical examination, imaging techniques (i.e. ultrasound, x-ray, CT scans, Magnetic Resonance Imaging (MRI), other measures with technical devices (i.e. electrocardiogram), vital signs, by measuring laboratory parameters and recording adverse events. For example, adverse events in non-chimpanzee primates in the uses and methods according to the invention may be examined by histopathological and/or histochemical methods. The above terms are also referred to e.g. in the Preclinical safety evaluation of biotechnology-derived pharmaceuticals S6; ICH Harmonised Tripartite Guideline; ICH Steering Committee meeting on Jul. 16, 1997.
In a further embodiment, the invention provides a kit comprising an multispecific antibody construct of the invention, an multispecific antibody construct produced according to the process of the invention, a polynucleotide of the invention, a vector of the invention, and/or a host cell of the invention.
In the context of the present invention, the term “kit” means two or more components—one of which corresponding to the multispecific antibody construct, the pharmaceutical composition, the vector or the host cell of the invention—packaged together in a container, recipient or otherwise. A kit can hence be described as a set of products and/or utensils that are sufficient to achieve a certain goal, which can be marketed as a single unit.
The kit may comprise one or more recipients (such as vials, ampoules, containers, syringes, bottles, bags) of any appropriate shape, size and material (preferably waterproof, e.g. plastic or glass) containing the multispecific antibody construct or the pharmaceutical composition of the present invention in an appropriate dosage for administration (see above). The kit may additionally contain directions for use (e.g. in the form of a leaflet or instruction manual), means for administering the multispecific antibody construct of the present invention such as a syringe, pump, infuser or the like, means for reconstituting the multispecific antibody construct of the invention and/or means for diluting the multispecific antibody construct of the invention.
The invention also provides kits for a single-dose administration unit. The kit of the invention may also contain a first recipient comprising a dried/lyophilized multispecific antibody construct and a second recipient comprising an aqueous formulation. In certain embodiments of this invention, kits containing single-chambered and multi-chambered pre-filled syringes (e.g., liquid syringes and lyosyringes) are provided.
EXAMPLES
Generation and Characterization of Anti-Mesothelin Antibodies
Anti-Mesothelin Antibody Generation.
Fully human antibodies to human mesothelin were generated as previously described (US20170029502A1) or by immunizing XENOMOUSE® transgenic mice (U.S. Pat. Nos. 6,114,598; 6,162,963; 6,833,268; 7,049,426; 7,064,244, which are incorporated herein by references in their entirety; Green et al., 1994, Nature Genetics 7:13-21; Mendez et al., 1997, Nature Genetics 15:146-156; Green and Jakobovitis, 1998, J. Ex. Med, 188:483-495; Kellerman and Green, Current Opinion in Biotechnology 13, 593-597, 2002). Animals from the XMG4-K and XMG4-KL XENOMOUSE® strains were used for these immunizations. Animals were immunized with alternating soluble human mesothelin-His and cynomolgus mesothelin-His. Animals with the highest antigen-specific serum native titers directed against human mesothelin and cynomolgus mesothelin were used for hybridoma generation (Kohler and Milstein, 1975). Pooled lymphocytes from spleen and/or draining lymph node (from each harvest) were dissociated from lymphoid tissue by grinding in a suitable medium (for example, Dulbecco's Modified Eagle Medium (DMEM); Invitrogen, Carlsbad, CA). B cells were selected and/or expanded using standard methods, and fused with a suitable fusion partner using techniques that were known in the art. Hybridoma supernatants with binding to human mesothelin and cynomolgus mesothelin were then selected for further characterization.
Sequencing of Anti-Mesothelin Antibodies.
For XENOMOUSE®-derived antibodies, RNA (total or mRNA) was purified from wells containing the anti-mesothelin antibody-producing hybridoma cells using a Qiagen RNeasy mini or the Invitrogen mRNA catcher plus kit. Purified RNA was used to amplify the antibody heavy and light chain variable region (V) genes using cDNA synthesis via reverse transcription, followed by a polymerase chain reaction (RT-PCR). The fully human antibody gamma heavy chain was obtained using the Qiagen One Step Reverse Transcriptase PCR kit (Qiagen). The fully human kappa light chain was obtained using the Qiagen One Step Reverse Transcriptase PCR kit (Qiagen). Amino acid sequences were deduced from the corresponding nucleic acid sequences bioinformatically. The derived amino acid sequences were then analyzed to determine the germline sequence origin of the antibodies and to identify deviations from the germline sequence. The amino acid sequences corresponding to complementary determining regions (CDRs) of the sequenced antibodies were aligned and these alignments were used to group the clones by similarity.
Antibody Production.
Selected and sequenced anti-mesothelin antibody heavy and light chains were subcloned into mammalian expression vectors and individual antibodies were produced and purified. All antibodies were reformatted with human IgG1 SEFL2 (REF) heavy chain sequences.
Binding of Antibodies to Human and Cynomolgus Monkey Mesothelin.
Binding of anti-mesothelin antibodies to human mesothelin was confirmed by flow cytometry on CHO cells engineered to express human mesothelin (huMSLN-CHO). Human MSLN-transfected CHO cells were incubated with various concentrations of purified anti-mesothelin antibodies, washed, and labeled with a fluorescent-conjugated secondary antibody specific for human IgG. Cells were then analyzed by flow cytometry. The percentage of fluorescent positive cells was plotted against antibody concentration (FIG. 1) and the EC50 was determined using Prism GraphPad software (Table 1). The binding affinity of anti-human mesothelin antibodies to soluble forms of recombinant human and cynomolgus monkey (cyno) mesothelin was also measured by Octet assay (Table 1), quantifying association rate (Kon), disassociation rate (Kdis), and equilibrium binding constant (KD). These data demonstrated binding of all anti-MSLN antibodies to both human and cynomolgus monkey mesothelin.
TABLE 1
Binding of anti-MSLN antibodies to human and cyno Mesothelin (MSLN)
On Cell
Octet Binding
Octet Binding
Binding
human MSLN
Cyno MSLN
BioReg
human MSLN
Kon
Kdis
KD
Kon
Kdis
KD
PL#
ID
Clone
EC50 (uM)
(1/Ms)
(1/s)
(nM)
(1/Ms)
(1/s)
(nM)
PL-55235
4553
6F4
0.01
4.50E+05
8.77E−05
0.19
3.35E+05
1.75E−03
5.2
PL-55238
4559
7G11
0.003
5.48E+05
1.85E−04
0.34
2.94E+05
1.88E−03
6.4
PL-54455
3966
4H6
0.002
3.58E+05
5.16E−05
0.14
3.92E+05
7.64E−04
1.9
PL-54456
3967
4G12
0.001
8.42E+04
1.62E−05
0.19
1.24E+05
5.60E−04
4.5
Generation and Characterization of Anti-CD40 Agonist Antibodies
Anti-CD40 Antibody Generation.
Fully human antibodies to human CD40 were generated by immunizing XENOMOUSE® transgenic mice (U.S. Pat. Nos. 6,114,598; 6,162,963; 6,833,268; 7,049,426; 7,064,244, which are incorporated herein by references in their entirety; Green et al., 1994, Nature Genetics 7:13-21; Mendez et al., 1997, Nature Genetics 15:146-156; Green and Jakobovitis, 1998, J. Ex. Med, 188:483-495; Kellerman and Green, Current Opinion in Biotechnology 13, 593-597, 2002). Animals from the XMG4-K and XMG4-KL XENOMOUSE® strains were used for these immunizations. Multiple immunogens and routes of immunization were used to generate anti-human CD40 immune responses. For soluble recombinant protein immunizations, mice were immunized with alternating soluble human CD40-Fc and cynomolgus CD40-Fc. For cell-based immunizations, CHO-S cells were transiently transfected with either wild type human CD40 or cynomolgus CD40 as a source of immunogen. Animals were immunized with either of these transiently transfected CHO cells. Animals with the highest antigen-specific serum native titers directed against human CD40 and cynomolgus CD40 were used for hybridoma generation (Kohler and Milstein, 1975). Pooled lymphocytes from spleen and/or draining lymph node (from each harvest) were dissociated from lymphoid tissue by grinding in a suitable medium (for example, Dulbecco's Modified Eagle Medium (DMEM); Invitrogen, Carlsbad, CA). B cells were selected and/or expanded using standard methods and fused with a suitable fusion partner using techniques that were known in the art. Hybridoma supernatants with binding to human and cynomolgus monkey CD40 were identified.
Antibody Production.
Select hybridoma supernatants showing binding to human and cynomolgus monkey CD40 were used to produce purified anti-CD40 antibodies using techniques that were known to the art (Table 2).
TABLE 2
Anti-CD40 antibodies
Anti-
body
HC Sequence
IgG
ID
VH Germline
HC CDR3
Subclass
29H10
VH1|1-02/D5|
ERISMVRGVGHNWFAP
IgG4
5-18|RF1/JH5
(SEQ ID NO: 150)
4G7
VH1|1-02/D3|
EKITMTGIYFDY
IgG4
3-16|RF3/JH4
(SEQ ID NO: 198)
33H6
VH1|1-02/D1|
EKPRYFDSFYYYLMDV
IgG4
1-7|RF3/JH6
(SEQ ID NO: 210)
35F11
VH3|3-33/D5|
DGRNYVYFDN
IgG4
5-24|RF3/JH4
(SEQ ID NO: 186)
30A12
VH3|3-23/D6|
GYSNSWWYFDY
IgG4
6-13|RF1/JH4
(SEQ ID NO: 180)
36F3
VH6|6-01/D6|
GAAPFDY
IgG4
6-13|RF2/JH4
(SEQ ID NO: 144)
39C2
VH1|1-02/D1|
ERCRTTNCYLDY
IgG4
1-1|RF1/JH4
(SEQ ID NO: 192)
33H9
VH3|3-33/D7|
GGGHWNYEGHYYGMDV
IgG4
7-27|RF1/JH6
(SEQ ID NO: 138)
37A6
VH3|3-11/D6|
DLAAGATGGLDC
IgG4
6-6|RF2/JH4
(SEQ ID NO: 174)
Anti-CD40 Antibody Binding to Human and Cynomolgus Monkey CD40.
The binding affinity of anti-human CD40 antibodies to human and cynomolgus monkey CD40 was measured by Octet assay (Table 3), quantifying association rate (Kon), disassociation rate (Kdis), and equilibrium binding constant (KD). Cross-reactivity of anti-CD40 antibodies to related TNF receptor superfamily (TNFRSF) members was evaluated by expressing human TNFR1, TNFR2, TNFR10, or TNFR14 on HEK293 cells by transient transfection of expression vectors encoding these genes. Binding of indicated anti-human CD40 antibody to these transfected cells was determined by flow cytometry. Evaluating geometric mean florescent intensity relative to control cells demonstrated minimal binding of anti-CD40 to other TNFRSF members (Table 4). Cross-reactivity of anti-CD40 antibodies to cynomolgus monkey and mouse CD40 was evaluated by expressing cynomolgus monkey or mouse CD40 on HEK293 cells by by transient transfection of expression vectors encoding these genes. Binding of indicated anti-human CD40 antibody to cells overexpressing cynomolgus monkey and mouse CD40 was determined by flow cytometry. Evaluating geometric mean florescent intensity relative to control cells demonstrated robust binding of anti-CD40 to cynomolgus monkey (cyno) CD40, but no binding to mouse CD40 (Table 5). Taken together these data demonstrate strong and equivalent binding of anti-CD40 antibodies to human and cynomolgus monkey CD40, but minimal binding to related TNFRSF members or mouse CD40.
TABLE 3
Binding affinity of anti-CD40 antibodies to human and cyno CD40
Human CD40
Cyno CD40
Antibody
kon
kdis
KD
kon
kdis
KD
ID
(1/Ms)
(1/s)
(nM)
(1/Ms)
(1/s)
(nM)
29H10
3.98E+05
1.64E−04
0.41
6.12E+05
2.44E−04
0.39
4G7
1.23E+06
1.08E−03
0.88
1.13E+06
1.93E−03
1.72
33H6
5.09E+05
6.80E−04
1.34
5.56E+05
5.77E−04
1.04
35F11
5.56E+05
3.10E−04
0.55
5.06E+05
3.14E−04
0.62
30A12
5.33E+05
3.68E−04
0.69
5.44E+05
3.06E−04
0.56
36F3
6.45E+04
4.43E−04
6.87
5.22E+04
2.10E−04
4.02
39C2
5.99E+05
6.14E−04
1.02
5.18E+05
3.76E−04
0.73
33H9
4.07E+05
2.38E−04
0.58
4.02E+05
1.68E−04
4.17
37A6
6.12E+05
6.72E−04
1.10
5.31E+05
3.87E−04
0.73
TABLE 4
Absence of anti-CD40 antibody binding to related TNF receptor
superfamily members (fold over control values)
Antibody
ID
TNFR1
TNFR2
TNFR10
TNFR14
29H10
0.98
0.88
0.89
0.84
4G7
0.97
0.90
0.87
0.89
33H6
1.00
0.81
0.77
0.80
35F11
1.00
0.85
0.73
0.74
30A12
1.07
0.89
0.91
0.96
36F3
0.99
0.92
0.86
0.88
39C2
1.00
0.90
0.86
0.89
33H9
1.03
0.93
0.89
0.88
37A6
0.99
0.87
0.88
0.87
TABLE 5
Species cross-reactivity of anti-CD40 antibodies
to cyno and mouse CD40 (fold over control values)
Antibody
ID
Cyno
Mouse
29H10
71
0.8
4G7
57
0.9
33H6
74
0.9
35F11
76
0.8
30A12
71
1.3
36F3
82
0.9
39C2
87
0.9
33H9
73
0.9
37A6
92
0.9
Cross-Linking-Dependent Activation of CD40 by Anti-CD40 Antibodies.
Stimulation of the CD40 receptor on human B cells results in activation ad proliferation. Purified primary human B cells were seeded into 384-well assay plates and treated with IL-4/IL-21 as co-mitogens, varying concentrations of anti-CD40 antibodies, and the presence (FIG. 2A) or absence (FIG. 2B) of protein G. A single molecule of Protein G is capable of binding multiple IgG molecules and can thus cross-link antibodies in solution. Cells were incubated for 5 days and cell proliferation was examined using CellTiter-Glo. An irrelevant IgG4 isotype antibody was included as a negative control as all anti-CD40 antibodies examined were IgG4. EC50 and percent maximum activity were calculated (Table 6). All anti-CD40 antibodies induced robust proliferation of B cells in the presence of protein G but had minimal activity in the absence of protein G, indicating that anti-CD40 antibody binding to CD40 alone was insufficient to stimulate CD40 and that additional cross-linking of the antibodies was required.
TABLE 6
Activity of anti-CD40 antibodies with and without
crosslinking in human B cell functional assay
No
With
No
Crosslinking
With
Crosslinking
Antibody
Crosslinking
Max Fold
Crosslinking
Max Fold
ID
EC50 (nM)
Change
EC50 (nM)
Change
29H10
>16.7
1.35
0.235
18.22
4G7
>16.7
1.19
0.430
18.05
33H6
>16.7
1.21
0.237
18.24
35F11
>16.7
1.33
0.371
24.16
30A12
>16.7
1.45
0.362
23.78
36F3
>16.7
1.83
0.558
16.85
39C2
>16.7
1.24
0.529
23.01
33H9
>16.7
1.35
0.344
23.17
37A6
>16.7
1.19
0.504
27.09
Effect of Anti-CD40 Antibodies on Binding to Human CD40 Ligand to Human CD40.
To evaluate the ability of the anti-CD40 antibodies to block CD40 ligand interactions with CD40, a flow cytometry-based ligand binding assay was performed to measure the binding of florescent-labeled soluble human CD40L to human CD40 over-expressed on 293T cells by transient transfection with an expression vector encoding this gene. Percent ligand binding inhibition was calculated as [(CD40L binding gMFI in the absence of anti-CD40)−(CD40L binding gMFI in the presence of anti-CD40)]/(CD40L binding gMFI in the absence of anti-CD40). gMFI: geometric mean fluorescent intensity. All anti-CD40 antibodies show minimal effects on the ability of CD40L to bind to the CD40 receptor (Table 7).
TABLE 7
Anti-CD40 antibodies do not block CD40-CD40L interactions
Ligand Binding Inhibition (%)
Antibody
Ligand
ID
20 ug/ml
10 ug/ml
5 ug/ml
2.5 ug/ml
Blocker
29H10
−7%
1%
−8%
−11%
No
4G7
3%
14%
24%
21%
No
33H6
7%
11%
4%
−8%
No
35F11
8%
51%
−5%
−15%
No
30A12
−3%
−8%
−15%
−16%
No
36F3
1%
14%
10%
1%
No
39C2
2%
3%
−6%
7%
No
33H9
1%
3%
9%
−3%
No
37A6
12%
6%
2%
−19%
No
Some antibodies specific for TNFRSF members have been shown to potentiate activation of the receptor by its normal ligand, potentially by clustering the receptor and decreasing the threshold for ligand-induced activation. To evaluate the ability of the anti-CD40 antibodies to potentiate CD40 ligand activity, purified primary human B cells were treated with various concentrations of recombinant human CD40L in the presence or absence of 1 μg/ml of the indicated CD40 antibody. Cells were incubated for 5 days and cell proliferation was examined using CellTiter-Glo. None of the anti-CD40 antibodies induced a significant change in the EC50 of CD40 ligand to stimulate proliferation of human B cells (Table 8).
TABLE 8
Anti-CD40 antibodies do not potentiate activity of CD40L
Antibody
CD40L EC50
ID
(ug/ml)
No Antibody
0.001085
29H10
0.000715
4G7
0.00104
33H6
0.001135
35F11
0.006655
30A12
0.00081
36F3
0.012975
39C2
0.000985
33H9
No Activity
37A6
0.00139
Sequencing of Anti-CD40 Antibodies.
RNA (total or mRNA) was purified from wells containing the anti-mesothelin antibody-producing hybridoma cells using a Qiagen RNeasy mini or the Invitrogen mRNA catcher plus kit. Purified RNA was used to amplify the antibody heavy and light chain variable region (V) genes using cDNA synthesis via reverse transcription, followed by a polymerase chain reaction (RT-PCR). The fully human antibody gamma heavy chain was obtained using the Qiagen One Step Reverse Transcriptase PCR kit (Qiagen). The fully human kappa light chain was obtained using the Qiagen One Step Reverse Transcriptase PCR kit (Qiagen). Amino acid sequences were deduced from the corresponding nucleic acid sequences bioinformatically. The derived amino acid sequences were then analyzed to determine the germline sequence origin of the antibodies and to identify deviations from the germline sequence. The amino acid sequences corresponding to complementary determining regions (CDRs) of the sequenced antibodies were aligned and these alignments were used to group the clones by similarity.
Optimization of Anti-CD40 Antibody Sequences.
Engineering of select anti-CD40 antibodies was performed to remove potential sequence liabilities in the antibody heavy and light chain variable regions by standard recombinant DNA techniques. These antibodies were produced by over-expression in cell lines and purified using techniques that were known in the art. Purified antibodies were then evaluated in a human B cell proliferation assay with and without protein G cross-linking, as described above. EC50 and percent maximum activity were calculated (Table 9), showing that many of the engineered antibody variants maintained similar cross-linking dependent agonist activity as their parental antibody sequence.
TABLE 9
Functional activity of engineered variants of anti-CD40 antibodies
No
With
No
Crosslinking
With
Crosslinking
Antibody
Antibody
Crosslinking
% Max
Crosslinking
% Max
Name
ID
EC50 (nM)
Activity
EC50 (nM)
Activity
29H10
4877-1
>16.7
4.4
0.37
65.9
30A12
4878-1
>16.7
8.6
0.40
89.1
30A12.001
4894-1
>5.93
12.2
0.08
87.2
30A12.002
4879-1
>16.7
19.0
0.36
89.2
30A12.003
4880-1
>16.7
1.2
0.41
83.3
33H6
4883-1
>16.7
6.5
0.26
73.4
33H6.001
4884-1
>16.7
10.8
0.46
92.7
33H6.002
4885-1
>16.7
11.5
0.40
81.2
33H6.003
4895-1
>6.22
6.5
0.43
61.4
33H6.004
4886-1
>16.7
20.9
0.44
73.5
33H9
4897-1
>13.4
2.3
0.19
88.9
35F11
4868-1
>16.7
4.4
0.30
119.7
35F11.001
5052-2
>16.7
12.5
0.85
96.5
35F11.002
5053-2
>16.7
6.4
0.77
84.2
35F11.003
5054-2
>16.7
10.5
0.60
74.6
35F11.004
5055-2
>16.7
10.0
0.90
83.7
35F11.005
5056-2
>16.7
5.4
0.68
77.8
35F11.006
5057-2
>16.7
4.8
0.49
109.0
36F3
4891-1
>16.7
8.2
0.30
81.9
37A6
4865-1
>16.7
0.4
0.30
80.9
37A6.001
4866-1
>16.7
−0.2
0.32
86.7
37A6.002
4892-1
>5.87
−1.9
0.11
87.3
37A6.003
4867-1
>16.7
−1.1
0.21
73.0
39C2
4887-1
>16.7
6.1
0.21
76.6
39C2.001
4888-1
>16.7
1.2
>16.7
2.2
39C2.002
4889-1
>16.7
21.9
4.36
86.5
39C2.003
4890-1
>16.7
4.6
>16.7
1.7
4G7
4869-1
>16.7
6.0
0.50
70.5
4G7.001
4893-1
>5.99
2.7
0.83
80.5
4G7.002
4870-1
>16.7
2.1
0.62
72.2
4G7.003
4871-1
>16.7
3.9
0.77
89.1
4G7.004
4872-1
>16.7
2.3
1.01
96.8
Generation and Characterization of Mesothelin-Targeted CD40 Agonist Bivalent B1-Specific Antibodies
Bispecific Antibody Production.
In order to generate a mesothelin-dependent CD40 agonist, bivalent bispecific antibodies capable of binding to both human mesothelin and human CD40 were generated in either an IgG-Fab format (FIG. 3A) or an IgG-scFv format (FIG. 3B) using the variable region binding domains of the anti-mesothelin and anti-CD40 antibodies described above.
Generation and Evaluation of Mesothelin x CD40 Bispecific Agonist Antibodies in the IgG-Fab Format.
A panel of mesothelin x CD40 bispecific antibodies were generated in the IgG-Fab format (Table 10) and evaluated for binding to soluble forms of human and cynomolgus monkey CD40 and human and cynomolgus monkey mesothelin using the Octet assay (Table 11). Association rate (Kon), disassociation rate (Kdis), and equilibrium binding constant (KD) were calculated. The majority of bispecific antibodies showed high affinity binding to both human and cynomolgus monkey CD40 and mesothelin. These bispecific antibodies were next evaluated for their ability to induce mesothelin-dependent activation of human B cells. CHO cells expressing human mesothelin were seeded into a 96 well plate. The next day varying concentrations of the mesothelin x CD40 IgG-Fab antibodies were added to the wells along with purified human B cells and the plates were incubated for an additional 48 hours. Upregulation of CD86, a marker of CD40-mediated B cell activation, was quantified on B cells by flow cytometry. EC50 values for CD86 upregulation were calculated and demonstrate that the majority of mesothelin x CD40 IgG-Fab bispecific antibodies were able to B cell activation in the presence of CHO cells expressing human mesothelin (Table 12).
TABLE 10
Anti-CD40xMSLN IgG-Fab molecules
Antibody
IgG
Fab
IgG
Fab
ID
(MSLN)
(CD40)
(CD40)
(MSLN)
13468-1
4G12
30A12
5966-1
4H6
37A6
5978-1
7G11
33H9
13473-1
30A12
4G12
13474-1
35F11
4G12
13469-1
4G12
35F11
5967-1
6F4
29H10
6057-1
7G11
37A6
5991-1
30A12
6F4
6003-1
35F11
6F4
13470-1
4G12
37A6
5968-1
6F4
30A12
6058-1
7G11
39C2
5992-1
30A12
7G11
13475-1
36F3
4G12
13471-1
4G12
39C2
5970-1
6F4
33H9
5982-1
4G7
4H6
6007-1
36F3
6F4
5960-1
4H6
29H10
5972-1
6F4
36F3
5983-1
4G7
6F4
5995-1
33H6
6F4
5946-1
37A6
4H6
5961-1
4H6
30A12
5973-1
6F4
37A6
13472-1
29H10
4G12
5998-1
33H9
4H6
5947-1
37A6
7G11
5963-1
4H6
33H9
5975-1
7G11
29H10
5987-1
29H10
6F4
5999-1
33H9
6F4
5965-1
4H6
36F3
5976-1
7G11
30A12
5988-1
29H10
7G11
6000-1
33H9
7G11
TABLE 11
Anti-CD40xMSLN IgG-Fab molecule binding to human and cynomolgus monkey CD40 and mesothelin
huCD40(1-193)
cynoCD40(1-193)
huMSLN(296-598)
cynoMSLN(296-598)
Antibody
KD
ka
kd
KD
ka
kd
KD
ka
kd
KD
ka
kd
ID
(nM)
(M−1s−1)
(s−1)
(nM)
(M−1s−1)
(s−1)
(nM)
(M−1s−1)
(s−1)
(nM)
(M−1s−1)
(s−1)
5959-1
0.4
5.11E+05
2.14E−04
0.7
6.21E+05
4.28E−04
<0.1
2.29E+05
>1.00E−05
6.0
1.10E+05
6.58E−04
5960-1
0.4
4.20E+05
1.82E−04
0.5
3.55E+05
1.76E−04
0.2
7.98E+05
1.79E−04
2.5
3.66E+05
9.16E−04
5961-1
0.6
6.22E+05
3.42E−04
0.8
3.39E+05
2.66E−04
<0.1
6.80E+05
>1.00E−05
2.7
3.56E+05
9.58E−04
5963-1
<0.1
8.85E+04
>1.00E−05
0.8
1.47E+05
1.15E−04
0.2
8.46E+05
1.56E−04
2.9
3.10E+05
9.03E−04
5965-1
2.5
1.19E+05
2.97E−04
2.7
9.51E+04
2.55E−04
0.2
8.03E+05
1.40E−04
2.1
4.24E+05
8.96E−04
5966-1
0.7
5.84E+05
4.03E−04
0.9
4.20E+05
3.58E−04
0.2
8.78E+05
1.76E−04
2.5
3.78E+05
9.40E−04
5967-1
0.8
3.75E+05
2.86E−04
<0.1
1.83E+05
>1.00E−05
0.3
9.12E+05
2.89E−04
6.4
3.71E+05
2.36E−03
5968-1
0.4
6.50E+05
2.56E−04
0.7
5.98E+05
4.14E−04
0.3
1.03E+06
3.53E−04
5.1
5.56E+05
2.82E−03
5970-1
1.6
2.45E+05
3.95E−04
1.3
1.63E+05
2.08E−04
0.3
7.74E+05
2.58E−04
5.8
4.31E+05
2.48E−03
5972-1
4.0
1.34E+05
5.31E−04
1.7
8.06E+04
1.37E−04
0.5
5.68E+05
2.70E−04
4.6
4.54E+05
2.10E−03
5973-1
0.6
5.41E+05
3.25E−04
0.6
6.69E+05
4.04E−04
0.5
4.51E+05
2.23E−04
5.5
3.90E+05
2.13E−03
5975-1
<0.2
4.41E+05
>1.00E−05
0.8
5.33E+05
4.02E−04
0.8
4.20E+05
3.41E−04
6.6
3.39E+05
2.24E−03
5976-1
0.6
9.01E+05
5.25E−04
0.3
7.95E+05
2.32E−04
0.8
4.06E+05
3.30E−04
7.6
3.15E+05
2.40E−03
5978-1
<0.3
7.77E+04
>1.00E−05
1.0
1.30E+05
1.31E−04
0.8
3.90E+05
2.98E−04
8.5
2.76E+05
2.33E−03
6057-1
0.8
6.46E+05
4.97E−04
0.7
1.00E+06
7.04E−04
0.8
4.30E+05
3.65E−04
9.2
2.54E+05
2.33E−03
6058-1
0.6
9.27E+05
5.29E−04
1.0
6.01E+05
4.93E−04
0.8
3.81E+05
3.17E−04
6.8
3.42E+05
2.32E−03
5982-1
1.2
1.68E+06
1.98E−03
1.5
1.28E+06
1.89E−03
<0.1
2.17E+05
>1.00E−05
4.7
2.27E+05
1.06E−03
5983-1
1.7
1.12E+06
1.95E−03
1.5
1.43E+06
2.11E−03
1.0
2.63E+05
2.72E−04
12.3
3.42E+05
4.21E−03
5987-1
0.7
6.00E+05
4.23E−04
0.7
7.52E+05
5.26E−04
1.0
4.24E+05
4.39E−04
18.3
2.10E+05
3.83E−03
5988-1
0.3
1.66E+06
4.76E−04
0.2
2.90E+06
6.54E−04
2.5
1.44E+05
3.61E−04
29.4
7.72E+04
2.27E−03
5991-1
0.4
1.08E+06
4.67E−04
0.2
1.86E+06
4.23E−04
1.3
1.81E+05
2.42E−04
31.9
1.52E+05
4.83E−03
5992-1
0.3
1.34E+06
4.21E−04
0.3
1.98E+06
5.32E−04
1.9
1.44E+05
2.68E−04
25.5
1.05E+05
2.67E−03
5995-1
0.4
1.06E+06
3.80E−04
0.2
1.80E+06
3.77E−04
0.9
2.81E+05
2.47E−04
26.2
1.12E+05
2.93E−03
5998-1
0.3
7.12E+05
2.26E−04
0.2
1.07E+06
2.04E−04
0.6
6.20E+05
3.81E−04
15.6
6.72E+04
1.05E−03
5999-1
0.2
5.80E+05
1.11E−04
0.6
3.95E+05
2.44E−04
1.0
3.38E+05
3.22E−04
30.9
1.26E+05
3.89E−03
6000-1
0.3
6.59E+05
1.83E−04
0.5
4.10E+05
1.99E−04
1.1
3.64E+05
3.94E−04
40.0
5.37E+04
2.15E−03
6003-1
0.7
1.14E+06
8.03E−04
0.5
1.58E+06
7.73E−04
1.2
2.45E+05
2.95E−04
62.6
8.58E+04
5.37E−03
6007-1
3.3
1.41E+05
4.63E−04
2.7
2.44E+05
6.62E−04
0.8
4.92E+05
4.09E−04
40.2
1.30E+05
5.23E−03
5946-1
1.0
5.89E+05
6.01E−04
0.9
5.91E+05
5.20E−04
0.9
4.06E+05
3.61E−04
3.1
2.64E+05
8.25E−04
5947-1
1.1
5.14E+05
5.72E−04
1.1
5.77E+05
6.17E−04
1.2
2.77E+05
3.46E−04
27.3
8.60E+04
2.35E−03
TABLE 12
Anti-CD40xMSLN IgG-Fab molecule functional activity on human B
cells in the presence of CHO cells expressing human mesothelin
Antibody
EC50
ID
(nM)
13468-1
0.007
5966-1
0.008
5978-1
0.033
13473-1
0.007
13474-1
0.009
13469-1
0.011
5967-1
0.005
6057-1
0.018
5991-1
0.004
6003-1
0.007
13470-1
0.008
5968-1
0.004
6058-1
0.010
5992-1
0.007
13475-1
0.015
13471-1
0.016
5970-1
0.005
5982-1
0.005
6007-1
0.009
5960-1
0.006
5972-1
0.007
5983-1
0.004
5995-1
0.006
5946-1
0.007
5961-1
0.004
5973-1
0.006
13472-1
>0.523
5998-1
0.007
5947-1
0.003
5963-1
0.022
5975-1
0.022
5987-1
0.003
5999-1
0.005
5965-1
0.020
5976-1
0.010
5988-1
0.004
6000-1
0.002
Generation and Evaluation of Mesothelin x CD40 Bispecific Agonist Antibodies in the IgG-scFv Format.
A panel of mesothelin x CD40 bispecific antibodies were generated in the IgG-scFv format (Table 13) and evaluated for binding to soluble forms of human and cynomolgus monkey CD40 and human and cynomolgus monkey mesothelin using the Octet assay (Table 14). Association rate (Kon), disassociation rate (Kdis), and equilibrium binding constant (KD) were calculated. The majority of bispecific antibodies showed high affinity binding to both human and cynomolgus monkey CD40 and mesothelin. These bispecific antibodies were next evaluated for their ability to induce mesothelin-dependent activation of human B cells. CHO cells expressing human mesothelin were seeded into a 96 well plate. The next day varying concentrations of the mesothelin x CD40 IgG-scFv antibodies were added to the wells along with purified human B cells and the plates were incubated for an additional 48 hours. Upregulation of CD86, a marker of CD40-mediated B cell activation, was quantified on B cells by flow cytometry. EC50 values for CD86 upregulation were calculated and demonstrate that the majority of mesothelin x CD40 IgG-scFv bispecific antibodies were able to B cell activation in the presence of CHO cells expressing human mesothelin (Table 15).
TABLE 13
Anti-CD40xMSLN IgG-scFv molecules
Antibody
IgG
scFv
IgG
scFv
ID
(MSLN)
(CD40)
(CD40)
(MSLN)
6028-2
4H6
36F3
6030-2
4H6
39C2
6032-2
6F4
29H10
6043-2
30A12
4H6
6044-2
30A12
6F4
6033-2
6F4
30A12
6034-2
6F4
33H6
6035-2
6F4
33H9
6056-2
6F4
39C2
6039-2
4G7
4H6
6040-2
4G7
6F4
6041-2
29H10
4H6
6042-2
29H10
6F4
6045-2
33H6
4H6
6046-2
33H6
6F4
6047-2
33H9
4H6
6048-2
33H9
6F4
6049-2
35F11
4H6
6050-2
35F11
6F4
6051-2
36F3
4H6
6052-2
36F3
6F4
6055-2
37A6
4H6
6054-2
37A6
6F4
6053-2
39C2
4H6
6023-2
39C2
6F4
TABLE 14
Anti-CD40xMSLN IgG-scFv molecule binding to human and cynomolgus monkey CD40 and mesothelin
huCD40(1-193)
cynoCD40(1-193)
huMSLN(296-598)
cynoMSLN(296-598)
Antibody
KD
ka
kd
KD
ka
kd
KD
ka
kd
KD
ka
kd
ID
(nM)
(M−1s−1)
(s−1)
(nM)
(M−1s−1)
(s−1)
(nM)
(M−1s−1)
(s−1)
(nM)
(M−1s−1)
(s−1)
6028-2
10
7.69E+04
7.67E−04
7.1
9.64E+04
6.87E−04
0.2
7.33E+05
1.43E−04
1.8
3.71E+05
6.80E−04
6030-2
7.9
2.14E+05
1.68E−03
6.0
3.01E+05
1.81E−03
0.2
7.08E+05
1.75E−04
1.9
3.53E+05
6.87E−04
6032-2
2.0
2.04E+05
4.07E−04
1.7
2.38E+05
4.07E−04
0.4
6.92E+05
3.06E−04
5.8
3.45E+05
1.99E−03
6043-2
1.2
3.21E+05
4.07E−04
0.9
4.22E+05
4.07E−04
0.1
4.44E+05
3.87E−05
4.3
2.76E+05
1.20E−03
6044-2
1.3
3.24E+05
4.24E−04
0.8
4.85E+05
3.98E−04
1.5
3.30E+05
5.06E−04
17
3.43E+05
5.87E−03
6033-2
4.2
3.11E+05
1.32E−03
2.9
4.88E+05
1.42E−03
0.4
4.49E+05
1.97E−04
5.9
3.31E+05
1.94E−03
6034-2
2.1
1.66E+05
3.50E−04
2.1
1.82E+05
3.84E−04
0.3
6.00E+05
1.96E−04
5.4
2.96E+05
1.59E−03
6035-2
<0.1
1.03E+05
<1.00E−05
<0.1
9.43E+04
<1.00E−05
0.3
6.75E+05
2.29E−04
6.3
2.71E+05
1.71E−03
6056-2
4.4
3.63E+05
1.59E−03
5.8
2.98E+05
1.73E−03
0.3
7.19E+05
2.18E−04
5.1
3.43E+05
1.76E−03
6039-2
1.4
1.12E+06
1.61E−03
2.1
1.04E+06
2.21E−03
0.3
5.13E+05
1.77E−04
5.4
2.81E+05
1.50E−03
6040-2
1.3
1.39E+06
1.86E−03
1.9
9.24E+05
1.73E−03
1.2
4.24E+05
5.16E−04
32
2.35E+05
7.63E−03
6041-2
0.5
7.09E+05
3.57E−04
0.6
5.39E+05
3.47E−04
0.4
5.04E+05
1.79E−04
5.7
1.58E+05
9.05E−04
6042-2
0.7
6.32E+05
4.29E−04
0.8
3.94E+05
3.03E−04
0.9
5.29E+05
4.60E−04
20
2.55E+05
5.04E−03
6045-2
0.4
8.81E+05
3.87E−04
0.6
5.80E+05
3.27E−04
0.3
5.23E+05
1.45E−04
4.6
1.87E+05
8.65E−04
6046-2
0.5
8.93E+05
4.05E−04
0.5
5.94E+05
3.14E−04
0.9
5.27E+05
4.76E−04
18
2.50E+05
4.59E−03
6047-2
0.2
5.77E+05
1.32E−04
<0.3
3.46E+04
<1.00E−05
0.4
3.75E+05
1.38E−04
6.0
1.68E+05
1.01E−03
6048-2
0.5
5.45E+05
2.59E−04
0.3
4.26E+05
1.33E−04
1.0
5.29E+05
5.53E−04
22
2.39E+05
5.35E−03
6049-2
0.9
8.34E+05
7.21E−04
1.2
5.06E+05
5.82E−04
0.3
5.36E+05
1.71E−04
5.1
1.85E+05
9.53E−04
6050-2
0.8
7.97E+05
6.49E−04
1.2
5.12E+05
6.09E−04
0.8
5.41E+05
4.51E−04
15
2.77E+05
4.27E−03
6051-2
3.5
1.24E+05
4.31E−04
4.7
1.00E+05
4.66E−04
0.2
5.99E+05
1.35E−04
5.5
1.91E+05
1.05E−03
6052-2
2.5
2.18E+05
5.56E−04
3.3
1.05E+05
3.50E−04
0.7
7.13E+05
5.33E−04
19
2.69E+05
5.19E−03
6055-2
0.5
1.46E+06
7.87E−04
0.8
7.45E+05
5.70E−04
0.4
5.52E+05
2.11E−04
6.1
1.79E+05
1.09E−03
6054-2
0.8
4.38E+05
3.33E−04
1.4
2.77E+05
4.00E−04
1.3
3.67E+05
4.62E−04
17
3.36E+05
5.78E−03
6053-2
0.9
4.53E+05
4.27E−04
0.5
2.63E+05
1.25E−04
0.4
3.41E+05
1.51E−04
4.3
2.52E+05
1.09E−03
6023-2
1.0
4.31E+05
4.40E−04
0.9
4.47E+05
4.13E−04
1.1
4.32E+05
4.60E−04
16
3.26E+05
5.35E−03
TABLE 15
Anti-CD40xMSLN IgG-scFv molecule functional activity on human B
cells in the presence of CHO cells expressing human mesothelin
Antibody
EC50
ID
(nM)
6028-2
0.012240302
6030-2
0.010141789
6032-2
0.009349861
6043-2
0.007758607
6044-2
0.005001671
6033-2
0.006030707
6034-2
0.007262489
6035-2
0.016708182
6056-2
0.004577206
6039-2
0.003317003
6040-2
0.002665906
6041-2
0.004479453
6042-2
0.003988474
6045-2
0.004663271
6046-2
0.004723116
6047-2
0.005131571
6048-2
0.004342491
6049-2
0.005853663
6050-2
0.003388309
6051-2
0.003753076
6052-2
0.003155443
6055-2
0.004340411
6054-2
0.003331971
6053-2
0.004033184
6023-2
0.002805537
Sequence Optimization of Mesothelin x CD40 Bispecific Agonist Antibodies in the IgG-scFv Format
Engineering of select mesothelin x CD40 bispecific IgG-scFv antibodies was performed to remove potential sequence liabilities in the antibody heavy and light chain variable regions by standard recombinant DNA techniques. These antibodies were produced by over-expression in cell lines and purified using techniques that were known in the art. These bispecific antibodies were next evaluated for their ability to induce mesothelin-dependent activation of human B cells. CHO cells expressing human mesothelin were seeded into a 96 well plate. The next day varying concentrations of the mesothelin x CD40 IgG-scFv sequence variant antibodies were added to the wells along with purified human B cells and the plates were incubated for an additional 48 hours. Upregulation of CD86, a marker of CD40-mediated B cell activation, was quantified on B cells by flow cytometry. EC50 values for CD86 upregulation were calculated and demonstrate that the majority of mesothelin x CD40 IgG-scFv sequence variant bispecific antibodies maintain the ability to induce B cell activation in the presence of CHO cells expressing human mesothelin (Table 16).
TABLE 16
Sequence optimized anti-CD40xMSLN IgG-scFv molecule
functional activity on human B cells in the presence
of CHO cells expressing human mesothelin
Antibody
EC50
ID
(nM)
8861-1
0.00332
8866-1
0.00306
8862-1
0.00295
8863-1
0.00557
8869-1
0.00181
8871-1
0.00259
8873-1
0.00311
8875-1
0.00241
8867-1
0.00216
8868-1
0.00363
8864-1
0.00283
8870-1
0.00267
8872-1
0.00267
8874-1
0.00262
8876-1
0.00171
8865-1
0.00329
6041-3
0.00395
8764-1
0.00434
8768-1
0.00334
8769-1
0.00434
8770-1
0.02176
8771-1
0.05341
8772-1
0.17205
8773-1
0.42410
8774-1
0.00409
8775-1
0.00309
8776-1
0.02073
8777-1
0.01153
8778-1
0.00362
8765-1
0.00305
8779-1
0.01746
8780-1
0.01673
8781-1
0.17750
8782-1
0.42500
8783-1
0.00301
8784-1
0.00311
8785-1
0.00293
8786-1
0.00322
8787-1
0.00274
8788-1
0.00371
8789-1
0.00321
8790-1
0.00480
8791-1
0.00329
8766-1
0.00355
8792-1
0.00439
8793-1
0.00405
8794-1
0.00378
8795-1
0.00511
8796-1
0.00437
8797-1
0.00384
8798-1
0.00342
8804-1
0.00323
8805-1
0.00406
8806-1
0.00326
8807-1
0.00342
8808-1
0.00331
8809-1
0.00386
8810-1
0.00451
8811-1
0.00436
8812-1
0.00415
8813-1
0.00356
8814-1
0.00453
8815-1
0.00368
8816-1
0.00438
8817-1
0.00342
8818-1
0.00518
8819-1
0.00387
8820-1
0.00366
8821-1
0.00433
8822-1
0.00404
8823-1
0.00351
8824-1
0.00331
8825-1
0.00255
8767-1
0.00209
8826-1
0.04585
8827-1
0.06588
8828-1
>0.635
8829-1
>0.635
8830-1
0.00559
8831-1
0.00523
8832-1
0.00572
8833-1
0.00788
8834-1
0.03859
8835-1
0.06977
8836-1
>0.635
8837-1
>0.635
8838-1
>0.635
8839-1
>0.635
8840-1
0.00641
8841-1
0.00572
8842-1
0.00430
8843-1
0.00376
8844-1
0.00263
8845-1
0.00362
8846-1
0.00542
8847-1
>0.635
8848-1
0.28130
8849-1
0.00315
8850-1
0.00353
8851-1
0.00648
8852-1
0.12325
8853-1
0.05720
6052-3
0.00445
8854-1
0.00303
8855-1
0.00354
8856-1
0.00363
8857-1
0.00346
8858-1
0.00357
8859-1
0.00300
8860-1
0.00357
Effect of Varying Levels of Mesothelin on Activity of Select Mesothelin x CD40 Bispecific Antibodies in a Human B Cell Functional Assay
MC38 cells were engineered to express varying levels of human mesothelin ranging from low (MC38.MSLN1) to high (MC38.MSLN5). Given that MC38 cells are derived from mouse, they do not express human mesothelin (FIG. 4). Parental MC38 cells and MC38 cells expressing varying levels of human mesothelin were seeded into 96 well plates and cultured overnight. The next day, mesothelin x CD40 bispecific antibodies were added to the cells at varying concentrations. Isolated human B cells were then added at to the wells and the plates were incubated for an additional 48 hours. Upregulation of CD86 on B cells was evaluated by flow cytometry and used as a measure of B cell activation. EC50 and maximum activity (Emax) values were calculated and demonstrate that the mesothelin x CD40 bispecific antibodies were able to induce B cell activation across all levels of MSLN expression (Table 17). Cell lines expressing lower levels of mesothelin induced lower maximum activity of the mesothelin x CD40 bispecific antibodies, as measured by the geometric mean fluorescence intensity of CD86 upregulation on B cells. Mesothelin x CD40 bispecific antibodies had no activity in the presence of parental MC38 cells, consistent with the mesothelin-dependent activity of these molecules for CD40 agonist activity.
TABLE 17
Activity of anti-CD40xMSLN bispecific molecules in human B cell and monocyte-
derived dendritic cell assays in the presence of varying levels of mesothelin
Antibody ID
6041
8765
8766
8767
8945
8947
Human B Cell
MC38.MSLN1
0.2326
0.2287
0.2735
0.1472
0.2752
0.2687
Functional
EC50 (pM)
Assay
MC38.MSLN2
0.5723
0.6028
0.6877
0.4584
0.6637
0.6626
(CD86
EC50 (pM)
upregulation)
MC38.MSLN3
0.801
0.6696
0.8764
0.5357
1.0162
0.6689
EC50 (pM)
MC38.MSLN4
0.9542
0.8518
1.1365
0.7048
1.4765
0.9471
EC50 (pM)
MC38.MSLN5
1.6005
0.8549
2.0058
1.2579
2.0122
1.0863
EC50 (pM)
MC38 parental
∞
∞
∞
∞
∞
∞
EC50 (pM)
MC38.MSLN1
803.9
903
849
742.1
660.2
809.5
Emax (MFI)
MC38.MSLN2
1169
1318
1223
1173
978.6
1259
Emax (MFI)
MC38.MSLN3
1895
1861
1869
1849
1479
1733
Emax (MFI)
MC38.MSLN4
1325
1400
1399
1341
1283
1406
Emax (MFI)
MC38.MSLN5
1396
1406
1474
1349
1186
1389
Emax (MFI)
MC38 parental
Bkgd
Bkgd
Bkgd
Bkgd
Bkgd
Bkgd
Emax (MFI)
Human Monocyte-
MC38.MSLN2
0.179
0.089
0.183
0.101
0.168
0.184
Derived Dendritic
EC50 (nM)
Cell Functional
MC38.MSLN5
0.241
0.231
0.26
0.248
0.414
0.399
Assay
EC50 (nM)
(IL12p40
MC38 parental
∞
∞
∞
∞
∞
∞
production)
EC50 (nM)
MC38.MSLN2
1142
952
1205
1116
338.1
1010
Emax (IL12p40
pg/ml)
MC38.MSLN5
2400
2148
2343
2349
1004
1869
EC50 (nM)
MC38 parental
Bkgd
Bkgd
Bkgd
Bkgd
Bkgd
Bkgd
Emax (IL12p40
pg/ml)
* Poor curve fit
Bkgd = Background level of assay
Effect of Varying Levels of Mesothelin on Activity of Select Mesothelin x CD40 Bispecific Antibodies in a Monocyte-Derived Dendritic Cell Functional Assay.
MC38 cells engineered to express varying levels of human mesothelin (FIG. 4) or parental MC38 cells were seeded into 96 well plates and cultured overnight. The next day, mesothelin x CD40 bispecific antibodies were added to the cells at varying concentrations. Monocyte-derived dendritic cells differentiated from human monocytes using GMCSF and IL4 were added to the wells and the plates were incubated for an additional 48 hours. Supernatants from each well were collected and concentrations of IL12p40 secreted from dendritic cells quantified using an ELISA kit. EC50 and maximum activity (Emax) values were calculated and demonstrate that the mesothelin x CD40 bispecific antibodies were able to induce dendritic cell activation across both high and low levels of MSLN expression (Table 17). Cell lines expressing lower levels of mesothelin induced lower maximum activity of the mesothelin x CD40 bispecific antibodies. Mesothelin x CD40 bispecific antibodies had no activity in the presence of parental MC38 cells, consistent with the mesothelin-dependent activity of these molecules for CD40 agonist activity.
Activity of Select Mesothelin x CD40 Bispecific Antibodies in Cynomolgus Monkey B Cell Functional Assay with Cynomolgus Monkey Mesothelin-Expressing CHO Cells.
CHO cells engineered to express cynomolgus monkey mesothelin were seeded into 96 well plates and cultured overnight. The next day, select mesothelin x CD40 bispecific antibodies were added to the cells at varying concentrations. Isolated cynomolgus monkey B cells were then added at to the wells and the plates were incubated for an additional 48 hours. Upregulation of CD23 on the cynomolgus monkey B cells was evaluated by flow cytometry and used as a measure of CD40-induced B cell activation. EC50 were calculated and demonstrate that the mesothelin x CD40 bispecific antibodies are able to induce activation of cynomolgus monkey B cells in the presence of cynomolgus monkey mesothelin (Table 18).
TABLE 18
Activity of anti-CD40xMSLN bispecific molecules
on cynomolgus monkey B cells stimulated with CHO
cells expressing cynomolgus monkey mesothelin
Antibody
EC50
ID
(nM)
6041
0.0012
8765
0.0013
8766
0.0016
8767
0.0014
8945
0.0018
8947
0.0014
Pharmacokinetics and Stability of Mesothelin x CD40 Bispecific Antibodies in Mice.
In order to characterize the stability of mesothelin x CD40 bispecific antibodies in vivo, select mesothelin x CD40 bispecific molecules were injected into mice a 1 mg/kg dose. Animals were bled at varying timepoints after injection and serum isolated. Immunoassays were used to quantify the concentration of mesothelin x CD40 bispecific antibodies in serum, either capturing with human CD40 and detecting with anti-human IgG or capturing with human mesothelin and detecting with anti-human IgG. The combination of these two assays provide the ability to detect molecule degradation or instability. The CD40 or mesothelin capture assays yielded equivalent results, suggesting the molecules remained intact over the course of 14 days in vivo (FIG. 5). All molecules with the exception of one had similar pharmacokinetic properties.
Immunostimulatory and Anti-Tumor Activity of a Tumor-Targeted CD40 Agonist Bispecific Antibody in Mouse Models
Generation of a mouse surrogate human EPCAM-dependent CD40 agonist bispecific antibody and human EPCAM-expressing mouse tumor cell lines.
The anti-mouse CD40 agonist antibody (clone FGK45) and anti-human EPCAM antibody (clone 4-7) was used to generate a surrogate CD40 bispecific antibody in the IgG-scFv format with a mouse IgG1 N297G Fc domain (anti-muCD40 x huEPCAM bispecific antibody). The bispecific antibody contains anti-CD40 at the N-terminus of the molecule and the anti-EPCAM as scFv at the C-terminus of the molecule. Human EPCAM was over-expressed in the mouse MC38 colon carcinoma cell line and the mouse B16F10 melanoma cell line by transduction with a retrovirus encoding both human EPCAM and the human truncated nerve growth factor receptor (NGFR) reporter gene (FIG. 6). Human EpCAM-MC38 or human EpCAM-B16 tumor cells were inoculated in the right flank at 3e5 cells per implant and allowed to grow for 24 days or 11 days, respectively. Tumors were measured twice a week with digital calipers, demonstrating that the tumor cell lines expressing human EPCAM maintained the ability to grow and form tumors in mice. Flow cytometry on tumors harvested from mice and subjected to enzymatic disassociation demonstrated that human EPCAM expression was maintained on the surface of tumor cells during in vivo tumor formation (FIG. 6).
Human EPCAM-Dependent Agonist Activity of the EPCAMx CD40 Agonist Antibody on Mouse B Cells.
Human EpCAM overexpressing MC38 cells (huEpCAM-MC38) or parental MC38 cells were seeded into 96 plates and cultured overnight. The next day, the anti-muCD40 x huEPCAM bispecific antibody, the parental anti-CD40 antibody (FGK54), or an isotype control antibody was added to the cells at varying concentrations. Isolated mouse B cells were then added at to the wells and the plates were incubated for an additional 48 hours. Upregulation of CD86 on B cells was evaluated by flow cytometry and used as a measure of B cell activation. EC50 values were calculated and demonstrate that the anti-muCD40 x huEPCAM bispecific antibody was able to induce mouse B cell activation (FIG. 7). The anti-muCD40 x huEPCAM bispecific antibody demonstrated robust agonist activity that was dependent on the presence of human EPCAM and showed dramatically higher potency in activating B cells compared to the FGK45 anti-CD40 monoclonal antibody.
In Vivo Immunostimulatory Activity Ofthe Anti-muCD40 x huEPCAM Bispecific Antibody in the MC38 Tumor Model
To evaluate the effect of a tumor-targeted CD40 agonist bispecific antibody on immune cell activation in vivo, human EpCAM-expressing MC38 tumor cells were inoculated in the right flank of mice at 3e5 cells per implant and allowed to grow for 8-10 days. The mice were then randomized by tumor volume (60-100 mm3) and treated with indicated antibodies administered intraperitoneally at 5 mg/kg. Tumors, tumor draining lymph nodes (dLNs), and non-draining lymph nodes (ndLNs) were harvested at 24-48 hours post-treatment and single cell suspension prepared by enzymatic digestion of tissues. Flow cytometry analysis was performed to determine cell proportion and phenotypes, staining for surface immune cell lineage markers and activation markers, and intracellular cytokines (FIG. 8). As expected, CD40 agonist antibody (anti-CD40) treatment activated dendritic cells (DCs) located in tumor and in peripheral tissues including dLN and ndLN. In contrast, the anti-muCD40 x huEPCAM bispecific antibody only activated tumor infiltrating DCs in the human EPCAM-expressing MC38 tumors, but not DCs in peripheral tissues (dLN and ndLN) (FIG. 8A). In addition, the anti-muCD40 x huEPCAM bispecific antibody increased the CD8 T cell to regulatory T cell ratio and interferon gamma (IFNg)-producing CD4+ T cells in the tumor (FIG. 8B). Total T cells were also isolated from spleens of huEpCAM-expressing MC38 tumor-bearing mice that had been treated with the indicated antibodies. Bone marrow-derived dendritic cells (BMDCs) were generated from naïve C57BL/6 bone marrow cells by incubating with recombinant GM-CSF and IL4 for 7 days. BMDCs were pulsed with the indicated tumor cells overnight and then co-cultured with isolated T cells for 18 hours. An ELISPOT assay was used to measure the production of IFNg by antigen specific T cells, demonstrating that the anti-muCD40 x huEPCAM bispecific antibody significantly increases T cells specific for both human EPCAM-expressing MC38 and parental MC38 antigens (FIG. 9). Taken together, these data demonstrate that a tumor-targeted CD40 agonist bispecific antibody can activate myeloid population in the tumor, such as DCs, in a tumor-associated antigen dependent manner, leading to enhanced anti-tumor T cell responses.
In Vivo Immunostimulatory Activity Ofthe Anti-muCD40 x huEPCAM Bispecific Antibody in the B16F10 Tumor Model
To evaluate the effect of a tumor-targeted CD40 agonist bispecific antibody on immune cell activation in an additional tumor model, vector control or human EpCAM-expressing B16F10 tumor cells were inoculated in the right flank of mice at 3e5 cells per implant and allowed to grow for 8-10 days. The mice were then randomized by tumor volume (60-100 mm3) and treated with indicated antibodies administered intraperitoneally at 5 mg/kg. Tumors, tumor dLNs, and ndLNs were harvested at 24-48 hours post-treatment and single cell suspension prepared by enzymatic digestion of tissues. Flow cytometry analysis was performed to determine cell proportion and phenotypes, staining for surface immune cell lineage markers and activation markers, and intracellular cytokines (FIG. 10). As expected, CD40 agonist antibody (anti-CD40) treatment DCs located in tumor and in peripheral tissues including dLN and ndLN in parental huEpCAM negative B16F10 tumors and in huEpCAM-expressing B16F10 tumors. In contrast, the anti-muCD40 x huEPCAM bispecific antibody only activated tumor infiltrating DCs in huEpCAM-expressing B16F10 tumors, but not in parental huEpCAM-B16F10 tumor. The anti-muCD40 x huEPCAM bispecific antibody did not activate DCs in dLN or ndLN, regardless of whether these mice had human EPCAM-expressing or non-expressing B16F10 tumors (FIG. 10A). In addition, the anti-muCD40 x huEPCAM bispecific antibody increased IFNg-producing effector CD4+ and CD8+ T cells in human EPCAM-expressing B16F10 tumors, but not in parental B16F10 tumors (FIG. 10B). These data provide additional evidence that a tumor-targeted CD40 agonist bispecific antibody can activate tumor infiltrating immune cells in a tumor-associated antigen dependent manner to enhance anti-tumor T cell responses.
The Anti-muCD40 x huEPCAM Bispecific Antibody does not Induce Upregulation of Systemic Serum Cytokines or Liver Damage in Mice
CD40 agonist antibodies have shown dose-limiting toxicities in clinical trials, including liver damage and elevated serum cytokine levels, presumably due to systemic immune cell activation. To compare systemic immune cell activation and liver damage between a non-targeted CD40 agonist antibody and a tumor-targeted CD40 agonist bispecific antibody, mice bearing established human EPCAM-expressing MC38 tumors (described above) were treated with a non-specific isotype control antibody, a murine CD40 agonist antibody (anti-CD40), a CD40 antibody bearing a mutation in the Fc domain that decreases Fc receptor binding rendering it a poor agonist (anti-CD40 N297G), or the anti-muCD40 x huEPCAM bispecific antibody (anti-CD40xhuEPCAM) and serum was collected 24-48 hours later. Concentrations of select cytokines was measured using mouse cytokine/chemokine multiplex assay kit. The anti-CD40 antibody increased concentrations of several pro-inflammatory cytokines in the serum of mice, consistent with systemic immune cell activation. In contrast, neither the anti-CD40 N297G nor the anti-muCD40 x huEPCAM bispecific antibody induced increased serum cytokine concentrations (FIG. 11A). Similar results were observed in the B16F10 tumor model, where, in contrast to the non-targeted anti-CD40 antibody, the anti-muCD40 x huEPCAM bispecific antibody did not induce an increase in serum cytokine concentrations in either mice bearing vector control B16F10 tumors or mice bearing human EPCAM-expressing B16F10 tumors (FIG. 11B). The livers of mice bearing human EPCAM-expressing MC38 tumors and treated with anti-CD40 agonist antibody or the anti-muCD40 x huEPCAM bispecific antibody were also were fixed in 10% Neutral buffered formalin, embedded in paraffin, sectioned, and stained with Hematoxylin and Eosin for histological analysis. While the anti-CD40 agonist antibody induced multifocal mononuclear cell infiltration in the liver and these livers contained single cell necrosis figures, livers from the anti-muCD40 x huEPCAM bispecific antibody-treated mice did not show any distinguishable histopathological changes (FIG. 11C). Taken together, these data indicate that a tumor-targeted CD40 agonist antibody is capable of inducing local immune cell activation in the tumor, without leading to systemic cytokine production or liver damage that has been associated with anti-CD40-mediated toxicity.
Anti-Tumor Effects of Human EPCAMx Murine CD40 Bispecific Antibody in Mouse Tumor Model
To evaluate the effect of a tumor-targeted CD40 agonist antibody on immune-mediated inhibition of tumor growth and the potential for this therapeutic approach to combine with blockade of the immune checkpoint inhibitor PD1, mice bearing human EPCAM-expressing MC38 tumors were treated with an isotype control antibody, anti-CD40 agonist antibody, anti-PDL1 (that blocks interactions between PD1 and PDL1), anti-muCD40 x huEPCAM bispecific antibody, the combination of anti-CD40 with anti-PDL1, and the combination of anti-muCD40 x huEPCAM bispecific with anti-PDL1 (FIG. 12). Single agent treatment with anti-CD40 agonist antibody or anti-PDL1 blocking antibody had minimal effect on tumor growth (FIG. 12A) or on improving survival (FIG. 12B) relative to isotype control antibody treatment, while the combination of anti-CD40 agonist and anti-PDL1 significantly inhibited tumor growth. Strikingly, treatment with the anti-muCD40 x huEPCAM bispecific agonist antibody dramatically inhibited tumor growth and increased animal survival compared to other monotherapy treatments. Moreover, the combination of the anti-muCD40 x huEPCAM bispecific antibody with anti-PDL1 led to complete regression of tumors, with all animals surviving until the end of the study. These complete responder animals were housed for 3 months without treatment and no evidence of tumor reappearance, after which they were subject to tumor re-challenge with either human EPCAM-expressing MC38 tumor cells or B16F10 tumor cells (FIG. 13). These animals complete rejected the human EpCAM-expressing MC38 tumor cells, while control B16F10 tumor grew as expected. Both tumor lines grew as expected in age-matched control animals that had not previously been exposed to human EPCAM-expressing MC38 tumors or the anti-muCD40 x huEPCAM bispecific antibody. Taken together, these data demonstrate that tumor-targeted CD40 agonist antibody therapy can enhance anti-tumor immune responses, leading to regression of established tumors that is further enhanced by combination with PD1/PDL1 blockade. In addition, the combination of tumor-targeted CD40 agonist treatment with PD1/PDL1 blockade can induce long-lasting immune memory that can protect against subsequent tumor re-challenge
All publications, patents, and patent applications discussed and cited herein are hereby incorporated by reference in their entireties. It is understood that the disclosed invention is not limited to the particular methodology, protocols and materials described as these can vary. It is also understood that the terminology used herein is for the purposes of describing particular embodiments only and is not intended to limit the scope of the appended claims.
Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims.
Human CD40 >NP_001241.1 tumor necrosis factor
receptor superfamily member 5 isoform 1
precursor [Homo sapiens]
(SEQ ID NO: 1)
MVRLPLQCVLWGCLLTAVHPEPPTACREKQYLINSQCCSL
CQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHCHQH
KYCDPNLGLRVQQKGTSETDTICTCEEGWHCTSEACESCV
LHRSCSPGFGVKQIATGVSDTICEPCPVGFFSNVSSAFEK
CHPWTSCETKDLVVQQAGTNKTDVVCGPQDRLRALVVIPI
IFGILFAILLVLVFIKKVAKKPTNKAPHPKQEPQEINFPD
DLPGSNTAAPVQETLHGCQPVTQEDGKESRISVQERQ
Human mesothelin >NP_005814.2 mesothelin
isoform 1 preproprotein [Homo sapiens]
(SEQ ID NO: 2)
MALPTARPLLGSCGTPALGSLLFLLFSLGWVQPSRTLAGE
TGQEAAPLDGVLANPPNISSLSPRQLLGFPCAEVSGLSTE
RVRELAVALAQKNVKLSTEQLRCLAHRLSEPPEDLDALPL
DLLLFLNPDAFSGPQACTRFFSRITKANVDLLPRGAPERQ
RLLPAALACWGVRGSLLSEADVRALGGLACDLPGRFVAES
AEVLLPRLVSCPGPLDQDQQEAARAALQGGGPPYGPPSTW
SVSTMDALRGLLPVLGQPIIRSIPQGIVAAWRQRSSRDPS
WRQPERTILRPRFRREVEKTACPSGKKAREIDESLIFYKK
WELEACVDAALLATQMDRVNAIPFTYEQLDVLKHKLDELY
PQGYPESVIQHLGYLFLKMSPEDIRKWNVTSLETLKALLE
VNKGHEMSPQVATLIDRFVKGRGQLDKDTLDTLTAFYPGY
LCSLSPEELSSVPPSSIWAVRPQDLDTCDPRQLDVLYPKA
RLAFQNMNGSEYFVKIQSFLGGAPTEDLKALSQQNVSMDL
ATFMKLRTDAVLPLTVAEVQKLLGPHVEGLKAEERHRPVR
DWILRQRQDDLDTLGLGLQGGIPNGYLVLDLSMQEALSGT
PCLLGPGPVLTVLALLLASTLA
TABLE 19
CD40 Antibody VLs and VHs
iPS
#
Ab
Description
Type
LC
HC
iPS: 556524
21-230_33H9
(R501)L_v2_VL_PE_13641057
NA
CAGGCTGTGCCGACTCAGCCCTCTTCCCTCTCTGCA
CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGT
TCTCCTGGAGCATCAGCCAGTCTCACCTGCACCTTA
CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAG
CGCAGTGGCATCAATGTTGGTTCCTCCAGGATATA
CGTCTGGATTCACCTTCAGTAGCCATGGCATGCACT
TTGGTACCAGCAGAAGCCAGGGAGTCCTCCCCAGT
GGGTCCGCCAACCTCCAGGCAAGGGGCTGGAGTGG
TTCTCCTGAGGTACACATCAGACTCAGATAAATTG
GTGGCAGTTATCTGGTATGATGGAAGTAATGAATA
CAGGGCTCTGGAGTCCCCAGCCGCTTCTCTGGATC
CTATGGAGACTCCGTGAAGGGCCGATTCACCATCT
CAAAGATGCTTCGGCCAATGCAGGACTTTTACTCA
CCAGAGACAATTCCAAGAACACGCTGTATCTGCAA
TCTCTGGGCTCCAGTCTGAGGATGAGGCTGACTAT
ATGAACAGCCTGAGAGTCGAGGACACGGCTGTGTA
TACTGTATGATTTGGCACAGCAGCGCTGTGGTATTC
TTACTGTACGAGAGGGGGGGGCCACTGGAACTACG
GGCGGAGGGACCAAACTGACCGTCCTAGGT
AGGGCCACTACTATGGTATGGACGTCTGGGGCCAA
(SEQ ID NO: 3)
GGGACCACGGTCACCGTCTCCTCA
(SEQ ID NO: 4)
AA
QAVPTQPSSLSASPGASASLTCTLRSGINVGSSRIYWY
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSHGMHW
QQKPGSPPQFLLRYTSDSDKLQGSGVPSRFSGSKDAS
VRQPPGKGLEWVAVIWYDGSNEYYGDSVKGRFTISR
ANAGLLLISGLQSEDEADYYCMIWHSSAVVFGGGTK
DNSKNTLYLQMNSLRVEDTAVYYCTRGGGHWNYEG
LTVLG
HYYGMDVWGQGTTVTVSS
(SEQ ID NO: 5)
(SEQ ID NO: 6)
iPS: 555854
21-230_36F3
(R246)G_v1_VH_PE_13623569
NA
GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTC
CAGGTACAGCTGCAACAGTCAGGTCCAGGACTGGT
TTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCA
GAAGCCCTCGCAGACCCTCTCACTCACCTGTGCCA
GGGCCAGTCAGAGTGTTAGCAGCAACTACTTAGCC
TCTCCGGGGACAGTGTCTCTAGCAGCCGTACTGCTT
TGGTACCAACAGAAACCTGGCCAGGCTCCCAGGGC
GGAACTGGATCAGGCAGTCCCCATCGAGAGGCCTT
CCTTATCTATGCTGCATCCAACAGGGCCGCTGGCA
GAGTGGCTGGGAAGGACATACTACAGGTCCAAGTG
TCTCAGACAGGTTCAGTGGCAGTGGGTCTGGGACA
GTATCATGATTATTCAGTATCTGTGAAAAGTCGAA
GACTTCACTCTCACCATCAGCAGACTGGAGCCTGA
TAACCATCGACCCAGACACATCCAAGAACCAGTTC
AGATTTTGCAGTGTATTTCTGTCAGCAGTATGGTAG
TCCCTGCAGCTGAACTCTGTGACTCCCGAGGACAC
CTCACCGCTCACTTTCGGCGGAGGGACTAAGGTGG
GGCTGTTTATTATTGTGCAAGAGGGGCTGCTCCCTT
AGATCAAACGA
TGACTACTGGGGCCAGGGAACCCTGGTCACCGTCT
(SEQ ID NO: 7)
CCTCA
(SEQ ID NO: 8)
AA
EIVLTQSPGTLSLSPGERATLSCRASQSVSSNYLAWY
QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSSRTAWN
QQKPGQAPRALIYAASNRAAGISDRFSGSGSGTDFTL
WIRQSPSRGLEWLGRTYYRSKWYHDYSVSVKSRITID
TISRLEPEDFAVYFCQQYGSSPLTFGGGTKVEIKR
PDTSKNQFSLQLNSVTPEDTAVYYCARGAAPFDYWG
(SEQ ID NO: 9)
QGTLVTVSS
(SEQ ID NO: 10)
iPS: 555836
21-230_29H10
(R146)G_v1_VH_PE_13623469
NA
GACATCCAGATGACCCAGTCTCCATCCTCACTGTCT
CAGGTGCAACTGGTGCAGTCTGGGGCTGAGGTGAC
GCATCTGTAGGAGACAGAGTCACCATCACCTGTCG
GAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGG
GGCGAGTCAGGACATTAGCAATAATTTAGCCTGGT
CTTCTGGATACACCTTCGCCGGCTACTATATGCACT
TTCAGCAGAAACCAGGGAAACCCCCTAAGTCCCTG
GGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGG
ATGTATGCTGCATCCAGTTTGCACAGTGGAGTCCC
ATGGGATGGATCAACCCTCACAGTGGTGGCACAAA
ATCAACGTTCAGCGGCAGTGGATCTGGGACAGATT
CTATGCACAGAAGTTTCAGGACAGGGTCACCATGA
TCACTTTCACCATCAGCAGCCTGCAGCCTGAAGAT
CCAGGGACACGTCCATCAACACAGCCTACATGGAA
TTTGCAACTTATTACTGCCAACAGTATAATAGTTAC
CTGAGCAGGCTGAGATCTGACGACACGGCCGTGTA
CCTCTCACTTTCGGCGGAGGGACCAAGGTGGAGAT
TTACTGTGCGAGAGAACGTATTTCTATGGTTCGGG
CAGACGA
GAGTCGGGCACAACTGGTTCGCCCCCTGGGGCCAG
(SEQ ID NO: 11)
GGAACCCTGGTCACCGTCTCCTCA
(SEQ ID NO: 12)
AA
DIQMTQSPSSLSASVGDRVTITCRASQDISNNLAWFQ
QVQLVQSGAEVTKPGASVKVSCKASGYTFAGYYMH
QKPGKPPKSLMYAASSLHSGVPSTFSGSGSGTDFTFTI
WVRQAPGQGLEWMGWINPHSGGTNYAQKFQDRVT
SSLQPEDFATYYCQQYNSYPLTFGGGTKVEIRR
MTRDTSINTAYMELSRLRSDDTAVYYCARERISMVR
(SEQ ID NO: 13)
GVGHNWFAPWGQGTLVTVSS
(SEQ ID NO: 14)
iPS: 555842
21-230_30B9
(R161)G_v1_VH_PE_13623484
NA
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCT
CAGGTGCAGCTGGTGCAGTCCGGGACTGAAATGAA
GCATCTGTAGGAGACAGAGTCACCATCACTTGCCG
GAAGCCTGGGGCCTCAATGAAGGTCTCCTGCCAGA
GGCAAGTCAGGGCATTAGAAATGATTTAGGCTGGT
CTTCTGGATACACCTTCATCGCCTACTATATACACT
ATCAGCAGAAACCAGGGAAAGCCCCTAAGCGCCT
GGGTGCGACAGGCCCCTGGACAAGGACTTGAGTGG
GATCTCTGCTGCATTCAGTTTGCAAAGTGGGGTCCC
ATGGGATGGCTCAACCCTGACAGTGGTGGCACAAA
ATCAAGGTTCAGCGTCAGTGGATCTGGGACAGAAT
CTTTGCCCCGAGGTTTCAGGACAGAGTCACCATGA
TCACTCTCACAATCAGCAGCCTGCAGCCTGAAGAT
CCAGGGACACGTCCATCACCACAGCCTACATGGAA
TTTGCAACTTATTACTGTCTACAGTATAATAGTTAC
CTGAGCAGCCTGAGATCTGACGACACGGCCGTGTA
CCGTGGACGTTCGGCCAAGGGACCAAGGTGGAAAT
TTACTGTGCGAGAGAGAAGTTTAACTACAACTATG
CAAACGA
GTGCTTTTGATATCTGGGGCCAAGGGACAATGGTC
(SEQ ID NO: 15)
ACCGTCTCTTCA
(SEQ ID NO: 16)
AA
DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQ
QVQLVQSGTEMKKPGASMKVSCQTSGYTFIAYYIHW
QKPGKAPKRLISAAFSLQSGVPSRFSVSGSGTEFTLTIS
VRQAPGQGLEWMGWLNPDSGGTNFAPRFQDRVTMT
SLQPEDFATYYCLQYNSYPWTFGQGTKVEIKR
RDTSITTAYMELSSLRSDDTAVYYCAREKFNYNYGA
(SEQ ID NO: 17)
FDIWGQGTMVTVSS
(SEQ ID NO: 18)
iPS: 555844
21-230_31H6
(R177)G_v1_VH_PE_13623500
NA
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCT
CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAA
GCATCTGTAGGAGACAGAGTCACCATCACTTGCCG
GAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGG
GGCAAGTCAGGGCATTAGAAATGAGTTAGGCTGGT
CTTCTGGATACACCTTCACCGACTACTATATACACT
ATCAGCAGAAACCAGGGAAAGCCCCTAAGCGCCT
GGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGG
GATCTATGCTGCATCCAGTTTGGACAGTGGGGTCC
ATGGGTTGGATCAACCCTAACAGTGGTGACACAAG
CATCAAGGTTCAGCGGCAGTAGATCTGGGTCAGAA
CTATGCACAGAAGTTTCAGGACAGGGTCACCGTGA
TTCACTCTCACAATCAGCAGCCTGCAGCCTGAAGA
CCAGGGACACGTCCATCAACACAGCCTACATGGAG
TTTTGCAACTTATTACTGTCTACAATATAGTGGGTC
CTGAGTAGGCTGAAATCTGACGACACGGCCGTGTA
CCCTCTCACTTTCGGCGGAGGGACCAAGGTGGAGA
TTACTGTGCGAGAGAGGTGGGGGGCTATGGTTCGG
TCAAACGA
GGACCTACCGCTATTACGGTATGGACGTCTGGGGC
(SEQ ID NO: 19)
CAAGGGACCACGGTCACCGTCTCCTCA
(SEQ ID NO: 20)
AA
DIQMTQSPSSLSASVGDRVTITCRASQGIRNELGWYQ
QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYIH
QKPGKAPKRLIYAASSLDSGVPSRFSGSRSGSEFTLTIS
WVRQAPGQGLEWMGWINPNSGDTSYAQKFQDRVT
SLQPEDFATYYCLQYSGSPLTFGGGTKVEIKR
VTRDTSINTAYMELSRLKSDDTAVYYCAREVGGYGS
(SEQ ID NO: 21)
GTYRYYGMDVWGQGTTVTVSS
(SEQ ID NO: 22)
iPS: 556022
21-230_33H12
(R213)G_v1_VH_PE_13623536
NA
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCT
CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAA
GCATCTGTAGGAGACAGAATCACCATCACTTGCCG
GAAGCCTGGGGCCTCAGTGAAGGTCTCCTGTAAGG
GGCAAGTCAGGACATTAGAAATGATTTAGGCTGGT
CTTCTGGATACACCTTCACCGACTACTATATTCACT
ATCAGCAGAAACCAGGGAAAGCCCCTAAGCGCCT
GGGTGCGACAGGCCCCTGGACAAGTACTTGAGTGG
GATCTTTGGTGCATCCAATTTGCAAAGTGGGGTCC
ATGGGATGGATCAACCCTAACAGTGGCGGCACAAA
CATCAAGGTTCAGCGGCAGTAGATCTGGGACAGAA
CTATGCACAGAAGTTTCAGGGCAGGGTCACCATGA
TTCACTCTCACAATCAGCAGCCTGCAGCCTGAAGA
CCAGGGACACGTCCATCAATACAGCCTACATGGAG
TTTTGCAACATATTATTGTCTACAACATAATATTGC
GTGAGCAGGCTGAGATCTGACGACACGGCCGTGTA
TCCGCTCACCTTCGGCGGAGGGACCAAGGTGGAGA
TTACTGTGCGAGAGAAGATGGGGCAGCAGTTGGTC
GCAAACGA
CCCTCTACTACTACTACGGTATGGACGTCTGGGGC
(SEQ ID NO: 23)
CAAGGGACCACGGTCACCGTCTCCTCA
(SEQ ID NO: 24)
AA
DIQMTQSPSSLSASVGDRITITCRASQDIRNDLGWYQ
QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYIH
QKPGKAPKRLIFGASNLQSGVPSRFSGSRSGTEFTLTIS
WVRQAPGQVLEWMGWINPNSGGTNYAQKFQGRVT
SLQPEDFATYYCLQHNIAPLTFGGGTKVESKR
MTRDTSINTAYMEVSRLRSDDTAVYYCAREDGAAV
(SEQ ID NO: 25)
GPLYYYYGMDVWGQGTTVTVSS
(SEQ ID NO: 26)
iPS: 555860
21-230_37A6
(R268)G_v1_VH_PE_13623591
NA
TCCTATGAGCTGACTCAGCCACCCTCAGTGTCCGTG
CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCTTAGT
TCCCCAGGACAGACAGCCAGCATCACCTGCTCTGG
CAAGCCTGGAGGGTCCCTGAGACTCTCCTGTGCAG
AGAAAGGTTGGGAAATAAATATATTTGCTGGTATC
CCTCTGAATTCACCTTCAGTGACTACTACATGAGCT
AGCAGAAGCCAGGCCAGTCCCCTGTTCTGGTCATC
GGATCCGCCAGGCTCCAGGGAAGGGGCTGGAGTG
TATCAAGATTTCAAGCGGCCCTCAGGGATCCCTGA
GGTTTCATATATTAGTCGAAGTGGTGATACCATAT
GCGATTCTCTGGCTCCAACTCTGGGATCACAGCCA
ACTACGCAGACTCTGTGAAGGGCCGATTCACCATC
CTCTGACCATCAGCGGGACCCAGGCTATGGATGAG
TCCAGGGACAACGCCAAGAACTCACTGTATCTGCA
GCTGACTATTACTGTCAGGCGTGGGACAGCAGAAC
AATGAATGGCCTGCGAGCCGAAGACACGGCCGTGT
TGTGGTATTCGGCGGAGGGACCAAGCTGACCGTCC
ATTACTGTGCGAGAGACTTAGCAGCAGGTGCTACA
TAGGT
GGGGGCCTTGACTGCTGGGGCCAGGGAACCCTGGT
(SEQ ID NO: 27)
CACCGTCTCCTCA
(SEQ ID NO: 28)
AA
SYELTQPPSVSVSPGQTASITCSGERLGNKYICWYQQ
QVQLVESGGGLVKPGGSLRLSCAASEFTFSDYYMSW
KPGQSPVLVIYQDFKRPSGIPERFSGSNSGITATLTISG
IRQAPGKGLEWVSYISRSGDTIYYADSVKGRFTISRDN
TQAMDEADYYCQAWDSRTVVFGGGTKLTVLG
AKNSLYLQMNGLRAEDTAVYYCARDLAAGATGGLD
(SEQ ID NO: 29)
CWGQGTLVTVSS
(SEQ ID NO: 30)
iPS: 555840
21-230_30A12
(R168)G_v1_VH_PE_13623491
NA
CAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGG
GAGGTGCAGCTGCTGGAGTCTGGGGGAGGCTTGGT
TCTCCTGGACAGTCGATCACCATCTCCTGCACTGGA
ACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAG
ACCAGCAGTGATGTTGGGAATTATAACCTTGTCTC
CCTCTGGATTCACCTTTAGTAGAAATGCCATGAGTT
CTGGTACCAACAGCACCCAGGCAAAGCCCCCAAAC
GGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTG
TCATGATTTTTGAGGTCAATCAGCGGCCCTCAGGG
GGTCTCAGCTACTGGTGGTAGTGGTATTAGCACAT
GTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCACC
ACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC
ACGGCCTCCCTGACAATCTCTGGGCTCCAGGCTGC
TCCAGAGACAATTCCAAGAACACGCTGTATCTGCA
GGACGAGGCTGATTATTTCTGCTGCTCATATACAA
AATGAACAGTCTGAGAGCCGAGGACACGGCCGTAT
CTAGTAGCACTTATGTGATATTCGGCGGAGGGACC
ATTACTGTGCGAGAGGTTATAGCAACAGCTGGTGG
AAGCTGACCGTCCTAGGT
TACTTTGACTACTGGGGCCAGGGAACCCTGGTCAC
(SEQ ID NO: 31)
CGTCTCCTCA
(SEQ ID NO: 32)
AA
QSALTQPASVSGSPGQSITISCTGTSSDVGNYNLVSW
EVQLLESGGGLVQPGGSLRLSCAASGFTFSRNAMSW
YQQHPGKAPKLMIFEVNQRPSGVSNRFSGSKSGTTAS
VRQAPGKGLEWVSATGGSGISTYYADSVKGRFTISRD
LTISGLQAADEADYFCCSYTTSSTYVIFGGGTKLTVL
NSKNTLYLQMNSLRAEDTAVYYCARGYSNSWWYFD
G
YWGQGTLVTVSS
(SEQ ID NO: 33)
(SEQ ID NO: 34)
iPS: 555852
21-230_35F11
(R239)G_v1_VH_PE_13623562
NA
CAGTCTGCCCTGACTCAGCCTCGCTCAGTGTCCGG
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGT
GTCTCCTGGACAGTCAGTCACCATCTCCTGCACTGG
CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAG
AACCAGCAGTGATGTTGGTGGTTATATCTTTGTCTC
CGTCTGGATTCACCCTCAGTAGCTATGGCATGCACT
CTGGTACCAACAACACCCAGGCAAAGCCCCCAAAC
GGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTG
TCATGATTTATGATGTCAGTAAGCGGCCCTCTGGG
GGTGGCAGTTATATGGTATGATGGAAGTAATAAAT
GTCCCTGATCGCTTCTCTGGCTCCAAGTCTGTCAAC
ACTATGCAGACTCCGTGAAGGGCCGAGTCACCATC
ACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGA
TCCAGAGACAATTCCAAGAACACGCTGTATCTGCA
GGATGAGACTGATTATTACTGCTGCTCATATGCAG
AATGAATAGCCTGAGAGCCGAGGACACGGCTGTGT
GCAACTACACTTATGTCTTCGGAACTGGGACCAAG
ATTACTGTACGAGAGATGGCCGGAACTACGTCTAC
GTCACCGTCCTAGGT
TTTGACAACTGGGGCCAGGGAACCCTGGTCACCGT
(SEQ ID NO: 35)
CTCCTCA
(SEQ ID NO: 36)
AA
QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYIFVSWY
QVQLVESGGGVVQPGRSLRLSCAASGFTLSSYGMHW
QQHPGKAPKLMIYDVSKRPSGVPDRFSGSKSVNTASL
VRQAPGKGLEWVAVIWYDGSNKYYADSVKGRVTIS
TISGLQAEDETDYYCCSYAGNYTYVFGTGTKVTVLG
RDNSKNTLYLQMNSLRAEDTAVYYCTRDGRNYVYF
(SEQ ID NO: 37)
DNWGQGTLVTVSS
(SEQ ID NO: 38)
iPS: 555862
21-230_39C2
(R301)G_v1_VH_PE_13623624
NA
CAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGG
CAGGTGCAGCTGGTGCAGTCTGGGACTGAGGTGAA
TCTCCTGGACAGTCGATCACCATCTCCTGCACTGGA
GAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGG
ACCAGCAGTGATGTTGGGAATTATAACCTTGTCTC
CTTCTGGATACACCTTCCCCGGCTACTATATGCACT
CTGGTACCAACAGCACCCAGGCAAAGCCCCCAAAC
GGGTGCGACAGGCCCCTGGACAGGGGCTTGAGTGG
TCATGATTTATGAGGTCAATAGGCGGCCCTCAGGG
ATGGGATGGATCAACCCTGACAGTGGTGGCACAAA
GTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAAC
GTATACACAGAAGTTTCAGGGCAGGGTCACCTTGA
ACGGCCTCCCTGACAATCTCTGGGCTCCAGGCTGA
CCAGGGACGCGTCCGTCAGCACAGCCTACATTGAC
GGACGAGGCTGAATATTACTGCTGCTCATATGCAG
CTGAACAGGCTGAGATCTGACGACACGGCCGTATA
GTAGAGACACTTTCGTGGTGTTCGGCGGAGGGACC
TTACTGTGCGAGAGAGAGGTGTAGGACTACCAACT
AAGCTGACCGTCCTAGGT
GCTATTTGGACTACTGGGGCCAGGGAAGTCTGGTC
(SEQ ID NO: 39)
ACCGTCTCCTCA
(SEQ ID NO: 40)
AA
QSALTQPASVSGSPGQSITISCTGTSSDVGNYNLVSW
QVQLVQSGTEVKKPGASVKVSCKASGYTFPGYYMH
YQQHPGKAPKLMIYEVNRRPSGVSNRFSGSKSGNTA
WVRQAPGQGLEWMGWINPDSGGTKYTQKFQGRVTL
SLTISGLQAEDEAEYYCCSYAGRDTFVVFGGGTKLTV
TRDASVSTAYIDLNRLRSDDTAVYYCARERCRTTNC
LG
YLDYWGQGSLVTVSS
(SEQ ID NO: 41)
(SEQ ID NO: 42)
iPS: 556018
21-230_4G7
(R013)G_v1_VH_PE_13623336
NA
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCT
CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAA
GCATCTGTAGGAGACATTCTCACCATCACTTGCCG
GAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGG
GGCAAGTCAGAACATTACCACCTATTTAAATTGGT
CTTCTGGATACACCTTCGCCGGCTACTATATGCACT
ATCAGCAGAAACCAGGGAAAGCCCCTAACCTCCTG
GGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGG
ATCTCTGCTGCATCCCGTTTGCGAAGTGGGGTCCCA
ATGGGATGGATCAACCCTGACAGTGGAGGCACAA
TCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTT
ACTTTGCACAGCAGTTTCAGGGCAGGGTCACCATG
CACTCTCACCATCAGCAGTCTGCAACCTGTAGATTT
ACCAGGGATACGTCCATCAGCACAGCCTACATGGA
TACAACTTTCTACTGTCAACAGACTTTCACTACCCC
GGTGAGCAGGCTGAGATCTGACGACACGGCCGTGT
GTGGACGTTCGGCCAAGGGACCAAGGTGGAGATC
TTTACTGTGCGAGAGAGAAGATAACTATGACTGGT
AAACGA
ATTTACTTTGACTATTGGGGCCAGGGAACCCTGGT
(SEQ ID NO: 43)
CACCGTCTCCTCA
(SEQ ID NO: 44)
AA
DIQMTQSPSSLSASVGDILTITCRASQNITTYLNWYQQ
QVQLVQSGAEVKKPGASVKVSCKASGYTFAGYYMH
KPGKAPNLLISAASRLRSGVPSRFSGSGSGTDFTLTISS
WVRQAPGQGLEWMGWINPDSGGTNFAQQFQGRVT
LQPVDFTTFYCQQTFTTPWTFGQGTKVEIKR
MTRDTSISTAYMEVSRLRSDDTAVFYCAREKITMTGI
(SEQ ID NO: 45)
YFDYWGQGTLVTVSS
(SEQ ID NO: 46)
iPS: 555826
21-230_17H5
(R072)G_v1_VH_PE_13623395
NA
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCT
CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAA
GCATCTGTAGGAGACAGAGTCACCATCACTTGCCG
GAAGTCTGGGGCCTCAGTGAAGGTCTCCTGCAAGG
GGCAAGTCAGGGCATTAGAAATGATTTAGGCTGGT
CTTCTGGATACACCTTCGCCGGCTACTATATACACT
ATCAGCAGAAACCAGGGAAAGCCCCTAAGCGCCT
GGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGG
GATCTATCCTGCATCCAGTTTACAAAGTGGGGTCC
ATGGGATGGATCAACCCTGACAGTGGTGACACAAA
CATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAA
CTATGCACAGAAGTTTCAGGGCAGGGTCACCATGA
TTCACTCTCACAATCAGCAGCCTGCAGCCTGAAGA
CCAGGGACACGTCCATCAGTACAGCCTACATGGAG
TTTTGCAACTTATTACTGTCTACAGCATAATAGTTA
CTGAGCAGGCTGAGATCTGACGACACGGCCGTGTA
CCCTCTCACTTTCGGCGGAGGGACCAAGGTGGAGA
TTACTGTGCGAGAGAGAGGTTAACACATTGTGGTG
TCAAGCGA
GTGACTGCTATTCCCAATGGTTCGACCCCTGGGGC
(SEQ ID NO: 47)
CAGGGAACCCTGGTCACCGTCTCCTCA
(SEQ ID NO: 48)
AA
DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQ
QVQLVQSGAEVKKSGASVKVSCKASGYTFAGYYIH
QKPGKAPKRLIYPASSLQSGVPSRFSGSGSGTEFTLTIS
WVRQAPGQGLEWMGWINPDSGDTNYAQKFQGRVT
SLQPEDFATYYCLQHNSYPLTFGGGTKVEIKR
MTRDTSISTAYMELSRLRSDDTAVYYCARERLTHCG
(SEQ ID NO: 49)
GDCYSQWFDPWGQGTLVTVSS
(SEQ ID NO: 50)
iPS: 556020
21-230_33H6
(R203)G_v1_VH_PE_13623526
NA
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCT
CAGGTGCAACTGGTGCAGTCTGGGGCTGAAGTGAA
GCATCTGTAGGAGACAGAGTCACCATCACTTGCCG
GAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGG
GGCAGGTCAGAACATTAGCAGGCATTTAAATTGGT
CTTCTGGATACACCTTCCCCGGCTACTATATGTACT
ATCAGCAGAATCCAGGGAAAGCCCCTAAGGTCCTG
GGTTGCGACAGGCCCCTGGACAAGGACTTGAGTGG
ATCCATCCTGCATCCAGTTTGCCAAGTGGGGTCCC
ATGGGATGGATCAACCCTGACAGTGGTGACACAAA
GTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATT
CTATGCACAGAAGTTTCAGGGCAGGGTCACCATGA
TCAGTCTTACCATCAGCAGTCTGCAACCTGAAGAT
CCAGGGACACGTCCATCAGCACAGCCTTTATGGAG
TTTGGAACTTACTTCTGTCAACAGAGTTACAGTACC
CTGAGCAGGCTGAGATCAGACGACACGGCCGTGTA
CCTCCCACTTTCGGCGGAGGGACCAAGGTGGAGCT
TTACTGTGCGAGAGAGAAGCCCAGATATTTTGACT
CAAACGA
CCTTCTACTACTACCTTATGGACGTCTGGGGCCAAG
(SEQ ID NO: 51)
GGACCACGGTCACCGTCTCCTCA
(SEQ ID NO: 52)
AA
DIQMTQSPSSLSASVGDRVTITCRAGQNISRHLNWYQ
QVQLVQSGAEVKKPGASVKVSCKASGYTFPGYYMY
QNPGKAPKVLIHPASSLPSGVPSRFSGSGSGTDFSLTIS
WLRQAPGQGLEWMGWINPDSGDTNYAQKFQGRVT
SLQPEDFGTYFCQQSYSTPPTFGGGTKVELKR
MTRDTSISTAFMELSRLRSDDTAVYYCAREKPRYFDS
(SEQ ID NO: 53)
FYYYLMDVWGQGTTVTVSS
(SEQ ID NO: 54)
TABLE 20A
CD40 Antibody VL CDRs
iPS#
Ab
Type
CDR1
CDR2
CDR3
iPS:
21-
NA
ACCTTACGCAGTGGCATCAATGTTGGTT
TACACATCAGACTCAGATAAAT
ATGATTTGGCACAGCAGCGCTG
556524
230_33H9
CCTCCAGGATATAT
TGCAGGGCTCT
TGGTA
(SEQ ID NO: 55)
(SEQ ID NO: 56)
(SEQ ID NO: 57)
AA
TLRSGINVGSSRIY
YTSDSDKLQGS
MIWHSSAVV
(SEQ ID NO: 58)
(SEQ ID NO: 59)
(SEQ ID NO: 60)
iPS:
21-
NA
AGGGCCAGTCAGAGTGTTAGCAGCAAC
GCTGCATCCAACAGGGCCGCT
CAGCAGTATGGTAGCTCACCGC
555854
230_36F3
TACTTAGCC
(SEQ ID NO: 62)
TCACT
(SEQ ID NO: 61)
(SEQ ID NO: 63)
AA
RASQSVSSNYLA
AASNRAA
QQYGSSPLT
(SEQ ID NO: 64)
(SEQ ID NO: 65)
(SEQ ID NO: 66)
iPS:
21-
NA
CGGGCGAGTCAGGACATTAGCAATAAT
GCTGCATCCAGTTTGCACAGT
CAACAGTATAATAGTTACCCTC
555836
230_29H10
TTAGCC
(SEQ ID NO: 68)
TCACT
(SEQ ID NO: 67)
(SEQ ID NO: 69)
AA
RASQDISNNLA
AASSLHS
QQYNSYPLT
(SEQ ID NO: 70)
(SEQ ID NO: 71)
(SEQ ID NO: 72)
iPS:
21-
NA
CGGGCAAGTCAGGGCATTAGAAATGAT
GCTGCATTCAGTTTGCAAAGT
CTACAGTATAATAGTTACCCGT
555842
230_30B9
TTAGGC
(SEQ ID NO: 74)
GGACG
(SEQ ID NO: 73)
(SEQ ID NO: 75)
AA
RASQGIRNDLG
AAFSLQS
LQYNSYPWT
(SEQ ID NO: 76)
(SEQ ID NO: 77)
(SEQ ID NO: 78)
iPS:
21-
NA
CGGGCAAGTCAGGGCATTAGAAATGAG
GCTGCATCCAGTTTGGACAGT
CTACAATATAGTGGGTCCCCTC
555844
230_31H6
TTAGGC
(SEQ ID NO: 80)
TCACT
(SEQ ID NO: 79)
(SEQ ID NO: 81)
AA
RASQGIRNELG
AASSLDS
LQYSGSPLT
(SEQ ID NO: 82)
(SEQ ID NO: 83)
(SEQ ID NO: 84)
iPS:
21-
NA
CGGGCAAGTCAGGACATTAGAAATGAT
GGTGCATCCAATTTGCAAAGT
CTACAACATAATATTGCTCCGC
556022
230_33H12
TTAGGC
(SEQ ID NO: 86)
TCACC
(SEQ ID NO: 85)
(SEQ ID NO: 87)
AA
RASQDIRNDLG
GASNLQS
LQHNIAPLT
(SEQ ID NO: 88)
(SEQ ID NO: 89)
(SEQ ID NO: 90)
iPS:
21-
NA
TCTGGAGAAAGGTTGGGAAATAAATAT
CAAGATTTCAAGCGGCCCTCA
CAGGCGTGGGACAGCAGAACT
555860
230_37A6
ATTTGC
(SEQ ID NO: 92)
GTGGTA
(SEQ ID NO: 91)
(SEQ ID NO: 93)
AA
SGERLGNKYIC
QDFKRPS
QAWDSRTVV
(SEQ ID NO: 94)
(SEQ ID NO: 95)
(SEQ ID NO: 96)
iPS:
21-
NA
ACTGGAACCAGCAGTGATGTTGGGAATT
GAGGTCAATCAGCGGCCCTCA
TGCTCATATACAACTAGTAGCA
555840
230_30A12
ATAACCTTGTCTCC
(SEQ ID NO: 98)
CTTATGTGATA
(SEQ ID NO: 97)
(SEQ ID NO: 99)
AA
TGTSSDVGNYNLVS
EVNQRPS
CSYTTSSTYVI
(SEQ ID NO: 100)
(SEQ ID NO: 101)
(SEQ ID NO: 102)
iPS:
21-
NA
ACTGGAACCAGCAGTGATGTTGGTGGTT
GATGTCAGTAAGCGGCCCTCT
TGCTCATATGCAGGCAACTACA
555852
230_35F11
ATATCTTTGTCTCC
(SEQ ID NO: 104)
CTTATGTC
(SEQ ID NO: 103)
(SEQ ID NO: 105)
AA
TGTSSDVGGYIFVS
DVSKRPS
CSYAGNYTYV
(SEQ ID NO: 106)
(SEQ ID NO: 107)
(SEQ ID NO: 108)
iPS:
21-
NA
ACTGGAACCAGCAGTGATGTTGGGAATT
GAGGTCAATAGGCGGCCCTCA
TGCTCATATGCAGGTAGAGACA
555862
230_39C2
ATAACCTTGTCTCC
(SEQ ID NO: 110)
CTTTCGTGGTG
(SEQ ID NO: 109)
(SEQ ID NO: 111)
AA
TGTSSDVGNYNLVS
EVNRRPS
CSYAGRDTFVV
(SEQ ID NO: 112)
(SEQ ID NO: 113)
(SEQ ID NO: 114)
iPS:
21-
NA
CGGGCAAGTCAGAACATTACCACCTATT
GCTGCATCCCGTTTGCGAAGT
CAACAGACTTTCACTACCCCGT
556018
230_4G7
TAAAT
(SEQ ID NO: 116)
GGACG
(SEQ ID NO: 115)
(SEQ ID NO: 117)
AA
RASQNITTYLN
AASRLRS
QQTFTTPWT
(SEQ ID NO: 118)
(SEQ ID NO: 119)
(SEQ ID NO: 120)
iPS:
21-
NA
CGGGCAAGTCAGGGCATTAGAAATGAT
CCTGCATCCAGTTTACAAAGT
CTACAGCATAATAGTTACCCTC
555826
230_17H5
TTAGGC
(SEQ ID NO: 122)
TCACT
(SEQ ID NO: 121)
(SEQ ID NO: 123)
AA
RASQGIRNDLG
PASSLQS
LQHNSYPLT
(SEQ ID NO: 124)
(SEQ ID NO: 125)
(SEQ ID NO: 126)
iPS:
21-
NA
CGGGCAGGTCAGAACATTAGCAGGCAT
CCTGCATCCAGTTTGCCAAGT
CAACAGAGTTACAGTACCCCTC
556020
230_33H6
TTAAAT
(SEQ ID NO: 128)
CCACT
(SEQ ID NO: 127)
(SEQ ID NO: 129)
AA
RAGQNISRHLN
PASSLPS
QQSYSTPPT
(SEQ ID NO: 130)
(SEQ ID NO: 131)
(SEQ ID NO: 132)
TABLE 20B
CD40 Antibody VH CDRs
iPS#
Ab
Type
CDR1
CDR2
CDR3
iPS:
21-
NA
AGCCATGGCATG
GTTATCTGGTATGATGGAAGTAATGAATACT
GGGGGGGGCCACTGGAACTACGAGGGCCA
556524
230_33H9
CAC
ATGGAGACTCCGTGAAGGGC
CTACTATGGTATGGACGTC
(SEQ ID NO: 133)
(SEQ ID NO: 134)
(SEQ ID NO: 135)
AA
SHGMH
VIWYDGSNEYYGDSVKG
GGGHWNYEGHYYGMDV
(SEQ ID NO: 136)
(SEQ ID NO: 137)
(SEQ ID NO: 138)
iPS:
21-
NA
AGCAGCCGTACT
AGGACATACTACAGGTCCAAGTGGTATCATG
GGGGCTGCTCCCTTTGACTAC
555854
230_36F3
GCTTGGAAC
ATTATTCAGTATCTGTGAAAAGT
(SEQ ID NO: 141)
(SEQ ID NO: 139)
(SEQ ID NO: 140)
AA
SSRTAWN
RTYYRSKWYHDYSVSVKS
GAAPFDY
(SEQ ID NO: 142)
(SEQ ID NO: 143)
(SEQ ID NO: 144)
iPS:
21-
NA
GGCTACTATATG
TGGATCAACCCTCACAGTGGTGGCACAAACT
GAACGTATTTCTATGGTTCGGGGAGTCGGG
555836
230_29H10
CAC
ATGCACAGAAGTTTCAGGAC
CACAACTGGTTCGCCCCC
(SEQ ID NO: 145)
(SEQ ID NO: 146)
(SEQ ID NO: 147)
AA
GYYMH
WINPHSGGTNYAQKFQD
ERISMVRGVGHNWFAP
(SEQ ID NO: 148)
(SEQ ID NO: 149)
(SEQ ID NO: 150)
iPS:
21-
NA
GCCTACTATATA
TGGCTCAACCCTGACAGTGGTGGCACAAACT
GAGAAGTTTAACTACAACTATGGTGCTTTT
555842
230_30B9
CAC
TTGCCCCGAGGTTTCAGGAC
GATATC
(SEQ ID NO: 151)
(SEQ ID NO: 152)
(SEQ ID NO: 153)
AA
AYYIH
WLNPDSGGTNFAPRFQD
EKFNYNYGAFDI
(SEQ ID NO: 154)
(SEQ ID NO: 155)
(SEQ ID NO: 156)
iPS:
21-
NA
GACTACTATATA
TGGATCAACCCTAACAGTGGTGACACAAGCT
GAGGTGGGGGGCTATGGTTCGGGGACCTA
555844
230_31H6
CAC
ATGCACAGAAGTTTCAGGAC
CCGCTATTACGGTATGGACGTC
(SEQ ID NO: 157)
(SEQ ID NO: 158)
(SEQ ID NO: 159)
AA
DYYIH
WINPNSGDTSYAQKFQD
EVGGYGSGTYRYYGMDV
(SEQ ID NO: 160)
(SEQ ID NO: 161)
(SEQ ID NO: 162)
iPS:
21-
NA
GACTACTATATT
TGGATCAACCCTAACAGTGGCGGCACAAACT
GAAGATGGGGCAGCAGTTGGTCCCCTCTA
556022
230_33H12
CAC
ATGCACAGAAGTTTCAGGGC
CTACTACTACGGTATGGACGTC
(SEQ ID NO: 163)
(SEQ ID NO: 164)
(SEQ ID NO: 165)
AA
DYYIH
WINPNSGGTNYAQKFQG
EDGAAVGPLYYYYGMDV
(SEQ ID NO: 166)
(SEQ ID NO: 167)
(SEQ ID NO: 168)
iPS:
21-
NA
GACTACTACATG
TATATTAGTCGAAGTGGTGATACCATATACT
GACTTAGCAGCAGGTGCTACAGGGGGCCT
555860
230_37A6
AGC
ACGCAGACTCTGTGAAGGGC
TGACTGC
(SEQ ID NO: 169)
(SEQ ID NO: 170)
(SEQ ID NO: 171)
AA
DYYMS
YISRSGDTIYYADSVKG
DLAAGATGGLDC
(SEQ ID NO: 172)
(SEQ ID NO: 173)
(SEQ ID NO: 174)
iPS:
21-
NA
AGAAATGCCATG
GCTACTGGTGGTAGTGGTATTAGCACATACT
GGTTATAGCAACAGCTGGTGGTACTTTGAC
555840
230_30A12
AGT
ACGCAGACTCCGTGAAGGGC
TAC
(SEQ ID NO: 175)
(SEQ ID NO: 176)
(SEQ ID NO: 177)
AA
RNAMS
ATGGSGISTYYADSVKG
GYSNSWWYFDY
(SEQ ID NO: 178)
(SEQ ID NO: 179)
(SEQ ID NO: 180)
iPS:
21-
NA
AGCTATGGCATG
GTTATATGGTATGATGGAAGTAATAAATACT
GATGGCCGGAACTACGTCTACTTTGACAAC
555852
230_35F11
CAC
ATGCAGACTCCGTGAAGGGC
(SEQ ID NO: 183)
(SEQ ID NO: 181)
(SEQ ID NO: 182)
AA
SYGMH
VIWYDGSNKYYADSVKG
DGRNYVYFDN
(SEQ ID NO: 184)
(SEQ ID NO: 185)
(SEQ ID NO: 186)
iPS:
21-
NA
GGCTACTATATG
TGGATCAACCCTGACAGTGGTGGCACAAAGT
GAGAGGTGTAGGACTACCAACTGCTATTTG
555862
230_39C2
CAC
ATACACAGAAGTTTCAGGGC
GACTAC
(SEQ ID NO: 187)
(SEQ ID NO: 188)
(SEQ ID NO: 189)
AA
GYYMH
WINPDSGGTKYTQKFQG
ERCRTTNCYLDY
(SEQ ID NO: 190)
(SEQ ID NO: 191)
(SEQ ID NO: 192)
iPS:
21-
NA
GGCTACTATATG
TGGATCAACCCTGACAGTGGAGGCACAAACT
GAGAAGATAACTATGACTGGTATTTACTTT
556018
230_4G7
CAC
TTGCACAGCAGTTTCAGGGC
GACTAT
(SEQ ID NO: 193)
(SEQ ID NO: 194)
(SEQ ID NO: 195)
AA
GYYMH
WINPDSGGTNFAQQFQG
EKITMTGIYFDY
(SEQ ID NO: 196)
(SEQ ID NO: 197)
(SEQ ID NO: 198)
iPS:
21-
NA
GGCTACTATATA
TGGATCAACCCTGACAGTGGTGACACAAACT
GAGAGGTTAACACATTGTGGTGGTGACTG
555826
230_17H5
CAC
ATGCACAGAAGTTTCAGGGC
CTATTCCCAATGGTTCGACCCC
(SEQ ID NO: 199)
(SEQ ID NO: 200)
(SEQ ID NO: 201)
AA
GYYIH
WINPDSGDTNYAQKFQG
ERLTHCGGDCYSQWFDP
(SEQ ID NO: 202)
(SEQ ID NO: 203)
(SEQ ID NO: 204)
iPS:
21-
NA
GGCTACTATATG
TGGATCAACCCTGACAGTGGTGACACAAACT
GAGAAGCCCAGATATTTTGACTCCTTCTAC
556020
230_33H6
TAC
ATGCACAGAAGTTTCAGGGC
TACTACCTTATGGACGTC
(SEQ ID NO: 205)
(SEQ ID NO: 206)
(SEQ ID NO: 207)
AA
GYYMY
WINPDSGDTNYAQKFQG
EKPRYFDSFYYYLMDV
(SEQ ID NO: 208)
(SEQ ID NO: 209)
(SEQ ID NO: 210)
TABLE 21
MSLN Antibody VL and VH Sequences
IPS
#
Ab
Type
LC
HC
iPS: 563560
7G11
NA
GACATTGTGATGACTCAGTCTCCAGACTCCCTGGC
GAGGTGCAGCTGGTCGAGTCTGGAGGAGGCTTGAT
TGTGTCTCTGGGCGAGAGGGCCACCATCAACTGCA
CCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAG
AGTCCAGCCAGAGTGTTTTATACAGCTCCAACAAT
TCTCTGGGTTCACCGTCAGTAGCAAGTTCATGACC
AAGAACTACTTAGCTTGGTACCAGCAGAAACCAGG
TGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGT
ACAGCCTCCTAAGCTGCTCATTTACTGGGCATCTA
GGGTCTCAGTTATTTATAGCGGTGGTAAGACATAC
CCCGAGAATCCGGGGTCCCTGACCGATTCAGTGGC
TACGCAGACTCCGTGAAGGGCCGATTCACCATCTC
AGCGGGTCTGGGACAGATTTCACTCTCACCATCAG
CAGAGACAATTCCAAGAACACGCTGTATCTTCAAA
CAGCCTGCAGGCTGAAGATGTGGCAGTTTATTACT
TGAACAGCCTGAGAGCCGAGGACACGGCCGTGTA
GTCAGCAATATTATAGTACTCCTCCGACGTTCGGC
TTACTGTGCGAGAGATAGCGGTGGCTGGGGGTACT
CAAGGGACCAAGGTGGAGATCAAACG
TTGACTACTGGGGCCAGGGAACCCTGGTCACCGTG
(SEQ ID NO: 211)
TCCTCA
(SEQ ID NO: 212)
AA
DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKN
EVQLVESGGGLIQPGGSLRLSCAVSGFTVSSKFMTW
YLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGS
VRQAPGKGLEWVSVIYSGGKTYYADSVKGRFTISRD
GTDFTLTISSLQAEDVAVYYCQQYYSTPPTFGQGTKV
NSKNTLYLQMNSLRAEDTAVYYCARDSGGWGYFDY
EIKR
WGQGTLVTVSS
(SEQ ID NO: 213)
(SEQ ID NO: 214)
iPS: 563637
6F4
NA
GACATCCAGATGACCCAGTCTCCATCTTCCGTGTCT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGT
GCTTCTGTCGGAGACAGAGTCACCATCACTTGTCG
CAAGCCTGGAGGGTCCCTGAGACTCTCCTGTGCAG
GGCGAGTCAGGATATTAGCAGGTGGTTAGCCTGGT
CCTCTGGATTCACCTTCAGTGACTACTACATGAGCT
ATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCT
GGATCCGCCAGGCTCCAGGGAAGGGGCTGGAGTG
GATTTCTGCTGCATCCAGATTGCAAAGTGGAGTCC
GATTTCATACATTAGTAGCAGTGAAAGTATCATAT
CATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAT
ATTACGTAGACTCTGTGAAGGGCCGATTCACCATC
TTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGA
TCCAGGGACAACGCCAAGAACTCACTGTATCTGCA
TTTTGCAATTTACTATTGTCAACAGGCTAAAAGTTT
AATGAACAGCCTGAGAGCCGAGGACACGGCCGTG
TCCTCGGACGTTCGGCCAAGGGACCAAGGTGGAA
TATTACTGTGCGAGAGATGTTGGGAGCCACTTTGA
ATCAAACGA
CTACTGGGGCCAGGGAACCCTGGTCACCGTGTCCT
(SEQ ID NO: 215)
CA
(SEQ ID NO: 216)
AA
DIQMTQSPSSVSASVGDRVTITCRASQDISRWLAWYQ
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSW
QKPGKAPKLLISAASRLQSGVPSRFSGSGSGTDFTLTI
IRQAPGKGLEWISYISSSESIIYYVDSVKGRFTISRDNA
SSLQPEDFAIYYCQQAKSFPRTFGQGTKVEIKR
KNSLYLQMNSLRAEDTAVYYCARDVGSHFDYWGQ
(SEQ ID NO: 217)
GTLVTVSS
(SEQ ID NO: 218)
iPS: 344086
4G12
NA
AA
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDVHW
QVQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWG
YQQVPGTAPKLLIYGNSKRPSGVPDRFSGSKSGTSAS
WIRQPPGKGLEWIGSIYYSGITNYNPSLKSRVTISVDT
LAITGLQAEDEADYYCQSYDSSLGGWVFGGGTKLTV
SKNQFSLKLSSVTAADTAVYYCARPSNYDAFDIWGQ
L
GTMVTVSS
(SEQ ID NO: 219)
(SEQ ID NO: 220)
iPS: 344090
4H6
NA
AA
DIQMTQSPSSVSASVGDRVTITCRASQGITRWLAWY
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTW
QQKPGKAPKLLIYAASVLQSGVPSRFSGSGSGTDFTL
IRQAPGKGLEWISYISSSGSTIYYADSVKGRFTISRDN
TISSLQPEDFATYYCQQSNSFPRTFGQGTKVEIK
AKNSLYLQMNSLRAEDTAVYYCARDRNSHFDYWG
(SEQ ID NO: 221)
QGTLVTVSS
(SEQ ID NO: 222)
TABLE 22A
MSLN Antibody VL CDRs
iPS#
Ab
Type
CDR1
CDR2
CDR3
iPS:
7G11
NA
AAGTCCAGCCAGAGTGTTTTATACAGCTCCAAC
TGGGCATCTACCCGA
CAGCAATATTATAGTACTCC
563560
AATAAGAACTACTTAGCT
GAATCC
TCCGACG
(SEQ ID NO: 223)
(SEQ ID NO: 224)
(SEQ ID NO: 225)
AA
KSSQSVLYSSNNKNYLA
WASTRES
QQYYSTPPT
(SEQ ID NO: 226)
(SEQ ID NO: 227)
(SEQ ID NO: 228)
iPS:
6F4
NA
CGGGCGAGTCAGGATATTAGCAGGTGGTTAGCC
GCTGCATCCAGATTG
CAACAGGCTAAAAGTTTTCC
563637
(SEQ ID NO: 229)
CAAAGT
TCGGACG
(SEQ ID NO: 230)
(SEQ ID NO: 231)
AA
RASQDISRWLA
AASRLQS
QQAKSFPRT
(SEQ ID NO: 232)
(SEQ ID NO: 233)
(SEQ ID NO: 234)
iPS:
4G12
NA
No nuc. seq available
No nuc. seq available
No nuc. seq available
344086
AA
TGSSSNIGAGYDVH
GNSKRPS
QSYDSSLGGWV
(SEQ ID NO: 235)
(SEQ ID NO: 236)
(SEQ ID NO: 237)
iPS:
4H6
NA
No nuc. seq available
No nuc. seq available
No nuc. seq available
344090
AA
RASQGITRWLA
AASVLQS
QQSNSFPRT
(SEQ ID NO: 238)
(SEQ ID NO: 239)
(SEQ ID NO: 240)
TABLE 22B
MSLN Antibody VH CDRs
iPS#
Ab
Type
CDR1
CDR2
CDR3
iPS:
7G11
NA
AGCAAGTTCAT
GTTATTTATAGCGGTGGTAAGACATACTACGCAGACTCC
GATAGCGGTGGCTGGGGGTACT
563560
GACC
GTGAAGGGC
TTGACTAC
(SEQ ID NO: 241)
(SEQ ID NO: 242)
(SEQ ID NO: 243)
AA
SKFMT
VIYSGGKTYYADSVKG
DSGGWGYFDY
(SEQ ID NO: 244)
(SEQ ID NO: 245)
(SEQ ID NO: 246)
iPS:
6F4
NA
GACTACTACAT
TACATTAGTAGCAGTGAAAGTATCATATATTACGTAGAC
GATGTTGGGAGCCACTTTGACTA
563637
GAGC
TCTGTGAAGGGC
C
(SEQ ID NO: 247)
(SEQ ID NO: 248)
(SEQ ID NO: 249)
AA
DYYMS
YISSSESIIYYVDSVKG
DVGSHFDY
(SEQ ID NO: 250)
(SEQ ID NO: 251)
(SEQ ID NO: 252)
iPS:
4G12
NA
No nuc. seq
No nuc. seq available
No nuc. seq available
344086
available
AA
SSSYYWG
SIYYSGITNYNPSLKS
PSNYDAFDI
(SEQ ID NO: 253)
(SEQ ID NO: 254)
(SEQ ID NO: 255)
iPS:
4H6
NA
No nuc. seq
No nuc. seq available
No nuc. seq available
344090
available
AA
DYYMT
YISSSGSTIYYADSVKG
DRNSHFDY
(SEQ ID NO: 256)
(SEQ ID NO: 257)
(SEQ ID NO: 258)
TABLE 23
MSLN scFv Full Sequences
iPS#
Ab
Type
SCFV
7G11
NA
No nuc. seq available
AA
EVQLVESGGGLIQPGGSLRLSCAVSGFTVSSKFMTWVRQAPGKGLEWVSVIYSGGKTYYADSVKGRFTISRD
NSKNTLYLQMNSLRAEDTAVYYCARDSGGWGYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSP
DSLAVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTI
SSLQAEDVAVYYCQQYYSTPPTFGQGTKVEIK
(SEQ ID NO: 259)
6F4
NA
No nuc. seq available
AA
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWISYISSSESIIYYVDSVKGRFTISRDN
AKNSLYLQMNSLRAEDTAVYYCARDVGSHFDYWGQGTLVTVSSGGGGSGGGGSGGGGS
DIQMTQSPSSVSASVGDRVTITCRASQDISRWLAWYQQKPGKAPKLLISAASRLQSGVPSRFSGSGSGTDFTL
TISSLQPEDFAIYYCQQAKSFPRTFGQGTKVEIK
(SEQ ID NO: 260)
iPS:
4G12
NA
No nuc. seq available
344086
AA
QVQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLEWIGSIYYSGITNYNPSLKSRVTISVD
TSKNQFSLKLSSVTAADTAVYYCARPSNYDAFDIWGQGTMVTVSSGGGGSGGGGSGGGGSQSVLTQPPSVS
GAPGQRVTISCTGSSSNIGAGYDVHWYQQVPGTAPKLLIYGNSKRPSGVPDRFSGSKSGTSASLAITGLQAED
EADYYCQSYDSSLGGWVFGGGTKLTVL
(SEQ ID NO: 261)
iPS:
4H6
NA
No nuc. seq available
344090
AA
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIRQAPGKGLEWISYISSSGSTIYYADSVKGRFTISRD
NAKNSLYLQMNSLRAEDTAVYYCARDRNSHFDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSV
SASVGDRVTITCRASQGITRWLAWYQQKPGKAPKLLIYAASVLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA
TYYCQQSNSFPRTFGQGTKVEIK
(SEQ ID NO: 262)
TABLE 24A
CD40-MSLN IgG-scFv Full Sequences
iPS #
Ab
Type
SCFV_HC
iPS: 577383
21-230_4G7_IgG_21-233_4H6_scFv
NA
CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAG
CCTGGGGCCTCAGTGAAGGTGTCCTGCAAGGCTTCTGGAT
ACACCTTCGCCGGCTACTATATGCACTGGGTGCGACAGGC
CCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAACCCT
GACAGTGGAGGCACAAACTTTGCACAGCAGTTTCAGGGCA
GGGTCACCATGACCAGGGATACGTCCATCAGCACAGCCTA
CATGGAGGTGAGCAGGCTGAGATCTGACGACACGGCCGT
GTTTTACTGTGCGAGAGAGAAGATCACTATGACTGGTATT
TACTTTGACTATTGGGGCCAGGGAACCCTGGTCACCGTGT
CCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGC
ACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTG
GGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGG
TGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACAC
CTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCA
GCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCA
GACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACC
AAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAA
ACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGG
GGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGA
CACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTG
GTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCA
ACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGCAGCACGTACCGTTTG
CGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAAT
GGCAAGGAGTACAAGTGCAAGGTGTCCAACAAAGCCCTC
CCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGC
AGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCG
GGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCT
GGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGG
GAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACG
CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAG
CAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAA
CGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACC
ACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTGGTGG
CGGATCGGGAGGTGGCGGATCCCAGGTGCAGCTGGTCGA
GTCTGGGGGAGGCTTGGTCAAGCCTGGAGGGTCCCTGAGA
CTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTGACTACTA
CATGACCTGGATCAGGCAGGCTCCAGGGAAGTGCCTGGAG
TGGATTTCATACATTAGTAGTAGTGGTAGTACCATCTACTA
CGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGGGAC
AACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGA
GAGCCGAGGACACGGCCGTGTATTACTGTGCGAGAGATCG
GAACTCCCACTTTGACTATTGGGGCCAGGGAACCCTGGTC
ACCGTGTCCTCAGGAGGGGGCGGATCTGGCGGCGGAGGA
AGCGGTGGGGGCGGCTCCGACATTCAGATGACCCAGTCTC
CATCTTCCGTGTCTGCATCTGTAGGGGACAGAGTCACCAT
CACTTGTCGGGCGAGTCAGGGTATTACCAGGTGGTTAGCC
TGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGA
TCTATGCTGCATCCGTTTTGCAAAGTGGGGTCCCATCAAG
GTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACC
ATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTACTATT
GTCAACAGTCTAACAGTTTCCCTCGGACGTTCGGCTGCGG
GACCAAGGTGGAAATCAAACGG
(SEQ ID NO: 263)
AA
QVQLVQSGAEVKKPGASVKVSCKASGYTFAGYYMHWVRQ
APGQGLEWMGWINPDSGGTNFAQQFQGRVTMTRDTSISTAY
MEVSRLRSDDTAVFYCAREKITMTGIYFDYWGQGTLVTVSS
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN
SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP
KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN
AKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLV
KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT
VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWI
RQAPGKCLEWISYISSSGSTIYYADSVKGRFTISRDNAKNSLY
LQMNSLRAEDTAVYYCARDRNSHFDYWGQGTLVTVSSGGG
GSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIT
RWLAWYQQKPGKAPKLLIYAASVLQSGVPSRFSGSGSGTDF
TLTISSLQPEDFATYYCQQSNSFPRTFGCGTKVEIKR
(SEQ ID NO: 265)
iPS: 577388
21-230_4G7_IgG_21-233_6F4_scFv
NA
CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAG
CCTGGGGCCTCAGTGAAGGTGTCCTGCAAGGCTTCTGGAT
ACACCTTCGCCGGCTACTATATGCACTGGGTGCGACAGGC
CCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAACCCT
GACAGTGGAGGCACAAACTTTGCACAGCAGTTTCAGGGCA
GGGTCACCATGACCAGGGATACGTCCATCAGCACAGCCTA
CATGGAGGTGAGCAGGCTGAGATCTGACGACACGGCCGT
GTTTTACTGTGCGAGAGAGAAGATCACTATGACTGGTATT
TACTTTGACTATTGGGGCCAGGGAACCCTGGTCACCGTGT
CCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGC
ACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTG
GGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGG
TGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACAC
CTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCA
GCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCA
GACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACC
AAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAA
ACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGG
GGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGA
CACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTG
GTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCA
ACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGCAGCACGTACCGTTTG
CGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAAT
GGCAAGGAGTACAAGTGCAAGGTGTCCAACAAAGCCCTC
CCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGC
AGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCG
GGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCT
GGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGG
GAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACG
CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAG
CAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAA
CGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACC
ACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTGGTGG
CGGATCGGGAGGTGGCGGATCCCAGGTGCAGCTGGTGGA
GTCTGGGGGAGGCTTGGTCAAGCCTGGAGGGTCCCTGAGA
CTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTGACTACTA
CATGAGCTGGATCCGCCAGGCTCCAGGGAAGTGCCTGGAG
TGGATTTCATACATTAGTAGCAGTGAAAGTATCATCTATTA
CGTAGACTCTGTGAAGGGCCGATTCACCATCTCCAGGGAC
AACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGA
GAGCCGAGGACACGGCCGTGTATTACTGTGCGAGAGATGT
TGGGAGCCACTTTGACTACTGGGGCCAGGGAACCCTGGTC
ACCGTGTCCTCAGGAGGGGGCGGATCTGGCGGCGGAGGA
AGCGGTGGGGGCGGCTCCGACATCCAGATGACCCAGTCTC
CATCTTCCGTGTCTGCTTCTGTCGGAGACAGAGTCACCATC
ACTTGTCGGGCGAGTCAGGATATTAGCAGGTGGTTAGCCT
GGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGAT
TTCTGCTGCATCCAGATTGCAAAGTGGAGTCCCATCAAGG
TTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCA
TCAGCAGCCTGCAGCCTGAAGATTTTGCAATTTACTATTGT
CAACAGGCTAAAAGTTTTCCTCGGACGTTCGGCTGCGGGA
CCAAGGTGGAAATCAAACGG
(SEQ ID NO: 267)
AA
QVQLVQSGAEVKKPGASVKVSCKASGYTFAGYYMHWVRQ
APGQGLEWMGWINPDSGGTNFAQQFQGRVTMTRDTSISTAY
MEVSRLRSDDTAVFYCAREKITMTGIYFDYWGQGTLVTVSS
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN
SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP
KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN
AKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLV
KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT
VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWI
RQAPGKCLEWISYISSSESIIYYVDSVKGRFTISRDNAKNSLYL
QMNSLRAEDTAVYYCARDVGSHFDYWGQGTLVTVSSGGGG
SGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQDISR
WLAWYQQKPGKAPKLLISAASRLQSGVPSRFSGSGSGTDFTL
TISSLQPEDFAIYYCQQAKSFPRTFGCGTKVEIKR
(SEQ ID NO: 269)
iPS: 577393
21-230_29H10_IgG_21-233_4H6_scFv
NA
CAGGTGCAACTGGTGCAGTCTGGGGCTGAGGTGACGAAGC
CTGGGGCCTCAGTGAAGGTGTCCTGCAAGGCTTCTGGATA
CACCTTCGCCGGCTACTATATGCACTGGGTGCGACAGGCC
CCTGGACAAGGGCTTGAGTGGATGGGATGGATCAACCCTC
ACAGTGGTGGCACAAACTATGCACAGAAGTTTCAGGACAG
GGTCACCATGACCAGGGACACGTCCATCAACACAGCCTAC
ATGGAACTGAGCAGGCTGAGATCTGACGACACGGCCGTGT
ATTACTGTGCGAGAGAACGTATTTCTATGGTTCGGGGAGT
CGGGCACAACTGGTTCGCCCCCTGGGGCCAGGGAACCCTG
GTCACCGTGTCCTCAGCCTCCACCAAGGGCCCATCGGTCTT
CCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACA
GCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAAC
CGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGG
CGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCT
ACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTTT
GGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCC
AGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCT
TGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTG
AACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAA
ACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTC
ACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAG
GTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATA
ATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCAGCA
CGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAGGA
CTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCAAC
AAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAG
CCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCT
GACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCC
GTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTAC
AAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTTCTT
CCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAG
CAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTC
TGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCC
GGGTGGTGGCGGATCGGGAGGTGGCGGATCCCAGGTGCA
GCTGGTCGAGTCTGGGGGAGGCTTGGTCAAGCCTGGAGGG
TCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAG
TGACTACTACATGACCTGGATCAGGCAGGCTCCAGGGAAG
TGCCTGGAGTGGATTTCATACATTAGTAGTAGTGGTAGTA
CCATCTACTACGCAGACTCTGTGAAGGGCCGATTCACCAT
CTCCAGGGACAACGCCAAGAACTCACTGTATCTGCAAATG
AACAGCCTGAGAGCCGAGGACACGGCCGTGTATTACTGTG
CGAGAGATCGGAACTCCCACTTTGACTATTGGGGCCAGGG
AACCCTGGTCACCGTGTCCTCAGGAGGGGGCGGATCTGGC
GGCGGAGGAAGCGGTGGGGGCGGCTCCGACATTCAGATG
ACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGGGACAG
AGTCACCATCACTTGTCGGGCGAGTCAGGGTATTACCAGG
TGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTA
AGCTCCTGATCTATGCTGCATCCGTTTTGCAAAGTGGGGTC
CCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCA
CTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAAC
TTACTATTGTCAACAGTCTAACAGTTTCCCTCGGACGTTCG
GCTGCGGGACCAAGGTGGAAATCAAACGG
(SEQ ID NO: 271)
AA
QVQLVQSGAEVTKPGASVKVSCKASGYTFAGYYMHWVRQ
APGQGLEWMGWINPHSGGTNYAQKFQDRVTMTRDTSINTA
YMELSRLRSDDTAVYYCARERISMVRGVGHNWFAPWGQGT
LVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV
TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ
TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP
SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVD
GVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYK
CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQ
VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF
FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP
GGGGSGGGGSQVQLVESGGGLVKPGGSLRLSCAASGFTFSD
YYMTWIRQAPGKCLEWISYISSSGSTIYYADSVKGRFTISRDN
AKNSLYLQMNSLRAEDTAVYYCARDRNSHFDYWGQGTLVT
VSSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCR
ASQGITRWLAWYQQKPGKAPKLLIYAASVLQSGVPSRFSGSG
SGTDFTLTISSLQPEDFATYYCQQSNSFPRTFGCGTKVEIKR
(SEQ ID NO: 273)
iPS: 577397
21-230_29H10_IgG_21-233_6F4_scFv
NA
CAGGTGCAACTGGTGCAGTCTGGGGCTGAGGTGACGAAGC
CTGGGGCCTCAGTGAAGGTGTCCTGCAAGGCTTCTGGATA
CACCTTCGCCGGCTACTATATGCACTGGGTGCGACAGGCC
CCTGGACAAGGGCTTGAGTGGATGGGATGGATCAACCCTC
ACAGTGGTGGCACAAACTATGCACAGAAGTTTCAGGACAG
GGTCACCATGACCAGGGACACGTCCATCAACACAGCCTAC
ATGGAACTGAGCAGGCTGAGATCTGACGACACGGCCGTGT
ATTACTGTGCGAGAGAACGTATTTCTATGGTTCGGGGAGT
CGGGCACAACTGGTTCGCCCCCTGGGGCCAGGGAACCCTG
GTCACCGTGTCCTCAGCCTCCACCAAGGGCCCATCGGTCTT
CCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACA
GCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAAC
CGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGG
CGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCT
ACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTTT
GGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCC
AGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCT
TGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTG
AACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAA
ACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTC
ACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAG
GTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATA
ATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCAGCA
CGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAGGA
CTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCAAC
AAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAG
CCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCT
GACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCC
GTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTAC
AAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTTCTT
CCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAG
CAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTC
TGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCC
GGGTGGTGGCGGATCGGGAGGTGGCGGATCCCAGGTGCA
GCTGGTGGAGTCTGGGGGAGGCTTGGTCAAGCCTGGAGGG
TCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAG
TGACTACTACATGAGCTGGATCCGCCAGGCTCCAGGGAAG
TGCCTGGAGTGGATTTCATACATTAGTAGCAGTGAAAGTA
TCATCTATTACGTAGACTCTGTGAAGGGCCGATTCACCATC
TCCAGGGACAACGCCAAGAACTCACTGTATCTGCAAATGA
ACAGCCTGAGAGCCGAGGACACGGCCGTGTATTACTGTGC
GAGAGATGTTGGGAGCCACTTTGACTACTGGGGCCAGGGA
ACCCTGGTCACCGTGTCCTCAGGAGGGGGCGGATCTGGCG
GCGGAGGAAGCGGTGGGGGCGGCTCCGACATCCAGATGA
CCCAGTCTCCATCTTCCGTGTCTGCTTCTGTCGGAGACAGA
GTCACCATCACTTGTCGGGCGAGTCAGGATATTAGCAGGT
GGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAA
GCTCCTGATTTCTGCTGCATCCAGATTGCAAAGTGGAGTCC
CATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCAC
TCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAATTT
ACTATTGTCAACAGGCTAAAAGTTTTCCTCGGACGTTCGG
CTGCGGGACCAAGGTGGAAATCAAACGG
(SEQ ID NO: 275)
AA
QVQLVQSGAEVTKPGASVKVSCKASGYTFAGYYMHWVRQ
APGQGLEWMGWINPHSGGTNYAQKFQDRVTMTRDTSINTA
YMELSRLRSDDTAVYYCARERISMVRGVGHNWFAPWGQGT
LVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV
TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ
TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP
SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVD
GVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYK
CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQ
VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF
FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP
GGGGSGGGGSQVQLVESGGGLVKPGGSLRLSCAASGFTFSD
YYMSWIRQAPGKCLEWISYISSSESIIYYVDSVKGRFTISRDN
AKNSLYLQMNSLRAEDTAVYYCARDVGSHFDYWGQGTLVT
VSSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCR
ASQDISRWLAWYQQKPGKAPKLLISAASRLQSGVPSRFSGSG
SGTDFTLTISSLQPEDFAIYYCQQAKSFPRTFGCGTKVEIKR
(SEQ ID NO: 277)
iPS: 577401
21-230_30A12_IgG_21-233_4H6_scFv
NA
GAGGTGCAGCTGCTGGAGTCTGGGGGAGGCTTGGTACAGC
CTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTC
ACCTTTAGTAGAAATGCCATGAGTTGGGTCCGCCAGGCTC
CAGGGAAGGGGCTGGAGTGGGTGTCAGCTACTGGTGGTA
GTGGTATTAGCACATACTACGCAGACTCCGTGAAGGGCCG
GTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTAT
CTGCAAATGAACAGTCTGAGAGCCGAGGACACGGCCGTAT
ATTACTGTGCGAGAGGTTATAGCAACAGCTGGTGGTACTT
TGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTCCTCA
GCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTC
CTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGC
CTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGT
GGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCC
GGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGC
GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCT
ACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGT
GGACAAGAAAGTTGAGCCCAAATCTTGTGACAAAACTCAC
ACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGAC
CGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTC
ATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGG
ACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTA
CGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCC
GTGCGAGGAGCAGTACGGCAGCACGTACCGTTGCGTCAGC
GTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGG
AGTACAAGTGCAAGGTGTCCAACAAAGCCCTCCCAGCCCC
CATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCG
AGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAG
ATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAG
GCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAA
TGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTG
CTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCAC
CGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTTTCTC
ATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACG
CAGAAGAGCCTCTCCCTGTCTCCGGGTGGTGGCGGATCGG
GAGGTGGCGGATCCCAGGTGCAGCTGGTCGAGTCTGGGGG
AGGCTTGGTCAAGCCTGGAGGGTCCCTGAGACTCTCCTGT
GCAGCCTCTGGATTCACCTTCAGTGACTACTACATGACCTG
GATCAGGCAGGCTCCAGGGAAGTGCCTGGAGTGGATTTCA
TACATTAGTAGTAGTGGTAGTACCATCTACTACGCAGACT
CTGTGAAGGGCCGATTCACCATCTCCAGGGACAACGCCAA
GAACTCACTGTATCTGCAAATGAACAGCCTGAGAGCCGAG
GACACGGCCGTGTATTACTGTGCGAGAGATCGGAACTCCC
ACTTTGACTATTGGGGCCAGGGAACCCTGGTCACCGTGTC
CTCAGGAGGGGGCGGATCTGGCGGCGGAGGAAGCGGTGG
GGGCGGCTCCGACATTCAGATGACCCAGTCTCCATCTTCC
GTGTCTGCATCTGTAGGGGACAGAGTCACCATCACTTGTC
GGGCGAGTCAGGGTATTACCAGGTGGTTAGCCTGGTATCA
GCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCT
GCATCCGTTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCG
GCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAG
CCTGCAGCCTGAAGATTTTGCAACTTACTATTGTCAACAGT
CTAACAGTTTCCCTCGGACGTTCGGCTGCGGGACCAAGGT
GGAAATCAAACGG
(SEQ ID NO: 279)
AA
EVQLLESGGGLVQPGGSLRLSCAASGFTFSRNAMSWVRQAP
GKGLEWVSATGGSGISTYYADSVKGRFTISRDNSKNTLYLQ
MNSLRAEDTAVYYCARGYSNSWWYFDYWGQGTLVTVSSA
STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS
GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPK
PKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNA
KTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA
LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVK
GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGG
GGSQVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIR
QAPGKCLEWISYISSSGSTIYYADSVKGRFTISRDNAKNSLYL
QMNSLRAEDTAVYYCARDRNSHFDYWGQGTLVTVSSGGGG
SGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGITR
WLAWYQQKPGKAPKLLIYAASVLQSGVPSRFSGSGSGTDFT
LTISSLQPEDFATYYCQQSNSFPRTFGCGTKVEIKR
(SEQ ID NO: 281)
iPS: 577405
21-230_30A12_IgG_21-233_6F4_scFv
NA
GAGGTGCAGCTGCTGGAGTCTGGGGGAGGCTTGGTACAGC
CTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTC
ACCTTTAGTAGAAATGCCATGAGTTGGGTCCGCCAGGCTC
CAGGGAAGGGGCTGGAGTGGGTGTCAGCTACTGGTGGTA
GTGGTATTAGCACATACTACGCAGACTCCGTGAAGGGCCG
GTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTAT
CTGCAAATGAACAGTCTGAGAGCCGAGGACACGGCCGTAT
ATTACTGTGCGAGAGGTTATAGCAACAGCTGGTGGTACTT
TGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTCCTCA
GCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTC
CTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGC
CTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGT
GGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCC
GGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGC
GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCT
ACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGT
GGACAAGAAAGTTGAGCCCAAATCTTGTGACAAAACTCAC
ACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGAC
CGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTC
ATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGG
ACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTA
CGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCC
GTGCGAGGAGCAGTACGGCAGCACGTACCGTTGCGTCAGC
GTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGG
AGTACAAGTGCAAGGTGTCCAACAAAGCCCTCCCAGCCCC
CATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCG
AGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAG
ATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAG
GCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAA
TGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTG
CTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCAC
CGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTTTCTC
ATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACG
CAGAAGAGCCTCTCCCTGTCTCCGGGTGGTGGCGGATCGG
GAGGTGGCGGATCCCAGGTGCAGCTGGTGGAGTCTGGGG
GAGGCTTGGTCAAGCCTGGAGGGTCCCTGAGACTCTCCTG
TGCAGCCTCTGGATTCACCTTCAGTGACTACTACATGAGCT
GGATCCGCCAGGCTCCAGGGAAGTGCCTGGAGTGGATTTC
ATACATTAGTAGCAGTGAAAGTATCATCTATTACGTAGAC
TCTGTGAAGGGCCGATTCACCATCTCCAGGGACAACGCCA
AGAACTCACTGTATCTGCAAATGAACAGCCTGAGAGCCGA
GGACACGGCCGTGTATTACTGTGCGAGAGATGTTGGGAGC
CACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTGT
CCTCAGGAGGGGGCGGATCTGGCGGCGGAGGAAGCGGTG
GGGGCGGCTCCGACATCCAGATGACCCAGTCTCCATCTTC
CGTGTCTGCTTCTGTCGGAGACAGAGTCACCATCACTTGTC
GGGCGAGTCAGGATATTAGCAGGTGGTTAGCCTGGTATCA
GCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATTTCTGCT
GCATCCAGATTGCAAAGTGGAGTCCCATCAAGGTTCAGCG
GCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAG
CCTGCAGCCTGAAGATTTTGCAATTTACTATTGTCAACAGG
CTAAAAGTTTTCCTCGGACGTTCGGCTGCGGGACCAAGGT
GGAAATCAAACGG
(SEQ ID NO: 283)
AA
EVQLLESGGGLVQPGGSLRLSCAASGFTFSRNAMSWVRQAP
GKGLEWVSATGGSGISTYYADSVKGRFTISRDNSKNTLYLQ
MNSLRAEDTAVYYCARGYSNSWWYFDYWGQGTLVTVSSA
STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS
GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPK
PKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNA
KTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA
LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVK
GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGG
GGSQVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIR
QAPGKCLEWISYISSSESIIYYVDSVKGRFTISRDNAKNSLYLQ
MNSLRAEDTAVYYCARDVGSHFDYWGQGTLVTVSSGGGGS
GGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQDISRW
LAWYQQKPGKAPKLLISAASRLQSGVPSRFSGSGSGTDFTLTI
SSLQPEDFAIYYCQQAKSFPRTFGCGTKVEIKR
(SEQ ID NO: 285)
iPS: 577409
21-230_33H6_IgG_21-233_4H6_scFv
NA
CAGGTGCAACTGGTGCAGTCTGGGGCTGAAGTGAAGAAG
CCTGGGGCCTCAGTGAAGGTGTCCTGCAAGGCTTCTGGAT
ACACCTTCCCCGGCTACTATATGTACTGGTTGCGACAGGC
CCCTGGACAAGGACTTGAGTGGATGGGATGGATCAACCCT
GACAGTGGTGACACAAACTATGCACAGAAGTTTCAGGGCA
GGGTCACCATGACCAGGGACACGTCCATCAGCACAGCCTTTT
TATGGAGCTGAGCAGGCTGAGATCAGACGACACGGCCGT
GTATTACTGTGCGAGAGAGAAGCCCAGATATTTTGACTCC
TTCTACTACTACCTTATGGACGTCTGGGGCCAAGGGACCA
CGGTCACCGTGTCCTCAGCCTCCACCAAGGGCCCATCGGT
CTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGC
ACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCG
AACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAG
CGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGA
CTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCA
GCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAA
GCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAA
ATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCA
CCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTTCCCCCC
AAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAG
GTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTG
AGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCA
TAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCAG
CACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCC
AACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCA
AAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCC
TGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCA
GCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACAT
CGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAA
CTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCC
TTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGT
GGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGA
GGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTG
TCTCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCCAGG
TGCAGCTGGTCGAGTCTGGGGGAGGCTTGGTCAAGCCTGG
AGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCT
TCAGTGACTACTACATGACCTGGATCAGGCAGGCTCCAGG
GAAGTGCCTGGAGTGGATTTCATACATTAGTAGTAGTGGT
AGTACCATCTACTACGCAGACTCTGTGAAGGGCCGATTCA
CCATCTCCAGGGACAACGCCAAGAACTCACTGTATCTGCA
AATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTATTAC
TGTGCGAGAGATCGGAACTCCCACTTTGACTATTGGGGCC
AGGGAACCCTGGTCACCGTGTCCTCAGGAGGGGGCGGATC
TGGCGGCGGAGGAAGCGGTGGGGGCGGCTCCGACATTCA
GATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGGG
ACAGAGTCACCATCACTTGTCGGGCGAGTCAGGGTATTAC
CAGGTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGC
CCCTAAGCTCCTGATCTATGCTGCATCCGTTTTGCAAAGTG
GGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGA
TTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTG
CAACTTACTATTGTCAACAGTCTAACAGTTTCCCTCGGACG
TTCGGCTGCGGGACCAAGGTGGAAATCAAACGG
(SEQ ID NO: 287)
AA
QVQLVQSGAEVKKPGASVKVSCKASGYTFPGYYMYWLRQA
PGQGLEWMGWINPDSGDTNYAQKFQGRVTMTRDTSISTAF
MELSRLRSDDTAVYYCAREKPRYFDSFYYYLMDVWGQGTT
VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT
VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG
VEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKC
KVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVS
LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL
YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGG
GGSGGGGSQVQLVESGGGLVKPGGSLRLSCAASGFTFSDYY
MTWIRQAPGKCLEWISYISSSGSTIYYADSVKGRFTISRDNAK
NSLYLQMNSLRAEDTAVYYCARDRNSHFDYWGQGTLVTVS
SGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRAS
QGITRWLAWYQQKPGKAPKLLIYAASVLQSGVPSRFSGSGSG
TDFTLTISSLQPEDFATYYCQQSNSFPRTFGCGTKVEIKR
(SEQ ID NO: 289)
iPS: 577413
21-230_33H6_IgG_21-233_6F4_scFv
NA
CAGGTGCAACTGGTGCAGTCTGGGGCTGAAGTGAAGAAG
CCTGGGGCCTCAGTGAAGGTGTCCTGCAAGGCTTCTGGAT
ACACCTTCCCCGGCTACTATATGTACTGGTTGCGACAGGC
CCCTGGACAAGGACTTGAGTGGATGGGATGGATCAACCCT
GACAGTGGTGACACAAACTATGCACAGAAGTTTCAGGGCA
GGGTCACCATGACCAGGGACACGTCCATCAGCACAGCCTTTT
TATGGAGCTGAGCAGGCTGAGATCAGACGACACGGCCGT
GTATTACTGTGCGAGAGAGAAGCCCAGATATTTTGACTCC
TTCTACTACTACCTTATGGACGTCTGGGGCCAAGGGACCA
CGGTCACCGTGTCCTCAGCCTCCACCAAGGGCCCATCGGT
CTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGC
ACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCG
AACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAG
CGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGA
CTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCA
GCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAA
GCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAA
ATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCA
CCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTTCCCCCC
AAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAG
GTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTG
AGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCA
TAATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCAG
CACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAG
GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCC
AACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCA
AAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCC
TGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCA
GCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACAT
CGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAA
CTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCC
TTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGT
GGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGA
GGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTG
TCTCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCCAGG
TGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCAAGCCTGG
AGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCT
TCAGTGACTACTACATGAGCTGGATCCGCCAGGCTCCAGG
GAAGTGCCTGGAGTGGATTTCATACATTAGTAGCAGTGAA
AGTATCATCTATTACGTAGACTCTGTGAAGGGCCGATTCA
CCATCTCCAGGGACAACGCCAAGAACTCACTGTATCTGCA
AATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTATTAC
TGTGCGAGAGATGTTGGGAGCCACTTTGACTACTGGGGCC
AGGGAACCCTGGTCACCGTGTCCTCAGGAGGGGGCGGATC
TGGCGGCGGAGGAAGCGGTGGGGGCGGCTCCGACATCCA
GATGACCCAGTCTCCATCTTCCGTGTCTGCTTCTGTCGGAG
ACAGAGTCACCATCACTTGTCGGGCGAGTCAGGATATTAG
CAGGTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGC
CCCTAAGCTCCTGATTTCTGCTGCATCCAGATTGCAAAGTG
GAGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGA
TTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTG
CAATTTACTATTGTCAACAGGCTAAAAGTTTTCCTCGGACG
TTCGGCTGCGGGACCAAGGTGGAAATCAAACGG
(SEQ ID NO: 291)
AA
QVQLVQSGAEVKKPGASVKVSCKASGYTFPGYYMYWLRQA
PGQGLEWMGWINPDSGDTNYAQKFQGRVTMTRDTSISTAF
MELSRLRSDDTAVYYCAREKPRYFDSFYYYLMDVWGQGTT
VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT
VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG
VEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKC
KVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVS
LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL
YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGG
GGSGGGGSQVQLVESGGGLVKPGGSLRLSCAASGFTFSDYY
MSWIRQAPGKCLEWISYISSSESIIYYVDSVKGRFTISRDNAK
NSLYLQMNSLRAEDTAVYYCARDVGSHFDYWGQGTLVTVS
SGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRAS
QDISRWLAWYQQKPGKAPKLLISAASRLQSGVPSRFSGSGSG
TDFTLTISSLQPEDFAIYYCQQAKSFPRTFGCGTKVEIKR
(SEQ ID NO: 293)
iPS: 577417
21-230_33H9_IgG_21-233_4H6_scFv
NA
CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGTCCAGC
CTGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATT
CACCTTCAGTAGCCATGGCATGCACTGGGTCCGCCAACCT
CCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATCTGGTATG
ATGGAAGTAATGAATACTATGGAGACTCCGTGAAGGGCCG
ATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTAT
CTGCAAATGAACAGCCTGAGAGTCGAGGACACGGCTGTGT
ATTACTGTACGAGAGGGGGGGGCCACTGGAACTACGAGG
GCCACTACTATGGTATGGACGTCTGGGGCCAAGGGACCAC
GGTCACCGTGTCCTCAGCCTCCACCAAGGGCCCATCGGTC
TTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCA
CAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGA
ACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC
GGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGAC
TCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAG
CTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAG
CCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAA
TCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCAC
CTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCA
AAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGG
TCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGA
GGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCAT
AATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCAGC
ACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAGG
ACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAA
AGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCT
GCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAG
CCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATC
GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAAC
TACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCT
TCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTG
GCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAG
GCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGT
CTCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCCAGGT
GCAGCTGGTCGAGTCTGGGGGAGGCTTGGTCAAGCCTGGA
GGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTT
CAGTGACTACTACATGACCTGGATCAGGCAGGCTCCAGGG
AAGTGCCTGGAGTGGATTTCATACATTAGTAGTAGTGGTA
GTACCATCTACTACGCAGACTCTGTGAAGGGCCGATTCAC
CATCTCCAGGGACAACGCCAAGAACTCACTGTATCTGCAA
ATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTATTACT
GTGCGAGAGATCGGAACTCCCACTTTGACTATTGGGGCCA
GGGAACCCTGGTCACCGTGTCCTCAGGAGGGGGCGGATCT
GGCGGCGGAGGAAGCGGTGGGGGCGGCTCCGACATTCAG
ATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGGGA
CAGAGTCACCATCACTTGTCGGGCGAGTCAGGGTATTACC
AGGTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCC
CCTAAGCTCCTGATCTATGCTGCATCCGTTTTGCAAAGTGG
GGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAT
TTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGC
AACTTACTATTGTCAACAGTCTAACAGTTTCCCTCGGACGT
TCGGCTGCGGGACCAAGGTGGAAATCAAACGG
(SEQ ID NO: 295)
AA
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSHGMHWVRQPP
GKGLEWVAVIWYDGSNEYYGDSVKGRFTISRDNSKNTLYLQ
MNSLRVEDTAVYYCTRGGGHWNYEGHYYGMDVWGQGTT
VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT
VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG
VEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKC
KVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVS
LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL
YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGG
GGSGGGGSQVQLVESGGGLVKPGGSLRLSCAASGFTFSDYY
MTWIRQAPGKCLEWISYISSSGSTIYYADSVKGRFTISRDNAK
NSLYLQMNSLRAEDTAVYYCARDRNSHFDYWGQGTLVTVS
SGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRAS
QGITRWLAWYQQKPGKAPKLLIYAASVLQSGVPSRFSGSGSG
TDFTLTISSLQPEDFATYYCQQSNSFPRTFGCGTKVEIKR
(SEQ ID NO: 297)
iPS: 577421
21-230_33H9_IgG_21-233_6F4_scFv
NA
CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGTCCAGC
CTGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATT
CACCTTCAGTAGCCATGGCATGCACTGGGTCCGCCAACCT
CCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATCTGGTATG
ATGGAAGTAATGAATACTATGGAGACTCCGTGAAGGGCCG
ATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTAT
CTGCAAATGAACAGCCTGAGAGTCGAGGACACGGCTGTGT
ATTACTGTACGAGAGGGGGGGGCCACTGGAACTACGAGG
GCCACTACTATGGTATGGACGTCTGGGGCCAAGGGACCAC
GGTCACCGTGTCCTCAGCCTCCACCAAGGGCCCATCGGTC
TTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCA
CAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGA
ACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC
GGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGAC
TCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAG
CTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAG
CCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAA
TCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCAC
CTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCA
AAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGG
TCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGA
GGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCAT
AATGCCAAGACAAAGCCGTGCGAGGAGCAGTACGGCAGC
ACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCACCAGG
ACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTGTCCA
ACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAA
AGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCT
GCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAG
CCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATC
GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAAC
TACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCT
TCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTG
GCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAG
GCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGT
CTCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCCAGGT
GCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCAAGCCTGGA
GGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTT
CAGTGACTACTACATGAGCTGGATCCGCCAGGCTCCAGGG
AAGTGCCTGGAGTGGATTTCATACATTAGTAGCAGTGAAA
GTATCATCTATTACGTAGACTCTGTGAAGGGCCGATTCAC
CATCTCCAGGGACAACGCCAAGAACTCACTGTATCTGCAA
ATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTATTACT
GTGCGAGAGATGTTGGGAGCCACTTTGACTACTGGGGCCA
GGGAACCCTGGTCACCGTGTCCTCAGGAGGGGGCGGATCT
GGCGGCGGAGGAAGCGGTGGGGGCGGCTCCGACATCCAG
ATGACCCAGTCTCCATCTTCCGTGTCTGCTTCTGTCGGAGA
CAGAGTCACCATCACTTGTCGGGCGAGTCAGGATATTAGC
AGGTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCC
CCTAAGCTCCTGATTTCTGCTGCATCCAGATTGCAAAGTGG
AGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAT
TTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGC
AATTTACTATTGTCAACAGGCTAAAAGTTTTCCTCGGACGT
TCGGCTGCGGGACCAAGGTGGAAATCAAACGG
(SEQ ID NO: 299)
AA
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSHGMHWVRQPP
GKGLEWVAVIWYDGSNEYYGDSVKGRFTISRDNSKNTLYLQ
MNSLRVEDTAVYYCTRGGGHWNYEGHYYGMDVWGQGTT
VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT
VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG
VEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKC
KVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVS
LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL
YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGG
GGSGGGGSQVQLVESGGGLVKPGGSLRLSCAASGFTFSDYY
MSWIRQAPGKCLEWISYISSSESIIYYVDSVKGRFTISRDNAK
NSLYLQMNSLRAEDTAVYYCARDVGSHFDYWGQGTLVTVS
SGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRAS
QDISRWLAWYQQKPGKAPKLLISAASRLQSGVPSRFSGSGSG
TDFTLTISSLQPEDFAIYYCQQAKSFPRTFGCGTKVEIKR
(SEQ ID NO: 301)
iPS: 577425
21-230_35F11_IgG_21-233_4H6_scFv
NA
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGC
CTGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATT
CACCCTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGCT
CCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATCTGGTATG
ATGGAAGTAATAAATACTATGCAGACTCCGTGAAGGGCCG
AGTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTAT
CTGCAAATGAATAGCCTGAGAGCCGAGGACACGGCTGTGT
ATTACTGTACGAGAGATGGCCGGAACTACGTCTACTTTGA
CAACTGGGGCCAGGGAACCCTGGTCACCGTGTCCTCAGCC
TCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTC
CAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTG
GTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGA
ACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGC
TGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGG
TGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACAT
CTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGA
CAAGAAAGTTGAGCCCAAATCTTGTGACAAAACTCACACA
TGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGT
CAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATG
ATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACG
TGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGT
GGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGTG
CGAGGAGCAGTACGGCAGCACGTACCGTTGCGTCAGCGTC
CTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGT
ACAAGTGCAAGGTGTCCAACAAAGCCCTCCCAGCCCCCAT
CGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGA
ACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATG
ACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCT
TCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGG
GCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTG
GACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGT
GGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATG
CTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAG
AAGAGCCTCTCCCTGTCTCCGGGTGGTGGCGGATCGGGAG
GTGGCGGATCCCAGGTGCAGCTGGTCGAGTCTGGGGGAGG
CTTGGTCAAGCCTGGAGGGTCCCTGAGACTCTCCTGTGCA
GCCTCTGGATTCACCTTCAGTGACTACTACATGACCTGGAT
CAGGCAGGCTCCAGGGAAGTGCCTGGAGTGGATTTCATAC
ATTAGTAGTAGTGGTAGTACCATCTACTACGCAGACTCTG
TGAAGGGCCGATTCACCATCTCCAGGGACAACGCCAAGAA
CTCACTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGAC
ACGGCCGTGTATTACTGTGCGAGAGATCGGAACTCCCACT
TTGACTATTGGGGCCAGGGAACCCTGGTCACCGTGTCCTC
AGGAGGGGGCGGATCTGGCGGCGGAGGAAGCGGTGGGGG
CGGCTCCGACATTCAGATGACCCAGTCTCCATCTTCCGTGT
CTGCATCTGTAGGGGACAGAGTCACCATCACTTGTCGGGC
GAGTCAGGGTATTACCAGGTGGTTAGCCTGGTATCAGCAG
AAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCAT
CCGTTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGCAG
TGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTG
CAGCCTGAAGATTTTGCAACTTACTATTGTCAACAGTCTAA
CAGTTTCCCTCGGACGTTCGGCTGCGGGACCAAGGTGGAA
ATCAAACGG
(SEQ ID NO: 303)
AA
QVQLVESGGGVVQPGRSLRLSCAASGFTLSSYGMHWVRQAP
GKGLEWVAVIWYDGSNKYYADSVKGRVTISRDNSKNTLYL
QMNSLRAEDTAVYYCTRDGRNYVYFDNWGQGTLVTVSSAS
TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSG
ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP
KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNA
KTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA
LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVK
GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGG
GGSQVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIR
QAPGKCLEWISYISSSGSTIYYADSVKGRFTISRDNAKNSLYL
QMNSLRAEDTAVYYCARDRNSHFDYWGQGTLVTVSSGGGG
SGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGITR
WLAWYQQKPGKAPKLLIYAASVLQSGVPSRFSGSGSGTDFT
LTISSLQPEDFATYYCQQSNSFPRTFGCGTKVEIKR
(SEQ ID NO: 305)
iPS: 577429
21-230_35F11_IgG_21-233_6F4_scFv
NA
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGC
CTGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATT
CACCCTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGCT
CCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATCTGGTATG
ATGGAAGTAATAAATACTATGCAGACTCCGTGAAGGGCCG
AGTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTAT
CTGCAAATGAATAGCCTGAGAGCCGAGGACACGGCTGTGT
ATTACTGTACGAGAGATGGCCGGAACTACGTCTACTTTGA
CAACTGGGGCCAGGGAACCCTGGTCACCGTGTCCTCAGCC
TCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTC
CAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTG
GTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGA
ACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGC
TGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGG
TGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACAT
CTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGA
CAAGAAAGTTGAGCCCAAATCTTGTGACAAAACTCACACA
TGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGT
CAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATG
ATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACG
TGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGT
GGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGTG
CGAGGAGCAGTACGGCAGCACGTACCGTTGCGTCAGCGTC
CTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGT
ACAAGTGCAAGGTGTCCAACAAAGCCCTCCCAGCCCCCAT
CGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGA
ACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATG
ACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCT
TCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGG
GCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTG
GACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGT
GGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATG
CTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAG
AAGAGCCTCTCCCTGTCTCCGGGTGGTGGCGGATCGGGAG
GTGGCGGATCCCAGGTGCAGCTGGTGGAGTCTGGGGGAG
GCTTGGTCAAGCCTGGAGGGTCCCTGAGACTCTCCTGTGC
AGCCTCTGGATTCACCTTCAGTGACTACTACATGAGCTGG
ATCCGCCAGGCTCCAGGGAAGTGCCTGGAGTGGATTTCAT
ACATTAGTAGCAGTGAAAGTATCATCTATTACGTAGACTC
TGTGAAGGGCCGATTCACCATCTCCAGGGACAACGCCAAG
AACTCACTGTATCTGCAAATGAACAGCCTGAGAGCCGAGG
ACACGGCCGTGTATTACTGTGCGAGAGATGTTGGGAGCCA
CTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTGTCC
TCAGGAGGGGGCGGATCTGGCGGCGGAGGAAGCGGTGGG
GGCGGCTCCGACATCCAGATGACCCAGTCTCCATCTTCCG
TGTCTGCTTCTGTCGGAGACAGAGTCACCATCACTTGTCGG
GCGAGTCAGGATATTAGCAGGTGGTTAGCCTGGTATCAGC
AGAAACCAGGGAAAGCCCCTAAGCTCCTGATTTCTGCTGC
ATCCAGATTGCAAAGTGGAGTCCCATCAAGGTTCAGCGGC
AGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCC
TGCAGCCTGAAGATTTTGCAATTTACTATTGTCAACAGGCT
AAAAGTTTTCCTCGGACGTTCGGCTGCGGGACCAAGGTGG
AAATCAAACGG
(SEQ ID NO: 307)
AA
QVQLVESGGGVVQPGRSLRLSCAASGFTLSSYGMHWVRQAP
GKGLEWVAVIWYDGSNKYYADSVKGRVTISRDNSKNTLYL
QMNSLRAEDTAVYYCTRDGRNYVYFDNWGQGTLVTVSSAS
TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSG
ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP
KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNA
KTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA
LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVK
GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGG
GGSQVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIR
QAPGKCLEWISYISSSESIIYYVDSVKGRFTISRDNAKNSLYLQ
MNSLRAEDTAVYYCARDVGSHFDYWGQGTLVTVSSGGGGS
GGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQDISRW
LAWYQQKPGKAPKLLISAASRLQSGVPSRFSGSGSGTDFTLTI
SSLQPEDFAIYYCQQAKSFPRTFGCGTKVEIKR
(SEQ ID NO: 309)
iPS: 577433
21-230_36F3_IgG_21-233_4H6_scFv
NA
CAGGTACAGCTGCAACAGTCAGGTCCAGGACTGGTGAAGC
CCTCGCAGACCCTCTCACTCACCTGTGCCATCTCCGGGGAC
AGTGTCTCTAGCAGCCGTACTGCTTGGAACTGGATCAGGC
AGTCCCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACATA
CTACAGGTCCAAGTGGTATCATGATTATTCAGTATCTGTGA
AAAGTCGAATCACCATCGACCCAGACACATCCAAGAACCA
GTTCTCCCTGCAGCTGAACTCTGTGACTCCCGAGGACACG
GCTGTTTATTATTGTGCAAGAGGGGCTGCTCCCTTTGACTA
CTGGGGCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCC
ACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCA
AGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGT
CAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAAC
TCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTG
TCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTG
ACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCT
GCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACA
AGAAAGTTGAGCCCAAATCTTGTGACAAAACTCACACATG
CCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCA
GTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGAT
CTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTG
AGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGG
ACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGTGCG
AGGAGCAGTACGGCAGCACGTACCGTTGCGTCAGCGTCCT
CACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTAC
AAGTGCAAGGTGTCCAACAAAGCCCTCCCAGCCCCCATCG
AGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAAC
CACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGAC
CAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC
TATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGC
AGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGA
CTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGG
ACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTC
CGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAG
AGCCTCTCCCTGTCTCCGGGTGGTGGCGGATCGGGAGGTG
GCGGATCCCAGGTGCAGCTGGTCGAGTCTGGGGGAGGCTT
GGTCAAGCCTGGAGGGTCCCTGAGACTCTCCTGTGCAGCC
TCTGGATTCACCTTCAGTGACTACTACATGACCTGGATCAG
GCAGGCTCCAGGGAAGTGCCTGGAGTGGATTTCATACATT
AGTAGTAGTGGTAGTACCATCTACTACGCAGACTCTGTGA
AGGGCCGATTCACCATCTCCAGGGACAACGCCAAGAACTC
ACTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACG
GCCGTGTATTACTGTGCGAGAGATCGGAACTCCCACTTTG
ACTATTGGGGCCAGGGAACCCTGGTCACCGTGTCCTCAGG
AGGGGGCGGATCTGGCGGCGGAGGAAGCGGTGGGGGCGG
CTCCGACATTCAGATGACCCAGTCTCCATCTTCCGTGTCTG
CATCTGTAGGGGACAGAGTCACCATCACTTGTCGGGCGAG
TCAGGGTATTACCAGGTGGTTAGCCTGGTATCAGCAGAAA
CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCG
TTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGG
ATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAG
CCTGAAGATTTTGCAACTTACTATTGTCAACAGTCTAACAG
TTTCCCTCGGACGTTCGGCTGCGGGACCAAGGTGGAAATC
AAACGG
(SEQ ID NO: 311)
AA
QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSSRTAWNWIRQS
PSRGLEWLGRTYYRSKWYHDYSVSVKSRITIDPDTSKNQFSL
QLNSVTPEDTAVYYCARGAAPFDYWGQGTLVTVSSASTKGP
SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTS
GVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS
DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW
QQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSQVQ
LVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIRQAPGKC
LEWISYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLR
AEDTAVYYCARDRNSHFDYWGQGTLVTVSSGGGGSGGGGS
GGGGSDIQMTQSPSSVSASVGDRVTITCRASQGITRWLAWYQ
QKPGKAPKLLIYAASVLQSGVPSRFSGSGSGTDFTLTISSLQPE
DFATYYCQQSNSFPRTFGCGTKVEIKR
(SEQ ID NO: 313)
iPS: 577437
21-230_36F3_IgG_21-233_6F4_scFv
NA
CAGGTACAGCTGCAACAGTCAGGTCCAGGACTGGTGAAGC
CCTCGCAGACCCTCTCACTCACCTGTGCCATCTCCGGGGAC
AGTGTCTCTAGCAGCCGTACTGCTTGGAACTGGATCAGGC
AGTCCCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACATA
CTACAGGTCCAAGTGGTATCATGATTATTCAGTATCTGTGA
AAAGTCGAATCACCATCGACCCAGACACATCCAAGAACCA
GTTCTCCCTGCAGCTGAACTCTGTGACTCCCGAGGACACG
GCTGTTTATTATTGTGCAAGAGGGGCTGCTCCCTTTGACTA
CTGGGGCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCC
ACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCA
AGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGT
CAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAAC
TCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTG
TCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTG
ACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCT
GCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACA
AGAAAGTTGAGCCCAAATCTTGTGACAAAACTCACACATG
CCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCA
GTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGAT
CTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTG
AGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGG
ACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGTGCG
AGGAGCAGTACGGCAGCACGTACCGTTGCGTCAGCGTCCT
CACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTAC
AAGTGCAAGGTGTCCAACAAAGCCCTCCCAGCCCCCATCG
AGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAAC
CACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGAC
CAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC
TATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGC
AGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGA
CTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGG
ACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTC
CGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAG
AGCCTCTCCCTGTCTCCGGGTGGTGGCGGATCGGGAGGTG
GCGGATCCCAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTT
GGTCAAGCCTGGAGGGTCCCTGAGACTCTCCTGTGCAGCC
TCTGGATTCACCTTCAGTGACTACTACATGAGCTGGATCCG
CCAGGCTCCAGGGAAGTGCCTGGAGTGGATTTCATACATT
AGTAGCAGTGAAAGTATCATCTATTACGTAGACTCTGTGA
AGGGCCGATTCACCATCTCCAGGGACAACGCCAAGAACTC
ACTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACG
GCCGTGTATTACTGTGCGAGAGATGTTGGGAGCCACTTTG
ACTACTGGGGCCAGGGAACCCTGGTCACCGTGTCCTCAGG
AGGGGGCGGATCTGGCGGCGGAGGAAGCGGTGGGGGCGG
CTCCGACATCCAGATGACCCAGTCTCCATCTTCCGTGTCTG
CTTCTGTCGGAGACAGAGTCACCATCACTTGTCGGGCGAG
TCAGGATATTAGCAGGTGGTTAGCCTGGTATCAGCAGAAA
CCAGGGAAAGCCCCTAAGCTCCTGATTTCTGCTGCATCCA
GATTGCAAAGTGGAGTCCCATCAAGGTTCAGCGGCAGTGG
ATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAG
CCTGAAGATTTTGCAATTTACTATTGTCAACAGGCTAAAA
GTTTTCCTCGGACGTTCGGCTGCGGGACCAAGGTGGAAAT
CAAACGG
(SEQ ID NO: 315)
AA
QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSSRTAWNWIRQS
PSRGLEWLGRTYYRSKWYHDYSVSVKSRITIDPDTSKNQFSL
QLNSVTPEDTAVYYCARGAAPFDYWGQGTLVTVSSASTKGP
SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTS
GVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS
DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW
QQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSQVQ
LVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKCL
EWISYISSSESIIYYVDSVKGRFTISRDNAKNSLYLQMNSLRAE
DTAVYYCARDVGSHFDYWGQGTLVTVSSGGGGSGGGGSGG
GGSDIQMTQSPSSVSASVGDRVTITCRASQDISRWLAWYQQK
PGKAPKLLISAASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDF
AIYYCQQAKSFPRTFGCGTKVEIKR
(SEQ ID NO: 317)
iPS: 577441
21-230_37A6_IgG_21-233_4H6_scFv
NA
CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCTTAGTCAAGC
CTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGAATTC
ACCTTCAGTGACTACTACATGAGCTGGATCCGCCAGGCTC
CAGGGAAGGGGCTGGAGTGGGTTTCATATATTAGTCGAAG
TGGTGATACCATCTACTACGCAGACTCTGTGAAGGGCCGA
TTCACCATCTCCAGGGACAACGCCAAGAACTCACTGTATC
TGCAAATGAATGGCCTGCGAGCCGAAGACACGGCCGTGTA
TTACTGTGCGAGAGACTTAGCAGCAGGTGCTACAGGGGGC
CTTGACTGCTGGGGCCAGGGAACCCTGGTCACCGTGTCCT
CAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACC
CTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGC
TGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGT
CGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTT
CCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCA
GCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGAC
CTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAG
GTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAAACTC
ACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGG
ACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACC
CTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGG
TGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTG
GTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAA
GCCGTGCGAGGAGCAGTACGGCAGCACGTACCGTTGCGTC
AGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCA
AGGAGTACAAGTGCAAGGTGTCCAACAAAGCCCTCCCAGC
CCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCC
CGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGG
AGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAA
AGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGC
AATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCC
GTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCT
CACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTT
CTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTAC
ACGCAGAAGAGCCTCTCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCCAGGTGCAGCTGGTCGAGTCTGG
GGGAGGCTTGGTCAAGCCTGGAGGGTCCCTGAGACTCTCC
TGTGCAGCCTCTGGATTCACCTTCAGTGACTACTACATGAC
CTGGATCAGGCAGGCTCCAGGGAAGTGCCTGGAGTGGATT
TCATACATTAGTAGTAGTGGTAGTACCATCTACTACGCAG
ACTCTGTGAAGGGCCGATTCACCATCTCCAGGGACAACGC
CAAGAACTCACTGTATCTGCAAATGAACAGCCTGAGAGCC
GAGGACACGGCCGTGTATTACTGTGCGAGAGATCGGAACT
CCCACTTTGACTATTGGGGCCAGGGAACCCTGGTCACCGT
GTCCTCAGGAGGGGGCGGATCTGGCGGCGGAGGAAGCGG
TGGGGGCGGCTCCGACATTCAGATGACCCAGTCTCCATCT
TCCGTGTCTGCATCTGTAGGGGACAGAGTCACCATCACTT
GTCGGGCGAGTCAGGGTATTACCAGGTGGTTAGCCTGGTA
TCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTAT
GCTGCATCCGTTTTGCAAAGTGGGGTCCCATCAAGGTTCA
GCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAG
CAGCCTGCAGCCTGAAGATTTTGCAACTTACTATTGTCAAC
AGTCTAACAGTTTCCCTCGGACGTTCGGCTGCGGGACCAA
GGTGGAAATCAAACGG
(SEQ ID NO: 319)
QVQLVESGGGLVKPGGSLRLSCAASEFTFSDYYMSWIRQAP
GKGLEWVSYISRSGDTIYYADSVKGRFTISRDNAKNSLYLQM
NGLRAEDTAVYYCARDLAAGATGGLDCWGQGTLVTVSSAS
TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSG
ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP
KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNA
KTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA
LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVK
GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGG
GGSQVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIR
QAPGKCLEWISYISSSGSTIYYADSVKGRFTISRDNAKNSLYL
QMNSLRAEDTAVYYCARDRNSHFDYWGQGTLVTVSSGGGG
SGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGITR
WLAWYQQKPGKAPKLLIYAASVLQSGVPSRFSGSGSGTDFT
LTISSLQPEDFATYYCQQSNSFPRTFGCGTKVEIKR
(SEQ ID NO: 321)
iPS: 577445
21-230_37A6_IgG_21-233_6F4_scFv
NA
CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCTTAGTCAAGC
CTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGAATTC
ACCTTCAGTGACTACTACATGAGCTGGATCCGCCAGGCTC
CAGGGAAGGGGCTGGAGTGGGTTTCATATATTAGTCGAAG
TGGTGATACCATCTACTACGCAGACTCTGTGAAGGGCCGA
TTCACCATCTCCAGGGACAACGCCAAGAACTCACTGTATC
TGCAAATGAATGGCCTGCGAGCCGAAGACACGGCCGTGTA
TTACTGTGCGAGAGACTTAGCAGCAGGTGCTACAGGGGGC
CTTGACTGCTGGGGCCAGGGAACCCTGGTCACCGTGTCCT
CAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACC
CTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGC
TGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGT
CGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTT
CCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCA
GCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGAC
CTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAG
GTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAAACTC
ACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGG
ACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACC
CTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGG
TGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTG
GTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAA
GCCGTGCGAGGAGCAGTACGGCAGCACGTACCGTTGCGTC
AGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCA
AGGAGTACAAGTGCAAGGTGTCCAACAAAGCCCTCCCAGC
CCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCC
CGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGG
AGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAA
AGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGC
AATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCC
GTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCT
CACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTT
CTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTAC
ACGCAGAAGAGCCTCTCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGCGCGGATCCCAGGTGCAGCTGGTGGAGTCTGG
GGGAGGCTTGGTCAAGCCTGGAGGGTCCCTGAGACTCTCC
TGTGCAGCCTCTGGATTCACCTTCAGTGACTACTACATGAG
CTGGATCCGCCAGGCTCCAGGGAAGTGCCTGGAGTGGATT
TCATACATTAGTAGCAGTGAAAGTATCATCTATTACGTAG
ACTCTGTGAAGGGCCGATTCACCATCTCCAGGGACAACGC
CAAGAACTCACTGTATCTGCAAATGAACAGCCTGAGAGCC
GAGGACACGGCCGTGTATTACTGTGCGAGAGATGTTGGGA
GCCACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGT
GTCCTCAGGAGGGGGCGGATCTGGCGGCGGAGGAAGCGG
TGGGGGCGGCTCCGACATCCAGATGACCCAGTCTCCATCT
TCCGTGTCTGCTTCTGTCGGAGACAGAGTCACCATCACTTG
TCGGGCGAGTCAGGATATTAGCAGGTGGTTAGCCTGGTAT
CAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATTTCTG
CTGCATCCAGATTGCAAAGTGGAGTCCCATCAAGGTTCAG
CGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGC
AGCCTGCAGCCTGAAGATTTTGCAATTTACTATTGTCAACA
GGCTAAAAGTTTTCCTCGGACGTTCGGCTGCGGGACCAAG
GTGGAAATCAAACGG
(SEQ ID NO: 323)
AA
QVQLVESGGGLVKPGGSLRLSCAASEFTFSDYYMSWIRQAP
GKGLEWVSYISRSGDTIYYADSVKGRFTISRDNAKNSLYLQM
NGLRAEDTAVYYCARDLAAGATGGLDCWGQGTLVTVSSAS
TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSG
ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP
KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNA
KTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA
LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVK
GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGG
GGSQVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIR
QAPGKCLEWISYISSSESIIYYVDSVKGRFTISRDNAKNSLYLQ
MNSLRAEDTAVYYCARDVGSHFDYWGQGTLVTVSSGGGGS
GGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQDISRW
LAWYQQKPGKAPKLLISAASRLQSGVPSRFSGSGSGTDFTLTI
SSLQPEDFAIYYCQQAKSFPRTFGCGTKVEIKR
(SEQ ID NO: 325)
iPS: 577449
21-230_392_IgG_21-233_4H6_scFv
NA
CAGGTGCAGCTGGTGCAGTCTGGGACTGAGGTGAAGAAG
CCTGGGGCCTCAGTGAAGGTGTCCTGCAAGGCTTCTGGAT
ACACCTTCCCCGGCTACTATATGCACTGGGTGCGACAGGC
CCCTGGACAGGGGCTTGAGTGGATGGGATGGATCAACCCT
GACAGTGGTGGCACAAAGTATACACAGAAGTTTCAGGGC
AGGGTCACCTTGACCAGGGACGCGTCCGTCAGCACAGCCT
ACATTGACCTGAACAGGCTGAGATCTGACGACACGGCCGT
ATATTACTGTGCGAGAGAGAGGTGTAGGACTACCAACTGC
TATTTGGACTACTGGGGCCAGGGAAGTCTGGTCACCGTGT
CCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGC
ACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTG
GGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGG
TGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACAC
CTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCA
GCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCA
GACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACC
AAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAA
ACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGG
GGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGA
CACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTG
GTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCA
ACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGCAGCACGTACCGTTTG
CGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAAT
GGCAAGGAGTACAAGTGCAAGGTGTCCAACAAAGCCCTC
CCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGC
AGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCG
GGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCT
GGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGG
GAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACG
CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAG
CAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAA
CGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACC
ACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTGGTGG
CGGATCGGGAGGTGGCGGATCCCAGGTGCAGCTGGTCGA
GTCTGGGGGAGGCTTGGTCAAGCCTGGAGGGTCCCTGAGA
CTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTGACTACTA
CATGACCTGGATCAGGCAGGCTCCAGGGAAGTGCCTGGAG
TGGATTTCATACATTAGTAGTAGTGGTAGTACCATCTACTA
CGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGGGAC
AACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGA
GAGCCGAGGACACGGCCGTGTATTACTGTGCGAGAGATCG
GAACTCCCACTTTGACTATTGGGGCCAGGGAACCCTGGTC
ACCGTGTCCTCAGGAGGGGGCGGATCTGGCGGCGGAGGA
AGCGGTGGGGGCGGCTCCGACATTCAGATGACCCAGTCTC
CATCTTCCGTGTCTGCATCTGTAGGGGACAGAGTCACCAT
CACTTGTCGGGCGAGTCAGGGTATTACCAGGTGGTTAGCC
TGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGA
TCTATGCTGCATCCGTTTTGCAAAGTGGGGTCCCATCAAG
GTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACC
ATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTACTATT
GTCAACAGTCTAACAGTTTCCCTCGGACGTTCGGCTGCGG
GACCAAGGTGGAAATCAAACGG
(SEQ ID NO: 327)
AA
QVQLVQSGTEVKKPGASVKVSCKASGYTFPGYYMHWVRQA
PGQGLEWMGWINPDSGGTKYTQKFQGRVTLTRDASVSTAYI
DLNRLRSDDTAVYYCARERCRTTNCYLDYWGQGSLVTVSS
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN
SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP
KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN
AKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLV
KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT
VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWI
RQAPGKCLEWISYISSSGSTIYYADSVKGRFTISRDNAKNSLY
LQMNSLRAEDTAVYYCARDRNSHFDYWGQGTLVTVSSGGG
GSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIT
RWLAWYQQKPGKAPKLLIYAASVLQSGVPSRFSGSGSGTDF
TLTISSLOPEDFATYYCQQSNSFPRTFGCGTKVEIKR
(SEQ ID NO: 329)
iPS: 577453
21-230_392_IgG_21-233_6F4_scFv
NA
CAGGTGCAGCTGGTGCAGTCTGGGACTGAGGTGAAGAAG
CCTGGGGCCTCAGTGAAGGTGTCCTGCAAGGCTTCTGGAT
ACACCTTCCCCGGCTACTATATGCACTGGGTGCGACAGGC
CCCTGGACAGGGGCTTGAGTGGATGGGATGGATCAACCCT
GACAGTGGTGGCACAAAGTATACACAGAAGTTTCAGGGC
AGGGTCACCTTGACCAGGGACGCGTCCGTCAGCACAGCCT
ACATTGACCTGAACAGGCTGAGATCTGACGACACGGCCGT
ATATTACTGTGCGAGAGAGAGGTGTAGGACTACCAACTGC
TATTTGGACTACTGGGGCCAGGGAAGTCTGGTCACCGTGT
CCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGC
ACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTG
GGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGG
TGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACAC
CTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCA
GCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCA
GACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACC
AAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAA
ACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGG
GGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGA
CACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTG
GTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCA
ACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGCAGCACGTACCGTTTG
CGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAAT
GGCAAGGAGTACAAGTGCAAGGTGTCCAACAAAGCCCTC
CCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGC
AGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCG
GGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCT
GGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGG
GAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACG
CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAG
CAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAA
CGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACC
ACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTGGTGG
CGGATCGGGAGGTGGCGGATCCCAGGTGCAGCTGGTGGA
GTCTGGGGGAGGCTTGGTCAAGCCTGGAGGGTCCCTGAGA
CTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTGACTACTA
CATGAGCTGGATCCGCCAGGCTCCAGGGAAGTGCCTGGAG
TGGATTTCATACATTAGTAGCAGTGAAAGTATCATCTATTA
CGTAGACTCTGTGAAGGGCCGATTCACCATCTCCAGGGAC
AACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGA
GAGCCGAGGACACGGCCGTGTATTACTGTGCGAGAGATGT
TGGGAGCCACTTTGACTACTGGGGCCAGGGAACCCTGGTC
ACCGTGTCCTCAGGAGGGGGCGGATCTGGCGGCGGAGGA
AGCGGTGGGGGCGGCTCCGACATCCAGATGACCCAGTCTC
CATCTTCCGTGTCTGCTTCTGTCGGAGACAGAGTCACCATC
ACTTGTCGGGCGAGTCAGGATATTAGCAGGTGGTTAGCCT
GGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGAT
TTCTGCTGCATCCAGATTGCAAAGTGGAGTCCCATCAAGG
TTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCA
TCAGCAGCCTGCAGCCTGAAGATTTTGCAATTTACTATTGT
CAACAGGCTAAAAGTTTTCCTCGGACGTTCGGCTGCGGGA
CCAAGGTGGAAATCAAACGG
(SEQ ID NO: 331)
AA
QVQLVQSGTEVKKPGASVKVSCKASGYTFPGYYMHWVRQA
PGQGLEWMGWINPDSGGTKYTQKFQGRVTLTRDASVSTAYI
DLNRLRSDDTAVYYCARERCRTTNCYLDYWGQGSLVTVSS
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN
SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP
KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN
AKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLV
KGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT
VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWI
RQAPGKCLEWISYISSSESIIYYVDSVKGRFTISRDNAKNSLYL
QMNSLRAEDTAVYYCARDVGSHFDYWGQGTLVTVSSGGGG
SGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQDISR
WLAWYQQKPGKAPKLLISAASRLQSGVPSRFSGSGSGTDFTL
TISSLQPEDFAIYYCQQAKSFPRTFGCGTKVEIKR
(SEQ ID NO: 333)
iPS #
LC
iPS: 577383
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATC
TGTAGGAGACATTCTCACCATCACTTGCCGGGCAAGTCAG
AACATTACCACCTATTTTTAAATTGGTATCAGCAGAAACCAG
GGAAAGCCCCTAACCTCCTGATCTCTGCTGCATCCCGTTTG
CGAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTG
GGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGT
AGATTTTACAACTTTCTACTGTCAACAGACTTTCACTACCC
CGTGGACGTTCGGCCAAGGGACCAAGGTGGAGATCAAAC
GAACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCT
GATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCC
TGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTG
GAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAG
AGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGC
CTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAG
AAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCC
TGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTG
T
(SEQ ID NO: 264)
DIQMTQSPSSLSASVGDILTITCRASQNITTYLNWYQQKPGKA
PNLLISAASRLRSGVPSRFSGSGSGTDFTLTISSLQPVDFTTFY
CQQTFTTPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA
SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDS
TYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGE
C
(SEQ ID NO: 266)
iPS: 577388
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATC
TGTAGGAGACATTCTCACCATCACTTGCCGGGCAAGTCAG
AACATTACCACCTATTTTTAAATTGGTATCAGCAGAAACCAG
GGAAAGCCCCTAACCTCCTGATCTCTGCTGCATCCCGTTTG
CGAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTG
GGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGT
AGATTTTACAACTTTCTACTGTCAACAGACTTTCACTACCC
CGTGGACGTTCGGCCAAGGGACCAAGGTGGAGATCAAAC
GAACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCT
GATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCC
TGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTG
GAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAG
AGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGC
CTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAG
AAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCC
TGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTG
T
(SEQ ID NO: 268)
DIQMTQSPSSLSASVGDILTITCRASQNITTYLNWYQQKPGKA
PNLLISAASRLRSGVPSRFSGSGSGTDFTLTISSLQPVDFTTFY
CQQTFTTPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA
SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDS
TYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGE
C
(SEQ ID NO: 270)
iPS: 577393
GACATCCAGATGACCCAGTCTCCATCCTCACTGTCTGCATC
TGTAGGAGACAGAGTCACCATCACCTGTCGGGCGAGTCAG
GACATTAGCAATAATTTAGCCTGGTTTCAGCAGAAACCAG
GGAAACCCCCTAAGTCCCTGATGTATGCTGCATCCAGTTT
GCACAGTGGAGTCCCATCAACGTTCAGCGGCAGTGGATCT
GGGACAGATTTCACTTTCACCATCAGCAGCCTGCAGCCTG
AAGATTTTGCAACTTATTACTGCCAACAGTATAATAGTTAC
CCTCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAGAC
GAACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCT
GATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCC
TGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTG
GAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAG
AGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGC
CTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAG
(SEQ ID NO: 272)
DIQMTQSPSSLSASVGDRVTITCRASQDISNNLAWFQQKPGK
PPKSLMYAASSLHSGVPSTFSGSGSGTDFTFTISSLQPEDFATY
YCQQYNSYPLTFGGGTKVEIRRTVAAPSVFIFPPSDEQLKSGT
ASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK
DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR
GEC
(SEQ ID NO: 274)
iPS: 577397
GACATCCAGATGACCCAGTCTCCATCCTCACTGTCTGCATC
TGTAGGAGACAGAGTCACCATCACCTGTCGGGCGAGTCAG
GACATTAGCAATAATTTAGCCTGGTTTCAGCAGAAACCAG
GGAAACCCCCTAAGTCCCTGATGTATGCTGCATCCAGTTT
GCACAGTGGAGTCCCATCAACGTTCAGCGGCAGTGGATCT
GGGACAGATTTCACTTTCACCATCAGCAGCCTGCAGCCTG
AAGATTTTGCAACTTATTACTGCCAACAGTATAATAGTTAC
CCTCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAGAC
GAACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCT
GATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCC
TGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTG
GAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAG
AGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGC
CTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAG
AAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCC
TGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTG
T
(SEQ ID NO: 276)
DIQMTQSPSSLSASVGDRVTITCRASQDISNNLAWFQQKPGK
PPKSLMYAASSLHSGVPSTFSGSGSGTDFTFTISSLQPEDFATY
YCQQYNSYPLTFGGGTKVEIRRTVAAPSVFIFPPSDEQLKSGT
ASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK
DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR
GEC
(SEQ ID NO: 278)
iPS: 577401
CAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGAGCCC
TGGACAGTCGATCACCATCTCCTGCACTGGAACCAGCAGT
GATGTTGGGAATTATAACCTTGTCTCCTGGTACCAACAGC
ACCCAGGCAAAGCCCCCAAACTCATGATTTTTTTGAGGTCAA
TCAGCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCA
AGTCTGGCACCACGGCCTCCCTGACAATCTCTGGGCTCCA
GGCTGCGGACGAGGCTGATTATTTCTGCTGCTCATATACA
ACTAGTAGCACTTATGTGATCTTCGGCGGAGGGACCAAGC
TGACCGTCCTAGGTCAGCCCAAGGCTGCACCCTCGGTCAC
TCTGTTCCCGCCCTCCTCTGAGGAGCTTCAAGCCAACAAG
GCCACACTGGTGTGTCTCATCAGTGACTTCTACCCGGGAG
CCGTGACAGTGGCCTGGAAGGCAGATAGCAGCCCCGTCAA
GGCGGGAGTGGAAACCACCACACCCTCCAAACAAAGCAA
CAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCT
GAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCCAGGTC
ACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCT
ACAGAATGTTCA
(SEQ ID NO: 280)
QSALTQPASVSGSPGQSITISCTGTSSDVGNYNLVSWYQQHP
GKAPKLMIFEVNQRPSGVSNRFSGSKSGTTASLTISGLQAADE
ADYFCCSYTTSSTYVIFGGGTKLTVLGQPKAAPSVTLFPPSSE
ELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPS
KQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
APTECS
(SEQ ID NO: 282)
iPS: 577405
CAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGAGCCC
TGGACAGTCGATCACCATCTCCTGCACTGGAACCAGCAGT
GATGTTGGGAATTATAACCTTGTCTCCTGGTACCAACAGC
ACCCAGGCAAAGCCCCCAAACTCATGATTTTTTTGAGGTCAA
TCAGCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCA
AGTCTGGCACCACGGCCTCCCTGACAATCTCTGGGCTCCA
GGCTGCGGACGAGGCTGATTATTTCTGCTGCTCATATACA
ACTAGTAGCACTTATGTGATCTTCGGCGGAGGGACCAAGC
TGACCGTCCTAGGTCAGCCCAAGGCTGCACCCTCGGTCAC
TCTGTTCCCGCCCTCCTCTGAGGAGCTTCAAGCCAACAAG
GCCACACTGGTGTGTCTCATCAGTGACTTCTACCCGGGAG
CCGTGACAGTGGCCTGGAAGGCAGATAGCAGCCCCGTCAA
GGCGGGAGTGGAAACCACCACACCCTCCAAACAAAGCAA
CAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCT
GAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCCAGGTC
ACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCT
ACAGAATGTTCA
(SEQ ID NO: 284)
QSALTQPASVSGSPGQSITISCTGTSSDVGNYNLVSWYQQHP
GKAPKLMIFEVNQRPSGVSNRFSGSKSGTTASLTISGLQAADE
ADYFCCSYTTSSTYVIFGGGTKLTVLGQPKAAPSVTLFPPSSE
ELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPS
KQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
APTECS
(SEQ ID NO: 286)
iPS: 577409
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATC
TGTAGGAGACAGAGTCACCATCACTTGCCGGGCAGGTCAG
AACATTAGCAGGCATTTAAATTGGTATCAGCAGAATCCAG
GGAAAGCCCCTAAGGTCCTGATCCATCCTGCATCCAGTTTT
GCCAAGTGGGGTCCCGTCAAGGTTCAGTGGCAGTGGATCT
GGGACAGATTTCAGTCTTACCATCAGCAGTCTGCAACCTG
AAGATTTTGGAACTTACTTCTGTCAACAGAGTTACAGTAC
CCCTCCCACTTTCGGCGGAGGGACCAAGGTGGAGCTCAAA
CGAACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATC
TGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTTGTGTGC
CTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGT
GGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGA
GAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG
CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAG
AAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCC
TGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTG
(SEQ ID NO: 288)
DIQMTQSPSSLSASVGDRVTITCRAGQNISRHLNWYQQNPGK
APKVLIHPASSLPSGVPSRFSGSGSGTDFSLTISSLQPEDFGTYF
CQQSYSTPPTFGGGTKVELKRTVAAPSVFIFPPSDEQLKSGTA
SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDS
TYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGE
C
(SEQ ID NO: 290)
iPS: 577413
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATC
TGTAGGAGACAGAGTCACCATCACTTGCCGGGCAGGTCAG
AACATTAGCAGGCATTTAAATTGGTATCAGCAGAATCCAG
GGAAAGCCCCTAAGGTCCTGATCCATCCTGCATCCAGTTTT
GCCAAGTGGGGTCCCGTCAAGGTTCAGTGGCAGTGGATCT
GGGACAGATTTCAGTCTTACCATCAGCAGTCTGCAACCTG
AAGATTTTGGAACTTACTTCTGTCAACAGAGTTACAGTAC
CCCTCCCACTTTCGGCGGAGGGACCAAGGTGGAGCTCAAA
CGAACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATC
TGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTTGTGTGC
CTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGT
GGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGA
GAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG
CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAG
AAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCC
TGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTG
T
(SEQ ID NO: 292)
DIQMTQSPSSLSASVGDRVTITCRAGQNISRHLNWYQQNPGK
APKVLIHPASSLPSGVPSRFSGSGSGTDFSLTISSLQPEDFGTYF
CQQSYSTPPTFGGGTKVELKRTVAAPSVFIFPPSDEQLKSGTA
SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDS
TYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGE
C
(SEQ ID NO: 294)
iPS: 577417
CAGGCTGTGCCGACTCAGCCCTCTTCCCTCTCTGCATCTCC
TGGAGCATCAGCCAGTCTCACCTGCACCTTACGCAGTGGC
ATCAATGTTGGTTCCTCCAGGATCTATTGGTACCAGCAGA
AGCCAGGGAGTCCTCCCCAGTTTCTCCTGAGGTACACATC
AGACTCAGATAAATTGCAGGGCTCTGGAGTCCCCAGCCGC
TTCTCTGGATCCAAAGATGCTTCGGCCAATGCAGGACTTTT
ACTCATCTCTGGGCTCCAGTCTGAGGATGAGGCTGACTAT
TACTGTATGATTTGGCACAGCAGCGCTGTGGTATTCGGCG
GAGGGACCAAACTGACCGTCCTAGGTCAGCCCAAGGCTGC
ACCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTC
AAGCCAACAAGGCCACACTGGTGTGTCTCATCAGTGACTT
CTACCCGGGAGCCGTGACAGTGGCCTGGAAGGCAGATAG
CAGCCCCGTCAAGGCGGGAGTGGAAACCACCACACCCTCC
AAACAAAGCAACAACAAGTACGCGGCCAGCAGCTATCTG
AGCCTGACGCCTGAGCAGTGGAAGTCCCACAGAAGCTACA
GCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGA
CAGTGGCCCCTACAGAATGTTCA
(SEQ ID NO: 296)
QAVPTQPSSLSASPGASASLTCTLRSGINVGSSRIYWYQQKPG
SPPQFLLRYTSDSDKLQGSGVPSRFSGSKDASANAGLLLISGL
QSEDEADYYCMIWHSSAVVFGGGTKLTVLGQPKAAPSVTLF
PPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVE
TTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS
(SEQ ID NO: 298)
iPS: 577421
CAGGCTGTGCCGACTCAGCCCTCTTCCCTCTCTGCATCTCC
TGGAGCATCAGCCAGTCTCACCTGCACCTTACGCAGTGGC
ATCAATGTTGGTTCCTCCAGGATCTATTGGTACCAGCAGA
AGCCAGGGAGTCCTCCCCAGTTTCTCCTGAGGTACACATC
AGACTCAGATAAATTGCAGGGCTCTGGAGTCCCCAGCCGC
TTCTCTGGATCCAAAGATGCTTCGGCCAATGCAGGACTTTT
ACTCATCTCTGGGCTCCAGTCTGAGGATGAGGCTGACTAT
TACTGTATGATTTGGCACAGCAGCGCTGTGGTATTCGGCG
GAGGGACCAAACTGACCGTCCTAGGTCAGCCCAAGGCTGC
ACCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTC
AAGCCAACAAGGCCACACTGGTGTGTCTCATCAGTGACTT
CTACCCGGGAGCCGTGACAGTGGCCTGGAAGGCAGATAG
CAGCCCCGTCAAGGCGGGAGTGGAAACCACCACACCCTCC
AAACAAAGCAACAACAAGTACGCGGCCAGCAGCTATCTG
AGCCTGACGCCTGAGCAGTGGAAGTCCCACAGAAGCTACA
GCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGA
CAGTGGCCCCTACAGAATGTTCA
(SEQ ID NO: 300)
QAVPTQPSSLSASPGASASLTCTLRSGINVGSSRIYWYQQKPG
SPPQFLLRYTSDSDKLQGSGVPSRFSGSKDASANAGLLLISGL
QSEDEADYYCMIWHSSAVVFGGGTKLTVLGQPKAAPSVTLF
PPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVE
TTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS
(SEQ ID NO: 302)
iPS: 577425
CAGTCTGCCCTGACTCAGCCTCGCTCAGTGTCCGGGAGCC
CTGGACAGTCAGTCACCATCTCCTGCACTGGAACCAGCAG
TGATGTTGGTGGTTATATCTTTGTCTCCTGGTACCAACAAC
ACCCAGGCAAAGCCCCCAAACTCATGATTTATGATGTCAG
TAAGCGGCCCTCTGGGGTCCCTGATCGCTTCTCTGGCTCCA
AGTCTGTCAACACGGCCTCCCTGACCATCTCTGGGCTCCA
GGCTGAGGATGAGACTGATTATTACTGCTGCTCATATGCA
GGCAACTACACTTATGTCTTCGGAACTGGGACCAAGGTCA
CCGTCCTAGGTCAGCCCAAGGCTGCACCCTCGGTCACTCT
GTTCCCGCCCTCCTCTGAGGAGCTTCAAGCCAACAAGGCC
ACACTGGTGTGTCTCATCAGTGACTTCTACCCGGGAGCCG
TGACAGTGGCCTGGAAGGCAGATAGCAGCCCCGTCAAGG
CGGGAGTGGAAACCACCACACCCTCCAAACAAAGCAACA
ACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGA
GCAGTGGAAGTCCCACAGAAGCTACAGCTGCCAGGTCACG
CATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACA
GAATGTTCA
(SEQ ID NO: 304)
QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYIFVSWYQQHPG
KAPKLMIYDVSKRPSGVPDRFSGSKSVNTASLTISGLQAEDET
DYYCCSYAGNYTYVFGTGTKVTVLGQPKAAPSVTLFPPSSEE
LQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPS
KQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
APTECS
(SEQ ID NO: 306)
iPS: 577429
CAGTCTGCCCTGACTCAGCCTCGCTCAGTGTCCGGGAGCC
CTGGACAGTCAGTCACCATCTCCTGCACTGGAACCAGCAG
TGATGTTGGTGGTTATATCTTTGTCTCCTGGTACCAACAAC
ACCCAGGCAAAGCCCCCAAACTCATGATTTATGATGTCAG
TAAGCGGCCCTCTGGGGTCCCTGATCGCTTCTCTGGCTCCA
AGTCTGTCAACACGGCCTCCCTGACCATCTCTGGGCTCCA
GGCTGAGGATGAGACTGATTATTACTGCTGCTCATATGCA
GGCAACTACACTTATGTCTTCGGAACTGGGACCAAGGTCA
CCGTCCTAGGTCAGCCCAAGGCTGCACCCTCGGTCACTCT
GTTCCCGCCCTCCTCTGAGGAGCTTCAAGCCAACAAGGCC
ACACTGGTGTGTCTCATCAGTGACTTCTACCCGGGAGCCG
TGACAGTGGCCTGGAAGGCAGATAGCAGCCCCGTCAAGG
CGGGAGTGGAAACCACCACACCCTCCAAACAAAGCAACA
ACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGA
GCAGTGGAAGTCCCACAGAAGCTACAGCTGCCAGGTCACG
CATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACA
GAATGTTCA
(SEQ ID NO: 308)
QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYIFVSWYQQHPG
KAPKLMIYDVSKRPSGVPDRFSGSKSVNTASLTISGLQAEDET
DYYCCSYAGNYTYVFGTGTKVTVLGQPKAAPSVTLFPPSSEE
LQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPS
KQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
APTECS
(SEQ ID NO: 310)
iPS: 577433
GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTC
TCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAG
AGTGTTAGCAGCAACTACTTAGCCTGGTACCAACAGAAAC
CTGGCCAGGCTCCCAGGGCCCTTATCTATGCTGCATCCAA
CAGGGCCGCTGGCATCTCAGACAGGTTCAGTGGCAGTGGG
TCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGC
CTGAAGATTTTGCAGTGTATTTCTGTCAGCAGTATGGTAGC
TCACCGCTCACTTTCGGCGGAGGGACTAAGGTGGAGATCA
AACGAACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCA
TCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTTGTGTG
CCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAG
TGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGG
AGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACA
GCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGA
GAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGC
CTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGT
GT
(SEQ ID NO: 312)
EIVLTQSPGTLSLSPGERATLSCRASQSVSSNYLAWYQQKPG
QAPRALIYAASNRAAGISDRFSGSGSGTDFTLTISRLEPEDFAV
YFCQQYGSSPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSG
TASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK
DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR
GEC
(SEQ ID NO: 314)
iPS: 577437
GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTC
TCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAG
AGTGTTAGCAGCAACTACTTAGCCTGGTACCAACAGAAAC
CTGGCCAGGCTCCCAGGGCCCTTATCTATGCTGCATCCAA
CAGGGCCGCTGGCATCTCAGACAGGTTCAGTGGCAGTGGG
TCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGC
CTGAAGATTTTGCAGTGTATTTCTGTCAGCAGTATGGTAGC
TCACCGCTCACTTTCGGCGGAGGGACTAAGGTGGAGATCA
AACGAACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCA
TCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTTGTGTG
CCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAG
TGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGG
AGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACA
GCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGA
GAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGC
CTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGT
GT
(SEQ ID NO: 316)
EIVLTQSPGTLSLSPGERATLSCRASQSVSSNYLAWYQQKPG
QAPRALIYAASNRAAGISDRFSGSGSGTDFTLTISRLEPEDFAV
YFCQQYGSSPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSG
TASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK
DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR
GEC
(SEQ ID NO: 318)
iPS: 577441
TCCTATGAGCTGACTCAGCCACCCTCAGTGTCCGTGTCCCC
AGGACAGACAGCCAGCATCACCTGCTCTGGAGAAAGGTTG
GGAAATAAATATATTTGCTGGTATCAGCAGAAGCCAGGCC
AGTCCCCTGTTTTCTGGTCATCTATCAAGATTTCAAGCGGCCC
TCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTCTGGGA
TCACAGCCACTCTGACCATCAGCGGGACCCAGGCTATGGA
TGAGGCTGACTATTACTGTCAGGCGTGGGACAGCAGAACT
GTGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGGTC
AGCCCAAGGCTGCACCCTCGGTCACTCTGTTCCCGCCCTCC
TCTGAGGAGCTTCAAGCCAACAAGGCCACACTGGTGTGTC
TCATCAGTGACTTCTACCCGGGAGCCGTGACAGTGGCCTG
GAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAAAC
CACCACACCCTCCAAACAAAGCAACAACAAGTACGCGGC
CAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCC
CACAGAAGCTACAGCTGCCAGGTCACGCATGAAGGGAGC
ACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCA
(SEQ ID NO: 320)
SYELTQPPSVSVSPGQTASITCSGERLGNKYICWYQQKPGQSP
VLVIYQDFKRPSGIPERFSGSNSGITATLTISGTQAMDEADYY
CQAWDSRTVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQAN
KATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSN
NKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTEC
S
(SEQ ID NO: 322)
iPS: 577445
TCCTATGAGCTGACTCAGCCACCCTCAGTGTCCGTGTCCCC
AGGACAGACAGCCAGCATCACCTGCTCTGGAGAAAGGTTG
GGAAATAAATATATTTGCTGGTATCAGCAGAAGCCAGGCC
AGTCCCCTGTTTTCTGGTCATCTATCAAGATTTCAAGCGGCCC
TCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTCTGGGA
TCACAGCCACTCTGACCATCAGCGGGACCCAGGCTATGGA
TGAGGCTGACTATTACTGTCAGGCGTGGGACAGCAGAACT
GTGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGGTC
AGCCCAAGGCTGCACCCTCGGTCACTCTGTTCCCGCCCTCC
TCTGAGGAGCTTCAAGCCAACAAGGCCACACTGGTGTGTC
TCATCAGTGACTTCTACCCGGGAGCCGTGACAGTGGCCTG
GAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAAAC
CACCACACCCTCCAAACAAAGCAACAACAAGTACGCGGC
CAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCC
CACAGAAGCTACAGCTGCCAGGTCACGCATGAAGGGAGC
ACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCA
(SEQ ID NO: 324)
SYELTQPPSVSVSPGQTASITCSGERLGNKYICWYQQKPGQSP
VLVIYQDFKRPSGIPERFSGSNSGITATLTISGTQAMDEADYY
CQAWDSRTVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQAN
KATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSN
NKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTEC
S
(SEQ ID NO: 326)
iPS: 577449
CAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGAGCCC
TGGACAGTCGATCACCATCTCCTGCACTGGAACCAGCAGT
GATGTTGGGAATTATAACCTTGTCTCCTGGTACCAACAGC
ACCCAGGCAAAGCCCCCAAACTCATGATTTATGAGGTCAA
TAGGCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCA
AGTCTGGCAACACGGCCTCCCTGACAATCTCTGGGCTCCA
GGCTGAGGACGAGGCTGAATATTACTGCTGCTCATATGCA
GGTAGAGACACTTTCGTGGTGTTCGGCGGAGGGACCAAGC
TGACCGTCCTAGGTCAGCCCAAGGCTGCACCCTCGGTCAC
TCTGTTCCCGCCCTCCTCTGAGGAGCTTCAAGCCAACAAG
GCCACACTGGTGTGTCTCATCAGTGACTTCTACCCGGGAG
CCGTGACAGTGGCCTGGAAGGCAGATAGCAGCCCCGTCAA
GGCGGGAGTGGAAACCACCACACCCTCCAAACAAAGCAA
CAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCT
GAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCCAGGTC
ACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCT
ACAGAATGTTCA
(SEQ ID NO: 328)
QSALTQPASVSGSPGQSITISCTGTSSDVGNYNLVSWYQQHP
GKAPKLMIYEVNRRPSGVSNRFSGSKSGNTASLTISGLQAED
EAEYYCCSYAGRDTFVVFGGGTKLTVLGQPKAAPSVTLFPPS
SEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETT
TPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS
(SEQ ID NO: 330)
iPS: 577453
CAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGAGCCC
TGGACAGTCGATCACCATCTCCTGCACTGGAACCAGCAGT
GATGTTGGGAATTATAACCTTGTCTCCTGGTACCAACAGC
ACCCAGGCAAAGCCCCCAAACTCATGATTTATGAGGTCAA
TAGGCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCA
AGTCTGGCAACACGGCCTCCCTGACAATCTCTGGGCTCCA
GGCTGAGGACGAGGCTGAATATTACTGCTGCTCATATGCA
GGTAGAGACACTTTCGTGGTGTTCGGCGGAGGGACCAAGC
TGACCGTCCTAGGTCAGCCCAAGGCTGCACCCTCGGTCAC
TCTGTTCCCGCCCTCCTCTGAGGAGCTTCAAGCCAACAAG
GCCACACTGGTGTGTCTCATCAGTGACTTCTACCCGGGAG
CCGTGACAGTGGCCTGGAAGGCAGATAGCAGCCCCGTCAA
GGCGGGAGTGGAAACCACCACACCCTCCAAACAAAGCAA
CAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCT
GAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCCAGGTC
ACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCT
ACAGAATGTTCA
(SEQ ID NO: 332)
QSALTQPASVSGSPGQSITISCTGTSSDVGNYNLVSWYQQHP
GKAPKLMIYEVNRRPSGVSNRFSGSKSGNTASLTISGLQAED
EAEYYCCSYAGRDTFVVFGGGTKLTVLGQPKAAPSVTLFPPS
SEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETT
TPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS
(SEQ ID NO: 334)
TABLE 25
IgG-scFv v1 Full Sequences
Ab
Type
SCFV_HC
iPS: 616974
SST205802
NA
CAGGTACAGCTGCAACAGTCAGGTCCAGGACTGGTGAAGC
CCTCGCAGACCCTCTCACTCACCTGTGCCATCTCCGGGGAC
AGTGTCTCTAGCAGCCGTACTGCTTGGAACTGGATCAGGCA
GTCCCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACATAC
TACAGGTCCAAGTGGTATCATGATTATTCAGTATCTGTGAA
AAGTCGAATCACCATCGACCCAGACACATCCAAGAACCAG
TTCTCCCTGCAGCTGAACTCTGTGACTCCCGAGGACACGGC
TGTTTATTATTGTGCAAGAGGGGCTGCTCCCTTTGACTACT
GGGGCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCCACC
AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAG
GACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGG
CGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTAC
AGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTG
CCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGT
GAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTT
GAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTG
CCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCT
TCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACC
CCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAG
ACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGA
GGTGCATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTAC
GGCAGCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGCA
CCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTG
TCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTC
CAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACC
CTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCA
GCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATC
GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACT
ACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTC
TTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGC
AGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCT
CTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCC
GGGTGGTGGCGGATCGGGAGGTGGCGGATCCCAGGTGCAG
CTGGTGGAGTCTGGGGGAGGCTTGGTCAAGCCTGGAGGGT
CCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGT
GACTACTACATGAGCTGGATCCGCCAGGCTCCAGGGAAGT
GCCTGGAGTGGATTTCATACATTAGTAGCAGTGAAAGTATC
ATCTATTACGTAGACGCTGTGAAGGGCCGATTCACCATCTC
CAGGGACAACGCCAAGAACTCACTGTATCTGCAAATGAAC
AGCCTGAGAGCCGAGGACACGGCCGTGTATTACTGTGCGA
GAGATGTTGGGAGCCACTTTGACTACTGGGGCCAGGGAAC
CCTGGTCACCGTGTCCTCAGGAGGGGGCGGATCTGGCGGC
GGAGGAAGCGGTGGGGGCGGCTCCGACATCCAGATGACCC
AGTCTCCATCTTCCGTGTCTGCTTCTGTCGGAGACAGAGTC
ACCATCACTTGTCGGGCGAGTCAGGATATTAGCAGGTGGTT
AGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTC
CTGATTTCTGCTGCATCCAGATTGCAAAGTGGAGTCCCATC
AAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCA
CCATCAGCAGCCTGCAGCCTGAAGATTTTGCAATTTACTAT
TGTCAACAGGCTAAAAGTTTTCCTCGGACGTTCGGCTGCGG
GACCAAGGTGGAAATCAAACGG
(SEQ ID NO: 335)
AA
QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSSRTAWNWIRQSP
SRGLEWLGRTYYRSKWYHDYSVSVKSRITIDPDTSKNQFSLQ
LNSVTPEDTAVYYCARGAAPFDYWGQGTLVTVSSASTKGPSV
FPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH
TFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKV
DKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR
TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQY
GSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK
AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE
WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSQVQLVESG
GGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKCLEWISYI
SSSESIIYYVDAVKGRFTISRDNAKNSLYLQMNSLRAEDTAVY
YCARDVGSHFDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQ
MTQSPSSVSASVGDRVTITCRASQDISRWLAWYQQKPGKAPK
LLISAASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAIYYC
QQAKSFPRTFGCGTKVEIKR
(SEQ ID NO: 337)
iPS: 577393
SST206069
NA
CAGGTGCAACTGGTGCAGTCTGGGGCTGAGGTGACGAAGC
CTGGGGCCTCAGTGAAGGTGTCCTGCAAGGCTTCTGGATAC
ACCTTCGCCGGCTACTATATGCACTGGGTGCGACAGGCCCC
TGGACAAGGGCTTGAGTGGATGGGATGGATCAACCCTCAC
AGTGGTGGCACAAACTATGCACAGAAGTTTCAGGACAGGG
TCACCATGACCAGGGACACGTCCATCAACACAGCCTACAT
GGAACTGAGCAGGCTGAGATCTGACGACACGGCCGTGTAT
TACTGTGCGAGAGAACGTATTTCTATGGTTCGGGGAGTCGG
GCACAACTGGTTCGCCCCCTGGGGCCAGGGAACCCTGGTC
ACCGTGTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCC
CCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCG
GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGT
GACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTG
CACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTC
CCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCA
CCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAA
CACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGAC
AAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCT
GGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGG
ACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTG
GTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCA
ACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGCAGCACGTACCGTTGC
GTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGG
CAAGGAGTACAAGTGCAAGGTGTCCAACAAAGCCCTCCCA
GCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGC
CCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGA
GGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTC
AAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGA
GCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCC
CGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGC
TCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTT
CTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACA
CGCAGAAGAGCCTCTCCCTGTCTCCGGGTGGTGGCGGATCG
GGAGGTGGCGGATCCCAGGTGCAGCTGGTCGAGTCTGGGG
GAGGCTTGGTCAAGCCTGGAGGGTCCCTGAGACTCTCCTGT
GCAGCCTCTGGATTCACCTTCAGTGACTACTACATGACCTG
GATCAGGCAGGCTCCAGGGAAGTGCCTGGAGTGGATTTCA
TACATTAGTAGTAGTGGTAGTACCATCTACTACGCAGACTC
TGTGAAGGGCCGATTCACCATCTCCAGGGACAACGCCAAG
AACTCACTGTATCTGCAAATGAACAGCCTGAGAGCCGAGG
ACACGGCCGTGTATTACTGTGCGAGAGATCGGAACTCCCAC
TTTGACTATTGGGGCCAGGGAACCCTGGTCACCGTGTCCTC
AGGAGGGGGCGGATCTGGCGGCGGAGGAAGCGGTGGGGG
CGGCTCCGACATTCAGATGACCCAGTCTCCATCTTCCGTGT
CTGCATCTGTAGGGGACAGAGTCACCATCACTTGTCGGGCG
AGTCAGGGTATTACCAGGTGGTTAGCCTGGTATCAGCAGA
AACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCC
GTTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGG
ATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGC
CTGAAGATTTTGCAACTTACTATTGTCAACAGTCTAACAGT
TTCCCTCGGACGTTCGGCTGCGGGACCAAGGTGGAAATCA
AACGG
(SEQ ID NO: 339)
AA
QVQLVQSGAEVTKPGASVKVSCKASGYTFAGYYMHWVRQA
PGQGLEWMGWINPHSGGTNYAQKFQDRVTMTRDTSINTAYM
ELSRLRSDDTAVYYCARERISMVRGVGHNWFAPWGQGTLVT
VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS
WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLF
PPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH
NAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLV
KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGG
GSQVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIRQA
PGKCLEWISYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQM
NSLRAEDTAVYYCARDRNSHFDYWGQGTLVTVSSGGGGSGG
GGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGITRWLA
WYQQKPGKAPKLLIYAASVLQSGVPSRFSGSGSGTDFTLTISS
LQPEDFATYYCQQSNSFPRTFGCGTKVEIKR
(SEQ ID NO: 341)
iPS: 598009
SST206070
NA
CAGGTGCAACTGGTGCAGTCTGGGGCTGAGGTGACGAAGC
CTGGGGCCTCAGTGAAGGTGTCCTGCAAGGCTTCTGGATAC
ACCTTCGCCGGCTACTATATGCACTGGGTGCGACAGGCCCC
TGGACAAGGGCTTGAGTGGATGGGATGGATCAACCCTCAC
AGTGGTGGCACAAACTATGCACAGAAGTTTCAGGACAGGG
TCACCATGACCAGGGACACGTCCATCAACACAGCCTACAT
GGAACTGAGCAGGCTGAGATCTGACGACACGGCCGTGTAT
TACTGTGCGAGAGAACGTATTTCTATGGTTCGGGGAGTCGG
GCACAACTGGTTCGCCCCCTGGGGCCAGGGAACCCTGGTC
ACCGTGTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTTTCCC
CCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCG
GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGT
GACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTG
CACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTC
CCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCA
CCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAA
CACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGAC
AAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCT
GGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGG
ACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTG
GTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCA
ACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGCAGCACGTACCGTTTTGC
GTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGG
CAAGGAGTACAAGTGCAAGGTGTCCAACAAAGCCCTCCCA
GCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGC
CCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGA
GGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTC
AAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGA
GCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCC
CGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGC
TCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTT
CTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACA
CGCAGAAGAGCCTCTCCCTGTCTCCGGGTGGTGGCGGATCG
GGAGGTGGCGGATCCCAGGTGCAGCTGGTCGAGTCTGGGG
GAGGCTTGGTCAAGCCTGGAGGGTCCCTGAGACTCTCCTGT
GCAGCCTCTGGATTCACCTTCAGTGACTACTACATGACCTG
GATCAGGCAGGCTCCAGGGAAGTGCCTGGAGTGGATTTCA
TACATTAGTAGTAGTGGTAGTACCATCTACTACGCAGAATC
TGTGAAGGGCCGATTCACCATCTCCAGGGACAACGCCAAG
AACTCACTGTATCTGCAAATGAACAGCCTGAGAGCCGAGG
ACACGGCCGTGTATTACTGTGCGAGAGATCGGAACTCCCAC
TTTGACTATTGGGGCCAGGGAACCCTGGTCACCGTGTCCTC
AGGAGGGGGCGGATCTGGCGGCGGAGGAAGCGGTGGGGG
CGGCTCCGACATTCAGATGACCCAGTCTCCATCTTCCGTGT
CTGCATCTGTAGGGGACAGAGTCACCATCACTTGTCGGGCG
AGTCAGGGTATTACCAGGTGGTTAGCCTGGTATCAGCAGA
AACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCC
GTTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGG
ATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGC
CTGAAGATTTTGCAACTTACTATTGTCAACAGTCTAACAGT
TTCCCTCGGACGTTCGGCTGCGGGACCAAGGTGGAAATCA
AACGG
(SEQ ID NO: 343)
AA
QVQLVQSGAEVTKPGASVKVSCKASGYTFAGYYMHWVRQA
PGQGLEWMGWINPHSGGTNYAQKFQDRVTMTRDTSINTAYM
ELSRLRSDDTAVYYCARERISMVRGVGHNWFAPWGQGTLVT
VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS
WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLF
PPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH
NAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLV
KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGG
GSQVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIRQA
PGKCLEWISYISSSGSTIYYAESVKGRFTISRDNAKNSLYLQMN
SLRAEDTAVYYCARDRNSHFDYWGQGTLVTVSSGGGGSGGG
GSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGITRWLAW
YQQKPGKAPKLLIYAASVLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCQQSNSFPRTFGCGTKVEIKR
(SEQ ID NO: 345)
iPS: 612501
SST206082
NA
GAGGTGCAGCTGCTGGAGTCTGGGGGAGGCTTGGTACAGC
CTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTC
ACCTTTAGTAGAAATGCCATGAGTTGGGTCCGCCAGGCTCC
AGGGAAGGGGCTGGAGTGGGTGTCAGCTACTGGTGGTAGT
GGTATTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTTT
CACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGC
AAATGAACAGTCTGAGAGCCGAGGACACGGCCGTATATTA
CTGTGCGAGAGGTTATAGCAACAGCTGGTGGTACTTTGACT
ACTGGGGCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCC
ACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAA
GAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTC
AAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTC
AGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCC
TACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACC
GTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAA
CGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAA
GTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACC
GTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTTTCC
TCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACG
AAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAAGCCGTGCGAGGAGCAG
TACGGCAGCACGTACCGTTGCGTCAGCGTCCTCACCGTCCT
GCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAG
GTGTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCA
TCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTA
CACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAG
GTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGA
CATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAAC
AACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTC
CTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGT
GGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAG
GCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTC
TCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCCAGGTG
CAGCTGGTGGAGTCTGGGGGAGGCTTGGTCAAGCCTGGAG
GGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTC
AGTGACTACTACATGAGCTGGATCCGCCAGGCTCCAGGGA
AGTGCCTGGAGTGGATTTCATACATTAGTAGCAGTGAAAGT
ATCATCTATTACGTAGACGCTGTGAAGGGCCGATTCACCAT
CTCCAGGGACAACGCCAAGAACTCACTGTATCTGCAAATG
AACAGCCTGAGAGCCGAGGACACGGCCGTGTATTACTGTG
CGAGAGATGTTGGGAGCCACTTTGACTACTGGGGCCAGGG
AACCCTGGTCACCGTGTCCTCAGGAGGGGGCGGATCTGGC
GGCGGAGGAAGCGGTGGGGGCGGCTCCGACATCCAGATGA
CCCAGTCTCCATCTTCCGTGTCTGCTTCTGTCGGAGACAGA
GTCACCATCACTTGTCGGGCGAGTCAGGATATTAGCAGGTG
GTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAG
CTCCTGATTTCTGCTGCATCCAGATTGCAAAGTGGAGTCCC
ATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTC
TCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAATTTAC
TATTGTCAACAGGCTAAAAGTTTTCCTCGGACGTTCGGCTG
CGGGACCAAGGTGGAAATCAAACGG
(SEQ ID NO: 347)
AA
EVQLLESGGGLVQPGGSLRLSCAASGFTFSRNAMSWVRQAPG
KGLEWVSATGGSGISTYYADSVKGRFTISRDNSKNTLYLQMN
SLRAEDTAVYYCARGYSNSWWYFDYWGQGTLVTVSSASTK
GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS
NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT
LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKP
CEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSQVQL
VESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKCLE
WISYISSSESIIYYVDAVKGRFTISRDNAKNSLYLQMNSLRAED
TAVYYCARDVGSHFDYWGQGTLVTVSSGGGGSGGGGSGGG
GSDIQMTQSPSSVSASVGDRVTITCRASQDISRWLAWYQQKP
GKAPKLLISAASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDF
AIYYCQQAKSFPRTFGCGTKVEIKR
(SEQ ID NO: 349)
iPS: 612522
SST206096
NA
CAGGTGCAACTGGTGCAGTCTGGGGCTGAAGTGAAGAAGC
CTGGGGCCTCAGTGAAGGTGTCCTGCAAGGCTTCTGGATAC
ACCTTCCCCGGCTACTATATGTACTGGTTGCGACAGGCCCC
TGGACAAGGACTTGAGTGGATGGGATGGATCAACCCTGAC
AGTGGTGACACAAACTATGCACAGAAGTTTCAGGGCAGGG
TCACCATGACCAGGGACACGTCCATCAGCACAGCCTTTATG
GAGCTGAGCAGGCTGAGATCAGACGACACGGCCGTGTATT
ACTGTGCGAGAGAGAAGCCCAGATATTTTTTGACTCCTTCTAC
TACTACCTTATGGACGTCTGGGGCCAAGGGACCACGGTCAC
CGTGTCCTCAaAGCCTCCACCAAGGGCCCATCGGTCTTCCCCC
TGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGC
CCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGA
CGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCA
CACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCT
CAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCC
AGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACAC
CAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAA
ACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGG
GGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACA
CCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTG
GTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACT
GGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAA
GCCGTGCGAGGAGCAGTACGGCAGCACGTACCGTTGCGTC
AGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAA
GGAGTACAAGTGCAAGGTGTCCAACAAAGCCCTCCCAGCC
CCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCC
GAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGA
GATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAA
GGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCA
ATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGT
GCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCA
CCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGC
AGAAGAGCCTCTCCCTGTCTCCGGGTGGTGGCGGATCGGG
AGGTGGCGGATCCCAGGTGCAGCTGGTGGAGTCTGGGGGA
GGCTTGGTCAAGCCTGGAGGGTCCCTGAGACTCTCCTGTGC
AGCCTCTGGATTCACCTTCAGTGACTACTACATGAGCTGGA
TCCGCCAGGCTCCAGGGAAGTGCCTGGAGTGGATTTCATAC
ATTAGTAGCAGTGAAAGTATCATCTATTACGTAGACGCTGT
GAAGGGCCGATTCACCATCTCCAGGGACAACGCCAAGAAC
TCACTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACA
CGGCCGTGTATTACTGTGCGAGAGATGTTGGGAGCCACTTT
GACTACTGGGGCCAGGGAACCCTGGTCACCGTGTCCTCAG
GAGGGGGCGGATCTGGCGGCGGAGGAAGCGGTGGGGGCG
GCTCCGACATCCAGATGACCCAGTCTCCATCTTCCGTGTCT
GCTTCTGTCGGAGACAGAGTCACCATCACTTGTCGGGCGAG
TCAGGATATTAGCAGGTGGTTAGCCTGGTATCAGCAGAAA
CCAGGGAAAGCCCCTAAGCTCCTGATTTCTGCTGCATCCAG
ATTGCAAAGTGGAGTCCCATCAAGGTTCAGCGGCAGTGGA
TCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCC
TGAAGATTTTGCAATTTACTATTGTCAACAGGCTAAAAGTT
TTCCTCGGACGTTCGGCTGCGGGACCAAGGTGGAAATCAA
ACGG
(SEQ ID NO: 351)
AA
QVQLVQSGAEVKKPGASVKVSCKASGYTFPGYYMYWLRQA
PGQGLEWMGWINPDSGDTNYAQKFQGRVTMTRDTSISTAFM
ELSRLRSDDTAVYYCAREKPRYFDSFYYYLMDVWGQGTTVT
VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS
WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLF
PPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH
NAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLV
KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGG
GSQVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQA
PGKCLEWISYISSSESIIYYVDAVKGRFTISRDNAKNSLYLQMN
SLRAEDTAVYYCARDVGSHFDYWGQGTLVTVSSGGGGSGGG
GSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQDISRWLAW
YQQKPGKAPKLLISAASRLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFAIYYCQQAKSFPRTFGCGTKVEIKR
(SEQ ID NO: 353)
iPS: 612584
SST206128
NA
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGC
CTGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTC
ACCCTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCC
AGGCAAGGGGCTGGAGTGGGTGGCAGTTATCTGGTATGAT
GGAAGTAATAAATACTATGCAGACTCCGTGAAGGGCCGAG
TCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTG
CAAATGAATAGCCTGAGAGCCGAGGACACGGCTGTGTATT
ACTGTACGAGAGATGGCCGGAACTACGTCTACTTTGACAAC
TGGGGCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCCAC
CAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGA
GCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAA
GGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAG
GCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA
CAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGT
GCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACG
TGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGT
TGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGT
GCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTC
TTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGAC
CCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAA
GACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGG
AGGTGCATAATGCCAAGACAAAGCCGTGCGAGGAGCAGTA
CGGCAGCACGTACCGTTGCGTCAGCGTCCTCACCGTCCTGC
ACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGT
GTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCT
CCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACAC
CCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTC
AGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACAT
CGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAAC
TACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTT
CTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGC
AGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCT
CTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCC
GGGTGGTGGCGGATCGGGAGGTGGCGGATCCCAGGTGCAG
CTGGTGGAGTCTGGGGGAGGCTTGGTCAAGCCTGGAGGGT
CCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGT
GACTACTACATGAGCTGGATCCGCCAGGCTCCAGGGAAGT
GCCTGGAGTGGATTTCATACATTAGTAGCAGTGAAAGTATC
ATCTATTACGTAGACGCTGTGAAGGGCCGATTCACCATCTC
CAGGGACAACGCCAAGAACTCACTGTATCTGCAAATGAAC
AGCCTGAGAGCCGAGGACACGGCCGTGTATTACTGTGCGA
GAGATGTTGGGAGCCACTTTGACTACTGGGGCCAGGGAAC
CCTGGTCACCGTGTCCTCAGGAGGGGGCGGATCTGGCGGC
GGAGGAAGCGGTGGGGGCGGCTCCGACATCCAGATGACCC
AGTCTCCATCTTCCGTGTCTGCTTCTGTCGGAGACAGAGTC
ACCATCACTTGTCGGGCGAGTCAGGATATTAGCAGGTGGTT
AGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTC
CTGATTTCTGCTGCATCCAGATTGCAAAGTGGAGTCCCATC
AAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCA
CCATCAGCAGCCTGCAGCCTGAAGATTTTGCAATTTACTAT
TGTCAACAGGCTAAAAGTTTTCCTCGGACGTTCGGCTGCGG
GACCAAGGTGGAAATCAAACGG
(SEQ ID NO: 355)
AA
QVQLVESGGGVVQPGRSLRLSCAASGFTLSSYGMHWVRQAP
GKGLEWVAVIWYDGSNKYYADSVKGRVTISRDNSKNTLYLQ
MNSLRAEDTAVYYCTRDGRNYVYFDNWGQGTLVTVSSASTK
GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT
SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS
NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT
LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKP
CEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSQVQL
VESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKCLE
WISYISSSESIIYYVDAVKGRFTISRDNAKNSLYLQMNSLRAED
TAVYYCARDVGSHFDYWGQGTLVTVSSGGGGSGGGGSGGG
GSDIQMTQSPSSVSASVGDRVTITCRASQDISRWLAWYQQKP
GKAPKLLISAASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDF
AIYYCQQAKSFPRTFGCGTKVEIKR
(SEQ ID NO: 357)
IPS #
LC
iPS: 616974
CAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGAGCCC
TGGACAGTCGATCACCATCTCCTGCACTGGAACCAGCAGTG
ATGTTGGGAATTATAACCTTGTCTCCTGGTACCAACAGCAC
CCAGGCAAAGCCCCCAAACTCATGATTTATGAGGTCAATA
GGCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCAAG
TCTGGCAACACGGCCTCCCTGACAATCTCTGGGCTCCAGGC
TGAGGACGAGGCTGAATATTACTGCTCCTCATATGCAGGTA
GAGACACTTTCGTGGTGTTCGGCGGAGGGACCAAGCTGAC
CGTCCTAGGTCAGCCCAAGGCTGCACCCTCGGTCACTCTGT
TCCCGCCCTCCTCTGAGGAGCTTCAAGCCAACAAGGCCACA
CTGGTGTGTCTCATCAGTGACTTCTACCCGGGAGCCGTGAC
AGTGGCCTGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGA
GTGGAAACCACCACACCCTCCAAACAAAGCAACAACAAGT
ACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTG
GAAGTCCCACAGAAGCTACAGCTGCCAGGTCACGCATGAA
GGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTT
CA
(SEQ ID NO: 336)
QSALTQPASVSGSPGQSITISCTGTSSDVGNYNLVSWYQQHPG
KAPKLMIYEVNRRPSGVSNRFSGSKSGNTASLTISGLQAEDEA
EYYCSSYAGRDTFVVFGGGTKLTVLGQPKAAPSVTLFPPSSEE
LQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSK
QSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAP
TECS
(SEQ ID NO: 338)
iPS: 577393
GACATCCAGATGACCCAGTCTCCATCCTCACTGTCTGCATC
TGTAGGAGACAGAGTCACCATCACCTGTCGGGCGAGTCAG
GACATTAGCAATAATTTAGCCTGGTTTCAGCAGAAACCAGG
GAAACCCCCTAAGTCCCTGATGTATGCTGCATCCAGTTTGC
ACAGTGGAGTCCCATCAACGTTCAGCGGCAGTGGATCTGG
GACAGATTTCACTTTCACCATCAGCAGCCTGCAGCCTGAAG
ATTTTGCAACTTATTACTGCCAACAGTATAATAGTTACCCT
CTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAGACGAA
CGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATG
AGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTG
AATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGG
TGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTC
ACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCA
GCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAA
AGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGC
CCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
(SEQ ID NO: 340)
DIQMTQSPSSLSASVGDRVTITCRASQDISNNLAWFQQKPGKP
PKSLMYAASSLHSGVPSTFSGSGSGTDFTFTISSLQPEDFATY
YCQQYNSYPLTFGGGTKVEIRRTVAAPSVFIFPPSDEQLKSGT
ASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDST
YSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
(SEQ ID NO: 342)
iPS: 598009
GACATCCAGATGACCCAGTCTCCATCCTCACTGTCTGCATC
TGTAGGAGACAGAGTCACCATCACCTGTCGGGCGAGTCAG
GACATTAGCAATAATTTAGCCTGGTTTCAGCAGAAACCAGG
GAAACCCCCTAAGTCCCTGATGTATGCTGCATCCAGTTTGC
ACAGTGGAGTCCCATCAACGTTCAGCGGCAGTGGATCTGG
GACAGATTTCACTTTCACCATCAGCAGCCTGCAGCCTGAAG
ATTTTGCAACTTATTACTGCCAACAGTATAATAGTTACCCT
CTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAGACGAA
CGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATG
AGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTG
AATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGG
TGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTC
ACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCA
GCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAA
AGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGC
CCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
(SEQ ID NO: 344)
DIQMTQSPSSLSASVGDRVTITCRASQDISNNLAWFQQKPGKP
PKSLMYAASSLHSGVPSTFSGSGSGTDFTFTISSLQPEDFATY
YCQQYNSYPLTFGGGTKVEIRRTVAAPSVFIFPPSDEQLKSGT
ASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDST
YSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
(SEQ ID NO: 346)
iPS: 612501
CAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGAGCCC
TGGACAGTCGATCACCATCTCCTGCACTGGAACCAGCAGTG
ATGTTGGGAATTATAACCTTGTCTCCTGGTACCAACAGCAC
CCAGGCAAAGCCCCCAAACTCATGATTTTTGAGGTCAATCA
GCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCAAGT
CTGGCACCACGGCCTCCCTGACAATCTCTGGGCTCCAGGCT
GCGGACGAGGCTGATTATTTCTGCTCCTCATATACAACTAG
TAGCACTTATGTGATCTTCGGCGGAGGGACCAAGCTGACCG
TCCTAGGTCAGCCCAAGGCTGCACCCTCGGTCACTCTGTTTC
CCGCCCTCCTCTGAGGAGCTTCAAGCCAACAAGGCCACACT
GGTGTGTCTCATCAGTGACTTCTACCCGGGAGCCGTGACAG
TGGCCTGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGT
GGAAACCACCACACCCTCCAAACAAAGCAACAACAAGTAC
GCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGA
AGTCCCACAGAAGCTACAGCTGCCAGGTCACGCATGAAGG
GAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCA
(SEQ ID NO: 348)
QSALTQPASVSGSPGQSITISCTGTSSDVGNYNLVSWYQQHPG
KAPKLMIFEVNQRPSGVSNRFSGSKSGTTASLTISGLQAADEA
DYFCSSYTTSSTYVIFGGGTKLTVLGQPKAAPSVTLFPPSSEE
LQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQ
SNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPT
ECS
(SEQ ID NO: 350)
iPS: 612522
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATC
TGTAGGAGACAGAGTCACCATCACTTGCCGGGCAGGTCAG
AACATTGCCAGGCATTTAAATTGGTATCAGCAGAATCCAGG
GAAAGCCCCTAAGGTCCTGATCCATCCTGCATCCAGTTTGC
CAAGTGGGGTCCCGTCAAGGTTCAGTGGCAGTGGATCTGG
GACAGATTTCAGTCTTACCATCAGCAGTCTGCAACCTGAAG
ATTTTGGAACTTACTTCTGTCAACAGAGTTACAGTACCCCT
CCCACTTTCGGCGGAGGGACCAAGGTGGAGCTCAAACGAA
CGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATG
AGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTG
AATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGG
TGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTC
ACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCA
GCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAA
AGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGC
CCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
(SEQ ID NO: 352)
DIQMTQSPSSLSASVGDRVTITCRAGQNIARHLNWYQQNPGK
APKVLIHPASSLPSGVPSRFSGSGSGTDFSLTISSLQPEDFG
TYFCQQSYSTPPTFGGGTKVELKRTVAAPSVFIFPPSDEQLK
SGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDS
KDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
RGEC
(SEQ ID NO: 354)
iPS: 612584
CAGTCTGCCCTGACTCAGCCTCGCTCAGTGTCCGGGAGCCC
TGGACAGTCAGTCACCATCTCCTGCACTGGAACCAGCAGTG
ATGTTGGTGGTTATATCTTTGTCTCCTGGTACCAACAACAC
CCAGGCAAAGCCCCCAAACTCATGATTTATGATGTCAGTAA
GCGGCCCTCTGGGGTCCCTGATCGCTTCTCTGGCTCCAAGT
CTGTCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCT
GAGGATGAGACTGATTATTACTGCTCCTCATATGCAGGCAA
CTACGCTTATGTCTTCGGAACTGGGACCAAGGTCACCGTCC
TAGGTCAGCCCAAGGCTGCACCCTCGGTCACTCTGTTCCCG
CCCTCCTCTGAGGAGCTTCAAGCCAACAAGGCCACACTGGT
GTGTCTCATCAGTGACTTCTACCCGGGAGCCGTGACAGTGG
CCTGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGA
AACCACCACACCCTCCAAACAAAGCAACAACAAGTACGCG
GCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGT
CCCACAGAAGCTACAGCTGCCAGGTCACGCATGAAGGGAG
CACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCA
(SEQ ID NO: 356)
QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYIFVSWYQQHPG
KAPKLMIYDVSKRPSGVPDRFSGSKSVNTASLTISGLQAEDET
DYYCSSYAGNYAYVFGTGTKVTVLGQPKAAPSVTLFPPSSEE
LQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSK
QSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAP
TECS
(SEQ ID NO: 358)
TABLE 26
MSLN-CD40 IgG-scFv Full length
iPS: 577300
21-233_4H6_IgG_21-230_4G7_scFv
NA
CAGGTGCAGCTGGTCGAGTCTGGGGGAGGCTTGGTCAAGC
GACATTCAGATGACCCAGTCTCCATCTTCCGTGTCTGCATC
CTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTC
TGTAGGGGACAGAGTCACCATCACTTGTCGGGCGAGTCAG
ACCTTCAGTGACTACTACATGACCTGGATCAGGCAGGCTC
GGTATTACCAGGTGGTTAGCCTGGTATCAGCAGAAACCAG
CAGGGAAGGGGCTGGAGTGGATTTCATACATTAGTAGTAG
GGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCGTTTTG
TGGTAGTACCATCTACTACGCAGACTCTGTGAAGGGCCGA
CAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTG
TTCACCATCTCCAGGGACAACGCCAAGAACTCACTGTATCT
GGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGA
GCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTAT
AGATTTTGCAACTTACTATTGTCAACAGTCTAACAGTTTCC
TACTGTGCGAGAGATCGGAACTCCCACTTTGACTATTGGG
CTCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACG
GCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCCACCAA
GACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTG
GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCA
ATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG
CCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGA
CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
AGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAG
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
TGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAA
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGT
CACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGA
GAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGT
GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
TGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCG
(SEQ ID NO: 360)
TGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCT
CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACG
AAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAAGCCGTGCGAGGAGCA
GTACGGCAGCACGTACCGTTGCGTCAGCGTCCTCACCGTCC
TGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAA
GGTGTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACC
ATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGT
ACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCA
GGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCG
ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGA
ACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG
CTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCC
CTGTCTCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCC
AGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCC
TGGGGCCTCAGTGAAGGTGTCCTGCAAGGCTTCTGGATAC
ACCTTCGCCGGCTACTATATGCACTGGGTGCGACAGGCCC
CTGGACAATGCCTTGAGTGGATGGGATGGATCAACCCTGA
CAGTGGAGGCACAAACTTTGCACAGCAGTTTCAGGGCAGG
GTCACCATGACCAGGGATACGTCCATCAGCACAGCCTACA
TGGAGGTGAGCAGGCTGAGATCTGACGACACGGCCGTGTT
TTACTGTGCGAGAGAGAAGATCACTATGACTGGTATTTACT
TTGACTATTGGGGCCAGGGAACCCTGGTCACCGTGTCCTCA
GGAGGGGGCGGATCTGGCGGCGGAGGAAGCGGTGGGGGC
GGCTCCGACATCCAGATGACCCAGTCTCCATCCTCCCTGTC
TGCATCTGTAGGAGACATTCTCACCATCACTTGCCGGGCAA
GTCAGAACATTACCACCTATTTAAATTGGTATCAGCAGAA
ACCAGGGAAAGCCCCTAACCTCCTGATCTCTGCTGCATCCC
GTTTGCGAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGG
ATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAAC
CTGTAGATTTTACAACTTTCTACTGTCAACAGACTTTCACT
ACCCCGTGGACGTTCGGCTGCGGGACCAAGGTGGAGATCA
AACGA
(SEQ ID NO: 359)
AA
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIRQAP
DIQMTQSPSSVSASVGDRVTITCRASQGITRWLAWYQQKPGK
GKGLEWISYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMN
APKLLIYAASVLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATY
SLRAEDTAVYYCARDRNSHFDYWGQGTLVTVSSASTKGPSV
YCQQSNSFPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGT
FPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV
ASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD
HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK
STYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG
VDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI
EC
SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE
(SEQ ID NO: 362)
QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIA
VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ
GNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSQVQLV
QSGAEVKKPGASVKVSCKASGYTFAGYYMHWVRQAPGQCL
EWMGWINPDSGGTNFAQQFQGRVTMTRDTSISTAYMEVSRL
RSDDTAVFYCAREKITMTGIYFDYWGQGTLVTVSSGGGGSG
GGGSGGGGSDIQMTQSPSSLSASVGDILTITCRASQNITTYLN
WYQQKPGKAPNLLISAASRLRSGVPSRFSGSGSGTDFTLTISSL
QPVDFTTFYCQQTFTTPWTFGCGTKVEIKR
(SEQ ID NO: 361)
iPS: 577307
21-233_4H6_IgG_21-230_29H10_scFv
NA
CAGGTGCAGCTGGTCGAGTCTGGGGGAGGCTTGGTCAAGC
GACATTCAGATGACCCAGTCTCCATCTTCCGTGTCTGCATC
CTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTC
TGTAGGGGACAGAGTCACCATCACTTGTCGGGCGAGTCAG
ACCTTCAGTGACTACTACATGACCTGGATCAGGCAGGCTC
GGTATTACCAGGTGGTTAGCCTGGTATCAGCAGAAACCAG
CAGGGAAGGGGCTGGAGTGGATTTCATACATTAGTAGTAG
GGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCGTTTTG
TGGTAGTACCATCTACTACGCAGACTCTGTGAAGGGCCGA
CAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTG
TTCACCATCTCCAGGGACAACGCCAAGAACTCACTGTATCT
GGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGA
GCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTAT
AGATTTTGCAACTTACTATTGTCAACAGTCTAACAGTTTCC
TACTGTGCGAGAGATCGGAACTCCCACTTTGACTATTGGG
CTCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACG
GCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCCACCAA
GACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTG
GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCA
ATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG
CCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGA
CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
AGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAG
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
TGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAA
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGT
CACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGA
GAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGT
GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
TGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCG
(SEQ ID NO: 364)
TGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCT
CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACG
AAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAAGCCGTGCGAGGAGCA
GTACGGCAGCACGTACCGTTGCGTCAGCGTCCTCACCGTCC
TGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAA
GGTGTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACC
ATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGT
ACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCA
GGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCG
ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGA
ACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG
CTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCC
CTGTCTCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCC
AGGTGCAACTGGTGCAGTCTGGGGCTGAGGTGACGAAGCC
TGGGGCCTCAGTGAAGGTGTCCTGCAAGGCTTCTGGATAC
ACCTTCGCCGGCTACTATATGCACTGGGTGCGACAGGCCC
CTGGACAATGCCTTGAGTGGATGGGATGGATCAACCCTCA
CAGTGGTGGCACAAACTATGCACAGAAGTTTCAGGACAGG
GTCACCATGACCAGGGACACGTCCATCAACACAGCCTACA
TGGAACTGAGCAGGCTGAGATCTGACGACACGGCCGTGTA
TTACTGTGCGAGAGAACGTATTTCTATGGTTCGGGGAGTCG
GGCACAACTGGTTCGCCCCCTGGGGCCAGGGAACCCTGGT
CACCGTGTCCTCAGGAGGGGGCGGATCTGGCGGCGGAGGA
AGCGGTGGGGGCGGCTCCGACATCCAGATGACCCAGTCTC
CATCCTCACTGTCTGCATCTGTAGGAGACAGAGTCACCATC
ACCTGTCGGGCGAGTCAGGACATTAGCAATAATTTAGCCT
GGTTTCAGCAGAAACCAGGGAAACCCCCTAAGTCCCTGAT
GTATGCTGCATCCAGTTTGCACAGTGGAGTCCCATCAACGT
TCAGCGGCAGTGGATCTGGGACAGATTTCACTTTCACCATC
AGCAGCCTGCAGCCTGAAGATTTTGCAACTTATTACTGCCA
ACAGTATAATAGTTACCCTCTCACTTTCGGCTGCGGGACCA
AGGTGGAGATCAGACGA
(SEQ ID NO: 363)
AA
QVQLESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIRQAP
DIQMTQSPSSVSASVGDRVTITCRASQGITRWLAWYQQKPGK
GKGLEWISYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMN
APKLLIYAASVLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATY
SLRAEDTAVYYCARDRNSHFDYWGQGTLVTVSSASTKGPSV
YCQQSNSFPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGT
FPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV
ASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD
HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK
STYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG
VDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI
EC
SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE
(SEQ ID NO: 366)
QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIA
VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ
GNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSQVQLV
QSGAEVTKPGASVKVSCKASGYTFAGYYMHWVRQAPGQCL
EWMGWINPHSGGTNYAQKFQDRVTMTRDTSINTAYMELSRL
RSDDTAVYYCARERISMVRGVGHNWFAPWGQGTLVTVSSG
GGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQDI
SNNLAWFQQKPGKPPKSLMYAASSLHSGVPSTFSGSGSGTDF
TFTISSLQPEDFATYYCQQYNSYPLTFGCGTKVEIRR
(SEQ ID NO: 365)
iPS: 577312
21-233_4H6_IgG_21-230_30A12_scFv
NA
CAGGTGCAGCTGGTCGAGTCTGGGGGAGGCTTGGTCAAGC
GACATTCAGATGACCCAGTCTCCATCTTCCGTGTCTGCATC
CTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTC
TGTAGGGGACAGAGTCACCATCACTTGTCGGGCGAGTCAG
ACCTTCAGTGACTACTACATGACCTGGATCAGGCAGGCTC
GGTATTACCAGGTGGTTAGCCTGGTATCAGCAGAAACCAG
CAGGGAAGGGGCTGGAGTGGATTTCATACATTAGTAGTAG
GGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCGTTTTG
TGGTAGTACCATCTACTACGCAGACTCTGTGAAGGGCCGA
CAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTG
TTCACCATCTCCAGGGACAACGCCAAGAACTCACTGTATCT
GGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGA
GCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTAT
AGATTTTGCAACTTACTATTGTCAACAGTCTAACAGTTTCC
TACTGTGCGAGAGATCGGAACTCCCACTTTGACTATTGGG
CTCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACG
GCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCCACCAA
GACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTG
GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCA
ATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG
CCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGA
CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
AGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAG
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
TGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAA
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGT
CACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGA
GAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGT
GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
TGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCG
(SEQ ID NO: 368)
TGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCT
CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACG
AAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAAGCCGTGCGAGGAGCA
GTACGGCAGCACGTACCGTTGCGTCAGCGTCCTCACCGTCC
TGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAA
GGTGTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACC
ATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGT
ACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCA
GGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCG
ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGA
ACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG
CTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCC
CTGTCTCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCG
AGGTGCAGCTGCTGGAGTCTGGGGGAGGCTTGGTACAGCC
TGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCA
CCTTTAGTAGAAATGCCATGAGTTGGGTCCGCCAGGCTCC
AGGGAAGTGCCTGGAGTGGGTGTCAGCTACTGGTGGTAGT
GGTATTAGCACATACTACGCAGACTCCGTGAAGGGCCGGT
TCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCT
GCAAATGAACAGTCTGAGAGCCGAGGACACGGCCGTATAT
TACTGTGCGAGAGGTTATAGCAACAGCTGGTGGTACTTTG
ACTACTGGGGCCAGGGAACCCTGGTCACCGTGTCCTCAGG
AGGGGGCGGATCTGGCGGCGGAGGAAGCGGTGGGGGCGG
CTCCCAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGA
GCCCTGGACAGTCGATCACCATCTCCTGCACTGGAACCAG
CAGTGATGTTGGGAATTATAACCTTGTCTCCTGGTACCAAC
AGCACCCAGGCAAAGCCCCCAAACTCATGATTTTTGAGGT
CAATCAGCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCT
CCAAGTCTGGCACCACGGCCTCCCTGACAATCTCTGGGCTC
CAGGCTGCGGACGAGGCTGATTATTTCTGCTGCTCATATAC
AACTAGTAGCACTTATGTGATCTTCGGCTGCGGGACCAAG
CTGACCGTCCTAGGT
(SEQ ID NO: 367)
AA
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIRQAP
DIQMTQSPSSVSASVGDRVTITCRASQGITRWLAWYQQKPGK
GKGLEWISYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMN
APKLLIYAASVLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATY
SLRAEDTAVYYCARDRNSHFDYWGQGTLVTVSSASTKGPSV
YCQQSNSFPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGT
FPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV
ASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD
HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK
STYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG
VDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI
EC
SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE
(SEQ ID NO: 370)
QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIA
VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ
GNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSEVQLL
ESGGGLVQPGGSLRLSCAASGFTFSRNAMSWVRQAPGKCLE
WVSATGGSGISTYYADSVKGRFTISRDNSKNTLYLQMNSLRA
EDTAVYYCARGYSNSWWYFDYWGQGTLVTVSSGGGGSGG
GGSGGGGSQSALTQPASVSGSPGQSITISCTGTSSDVGNYNLV
SWYQQHPGKAPKLMIFEVNQRPSGVSNRFSGSKSGTTASLTIS
GLQAADEADYFCCSYTTSSTYVIFGCGTKLTVLG
(SEQ ID NO: 369)
iPS: 577317
21-233_4H6_IgG_21-230_33H6_scFv
NA
CAGGTGCAGCTGGTCGAGTCTGGGGGAGGCTTGGTCAAGC
GACATTCAGATGACCCAGTCTCCATCTTCCGTGTCTGCATC
CTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTC
TGTAGGGGACAGAGTCACCATCACTTGTCGGGCGAGTCAG
ACCTTCAGTGACTACTACATGACCTGGATCAGGCAGGCTC
GGTATTACCAGGTGGTTAGCCTGGTATCAGCAGAAACCAG
CAGGGAAGGGGCTGGAGTGGATTTCATACATTAGTAGTAG
GGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCGTTTTG
TGGTAGTACCATCTACTACGCAGACTCTGTGAAGGGCCGA
CAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTG
TTCACCATCTCCAGGGACAACGCCAAGAACTCACTGTATCT
GGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGA
GCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTAT
AGATTTTGCAACTTACTATTGTCAACAGTCTAACAGTTTCC
TACTGTGCGAGAGATCGGAACTCCCACTTTGACTATTGGG
CTCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACG
GCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCCACCAA
GACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTG
GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCA
ATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG
CCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGA
CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
AGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAG
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
TGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAA
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGT
CACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGA
GAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGT
GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
TGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCG
(SEQ ID NO: 372)
TGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCT
CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACG
AAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAAGCCGTGCGAGGAGCA
GTACGGCAGCACGTACCGTTGCGTCAGCGTCCTCACCGTCC
TGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAA
GGTGTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACC
ATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGT
ACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCA
GGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCG
ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGA
ACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG
CTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCC
CTGTCTCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCC
AGGTGCAACTGGTGCAGTCTGGGGCTGAAGTGAAGAAGCC
TGGGGCCTCAGTGAAGGTGTCCTGCAAGGCTTCTGGATAC
ACCTTCCCCGGCTACTATATGTACTGGTTGCGACAGGCCCC
TGGACAATGCCTTGAGTGGATGGGATGGATCAACCCTGAC
AGTGGTGACACAAACTATGCACAGAAGTTTCAGGGCAGGG
TCACCATGACCAGGGACACGTCCATCAGCACAGCCTTTAT
GGAGCTGAGCAGGCTGAGATCAGACGACACGGCCGTGTAT
TACTGTGCGAGAGAGAAGCCCAGATATTTTGACTCCTTCTA
CTACTACCTTATGGACGTCTGGGGCCAAGGGACCACGGTC
ACCGTGTCCTCAGGAGGGGGCGGATCTGGCGGCGGAGGAA
GCGGTGGGGGCGGCTCCGACATCCAGATGACCCAGTCTCC
ATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCA
CTTGCCGGGCAGGTCAGAACATTAGCAGGCATTTAAATTG
GTATCAGCAGAATCCAGGGAAAGCCCCTAAGGTCCTGATC
CATCCTGCATCCAGTTTGCCAAGTGGGGTCCCGTCAAGGTT
CAGTGGCAGTGGATCTGGGACAGATTTCAGTCTTACCATC
AGCAGTCTGCAACCTGAAGATTTTGGAACTTACTTCTGTCA
ACAGAGTTACAGTACCCCTCCCACTTTCGGCTGCGGGACC
AAGGTGGAGCTCAAACGA
(SEQ ID NO: 371)
AA
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIRQAP
DIQMTQSPSSVSASVGDRVTITCRASQGITRWLAWYQQKPGK
GKGLEWISYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMN
APKLLIYAASVLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATY
SLRAEDTAVYYCARDRNSHFDYWGQGTLVTVSSASTKGPSV
YCQQSNSFPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGT
FPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV
ASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD
HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK
STYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG
VDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI
EC
SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE
(SEQ ID NO: 374)
QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIA
VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ
GNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSQVQLV
QSGAEVKKPGASVKVSCKASGYTFPGYYMYWLRQAPGQCL
EWMGWINPDSGDTNYAQKFQGRVTMTRDTSISTAFMELSRL
RSDDTAVYYCAREKPRYFDSFYYYLMDVWGQGTTVTVSSG
GGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRAGQN
ISRHLNWYQQNPGKAPKVLIHPASSLPSGVPSRFSGSGSGTDF
SLTISSLQPEDFGTYFCQQSYSTPPTFGCGTKVELKR
(SEQ ID NO: 373)
iPS: 577322
21-233_4H6_IgG_21-230_33H9_scFv
NA
CAGGTGCAGCTGGTCGAGTCTGGGGGAGGCTTGGTCAAGC
GACATTCAGATGACCCAGTCTCCATCTTCCGTGTCTGCATC
CTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTC
TGTAGGGGACAGAGTCACCATCACTTGTCGGGCGAGTCAG
ACCTTCAGTGACTACTACATGACCTGGATCAGGCAGGCTC
GGTATTACCAGGTGGTTAGCCTGGTATCAGCAGAAACCAG
CAGGGAAGGGGCTGGAGTGGATTTCATACATTAGTAGTAG
GGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCGTTTTG
TGGTAGTACCATCTACTACGCAGACTCTGTGAAGGGCCGA
CAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTG
TTCACCATCTCCAGGGACAACGCCAAGAACTCACTGTATCT
GGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGA
GCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTAT
AGATTTTGCAACTTACTATTGTCAACAGTCTAACAGTTTCC
TACTGTGCGAGAGATCGGAACTCCCACTTTGACTATTGGG
CTCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACG
GCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCCACCAA
GACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTG
GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCA
ATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG
CCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGA
CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
AGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAG
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
TGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAA
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGT
CACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGA
GAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGT
GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
TGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCG
(SEQ ID NO: 376)
TGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCT
CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACG
AAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAAGCCGTGCGAGGAGCA
GTACGGCAGCACGTACCGTTGCGTCAGCGTCCTCACCGTCC
TGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAA
GGTGTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACC
ATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGT
ACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCA
GGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCG
ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGA
ACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG
CTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCC
CTGTCTCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCC
AGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCA
CCTTCAGTAGCCATGGCATGCACTGGGTCCGCCAACCTCCA
GGCAAGTGCCTGGAGTGGGTGGCAGTTATCTGGTATGATG
GAAGTAATGAATACTATGGAGACTCCGTGAAGGGCCGATT
CACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTG
CAAATGAACAGCCTGAGAGTCGAGGACACGGCTGTGTATT
ACTGTACGAGAGGGGGGGGCCACTGGAACTACGAGGGCC
ACTACTATGGTATGGACGTCTGGGGCCAAGGGACCACGGT
CACCGTGTCCTCAGGAGGGGGCGGATCTGGCGGCGGAGGA
AGCGGTGGGGGCGGCTCCCAGGCTGTGCCGACTCAGCCCT
CTTCCCTCTCTGCATCTCCTGGAGCATCAGCCAGTCTCACC
TGCACCTTACGCAGTGGCATCAATGTTGGTTCCTCCAGGAT
CTATTGGTACCAGCAGAAGCCAGGGAGTCCTCCCCAGTTT
CTCCTGAGGTACACATCAGACTCAGATAAATTGCAGGGCT
CTGGAGTCCCCAGCCGCTTCTCTGGATCCAAAGATGCTTCG
GCCAATGCAGGACTTTTACTCATCTCTGGGCTCCAGTCTGA
GGATGAGGCTGACTATTACTGTATGATTTGGCACAGCAGC
GCTGTGGTATTCGGCTGCGGGACCAAACTGACCGTCCTAG
GT
(SEQ ID NO: 375)
AA
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIRQAP
DIQMTQSPSSVSASVGDRVTITCRASQGITRWLAWYQQKPGK
GKGLEWISYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMN
APKLLIYAASVLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATY
SLRAEDTAVYYCARDRNSHFDYWGQGTLVTVSSASTKGPSV
YCQQSNSFPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGT
FPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV
ASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD
HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK
STYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG
VDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI
EC
SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE
(SEQ ID NO: 378)
QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIA
VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ
GNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSQVQLV
ESGGGVVQPGRSLRLSCAASGFTFSSHGMHWVRQPPGKCLE
WVAVIWYDGSNEYYGDSVKGRFTISRDNSKNTLYLQMNSLR
VEDTAVYYCTRGGGHWNYEGHYYGMDVWGQGTTVTVSSG
GGGSGGGGSGGGGSQAVPTQPSSLSASPGASASLTCTLRSGIN
VGSSRIYWYQQKPGSPPQFLLRYTSDSDKLQGSGVPSRFSGSK
DASANAGLLLISGLQSEDEADYYCMIWHSSAVVFGCGTKLTV
LG
(SEQ ID NO: 377)
iPS: 577327
21-233_4H6_IgG_21-230_35F11_scFv
NA
CAGGTGCAGCTGGTCGAGTCTGGGGGAGGCTTGGTCAAGC
GACATTCAGATGACCCAGTCTCCATCTTCCGTGTCTGCATC
CTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTC
TGTAGGGGACAGAGTCACCATCACTTGTCGGGCGAGTCAG
ACCTTCAGTGACTACTACATGACCTGGATCAGGCAGGCTC
GGTATTACCAGGTGGTTAGCCTGGTATCAGCAGAAACCAG
CAGGGAAGGGGCTGGAGTGGATTTCATACATTAGTAGTAG
GGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCGTTTTG
TGGTAGTACCATCTACTACGCAGACTCTGTGAAGGGCCGA
CAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTG
TTCACCATCTCCAGGGACAACGCCAAGAACTCACTGTATCT
GGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGA
GCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTAT
AGATTTTGCAACTTACTATTGTCAACAGTCTAACAGTTTCC
TACTGTGCGAGAGATCGGAACTCCCACTTTGACTATTGGG
CTCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACG
GCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCCACCAA
GACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTG
GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCA
ATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG
CCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGA
CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
AGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAG
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
TGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAA
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGT
CACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGA
GAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGT
GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
TGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCG
(SEQ ID NO: 380)
TGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCT
CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACG
AAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAAGCCGTGCGAGGAGCA
GTACGGCAGCACGTACCGTTGCGTCAGCGTCCTCACCGTCC
TGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAA
GGTGTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACC
ATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGT
ACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCA
GGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCG
ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGA
ACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG
CTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCC
CTGTCTCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCC
AGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCA
CCCTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCC
AGGCAAGTGCCTGGAGTGGGTGGCAGTTATCTGGTATGAT
GGAAGTAATAAATACTATGCAGACTCCGTGAAGGGCCGAG
TCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCT
GCAAATGAATAGCCTGAGAGCCGAGGACACGGCTGTGTAT
TACTGTACGAGAGATGGCCGGAACTACGTCTACTTTGACA
ACTGGGGCCAGGGAACCCTGGTCACCGTGTCCTCAGGAGG
GGGCGGATCTGGCGGCGGAGGAAGCGGTGGGGGCGGCTC
CCAGTCTGCCCTGACTCAGCCTCGCTCAGTGTCCGGGAGCC
CTGGACAGTCAGTCACCATCTCCTGCACTGGAACCAGCAG
TGATGTTGGTGGTTATATCTTTGTCTCCTGGTACCAACAAC
ACCCAGGCAAAGCCCCCAAACTCATGATTTATGATGTCAG
TAAGCGGCCCTCTGGGGTCCCTGATCGCTTCTCTGGCTCCA
AGTCTGTCAACACGGCCTCCCTGACCATCTCTGGGCTCCAG
GCTGAGGATGAGACTGATTATTACTGCTGCTCATATGCAG
GCAACTACACTTATGTCTTCGGATGCGGGACCAAGGTCAC
CGTCCTAGGT
(SEQ ID NO: 379)
AA
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIRQAP
DIQMTQSPSSVSASVGDRVTITCRASQGITRWLAWYQQKPGK
GKGLEWISYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMN
APKLLIYAASVLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATY
SLRAEDTAVYYCARDRNSHFDYWGQGTLVTVSSASTKGPSV
YCQQSNSFPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGT
FPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV
ASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD
HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK
STYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG
VDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI
EC
SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE
(SEQ ID NO: 382)
QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIA
VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ
GNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSQVQLV
ESGGGVVQPGRSLRLSCAASGFTLSSYGMHWVRQAPGKCLE
WVAVIWYDGSNKYYADSVKGRVTISRDNSKNTLYLQMNSL
RAEDTAVYYCTRDGRNYVYFDNWGQGTLVTVSSGGGGSGG
GGSGGGGSQSALTQPRSVSGSPGQSVTISCTGTSSDVGGYIFV
SWYQQHPGKAPKLMIYDVSKRPSGVPDRFSGSKSVNTASLTI
SGLQAEDETDYYCCSYAGNYTYVFGCGTKVTVLG
(SEQ ID NO: 381)
iPS: 577332
21-233_4H6_IgG_21-230_36F3_scFv
NA
CAGGTGCAGCTGGTCGAGTCTGGGGGAGGCTTGGTCAAGC
GACATTCAGATGACCCAGTCTCCATCTTCCGTGTCTGCATC
CTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTC
TGTAGGGGACAGAGTCACCATCACTTGTCGGGCGAGTCAG
ACCTTCAGTGACTACTACATGACCTGGATCAGGCAGGCTC
GGTATTACCAGGTGGTTAGCCTGGTATCAGCAGAAACCAG
CAGGGAAGGGGCTGGAGTGGATTTCATACATTAGTAGTAG
GGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCGTTTTG
TGGTAGTACCATCTACTACGCAGACTCTGTGAAGGGCCGA
CAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTG
TTCACCATCTCCAGGGACAACGCCAAGAACTCACTGTATCT
GGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGA
GCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTAT
AGATTTTGCAACTTACTATTGTCAACAGTCTAACAGTTTCC
TACTGTGCGAGAGATCGGAACTCCCACTTTGACTATTGGG
CTCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACG
GCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCCACCAA
GACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTG
GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCA
ATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG
CCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGA
CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
AGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAG
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
TGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAA
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGT
CACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGA
GAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGT
GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
TGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCG
(SEQ ID NO: 384)
TGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCT
CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACG
AAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAAGCCGTGCGAGGAGCA
GTACGGCAGCACGTACCGTTGCGTCAGCGTCCTCACCGTCC
TGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAA
GGTGTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACC
ATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGT
ACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCA
GGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCG
ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGA
ACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG
CTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCC
CTGTCTCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCC
AGGTACAGCTGCAACAGTCAGGTCCAGGACTGGTGAAGCC
CTCGCAGACCCTCTCACTCACCTGTGCCATCTCCGGGGACA
GTGTCTCTAGCAGCCGTACTGCTTGGAACTGGATCAGGCA
GTCCCCATCGAGATGCCTTGAGTGGCTGGGAAGGACATAC
TACAGGTCCAAGTGGTATCATGATTATTCAGTATCTGTGAA
AAGTCGAATCACCATCGACCCAGACACATCCAAGAACCAG
TTCTCCCTGCAGCTGAACTCTGTGACTCCCGAGGACACGGC
TGTTTATTATTGTGCAAGAGGGGCTGCTCCCTTTGACTACT
GGGGCCAGGGAACCCTGGTCACCGTGTCCTCAGGAGGGGG
CGGATCTGGCGGCGGAGGAAGCGGTGGGGGCGGCTCCGA
AATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTC
CAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAG
TGTTAGCAGCAACTACTTAGCCTGGTACCAACAGAAACCT
GGCCAGGCTCCCAGGGCCCTTATCTATGCTGCATCCAACA
GGGCCGCTGGCATCTCAGACAGGTTCAGTGGCAGTGGGTC
TGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCT
GAAGATTTTGCAGTGTATTTCTGTCAGCAGTATGGTAGCTC
ACCGCTCACTTTCGGCTGCGGGACTAAGGTGGAGATCAAA
CGA
(SEQ ID NO: 383)
AA
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIRQAP
DIQMTQSPSSVSASVGDRVTITCRASQGITRWLAWYQQKPGK
GKGLEWISYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMN
APKLLIYAASVLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATY
SLRAEDTAVYYCARDRNSHFDYWGQGTLVTVSSASTKGPSV
YCQQSNSFPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGT
FPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV
ASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD
HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK
STYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG
VDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI
EC
SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE
(SEQ ID NO: 386)
QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIA
VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ
GNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSQVQLQ
QSGPGLVKPSQTLSLTCAISGDSVSSSRTAWNWIRQSPSRCLE
WLGRTYYRSKWYHDYSVSVKSRITIDPDTSKNQFSLQLNSVT
PEDTAVYYCARGAAPFDYWGQGTLVTVSSGGGGSGGGGSG
GGGSEIVLTQSPGTLSLSPGERATLSCRASQSVSSNYLAWYQQ
KPGQAPRALIYAASNRAAGISDRFSGSGSGTDFTLTISRLEPED
FAVYFCQQYGSSPLTFGCGTKVEIKR
(SEQ ID NO: 385)
iSP: 577337
21-233_4H6_IgG_21-230_37A6_scFv
NA
CAGGTGCAGCTGGTCGAGTCTGGGGGAGGCTTGGTCAAGC
GACATTCAGATGACCCAGTCTCCATCTTCCGTGTCTGCATC
CTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTC
TGTAGGGGACAGAGTCACCATCACTTGTCGGGCGAGTCAG
ACCTTCAGTGACTACTACATGACCTGGATCAGGCAGGCTC
GGTATTACCAGGTGGTTAGCCTGGTATCAGCAGAAACCAG
CAGGGAAGGGGCTGGAGTGGATTTCATACATTAGTAGTAG
GGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCGTTTTG
TGGTAGTACCATCTACTACGCAGACTCTGTGAAGGGCCGA
CAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTG
TTCACCATCTCCAGGGACAACGCCAAGAACTCACTGTATCT
GGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGA
GCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTAT
AGATTTTGCAACTTACTATTGTCAACAGTCTAACAGTTTCC
TACTGTGCGAGAGATCGGAACTCCCACTTTGACTATTGGG
CTCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACG
GCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCCACCAA
GACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTG
GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCA
ATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG
CCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGA
CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
AGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAG
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
TGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAA
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGT
CACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGA
GAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGT
GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
TGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCG
(SEQ ID NO: 388)
TGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCT
CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACG
AAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAAGCCGTGCGAGGAGCA
GTACGGCAGCACGTACCGTTGCGTCAGCGTCCTCACCGTCC
TGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAA
GGTGTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACC
ATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGT
ACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCA
GGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCG
ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGA
ACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG
CTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCC
CTGTCTCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCC
AGGTGCAGTTGGTGGAGTCTGGGGGAGGCTTAGTCAAGCC
TGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGAATTCA
CCTTCAGTGACTACTACATGAGCTGGATCCGCCAGGCTCCA
GGGAAGTGCCTGGAGTGGGTTTCATATATTAGTCGAAGTG
GTGATACCATCTACTACGCAGACTCTGTGAAGGGCCGATT
CACCATCTCCAGGGACAACGCCAAGAACTCACTGTATCTG
CAAATGAATGGCCTGCGAGCCGAAGACACGGCCGTGTATT
ACTGTGCGAGAGACTTAGCAGCAGGTGCTACAGGGGGCCT
TGACTGCTGGGGCCAGGGAACCCTGGTCACCGTGTCCTCA
GGAGGGGGCGGATCTGGCGGCGGAGGAAGCGGTGGGGGC
GGCTCCTCCTATGAGCTGACTCAGCCACCCTCAGTGTCCGT
GTCCCCAGGACAGACAGCCAGCATCACCTGCTCTGGAGAA
AGGTTGGGAAATAAATATATTTGCTGGTATCAGCAGAAGC
CAGGCCAGTCCCCTGTTCTGGTCATCTATCAAGATTTCAAG
CGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTC
TGGGATCACAGCCACTCTGACCATCAGCGGGACCCAGGCT
ATGGATGAGGCTGACTATTACTGTCAGGCGTGGGACAGCA
GAACTGTGGTATTCGGCTGCGGGACCAAGCTGACCGTCCT
AGGT
(SEQ ID NO: 387)
AA
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIRQAP
DIQMTQSPSSVSASVGDRVTITCRASQGITRWLAWYQQKPGK
GKGLEWISYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMN
APKLLIYAASVLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATY
SLRAEDTAVYYCARDRNSHFDYWGQGTLVTVSSASTKGPSV
YCQQSNSFPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGT
FPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV
ASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD
HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK
STYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG
VDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI
EC
SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE
(SEQ ID NO: 390)
QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIA
VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ
GNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSQVQLV
ESGGGLVKPGGSLRLSCAASEFTFSDYYMSWIRQAPGKCLEW
VSYISRSGDTIYYADSVKGRFTISRDNAKNSLYLQMNGLRAE
DTAVYYCARDLAAGATGGLDCWGQGTLVTVSSGGGGSGGG
GSGGGGSSYELTQPPSVSVSPGQTASITCSGERLGNKYICWYQ
QKPGQSPVLVIYQDFKRPSGIPERFSGSNSGITATLTISGTQAM
DEADYYCQAWDSRTVVFGCGTKLTVLG
(SEQ ID NO: 389)
iPS: 577342
21-233_4H6_IgG_21-230_39C2_scFv
NA
CAGGTGCAGCTGGTCGAGTCTGGGGGAGGCTTGGTCAAGC
GACATTCAGATGACCCAGTCTCCATCTTCCGTGTCTGCATC
CTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTC
TGTAGGGGACAGAGTCACCATCACTTGTCGGGCGAGTCAG
ACCTTCAGTGACTACTACATGACCTGGATCAGGCAGGCTC
GGTATTACCAGGTGGTTAGCCTGGTATCAGCAGAAACCAG
CAGGGAAGGGGCTGGAGTGGATTTCATACATTAGTAGTAG
GGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCGTTTTG
TGGTAGTACCATCTACTACGCAGACTCTGTGAAGGGCCGA
CAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTG
TTCACCATCTCCAGGGACAACGCCAAGAACTCACTGTATCT
GGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGA
GCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTAT
AGATTTTGCAACTTACTATTGTCAACAGTCTAACAGTTTCC
TACTGTGCGAGAGATCGGAACTCCCACTTTGACTATTGGG
CTCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACG
GCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCCACCAA
GACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTG
GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCA
ATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG
CCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGA
CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
AGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAG
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
TGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAA
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGT
CACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGA
GAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGT
GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
TGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCG
(SEQ ID NO: 392)
TGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCT
CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACG
AAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAAGCCGTGCGAGGAGCA
GTACGGCAGCACGTACCGTTGCGTCAGCGTCCTCACCGTCC
TGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAA
GGTGTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACC
ATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGT
ACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCA
GGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCG
ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGA
ACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG
CTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCC
CTGTCTCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCC
AGGTGCAGCTGGTGCAGTCTGGGACTGAGGTGAAGAAGCC
TGGGGCCTCAGTGAAGGTGTCCTGCAAGGCTTCTGGATAC
ACCTTCCCCGGCTACTATATGCACTGGGTGCGACAGGCCCC
TGGACAGTGCCTTGAGTGGATGGGATGGATCAACCCTGAC
AGTGGTGGCACAAAGTATACACAGAAGTTTCAGGGCAGGG
TCACCTTGACCAGGGACGCGTCCGTCAGCACAGCCTACAT
TGACCTGAACAGGCTGAGATCTGACGACACGGCCGTATAT
TACTGTGCGAGAGAGAGGTGTAGGACTACCAACTGCTATT
TGGACTACTGGGGCCAGGGAAGTCTGGTCACCGTGTCCTC
AGGAGGGGGCGGATCTGGCGGCGGAGGAAGCGGTGGGGG
CGGCTCCCAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTG
GGAGCCCTGGACAGTCGATCACCATCTCCTGCACTGGAAC
CAGCAGTGATGTTGGGAATTATAACCTTGTCTCCTGGTACC
AACAGCACCCAGGCAAAGCCCCCAAACTCATGATTTATGA
GGTCAATAGGCGGCCCTCAGGGGTTTCTAATCGCTTCTCTG
GCTCCAAGTCTGGCAACACGGCCTCCCTGACAATCTCTGG
GCTCCAGGCTGAGGACGAGGCTGAATATTACTGCTGCTCA
TATGCAGGTAGAGACACTTTCGTGGTGTTCGGCTGCGGGA
CCAAGCTGACCGTCCTAGGT
(SEQ ID NO: 391)
AA
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIRQAP
DIQMTQSPSSVSASVGDRVTITCRASQGITRWLAWYQQKPGK
GKGLEWISYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMN
APKLLIYAASVLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATY
SLRAEDTAVYYCARDRNSHFDYWGQGTLVTVSSASTKGPSV
YCQQSNSFPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGT
FPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV
ASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD
HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK
STYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG
VDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI
EC
SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE
(SEQ ID NO: 394)
QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIA
VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ
GNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSQVQLV
QSGTEVKKPGASVKVSCKASGYTFPGYYMHWVRQAPGQCL
EWMGWINPDSGGTKYTQKFQGRVTLTRDASVSTAYIDLNRL
RSDDTAVYYCARERCRTTNCYLDYWGQGSLVTVSSGGGGSG
GGGSGGGGSQSALTQPASVSGSPGQSITISCTGTSSDVGNYNL
VSWYQQHPGKAPKLMIYEVNRRPSGVSNRFSGSKSGNTASLT
ISGLQAEDEAEYYCCSYAGRDTFVVFGCGTKLTVLG
(SEQ ID NO: 393)
iPS: 577347
21-233_6F4_IgG_21-230_4G7_scFv
NA
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCAAGC
GACATCCAGATGACCCAGTCTCCATCTTCCGTGTCTGCTTC
CTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTC
TGTCGGAGACAGAGTCACCATCACTTGTCGGGCGAGTCAG
ACCTTCAGTGACTACTACATGAGCTGGATCCGCCAGGCTCC
GATATTAGCAGGTGGTTAGCCTGGTATCAGCAGAAACCAG
AGGGAAGGGGCTGGAGTGGATTTCATACATTAGTAGCAGT
GGAAAGCCCCTAAGCTCCTGATTTCTGCTGCATCCAGATTG
GAAAGTATCATCTATTACGTAGACTCTGTGAAGGGCCGAT
CAAAGTGGAGTCCCATCAAGGTTCAGCGGCAGTGGATCTG
TCACCATCTCCAGGGACAACGCCAAGAACTCACTGTATCT
GGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGA
GCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTAT
AGATTTTGCAATTTACTATTGTCAACAGGCTAAAAGTTTTC
TACTGTGCGAGAGATGTTGGGAGCCACTTTGACTACTGGG
CTCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACG
GCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCCACCAA
GACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTG
GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCA
ATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG
CCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGA
CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
AGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAG
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
TGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAA
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGT
CACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGA
GAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGT
GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
TGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCG
(SEQ ID NO: 396)
TGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCT
CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACG
AAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAAGCCGTGCGAGGAGCA
GTACGGCAGCACGTACCGTTGCGTCAGCGTCCTCACCGTCC
TGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAA
GGTGTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACC
ATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGT
ACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCA
GGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCG
ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGA
ACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG
CTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCC
CTGTCTCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCC
AGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCC
TGGGGCCTCAGTGAAGGTGTCCTGCAAGGCTTCTGGATAC
ACCTTCGCCGGCTACTATATGCACTGGGTGCGACAGGCCC
CTGGACAATGCCTTGAGTGGATGGGATGGATCAACCCTGA
CAGTGGAGGCACAAACTTTGCACAGCAGTTTCAGGGCAGG
GTCACCATGACCAGGGATACGTCCATCAGCACAGCCTACA
TGGAGGTGAGCAGGCTGAGATCTGACGACACGGCCGTGTT
TTACTGTGCGAGAGAGAAGATCACTATGACTGGTATTTACT
TTGACTATTGGGGCCAGGGAACCCTGGTCACCGTGTCCTCA
GGAGGGGGCGGATCTGGCGGCGGAGGAAGCGGTGGGGGC
GGCTCCGACATCCAGATGACCCAGTCTCCATCCTCCCTGTC
TGCATCTGTAGGAGACATTCTCACCATCACTTGCCGGGCAA
GTCAGAACATTACCACCTATTTAAATTGGTATCAGCAGAA
ACCAGGGAAAGCCCCTAACCTCCTGATCTCTGCTGCATCCC
GTTTGCGAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGG
ATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAAC
CTGTAGATTTTACAACTTTCTACTGTCAACAGACTTTCACT
ACCCCGTGGACGTTCGGCTGCGGGACCAAGGTGGAGATCA
AACGA
(SEQ ID NO: 395)
AA
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPG
DIQMTQSPSSVSASVGDRVTITCRASQDISRWLAWYQQKPGK
KGLEWISYISSSESIIYYVDSVKGRFTISRDNAKNSLYLQMNSL
APKLLISAASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAIYY
RAEDTAVYYCARDVGSHFDYWGQGTLVTVSSASTKGPSVFP
CQQAKSFPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA
LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHT
SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDS
FPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVD
TYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGE
KKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR
C
TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQ
(SEQ ID NO: 398)
YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
KAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG
NVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSQVQLVQ
SGAEVKKPGASVKVSCKASGYTFAGYYMHWVRQAPGQCLE
WMGWINPDSGGTNFAQQFQGRVTMTRDTSISTAYMEVSRLR
SDDTAVFYCAREKITMTGIYFDYWGQGTLVTVSSGGGGSGG
GGSGGGGSDIQMTQSPSSLSASVGDILTITCRASQNITTYLNW
YQQKPGKAPNLLISAASRLRSGVPSRFSGSGSGTDFTLTISSLQ
PVDFTTFYCQQTFTTPWTFGCGTKVEIKR
(SEQ ID NO: 397)
iPS: 577351
21-233_6F4_IgG_21-230_29H10_scFv
NA
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCAAGC
GACATCCAGATGACCCAGTCTCCATCTTCCGTGTCTGCTTC
CTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTC
TGTCGGAGACAGAGTCACCATCACTTGTCGGGCGAGTCAG
ACCTTCAGTGACTACTACATGAGCTGGATCCGCCAGGCTCC
GATATTAGCAGGTGGTTAGCCTGGTATCAGCAGAAACCAG
AGGGAAGGGGCTGGAGTGGATTTCATACATTAGTAGCAGT
GGAAAGCCCCTAAGCTCCTGATTTCTGCTGCATCCAGATTG
GAAAGTATCATCTATTACGTAGACTCTGTGAAGGGCCGAT
CAAAGTGGAGTCCCATCAAGGTTCAGCGGCAGTGGATCTG
TCACCATCTCCAGGGACAACGCCAAGAACTCACTGTATCT
GGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGA
GCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTAT
AGATTTTGCAATTTACTATTGTCAACAGGCTAAAAGTTTTC
TACTGTGCGAGAGATGTTGGGAGCCACTTTGACTACTGGG
CTCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACG
GCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCCACCAA
GACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTG
GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCA
ATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG
CCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGA
CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
AGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAG
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
TGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAA
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGT
CACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGA
GAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGT
GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
TGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCG
(SEQ ID NO: 400)
TGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCT
CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACG
AAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAAGCCGTGCGAGGAGCA
GTACGGCAGCACGTACCGTTGCGTCAGCGTCCTCACCGTCC
TGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAA
GGTGTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACC
ATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGT
ACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCA
GGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCG
ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGA
ACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG
CTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCC
CTGTCTCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCC
AGGTGCAACTGGTGCAGTCTGGGGCTGAGGTGACGAAGCC
TGGGGCCTCAGTGAAGGTGTCCTGCAAGGCTTCTGGATAC
ACCTTCGCCGGCTACTATATGCACTGGGTGCGACAGGCCC
CTGGACAATGCCTTGAGTGGATGGGATGGATCAACCCTCA
CAGTGGTGGCACAAACTATGCACAGAAGTTTCAGGACAGG
GTCACCATGACCAGGGACACGTCCATCAACACAGCCTACA
TGGAACTGAGCAGGCTGAGATCTGACGACACGGCCGTGTA
TTACTGTGCGAGAGAACGTATTTCTATGGTTCGGGGAGTCG
GGCACAACTGGTTCGCCCCCTGGGGCCAGGGAACCCTGGT
CACCGTGTCCTCAGGAGGGGGCGGATCTGGCGGCGGAGGA
AGCGGTGGGGGCGGCTCCGACATCCAGATGACCCAGTCTC
CATCCTCACTGTCTGCATCTGTAGGAGACAGAGTCACCATC
ACCTGTCGGGCGAGTCAGGACATTAGCAATAATTTAGCCT
GGTTTCAGCAGAAACCAGGGAAACCCCCTAAGTCCCTGAT
GTATGCTGCATCCAGTTTGCACAGTGGAGTCCCATCAACGT
TCAGCGGCAGTGGATCTGGGACAGATTTCACTTTCACCATC
AGCAGCCTGCAGCCTGAAGATTTTGCAACTTATTACTGCCA
ACAGTATAATAGTTACCCTCTCACTTTCGGCTGCGGGACCA
AGGTGGAGATCAGACGA
(SEQ ID NO: 399)
AA
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPG
DIQMTQSPSSVSASVGDRVTITCRASQDISRWLAWYQQKPGK
KGLEWISYISSSESIIYYVDSVKGRFTISRDNAKNSLYLQMNSL
APKLLISAASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAIYY
RAEDTAVYYCARDVGSHFDYWGQGTLVTVSSASTKGPSVFP
CQQAKSFPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA
LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHT
SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDS
FPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVD
TYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGE
KKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR
C
TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQ
(SEQ ID NO: 402)
YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
KAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG
NVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSQVQLVQ
SGAEVTKPGASVKVSCKASGYTFAGYYMHWVRQAPGQCLE
WMGWINPHSGGTNYAQKFQDRVTMTRDTSINTAYMELSRLR
SDDTAVYYCARERISMVRGVGHNWFAPWGQGTLVTVSSGG
GGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQDIS
NNLAWFQQKPGKPPKSLMYAASSLHSGVPSTFSGSGSGTDFT
FTISSLQPEDFATYYCQQYNSYPLTFGCGTKVEIRR
(SEQ ID NO: 401)
iPS: 577355
21-233_6F4_IgG_21-230_30A12_scFv
NA
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCAAGC
GACATCCAGATGACCCAGTCTCCATCTTCCGTGTCTGCTTC
CTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTC
TGTCGGAGACAGAGTCACCATCACTTGTCGGGCGAGTCAG
ACCTTCAGTGACTACTACATGAGCTGGATCCGCCAGGCTCC
GATATTAGCAGGTGGTTAGCCTGGTATCAGCAGAAACCAG
AGGGAAGGGGCTGGAGTGGATTTCATACATTAGTAGCAGT
GGAAAGCCCCTAAGCTCCTGATTTCTGCTGCATCCAGATTG
GAAAGTATCATCTATTACGTAGACTCTGTGAAGGGCCGAT
CAAAGTGGAGTCCCATCAAGGTTCAGCGGCAGTGGATCTG
TCACCATCTCCAGGGACAACGCCAAGAACTCACTGTATCT
GGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGA
GCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTAT
AGATTTTGCAATTTACTATTGTCAACAGGCTAAAAGTTTTC
TACTGTGCGAGAGATGTTGGGAGCCACTTTGACTACTGGG
CTCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACG
GCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCCACCAA
GACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTG
GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCA
ATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG
CCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGA
CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
AGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAG
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
TGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAA
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGT
CACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGA
GAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGT
GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
TGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCG
(SEQ ID NO: 404)
TGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCT
CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACG
AAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAAGCCGTGCGAGGAGCA
GTACGGCAGCACGTACCGTTGCGTCAGCGTCCTCACCGTCC
TGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAA
GGTGTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACC
ATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGT
ACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCA
GGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCG
ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGA
ACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG
CTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCC
CTGTCTCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCG
AGGTGCAGCTGCTGGAGTCTGGGGGAGGCTTGGTACAGCC
TGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCA
CCTTTAGTAGAAATGCCATGAGTTGGGTCCGCCAGGCTCC
AGGGAAGTGCCTGGAGTGGGTGTCAGCTACTGGTGGTAGT
GGTATTAGCACATACTACGCAGACTCCGTGAAGGGCCGGT
TCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCT
GCAAATGAACAGTCTGAGAGCCGAGGACACGGCCGTATAT
TACTGTGCGAGAGGTTATAGCAACAGCTGGTGGTACTTTG
ACTACTGGGGCCAGGGAACCCTGGTCACCGTGTCCTCAGG
AGGGGGCGGATCTGGCGGCGGAGGAAGCGGTGGGGGCGG
CTCCCAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGA
GCCCTGGACAGTCGATCACCATCTCCTGCACTGGAACCAG
CAGTGATGTTGGGAATTATAACCTTGTCTCCTGGTACCAAC
AGCACCCAGGCAAAGCCCCCAAACTCATGATTTTTGAGGT
CAATCAGCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCT
CCAAGTCTGGCACCACGGCCTCCCTGACAATCTCTGGGCTC
CAGGCTGCGGACGAGGCTGATTATTTCTGCTGCTCATATAC
AACTAGTAGCACTTATGTGATCTTCGGCTGCGGGACCAAG
CTGACCGTCCTAGGT
(SEQ ID NO: 403)
AA
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPG
DIQMTQSPSSVSASVGDRVTITCRASQDISRWLAWQQKPGK
KGLEWISYISSSESIIYYVDSVKGRFTISRDNAKNSLYLQMNSL
APKLLISAASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAIYY
RAEDTAVYYCARDVGSHFDYWGQGTLVTVSSASTKGPSVFP
CQQAKSFPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA
LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHT
SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDS
FPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVD
TYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGE
KKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR
C
TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQ
(SEQ ID NO: 406)
YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
KAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG
NVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSEVQLLES
GGGLVQPGGSLRLSCAASGFTFSRNAMSWVRQAPGKCLEWV
SATGGSGISTYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
TAVYYCARGYSNSWWYFDYWGQGTLVTVSSGGGGSGGGGS
GGGGSQSALTQPASVSGSPGQSITISCTGTSSDVGNYNLVSWY
QQHPGKAPKLMIFEVNQRPSGVSNRFSGSKSGTTASLTISGLQ
AADEADYFCCSYTTSSTYVIFGCGTKLTVLG
(SEQ ID NO: 405)
iPS: 577359
21-233_6F4_IgG_21-230_33H6_scFv
NA
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCAAGC
GACATCCAGATGACCCAGTCTCCATCTTCCGTGTCTGCTTC
CTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTC
TGTCGGAGACAGAGTCACCATCACTTGTCGGGCGAGTCAG
ACCTTCAGTGACTACTACATGAGCTGGATCCGCCAGGCTCC
GATATTAGCAGGTGGTTAGCCTGGTATCAGCAGAAACCAG
AGGGAAGGGGCTGGAGTGGATTTCATACATTAGTAGCAGT
GGAAAGCCCCTAAGCTCCTGATTTCTGCTGCATCCAGATTG
GAAAGTATCATCTATTACGTAGACTCTGTGAAGGGCCGAT
CAAAGTGGAGTCCCATCAAGGTTCAGCGGCAGTGGATCTG
TCACCATCTCCAGGGACAACGCCAAGAACTCACTGTATCT
GGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGA
GCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTAT
AGATTTTGCAATTTACTATTGTCAACAGGCTAAAAGTTTTC
TACTGTGCGAGAGATGTTGGGAGCCACTTTGACTACTGGG
CTCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACG
GCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCCACCAA
GACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTG
GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCA
ATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG
CCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGA
CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
AGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAG
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
TGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAA
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGT
CACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGA
GAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGT
GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
TGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCG
(SEQ ID NO: 408)
TGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCT
CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACG
AAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAAGCCGTGCGAGGAGCA
GTACGGCAGCACGTACCGTTGCGTCAGCGTCCTCACCGTCC
TGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAA
GGTGTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACC
ATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGT
ACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCA
GGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCG
ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGA
ACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG
CTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCC
CTGTCTCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCC
AGGTGCAACTGGTGCAGTCTGGGGCTGAAGTGAAGAAGCC
TGGGGCCTCAGTGAAGGTGTCCTGCAAGGCTTCTGGATAC
ACCTTCCCCGGCTACTATATGTACTGGTTGCGACAGGCCCC
TGGACAATGCCTTGAGTGGATGGGATGGATCAACCCTGAC
AGTGGTGACACAAACTATGCACAGAAGTTTCAGGGCAGGG
TCACCATGACCAGGGACACGTCCATCAGCACAGCCTTTAT
GGAGCTGAGCAGGCTGAGATCAGACGACACGGCCGTGTAT
TACTGTGCGAGAGAGAAGCCCAGATATTTTGACTCCTTCTA
CTACTACCTTATGGACGTCTGGGGCCAAGGGACCACGGTC
ACCGTGTCCTCAGGAGGGGGCGGATCTGGCGGCGGAGGAA
GCGGTGGGGGCGGCTCCGACATCCAGATGACCCAGTCTCC
ATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCA
CTTGCCGGGCAGGTCAGAACATTAGCAGGCATTTAAATTG
GTATCAGCAGAATCCAGGGAAAGCCCCTAAGGTCCTGATC
CATCCTGCATCCAGTTTGCCAAGTGGGGTCCCGTCAAGGTT
CAGTGGCAGTGGATCTGGGACAGATTTCAGTCTTACCATC
AGCAGTCTGCAACCTGAAGATTTTGGAACTTACTTCTGTCA
ACAGAGTTACAGTACCCCTCCCACTTTCGGCTGCGGGACC
AAGGTGGAGCTCAAACGA
(SEQ ID NO: 407)
AA
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPG
DIQMTQSPSSVSASVGDRVTITCRASQDISRWLAWYQQKPGK
KGLEWISYISSSESIIYYVDSVKGRFTISRDNAKNSLYLQMNSL
APKLLISAASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAIYY
RAEDTAVYYCARDVGSHFDYWGQGTLVTVSSASTKGPSVFP
CQQAKSFPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA
LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHT
SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDS
FPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVD
TYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGE
KKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR
C
TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQ
(SEQ ID NO: 410)
YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
KAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG
NVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSQVQLVQ
SGAEVKKPGASVKVSCKASGYTFPGYYMYWLRQAPGQCLE
WMGWINPDSGDTNYAQKFQGRVTMTRDTSISTAFMELSRLR
SDDTAVYYCAREKPRYFDSFYYYLMDVWGQGTTVTVSSGG
GGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRAGQNIS
RHLNWYQQNPGKAPKVLIHPASSLPSGVPSRFSGSGSGTDFSL
TISSLQPEDFGTYFCQQSYSTPPTFGCGTKVELKR
(SEQ ID NO: 409)
iPS: 577363
21-233_6F4_IgG_21-230_33H9_scFv
NA
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCAAGC
GACATCCAGATGACCCAGTCTCCATCTTCCGTGTCTGCTTC
CTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTC
TGTCGGAGACAGAGTCACCATCACTTGTCGGGCGAGTCAG
ACCTTCAGTGACTACTACATGAGCTGGATCCGCCAGGCTCC
GATATTAGCAGGTGGTTAGCCTGGTATCAGCAGAAACCAG
AGGGAAGGGGCTGGAGTGGATTTCATACATTAGTAGCAGT
GGAAAGCCCCTAAGCTCCTGATTTCTGCTGCATCCAGATTG
GAAAGTATCATCTATTACGTAGACTCTGTGAAGGGCCGAT
CAAAGTGGAGTCCCATCAAGGTTCAGCGGCAGTGGATCTG
TCACCATCTCCAGGGACAACGCCAAGAACTCACTGTATCT
GGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGA
GCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTAT
AGATTTTGCAATTTACTATTGTCAACAGGCTAAAAGTTTTC
TACTGTGCGAGAGATGTTGGGAGCCACTTTGACTACTGGG
CTCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACG
GCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCCACCAA
GACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTG
GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCA
ATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG
CCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGA
CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
AGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAG
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
TGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAA
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGT
CACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGA
GAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGT
GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
TGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCG
(SEQ ID NO: 412)
TGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCT
CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACG
AAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAAGCCGTGCGAGGAGCA
GTACGGCAGCACGTACCGTTGCGTCAGCGTCCTCACCGTCC
TGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAA
GGTGTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACC
ATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGT
ACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCA
GGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCG
ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGA
ACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG
CTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCC
CTGTCTCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCC
AGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCA
CCTTCAGTAGCCATGGCATGCACTGGGTCCGCCAACCTCCA
GGCAAGTGCCTGGAGTGGGTGGCAGTTATCTGGTATGATG
GAAGTAATGAATACTATGGAGACTCCGTGAAGGGCCGATT
CACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTG
CAAATGAACAGCCTGAGAGTCGAGGACACGGCTGTGTATT
ACTGTACGAGAGGGGGGGGCCACTGGAACTACGAGGGCC
ACTACTATGGTATGGACGTCTGGGGCCAAGGGACCACGGT
CACCGTGTCCTCAGGAGGGGGCGGATCTGGCGGCGGAGGA
AGCGGTGGGGGCGGCTCCCAGGCTGTGCCGACTCAGCCCT
CTTCCCTCTCTGCATCTCCTGGAGCATCAGCCAGTCTCACC
TGCACCTTACGCAGTGGCATCAATGTTGGTTCCTCCAGGAT
CTATTGGTACCAGCAGAAGCCAGGGAGTCCTCCCCAGTTT
CTCCTGAGGTACACATCAGACTCAGATAAATTGCAGGGCT
CTGGAGTCCCCAGCCGCTTCTCTGGATCCAAAGATGCTTCG
GCCAATGCAGGACTTTTACTCATCTCTGGGCTCCAGTCTGA
GGATGAGGCTGACTATTACTGTATGATTTGGCACAGCAGC
GCTGTGGTATTCGGCTGCGGGACCAAACTGACCGTCCTAG
GT
(SEQ ID NO: 411)
AA
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPG
DIQMTQSPSSVSASVGDRVTITCRASQDISRWLAWYQQKPGK
KGLEWISYISSSESIIYYVDSVKGRFTISRDNAKNSLYLQMNSL
APKLLISAASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAIYY
RAEDTAVYYCARDVGSHFDYWGQGTLVTVSSASTKGPSVFP
CQQAKSFPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA
LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHT
SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDS
FPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVD
TYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGE
KKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR
C
TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQ
(SEQ ID NO: 414)
YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
KAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG
NVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSQVQLVE
SGGGVVQPGRSLRLSCAASGFTFSSHGMHWVRQPPGKCLEW
VAVIWYDGSNEYYGDSVKGRFTISRDNSKNTLYLQMNSLRV
EDTAVYYCTRGGGHWNYEGHYYGMDVWGQGTTVTVSSGG
GGSGGGGSGGGGSQAVPTQPSSLSASPGASASLTCTLRSGINV
GSSRIYWYQQKPGSPPQFLLRYTSDSDKLQGSGVPSRFSGSKD
ASANAGLLLISGLQSEDEADYYCMIWHSSAVVFGCGTKLTVL
G
(SEQ ID NO: 413)
iPS: 577367
21-233_6F4_IgG_21-230_35F11_scFv
NA
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCAAGC
GACATCCAGATGACCCAGTCTCCATCTTCCGTGTCTGCTTC
CTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTC
TGTCGGAGACAGAGTCACCATCACTTGTCGGGCGAGTCAG
ACCTTCAGTGACTACTACATGAGCTGGATCCGCCAGGCTCC
GATATTAGCAGGTGGTTAGCCTGGTATCAGCAGAAACCAG
AGGGAAGGGGCTGGAGTGGATTTCATACATTAGTAGCAGT
GGAAAGCCCCTAAGCTCCTGATTTCTGCTGCATCCAGATTG
GAAAGTATCATCTATTACGTAGACTCTGTGAAGGGCCGAT
CAAAGTGGAGTCCCATCAAGGTTCAGCGGCAGTGGATCTG
TCACCATCTCCAGGGACAACGCCAAGAACTCACTGTATCT
GGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGA
GCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTAT
AGATTTTGCAATTTACTATTGTCAACAGGCTAAAAGTTTTC
TACTGTGCGAGAGATGTTGGGAGCCACTTTGACTACTGGG
CTCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACG
GCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCCACCAA
GACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTG
GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCA
ATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG
CCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGA
CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
AGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAG
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
TGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAA
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGT
CACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGA
GAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGT
GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
TGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCG
(SEQ ID NO: 416)
TGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCT
CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACG
AAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAAGCCGTGCGAGGAGCA
GTACGGCAGCACGTACCGTTGCGTCAGCGTCCTCACCGTCC
TGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAA
GGTGTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACC
ATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGT
ACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCA
GGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCG
ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGA
ACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG
CTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCC
CTGTCTCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCC
AGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCC
TGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCA
CCCTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCC
AGGCAAGTGCCTGGAGTGGGTGGCAGTTATCTGGTATGAT
GGAAGTAATAAATACTATGCAGACTCCGTGAAGGGCCGAG
TCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCT
GCAAATGAATAGCCTGAGAGCCGAGGACACGGCTGTGTAT
TACTGTACGAGAGATGGCCGGAACTACGTCTACTTTGACA
ACTGGGGCCAGGGAACCCTGGTCACCGTGTCCTCAGGAGG
GGGCGGATCTGGCGGCGGAGGAAGCGGTGGGGGCGGCTC
CCAGTCTGCCCTGACTCAGCCTCGCTCAGTGTCCGGGAGCC
CTGGACAGTCAGTCACCATCTCCTGCACTGGAACCAGCAG
TGATGTTGGTGGTTATATCTTTGTCTCCTGGTACCAACAAC
ACCCAGGCAAAGCCCCCAAACTCATGATTTATGATGTCAG
TAAGCGGCCCTCTGGGGTCCCTGATCGCTTCTCTGGCTCCA
AGTCTGTCAACACGGCCTCCCTGACCATCTCTGGGCTCCAG
GCTGAGGATGAGACTGATTATTACTGCTGCTCATATGCAG
GCAACTACACTTATGTCTTCGGATGCGGGACCAAGGTCAC
CGTCCTAGGT
(SEQ ID NO: 415)
AA
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPG
DIQMTQSPSSVSASVGDRVTITCRASQDISRWLAWYQQKPGK
KGLEWISYISSSESIIYYVDSVKGRFTISRDNAKNSLYLQMNSL
APKLLISAASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAIYY
RAEDTAVYYCARDVGSHFDYWGQGTLVTVSSASTKGPSVFP
CQQAKSFPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA
LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHT
SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDS
FPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVD
TYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGE
KKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR
C
TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQ
(SEQ ID NO: 418)
YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
KAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG
NVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSQVQLVE
SGGGVVQPGRSLRLSCAASGFTLSSYGMHWVRQAPGKCLEW
VAVIWYDGSNKYYADSVKGRVTISRDNSKNTLYLQMNSLRA
EDTAVYYCTRDGRNYVYFDNWGQGTLVTVSSGGGGSGGGG
SGGGGSQSALTQPRSVSGSPGQSVTISCTGTSSDVGGYIFVSW
YQQHPGKAPKLMIYDVSKRPSGVPDRFSGSKSVNTASLTISGL
QAEDETDYYCCSYAGNYTYVFGCGTKVTVLG
(SEQ ID NO: 417)
iPS: 577371
21-233_6F4_IgG_21-230_36F3_scFv
NA
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCAAGC
GACATCCAGATGACCCAGTCTCCATCTTCCGTGTCTGCTTC
CTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTC
TGTCGGAGACAGAGTCACCATCACTTGTCGGGCGAGTCAG
ACCTTCAGTGACTACTACATGAGCTGGATCCGCCAGGCTCC
GATATTAGCAGGTGGTTAGCCTGGTATCAGCAGAAACCAG
AGGGAAGGGGCTGGAGTGGATTTCATACATTAGTAGCAGT
GGAAAGCCCCTAAGCTCCTGATTTCTGCTGCATCCAGATTG
GAAAGTATCATCTATTACGTAGACTCTGTGAAGGGCCGAT
CAAAGTGGAGTCCCATCAAGGTTCAGCGGCAGTGGATCTG
TCACCATCTCCAGGGACAACGCCAAGAACTCACTGTATCT
GGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGA
GCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTAT
AGATTTTGCAATTTACTATTGTCAACAGGCTAAAAGTTTTC
TACTGTGCGAGAGATGTTGGGAGCCACTTTGACTACTGGG
CTCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACG
GCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCCACCAA
GACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTG
GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCA
ATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG
CCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGA
CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
AGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAG
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
TGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAA
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGT
CACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGA
GAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGT
GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
TGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCG
(SEQ ID NO: 420)
TGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCT
CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACG
AAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAAGCCGTGCGAGGAGCA
GTACGGCAGCACGTACCGTTGCGTCAGCGTCCTCACCGTCC
TGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAA
GGTGTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACC
ATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGT
ACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCA
GGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCG
ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGA
ACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG
CTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCC
CTGTCTCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCC
AGGTACAGCTGCAACAGTCAGGTCCAGGACTGGTGAAGCC
CTCGCAGACCCTCTCACTCACCTGTGCCATCTCCGGGGACA
GTGTCTCTAGCAGCCGTACTGCTTGGAACTGGATCAGGCA
GTCCCCATCGAGATGCCTTGAGTGGCTGGGAAGGACATAC
TACAGGTCCAAGTGGTATCATGATTATTCAGTATCTGTGAA
AAGTCGAATCACCATCGACCCAGACACATCCAAGAACCAG
TTCTCCCTGCAGCTGAACTCTGTGACTCCCGAGGACACGGC
TGTTTATTATTGTGCAAGAGGGGCTGCTCCCTTTGACTACT
GGGGCCAGGGAACCCTGGTCACCGTGTCCTCAGGAGGGGG
CGGATCTGGCGGCGGAGGAAGCGGTGGGGGCGGCTCCGA
AATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTC
CAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAG
TGTTAGCAGCAACTACTTAGCCTGGTACCAACAGAAACCT
GGCCAGGCTCCCAGGGCCCTTATCTATGCTGCATCCAACA
GGGCCGCTGGCATCTCAGACAGGTTCAGTGGCAGTGGGTC
TGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCT
GAAGATTTTGCAGTGTATTTCTGTCAGCAGTATGGTAGCTC
ACCGCTCACTTTCGGCTGCGGGACTAAGGTGGAGATCAAA
CGA
(SEQ ID NO: 419)
AA
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPG
DIQMTQSPSSVSASVGDRVTITCRASQDISRWLAWYQQKPGK
KGLEWISYISSSESIIYYVDSVKGRFTISRDNAKNSLYLQMNSL
APKLLISAASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAIYY
RAEDTAVYYCARDVGSHFDYWGQGTLVTVSSASTKGPSVFP
CQQAKSFPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA
LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHT
SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDS
FPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVD
TYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGE
KKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR
C
TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQ
(SEQ ID NO: 422)
YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
KAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG
NVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSQVQLQQ
SGPGLVKPSQTLSLTCAISGDSVSSSRTAWNWIRQSPSRCLEW
LGRTYYRSKWYHDYSVSVKSRITIDPDTSKNQFSLQLNSVTPE
DTAVYYCARGAAPFDYWGQGTLVTVSSGGGGSGGGGSGGG
GSEIVLTQSPGTLSLSPGERATLSCRASQSVSSNYLAWYQQKP
GQAPRALIYAASNRAAGISDRFSGSGSGTDFTLTISRLEPEDFA
VYFCQQYGSSPLTFGCGTKVEIKR
(SEQ ID NO: 421)
iPS: 577375
21-233_6F4_IgG_21-230_37A6_scFv
NA
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCAAGC
GACATCCAGATGACCCAGTCTCCATCTTCCGTGTCTGCTTC
CTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTC
TGTCGGAGACAGAGTCACCATCACTTGTCGGGCGAGTCAG
ACCTTCAGTGACTACTACATGAGCTGGATCCGCCAGGCTCC
GATATTAGCAGGTGGTTAGCCTGGTATCAGCAGAAACCAG
AGGGAAGGGGCTGGAGTGGATTTCATACATTAGTAGCAGT
GGAAAGCCCCTAAGCTCCTGATTTCTGCTGCATCCAGATTG
GAAAGTATCATCTATTACGTAGACTCTGTGAAGGGCCGAT
CAAAGTGGAGTCCCATCAAGGTTCAGCGGCAGTGGATCTG
TCACCATCTCCAGGGACAACGCCAAGAACTCACTGTATCT
GGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGA
GCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTAT
AGATTTTGCAATTTACTATTGTCAACAGGCTAAAAGTTTTC
TACTGTGCGAGAGATGTTGGGAGCCACTTTGACTACTGGG
CTCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACG
GCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCCACCAA
GACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTG
GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCA
ATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG
CCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGA
CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
AGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAG
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
TGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAA
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGT
CACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGA
GAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGT
GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
TGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCG
(SEQ ID NO: 424)
TGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCT
CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACG
AAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAAGCCGTGCGAGGAGCA
GTACGGCAGCACGTACCGTTGCGTCAGCGTCCTCACCGTCC
TGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAA
GGTGTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACC
ATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGT
ACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCA
GGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCG
ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGA
ACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG
CTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCC
CTGTCTCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCC
AGGTGCAGTTGGTGGAGTCTGGGGGAGGCTTAGTCAAGCC
TGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGAATTCA
CCTTCAGTGACTACTACATGAGCTGGATCCGCCAGGCTCCA
GGGAAGTGCCTGGAGTGGGTTTCATATATTAGTCGAAGTG
GTGATACCATCTACTACGCAGACTCTGTGAAGGGCCGATT
CACCATCTCCAGGGACAACGCCAAGAACTCACTGTATCTG
CAAATGAATGGCCTGCGAGCCGAAGACACGGCCGTGTATT
ACTGTGCGAGAGACTTAGCAGCAGGTGCTACAGGGGGCCT
TGACTGCTGGGGCCAGGGAACCCTGGTCACCGTGTCCTCA
GGAGGGGGCGGATCTGGCGGCGGAGGAAGCGGTGGGGGC
GGCTCCTCCTATGAGCTGACTCAGCCACCCTCAGTGTCCGT
GTCCCCAGGACAGACAGCCAGCATCACCTGCTCTGGAGAA
AGGTTGGGAAATAAATATATTTGCTGGTATCAGCAGAAGC
CAGGCCAGTCCCCTGTTCTGGTCATCTATCAAGATTTCAAG
CGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTC
TGGGATCACAGCCACTCTGACCATCAGCGGGACCCAGGCT
ATGGATGAGGCTGACTATTACTGTCAGGCGTGGGACAGCA
GAACTGTGGTATTCGGCTGCGGGACCAAGCTGACCGTCCT
AGGT
(SEQ ID NO: 423)
AA
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPG
DIQMTQSPSSVSASVGDRVTITCRASQDISWLAWYQQKPGK
KGLEWISYISSSESIIYYVDSVKGRFTISRDNAKNSLYLQMNSL
APKLLISAASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAIYY
RAEDTAVYYCARDVGSHFDYWGQGTLVTVSSASTKGPSVFP
CQQAKSFPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA
LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHT
SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDS
FPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVD
TYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGE
KKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR
C
TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQ
(SEQ ID NO: 426)
YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
KAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG
NVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSQVQLVE
SGGGLVKPGGSLRLSCAASEFTFSDYYMSWIRQAPGKCLEW
VSYISRSGDTIYYADSVKGRFTISRDNAKNSLYLQMNGLRAE
DTAVYYCARDLAAGATGGLDCWGQGTLVTVSSGGGGSGGG
GSGGGGSSYELTQPPSVSVSPGQTASITCSGERLGNKYICWYQ
QKPGQSPVLVIYQDFKRPSGIPERFSGSNSGITATLTISGTQAM
DEADYYCQAWDSRTVVFGCGTKLTVLG
(SEQ ID NO: 425)
iPS: 577379
21-233_6F4_IgG_21-230_39C2_scFv
NA
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCAAGC
GACATCCAGATGACCCAGTCTCCATCTTCCGTGTCTGCTTC
CTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTC
TGTCGGAGACAGAGTCACCATCACTTGTCGGGCGAGTCAG
ACCTTCAGTGACTACTACATGAGCTGGATCCGCCAGGCTCC
GATATTAGCAGGTGGTTAGCCTGGTATCAGCAGAAACCAG
AGGGAAGGGGCTGGAGTGGATTTCATACATTAGTAGCAGT
GGAAAGCCCCTAAGCTCCTGATTTCTGCTGCATCCAGATTG
GAAAGTATCATCTATTACGTAGACTCTGTGAAGGGCCGAT
CAAAGTGGAGTCCCATCAAGGTTCAGCGGCAGTGGATCTG
TCACCATCTCCAGGGACAACGCCAAGAACTCACTGTATCT
GGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGA
GCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTAT
AGATTTTGCAATTTACTATTGTCAACAGGCTAAAAGTTTTC
TACTGTGCGAGAGATGTTGGGAGCCACTTTGACTACTGGG
CTCGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACG
GCCAGGGAACCCTGGTCACCGTGTCCTCAGCCTCCACCAA
GACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTG
GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCA
ATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG
CCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA
CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGA
CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC
AGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAG
GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA
TGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC
AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAA
CCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGT
CACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGA
GAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGT
GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
TGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCG
(SEQ ID NO: 428)
TGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCT
CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACG
AAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAAGCCGTGCGAGGAGCA
GTACGGCAGCACGTACCGTTGCGTCAGCGTCCTCACCGTCC
TGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAA
GGTGTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACC
ATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGT
ACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCA
GGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCG
ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGA
ACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG
CTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCC
CTGTCTCCGGGTGGTGGCGGATCGGGAGGTGGCGGATCCC
AGGTGCAGCTGGTGCAGTCTGGGACTGAGGTGAAGAAGCC
TGGGGCCTCAGTGAAGGTGTCCTGCAAGGCTTCTGGATAC
ACCTTCCCCGGCTACTATATGCACTGGGTGCGACAGGCCCC
TGGACAGTGCCTTGAGTGGATGGGATGGATCAACCCTGAC
AGTGGTGGCACAAAGTATACACAGAAGTTTCAGGGCAGGG
TCACCTTGACCAGGGACGCGTCCGTCAGCACAGCCTACAT
TGACCTGAACAGGCTGAGATCTGACGACACGGCCGTATAT
TACTGTGCGAGAGAGAGGTGTAGGACTACCAACTGCTATT
TGGACTACTGGGGCCAGGGAAGTCTGGTCACCGTGTCCTC
AGGAGGGGGCGGATCTGGCGGCGGAGGAAGCGGTGGGGG
CGGCTCCCAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTG
GGAGCCCTGGACAGTCGATCACCATCTCCTGCACTGGAAC
CAGCAGTGATGTTGGGAATTATAACCTTGTCTCCTGGTACC
AACAGCACCCAGGCAAAGCCCCCAAACTCATGATTTATGA
GGTCAATAGGCGGCCCTCAGGGGTTTCTAATCGCTTCTCTG
GCTCCAAGTCTGGCAACACGGCCTCCCTGACAATCTCTGG
GCTCCAGGCTGAGGACGAGGCTGAATATTACTGCTGCTCA
TATGCAGGTAGAGACACTTTCGTGGTGTTCGGCTGCGGGA
CCAAGCTGACCGTCCTAGGT
(SEQ ID NO: 427)
AA
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPG
DIQMTQSPSSVSASVGDRVTITCRASQDISRWLAWYQQKPGK
KGLEWISYISSSESIIYYVDSVKGRFTISRDNAKNSLYLQMNSL
APKLLISAASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAIYY
RAEDTAVYYCARDVGSHFDYWGQGTLVTVSSASTKGPSVFP
CQQAKSFPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA
LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHT
SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDS
FPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVD
TYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGE
KKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR
C
TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQ
(SEQ ID NO: 430)
YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
KAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV
EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG
NVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSQVQLVQ
SGTEVKKPGASVKVSCKASGYTFPGYYMHWVRQAPGQCLE
WMGWINPDSGGTKYTQKFQGRVTLTRDASVSTAYIDLNRLR
SDDTAVYYCARERCRTTNCYLDYWGQGSLVTVSSGGGGSG
GGGSGGGGSQSALTQPASVSGSPGQSITISCTGTSSDVGNYNL
VSWYQQHPGKAPKLMIYEVNRRPSGVSNRFSGSKSGNTASLT
ISGLQAEDEAEYYCCSYAGRDTFVVFGCGTKLTVLG
(SEQ ID NO: 429)
TABLE 27A
CD-40-MSLN IgG-Fab
iPS #
Ab
Description
Type
LC_E
LC_K
IgFab_HCv1
iPS:
21-
[hu anti-<hu CD40>
NA
GACATCCAGATGACCCAGTCTCCATC
CAGTCAGTGTTGACGCAGCCGCCC
CAGGTGCAGCTGGTGCAGTCTGGG
576257
230_4G7_IgG_21-
21-230_4G7VH]::
CTCCCTGTCTGCATCTGTAGGAGACA
TCAGTGTCTGGGGCCCCAGGGCAG
GCTGAGGTGAAGAAGCCTGGGGCC
233_4G12__Fab
huIgG1zSEFL2*
TTCTCACCATCACTTGCCGGGCAAGT
AGGGTCACCATCTCCTGCACTGGG
TCAGTGAAGGTGTCCTGCAAGGCT
GK-K::(G4S)2::[hu
CAGAACATTACCACCTATTTAAATTG
AGCAGCTCCAACATCGGGGCAGGT
TCTGGATACACCTTCGCCGGCTACT
anti-<hu
GTATCAGCAGAAACCAGGGAAAGCC
TATGATGTTCACTGGTACCAGCAG
ATATGCACTGGGTGCGACAGGCCC
Mesothelin>
CCTAACCTCCTGATCTCTGCTGCATC
GTTCCAGGAACAGCCCCCAAACTC
CTGGACAAGGGCTTGAGTGGATGG
4G12VH]::huIgG1z-
CCGTTTGCGAAGTGGGGTCCCATCAA
CTCATCTATGGTAACAGCAAGCGG
GATGGATCAACCCTGACAGTGGAG
CH1-E::EPKSC +
GGTTCAGTGGCAGTGGATCTGGGAC
CCCTCAGGGGTCCCTGACCGATTCT
GCACAAACTTTGCACAGCAGTTTC
[anti-<hu CD40>
AGATTTCACTCTCACCATCAGCAGTC
CTGGCTCCAAGTCTGGCACCTCAGC
AGGGCAGGGTCACCATGACCAGGG
21-230_4G7VL]::
TGCAACCTGTAGATTTTACAACTTTC
CTCCCTGGCCATCACTGGGCTCCAG
ATACGTCCATCAGCACAGCCTACA
huKLC-S176E +
TACTGTCAACAGACTTTCACTACCCC
GCTGAGGATGAGGCTGATTATTAC
TGGAGGTGAGCAGGCTGAGATCTG
[anti-<hu
GTGGACGTTCGGCCAAGGGACCAAG
TGCCAGTCCTATGACAGCAGCCTG
ACGACACGGCCGTGTTTTACTGTGC
Mesothelin>
GTGGAGATCAAACGAACGGTGGCTG
GGTGGTTGGGTGTTCGGCGGAGGG
GAGAGAGAAGATCACTATGACTGG
4G12VL]::huLLC2-
CACCATCTGTCTTCATCTTCCCGCCAT
ACCAAGCTGACCGTCCTACAGCCC
TATTTACTTTGACTATTGGGGCCAG
K(IgG-K(IgG-Fab);
CTGATGAGCAGTTGAAATCTGGAACT
AAGGCTGCACCCTCGGTCACTCTGT
GGAACCCTGGTCACCGTGTCCTCA
LMRID: SS-30855
GCCTCTGTTGTGTGCCTGCTGAATAA
TCCCGCCCTCCTCTGAGGAGCTTCA
GCCTCCACCAAGGGCCCATCGGTC
CTTCTATCCCAGAGAGGCCAAAGTAC
AGCCAACAAGGCCACACTGGTGTG
TTCCCCCTGGCACCCTCCTCCAAGA
AGTGGAAGGTGGATAACGCCCTCCA
TCTCATCAGTGACTTCTACCCGGGA
GCACCTCTGGGGGCACAGCGGCCC
ATCGGGTAACTCCCAGGAGAGTGTC
GCCGTGACAGTGGCCTGGAAGGCA
TGGGCTGCCTGGTCAAGGACTACTT
ACAGAGCAGGACAGCAAGGACAGCA
GATAGCAGCCCCGTCAAGGCGGGA
CCCCGAACCGGTGACGGTGTCGTG
CCTACAGCCTCGAAAGCACCCTGACG
GTGGAAACCACCACACCCTCCAAA
GAACTCAGGCGCCCTGACCAGCGG
CTGAGCAAAGCAGACTACGAGAAAC
CAAAGCAACAACAAGTACGCGGCC
CGTGCACACCTTCCCGGCTGTCCTA
ACAAAGTCTACGCCTGCGAAGTCACC
AAGAGCTATCTGAGCCTGACGCCT
CAGTCCTCAGGACTCTACTCCCTCA
CATCAGGGCCTGAGCTCGCCCGTCAC
GAGCAGTGGAAGTCCCACAGAAGC
AGAGCGTGGTGACCGTGCCCTCCA
AAAGAGCTTCAACAGGGGAGAGTGT
TACAGCTGCCAGGTCACGCATGAA
GCAGCTTGGGCACCCAGACCTACA
(SEQ ID NO: 431)
GGGAGCACCGTGGAGAAGACAGTG
TCTGCAACGTGAATCACAAGCCCA
GCCCCTACAGAATGTTCA
GCAACACCAAGGTGGACAAGAAAG
(SEQ ID NO: 432)
TTGAGCCCAAATCTTGTGACAAAA
CTCACACATGCCCACCGTGCCCAG
CACCTGAACTCCTGGGGGGACCGT
CAGTCTTCCTCTTCCCCCCAAAACC
CAAGGACACCCTCATGATCTCCCG
GACCCCTGAGGTCACATGCGTGGT
GGTGGACGTGAGCCACGAAGACCC
TGAGGTCAAGTTCAACTGGTACGT
GGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGTGCGAGGAGCA
GTACGGCAGCACGTACCGTTGCGT
CAGCGTCCTCACCGTCCTGCACCAG
GACTGGCTGAATGGCAAGGAGTAC
AAGTGCAAGGTGTCCAACAAAGCC
CTCCCAGCCCCCATCGAGAAAACC
ATCTCCAAAGCCAAAGGGCAGCCC
CGAGAACCACAGGTGTACACCCTG
CCCCCATCCCGGGAGGAGATGACC
AAGAACCAGGTCAGCCTGACCTGC
CTGGTCAAAGGCTTCTATCCCAGCG
ACATCGCCGTGGAGTGGGAGAGCA
ATGGGCAGCCGGAGAACAACTACA
AGACCACGCCTCCCGTGCTGGACT
CCGACGGCTCCTTCTTCCTCTATAG
CAAGCTCACCGTGGACAAGAGCAG
GTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTG
CACAACCACTACACGCAGAAGAGC
CTCTCCCTGTCTCCGGGTGGTGGCG
GATCGGGAGGTGGCGGATCCCAGG
TGCAGCTGCAGGAGTCGGGCCCAG
GACTGGTGAAGCCTTCGGAAACCC
TGTCCCTCACCTGCACTGTCTCTGG
TGGCTCCATCAGCAGTAGTAGTTAC
TACTGGGGCTGGATCAGGCAGCCC
CCAGGGAAGGGGCTGGAGTGGATT
GGGAGTATCTATTATAGTGGGATC
ACCAACTACAACCCGTCCCTCAAG
AGTCGAGTCACCATCTCCGTAGAC
ACGTCCAAGAACCAGTTCTCCCTG
AAGCTGAGTTCTGTGACCGCCGCA
GACACGGCCGTGTATTACTGTGCG
AGATCCAGTAACTACGATGCTTTTG
ATATCTGGGGCCAAGGGACAATGG
TCACCGTGTCCTCAGCAAGCACGA
AGGGGCCGTCCGTATTTCCGCTTGC
GCCCTCGTCGAAGTCAACTTCGGG
AGGGACCGCGGCACTTGGCTGTCT
TGTCAAAGATTACTTCCCTGAGCCA
GTGACAGTCAGCTGGAATTCCGGT
GCCCTCACGTCAGGAGTACATACA
TTCCCTGCGGTATTGCAGTCCTCCG
GACTCTACTCCCTGGAGTCGGTGGT
AACGGTGCCCAGCTCCAGCTTGGG
GACCCAGACGTACATTTGTAACGT
GAATCACAAACCAAGCAATACTAA
GGTAGATAAGAAAGTAGAACCGAA
GAGCTGC
(SEQ ID NO: 433)
AA
DIQMTQSPSSLSASVGDILTITCRASQNI
QSVLTQPPSVSGAPGQRVTISCTGSSS
QVQLVQSGAEVKKPGASVKVSCKAS
TTYLNWYQQKPGKAPNLLISAASRLRS
NIGAGYDVHWYQQVPGTAPKLLIYG
GYTFAGYYMHWVRQAPGQGLEWM
GVPSRFSGSGSGTDFTLTISSLQPVDFT
NSKRPSGVPDRFSGSKSGTSASLAIT
GWINPDSGGTNFAQQFQGRVTMTRD
TFYCQQTFTTPWTFGQGTKVEIKRTVA
GLQAEDEADYYCQSYDSSLGGWVF
TSISTAYMEVSRLRSDDTAVFYCARE
APSVFIFPPSDEQLKSGTASVVCLLNNF
GGGTKLTVLQPKAAPSVTLFPPSSEE
KITMTGIYFDYWGQGTLVTVSSAST
YPREAKVQWKVDNALQSGNSQESVTE
LQANKATLVCLISDFYPGAVTVAWK
KGPSVFPLAPSSKSTSGGTAALGCLV
QDSKDSTYSLESTLTLSKADYEKHKVY
ADSSPVKAGVETTTPSKQSNNKYAA
KDYFPEPVTVSWNSGALTSGVHTFP
ACEVTHQGLSSPVTKSFNRGEC
KSYLSLTPEQWKSHRSYSCQVTHEG
AVLQSSGLYSLKSVVTVPSSSLGTQT
(SEQ ID NO: 434)
STVEKTVAPTECS
YICNVNHKPSNTKVDKKVEPKSCDK
(SEQ ID NO: 435)
THTCPPCPAPELLGGPSVFLFPPKPKD
TLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPCEEQYGST
YRCVSVLTVLHQDWLNGKEYKCKV
SNKALPAPIEKTISKAKGQPREPQVY
TLPPSREEMTKNQVSLTCLVKGFYPS
DIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGS
GGGGSQVQLQESGPGLVKPSETLSLT
CTVSGGSISSSSYYWGWIRQPPGKGL
EWIGSIYYSGITNYNPSLKSRVTISVD
TSKNQFSLKLSSVTAADTAVYYCAR
SSNYDAFDIWGQGTMVTVSSASTKG
PSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAV
LQSSGLYSLESVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 436)
iPS:
21-
[hu anti-<hu CD40>
NA
GACATCCAGATGACCCAGTCTCCATC
GACATTCAGATGACCCAGTCTCCAT
CAGGTGCAGCTGGTGCAGTCTGGG
576265
230_4G7_IgG_21-
21-230_4G7VH]::
CTCCCTGTCTGCATCTGTAGGAGACA
CTTCCGTGTCTGCATCTGTAGGGGA
GCTGAGGTGAAGAAGCCTGGGGCC
233_4H6__Fab
huIgG1zSEFL2*
TTCTCACCATCACTTGCCGGGCAAGT
CAGAGTCACCATCACTTGTCGGGC
TCAGTGAAGGTGTCCTGCAAGGCT
GK-K::(G4S)2::
CAGAACATTACCACCTATTTAAATTG
GAGTCAGGGTATTACCAGGTGGTT
TCTGGATACACCTTCGCCGGCTACT
[hu anti-
GTATCAGCAGAAACCAGGGAAAGCC
AGCCTGGTATCAGCAGAAACCAGG
ATATGCACTGGGTGCGACAGGCCC
<hu Mesothelin>
CCTAACCTCCTGATCTCTGCTGCATC
GAAAGCCCCTAAGCTCCTGATCTAT
CTGGACAAGGGCTTGAGTGGATGG
4H6VH]::huIgG1z-
CCGTTTGCGAAGTGGGGTCCCATCAA
GCTGCATCCGTTTTGCAAAGTGGG
GATGGATCAACCCTGACAGTGGAG
CH1-E::EPKSC +
GGTTCAGTGGCAGTGGATCTGGGAC
GTCCCATCAAGGTTCAGCGGCAGT
GCACAAACTTTGCACAGCAGTTTC
[anti-<hu CD40>
AGATTTCACTCTCACCATCAGCAGTC
GGATCTGGGACAGATTTCACTCTCA
AGGGCAGGGTCACCATGACCAGGG
21-230_4G7VL]::
TGCAACCTGTAGATTTTACAACTTTC
CCATCAGCAGCCTGCAGCCTGAAG
ATACGTCCATCAGCACAGCCTACA
huKLC-S176E +
TACTGTCAACAGACTTTCACTACCCC
ATTTTGCAACTTACTATTGTCAACA
TGGAGGTGAGCAGGCTGAGATCTG
[anti-<hu
GTGGACGTTCGGCCAAGGGACCAAG
GTCTAACAGTTTCCCTCGGACGTTC
ACGACACGGCCGTGTTTTACTGTGC
Mesothelin>
GTGGAGATCAAACGAACGGTGGCTG
GGCCAAGGGACCAAGGTGGAAATC
GAGAGAGAAGATCACTATGACTGG
4H6VL]::huKLC-
CACCATCTGTCTTCATCTTCCCGCCAT
AAACGGACGGTGGCTGCACCATCT
TATTTACTTTGACTATTGGGGCCAG
S176K (IgG-Fab);
CTGATGAGCAGTTGAAATCTGGAACT
GTCTTCATCTTCCCGCCATCTGATG
GGAACCCTGGTCACCGTGTCCTCA
LMRID: SS-30856
GCCTCTGTTGTGTGCCTGCTGAATAA
AGCAGTTGAAATCTGGAACTGCCT
GCCTCCACCAAGGGCCCATCGGTC
CTTCTATCCCAGAGAGGCCAAAGTAC
CTGTTGTGTGCCTGCTGAATAACTT
TTCCCCCTGGCACCCTCCTCCAAGA
AGTGGAAGGTGGATAACGCCCTCCA
CTATCCCAGAGAGGCCAAAGTACA
GCACCTCTGGGGGCACAGCGGCCC
ATCGGGTAACTCCCAGGAGAGTGTC
GTGGAAGGTGGATAACGCCCTCCA
TGGGCTGCCTGGTCAAGGACTACTT
ACAGAGCAGGACAGCAAGGACAGCA
ATCGGGTAACTCCCAGGAGAGTGT
CCCCGAACCGGTGACGGTGTCGTG
CCTACAGCCTCGAAAGCACCCTGACG
CACAGAGCAGGACAGCAAGGACA
GAACTCAGGCGCCCTGACCAGCGG
CTGAGCAAAGCAGACTACGAGAAAC
GCACCTACAGCCTCAAGAGCACCC
CGTGCACACCTTCCCGGCTGTCCTA
ACAAAGTCTACGCCTGCGAAGTCACC
TGACGCTGAGCAAAGCAGACTACG
CAGTCCTCAGGACTCTACTCCCTCA
CATCAGGGCCTGAGCTCGCCCGTCAC
AGAAACACAAAGTCTACGCCTGCG
AGAGCGTGGTGACCGTGCCCTCCA
AAAGAGCTTCAACAGGGGAGAGTGT
AAGTCACCCATCAGGGCCTGAGCT
GCAGCTTGGGCACCCAGACCTACA
(SEQ ID NO: 437)
CGCCCGTCACAAAGAGCTTCAACA
TCTGCAACGTGAATCACAAGCCCA
GGGGAGAGTGT
GCAACACCAAGGTGGACAAGAAAG
(SEQ ID NO: 438)
TTGAGCCCAAATCTTGTGACAAAA
CTCACACATGCCCACCGTGCCCAG
CACCTGAACTCCTGGGGGGACCGT
CAGTCTTCCTCTTCCCCCCAAAACC
CAAGGACACCCTCATGATCTCCCG
GACCCCTGAGGTCACATGCGTGGT
GGTGGACGTGAGCCACGAAGACCC
TGAGGTCAAGTTCAACTGGTACGT
GGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGTGCGAGGAGCA
GTACGGCAGCACGTACCGTTGCGT
CAGCGTCCTCACCGTCCTGCACCAG
GACTGGCTGAATGGCAAGGAGTAC
AAGTGCAAGGTGTCCAACAAAGCC
CTCCCAGCCCCCATCGAGAAAACC
ATCTCCAAAGCCAAAGGGCAGCCC
CGAGAACCACAGGTGTACACCCTG
CCCCCATCCCGGGAGGAGATGACC
AAGAACCAGGTCAGCCTGACCTGC
CTGGTCAAAGGCTTCTATCCCAGCG
ACATCGCCGTGGAGTGGGAGAGCA
ATGGGCAGCCGGAGAACAACTACA
AGACCACGCCTCCCGTGCTGGACT
CCGACGGCTCCTTCTTCCTCTATAG
CAAGCTCACCGTGGACAAGAGCAG
GTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTG
CACAACCACTACACGCAGAAGAGC
CTCTCCCTGTCTCCGGGTGGTGGCG
GATCGGGAGGTGGCGGATCCCAGG
TGCAGCTGGTCGAGTCTGGGGGAG
GCTTGGTCAAGCCTGGAGGGTCCC
TGAGACTCTCCTGTGCAGCCTCTGG
ATTCACCTTCAGTGACTACTACATG
ACCTGGATCAGGCAGGCTCCAGGG
AAGGGGCTGGAGTGGATTTCATAC
ATTAGTAGTAGTGGTAGTACCATCT
ACTACGCAGACTCTGTGAAGGGCC
GATTCACCATCTCCAGGGACAACG
CCAAGAACTCACTGTATCTGCAAA
TGAACAGCCTGAGAGCCGAGGACA
CGGCCGTGTATTACTGTGCGAGAG
ATCGGAACTCCCACTTTGACTATTG
GGGCCAGGGAACCCTGGTCACCGT
GTCCTCAGCAAGCACGAAGGGGCC
GTCCGTATTTCCGCTTGCGCCCTCG
TCGAAGTCAACTTCGGGAGGGACC
GCGGCACTTGGCTGTCTTGTCAAAG
ATTACTTCCCTGAGCCAGTGACAGT
CAGCTGGAATTCCGGTGCCCTCAC
GTCAGGAGTACATACATTCCCTGC
GGTATTGCAGTCCTCCGGACTCTAC
TCCCTGGAGTCGGTGGTAACGGTG
CCCAGCTCCAGCTTGGGGACCCAG
ACGTACATTTGTAACGTGAATCAC
AAACCAAGCAATACTAAGGTAGAT
AAGAAAGTAGAACCGAAGAGCTGC
(SEQ ID NO: 439)
AA
DIQMTQSPSSLSASVGDILTITCRASQNI
DIQMTQSPSSVSASVGDRVTITCRAS
QVQLVQSGAEVKKPGASVKVSCKAS
TTYLNWYQQKPGKAPNLLISAASRLRS
QGITRWLAWYQQKPGKAPKLLIYAA
GYTFAGYYMHWVRQAPGQGLEWM
GVPSRFSGSGSGTDFTLTISSLQPVDFT
SVLQSGVPSRFSGSGSGTDFTLTISSL
GWINPDSGGTNFAQQFQGRVTMTRD
TFYCQQTFTTPWTFGQGTKVEIKRTVA
QPEDFATYYCQQSNSFPRTFGQGTK
TSISTAYMEVSRLRSDDTAVFYCARE
APSVFIFPPSDEQLKSGTASVVCLLNNF
VEIKRTVAAPSVFIFPPSDEQLKSGTA
KITMTGIYFDYWGQGTLVTVSSAST
YPREAKVQWKVDNALQSGNSQESVTE
SVVCLLNNFYPREAKVQWKVDNAL
KGPSVFPLAPSSKSTSGGTAALGCLV
QDSKDSTYSLESTLTLSKADYEKHKVY
QSGNSQESVTEQDSKDSTYSLKSTLT
KDYFPEPVTVSWNSGALTSGVHTFP
ACEVTHQGLSSPVTKSFNRGEC
LSKADYEKHKVYACEVTHQGLSSPV
AVLQSSGLYSLKSVVTVPSSSLGTQT
(SEQ ID NO: 440)
TKSFNRGEC
YICNVNHKPSNTKVDKKVEPKSCDK
(SEQ ID NO: 441)
THTCPPCPAPELLGGPSVFLFPPKPKD
TLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPCEEQYGST
YRCVSVLTVLHQDWLNGKEYKCKV
SNKALPAPIEKTISKAKGQPREPQVY
TLPPSREEMTKNQVSLTCLVKGFYPS
DIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGS
GGGGSQVQLVESGGGLVKPGGSLRL
SCAASGFTFSDYYMTWIRQAPGKGL
EWISYISSSGSTIYYADSVKGRFTISR
DNAKNSLYLQMNSLRAEDTAVYYC
ARDRNSHFDYWGQGTLVTVSSASTK
GPSVFPLAPSSKSTSGGTAALGCLVK
DYFPEPVTVSWNSGALTSGVHTFPA
VLQSSGLYSLESVVTVPSSSLGTQTYI
CNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 442)
iPS:
21-
[hu anti-<hu CD40>
NA
GACATCCAGATGACCCAGTCTCCATC
GACATCCAGATGACCCAGTCTCCA
CAGGTGCAGCTGGTGCAGTCTGGG
576270
230_4G7_IgG_21-
21-230_4G7VH]::
CTCCCTGTCTGCATCTGTAGGAGACA
TCTTCCGTGTCTGCTTCTGTCGGAG
GCTGAGGTGAAGAAGCCTGGGGCC
233_6F4__Fab
huIgG1zSEFL2*
TTCTCACCATCACTTGCCGGGCAAGT
ACAGAGTCACCATCACTTGTCGGG
TCAGTGAAGGTGTCCTGCAAGGCT
GK-K::(G4S)2::
CAGAACATTACCACCTATTTAAATTG
CGAGTCAGGATATTAGCAGGTGGT
TCTGGATACACCTTCGCCGGCTACT
[hu anti-
GTATCAGCAGAAACCAGGGAAAGCC
TAGCCTGGTATCAGCAGAAACCAG
ATATGCACTGGGTGCGACAGGCCC
<hu Mesothelin>
CCTAACCTCCTGATCTCTGCTGCATC
GGAAAGCCCCTAAGCTCCTGATTTC
CTGGACAAGGGCTTGAGTGGATGG
6F4VH]::huIgG1z-
CCGTTTGCGAAGTGGGGTCCCATCAA
TGCTGCATCCAGATTGCAAAGTGG
GATGGATCAACCCTGACAGTGGAG
CH1-E::EPKSC +
GGTTCAGTGGCAGTGGATCTGGGAC
AGTCCCATCAAGGTTCAGCGGCAG
GCACAAACTTTGCACAGCAGTTTC
[anti-<hu CD40>
AGATTTCACTCTCACCATCAGCAGTC
TGGATCTGGGACAGATTTCACTCTC
AGGGCAGGGTCACCATGACCAGGG
21-230_4G7VL]::
TGCAACCTGTAGATTTTACAACTTTC
ACCATCAGCAGCCTGCAGCCTGAA
ATACGTCCATCAGCACAGCCTACA
huKLC-S176E +
TACTGTCAACAGACTTTCACTACCCC
GATTTTGCAATTTACTATTGTCAAC
TGGAGGTGAGCAGGCTGAGATCTG
[anti-<hu
GTGGACGTTCGGCCAAGGGACCAAG
AGGCTAAAAGTTTTCCTCGGACGTT
ACGACACGGCCGTGTTTTACTGTGC
Mesothelin>
GTGGAGATCAAACGAACGGTGGCTG
CGGCCAAGGGACCAAGGTGGAAAT
GAGAGAGAAGATCACTATGACTGG
6F4VL]::huKLC-
CACCATCTGTCTTCATCTTCCCGCCAT
CAAACGGACGGTGGCTGCACCATC
TATTTACTTTGACTATTGGGGCCAG
S176K (IgG-Fab);
CTGATGAGCAGTTGAAATCTGGAACT
TGTCTTCATCTTCCCGCCATCTGAT
GGAACCCTGGTCACCGTGTCCTCA
LMRID: SS-30857
GCCTCTGTTGTGTGCCTGCTGAATAA
GAGCAGTTGAAATCTGGAACTGCC
GCCTCCACCAAGGGCCCATCGGTC
CTTCTATCCCAGAGAGGCCAAAGTAC
TCTGTTGTGTGCCTGCTGAATAACT
TTCCCCCTGGCACCCTCCTCCAAGA
AGTGGAAGGTGGATAACGCCCTCCA
TCTATCCCAGAGAGGCCAAAGTAC
GCACCTCTGGGGGCACAGCGGCCC
ATCGGGTAACTCCCAGGAGAGTGTC
AGTGGAAGGTGGATAACGCCCTCC
TGGGCTGCCTGGTCAAGGACTACTT
ACAGAGCAGGACAGCAAGGACAGCA
AATCGGGTAACTCCCAGGAGAGTG
CCCCGAACCGGTGACGGTGTCGTG
CCTACAGCCTCGAAAGCACCCTGACG
TCACAGAGCAGGACAGCAAGGACA
GAACTCAGGCGCCCTGACCAGCGG
CTGAGCAAAGCAGACTACGAGAAAC
GCACCTACAGCCTCAAGAGCACCC
CGTGCACACCTTCCCGGCTGTCCTA
ACAAAGTCTACGCCTGCGAAGTCACC
TGACGCTGAGCAAAGCAGACTACG
CAGTCCTCAGGACTCTACTCCCTCA
CATCAGGGCCTGAGCTCGCCCGTCAC
AGAAACACAAAGTCTACGCCTGCG
AGAGCGTGGTGACCGTGCCCTCCA
AAAGAGCTTCAACAGGGGAGAGTGT
AAGTCACCCATCAGGGCCTGAGCT
GCAGCTTGGGCACCCAGACCTACA
(SEQ ID NO: 443)
CGCCCGTCACAAAGAGCTTCAACA
TCTGCAACGTGAATCACAAGCCCA
GGGGAGAGTGT
GCAACACCAAGGTGGACAAGAAAG
(SEQ ID NO: 444)
TTGAGCCCAAATCTTGTGACAAAA
CTCACACATGCCCACCGTGCCCAG
CACCTGAACTCCTGGGGGGACCGT
CAGTCTTCCTCTTCCCCCCAAAACC
CAAGGACACCCTCATGATCTCCCG
GACCCCTGAGGTCACATGCGTGGT
GGTGGACGTGAGCCACGAAGACCC
TGAGGTCAAGTTCAACTGGTACGT
GGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGTGCGAGGAGCA
GTACGGCAGCACGTACCGTTGCGT
CAGCGTCCTCACCGTCCTGCACCAG
GACTGGCTGAATGGCAAGGAGTAC
AAGTGCAAGGTGTCCAACAAAGCC
CTCCCAGCCCCCATCGAGAAAACC
ATCTCCAAAGCCAAAGGGCAGCCC
CGAGAACCACAGGTGTACACCCTG
CCCCCATCCCGGGAGGAGATGACC
AAGAACCAGGTCAGCCTGACCTGC
CTGGTCAAAGGCTTCTATCCCAGCG
ACATCGCCGTGGAGTGGGAGAGCA
ATGGGCAGCCGGAGAACAACTACA
AGACCACGCCTCCCGTGCTGGACT
CCGACGGCTCCTTCTTCCTCTATAG
CAAGCTCACCGTGGACAAGAGCAG
GTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTG
CACAACCACTACACGCAGAAGAGC
CTCTCCCTGTCTCCGGGTGGTGGCG
GATCGGGAGGTGGCGGATCCCAGG
TGCAGCTGGTGGAGTCTGGGGGAG
GCTTGGTCAAGCCTGGAGGGTCCC
TGAGACTCTCCTGTGCAGCCTCTGG
ATTCACCTTCAGTGACTACTACATG
AGCTGGATCCGCCAGGCTCCAGGG
AAGGGGCTGGAGTGGATTTCATAC
ATTAGTAGCAGTGAAAGTATCATC
TATTACGTAGACTCTGTGAAGGGC
CGATTCACCATCTCCAGGGACAAC
GCCAAGAACTCACTGTATCTGCAA
ATGAACAGCCTGAGAGCCGAGGAC
ACGGCCGTGTATTACTGTGCGAGA
GATGTTGGGAGCCACTTTGACTACT
GGGGCCAGGGAACCCTGGTCACCG
TGTCCTCAGCAAGCACGAAGGGGC
CGTCCGTATTTCCGCTTGCGCCCTC
GTCGAAGTCAACTTCGGGAGGGAC
CGCGGCACTTGGCTGTCTTGTCAAA
GATTACTTCCCTGAGCCAGTGACA
GTCAGCTGGAATTCCGGTGCCCTCA
CGTCAGGAGTACATACATTCCCTGC
GGTATTGCAGTCCTCCGGACTCTAC
TCCCTGGAGTCGGTGGTAACGGTG
CCCAGCTCCAGCTTGGGGACCCAG
ACGTACATTTGTAACGTGAATCAC
AAACCAAGCAATACTAAGGTAGAT
AAGAAAGTAGAACCGAAGAGCTGC
(SEQ ID NO: 445)
AA
DIQMTQSPSSLSASVGDILTITCRASQNI
DIQMTQSPSSVSASVGDRVTITCRAS
QVQLVQSGAEVKKPGASVKVSCKAS
TTYLNWYQQKPGKAPNLLISAASRLRS
QDISRWLAWYQQKPGKAPKLLISAA
GYTFAGYYMHWVRQAPGQGLEWM
GVPSRFSGSGSGTDFTLTISSLQPVDFT
SRLQSGVPSRFSGSGSGTDFTLTISSL
GWINPDSGGTNFAQQFQGRVTMTRD
TFYCQQTFTTPWTFGQGTKVEIKRTVA
QPEDFAIYYCQQAKSFPRTFGQGTKV
TSISTAYMEVSRLRSDDTAVFYCARE
APSVFIFPPSDEQLKSGTASVVCLLNNF
EIKRTVAAPSVFIFPPSDEQLKSGTAS
KITMTGIYFDYWGQGTLVTVSSAST
YPREAKVQWKVDNALQSGNSQESVTE
VVCLLNNFYPREAKVQWKVDNALQ
KGPSVFPLAPSSKSTSGGTAALGCLV
QDSKDSTYSLESTLTLSKADYEKHKVY
SGNSQESVTEQDSKDSTYSLKSTLTL
KDYFPEPVTVSWNSGALTSGVHTFP
ACEVTHQGLSSPVTKSFNRGEC
SKADYEKHKVYACEVTHQGLSSPVT
AVLQSSGLYSLKSVVTVPSSSLGTQT
(SEQ ID NO: 446)
KSFNRGEC
YICNVNHKPSNTKVDKKVEPKSCDK
(SEQ ID NO: 447)
THTCPPCPAPELLGGPSVFLFPPKPKD
TLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPCEEQYGST
YRCVSVLTVLHQDWLNGKEYKCKV
SNKALPAPIEKTISKAKGQPREPQVY
TLPPSREEMTKNQVSLTCLVKGFYPS
DIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGS
GGGGSQVQLVESGGGLVKPGGSLRL
SCAASGFTFSDYYMSWIRQAPGKGL
EWISYISSSESIIYYVDSVKGRFTISRD
NAKNSLYLQMNSLRAEDTAVYYCA
RDVGSHFDYWGQGTLVTVSSASTKG
PSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAV
LQSSGLYSLESVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 448)
iPS:
21-
[hu anti-<hu CD40>
NA
GACATCCAGATGACCCAGTCTCCATC
GACATTGTGATGACTCAGTCTCCAG
CAGGTGCAGCTGGTGCAGTCTGGG
576275
230_4G7_IgG_21-
21-230_4G7VH]::
CTCCCTGTCTGCATCTGTAGGAGACA
ACTCCCTGGCTGTGTCTCTGGGCGA
GCTGAGGTGAAGAAGCCTGGGGCC
233_7G11__Fab
huIgG1zSEFL2*
TTCTCACCATCACTTGCCGGGCAAGT
GAGGGCCACCATCAACTGCAAGTC
TCAGTGAAGGTGTCCTGCAAGGCT
GK-K::(G4S)2::
CAGAACATTACCACCTATTTAAATTG
CAGCCAGAGTGTTTTATACAGCTCC
TCTGGATACACCTTCGCCGGCTACT
[hu anti-
GTATCAGCAGAAACCAGGGAAAGCC
AACAATAAGAACTACTTAGCTTGG
ATATGCACTGGGTGCGACAGGCCC
<hu Mesothelin>
CCTAACCTCCTGATCTCTGCTGCATC
TACCAGCAGAAACCAGGACAGCCT
CTGGACAAGGGCTTGAGTGGATGG
7G1VH]::huIgG1z-
CCGTTTGCGAAGTGGGGTCCCATCAA
CCTAAGCTGCTCATTTACTGGGCAT
GATGGATCAACCCTGACAGTGGAG
CH1-E::EPKSC +
GGTTCAGTGGCAGTGGATCTGGGAC
CTACCCGAGAATCCGGGGTCCCTG
GCACAAACTTTGCACAGCAGTTTC
[anti-<hu CD40>
AGATTTCACTCTCACCATCAGCAGTC
ACCGATTCAGTGGCAGCGGGTCTG
AGGGCAGGGTCACCATGACCAGGG
21-230_4G7VL]::
TGCAACCTGTAGATTTTACAACTTTC
GGACAGATTTCACTCTCACCATCAG
ATACGTCCATCAGCACAGCCTACA
huKLC-S176E +
TACTGTCAACAGACTTTCACTACCCC
CAGCCTGCAGGCTGAAGATGTGGC
TGGAGGTGAGCAGGCTGAGATCTG
[anti-<hu
GTGGACGTTCGGCCAAGGGACCAAG
AGTTTATTACTGTCAGCAATATTAT
ACGACACGGCCGTGTTTTACTGTGC
Mesothelin>
GTGGAGATCAAACGAACGGTGGCTG
AGTACTCCTCCGACGTTCGGCCAA
GAGAGAGAAGATCACTATGACTGG
7G11VL]::huKLC-
CACCATCTGTCTTCATCTTCCCGCCAT
GGGACCAAGGTGGAGATCAAACGG
TATTTACTTTGACTATTGGGGCCAG
S176K(IgG-Fab);
CTGATGAGCAGTTGAAATCTGGAACT
ACGGTGGCTGCACCATCTGTCTTCA
GGAACCCTGGTCACCGTGTCCTCA
LMRID: SS-30858
GCCTCTGTTGTGTGCCTGCTGAATAA
TCTTCCCGCCATCTGATGAGCAGTT
GCCTCCACCAAGGGCCCATCGGTC
CTTCTATCCCAGAGAGGCCAAAGTAC
GAAATCTGGAACTGCCTCTGTTGTG
TTCCCCCTGGCACCCTCCTCCAAGA
AGTGGAAGGTGGATAACGCCCTCCA
TGCCTGCTGAATAACTTCTATCCCA
GCACCTCTGGGGGCACAGCGGCCC
ATCGGGTAACTCCCAGGAGAGTGTC
GAGAGGCCAAAGTACAGTGGAAGG
TGGGCTGCCTGGTCAAGGACTACTT
ACAGAGCAGGACAGCAAGGACAGCA
TGGATAACGCCCTCCAATCGGGTA
CCCCGAACCGGTGACGGTGTCGTG
CCTACAGCCTCGAAAGCACCCTGACG
ACTCCCAGGAGAGTGTCACAGAGC
GAACTCAGGCGCCCTGACCAGCGG
CTGAGCAAAGCAGACTACGAGAAAC
AGGACAGCAAGGACAGCACCTACA
CGTGCACACCTTCCCGGCTGTCCTA
ACAAAGTCTACGCCTGCGAAGTCACC
GCCTCAAGAGCACCCTGACGCTGA
CAGTCCTCAGGACTCTACTCCCTCA
CATCAGGGCCTGAGCTCGCCCGTCAC
GCAAAGCAGACTACGAGAAACACA
AGAGCGTGGTGACCGTGCCCTCCA
AAAGAGCTTCAACAGGGGAGAGTGT
AAGTCTACGCCTGCGAAGTCACCC
GCAGCTTGGGCACCCAGACCTACA
(SEQ ID NO: 449)
ATCAGGGCCTGAGCTCGCCCGTCA
TCTGCAACGTGAATCACAAGCCCA
CAAAGAGCTTCAACAGGGGAGAGT
GCAACACCAAGGTGGACAAGAAAG
GT
TTGAGCCCAAATCTTGTGACAAAA
(SEQ ID NO: 450)
CTCACACATGCCCACCGTGCCCAG
CACCTGAACTCCTGGGGGGACCGT
CAGTCTTCCTCTTCCCCCCAAAACC
CAAGGACACCCTCATGATCTCCCG
GACCCCTGAGGTCACATGCGTGGT
GGTGGACGTGAGCCACGAAGACCC
TGAGGTCAAGTTCAACTGGTACGT
GGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGTGCGAGGAGCA
GTACGGCAGCACGTACCGTTGCGT
CAGCGTCCTCACCGTCCTGCACCAG
GACTGGCTGAATGGCAAGGAGTAC
AAGTGCAAGGTGTCCAACAAAGCC
CTCCCAGCCCCCATCGAGAAAACC
ATCTCCAAAGCCAAAGGGCAGCCC
CGAGAACCACAGGTGTACACCCTG
CCCCCATCCCGGGAGGAGATGACC
AAGAACCAGGTCAGCCTGACCTGC
CTGGTCAAAGGCTTCTATCCCAGCG
ACATCGCCGTGGAGTGGGAGAGCA
ATGGGCAGCCGGAGAACAACTACA
AGACCACGCCTCCCGTGCTGGACT
CCGACGGCTCCTTCTTCCTCTATAG
CAAGCTCACCGTGGACAAGAGCAG
GTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTG
CACAACCACTACACGCAGAAGAGC
CTCTCCCTGTCTCCGGGTGGTGGCG
GATCGGGAGGTGGCGGATCCGAGG
TGCAGCTGGTCGAGTCTGGAGGAG
GCTTGATCCAGCCTGGGGGGTCCCT
GAGACTCTCCTGTGCAGTCTCTGGG
TTCACCGTCAGTAGCAAGTTCATGA
CCTGGGTCCGCCAGGCTCCAGGGA
AGGGGCTGGAGTGGGTGTCAGTTA
TTTATAGCGGTGGTAAGACATACT
ACGCAGACTCCGTGAAGGGCCGAT
TCACCATCTCCAGAGACAATTCCA
AGAACACGCTGTATCTTCAAATGA
ACAGCCTGAGAGCCGAGGACACGG
CCGTGTATTACTGTGCGAGAGATA
GCGGTGGCTGGGGGTACTTTGACT
ACTGGGGCCAGGGAACCCTGGTCA
CCGTGTCCTCAGCAAGCACGAAGG
GGCCGTCCGTATTTCCGCTTGCGCC
CTCGTCGAAGTCAACTTCGGGAGG
GACCGCGGCACTTGGCTGTCTTGTC
AAAGATTACTTCCCTGAGCCAGTG
ACAGTCAGCTGGAATTCCGGTGCC
CTCACGTCAGGAGTACATACATTCC
CTGCGGTATTGCAGTCCTCCGGACT
CTACTCCCTGGAGTCGGTGGTAAC
GGTGCCCAGCTCCAGCTTGGGGAC
CCAGACGTACATTTGTAACGTGAA
TCACAAACCAAGCAATACTAAGGT
AGATAAGAAAGTAGAACCGAAGA
GCTGC
(SEQ ID NO: 451)
AA
DIQMTQSPSSLSASVGDILTITCRASQNI
DIVMTQSPDSLAVSLGERATINCKSS
QVQLVQSGAEVKKPGASVKVSCKAS
TTYLNWYQQKPGKAPNLLISAASRLRS
QSVLYSSNNKNYLAWYQQKPGQPP
GYTFAGYYMHWVRQAPGQGLEWM
GVPSRFSGSGSGTDFTLTISSLQPVDFT
KLLIYWASTRESGVPDRFSGSGSGTD
GWINPDSGGTNFAQQFQGRVTMTRD
TFYCQQTFTTPWTFGQGTKVEIKRTVA
FTLTISSLQAEDVAVYYCQQYYSTPP
TSISTAYMEVSRLRSDDTAVFYCARE
APSVFIFPPSDEQLKSGTASVVCLLNNF
TFGQGTKVEIKRTVAAPSVFIFPPSDE
KITMTGIYFDYWGQGTLVTVSSAST
YPREAKVQWKVDNALQSGNSQESVTE
QLKSGTASVVCLLNNFYPREAKVQW
KGPSVFPLAPSSKSTSGGTAALGCLV
QDSKDSTYSLESTLTLSKADYEKHKVY
KVDNALQSGNSQESVTEQDSKDSTY
KDYFPEPVTVSWNSGALTSGVHTFP
ACEVTHQGLSSPVTKSFNRGEC
SLKSTLTLSKADYEKHKVYACEVTH
AVLQSSGLYSLKSVVTVPSSSLGTQT
(SEQ ID NO: 452)
QGLSSPVTKSFNRGEC
YICNVNHKPSNTKVDKKVEPKSCDK
(SEQ ID NO: 453)
THTCPPCPAPELLGGPSVFLFPPKPKD
TLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPCEEQYGST
YRCVSVLTVLHQDWLNGKEYKCKV
SNKALPAPIEKTISKAKGQPREPQVY
TLPPSREEMTKNQVSLTCLVKGFYPS
DIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGS
GGGGSEVQLVESGGGLIQPGGSLRLS
CAVSGFTVSSKFMTWVRQAPGKGLE
WVSVIYSGGKTYYADSVKGRFTISR
DNSKNTLYLQMNSLRAEDTAVYYC
ARDSGGWGYFDYWGQGTLVTVSSA
STKGPSVFPLAPSSKSTSGGTAALGC
LVKDYFPEPVTVSWNSGALTSGVHT
FPAVLQSSGLYSLESVVTVPSSSLGT
QTYICNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 454)
iPS:
21-
[hu anti-<hu CD40>
NA
GACATCCAGATGACCCAGTCTCCATC
CAGTCAGTGTTGACGCAGCCGCCC
CAGGTGCAACTGGTGCAGTCTGGG
576280
230_29H10_IgG_21-
21-230_29H10VH]::
CTCACTGTCTGCATCTGTAGGAGACA
TCAGTGTCTGGGGCCCCAGGGCAG
GCTGAGGTGACGAAGCCTGGGGCC
233_4G12__Fab
huIgG1zSEFL2*GK-
GAGTCACCATCACCTGTCGGGCGAGT
AGGGTCACCATCTCCTGCACTGGG
TCAGTGAAGGTGTCCTGCAAGGCT
K::(G4S)2::[hu anti-
CAGGACATTAGCAATAATTTAGCCTG
AGCAGCTCCAACATCGGGGCAGGT
TCTGGATACACCTTCGCCGGCTACT
<hu Mesothelin>
GTTTCAGCAGAAACCAGGGAAACCC
TATGATGTTCACTGGTACCAGCAG
ATATGCACTGGGTGCGACAGGCCC
4G12VH]::huIgG1z-
CCTAAGTCCCTGATGTATGCTGCATC
GTTCCAGGAACAGCCCCCAAACTC
CTGGACAAGGGCTTGAGTGGATGG
CH1-E::EPKSC +
CAGTTTGCACAGTGGAGTCCCATCAA
CTCATCTATGGTAACAGCAAGCGG
GATGGATCAACCCTCACAGTGGTG
[anti-<hu CD40>
CGTTCAGCGGCAGTGGATCTGGGAC
CCCTCAGGGGTCCCTGACCGATTCT
GCACAAACTATGCACAGAAGTTTC
21-230_29H10VL]::
AGATTTCACTTTCACCATCAGCAGCC
CTGGCTCCAAGTCTGGCACCTCAGC
AGGACAGGGTCACCATGACCAGGG
huKLC-S176E + [anti-
TGCAGCCTGAAGATTTTGCAACTTAT
CTCCCTGGCCATCACTGGGCTCCAG
ACACGTCCATCAACACAGCCTACA
<hu Mesothelin>
TACTGCCAACAGTATAATAGTTACCC
GCTGAGGATGAGGCTGATTATTAC
TGGAACTGAGCAGGCTGAGATCTG
4G12VL]::huLLC2-
TCTCACTTTCGGCGGAGGGACCAAGG
TGCCAGTCCTATGACAGCAGCCTG
ACGACACGGCCGTGTATTACTGTG
K(IgG-Fab);
TGGAGATCAGACGAACGGTGGCTGC
GGTGGTTGGGTGTTCGGCGGAGGG
CGAGAGAACGTATTTCTATGGTTCG
LMRID: SS-30859
ACCATCTGTCTTCATCTTCCCGCCATC
ACCAAGCTGACCGTCCTACAGCCC
GGGAGTCGGGCACAACTGGTTCGC
TGATGAGCAGTTGAAATCTGGAACTG
AAGGCTGCACCCTCGGTCACTCTGT
CCCCTGGGGCCAGGGAACCCTGGT
CCTCTGTTGTGTGCCTGCTGAATAAC
TCCCGCCCTCCTCTGAGGAGCTTCA
CACCGTGTCCTCAGCCTCCACCAAG
TTCTATCCCAGAGAGGCCAAAGTACA
AGCCAACAAGGCCACACTGGTGTG
GGCCCATCGGTCTTCCCCCTGGCAC
GTGGAAGGTGGATAACGCCCTCCAA
TCTCATCAGTGACTTCTACCCGGGA
CCTCCTCCAAGAGCACCTCTGGGG
TCGGGTAACTCCCAGGAGAGTGTCAC
GCCGTGACAGTGGCCTGGAAGGCA
GCACAGCGGCCCTGGGCTGCCTGG
AGAGCAGGACAGCAAGGACAGCACC
GATAGCAGCCCCGTCAAGGCGGGA
TCAAGGACTACTTCCCCGAACCGG
TACAGCCTCGAAAGCACCCTGACGCT
GTGGAAACCACCACACCCTCCAAA
TGACGGTGTCGTGGAACTCAGGCG
GAGCAAAGCAGACTACGAGAAACAC
CAAAGCAACAACAAGTACGCGGCC
CCCTGACCAGCGGCGTGCACACCT
AAAGTCTACGCCTGCGAAGTCACCCA
AAGAGCTATCTGAGCCTGACGCCT
TCCCGGCTGTCCTACAGTCCTCAGG
TCAGGGCCTGAGCTCGCCCGTCACAA
GAGCAGTGGAAGTCCCACAGAAGC
ACTCTACTCCCTCAAGAGCGTGGTG
AGAGCTTCAACAGGGGAGAGTGT
TACAGCTGCCAGGTCACGCATGAA
ACCGTGCCCTCCAGCAGCTTGGGC
(SEQ ID NO: 455)
GGGAGCACCGTGGAGAAGACAGTG
ACCCAGACCTACATCTGCAACGTG
GCCCCTACAGAATGTTCA
AATCACAAGCCCAGCAACACCAAG
(SEQ ID NO: 456)
GTGGACAAGAAAGTTGAGCCCAAA
TCTTGTGACAAAACTCACACATGCC
CACCGTGCCCAGCACCTGAACTCCT
GGGGGGACCGTCAGTCTTCCTCTTC
CCCCCAAAACCCAAGGACACCCTC
ATGATCTCCCGGACCCCTGAGGTC
ACATGCGTGGTGGTGGACGTGAGC
CACGAAGACCCTGAGGTCAAGTTC
AACTGGTACGTGGACGGCGTGGAG
GTGCATAATGCCAAGACAAAGCCG
TGCGAGGAGCAGTACGGCAGCACG
TACCGTTGCGTCAGCGTCCTCACCG
TCCTGCACCAGGACTGGCTGAATG
GCAAGGAGTACAAGTGCAAGGTGT
CCAACAAAGCCCTCCCAGCCCCCA
TCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGG
TGTACACCCTGCCCCCATCCCGGGA
GGAGATGACCAAGAACCAGGTCAG
CCTGACCTGCCTGGTCAAAGGCTTC
TATCCCAGCGACATCGCCGTGGAG
TGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCC
GTGCTGGACTCCGACGGCTCCTTCT
TCCTCTATAGCAAGCTCACCGTGGA
CAAGAGCAGGTGGCAGCAGGGGA
ACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACAC
GCAGAAGAGCCTCTCCCTGTCTCCG
GGTGGTGGCGGATCGGGAGGTGGC
GGATCCCAGGTGCAGCTGCAGGAG
TCGGGCCCAGGACTGGTGAAGCCT
TCGGAAACCCTGTCCCTCACCTGCA
CTGTCTCTGGTGGCTCCATCAGCAG
TAGTAGTTACTACTGGGGCTGGATC
AGGCAGCCCCCAGGGAAGGGGCTG
GAGTGGATTGGGAGTATCTATTAT
AGTGGGATCACCAACTACAACCCG
TCCCTCAAGAGTCGAGTCACCATCT
CCGTAGACACGTCCAAGAACCAGT
TCTCCCTGAAGCTGAGTTCTGTGAC
CGCCGCAGACACGGCCGTGTATTA
CTGTGCGAGATCCAGTAACTACGA
TGCTTTTGATATCTGGGGCCAAGGG
ACAATGGTCACCGTGTCCTCAGCA
AGCACGAAGGGGCCGTCCGTATTT
CCGCTTGCGCCCTCGTCGAAGTCAA
CTTCGGGAGGGACCGCGGCACTTG
GCTGTCTTGTCAAAGATTACTTCCC
TGAGCCAGTGACAGTCAGCTGGAA
TTCCGGTGCCCTCACGTCAGGAGTA
CATACATTCCCTGCGGTATTGCAGT
CCTCCGGACTCTACTCCCTGGAGTC
GGTGGTAACGGTGCCCAGCTCCAG
CTTGGGGACCCAGACGTACATTTGT
AACGTGAATCACAAACCAAGCAAT
ACTAAGGTAGATAAGAAAGTAGAA
CCGAAGAGCTGC
(SEQ ID NO: 457)
AA
DIQMTQSPSSLSASVGDRVTITCRASQD
QSVLTQPPSVSGAPGQRVTISCTGSSS
QVQLVQSGAEVTKPGASVKVSCKAS
ISNNLAWFQQKPGKPPKSLMYAASSLH
NIGAGYDVHWYQQVPGTAPKLLIYG
GYTFAGYYMHWVRQAPGQGLEWM
SGVPSTFSGSGSGTDFTFTISSLQPEDFA
NSKRPSGVPDRFSGSKSGTSASLAIT
GWINPHSGGTNYAQKFQDRVTMTR
TYYCQQYNSYPLTFGGGTKVEIRRTVA
GLQAEDEADYYCQSYDSSLGGWVF
DTSINTAYMELSRLRSDDTAVYYCA
APSVFIFPPSDEQLKSGTASVVCLLNNF
GGGTKLTVLQPKAAPSVTLFPPSSEE
RERISMVRGVGHNWFAPWGQGTLV
YPREAKVQWKVDNALQSGNSQESVTE
LQANKATLVCLISDFYPGAVTVAWK
TVSSASTKGPSVFPLAPSSKSTSGGTA
QDSKDSTYSLESTLTLSKADYEKHKVY
ADSSPVKAGVETTTPSKQSNNKYAA
ALGCLVKDYFPEPVTVSWNSGALTS
ACEVTHQGLSSPVTKSFNRGEC
KSYLSLTPEQWKSHRSYSCQVTHEG
GVHTFPAVLQSSGLYSLKSVVTVPSS
(SEQ ID NO: 458)
STVEKTVAPTECS
SLGTQTYICNVNHKPSNTKVDKKVE
(SEQ ID NO: 459)
PKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSH
EDPEVKFNWYVDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNG
KEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCL
VKGFYPSDIAVEWESNGQPENNYKT
TPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSL
SPGGGGSGGGGSQVQLQESGPGLVK
PSETLSLTCTVSGGSISSSSYYWGWIR
QPPGKGLEWIGSIYYSGITNYNPSLKS
RVTISVDTSKNQFSLKLSSVTAADTA
VYYCARSSNYDAFDIWGQGTMVTV
SSASTKGPSVFPLAPSSKSTSGGTAAL
GCLVKDYFPEPVTVSWNSGALTSGV
HTFPAVLQSSGLYSLESVVTVPSSSL
GTQTYICNVNHKPSNTKVDKKVEPK
SC
(SEQ ID NO: 460)
iPS:
21-
[hu anti-
NA
GACATCCAGATGACCCAGTCTCCATC
GACATTCAGATGACCCAGTCTCCAT
CAGGTGCAACTGGTGCAGTCTGGG
576285
230_29H10_IgG_
<hu CD40> 21-230_
CTCACTGTCTGCATCTGTAGGAGACA
CTTCCGTGTCTGCATCTGTAGGGGA
GCTGAGGTGACGAAGCCTGGGGCC
21-
29H10VH]::huIgG1zSEFL2*GK-
GAGTCACCATCACCTGTCGGGCGAGT
CAGAGTCACCATCACTTGTCGGGC
TCAGTGAAGGTGTCCTGCAAGGCT
233_4H6__Fab
K::(G4S)2::[hu anti-
CAGGACATTAGCAATAATTTAGCCTG
GAGTCAGGGTATTACCAGGTGGTT
TCTGGATACACCTTCGCCGGCTACT
<hu Mesothelin>
GTTTCAGCAGAAACCAGGGAAACCC
AGCCTGGTATCAGCAGAAACCAGG
ATATGCACTGGGTGCGACAGGCCC
4H6VH]::huIgG1z-
CCTAAGTCCCTGATGTATGCTGCATC
GAAAGCCCCTAAGCTCCTGATCTAT
CTGGACAAGGGCTTGAGTGGATGG
CH1-E::EPKSC + [anti-
CAGTTTGCACAGTGGAGTCCCATCAA
GCTGCATCCGTTTTGCAAAGTGGG
GATGGATCAACCCTCACAGTGGTG
<hu CD40>
CGTTCAGCGGCAGTGGATCTGGGAC
GTCCCATCAAGGTTCAGCGGCAGT
GCACAAACTATGCACAGAAGTTTC
21-230_29H10VL]::huKLC-
AGATTTCACTTTCACCATCAGCAGCC
GGATCTGGGACAGATTTCACTCTCA
AGGACAGGGTCACCATGACCAGGG
S176E + [anti-
TGCAGCCTGAAGATTTTGCAACTTAT
CCATCAGCAGCCTGCAGCCTGAAG
ACACGTCCATCAACACAGCCTACA
<hu Mesothelin>
TACTGCCAACAGTATAATAGTTACCC
ATTTTGCAACTTACTATTGTCAACA
TGGAACTGAGCAGGCTGAGATCTG
4H6VL]::huKLC-
TCTCACTTTCGGCGGAGGGACCAAGG
GTCTAACAGTTTCCCTCGGACGTTC
ACGACACGGCCGTGTATTACTGTG
S176K (IgG-Fab);
TGGAGATCAGACGAACGGTGGCTGC
GGCCAAGGGACCAAGGTGGAAATC
CGAGAGAACGTATTTCTATGGTTCG
LMRID: SS-30860
ACCATCTGTCTTCATCTTCCCGCCATC
AAACGGACGGTGGCTGCACCATCT
GGGAGTCGGGCACAACTGGTTCGC
TGATGAGCAGTTGAAATCTGGAACTG
GTCTTCATCTTCCCGCCATCTGATG
CCCCTGGGGCCAGGGAACCCTGGT
CCTCTGTTGTGTGCCTGCTGAATAAC
AGCAGTTGAAATCTGGAACTGCCT
CACCGTGTCCTCAGCCTCCACCAAG
TTCTATCCCAGAGAGGCCAAAGTACA
CTGTTGTGTGCCTGCTGAATAACTT
GGCCCATCGGTCTTCCCCCTGGCAC
GTGGAAGGTGGATAACGCCCTCCAA
CTATCCCAGAGAGGCCAAAGTACA
CCTCCTCCAAGAGCACCTCTGGGG
TCGGGTAACTCCCAGGAGAGTGTCAC
GTGGAAGGTGGATAACGCCCTCCA
GCACAGCGGCCCTGGGCTGCCTGG
AGAGCAGGACAGCAAGGACAGCACC
ATCGGGTAACTCCCAGGAGAGTGT
TCAAGGACTACTTCCCCGAACCGG
TACAGCCTCGAAAGCACCCTGACGCT
CACAGAGCAGGACAGCAAGGACA
TGACGGTGTCGTGGAACTCAGGCG
GAGCAAAGCAGACTACGAGAAACAC
GCACCTACAGCCTCAAGAGCACCC
CCCTGACCAGCGGCGTGCACACCT
AAAGTCTACGCCTGCGAAGTCACCCA
TGACGCTGAGCAAAGCAGACTACG
TCCCGGCTGTCCTACAGTCCTCAGG
TCAGGGCCTGAGCTCGCCCGTCACAA
AGAAACACAAAGTCTACGCCTGCG
ACTCTACTCCCTCAAGAGCGTGGTG
AGAGCTTCAACAGGGGAGAGTGT
AAGTCACCCATCAGGGCCTGAGCT
ACCGTGCCCTCCAGCAGCTTGGGC
(SEQ ID NO: 461)
CGCCCGTCACAAAGAGCTTCAACA
ACCCAGACCTACATCTGCAACGTG
GGGGAGAGTGT
AATCACAAGCCCAGCAACACCAAG
(SEQ ID NO: 462)
GTGGACAAGAAAGTTGAGCCCAAA
TCTTGTGACAAAACTCACACATGCC
CACCGTGCCCAGCACCTGAACTCCT
GGGGGGACCGTCAGTCTTCCTCTTC
CCCCCAAAACCCAAGGACACCCTC
ATGATCTCCCGGACCCCTGAGGTC
ACATGCGTGGTGGTGGACGTGAGC
CACGAAGACCCTGAGGTCAAGTTC
AACTGGTACGTGGACGGCGTGGAG
GTGCATAATGCCAAGACAAAGCCG
TGCGAGGAGCAGTACGGCAGCACG
TACCGTTGCGTCAGCGTCCTCACCG
TCCTGCACCAGGACTGGCTGAATG
GCAAGGAGTACAAGTGCAAGGTGT
CCAACAAAGCCCTCCCAGCCCCCA
TCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGG
TGTACACCCTGCCCCCATCCCGGGA
GGAGATGACCAAGAACCAGGTCAG
CCTGACCTGCCTGGTCAAAGGCTTC
TATCCCAGCGACATCGCCGTGGAG
TGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCC
GTGCTGGACTCCGACGGCTCCTTCT
TCCTCTATAGCAAGCTCACCGTGGA
CAAGAGCAGGTGGCAGCAGGGGA
ACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACAC
GCAGAAGAGCCTCTCCCTGTCTCCG
GGTGGTGGCGGATCGGGAGGTGGC
GGATCCCAGGTGCAGCTGGTCGAG
TCTGGGGGAGGCTTGGTCAAGCCT
GGAGGGTCCCTGAGACTCTCCTGT
GCAGCCTCTGGATTCACCTTCAGTG
ACTACTACATGACCTGGATCAGGC
AGGCTCCAGGGAAGGGGCTGGAGT
GGATTTCATACATTAGTAGTAGTGG
TAGTACCATCTACTACGCAGACTCT
GTGAAGGGCCGATTCACCATCTCC
AGGGACAACGCCAAGAACTCACTG
TATCTGCAAATGAACAGCCTGAGA
GCCGAGGACACGGCCGTGTATTAC
TGTGCGAGAGATCGGAACTCCCAC
TTTGACTATTGGGGCCAGGGAACC
CTGGTCACCGTGTCCTCAGCAAGC
ACGAAGGGGCCGTCCGTATTTCCG
CTTGCGCCCTCGTCGAAGTCAACTT
CGGGAGGGACCGCGGCACTTGGCT
GTCTTGTCAAAGATTACTTCCCTGA
GCCAGTGACAGTCAGCTGGAATTC
CGGTGCCCTCACGTCAGGAGTACA
TACATTCCCTGCGGTATTGCAGTCC
TCCGGACTCTACTCCCTGGAGTCGG
TGGTAACGGTGCCCAGCTCCAGCTT
GGGGACCCAGACGTACATTTGTAA
CGTGAATCACAAACCAAGCAATAC
TAAGGTAGATAAGAAAGTAGAACC
GAAGAGCTGC
(SEQ ID NO: 463)
AA
DIQMTQSPSSLSASVGDRVTITCRASQD
DIQMTQSPSSVSASVGDRVTITCRAS
QVQLVQSGAEVTKPGASVKVSCKAS
ISNNLAWFQQKPGKPPKSLMYAASSLH
QGITRWLAWYQQKPGKAPKLLIYAA
GYTFAGYYMHWVRQAPGQGLEWM
SGVPSTFSGSGSGTDFTFTISSLQPEDFA
SVLQSGVPSRFSGSGSGTDFTLTISSL
GWINPHSGGTNYAQKFQDRVTMTR
TYYCQQYNSYPLTFGGGTKVEIRRTVA
QPEDFATYYCQQSNSFPRTFGQGTK
DTSINTAYMELSRLRSDDTAVYYCA
APSVFIFPPSDEQLKSGTASVVCLLNNF
VEIKRTVAAPSVFIFPPSDEQLKSGTA
RERISMVRGVGHNWFAPWGQGTLV
YPREAKVQWKVDNALQSGNSQESVTE
SVVCLLNNFYPREAKVQWKVDNAL
TVSSASTKGPSVFPLAPSSKSTSGGTA
QDSKDSTYSLESTLTLSKADYEKHKVY
QSGNSQESVTEQDSKDSTYSLKSTLT
ALGCLVKDYFPEPVTVSWNSGALTS
ACEVTHQGLSSPVTKSFNRGEC
LSKADYEKHKVYACEVTHQGLSSPV
GVHTFPAVLQSSGLYSLKSVVTVPSS
(SEQ ID NO: 464)
TKSFNRGEC
SLGTQTYICNVNHKPSNTKVDKKVE
(SEQ ID NO: 465)
PKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSH
EDPEVKFNWYVDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNG
KEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCL
VKGFYPSDIAVEWESNGQPENNYKT
TPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSL
SPGGGGSGGGGSQVQLVESGGGLVK
PGGSLRLSCAASGFTFSDYYMTWIR
QAPGKGLEWISYISSSGSTIYYADSV
KGRFTISRDNAKNSLYLQMNSLRAE
DTAVYYCARDRNSHFDYWGQGTLV
TVSSASTKGPSVFPLAPSSKSTSGGTA
ALGCLVKDYFPEPVTVSWNSGALTS
GVHTFPAVLQSSGLYSLESVVTVPSS
SLGTQTYICNVNHKPSNTKVDKKVE
PKSC
(SEQ ID NO: 466)
iPS:
21-
[hu anti-
NA
GACATCCAGATGACCCAGTCTCCATC
GACATCCAGATGACCCAGTCTCCA
CAGGTGCAACTGGTGCAGTCTGGG
576288
230_29H10_IgG_
<hu CD40> 21-230_
CTCACTGTCTGCATCTGTAGGAGACA
TCTTCCGTGTCTGCTTCTGTCGGAG
GCTGAGGTGACGAAGCCTGGGGCC
21-
29H10VH]::huIgG1zSEFL2*GK-
GAGTCACCATCACCTGTCGGGCGAGT
ACAGAGTCACCATCACTTGTCGGG
TCAGTGAAGGTGTCCTGCAAGGCT
233_6F4__Fab
K::(G4S)2::[hu anti-
CAGGACATTAGCAATAATTTAGCCTG
CGAGTCAGGATATTAGCAGGTGGT
TCTGGATACACCTTCGCCGGCTACT
<hu Mesothelin>
GTTTCAGCAGAAACCAGGGAAACCC
TAGCCTGGTATCAGCAGAAACCAG
ATATGCACTGGGTGCGACAGGCCC
6F4VH]::huIgG1z-
CCTAAGTCCCTGATGTATGCTGCATC
GGAAAGCCCCTAAGCTCCTGATTTC
CTGGACAAGGGCTTGAGTGGATGG
CH1-E::EPKSC + [anti-
CAGTTTGCACAGTGGAGTCCCATCAA
TGCTGCATCCAGATTGCAAAGTGG
GATGGATCAACCCTCACAGTGGTG
<hu CD40>
CGTTCAGCGGCAGTGGATCTGGGAC
AGTCCCATCAAGGTTCAGCGGCAG
GCACAAACTATGCACAGAAGTTTC
21-230_29H10VL]::huKLC-
AGATTTCACTTTCACCATCAGCAGCC
TGGATCTGGGACAGATTTCACTCTC
AGGACAGGGTCACCATGACCAGGG
S176E + [anti-
TGCAGCCTGAAGATTTTGCAACTTAT
ACCATCAGCAGCCTGCAGCCTGAA
ACACGTCCATCAACACAGCCTACA
<hu Mesothelin>
TACTGCCAACAGTATAATAGTTACCC
GATTTTGCAATTTACTATTGTCAAC
TGGAACTGAGCAGGCTGAGATCTG
6F4VL]::huKLC-
TCTCACTTTCGGCGGAGGGACCAAGG
AGGCTAAAAGTTTTCCTCGGACGTT
ACGACACGGCCGTGTATTACTGTG
S176K (IgG-Fab);
TGGAGATCAGACGAACGGTGGCTGC
CGGCCAAGGGACCAAGGTGGAAAT
CGAGAGAACGTATTTCTATGGTTCG
LMRID: SS-30861
ACCATCTGTCTTCATCTTCCCGCCATC
CAAACGGACGGTGGCTGCACCATC
GGGAGTCGGGCACAACTGGTTCGC
TGATGAGCAGTTGAAATCTGGAACTG
TGTCTTCATCTTCCCGCCATCTGAT
CCCCTGGGGCCAGGGAACCCTGGT
CCTCTGTTGTGTGCCTGCTGAATAAC
GAGCAGTTGAAATCTGGAACTGCC
CACCGTGTCCTCAGCCTCCACCAAG
TTCTATCCCAGAGAGGCCAAAGTACA
TCTGTTGTGTGCCTGCTGAATAACT
GGCCCATCGGTCTTCCCCCTGGCAC
GTGGAAGGTGGATAACGCCCTCCAA
TCTATCCCAGAGAGGCCAAAGTAC
CCTCCTCCAAGAGCACCTCTGGGG
TCGGGTAACTCCCAGGAGAGTGTCAC
AGTGGAAGGTGGATAACGCCCTCC
GCACAGCGGCCCTGGGCTGCCTGG
AGAGCAGGACAGCAAGGACAGCACC
AATCGGGTAACTCCCAGGAGAGTG
TCAAGGACTACTTCCCCGAACCGG
TACAGCCTCGAAAGCACCCTGACGCT
TCACAGAGCAGGACAGCAAGGACA
TGACGGTGTCGTGGAACTCAGGCG
GAGCAAAGCAGACTACGAGAAACAC
GCACCTACAGCCTCAAGAGCACCC
CCCTGACCAGCGGCGTGCACACCT
AAAGTCTACGCCTGCGAAGTCACCCA
TGACGCTGAGCAAAGCAGACTACG
TCCCGGCTGTCCTACAGTCCTCAGG
TCAGGGCCTGAGCTCGCCCGTCACAA
AGAAACACAAAGTCTACGCCTGCG
ACTCTACTCCCTCAAGAGCGTGGTG
AGAGCTTCAACAGGGGAGAGTGT
AAGTCACCCATCAGGGCCTGAGCT
ACCGTGCCCTCCAGCAGCTTGGGC
(SEQ ID NO: 467)
CGCCCGTCACAAAGAGCTTCAACA
ACCCAGACCTACATCTGCAACGTG
GGGGAGAGTGT
AATCACAAGCCCAGCAACACCAAG
(SEQ ID NO: 468)
GTGGACAAGAAAGTTGAGCCCAAA
TCTTGTGACAAAACTCACACATGCC
CACCGTGCCCAGCACCTGAACTCCT
GGGGGGACCGTCAGTCTTCCTCTTC
CCCCCAAAACCCAAGGACACCCTC
ATGATCTCCCGGACCCCTGAGGTC
ACATGCGTGGTGGTGGACGTGAGC
CACGAAGACCCTGAGGTCAAGTTC
AACTGGTACGTGGACGGCGTGGAG
GTGCATAATGCCAAGACAAAGCCG
TGCGAGGAGCAGTACGGCAGCACG
TACCGTTGCGTCAGCGTCCTCACCG
TCCTGCACCAGGACTGGCTGAATG
GCAAGGAGTACAAGTGCAAGGTGT
CCAACAAAGCCCTCCCAGCCCCCA
TCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGG
TGTACACCCTGCCCCCATCCCGGGA
GGAGATGACCAAGAACCAGGTCAG
CCTGACCTGCCTGGTCAAAGGCTTC
TATCCCAGCGACATCGCCGTGGAG
TGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCC
GTGCTGGACTCCGACGGCTCCTTCT
TCCTCTATAGCAAGCTCACCGTGGA
CAAGAGCAGGTGGCAGCAGGGGA
ACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACAC
GCAGAAGAGCCTCTCCCTGTCTCCG
GGTGGTGGCGGATCGGGAGGTGGC
GGATCCCAGGTGCAGCTGGTGGAG
TCTGGGGGAGGCTTGGTCAAGCCT
GGAGGGTCCCTGAGACTCTCCTGT
GCAGCCTCTGGATTCACCTTCAGTG
ACTACTACATGAGCTGGATCCGCC
AGGCTCCAGGGAAGGGGCTGGAGT
GGATTTCATACATTAGTAGCAGTG
AAAGTATCATCTATTACGTAGACTC
TGTGAAGGGCCGATTCACCATCTCC
AGGGACAACGCCAAGAACTCACTG
TATCTGCAAATGAACAGCCTGAGA
GCCGAGGACACGGCCGTGTATTAC
TGTGCGAGAGATGTTGGGAGCCAC
TTTGACTACTGGGGCCAGGGAACC
CTGGTCACCGTGTCCTCAGCAAGC
ACGAAGGGGCCGTCCGTATTTCCG
CTTGCGCCCTCGTCGAAGTCAACTT
CGGGAGGGACCGCGGCACTTGGCT
GTCTTGTCAAAGATTACTTCCCTGA
GCCAGTGACAGTCAGCTGGAATTC
CGGTGCCCTCACGTCAGGAGTACA
TACATTCCCTGCGGTATTGCAGTCC
TCCGGACTCTACTCCCTGGAGTCGG
TGGTAACGGTGCCCAGCTCCAGCTT
GGGGACCCAGACGTACATTTGTAA
CGTGAATCACAAACCAAGCAATAC
TAAGGTAGATAAGAAAGTAGAACC
GAAGAGCTGC
(SEQ ID NO: 469)
AA
DIQMTQSPSSLSASVGDRVTITCRASQD
DIQMTQSPSSVSASVGDRVTITCRAS
QVQLVQSGAEVTKPGASVKVSCKAS
ISNNLAWFQQKPGKPPKSLMYAASSLH
QDISRWLAWYQQKPGKAPKLLISAA
GYTFAGYYMHWVRQAPGQGLEWM
SGVPSTFSGSGSGTDFTFTISSLQPEDFA
SRLQSGVPSRFSGSGSGTDFTLTISSL
GWINPHSGGTNYAQKFQDRVTMTR
TYYCQQYNSYPLTFGGGTKVEIRRTVA
QPEDFAIYYCQQAKSFPRTFGQGTKV
DTSINTAYMELSRLRSDDTAVYYCA
APSVFIFPPSDEQLKSGTASVVCLLNNF
EIKRTVAAPSVFIFPPSDEQLKSGTAS
RERISMVRGVGHNWFAPWGQGTLV
YPREAKVQWKVDNALQSGNSQESVTE
VVCLLNNFYPREAKVQWKVDNALQ
TVSSASTKGPSVFPLAPSSKSTSGGTA
QDSKDSTYSLESTLTLSKADYEKHKVY
SGNSQESVTEQDSKDSTYSLKSTLTL
ALGCLVKDYFPEPVTVSWNSGALTS
ACEVTHQGLSSPVTKSFNRGEC
SKADYEKHKVYACEVTHQGLSSPVT
GVHTFPAVLQSSGLYSLKSVVTVPSS
(SEQ ID NO: 470)
KSFNRGEC
SLGTQTYICNVNHKPSNTKVDKKVE
(SEQ ID NO: 471)
PKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSH
EDPEVKFNWYVDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNG
KEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCL
VKGFYPSDIAVEWESNGQPENNYKT
TPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSL
SPGGGGSGGGGSQVQLVESGGGLVK
PGGSLRLSCAASGFTFSDYYMSWIRQ
APGKGLEWISYISSSESIIYYVDSVKG
RFTISRDNAKNSLYLQMNSLRAEDT
AVYYCARDVGSHFDYWGQGTLVTV
SSASTKGPSVFPLAPSSKSTSGGTAAL
GCLVKDYFPEPVTVSWNSGALTSGV
HTFPAVLQSSGLYSLESVVTVPSSSL
GTQTYICNVNHKPSNTKVDKKVEPK
SC
(SEQ ID NO: 472)
iPS:
21-
[hu anti-
NA
GACATCCAGATGACCCAGTCTCCATC
GACATTGTGATGACTCAGTCTCCAG
CAGGTGCAACTGGTGCAGTCTGGG
576291
230_29H10_IgG_
<hu CD40> 21-230_
CTCACTGTCTGCATCTGTAGGAGACA
ACTCCCTGGCTGTGTCTCTGGGCGA
GCTGAGGTGACGAAGCCTGGGGCC
21-
29H10VH]::huIgG1zSEFL2*GK-
GAGTCACCATCACCTGTCGGGCGAGT
GAGGGCCACCATCAACTGCAAGTC
TCAGTGAAGGTGTCCTGCAAGGCT
233_7G11__Fab
K::(G4S)2::[hu anti-
CAGGACATTAGCAATAATTTAGCCTG
CAGCCAGAGTGTTTTATACAGCTCC
TCTGGATACACCTTCGCCGGCTACT
<hu Mesothelin>
GTTTCAGCAGAAACCAGGGAAACCC
AACAATAAGAACTACTTAGCTTGG
ATATGCACTGGGTGCGACAGGCCC
7G11VH]::huIgG1z-
CCTAAGTCCCTGATGTATGCTGCATC
TACCAGCAGAAACCAGGACAGCCT
CTGGACAAGGGCTTGAGTGGATGG
CH1-E::EPKSC + [anti-
CAGTTTGCACAGTGGAGTCCCATCAA
CCTAAGCTGCTCATTTACTGGGCAT
GATGGATCAACCCTCACAGTGGTG
<huCD40>
CGTTCAGCGGCAGTGGATCTGGGAC
CTACCCGAGAATCCGGGGTCCCTG
GCACAAACTATGCACAGAAGTTTC
21-230_29H10VL]::huKLC-
AGATTTCACTTTCACCATCAGCAGCC
ACCGATTCAGTGGCAGCGGGTCTG
AGGACAGGGTCACCATGACCAGGG
S176E + [anti-
TGCAGCCTGAAGATTTTGCAACTTAT
GGACAGATTTCACTCTCACCATCAG
ACACGTCCATCAACACAGCCTACA
<hu Mesothelin>
TACTGCCAACAGTATAATAGTTACCC
CAGCCTGCAGGCTGAAGATGTGGC
TGGAACTGAGCAGGCTGAGATCTG
7G11VL]::huKLC-
TCTCACTTTCGGCGGAGGGACCAAGG
AGTTTATTACTGTCAGCAATATTAT
ACGACACGGCCGTGTATTACTGTG
S176K (IgG-Fab);
TGGAGATCAGACGAACGGTGGCTGC
AGTACTCCTCCGACGTTCGGCCAA
CGAGAGAACGTATTTCTATGGTTCG
LMRID: SS-30862
ACCATCTGTCTTCATCTTCCCGCCATC
GGGACCAAGGTGGAGATCAAACGG
GGGAGTCGGGCACAACTGGTTCGC
TGATGAGCAGTTGAAATCTGGAACTG
ACGGTGGCTGCACCATCTGTCTTCA
CCCCTGGGGCCAGGGAACCCTGGT
CCTCTGTTGTGTGCCTGCTGAATAAC
TCTTCCCGCCATCTGATGAGCAGTT
CACCGTGTCCTCAGCCTCCACCAAG
TTCTATCCCAGAGAGGCCAAAGTACA
GAAATCTGGAACTGCCTCTGTTGTG
GGCCCATCGGTCTTCCCCCTGGCAC
GTGGAAGGTGGATAACGCCCTCCAA
TGCCTGCTGAATAACTTCTATCCCA
CCTCCTCCAAGAGCACCTCTGGGG
TCGGGTAACTCCCAGGAGAGTGTCAC
GAGAGGCCAAAGTACAGTGGAAGG
GCACAGCGGCCCTGGGCTGCCTGG
AGAGCAGGACAGCAAGGACAGCACC
TGGATAACGCCCTCCAATCGGGTA
TCAAGGACTACTTCCCCGAACCGG
TACAGCCTCGAAAGCACCCTGACGCT
ACTCCCAGGAGAGTGTCACAGAGC
TGACGGTGTCGTGGAACTCAGGCG
GAGCAAAGCAGACTACGAGAAACAC
AGGACAGCAAGGACAGCACCTACA
CCCTGACCAGCGGCGTGCACACCT
AAAGTCTACGCCTGCGAAGTCACCCA
GCCTCAAGAGCACCCTGACGCTGA
TCCCGGCTGTCCTACAGTCCTCAGG
TCAGGGCCTGAGCTCGCCCGTCACAA
GCAAAGCAGACTACGAGAAACACA
ACTCTACTCCCTCAAGAGCGTGGTG
AGAGCTTCAACAGGGGAGAGTGT
AAGTCTACGCCTGCGAAGTCACCC
ACCGTGCCCTCCAGCAGCTTGGGC
(SEQ ID NO: 473)
ATCAGGGCCTGAGCTCGCCCGTCA
ACCCAGACCTACATCTGCAACGTG
CAAAGAGCTTCAACAGGGGAGAGT
AATCACAAGCCCAGCAACACCAAG
GT
GTGGACAAGAAAGTTGAGCCCAAA
(SEQ ID NO: 474)
TCTTGTGACAAAACTCACACATGCC
CACCGTGCCCAGCACCTGAACTCCT
GGGGGGACCGTCAGTCTTCCTCTTC
CCCCCAAAACCCAAGGACACCCTC
ATGATCTCCCGGACCCCTGAGGTC
ACATGCGTGGTGGTGGACGTGAGC
CACGAAGACCCTGAGGTCAAGTTC
AACTGGTACGTGGACGGCGTGGAG
GTGCATAATGCCAAGACAAAGCCG
TGCGAGGAGCAGTACGGCAGCACG
TACCGTTGCGTCAGCGTCCTCACCG
TCCTGCACCAGGACTGGCTGAATG
GCAAGGAGTACAAGTGCAAGGTGT
CCAACAAAGCCCTCCCAGCCCCCA
TCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGG
TGTACACCCTGCCCCCATCCCGGGA
GGAGATGACCAAGAACCAGGTCAG
CCTGACCTGCCTGGTCAAAGGCTTC
TATCCCAGCGACATCGCCGTGGAG
TGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCC
GTGCTGGACTCCGACGGCTCCTTCT
TCCTCTATAGCAAGCTCACCGTGGA
CAAGAGCAGGTGGCAGCAGGGGA
ACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACAC
GCAGAAGAGCCTCTCCCTGTCTCCG
GGTGGTGGCGGATCGGGAGGTGGC
GGATCCGAGGTGCAGCTGGTCGAG
TCTGGAGGAGGCTTGATCCAGCCT
GGGGGGTCCCTGAGACTCTCCTGT
GCAGTCTCTGGGTTCACCGTCAGTA
GCAAGTTCATGACCTGGGTCCGCC
AGGCTCCAGGGAAGGGGCTGGAGT
GGGTGTCAGTTATTTATAGCGGTGG
TAAGACATACTACGCAGACTCCGT
GAAGGGCCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTA
TCTTCAAATGAACAGCCTGAGAGC
CGAGGACACGGCCGTGTATTACTG
TGCGAGAGATAGCGGTGGCTGGGG
GTACTTTGACTACTGGGGCCAGGG
AACCCTGGTCACCGTGTCCTCAGCA
AGCACGAAGGGGCCGTCCGTATTT
CCGCTTGCGCCCTCGTCGAAGTCAA
CTTCGGGAGGGACCGCGGCACTTG
GCTGTCTTGTCAAAGATTACTTCCC
TGAGCCAGTGACAGTCAGCTGGAA
TTCCGGTGCCCTCACGTCAGGAGTA
CATACATTCCCTGCGGTATTGCAGT
CCTCCGGACTCTACTCCCTGGAGTC
GGTGGTAACGGTGCCCAGCTCCAG
CTTGGGGACCCAGACGTACATTTGT
AACGTGAATCACAAACCAAGCAAT
ACTAAGGTAGATAAGAAAGTAGAA
CCGAAGAGCTGC
(SEQ ID NO: 475)
AA
DIQMTQSPSSLSASVGDRVTITCRASQD
DIVMTQSPDSLAVSLGERATINCKSS
QVQLVQSGAEVTKPGASVKVSCKAS
ISNNLAWFQQKPGKPPKSLMYAASSLH
QSVLYSSNNKNYLAWYQQKPGQPP
GYTFAGYYMHWVRQAPGQGLEWM
SGVPSTFSGSGSGTDFTFTISSLQPEDFA
KLLIYWASTRESGVPDRFSGSGSGTD
GWINPHSGGTNYAQKFQDRVTMTR
TYYCQQYNSYPLTFGGGTKVEIRRTVA
FTLTISSLQAEDVAVYYCQQYYSTPP
DTSINTAYMELSRLRSDDTAVYYCA
APSVFIFPPSDEQLKSGTASVVCLLNNF
TFGQGTKVEIKRTVAAPSVFIFPPSDE
RERISMVRGVGHNWFAPWGQGTLV
YPREAKVQWKVDNALQSGNSQESVTE
QLKSGTASVVCLLNNFYPREAKVQW
TVSSASTKGPSVFPLAPSSKSTSGGTA
QDSKDSTYSLESTLTLSKADYEKHKVY
KVDNALQSGNSQESVTEQDSKDSTY
ALGCLVKDYFPEPVTVSWNSGALTS
ACEVTHQGLSSPVTKSFNRGEC
SLKSTLTLSKADYEKHKVYACEVTH
GVHTFPAVLQSSGLYSLKSVVTVPSS
(SEQ ID NO: 476)
QGLSSPVTKSFNRGEC
SLGTQTYICNVNHKPSNTKVDKKVE
(SEQ ID NO: 477)
PKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSH
EDPEVKFNWYVDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNG
KEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCL
VKGFYPSDIAVEWESNGQPENNYKT
TPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSL
SPGGGGSGGGGSEVQLVESGGGLIQP
GGSLRLSCAVSGFTVSSKFMTWVRQ
APGKGLEWVSVIYSGGKTYYADSVK
GRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDSGGWGYFDYWGQGTL
VTVSSASTKGPSVFPLAPSSKSTSGGT
AALGCLVKDYFPEPVTVSWNSGALT
SGVHTFPAVLQSSGLYSLESVVTVPS
SSLGTQTYICNVNHKPSNTKVDKKV
EPKSC
(SEQ ID NO: 478)
iPS:
21-
[hu anti-
NA
CAGTCTGCCCTGACTCAGCCTGCCTC
CAGTCAGTGTTGACGCAGCCGCCC
GAGGTGCAGCTGCTGGAGTCTGGG
576294
230_30A12_IgG_
<hu CD40> 21-230_
CGTGTCTGGGAGCCCTGGACAGTCGA
TCAGTGTCTGGGGCCCCAGGGCAG
GGAGGCTTGGTACAGCCTGGGGGG
21-
30A12VH]::huIgG1zSEFL2*GK-
TCACCATCTCCTGCACTGGAACCAGC
AGGGTCACCATCTCCTGCACTGGG
TCCCTGAGACTCTCCTGTGCAGCCT
233_4G12__Fab
K::(G4S)2::[hu anti-
AGTGATGTTGGGAATTATAACCTTGT
AGCAGCTCCAACATCGGGGCAGGT
CTGGATTCACCTTTAGTAGAAATGC
<hu Mesothelin>
CTCCTGGTACCAACAGCACCCAGGCA
TATGATGTTCACTGGTACCAGCAG
CATGAGTTGGGTCCGCCAGGCTCC
4G12VH]::huIgG1z-
AAGCCCCCAAACTCATGATTTTTGAG
GTTCCAGGAACAGCCCCCAAACTC
AGGGAAGGGGCTGGAGTGGGTGTC
CH1-E::EPKSC + [anti-
GTCAATCAGCGGCCCTCAGGGGTTTC
CTCATCTATGGTAACAGCAAGCGG
AGCTACTGGTGGTAGTGGTATTAG
<hu CD40>
TAATCGCTTCTCTGGCTCCAAGTCTG
CCCTCAGGGGTCCCTGACCGATTCT
CACATACTACGCAGACTCCGTGAA
21-230_30A12VL]::huLLC2-
GCACCACGGCCTCCCTGACAATCTCT
CTGGCTCCAAGTCTGGCACCTCAGC
GGGCCGGTTCACCATCTCCAGAGA
E + [anti-
GGGCTCCAGGCTGCGGACGAGGCTG
CTCCCTGGCCATCACTGGGCTCCAG
CAATTCCAAGAACACGCTGTATCT
<hu Mesothelin>
ATTATTTCTGCTGCTCATATACAACT
GCTGAGGATGAGGCTGATTATTAC
GCAAATGAACAGTCTGAGAGCCGA
4G12VL]::huLLC2-
AGTAGCACTTATGTGATCTTCGGCGG
TGCCAGTCCTATGACAGCAGCCTG
GGACACGGCCGTATATTACTGTGC
K (IgG-Fab);
AGGGACCAAGCTGACCGTCCTAGGT
GGTGGTTGGGTGTTCGGCGGAGGG
GAGAGGTTATAGCAACAGCTGGTG
LMRID: SS-30863
CAGCCCAAGGCTGCACCCTCGGTCAC
ACCAAGCTGACCGTCCTACAGCCC
GTACTTTGACTACTGGGGCCAGGG
TCTGTTCCCGCCCTCCTCTGAGGAGC
AAGGCTGCACCCTCGGTCACTCTGT
AACCCTGGTCACCGTGTCCTCAGCC
TTCAAGCCAACAAGGCCACACTGGT
TCCCGCCCTCCTCTGAGGAGCTTCA
TCCACCAAGGGCCCATCGGTCTTCC
GTGTCTCATCAGTGACTTCTACCCGG
AGCCAACAAGGCCACACTGGTGTG
CCCTGGCACCCTCCTCCAAGAGCA
GAGCCGTGACAGTGGCCTGGAAGGC
TCTCATCAGTGACTTCTACCCGGGA
CCTCTGGGGGCACAGCGGCCCTGG
AGATAGCAGCCCCGTCAAGGCGGGA
GCCGTGACAGTGGCCTGGAAGGCA
GCTGCCTGGTCAAGGACTACTTCCC
GTGGAAACCACCACACCCTCCAAAC
GATAGCAGCCCCGTCAAGGCGGGA
CGAACCGGTGACGGTGTCGTGGAA
AAAGCAACAACAAGTACGCGGCCGA
GTGGAAACCACCACACCCTCCAAA
CTCAGGCGCCCTGACCAGCGGCGT
AAGCTATCTGAGCCTGACGCCTGAGC
CAAAGCAACAACAAGTACGCGGCC
GCACACCTTCCCGGCTGTCCTACAG
AGTGGAAGTCCCACAGAAGCTACAG
AAGAGCTATCTGAGCCTGACGCCT
TCCTCAGGACTCTACTCCCTCAAGA
CTGCCAGGTCACGCATGAAGGGAGC
GAGCAGTGGAAGTCCCACAGAAGC
GCGTGGTGACCGTGCCCTCCAGCA
ACCGTGGAGAAGACAGTGGCCCCTA
TACAGCTGCCAGGTCACGCATGAA
GCTTGGGCACCCAGACCTACATCT
CAGAATGTTCA
GGGAGCACCGTGGAGAAGACAGTG
GCAACGTGAATCACAAGCCCAGCA
(SEQ ID NO: 479)
GCCCCTACAGAATGTTCA
ACACCAAGGTGGACAAGAAAGTTG
(SEQ ID NO: 480)
AGCCCAAATCTTGTGACAAAACTC
ACACATGCCCACCGTGCCCAGCAC
CTGAACTCCTGGGGGGACCGTCAG
TCTTCCTCTTCCCCCCAAAACCCAA
GGACACCCTCATGATCTCCCGGAC
CCCTGAGGTCACATGCGTGGTGGT
GGACGTGAGCCACGAAGACCCTGA
GGTCAAGTTCAACTGGTACGTGGA
CGGCGTGGAGGTGCATAATGCCAA
GACAAAGCCGTGCGAGGAGCAGTA
CGGCAGCACGTACCGTTGCGTCAG
CGTCCTCACCGTCCTGCACCAGGAC
TGGCTGAATGGCAAGGAGTACAAG
TGCAAGGTGTCCAACAAAGCCCTC
CCAGCCCCCATCGAGAAAACCATC
TCCAAAGCCAAAGGGCAGCCCCGA
GAACCACAGGTGTACACCCTGCCC
CCATCCCGGGAGGAGATGACCAAG
AACCAGGTCAGCCTGACCTGCCTG
GTCAAAGGCTTCTATCCCAGCGAC
ATCGCCGTGGAGTGGGAGAGCAAT
GGGCAGCCGGAGAACAACTACAAG
ACCACGCCTCCCGTGCTGGACTCCG
ACGGCTCCTTCTTCCTCTATAGCAA
GCTCACCGTGGACAAGAGCAGGTG
GCAGCAGGGGAACGTCTTCTCATG
CTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTC
TCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCCAGGTGC
AGCTGCAGGAGTCGGGCCCAGGAC
TGGTGAAGCCTTCGGAAACCCTGT
CCCTCACCTGCACTGTCTCTGGTGG
CTCCATCAGCAGTAGTAGTTACTAC
TGGGGCTGGATCAGGCAGCCCCCA
GGGAAGGGGCTGGAGTGGATTGGG
AGTATCTATTATAGTGGGATCACCA
ACTACAACCCGTCCCTCAAGAGTC
GAGTCACCATCTCCGTAGACACGT
CCAAGAACCAGTTCTCCCTGAAGC
TGAGTTCTGTGACCGCCGCAGACA
CGGCCGTGTATTACTGTGCGAGATC
CAGTAACTACGATGCTTTTGATATC
TGGGGCCAAGGGACAATGGTCACC
GTGTCCTCAGCAAGCACGAAGGGG
CCGTCCGTATTTCCGCTTGCGCCCT
CGTCGAAGTCAACTTCGGGAGGGA
CCGCGGCACTTGGCTGTCTTGTCAA
AGATTACTTCCCTGAGCCAGTGAC
AGTCAGCTGGAATTCCGGTGCCCTC
ACGTCAGGAGTACATACATTCCCT
GCGGTATTGCAGTCCTCCGGACTCT
ACTCCCTGGAGTCGGTGGTAACGG
TGCCCAGCTCCAGCTTGGGGACCC
AGACGTACATTTGTAACGTGAATC
ACAAACCAAGCAATACTAAGGTAG
ATAAGAAAGTAGAACCGAAGAGCT
GC
(SEQ ID NO: 481)
AA
QSALTQPASVSGSPGQSITISCTGTSSD
QSVLTQPPSVSGAPGQRVTISCTGSSS
EVQLLESGGGLVQPGGSLRLSCAAS
VGNYNLVSWYQQHPGKAPKLMIFEVN
NIGAGYDVHWYQQVPGTAPKLLIYG
GFTFSRNAMSWVRQAPGKGLEWVS
QRPSGVSNRFSGSKSGTTASLTISGLQA
NSKRPSGVPDRFSGSKSGTSASLAIT
ATGGSGISTYYADSVKGRFTISRDNS
ADEADYFCCSYTTSSTYVIFGGGTKLT
GLQAEDEADYYCQSYDSSLGGWVF
KNTLYLQMNSLRAEDTAVYYCARG
VLGQPKAAPSVTLFPPSSEELQANKAT
GGGTKLTVLQPKAAPSVTLFPPSSEE
YSNSWWYFDYWGQGTLVTVSSAST
LVCLISDFYPGAVTVAWKADSSPVKA
LQANKATLVCLISDFYPGAVTVAWK
KGPSVFPLAPSSKSTSGGTAALGCLV
GVETTTPSKQSNNKYAAESYLSLTPEQ
ADSSPVKAGVETTTPSKQSNNKYAA
KDYFPEPVTVSWNSGALTSGVHTFP
WKSHRSYSCQVTHEGSTVEKTVAPTE
KSYLSLTPEQWKSHRSYSCQVTHEG
AVLQSSGLYSLKSVVTVPSSSLGTQT
CS
STVEKTVAPTECS
YICNVNHKPSNTKVDKKVEPKSCDK
(SEQ ID NO: 482)
(SEQ ID NO: 483)
THTCPPCPAPELLGGPSVFLFPPKPKD
TLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPCEEQYGST
YRCVSVLTVLHQDWLNGKEYKCKV
SNKALPAPIEKTISKAKGQPREPQVY
TLPPSREEMTKNQVSLTCLVKGFYPS
DIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGS
GGGGSQVQLQESGPGLVKPSETLSLT
CTVSGGSISSSSYYWGWIRQPPGKGL
EWIGSIYYSGITNYNPSLKSRVTISVD
TSKNQFSLKLSSVTAADTAVYYCAR
SSNYDAFDIWGQGTMVTVSSASTKG
PSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAV
LQSSGLYSLESVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 484)
iPS:
21-
[hu anti-
NA
CAGTCTGCCCTGACTCAGCCTGCCTC
GACATTCAGATGACCCAGTCTCCAT
GAGGTGCAGCTGCTGGAGTCTGGG
576299
230_30A12_IgG_
<huCD40> 21-230_
CGTGTCTGGGAGCCCTGGACAGTCGA
CTTCCGTGTCTGCATCTGTAGGGGA
GGAGGCTTGGTACAGCCTGGGGGG
21-
30A12VH]::huIgG1zSEFL2*GK-
TCACCATCTCCTGCACTGGAACCAGC
CAGAGTCACCATCACTTGTCGGGC
TCCCTGAGACTCTCCTGTGCAGCCT
233_4H6__Fab
K::(G4S)2::[hu anti-
AGTGATGTTGGGAATTATAACCTTGT
GAGTCAGGGTATTACCAGGTGGTT
CTGGATTCACCTTTAGTAGAAATGC
<hu Mesothelin>
CTCCTGGTACCAACAGCACCCAGGCA
AGCCTGGTATCAGCAGAAACCAGG
CATGAGTTGGGTCCGCCAGGCTCC
4H6VH]::huIgG1z-
AAGCCCCCAAACTCATGATTTTTGAG
GAAAGCCCCTAAGCTCCTGATCTAT
AGGGAAGGGGCTGGAGTGGGTGTC
CH1-E::EPKSC + [anti-
GTCAATCAGCGGCCCTCAGGGGTTTC
GCTGCATCCGTTTTGCAAAGTGGG
AGCTACTGGTGGTAGTGGTATTAG
<hu CD40>
TAATCGCTTCTCTGGCTCCAAGTCTG
GTCCCATCAAGGTTCAGCGGCAGT
CACATACTACGCAGACTCCGTGAA
21-230_30A12VL]::huLLC2-
GCACCACGGCCTCCCTGACAATCTCT
GGATCTGGGACAGATTTCACTCTCA
GGGCCGGTTCACCATCTCCAGAGA
E + [anti-
GGGCTCCAGGCTGCGGACGAGGCTG
CCATCAGCAGCCTGCAGCCTGAAG
CAATTCCAAGAACACGCTGTATCT
<hu Mesothelin>
ATTATTTCTGCTGCTCATATACAACT
ATTTTGCAACTTACTATTGTCAACA
GCAAATGAACAGTCTGAGAGCCGA
4H6VL]::huKLC-
AGTAGCACTTATGTGATCTTCGGCGG
GTCTAACAGTTTCCCTCGGACGTTC
GGACACGGCCGTATATTACTGTGC
S176K (IgG-Fab);
AGGGACCAAGCTGACCGTCCTAGGT
GGCCAAGGGACCAAGGTGGAAATC
GAGAGGTTATAGCAACAGCTGGTG
LMRID: SS-30864
CAGCCCAAGGCTGCACCCTCGGTCAC
AAACGGACGGTGGCTGCACCATCT
GTACTTTGACTACTGGGGCCAGGG
TCTGTTCCCGCCCTCCTCTGAGGAGC
GTCTTCATCTTCCCGCCATCTGATG
AACCCTGGTCACCGTGTCCTCAGCC
TTCAAGCCAACAAGGCCACACTGGT
AGCAGTTGAAATCTGGAACTGCCT
TCCACCAAGGGCCCATCGGTCTTCC
GTGTCTCATCAGTGACTTCTACCCGG
CTGTTGTGTGCCTGCTGAATAACTT
CCCTGGCACCCTCCTCCAAGAGCA
GAGCCGTGACAGTGGCCTGGAAGGC
CTATCCCAGAGAGGCCAAAGTACA
CCTCTGGGGGCACAGCGGCCCTGG
AGATAGCAGCCCCGTCAAGGCGGGA
GTGGAAGGTGGATAACGCCCTCCA
GCTGCCTGGTCAAGGACTACTTCCC
GTGGAAACCACCACACCCTCCAAAC
ATCGGGTAACTCCCAGGAGAGTGT
CGAACCGGTGACGGTGTCGTGGAA
AAAGCAACAACAAGTACGCGGCCGA
CACAGAGCAGGACAGCAAGGACA
CTCAGGCGCCCTGACCAGCGGCGT
AAGCTATCTGAGCCTGACGCCTGAGC
GCACCTACAGCCTCAAGAGCACCC
GCACACCTTCCCGGCTGTCCTACAG
AGTGGAAGTCCCACAGAAGCTACAG
TGACGCTGAGCAAAGCAGACTACG
TCCTCAGGACTCTACTCCCTCAAGA
CTGCCAGGTCACGCATGAAGGGAGC
AGAAACACAAAGTCTACGCCTGCG
GCGTGGTGACCGTGCCCTCCAGCA
ACCGTGGAGAAGACAGTGGCCCCTA
AAGTCACCCATCAGGGCCTGAGCT
GCTTGGGCACCCAGACCTACATCT
CAGAATGTTCA
CGCCCGTCACAAAGAGCTTCAACA
GCAACGTGAATCACAAGCCCAGCA
(SEQ ID NO: 485)
GGGGAGAGTGT
ACACCAAGGTGGACAAGAAAGTTG
(SEQ ID NO: 486)
AGCCCAAATCTTGTGACAAAACTC
ACACATGCCCACCGTGCCCAGCAC
CTGAACTCCTGGGGGGACCGTCAG
TCTTCCTCTTCCCCCCAAAACCCAA
GGACACCCTCATGATCTCCCGGAC
CCCTGAGGTCACATGCGTGGTGGT
GGACGTGAGCCACGAAGACCCTGA
GGTCAAGTTCAACTGGTACGTGGA
CGGCGTGGAGGTGCATAATGCCAA
GACAAAGCCGTGCGAGGAGCAGTA
CGGCAGCACGTACCGTTGCGTCAG
CGTCCTCACCGTCCTGCACCAGGAC
TGGCTGAATGGCAAGGAGTACAAG
TGCAAGGTGTCCAACAAAGCCCTC
CCAGCCCCCATCGAGAAAACCATC
TCCAAAGCCAAAGGGCAGCCCCGA
GAACCACAGGTGTACACCCTGCCC
CCATCCCGGGAGGAGATGACCAAG
AACCAGGTCAGCCTGACCTGCCTG
GTCAAAGGCTTCTATCCCAGCGAC
ATCGCCGTGGAGTGGGAGAGCAAT
GGGCAGCCGGAGAACAACTACAAG
ACCACGCCTCCCGTGCTGGACTCCG
ACGGCTCCTTCTTCCTCTATAGCAA
GCTCACCGTGGACAAGAGCAGGTG
GCAGCAGGGGAACGTCTTCTCATG
CTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTC
TCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCCAGGTGC
AGCTGGTCGAGTCTGGGGGAGGCT
TGGTCAAGCCTGGAGGGTCCCTGA
GACTCTCCTGTGCAGCCTCTGGATT
CACCTTCAGTGACTACTACATGACC
TGGATCAGGCAGGCTCCAGGGAAG
GGGCTGGAGTGGATTTCATACATT
AGTAGTAGTGGTAGTACCATCTACT
ACGCAGACTCTGTGAAGGGCCGAT
TCACCATCTCCAGGGACAACGCCA
AGAACTCACTGTATCTGCAAATGA
ACAGCCTGAGAGCCGAGGACACGG
CCGTGTATTACTGTGCGAGAGATC
GGAACTCCCACTTTGACTATTGGGG
CCAGGGAACCCTGGTCACCGTGTC
CTCAGCAAGCACGAAGGGGCCGTC
CGTATTTCCGCTTGCGCCCTCGTCG
AAGTCAACTTCGGGAGGGACCGCG
GCACTTGGCTGTCTTGTCAAAGATT
ACTTCCCTGAGCCAGTGACAGTCA
GCTGGAATTCCGGTGCCCTCACGTC
AGGAGTACATACATTCCCTGCGGT
ATTGCAGTCCTCCGGACTCTACTCC
CTGGAGTCGGTGGTAACGGTGCCC
AGCTCCAGCTTGGGGACCCAGACG
TACATTTGTAACGTGAATCACAAA
CCAAGCAATACTAAGGTAGATAAG
AAAGTAGAACCGAAGAGCTGC
(SEQ ID NO: 487)
AA
QSALTQPASVSGSPGQSITISCTGTSSD
DIQMTQSPSSVSASVGDRVTITCRAS
EVQLLESGGGLVQPGGSLRLSCAAS
VGNYNLVSWYQQHPGKAPKLMIFEVN
QGITRWLAWYQQKPGKAPKLLIYAA
GFTFSRNAMSWVRQAPGKGLEWVS
QRPSGVSNRFSGSKSGTTASLTISGLQA
SVLQSGVPSRFSGSGSGTDFTLTISSL
ATGGSGISTYYADSVKGRFTISRDNS
ADEADYFCCSYTTSSTYVIFGGGTKLT
QPEDFATYYCQQSNSFPRTFGQGTK
KNTLYLQMNSLRAEDTAVYYCARG
VLGQPKAAPSVTLFPPSSEELQANKAT
VEIKRTVAAPSVFIFPPSDEQLKSGTA
YSNSWWYFDYWGQGTLVTVSSAST
LVCLISDFYPGAVTVAWKADSSPVKA
SVVCLLNNFYPREAKVQWKVDNAL
KGPSVFPLAPSSKSTSGGTAALGCLV
GVETTTPSKQSNNKYAAESYLSLTPEQ
QSGNSQESVTEQDSKDSTYSLKSTLT
KDYFPEPVTVSWNSGALTSGVHTFP
WKSHRSYSCQVTHEGSTVEKTVAPTE
LSKADYEKHKVYACEVTHQGLSSPV
AVLQSSGLYSLKSVVTVPSSSLGTQT
CS
TKSFNRGEC
YICNVNHKPSNTKVDKKVEPKSCDK
(SEQ ID NO: 488)
(SEQ ID NO: 489)
THTCPPCPAPELLGGPSVFLFPPKPKD
TLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPCEEQYGST
YRCVSVLTVLHQDWLNGKEYKCKV
SNKALPAPIEKTISKAKGQPREPQVY
TLPPSREEMTKNQVSLTCLVKGFYPS
DIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGS
GGGGSQVQLVESGGGLVKPGGSLRL
SCAASGFTFSDYYMTWIRQAPGKGL
EWISYISSSGSTIYYADSVKGRFTISR
DNAKNSLYLQMNSLRAEDTAVYYC
ARDRNSHFDYWGQGTLVTVSSASTK
GPSVFPLAPSSKSTSGGTAALGCLVK
DYFPEPVTVSWNSGALTSGVHTFPA
VLQSSGLYSLESVVTVPSSSLGTQTYI
CNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 490)
iPS:
21-
[hu anti-
NA
CAGTCTGCCCTGACTCAGCCTGCCTC
GACATCCAGATGACCCAGTCTCCA
GAGGTGCAGCTGCTGGAGTCTGGG
576302
230_30A12_IgG_
<hu CD40> 21-230_
CGTGTCTGGGAGCCCTGGACAGTCGA
TCTTCCGTGTCTGCTTCTGTCGGAG
GGAGGCTTGGTACAGCCTGGGGGG
21-
30A12VH]::huIgG1zSEFL2*GK-
TCACCATCTCCTGCACTGGAACCAGC
ACAGAGTCACCATCACTTGTCGGG
TCCCTGAGACTCTCCTGTGCAGCCT
233_6F4__Fab
K::(G4S)2::[hu anti-
AGTGATGTTGGGAATTATAACCTTGT
CGAGTCAGGATATTAGCAGGTGGT
CTGGATTCACCTTTAGTAGAAATGC
<hu Mesothelin>
CTCCTGGTACCAACAGCACCCAGGCA
TAGCCTGGTATCAGCAGAAACCAG
CATGAGTTGGGTCCGCCAGGCTCC
6F4VH]::huIgG1z-
AAGCCCCCAAACTCATGATTTTTGAG
GGAAAGCCCCTAAGCTCCTGATTTC
AGGGAAGGGGCTGGAGTGGGTGTC
CH1-E::EPKSC + [anti-
GTCAATCAGCGGCCCTCAGGGGTTTC
TGCTGCATCCAGATTGCAAAGTGG
AGCTACTGGTGGTAGTGGTATTAG
<hu CD40>
TAATCGCTTCTCTGGCTCCAAGTCTG
AGTCCCATCAAGGTTCAGCGGCAG
CACATACTACGCAGACTCCGTGAA
21-230_30A12VL]::huLLC2-
GCACCACGGCCTCCCTGACAATCTCT
TGGATCTGGGACAGATTTCACTCTC
GGGCCGGTTCACCATCTCCAGAGA
E + [anti-
GGGCTCCAGGCTGCGGACGAGGCTG
ACCATCAGCAGCCTGCAGCCTGAA
CAATTCCAAGAACACGCTGTATCT
<hu Mesothelin>
ATTATTTCTGCTGCTCATATACAACT
GATTTTGCAATTTACTATTGTCAAC
GCAAATGAACAGTCTGAGAGCCGA
6F4VL]::huKLC-
AGTAGCACTTATGTGATCTTCGGCGG
AGGCTAAAAGTTTTCCTCGGACGTT
GGACACGGCCGTATATTACTGTGC
S176K (IgG-Fab);
AGGGACCAAGCTGACCGTCCTAGGT
CGGCCAAGGGACCAAGGTGGAAAT
GAGAGGTTATAGCAACAGCTGGTG
LMRID: SS-30865
CAGCCCAAGGCTGCACCCTCGGTCAC
CAAACGGACGGTGGCTGCACCATC
GTACTTTGACTACTGGGGCCAGGG
TCTGTTCCCGCCCTCCTCTGAGGAGC
TGTCTTCATCTTCCCGCCATCTGAT
AACCCTGGTCACCGTGTCCTCAGCC
TTCAAGCCAACAAGGCCACACTGGT
GAGCAGTTGAAATCTGGAACTGCC
TCCACCAAGGGCCCATCGGTCTTCC
GTGTCTCATCAGTGACTTCTACCCGG
TCTGTTGTGTGCCTGCTGAATAACT
CCCTGGCACCCTCCTCCAAGAGCA
GAGCCGTGACAGTGGCCTGGAAGGC
TCTATCCCAGAGAGGCCAAAGTAC
CCTCTGGGGGCACAGCGGCCCTGG
AGATAGCAGCCCCGTCAAGGCGGGA
AGTGGAAGGTGGATAACGCCCTCC
GCTGCCTGGTCAAGGACTACTTCCC
GTGGAAACCACCACACCCTCCAAAC
AATCGGGTAACTCCCAGGAGAGTG
CGAACCGGTGACGGTGTCGTGGAA
AAAGCAACAACAAGTACGCGGCCGA
TCACAGAGCAGGACAGCAAGGACA
CTCAGGCGCCCTGACCAGCGGCGT
AAGCTATCTGAGCCTGACGCCTGAGC
GCACCTACAGCCTCAAGAGCACCC
GCACACCTTCCCGGCTGTCCTACAG
AGTGGAAGTCCCACAGAAGCTACAG
TGACGCTGAGCAAAGCAGACTACG
TCCTCAGGACTCTACTCCCTCAAGA
CTGCCAGGTCACGCATGAAGGGAGC
AGAAACACAAAGTCTACGCCTGCG
GCGTGGTGACCGTGCCCTCCAGCA
ACCGTGGAGAAGACAGTGGCCCCTA
AAGTCACCCATCAGGGCCTGAGCT
GCTTGGGCACCCAGACCTACATCT
CAGAATGTTCA
CGCCCGTCACAAAGAGCTTCAACA
GCAACGTGAATCACAAGCCCAGCA
(SEQ ID NO: 491)
GGGGAGAGTGT
ACACCAAGGTGGACAAGAAAGTTG
(SEQ ID NO: 492)
AGCCCAAATCTTGTGACAAAACTC
ACACATGCCCACCGTGCCCAGCAC
CTGAACTCCTGGGGGGACCGTCAG
TCTTCCTCTTCCCCCCAAAACCCAA
GGACACCCTCATGATCTCCCGGAC
CCCTGAGGTCACATGCGTGGTGGT
GGACGTGAGCCACGAAGACCCTGA
GGTCAAGTTCAACTGGTACGTGGA
CGGCGTGGAGGTGCATAATGCCAA
GACAAAGCCGTGCGAGGAGCAGTA
CGGCAGCACGTACCGTTGCGTCAG
CGTCCTCACCGTCCTGCACCAGGAC
TGGCTGAATGGCAAGGAGTACAAG
TGCAAGGTGTCCAACAAAGCCCTC
CCAGCCCCCATCGAGAAAACCATC
TCCAAAGCCAAAGGGCAGCCCCGA
GAACCACAGGTGTACACCCTGCCC
CCATCCCGGGAGGAGATGACCAAG
AACCAGGTCAGCCTGACCTGCCTG
GTCAAAGGCTTCTATCCCAGCGAC
ATCGCCGTGGAGTGGGAGAGCAAT
GGGCAGCCGGAGAACAACTACAAG
ACCACGCCTCCCGTGCTGGACTCCG
ACGGCTCCTTCTTCCTCTATAGCAA
GCTCACCGTGGACAAGAGCAGGTG
GCAGCAGGGGAACGTCTTCTCATG
CTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTC
TCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCCAGGTGC
AGCTGGTGGAGTCTGGGGGAGGCT
TGGTCAAGCCTGGAGGGTCCCTGA
GACTCTCCTGTGCAGCCTCTGGATT
CACCTTCAGTGACTACTACATGAGC
TGGATCCGCCAGGCTCCAGGGAAG
GGGCTGGAGTGGATTTCATACATT
AGTAGCAGTGAAAGTATCATCTAT
TACGTAGACTCTGTGAAGGGCCGA
TTCACCATCTCCAGGGACAACGCC
AAGAACTCACTGTATCTGCAAATG
AACAGCCTGAGAGCCGAGGACACG
GCCGTGTATTACTGTGCGAGAGAT
GTTGGGAGCCACTTTGACTACTGG
GGCCAGGGAACCCTGGTCACCGTG
TCCTCAGCAAGCACGAAGGGGCCG
TCCGTATTTCCGCTTGCGCCCTCGT
CGAAGTCAACTTCGGGAGGGACCG
CGGCACTTGGCTGTCTTGTCAAAGA
TTACTTCCCTGAGCCAGTGACAGTC
AGCTGGAATTCCGGTGCCCTCACGT
CAGGAGTACATACATTCCCTGCGG
TATTGCAGTCCTCCGGACTCTACTC
CCTGGAGTCGGTGGTAACGGTGCC
CAGCTCCAGCTTGGGGACCCAGAC
GTACATTTGTAACGTGAATCACAA
ACCAAGCAATACTAAGGTAGATAA
GAAAGTAGAACCGAAGAGCTGC
(SEQ ID NO: 493)
AA
QSALTQPASVSGSPGQSITISCTGTSSD
DIQMTQSPSSVSASVGDRVTITCRAS
EVQLLESGGGLVQPGGSLRLSCAAS
VGNYNLVSWYQQHPGKAPKLMIFEVN
QDISRWLAWYQQKPGKAPKLLISAA
GFTFSRNAMSWVRQAPGKGLEWVS
QRPSGVSNRFSGSKSGTTASLTISGLQA
SRLQSGVPSRFSGSGSGTDFTLTISSL
ATGGSGISTYYADSVKGRFTISRDNS
ADEADYFCCSYTTSSTYVIFGGGTKLT
QPEDFAIYYCQQAKSFPRTFGQGTKV
KNTLYLQMNSLRAEDTAVYYCARG
VLGQPKAAPSVTLFPPSSEELQANKAT
EIKRTVAAPSVFIFPPSDEQLKSGTAS
YSNSWWYFDYWGQGTLVTVSSAST
LVCLISDFYPGAVTVAWKADSSPVKA
VVCLLNNFYPREAKVQWKVDNALQ
KGPSVFPLAPSSKSTSGGTAALGCLV
GVETTTPSKQSNNKYAAESYLSLTPEQ
SGNSQESVTEQDSKDSTYSLKSTLTL
KDYFPEPVTVSWNSGALTSGVHTFP
WKSHRSYSCQVTHEGSTVEKTVAPTE
SKADYEKHKVYACEVTHQGLSSPVT
AVLQSSGLYSLKSVVTVPSSSLGTQT
CS
KSFNRGEC
YICNVNHKPSNTKVDKKVEPKSCDK
(SEQ ID NO: 494)
(SEQ ID NO: 495)
THTCPPCPAPELLGGPSVFLFPPKPKD
TLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPCEEQYGST
YRCVSVLTVLHQDWLNGKEYKCKV
SNKALPAPIEKTISKAKGQPREPQVY
TLPPSREEMTKNQVSLTCLVKGFYPS
DIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGS
GGGGSQVQLVESGGGLVKPGGSLRL
SCAASGFTFSDYYMSWIRQAPGKGL
EWISYISSSESIIYYVDSVKGRFTISRD
NAKNSLYLQMNSLRAEDTAVYYCA
RDVGSHFDYWGQGTLVTVSSASTKG
PSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAV
LQSSGLYSLESVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 496)
iPS:
21-
[hu anti-
NA
CAGTCTGCCCTGACTCAGCCTGCCTC
GACATTGTGATGACTCAGTCTCCAG
GAGGTGCAGCTGCTGGAGTCTGGG
576305
230_30A12_IgG_
<hu CD40> 21-230_
CGTGTCTGGGAGCCCTGGACAGTCGA
ACTCCCTGGCTGTGTCTCTGGGCGA
GGAGGCTTGGTACAGCCTGGGGGG
21-
30A12VH]::huIgG1zSEFL2*GK-
TCACCATCTCCTGCACTGGAACCAGC
GAGGGCCACCATCAACTGCAAGTC
TCCCTGAGACTCTCCTGTGCAGCCT
233_7G11__Fab
K::(G4S)2::[hu anti-
AGTGATGTTGGGAATTATAACCTTGT
CAGCCAGAGTGTTTTATACAGCTCC
CTGGATTCACCTTTAGTAGAAATGC
<hu Mesothelin>
CTCCTGGTACCAACAGCACCCAGGCA
AACAATAAGAACTACTTAGCTTGG
CATGAGTTGGGTCCGCCAGGCTCC
7G11VH]::huIgG1z-
AAGCCCCCAAACTCATGATTTTTGAG
TACCAGCAGAAACCAGGACAGCCT
AGGGAAGGGGCTGGAGTGGGTGTC
CH1-E::EPKSC + [anti-
GTCAATCAGCGGCCCTCAGGGGTTTC
CCTAAGCTGCTCATTTACTGGGCAT
AGCTACTGGTGGTAGTGGTATTAG
<hu CD40>
TAATCGCTTCTCTGGCTCCAAGTCTG
CTACCCGAGAATCCGGGGTCCCTG
CACATACTACGCAGACTCCGTGAA
21-230_30A12VL]::huLLC2-
GCACCACGGCCTCCCTGACAATCTCT
ACCGATTCAGTGGCAGCGGGTCTG
GGGCCGGTTCACCATCTCCAGAGA
E + [anti-
GGGCTCCAGGCTGCGGACGAGGCTG
GGACAGATTTCACTCTCACCATCAG
CAATTCCAAGAACACGCTGTATCT
<hu Mesothelin>
ATTATTTCTGCTGCTCATATACAACT
CAGCCTGCAGGCTGAAGATGTGGC
GCAAATGAACAGTCTGAGAGCCGA
7G11VL]::huKLC-
AGTAGCACTTATGTGATCTTCGGCGG
AGTTTATTACTGTCAGCAATATTAT
GGACACGGCCGTATATTACTGTGC
S176K (IgG-Fab);
AGGGACCAAGCTGACCGTCCTAGGT
AGTACTCCTCCGACGTTCGGCCAA
GAGAGGTTATAGCAACAGCTGGTG
LMRID: SS-30866
CAGCCCAAGGCTGCACCCTCGGTCAC
GGGACCAAGGTGGAGATCAAACGG
GTACTTTGACTACTGGGGCCAGGG
TCTGTTCCCGCCCTCCTCTGAGGAGC
ACGGTGGCTGCACCATCTGTCTTCA
AACCCTGGTCACCGTGTCCTCAGCC
TTCAAGCCAACAAGGCCACACTGGT
TCTTCCCGCCATCTGATGAGCAGTT
TCCACCAAGGGCCCATCGGTCTTCC
GTGTCTCATCAGTGACTTCTACCCGG
GAAATCTGGAACTGCCTCTGTTGTG
CCCTGGCACCCTCCTCCAAGAGCA
GAGCCGTGACAGTGGCCTGGAAGGC
TGCCTGCTGAATAACTTCTATCCCA
CCTCTGGGGGCACAGCGGCCCTGG
AGATAGCAGCCCCGTCAAGGCGGGA
GAGAGGCCAAAGTACAGTGGAAGG
GCTGCCTGGTCAAGGACTACTTCCC
GTGGAAACCACCACACCCTCCAAAC
TGGATAACGCCCTCCAATCGGGTA
CGAACCGGTGACGGTGTCGTGGAA
AAAGCAACAACAAGTACGCGGCCGA
ACTCCCAGGAGAGTGTCACAGAGC
CTCAGGCGCCCTGACCAGCGGCGT
AAGCTATCTGAGCCTGACGCCTGAGC
AGGACAGCAAGGACAGCACCTACA
GCACACCTTCCCGGCTGTCCTACAG
AGTGGAAGTCCCACAGAAGCTACAG
GCCTCAAGAGCACCCTGACGCTGA
TCCTCAGGACTCTACTCCCTCAAGA
CTGCCAGGTCACGCATGAAGGGAGC
GCAAAGCAGACTACGAGAAACACA
GCGTGGTGACCGTGCCCTCCAGCA
ACCGTGGAGAAGACAGTGGCCCCTA
AAGTCTACGCCTGCGAAGTCACCC
GCTTGGGCACCCAGACCTACATCT
CAGAATGTTCA
ATCAGGGCCTGAGCTCGCCCGTCA
GCAACGTGAATCACAAGCCCAGCA
(SEQ ID NO: 497)
CAAAGAGCTTCAACAGGGGAGAGT
ACACCAAGGTGGACAAGAAAGTTG
GT
AGCCCAAATCTTGTGACAAAACTC
(SEQ ID NO: 498)
ACACATGCCCACCGTGCCCAGCAC
CTGAACTCCTGGGGGGACCGTCAG
TCTTCCTCTTCCCCCCAAAACCCAA
GGACACCCTCATGATCTCCCGGAC
CCCTGAGGTCACATGCGTGGTGGT
GGACGTGAGCCACGAAGACCCTGA
GGTCAAGTTCAACTGGTACGTGGA
CGGCGTGGAGGTGCATAATGCCAA
GACAAAGCCGTGCGAGGAGCAGTA
CGGCAGCACGTACCGTTGCGTCAG
CGTCCTCACCGTCCTGCACCAGGAC
TGGCTGAATGGCAAGGAGTACAAG
TGCAAGGTGTCCAACAAAGCCCTC
CCAGCCCCCATCGAGAAAACCATC
TCCAAAGCCAAAGGGCAGCCCCGA
GAACCACAGGTGTACACCCTGCCC
CCATCCCGGGAGGAGATGACCAAG
AACCAGGTCAGCCTGACCTGCCTG
GTCAAAGGCTTCTATCCCAGCGAC
ATCGCCGTGGAGTGGGAGAGCAAT
GGGCAGCCGGAGAACAACTACAAG
ACCACGCCTCCCGTGCTGGACTCCG
ACGGCTCCTTCTTCCTCTATAGCAA
GCTCACCGTGGACAAGAGCAGGTG
GCAGCAGGGGAACGTCTTCTCATG
CTCCGTGATGCATGAGGCTCTGCAC
AACCACTACACGCAGAAGAGCCTC
TCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCGAGGTGC
AGCTGGTCGAGTCTGGAGGAGGCT
TGATCCAGCCTGGGGGGTCCCTGA
GACTCTCCTGTGCAGTCTCTGGGTT
CACCGTCAGTAGCAAGTTCATGAC
CTGGGTCCGCCAGGCTCCAGGGAA
GGGGCTGGAGTGGGTGTCAGTTAT
TTATAGCGGTGGTAAGACATACTA
CGCAGACTCCGTGAAGGGCCGATT
CACCATCTCCAGAGACAATTCCAA
GAACACGCTGTATCTTCAAATGAA
CAGCCTGAGAGCCGAGGACACGGC
CGTGTATTACTGTGCGAGAGATAG
CGGTGGCTGGGGGTACTTTGACTA
CTGGGGCCAGGGAACCCTGGTCAC
CGTGTCCTCAGCAAGCACGAAGGG
GCCGTCCGTATTTCCGCTTGCGCCC
TCGTCGAAGTCAACTTCGGGAGGG
ACCGCGGCACTTGGCTGTCTTGTCA
AAGATTACTTCCCTGAGCCAGTGA
CAGTCAGCTGGAATTCCGGTGCCCT
CACGTCAGGAGTACATACATTCCCT
GCGGTATTGCAGTCCTCCGGACTCT
ACTCCCTGGAGTCGGTGGTAACGG
TGCCCAGCTCCAGCTTGGGGACCC
AGACGTACATTTGTAACGTGAATC
ACAAACCAAGCAATACTAAGGTAG
ATAAGAAAGTAGAACCGAAGAGCT
GC
(SEQ ID NO: 499)
AA
QSALTQPASVSGSPGQSITISCTGTSSD
DIVMTQSPDSLAVSLGERATINCKSS
EVQLLESGGGLVQPGGSLRLSCAAS
VGNYNLVSWYQQHPGKAPKLMIFEVN
QSVLYSSNNKNYLAWYQQKPGQPP
GFTFSRNAMSWVRQAPGKGLEWVS
QRPSGVSNRFSGSKSGTTASLTISGLQA
KLLIYWASTRESGVPDRFSGSGSGTD
ATGGSGISTYYADSVKGRFTISRDNS
ADEADYFCCSYTTSSTYVIFGGGTKLT
FTLTISSLQAEDVAVYYCQQYYSTPP
KNTLYLQMNSLRAEDTAVYYCARG
VLGQPKAAPSVTLFPPSSEELQANKAT
TFGQGTKVEIKRTVAAPSVFIFPPSDE
YSNSWWYFDYWGQGTLVTVSSAST
LVCLISDFYPGAVTVAWKADSSPVKA
QLKSGTASVVCLLNNFYPREAKVQW
KGPSVFPLAPSSKSTSGGTAALGCLV
GVETTTPSKQSNNKYAAESYLSLTPEQ
KVDNALQSGNSQESVTEQDSKDSTY
KDYFPEPVTVSWNSGALTSGVHTFP
WKSHRSYSCQVTHEGSTVEKTVAPTE
SLKSTLTLSKADYEKHKVYACEVTH
AVLQSSGLYSLKSVVTVPSSSLGTQT
CS
QGLSSPVTKSFNRGEC
YICNVNHKPSNTKVDKKVEPKSCDK
(SEQ ID NO: 500)
(SEQ ID NO: 501)
THTCPPCPAPELLGGPSVFLFPPKPKD
TLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPCEEQYGST
YRCVSVLTVLHQDWLNGKEYKCKV
SNKALPAPIEKTISKAKGQPREPQVY
TLPPSREEMTKNQVSLTCLVKGFYPS
DIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGS
GGGGSEVQLVESGGGLIQPGGSLRLS
CAVSGFTVSSKFMTWVRQAPGKGLE
WVSVIYSGGKTYYADSVKGRFTISR
DNSKNTLYLQMNSLRAEDTAVYYC
ARDSGGWGYFDYWGQGTLVTVSSA
STKGPSVFPLAPSSKSTSGGTAALGC
LVKDYFPEPVTVSWNSGALTSGVHT
FPAVLQSSGLYSLESVVTVPSSSLGT
QTYICNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 502)
iPS:
21-
[hu anti-
NA
GACATCCAGATGACCCAGTCTCCATC
CAGTCAGTGTTGACGCAGCCGCCC
CAGGTGCAACTGGTGCAGTCTGGG
576308
230_33H6_IgG_
<hu CD40> 21-230_
CTCCCTGTCTGCATCTGTAGGAGACA
TCAGTGTCTGGGGCCCCAGGGCAG
GCTGAAGTGAAGAAGCCTGGGGCC
21-
33H6VH]::huIgG1zSEFL2*GK-
GAGTCACCATCACTTGCCGGGCAGGT
AGGGTCACCATCTCCTGCACTGGG
TCAGTGAAGGTGTCCTGCAAGGCT
233_4G12__Fab
K::(G4S)2::[hu anti-
CAGAACATTAGCAGGCATTTAAATTG
AGCAGCTCCAACATCGGGGCAGGT
TCTGGATACACCTTCCCCGGCTACT
<hu Mesothelin>
GTATCAGCAGAATCCAGGGAAAGCC
TATGATGTTCACTGGTACCAGCAG
ATATGTACTGGTTGCGACAGGCCC
4G12VH]::huIgG1z-
CCTAAGGTCCTGATCCATCCTGCATC
GTTCCAGGAACAGCCCCCAAACTC
CTGGACAAGGACTTGAGTGGATGG
CH1-E::EPKSC + [anti-
CAGTTTGCCAAGTGGGGTCCCGTCAA
CTCATCTATGGTAACAGCAAGCGG
GATGGATCAACCCTGACAGTGGTG
<hu CD40>
GGTTCAGTGGCAGTGGATCTGGGAC
CCCTCAGGGGTCCCTGACCGATTCT
ACACAAACTATGCACAGAAGTTTC
21-230_33H6VL]::huKLC-
AGATTTCAGTCTTACCATCAGCAGTC
CTGGCTCCAAGTCTGGCACCTCAGC
AGGGCAGGGTCACCATGACCAGGG
S176E + [anti-
TGCAACCTGAAGATTTTGGAACTTAC
CTCCCTGGCCATCACTGGGCTCCAG
ACACGTCCATCAGCACAGCCTTTAT
<hu Mesothelin>
TTCTGTCAACAGAGTTACAGTACCCC
GCTGAGGATGAGGCTGATTATTAC
GGAGCTGAGCAGGCTGAGATCAGA
4G12VL]::huLLC2-
TCCCACTTTCGGCGGAGGGACCAAG
TGCCAGTCCTATGACAGCAGCCTG
CGACACGGCCGTGTATTACTGTGC
K (IgG-Fab);
GTGGAGCTCAAACGAACGGTGGCTG
GGTGGTTGGGTGTTCGGCGGAGGG
GAGAGAGAAGCCCAGATATTTTGA
LMRID: SS-30867
CACCATCTGTCTTCATCTTCCCGCCAT
ACCAAGCTGACCGTCCTACAGCCC
CTCCTTCTACTACTACCTTATGGAC
CTGATGAGCAGTTGAAATCTGGAACT
AAGGCTGCACCCTCGGTCACTCTGT
GTCTGGGGCCAAGGGACCACGGTC
GCCTCTGTTGTGTGCCTGCTGAATAA
TCCCGCCCTCCTCTGAGGAGCTTCA
ACCGTGTCCTCAGCCTCCACCAAG
CTTCTATCCCAGAGAGGCCAAAGTAC
AGCCAACAAGGCCACACTGGTGTG
GGCCCATCGGTCTTCCCCCTGGCAC
AGTGGAAGGTGGATAACGCCCTCCA
TCTCATCAGTGACTTCTACCCGGGA
CCTCCTCCAAGAGCACCTCTGGGG
ATCGGGTAACTCCCAGGAGAGTGTC
GCCGTGACAGTGGCCTGGAAGGCA
GCACAGCGGCCCTGGGCTGCCTGG
ACAGAGCAGGACAGCAAGGACAGCA
GATAGCAGCCCCGTCAAGGCGGGA
TCAAGGACTACTTCCCCGAACCGG
CCTACAGCCTCGAAAGCACCCTGACG
GTGGAAACCACCACACCCTCCAAA
TGACGGTGTCGTGGAACTCAGGCG
CTGAGCAAAGCAGACTACGAGAAAC
CAAAGCAACAACAAGTACGCGGCC
CCCTGACCAGCGGCGTGCACACCT
ACAAAGTCTACGCCTGCGAAGTCACC
AAGAGCTATCTGAGCCTGACGCCT
TCCCGGCTGTCCTACAGTCCTCAGG
CATCAGGGCCTGAGCTCGCCCGTCAC
GAGCAGTGGAAGTCCCACAGAAGC
ACTCTACTCCCTCAAGAGCGTGGTG
AAAGAGCTTCAACAGGGGAGAGTGT
TACAGCTGCCAGGTCACGCATGAA
ACCGTGCCCTCCAGCAGCTTGGGC
(SEQ ID NO: 503)
GGGAGCACCGTGGAGAAGACAGTG
ACCCAGACCTACATCTGCAACGTG
GCCCCTACAGAATGTTCA
AATCACAAGCCCAGCAACACCAAG
(SEQ ID NO: 504)
GTGGACAAGAAAGTTGAGCCCAAA
TCTTGTGACAAAACTCACACATGCC
CACCGTGCCCAGCACCTGAACTCCT
GGGGGGACCGTCAGTCTTCCTCTTC
CCCCCAAAACCCAAGGACACCCTC
ATGATCTCCCGGACCCCTGAGGTC
ACATGCGTGGTGGTGGACGTGAGC
CACGAAGACCCTGAGGTCAAGTTC
AACTGGTACGTGGACGGCGTGGAG
GTGCATAATGCCAAGACAAAGCCG
TGCGAGGAGCAGTACGGCAGCACG
TACCGTTGCGTCAGCGTCCTCACCG
TCCTGCACCAGGACTGGCTGAATG
GCAAGGAGTACAAGTGCAAGGTGT
CCAACAAAGCCCTCCCAGCCCCCA
TCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGG
TGTACACCCTGCCCCCATCCCGGGA
GGAGATGACCAAGAACCAGGTCAG
CCTGACCTGCCTGGTCAAAGGCTTC
TATCCCAGCGACATCGCCGTGGAG
TGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCC
GTGCTGGACTCCGACGGCTCCTTCT
TCCTCTATAGCAAGCTCACCGTGGA
CAAGAGCAGGTGGCAGCAGGGGA
ACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACAC
GCAGAAGAGCCTCTCCCTGTCTCCG
GGTGGTGGCGGATCGGGAGGTGGC
GGATCCCAGGTGCAGCTGCAGGAG
TCGGGCCCAGGACTGGTGAAGCCT
TCGGAAACCCTGTCCCTCACCTGCA
CTGTCTCTGGTGGCTCCATCAGCAG
TAGTAGTTACTACTGGGGCTGGATC
AGGCAGCCCCCAGGGAAGGGGCTG
GAGTGGATTGGGAGTATCTATTAT
AGTGGGATCACCAACTACAACCCG
TCCCTCAAGAGTCGAGTCACCATCT
CCGTAGACACGTCCAAGAACCAGT
TCTCCCTGAAGCTGAGTTCTGTGAC
CGCCGCAGACACGGCCGTGTATTA
CTGTGCGAGATCCAGTAACTACGA
TGCTTTTGATATCTGGGGCCAAGGG
ACAATGGTCACCGTGTCCTCAGCA
AGCACGAAGGGGCCGTCCGTATTT
CCGCTTGCGCCCTCGTCGAAGTCAA
CTTCGGGAGGGACCGCGGCACTTG
GCTGTCTTGTCAAAGATTACTTCCC
TGAGCCAGTGACAGTCAGCTGGAA
TTCCGGTGCCCTCACGTCAGGAGTA
CATACATTCCCTGCGGTATTGCAGT
CCTCCGGACTCTACTCCCTGGAGTC
GGTGGTAACGGTGCCCAGCTCCAG
CTTGGGGACCCAGACGTACATTTGT
AACGTGAATCACAAACCAAGCAAT
ACTAAGGTAGATAAGAAAGTAGAA
CCGAAGAGCTGC
(SEQ ID NO: 505)
AA
DIQMTQSPSSLSASVGDRVTITCRAGQ
QSVLTQPPSVSGAPGQRVTISCTGSSS
QVQLVQSGAEVKKPGASVKVSCKAS
NISRHLNWYQQNPGKAPKVLIHPASSL
NIGAGYDVHWYQQVPGTAPKLLIYG
GYTFPGYYMYWLRQAPGQGLEWM
PSGVPSRFSGSGSGTDFSLTISSLQPEDF
NSKRPSGVPDRFSGSKSGTSASLAIT
GWINPDSGDTNYAQKFQGRVTMTR
GTYFCQQSYSTPPTFGGGTKVELKRTV
GLQAEDEADYYCQSYDSSLGGWVF
DTSISTAFMELSRLRSDDTAVYYCAR
AAPSVFIFPPSDEQLKSGTASVVCLLNN
GGGTKLTVLQPKAAPSVTLFPPSSEE
EKPRYFDSFYYYLMDVWGQGTTVT
FYPREAKVQWKVDNALQSGNSQESVT
LQANKATLVCLISDFYPGAVTVAWK
VSSASTKGPSVFPLAPSSKSTSGGTA
EQDSKDSTYSLESTLTLSKADYEKHKV
ADSSPVKAGVETTTPSKQSNNKYAA
ALGCLVKDYFPEPVTVSWNSGALTS
YACEVTHQGLSSPVTKSFNRGEC
KSYLSLTPEQWKSHRSYSCQVTHEG
GVHTFPAVLQSSGLYSLKSVVTVPSS
(SEQ ID NO: 506)
STVEKTVAPTECS
SLGTQTYICNVNHKPSNTKVDKKVE
(SEQ ID NO: 507)
PKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSH
EDPEVKFNWYVDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNG
KEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCL
VKGFYPSDIAVEWESNGQPENNYKT
TPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSL
SPGGGGSGGGGSQVQLQESGPGLVK
PSETLSLTCTVSGGSISSSSYYWGWIR
QPPGKGLEWIGSIYYSGITNYNPSLKS
RVTISVDTSKNQFSLKLSSVTAADTA
VYYCARSSNYDAFDIWGQGTMVTV
SSASTKGPSVFPLAPSSKSTSGGTAAL
GCLVKDYFPEPVTVSWNSGALTSGV
HTFPAVLQSSGLYSLESVVTVPSSSL
GTQTYICNVNHKPSNTKVDKKVEPK
SC
(SEQ ID NO: 508)
iPS:
21-
[hu anti-
NA
GACATCCAGATGACCCAGTCTCCATC
GACATTCAGATGACCCAGTCTCCAT
CAGGTGCAACTGGTGCAGTCTGGG
576313
230_33H6_IgG_
<hu CD40> 21-230_
CTCCCTGTCTGCATCTGTAGGAGACA
CTTCCGTGTCTGCATCTGTAGGGGA
GCTGAAGTGAAGAAGCCTGGGGCC
21-
33H6VH]::huIgG1zSEFL2*GK-
GAGTCACCATCACTTGCCGGGCAGGT
CAGAGTCACCATCACTTGTCGGGC
TCAGTGAAGGTGTCCTGCAAGGCT
233_4H6__Fab
K::(G4S)2::[hu anti-
CAGAACATTAGCAGGCATTTAAATTG
GAGTCAGGGTATTACCAGGTGGTT
TCTGGATACACCTTCCCCGGCTACT
<hu Mesothelin>
GTATCAGCAGAATCCAGGGAAAGCC
AGCCTGGTATCAGCAGAAACCAGG
ATATGTACTGGTTGCGACAGGCCC
4H6VH]::huIgG1z-
CCTAAGGTCCTGATCCATCCTGCATC
GAAAGCCCCTAAGCTCCTGATCTAT
CTGGACAAGGACTTGAGTGGATGG
CH1-E::EPKSC + [anti-
CAGTTTGCCAAGTGGGGTCCCGTCAA
GCTGCATCCGTTTTGCAAAGTGGG
GATGGATCAACCCTGACAGTGGTG
<hu CD40>
GGTTCAGTGGCAGTGGATCTGGGAC
GTCCCATCAAGGTTCAGCGGCAGT
ACACAAACTATGCACAGAAGTTTC
21-230_33H6VL]::huKLC-
AGATTTCAGTCTTACCATCAGCAGTC
GGATCTGGGACAGATTTCACTCTCA
AGGGCAGGGTCACCATGACCAGGG
S176 E + [anti-
TGCAACCTGAAGATTTTGGAACTTAC
CCATCAGCAGCCTGCAGCCTGAAG
ACACGTCCATCAGCACAGCCTTTAT
<hu Mesothelin>
TTCTGTCAACAGAGTTACAGTACCCC
ATTTTGCAACTTACTATTGTCAACA
GGAGCTGAGCAGGCTGAGATCAGA
4H6VL]::huKLC-
TCCCACTTTCGGCGGAGGGACCAAG
GTCTAACAGTTTCCCTCGGACGTTC
CGACACGGCCGTGTATTACTGTGC
S176K (IgG-Fab);
GTGGAGCTCAAACGAACGGTGGCTG
GGCCAAGGGACCAAGGTGGAAATC
GAGAGAGAAGCCCAGATATTTTGA
LMRID: SS-30868
CACCATCTGTCTTCATCTTCCCGCCAT
AAACGGACGGTGGCTGCACCATCT
CTCCTTCTACTACTACCTTATGGAC
CTGATGAGCAGTTGAAATCTGGAACT
GTCTTCATCTTCCCGCCATCTGATG
GTCTGGGGCCAAGGGACCACGGTC
GCCTCTGTTGTGTGCCTGCTGAATAA
AGCAGTTGAAATCTGGAACTGCCT
ACCGTGTCCTCAGCCTCCACCAAG
CTTCTATCCCAGAGAGGCCAAAGTAC
CTGTTGTGTGCCTGCTGAATAACTT
GGCCCATCGGTCTTCCCCCTGGCAC
AGTGGAAGGTGGATAACGCCCTCCA
CTATCCCAGAGAGGCCAAAGTACA
CCTCCTCCAAGAGCACCTCTGGGG
ATCGGGTAACTCCCAGGAGAGTGTC
GTGGAAGGTGGATAACGCCCTCCA
GCACAGCGGCCCTGGGCTGCCTGG
ACAGAGCAGGACAGCAAGGACAGCA
ATCGGGTAACTCCCAGGAGAGTGT
TCAAGGACTACTTCCCCGAACCGG
CCTACAGCCTCGAAAGCACCCTGACG
CACAGAGCAGGACAGCAAGGACA
TGACGGTGTCGTGGAACTCAGGCG
CTGAGCAAAGCAGACTACGAGAAAC
GCACCTACAGCCTCAAGAGCACCC
CCCTGACCAGCGGCGTGCACACCT
ACAAAGTCTACGCCTGCGAAGTCACC
TGACGCTGAGCAAAGCAGACTACG
TCCCGGCTGTCCTACAGTCCTCAGG
CATCAGGGCCTGAGCTCGCCCGTCAC
AGAAACACAAAGTCTACGCCTGCG
ACTCTACTCCCTCAAGAGCGTGGTG
AAAGAGCTTCAACAGGGGAGAGTGT
AAGTCACCCATCAGGGCCTGAGCT
ACCGTGCCCTCCAGCAGCTTGGGC
(SEQ ID NO: 509)
CGCCCGTCACAAAGAGCTTCAACA
ACCCAGACCTACATCTGCAACGTG
GGGGAGAGTGT
AATCACAAGCCCAGCAACACCAAG
(SEQ ID NO: 510)
GTGGACAAGAAAGTTGAGCCCAAA
TCTTGTGACAAAACTCACACATGCC
CACCGTGCCCAGCACCTGAACTCCT
GGGGGGACCGTCAGTCTTCCTCTTC
CCCCCAAAACCCAAGGACACCCTC
ATGATCTCCCGGACCCCTGAGGTC
ACATGCGTGGTGGTGGACGTGAGC
CACGAAGACCCTGAGGTCAAGTTC
AACTGGTACGTGGACGGCGTGGAG
GTGCATAATGCCAAGACAAAGCCG
TGCGAGGAGCAGTACGGCAGCACG
TACCGTTGCGTCAGCGTCCTCACCG
TCCTGCACCAGGACTGGCTGAATG
GCAAGGAGTACAAGTGCAAGGTGT
CCAACAAAGCCCTCCCAGCCCCCA
TCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGG
TGTACACCCTGCCCCCATCCCGGGA
GGAGATGACCAAGAACCAGGTCAG
CCTGACCTGCCTGGTCAAAGGCTTC
TATCCCAGCGACATCGCCGTGGAG
TGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCC
GTGCTGGACTCCGACGGCTCCTTCT
TCCTCTATAGCAAGCTCACCGTGGA
CAAGAGCAGGTGGCAGCAGGGGA
ACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACAC
GCAGAAGAGCCTCTCCCTGTCTCCG
GGTGGTGGCGGATCGGGAGGTGGC
GGATCCCAGGTGCAGCTGGTCGAG
TCTGGGGGAGGCTTGGTCAAGCCT
GGAGGGTCCCTGAGACTCTCCTGT
GCAGCCTCTGGATTCACCTTCAGTG
ACTACTACATGACCTGGATCAGGC
AGGCTCCAGGGAAGGGGCTGGAGT
GGATTTCATACATTAGTAGTAGTGG
TAGTACCATCTACTACGCAGACTCT
GTGAAGGGCCGATTCACCATCTCC
AGGGACAACGCCAAGAACTCACTG
TATCTGCAAATGAACAGCCTGAGA
GCCGAGGACACGGCCGTGTATTAC
TGTGCGAGAGATCGGAACTCCCAC
TTTGACTATTGGGGCCAGGGAACC
CTGGTCACCGTGTCCTCAGCAAGC
ACGAAGGGGCCGTCCGTATTTCCG
CTTGCGCCCTCGTCGAAGTCAACTT
CGGGAGGGACCGCGGCACTTGGCT
GTCTTGTCAAAGATTACTTCCCTGA
GCCAGTGACAGTCAGCTGGAATTC
CGGTGCCCTCACGTCAGGAGTACA
TACATTCCCTGCGGTATTGCAGTCC
TCCGGACTCTACTCCCTGGAGTCGG
TGGTAACGGTGCCCAGCTCCAGCTT
GGGGACCCAGACGTACATTTGTAA
CGTGAATCACAAACCAAGCAATAC
TAAGGTAGATAAGAAAGTAGAACC
GAAGAGCTGC
(SEQ ID NO: 511)
AA
DIQMTQSPSSLSASVGDRVTITCRAGQ
DIQMTQSPSSVSASVGDRVTITCRAS
QVQLVQSGAEVKKPGASVKVSCKAS
NISRHLNWYQQNPGKAPKVLIHPASSL
QGITRWLAWYQQKPGKAPKLLIYAA
GYTFPGYYMYWLRQAPGQGLEWM
PSGVPSRFSGSGSGTDFSLTISSLQPEDF
SVLQSGVPSRFSGSGSGTDFTLTISSL
GWINPDSGDTNYAQKFQGRVTMTR
GTYFCQQSYSTPPTFGGGTKVELKRTV
QPEDFATYYCQQSNSFPRTFGQGTK
DTSISTAFMELSRLRSDDTAVYYCAR
AAPSVFIFPPSDEQLKSGTASVVCLLNN
VEIKRTVAAPSVFIFPPSDEQLKSGTA
EKPRYFDSFYYYLMDVWGQGTTVT
FYPREAKVQWKVDNALQSGNSQESVT
SVVCLLNNFYPREAKVQWKVDNAL
VSSASTKGPSVFPLAPSSKSTSGGTA
EQDSKDSTYSLESTLTLSKADYEKHKV
QSGNSQESVTEQDSKDSTYSLKSTLT
ALGCLVKDYFPEPVTVSWNSGALTS
YACEVTHQGLSSPVTKSFNRGEC
LSKADYEKHKVYACEVTHQGLSSPV
GVHTFPAVLQSSGLYSLKSVVTVPSS
(SEQ ID NO: 512)
TKSFNRGEC
SLGTQTYICNVNHKPSNTKVDKKVE
(SEQ ID NO: 513)
PKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSH
EDPEVKFNWYVDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNG
KEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCL
VKGFYPSDIAVEWESNGQPENNYKT
TPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSL
SPGGGGSGGGGSQVQLVESGGGLVK
PGGSLRLSCAASGFTFSDYYMTWIR
QAPGKGLEWISYISSSGSTIYYADSV
KGRFTISRDNAKNSLYLQMNSLRAE
DTAVYYCARDRNSHFDYWGQGTLV
TVSSASTKGPSVFPLAPSSKSTSGGTA
ALGCLVKDYFPEPVTVSWNSGALTS
GVHTFPAVLQSSGLYSLESVVTVPSS
SLGTQTYICNVNHKPSNTKVDKKVE
PKSC
(SEQ ID NO: 514)
iPS:
21-
[hu anti-
NA
GACATCCAGATGACCCAGTCTCCATC
GACATCCAGATGACCCAGTCTCCA
CAGGTGCAACTGGTGCAGTCTGGG
576316
230_33H6_IgG_
<hu CD40> 21-230_
CTCCCTGTCTGCATCTGTAGGAGACA
TCTTCCGTGTCTGCTTCTGTCGGAG
GCTGAAGTGAAGAAGCCTGGGGCC
21-
33H6VH]::huIgG1zSEFL2*GK-
GAGTCACCATCACTTGCCGGGCAGGT
ACAGAGTCACCATCACTTGTCGGG
TCAGTGAAGGTGTCCTGCAAGGCT
233_6F4__Fab
K::(G4S)2::[hu anti-
CAGAACATTAGCAGGCATTTAAATTG
CGAGTCAGGATATTAGCAGGTGGT
TCTGGATACACCTTCCCCGGCTACT
<hu Mesothelin>
GTATCAGCAGAATCCAGGGAAAGCC
TAGCCTGGTATCAGCAGAAACCAG
ATATGTACTGGTTGCGACAGGCCC
6F4VH]::huIgG1z-
CCTAAGGTCCTGATCCATCCTGCATC
GGAAAGCCCCTAAGCTCCTGATTTC
CTGGACAAGGACTTGAGTGGATGG
CH1-E::EPKSC + [anti-
CAGTTTGCCAAGTGGGGTCCCGTCAA
TGCTGCATCCAGATTGCAAAGTGG
GATGGATCAACCCTGACAGTGGTG
<hu CD40>
GGTTCAGTGGCAGTGGATCTGGGAC
AGTCCCATCAAGGTTCAGCGGCAG
ACACAAACTATGCACAGAAGTTTC
21-230_33H6VL]::huKLC-
AGATTTCAGTCTTACCATCAGCAGTC
TGGATCTGGGACAGATTTCACTCTC
AGGGCAGGGTCACCATGACCAGGG
S176E + [anti-
TGCAACCTGAAGATTTTGGAACTTAC
ACCATCAGCAGCCTGCAGCCTGAA
ACACGTCCATCAGCACAGCCTTTAT
<hu Mesothelin>
TTCTGTCAACAGAGTTACAGTACCCC
GATTTTGCAATTTACTATTGTCAAC
GGAGCTGAGCAGGCTGAGATCAGA
6F4VL]::huKLC-
TCCCACTTTCGGCGGAGGGACCAAG
AGGCTAAAAGTTTTCCTCGGACGTT
CGACACGGCCGTGTATTACTGTGC
S176K (IgG-Fab);
GTGGAGCTCAAACGAACGGTGGCTG
CGGCCAAGGGACCAAGGTGGAAAT
GAGAGAGAAGCCCAGATATTTTGA
LMRID: SS-30869
CACCATCTGTCTTCATCTTCCCGCCAT
CAAACGGACGGTGGCTGCACCATC
CTCCTTCTACTACTACCTTATGGAC
CTGATGAGCAGTTGAAATCTGGAACT
TGTCTTCATCTTCCCGCCATCTGAT
GTCTGGGGCCAAGGGACCACGGTC
GCCTCTGTTGTGTGCCTGCTGAATAA
GAGCAGTTGAAATCTGGAACTGCC
ACCGTGTCCTCAGCCTCCACCAAG
CTTCTATCCCAGAGAGGCCAAAGTAC
TCTGTTGTGTGCCTGCTGAATAACT
GGCCCATCGGTCTTCCCCCTGGCAC
AGTGGAAGGTGGATAACGCCCTCCA
TCTATCCCAGAGAGGCCAAAGTAC
CCTCCTCCAAGAGCACCTCTGGGG
ATCGGGTAACTCCCAGGAGAGTGTC
AGTGGAAGGTGGATAACGCCCTCC
GCACAGCGGCCCTGGGCTGCCTGG
ACAGAGCAGGACAGCAAGGACAGCA
AATCGGGTAACTCCCAGGAGAGTG
TCAAGGACTACTTCCCCGAACCGG
CCTACAGCCTCGAAAGCACCCTGACG
TCACAGAGCAGGACAGCAAGGACA
TGACGGTGTCGTGGAACTCAGGCG
CTGAGCAAAGCAGACTACGAGAAAC
GCACCTACAGCCTCAAGAGCACCC
CCCTGACCAGCGGCGTGCACACCT
ACAAAGTCTACGCCTGCGAAGTCACC
TGACGCTGAGCAAAGCAGACTACG
TCCCGGCTGTCCTACAGTCCTCAGG
CATCAGGGCCTGAGCTCGCCCGTCAC
AGAAACACAAAGTCTACGCCTGCG
ACTCTACTCCCTCAAGAGCGTGGTG
AAAGAGCTTCAACAGGGGAGAGTGT
AAGTCACCCATCAGGGCCTGAGCT
ACCGTGCCCTCCAGCAGCTTGGGC
(SEQ ID NO: 515)
CGCCCGTCACAAAGAGCTTCAACA
ACCCAGACCTACATCTGCAACGTG
GGGGAGAGTGT
AATCACAAGCCCAGCAACACCAAG
(SEQ ID NO: 516)
GTGGACAAGAAAGTTGAGCCCAAA
TCTTGTGACAAAACTCACACATGCC
CACCGTGCCCAGCACCTGAACTCCT
GGGGGGACCGTCAGTCTTCCTCTTC
CCCCCAAAACCCAAGGACACCCTC
ATGATCTCCCGGACCCCTGAGGTC
ACATGCGTGGTGGTGGACGTGAGC
CACGAAGACCCTGAGGTCAAGTTC
AACTGGTACGTGGACGGCGTGGAG
GTGCATAATGCCAAGACAAAGCCG
TGCGAGGAGCAGTACGGCAGCACG
TACCGTTGCGTCAGCGTCCTCACCG
TCCTGCACCAGGACTGGCTGAATG
GCAAGGAGTACAAGTGCAAGGTGT
CCAACAAAGCCCTCCCAGCCCCCA
TCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGG
TGTACACCCTGCCCCCATCCCGGGA
GGAGATGACCAAGAACCAGGTCAG
CCTGACCTGCCTGGTCAAAGGCTTC
TATCCCAGCGACATCGCCGTGGAG
TGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCC
GTGCTGGACTCCGACGGCTCCTTCT
TCCTCTATAGCAAGCTCACCGTGGA
CAAGAGCAGGTGGCAGCAGGGGA
ACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACAC
GCAGAAGAGCCTCTCCCTGTCTCCG
GGTGGTGGCGGATCGGGAGGTGGC
GGATCCCAGGTGCAGCTGGTGGAG
TCTGGGGGAGGCTTGGTCAAGCCT
GGAGGGTCCCTGAGACTCTCCTGT
GCAGCCTCTGGATTCACCTTCAGTG
ACTACTACATGAGCTGGATCCGCC
AGGCTCCAGGGAAGGGGCTGGAGT
GGATTTCATACATTAGTAGCAGTG
AAAGTATCATCTATTACGTAGACTC
TGTGAAGGGCCGATTCACCATCTCC
AGGGACAACGCCAAGAACTCACTG
TATCTGCAAATGAACAGCCTGAGA
GCCGAGGACACGGCCGTGTATTAC
TGTGCGAGAGATGTTGGGAGCCAC
TTTGACTACTGGGGCCAGGGAACC
CTGGTCACCGTGTCCTCAGCAAGC
ACGAAGGGGCCGTCCGTATTTCCG
CTTGCGCCCTCGTCGAAGTCAACTT
CGGGAGGGACCGCGGCACTTGGCT
GTCTTGTCAAAGATTACTTCCCTGA
GCCAGTGACAGTCAGCTGGAATTC
CGGTGCCCTCACGTCAGGAGTACA
TACATTCCCTGCGGTATTGCAGTCC
TCCGGACTCTACTCCCTGGAGTCGG
TGGTAACGGTGCCCAGCTCCAGCTT
GGGGACCCAGACGTACATTTGTAA
CGTGAATCACAAACCAAGCAATAC
TAAGGTAGATAAGAAAGTAGAACC
GAAGAGCTGC
(SEQ ID NO: 517)
AA
DIQMTQSPSSLSASVGDRVTITCRAGQ
DIQMTQSPSSVSASVGDRVTITCRAS
QVQLVQSGAEVKKPGASVKVSCKAS
NISRHLNWYQQNPGKAPKVLIHPASSL
QDISRWLAWYQQKPGKAPKLLISAA
GYTFPGYYMYWLRQAPGQGLEWM
PSGVPSRFSGSGSGTDFSLTISSLQPEDF
SRLQSGVPSRFSGSGSGTDFTLTISSL
GWINPDSGDTNYAQKFQGRVTMTR
GTYFCQQSYSTPPTFGGGTKVELKRTV
QPEDFAIYYCQQAKSFPRTFGQGTKV
DTSISTAFMELSRLRSDDTAVYYCAR
AAPSVFIFPPSDEQLKSGTASVVCLLNN
EIKRTVAAPSVFIFPPSDEQLKSGTAS
EKPRYFDSFYYYLMDVWGQGTTVT
FYPREAKVQWKVDNALQSGNSQESVT
VVCLLNNFYPREAKVQWKVDNALQ
VSSASTKGPSVFPLAPSSKSTSGGTA
EQDSKDSTYSLESTLTLSKADYEKHKV
SGNSQESVTEQDSKDSTYSLKSTLTL
ALGCLVKDYFPEPVTVSWNSGALTS
YACEVTHQGLSSPVTKSFNRGEC
SKADYEKHKVYACEVTHQGLSSPVT
GVHTFPAVLQSSGLYSLKSVVTVPSS
(SEQ ID NO: 518)
KSFNRGEC
SLGTQTYICNVNHKPSNTKVDKKVE
(SEQ ID NO: 519)
PKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSH
EDPEVKFNWYVDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNG
KEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCL
VKGFYPSDIAVEWESNGQPENNYKT
TPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSL
SPGGGGSGGGGSQVQLVESGGGLVK
PGGSLRLSCAASGFTFSDYYMSWIRQ
APGKGLEWISYISSSESIIYYVDSVKG
RFTISRDNAKNSLYLQMNSLRAEDT
AVYYCARDVGSHFDYWGQGTLVTV
SSASTKGPSVFPLAPSSKSTSGGTAAL
GCLVKDYFPEPVTVSWNSGALTSGV
HTFPAVLQSSGLYSLESVVTVPSSSL
GTQTYICNVNHKPSNTKVDKKVEPK
SC
(SEQ ID NO: 520)
iPS:
21-
[hu anti-
NA
GACATCCAGATGACCCAGTCTCCATC
GACATTGTGATGACTCAGTCTCCAG
CAGGTGCAACTGGTGCAGTCTGGG
576319
230_33H6_IgG_
<hu CD40> 21-230_
CTCCCTGTCTGCATCTGTAGGAGACA
ACTCCCTGGCTGTGTCTCTGGGCGA
GCTGAAGTGAAGAAGCCTGGGGCC
21-
33H6VH]::huIgG1zSEFL2*GK-
GAGTCACCATCACTTGCCGGGCAGGT
GAGGGCCACCATCAACTGCAAGTC
TCAGTGAAGGTGTCCTGCAAGGCT
233_7G11__Fab
K::(G4S)2::[hu anti-
CAGAACATTAGCAGGCATTTAAATTG
CAGCCAGAGTGTTTTATACAGCTCC
TCTGGATACACCTTCCCCGGCTACT
<hu Mesothelin>
GTATCAGCAGAATCCAGGGAAAGCC
AACAATAAGAACTACTTAGCTTGG
ATATGTACTGGTTGCGACAGGCCC
7G11VH]::huIgG1z-
CCTAAGGTCCTGATCCATCCTGCATC
TACCAGCAGAAACCAGGACAGCCT
CTGGACAAGGACTTGAGTGGATGG
CH1-E::EPKSC + [anti-
CAGTTTGCCAAGTGGGGTCCCGTCAA
CCTAAGCTGCTCATTTACTGGGCAT
GATGGATCAACCCTGACAGTGGTG
<hu CD40>
GGTTCAGTGGCAGTGGATCTGGGAC
CTACCCGAGAATCCGGGGTCCCTG
ACACAAACTATGCACAGAAGTTTC
21-230_33H6VL]::huKLC-
AGATTTCAGTCTTACCATCAGCAGTC
ACCGATTCAGTGGCAGCGGGTCTG
AGGGCAGGGTCACCATGACCAGGG
S176E + [anti-
TGCAACCTGAAGATTTTGGAACTTAC
GGACAGATTTCACTCTCACCATCAG
ACACGTCCATCAGCACAGCCTTTAT
<hu Mesothelin>
TTCTGTCAACAGAGTTACAGTACCCC
CAGCCTGCAGGCTGAAGATGTGGC
GGAGCTGAGCAGGCTGAGATCAGA
7G11VL]::huKLC-
TCCCACTTTCGGCGGAGGGACCAAG
AGTTTATTACTGTCAGCAATATTAT
CGACACGGCCGTGTATTACTGTGC
S176K (IgG-Fab);
GTGGAGCTCAAACGAACGGTGGCTG
AGTACTCCTCCGACGTTCGGCCAA
GAGAGAGAAGCCCAGATATTTTGA
LMRID: SS-30870
CACCATCTGTCTTCATCTTCCCGCCAT
GGGACCAAGGTGGAGATCAAACGG
CTCCTTCTACTACTACCTTATGGAC
CTGATGAGCAGTTGAAATCTGGAACT
ACGGTGGCTGCACCATCTGTCTTCA
GTCTGGGGCCAAGGGACCACGGTC
GCCTCTGTTGTGTGCCTGCTGAATAA
TCTTCCCGCCATCTGATGAGCAGTT
ACCGTGTCCTCAGCCTCCACCAAG
CTTCTATCCCAGAGAGGCCAAAGTAC
GAAATCTGGAACTGCCTCTGTTGTG
GGCCCATCGGTCTTCCCCCTGGCAC
AGTGGAAGGTGGATAACGCCCTCCA
TGCCTGCTGAATAACTTCTATCCCA
CCTCCTCCAAGAGCACCTCTGGGG
ATCGGGTAACTCCCAGGAGAGTGTC
GAGAGGCCAAAGTACAGTGGAAGG
GCACAGCGGCCCTGGGCTGCCTGG
ACAGAGCAGGACAGCAAGGACAGCA
TGGATAACGCCCTCCAATCGGGTA
TCAAGGACTACTTCCCCGAACCGG
CCTACAGCCTCGAAAGCACCCTGACG
ACTCCCAGGAGAGTGTCACAGAGC
TGACGGTGTCGTGGAACTCAGGCG
CTGAGCAAAGCAGACTACGAGAAAC
AGGACAGCAAGGACAGCACCTACA
CCCTGACCAGCGGCGTGCACACCT
ACAAAGTCTACGCCTGCGAAGTCACC
GCCTCAAGAGCACCCTGACGCTGA
TCCCGGCTGTCCTACAGTCCTCAGG
CATCAGGGCCTGAGCTCGCCCGTCAC
GCAAAGCAGACTACGAGAAACACA
ACTCTACTCCCTCAAGAGCGTGGTG
AAAGAGCTTCAACAGGGGAGAGTGT
AAGTCTACGCCTGCGAAGTCACCC
ACCGTGCCCTCCAGCAGCTTGGGC
(SEQ ID NO: 521)
ATCAGGGCCTGAGCTCGCCCGTCA
ACCCAGACCTACATCTGCAACGTG
CAAAGAGCTTCAACAGGGGAGAGT
AATCACAAGCCCAGCAACACCAAG
GT
GTGGACAAGAAAGTTGAGCCCAAA
(SEQ ID NO: 522)
TCTTGTGACAAAACTCACACATGCC
CACCGTGCCCAGCACCTGAACTCCT
GGGGGGACCGTCAGTCTTCCTCTTC
CCCCCAAAACCCAAGGACACCCTC
ATGATCTCCCGGACCCCTGAGGTC
ACATGCGTGGTGGTGGACGTGAGC
CACGAAGACCCTGAGGTCAAGTTC
AACTGGTACGTGGACGGCGTGGAG
GTGCATAATGCCAAGACAAAGCCG
TGCGAGGAGCAGTACGGCAGCACG
TACCGTTGCGTCAGCGTCCTCACCG
TCCTGCACCAGGACTGGCTGAATG
GCAAGGAGTACAAGTGCAAGGTGT
CCAACAAAGCCCTCCCAGCCCCCA
TCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGG
TGTACACCCTGCCCCCATCCCGGGA
GGAGATGACCAAGAACCAGGTCAG
CCTGACCTGCCTGGTCAAAGGCTTC
TATCCCAGCGACATCGCCGTGGAG
TGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCC
GTGCTGGACTCCGACGGCTCCTTCT
TCCTCTATAGCAAGCTCACCGTGGA
CAAGAGCAGGTGGCAGCAGGGGA
ACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACAC
GCAGAAGAGCCTCTCCCTGTCTCCG
GGTGGTGGCGGATCGGGAGGTGGC
GGATCCGAGGTGCAGCTGGTCGAG
TCTGGAGGAGGCTTGATCCAGCCT
GGGGGGTCCCTGAGACTCTCCTGT
GCAGTCTCTGGGTTCACCGTCAGTA
GCAAGTTCATGACCTGGGTCCGCC
AGGCTCCAGGGAAGGGGCTGGAGT
GGGTGTCAGTTATTTATAGCGGTGG
TAAGACATACTACGCAGACTCCGT
GAAGGGCCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTA
TCTTCAAATGAACAGCCTGAGAGC
CGAGGACACGGCCGTGTATTACTG
TGCGAGAGATAGCGGTGGCTGGGG
GTACTTTGACTACTGGGGCCAGGG
AACCCTGGTCACCGTGTCCTCAGCA
AGCACGAAGGGGCCGTCCGTATTT
CCGCTTGCGCCCTCGTCGAAGTCAA
CTTCGGGAGGGACCGCGGCACTTG
GCTGTCTTGTCAAAGATTACTTCCC
TGAGCCAGTGACAGTCAGCTGGAA
TTCCGGTGCCCTCACGTCAGGAGTA
CATACATTCCCTGCGGTATTGCAGT
CCTCCGGACTCTACTCCCTGGAGTC
GGTGGTAACGGTGCCCAGCTCCAG
CTTGGGGACCCAGACGTACATTTGT
AACGTGAATCACAAACCAAGCAAT
ACTAAGGTAGATAAGAAAGTAGAA
CCGAAGAGCTGC
(SEQ ID NO: 523)
AA
DIQMTQSPSSLSASVGDRVTITCRAGQ
DIVMTQSPDSLAVSLGERATINCKSS
QVQLVQSGAEVKKPGASVKVSCKAS
NISRHLNWYQQNPGKAPKVLIHPASSL
QSVLYSSNNKNYLAWYQQKPGQPP
GYTFPGYYMYWLRQAPGQGLEWM
PSGVPSRFSGSGSGTDFSLTISSLQPEDF
KLLIYWASTRESGVPDRFSGSGSGTD
GWINPDSGDTNYAQKFQGRVTMTR
GTYFCQQSYSTPPTFGGGTKVELKRTV
FTLTISSLQAEDVAVYYCQQYYSTPP
DTSISTAFMELSRLRSDDTAVYYCAR
AAPSVFIFPPSDEQLKSGTASVVCLLNN
TFGQGTKVEIKRTVAAPSVFIFPPSDE
EKPRYFDSFYYYLMDVWGQGTTVT
FYPREAKVQWKVDNALQSGNSQESVT
QLKSGTASVVCLLNNFYPREAKVQW
VSSASTKGPSVFPLAPSSKSTSGGTA
EQDSKDSTYSLESTLTLSKADYEKHKV
KVDNALQSGNSQESVTEQDSKDSTY
ALGCLVKDYFPEPVTVSWNSGALTS
YACEVTHQGLSSPVTKSFNRGEC
SLKSTLTLSKADYEKHKVYACEVTH
GVHTFPAVLQSSGLYSLKSVVTVPSS
(SEQ ID NO: 524)
QGLSSPVTKSFNRGEC
SLGTQTYICNVNHKPSNTKVDKKVE
(SEQ ID NO: 525)
PKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSH
EDPEVKFNWYVDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNG
KEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCL
VKGFYPSDIAVEWESNGQPENNYKT
TPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSL
SPGGGGSGGGGSEVQLVESGGGLIQP
GGSLRLSCAVSGFTVSSKFMTWVRQ
APGKGLEWVSVIYSGGKTYYADSVK
GRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDSGGWGYFDYWGQGTL
VTVSSASTKGPSVFPLAPSSKSTSGGT
AALGCLVKDYFPEPVTVSWNSGALT
SGVHTFPAVLQSSGLYSLESVVTVPS
SSLGTQTYICNVNHKPSNTKVDKKV
EPKSC
(SEQ ID NO: 526)
iPS:
21-
[hu anti-
NA
CAGGCTGTGCCGACTCAGCCCTCTTC
CAGTCAGTGTTGACGCAGCCGCCC
CAGGTGCAGTTGGTGGAGTCTGGG
576322
230_33H9_IgG_
<hu CD40> 21-230_
CCTCTCTGCATCTCCTGGAGCATCAG
TCAGTGTCTGGGGCCCCAGGGCAG
GGAGGCGTGGTCCAGCCTGGGAGG
21-
33H9VH]::huIgG1zSEFL2*GK-
CCAGTCTCACCTGCACCTTACGCAGT
AGGGTCACCATCTCCTGCACTGGG
TCCCTGAGACTCTCCTGTGCAGCGT
233_4G12__Fab
K::(G4S)2::[hu anti-
GGCATCAATGTTGGTTCCTCCAGGAT
AGCAGCTCCAACATCGGGGCAGGT
CTGGATTCACCTTCAGTAGCCATGG
<hu Mesothelin>
CTATTGGTACCAGCAGAAGCCAGGG
TATGATGTTCACTGGTACCAGCAG
CATGCACTGGGTCCGCCAACCTCC
4G12VH]::huIgG1z-
AGTCCTCCCCAGTTTCTCCTGAGGTA
GTTCCAGGAACAGCCCCCAAACTC
AGGCAAGGGGCTGGAGTGGGTGGC
CH1-E::EPKSC + [anti-
CACATCAGACTCAGATAAATTGCAG
CTCATCTATGGTAACAGCAAGCGG
AGTTATCTGGTATGATGGAAGTAA
<hu CD40>
GGCTCTGGAGTCCCCAGCCGCTTCTC
CCCTCAGGGGTCCCTGACCGATTCT
TGAATACTATGGAGACTCCGTGAA
21-230_33H9VL]::huLLC2-
TGGATCCAAAGATGCTTCGGCCAATG
CTGGCTCCAAGTCTGGCACCTCAGC
GGGCCGATTCACCATCTCCAGAGA
E + [anti-
CAGGACTTTTACTCATCTCTGGGCTC
CTCCCTGGCCATCACTGGGCTCCAG
CAATTCCAAGAACACGCTGTATCT
<hu Mesothelin>
CAGTCTGAGGATGAGGCTGACTATTA
GCTGAGGATGAGGCTGATTATTAC
GCAAATGAACAGCCTGAGAGTCGA
4G12VL]::huLLC2-
CTGTATGATTTGGCACAGCAGCGCTG
TGCCAGTCCTATGACAGCAGCCTG
GGACACGGCTGTGTATTACTGTAC
K (IgG-Fab);
TGGTATTCGGCGGAGGGACCAAACT
GGTGGTTGGGTGTTCGGCGGAGGG
GAGAGGGGGGGGCCACTGGAACTA
LMRID: SS-30871
GACCGTCCTAGGTCAGCCCAAGGCTG
ACCAAGCTGACCGTCCTACAGCCC
CGAGGGCCACTACTATGGTATGGA
CACCCTCGGTCACTCTGTTCCCGCCC
AAGGCTGCACCCTCGGTCACTCTGT
CGTCTGGGGCCAAGGGACCACGGT
TCCTCTGAGGAGCTTCAAGCCAACAA
TCCCGCCCTCCTCTGAGGAGCTTCA
CACCGTGTCCTCAGCCTCCACCAAG
GGCCACACTGGTGTGTCTCATCAGTG
AGCCAACAAGGCCACACTGGTGTG
GGCCCATCGGTCTTCCCCCTGGCAC
ACTTCTACCCGGGAGCCGTGACAGTG
TCTCATCAGTGACTTCTACCCGGGA
CCTCCTCCAAGAGCACCTCTGGGG
GCCTGGAAGGCAGATAGCAGCCCCG
GCCGTGACAGTGGCCTGGAAGGCA
GCACAGCGGCCCTGGGCTGCCTGG
TCAAGGCGGGAGTGGAAACCACCAC
GATAGCAGCCCCGTCAAGGCGGGA
TCAAGGACTACTTCCCCGAACCGG
ACCCTCCAAACAAAGCAACAACAAG
GTGGAAACCACCACACCCTCCAAA
TGACGGTGTCGTGGAACTCAGGCG
TACGCGGCCGAAAGCTATCTGAGCCT
CAAAGCAACAACAAGTACGCGGCC
CCCTGACCAGCGGCGTGCACACCT
GACGCCTGAGCAGTGGAAGTCCCAC
AAGAGCTATCTGAGCCTGACGCCT
TCCCGGCTGTCCTACAGTCCTCAGG
AGAAGCTACAGCTGCCAGGTCACGC
GAGCAGTGGAAGTCCCACAGAAGC
ACTCTACTCCCTCAAGAGCGTGGTG
ATGAAGGGAGCACCGTGGAGAAGAC
TACAGCTGCCAGGTCACGCATGAA
ACCGTGCCCTCCAGCAGCTTGGGC
AGTGGCCCCTACAGAATGTTCA
GGGAGCACCGTGGAGAAGACAGTG
ACCCAGACCTACATCTGCAACGTG
(SEQ ID NO: 527)
GCCCCTACAGAATGTTCA
AATCACAAGCCCAGCAACACCAAG
(SEQ ID NO: 528)
GTGGACAAGAAAGTTGAGCCCAAA
TCTTGTGACAAAACTCACACATGCC
CACCGTGCCCAGCACCTGAACTCCT
GGGGGGACCGTCAGTCTTCCTCTTC
CCCCCAAAACCCAAGGACACCCTC
ATGATCTCCCGGACCCCTGAGGTC
ACATGCGTGGTGGTGGACGTGAGC
CACGAAGACCCTGAGGTCAAGTTC
AACTGGTACGTGGACGGCGTGGAG
GTGCATAATGCCAAGACAAAGCCG
TGCGAGGAGCAGTACGGCAGCACG
TACCGTTGCGTCAGCGTCCTCACCG
TCCTGCACCAGGACTGGCTGAATG
GCAAGGAGTACAAGTGCAAGGTGT
CCAACAAAGCCCTCCCAGCCCCCA
TCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGG
TGTACACCCTGCCCCCATCCCGGGA
GGAGATGACCAAGAACCAGGTCAG
CCTGACCTGCCTGGTCAAAGGCTTC
TATCCCAGCGACATCGCCGTGGAG
TGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCC
GTGCTGGACTCCGACGGCTCCTTCT
TCCTCTATAGCAAGCTCACCGTGGA
CAAGAGCAGGTGGCAGCAGGGGA
ACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACAC
GCAGAAGAGCCTCTCCCTGTCTCCG
GGTGGTGGCGGATCGGGAGGTGGC
GGATCCCAGGTGCAGCTGCAGGAG
TCGGGCCCAGGACTGGTGAAGCCT
TCGGAAACCCTGTCCCTCACCTGCA
CTGTCTCTGGTGGCTCCATCAGCAG
TAGTAGTTACTACTGGGGCTGGATC
AGGCAGCCCCCAGGGAAGGGGCTG
GAGTGGATTGGGAGTATCTATTAT
AGTGGGATCACCAACTACAACCCG
TCCCTCAAGAGTCGAGTCACCATCT
CCGTAGACACGTCCAAGAACCAGT
TCTCCCTGAAGCTGAGTTCTGTGAC
CGCCGCAGACACGGCCGTGTATTA
CTGTGCGAGATCCAGTAACTACGA
TGCTTTTGATATCTGGGGCCAAGGG
ACAATGGTCACCGTGTCCTCAGCA
AGCACGAAGGGGCCGTCCGTATTT
CCGCTTGCGCCCTCGTCGAAGTCAA
CTTCGGGAGGGACCGCGGCACTTG
GCTGTCTTGTCAAAGATTACTTCCC
TGAGCCAGTGACAGTCAGCTGGAA
TTCCGGTGCCCTCACGTCAGGAGTA
CATACATTCCCTGCGGTATTGCAGT
CCTCCGGACTCTACTCCCTGGAGTC
GGTGGTAACGGTGCCCAGCTCCAG
CTTGGGGACCCAGACGTACATTTGT
AACGTGAATCACAAACCAAGCAAT
ACTAAGGTAGATAAGAAAGTAGAA
CCGAAGAGCTGC
(SEQ ID NO: 529)
AA
QAVPTQPSSLSASPGASASLTCTLRSGI
QSVLTQPPSVSGAPGQRVTISCTGSSS
QYQLVESGGGVVQPGRSLRLSCAAS
NVGSSRIYWYQQKPGSPPQFLLRYTSD
NIGAGYDVHWYQQVPGTAPKLLIYG
GFTFSSHGMHWVRQPPGKGLEWVA
SDKLQGSGVPSRFSGSKDASANAGLLL
NSKRPSGVPDRFSGSKSGTSASLAIT
VIWYDGSNEYYGDSVKGRFTISRDN
ISGLQSEDEADYYCMIWHSSAVVFGG
GLQAEDEADYYCQSYDSSLGGWVF
SKNTLYLQMNSLRVEDTAVYYCTRG
GTKLTVLGQPKAAPSVTLFPPSSEELQ
GGGTKLTVLQPKAAPSVTLFPPSSEE
GGHWNYEGHYYGMDVWGQGTTVT
ANKATLVCLISDFYPGAVTVAWKADS
LQANKATLVCLISDFYPGAVTVAWK
VSSASTKGPSVFPLAPSSKSTSGGTA
SPVKAGVETTTPSKQSNNKYAAESYLS
ADSSPVKAGVETTTPSKQSNNKYAA
ALGCLVKDYFPEPVTVSWNSGALTS
LTPEQWKSHRSYSCQVTHEGSTVEKT
KAYLSLTPEQWKSHRSYSCQVTHEG
GVHTFPAVLQSSGLYSLKSVVTVPSS
VAPTECS
STVEKTVAPTECS
SLGTQTYICNVNHKPSNTKVDKKVE
(SEQ ID NO: 530)
(SEQ ID NO: 531)
PKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSH
EDPEVKFNWYNDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNG
KEYKCKVSNKALPEPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCL
VKGFYPSDIAVEWESNGQPENNYKT
TPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSL
SPGGGGSGGGGSQVQLQESGPGLVK
PSETLSLTCTVSGGSISSSSYYWGWIR
QPPGKGLEWIGSIYYSGITNYNPSLKS
RVTISVDTSKNQFSLKLSSVTAADTA
VYYCARSSNYDAFDIWGQGTMVTV
SSASTKGPSVFPLAPSSKSTSGGTAAL
GCLVKDYFPEPVTVSWNSGALTSGV
HTFPAVLQSSGLYSLESVVTVPSSSL
GTQTYICNVNHKPSNTKVDKKVEPK
SC
(SEQ ID NO: 532)
iPS:
21-
[hu anti-
NA
2 CAGGCTGTGCCGACTCAGCCCTCTTC
GACATTCAGATGACCCAGTCTCCAT
CAGGTGCAGTTGGTGGAGTCTGGG
576327
230_33H9_IgG_
<hu CD40> 21-230_
CCTCTCTGCATCTCCTGGAGCATCAG
CTTCCGTGTCTGCATCTGTAGGGGA
GGAGGCGTGGTCCAGCCTGGGAGG
21-
33H9VH]::huIgG1zSEFL2*GK-
CCAGTCTCACCTGCACCTTACGCAGT
CAGAGTCACCATCACTTGTCGGGC
TCCCTGAGACTCTCCTGTGCAGCGT
233_4H6__Fab
K::(G4S)2::[hu anti-
GGCATCAATGTTGGTTCCTCCAGGAT
GAGTCAGGGTATTACCAGGTGGTT
CTGGATTCACCTTCAGTAGCCATGG
<hu Mesothelin>
CTATTGGTACCAGCAGAAGCCAGGG
AGCCTGGTATCAGCAGAAACCAGG
CATGCACTGGGTCCGCCAACCTCC
4H6VH]::huIgG1z-
AGTCCTCCCCAGTTTCTCCTGAGGTA
GAAAGCCCCTAAGCTCCTGATCTAT
AGGCAAGGGGCTGGAGTGGGTGGC
CH1-E::EPKSC + [anti-
CACATCAGACTCAGATAAATTGCAG
GCTGCATCCGTTTTGCAAAGTGGG
AGTTATCTGGTATGATGGAAGTAA
<hu CD40>
GGCTCTGGAGTCCCCAGCCGCTTCTC
GTCCCATCAAGGTTCAGCGGCAGT
TGAATACTATGGAGACTCCGTGAA
21-230_33H9VL]::huLLC2-
TGGATCCAAAGATGCTTCGGCCAATG
GGATCTGGGACAGATTTCACTCTCA
GGGCCGATTCACCATCTCCAGAGA
E + [anti-
CAGGACTTTTACTCATCTCTGGGCTC
CCATCAGCAGCCTGCAGCCTGAAG
CAATTCCAAGAACACGCTGTATCT
<hu Mesothelin>
CAGTCTGAGGATGAGGCTGACTATTA
ATTTTGCAACTTACTATTGTCAACA
GCAAATGAACAGCCTGAGAGTCGA
4H6VL]::huKLC-
CTGTATGATTTGGCACAGCAGCGCTG
GTCTAACAGTTTCCCTCGGACGTTC
GGACACGGCTGTGTATTACTGTAC
S176K (IgG-Fab);
TGGTATTCGGCGGAGGGACCAAACT
GGCCAAGGGACCAAGGTGGAAATC
GAGAGGGGGGGGCCACTGGAACTA
LMRID: SS-30872
GACCGTCCTAGGTCAGCCCAAGGCTG
AAACGGACGGTGGCTGCACCATCT
CGAGGGCCACTACTATGGTATGGA
CACCCTCGGTCACTCTGTTCCCGCCC
GTCTTCATCTTCCCGCCATCTGATG
CGTCTGGGGCCAAGGGACCACGGT
TCCTCTGAGGAGCTTCAAGCCAACAA
AGCAGTTGAAATCTGGAACTGCCT
CACCGTGTCCTCAGCCTCCACCAAG
GGCCACACTGGTGTGTCTCATCAGTG
CTGTTGTGTGCCTGCTGAATAACTT
GGCCCATCGGTCTTCCCCCTGGCAC
ACTTCTACCCGGGAGCCGTGACAGTG
CTATCCCAGAGAGGCCAAAGTACA
CCTCCTCCAAGAGCACCTCTGGGG
GCCTGGAAGGCAGATAGCAGCCCCG
GTGGAAGGTGGATAACGCCCTCCA
GCACAGCGGCCCTGGGCTGCCTGG
TCAAGGCGGGAGTGGAAACCACCAC
ATCGGGTAACTCCCAGGAGAGTGT
TCAAGGACTACTTCCCCGAACCGG
ACCCTCCAAACAAAGCAACAACAAG
CACAGAGCAGGACAGCAAGGACA
TGACGGTGTCGTGGAACTCAGGCG
TACGCGGCCGAAAGCTATCTGAGCCT
GCACCTACAGCCTCAAGAGCACCC
CCCTGACCAGCGGCGTGCACACCT
GACGCCTGAGCAGTGGAAGTCCCAC
TGACGCTGAGCAAAGCAGACTACG
TCCCGGCTGTCCTACAGTCCTCAGG
AGAAGCTACAGCTGCCAGGTCACGC
AGAAACACAAAGTCTACGCCTGCG
ACTCTACTCCCTCAAGAGCGTGGTG
ATGAAGGGAGCACCGTGGAGAAGAC
AAGTCACCCATCAGGGCCTGAGCT
ACCGTGCCCTCCAGCAGCTTGGGC
AGTGGCCCCTACAGAATGTTCA
CGCCCGTCACAAAGAGCTTCAACA
ACCCAGACCTACATCTGCAACGTG
(SEQ ID NO: 533)
GGGGAGAGTGT
AATCACAAGCCCAGCAACACCAAG
(SEQ ID NO: 534)
GTGGACAAGAAAGTTGAGCCCAAA
TCTTGTGACAAAACTCACACATGCC
CACCGTGCCCAGCACCTGAACTCCT
GGGGGGACCGTCAGTCTTCCTCTTC
CCCCCAAAACCCAAGGACACCCTC
ATGATCTCCCGGACCCCTGAGGTC
ACATGCGTGGTGGTGGACGTGAGC
CACGAAGACCCTGAGGTCAAGTTC
AACTGGTACGTGGACGGCGTGGAG
GTGCATAATGCCAAGACAAAGCCG
TGCGAGGAGCAGTACGGCAGCACG
TACCGTTGCGTCAGCGTCCTCACCG
TCCTGCACCAGGACTGGCTGAATG
GCAAGGAGTACAAGTGCAAGGTGT
CCAACAAAGCCCTCCCAGCCCCCA
TCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGG
TGTACACCCTGCCCCCATCCCGGGA
GGAGATGACCAAGAACCAGGTCAG
CCTGACCTGCCTGGTCAAAGGCTTC
TATCCCAGCGACATCGCCGTGGAG
TGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCC
GTGCTGGACTCCGACGGCTCCTTCT
TCCTCTATAGCAAGCTCACCGTGGA
CAAGAGCAGGTGGCAGCAGGGGA
ACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACAC
GCAGAAGAGCCTCTCCCTGTCTCCG
GGTGGTGGCGGATCGGGAGGTGGC
GGATCCCAGGTGCAGCTGGTCGAG
TCTGGGGGAGGCTTGGTCAAGCCT
GGAGGGTCCCTGAGACTCTCCTGT
GCAGCCTCTGGATTCACCTTCAGTG
ACTACTACATGACCTGGATCAGGC
AGGCTCCAGGGAAGGGGCTGGAGT
GGATTTCATACATTAGTAGTAGTGG
TAGTACCATCTACTACGCAGACTCT
GTGAAGGGCCGATTCACCATCTCC
AGGGACAACGCCAAGAACTCACTG
TATCTGCAAATGAACAGCCTGAGA
GCCGAGGACACGGCCGTGTATTAC
TGTGCGAGAGATCGGAACTCCCAC
TTTGACTATTGGGGCCAGGGAACC
CTGGTCACCGTGTCCTCAGCAAGC
ACGAAGGGGCCGTCCGTATTTCCG
CTTGCGCCCTCGTCGAAGTCAACTT
CGGGAGGGACCGCGGCACTTGGCT
GTCTTGTCAAAGATTACTTCCCTGA
GCCAGTGACAGTCAGCTGGAATTC
CGGTGCCCTCACGTCAGGAGTACA
TACATTCCCTGCGGTATTGCAGTCC
TCCGGACTCTACTCCCTGGAGTCGG
TGGTAACGGTGCCCAGCTCCAGCTT
GGGGACCCAGACGTACATTTGTAA
CGTGAATCACAAACCAAGCAATAC
TAAGGTAGATAAGAAAGTAGAACC
GAAGAGCTGC
(SEQ ID NO: 535)
AA
QAVPTQPSSLSASPGASASLTCTLRSGI
DIQMTQSPSSVSASVGDRVTITCRAS
QVQLVESGGGVVQPGRSLRLSCAAS
NVGSSRIYWYQQKPGSPPQFLLRYTSD
QGITRWLAWYQQKPGKAPKLLIYAA
GFTFSSHGMHWVRQPPGKGLEWVA
SDKLQGSGVPSRFSGSKDASANAGLLL
SVLQSGVPSRFSGSGSGTDFTLTISSL
VIWYDGSNEYYGDSVKGRFTISRDN
ISGLQSEDEADYYCMIWHSSAVVFGG
QPEDFATYYCQQSNSFPRTFGQGTK
SKNTLYLQMNSLRVEDTAVYYCTRG
GTKLTVLGQPKAAPSVTLFPPSSEELQ
VEIKRTVAAPSVFIFPPSDEQLKSGTA
GGHWNYEGHYYGMDVWGQGTTVT
ANKATLVCLISDFYPGAVTVAWKADS
SVVCLLNNFYPREAKVQWKVDNAL
VSSASTKGPSVFPLAPSSKSTSGGTA
SPVKAGVETTTPSKQSNNKYAAESYLS
QSGNSQESVTEQDSKDSTYSLKSTLT
ALGCLVKDYFPEPVTVSWNSGALTS
LTPEQWKSHRSYSCQVTHEGSTVEKT
LSKADYEKHKVYACEVTHQGLSSPV
GVHTFPAVLQSSGLYSLKSVVTVPSS
VAPTECS
TKSFNRGEC
SLGTQTYICNVNHKPSNTKVDKKVE
(SEQ ID NO: 536)
(SEQ ID NO: 537)
PKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSH
EDPEVKFNWYVDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNG
KEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCL
VKGFYPSDIAVEWESNGQPENNYKT
TPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSL
SPGGGGSGGGGSQVQLVESGGGLVK
PGGSLRLSCAASGFTFSDYYMTWIR
QAPGKGLEWISYISSSGSTIYYADSV
KGRFTISRDNAKNSLYLQMNSLRAE
DTAVYYCARDRNSHFDYWGQGTLV
TVSSASTKGPSVFPLAPSSKSTSGGTA
ALGCLVKDYFPEPVTVSWNSGALTS
GVHTFPAVLQSSGLYSLESVVTVPSS
SLGTQTYICNVNHKPSNTKVDKKVE
PKSC
(SEQ ID NO: 538)
iPS:
21-
[hu anti-
NA
CAGGCTGTGCCGACTCAGCCCTCTTC
GACATCCAGATGACCCAGTCTCCA
CAGGTGCAGTTGGTGGAGTCTGGG
576330
230_33H9_IgG_
<hu CD40> 21-230_
CCTCTCTGCATCTCCTGGAGCATCAG
TCTTCCGTGTCTGCTTCTGTCGGAG
GGAGGCGTGGTCCAGCCTGGGAGG
21-
33H9VH]::huIgG1zSEFL2*GK-
CCAGTCTCACCTGCACCTTACGCAGT
ACAGAGTCACCATCACTTGTCGGG
TCCCTGAGACTCTCCTGTGCAGCGT
233_6F4__Fab
K::(G4S)2::[hu anti-
GGCATCAATGTTGGTTCCTCCAGGAT
CGAGTCAGGATATTAGCAGGTGGT
CTGGATTCACCTTCAGTAGCCATGG
<hu Mesothelin>
CTATTGGTACCAGCAGAAGCCAGGG
TAGCCTGGTATCAGCAGAAACCAG
CATGCACTGGGTCCGCCAACCTCC
6F4VH]::huIgG1z-
AGTCCTCCCCAGTTTCTCCTGAGGTA
GGAAAGCCCCTAAGCTCCTGATTTC
AGGCAAGGGGCTGGAGTGGGTGGC
CH1-E::EPKSC + [anti-
CACATCAGACTCAGATAAATTGCAG
TGCTGCATCCAGATTGCAAAGTGG
AGTTATCTGGTATGATGGAAGTAA
<hu CD40>
GGCTCTGGAGTCCCCAGCCGCTTCTC
AGTCCCATCAAGGTTCAGCGGCAG
TGAATACTATGGAGACTCCGTGAA
21-230_33H9VL]::huLLC2-
TGGATCCAAAGATGCTTCGGCCAATG
TGGATCTGGGACAGATTTCACTCTC
GGGCCGATTCACCATCTCCAGAGA
E + [anti-
CAGGACTTTTACTCATCTCTGGGCTC
ACCATCAGCAGCCTGCAGCCTGAA
CAATTCCAAGAACACGCTGTATCT
<hu Mesothelin>
CAGTCTGAGGATGAGGCTGACTATTA
GATTTTGCAATTTACTATTGTCAAC
GCAAATGAACAGCCTGAGAGTCGA
6F4VL]::huKLC-
CTGTATGATTTGGCACAGCAGCGCTG
AGGCTAAAAGTTTTCCTCGGACGTT
GGACACGGCTGTGTATTACTGTAC
S176K (IgG-Fab);
TGGTATTCGGCGGAGGGACCAAACT
CGGCCAAGGGACCAAGGTGGAAAT
GAGAGGGGGGGGCCACTGGAACTA
LMRID: SS-30873
GACCGTCCTAGGTCAGCCCAAGGCTG
CAAACGGACGGTGGCTGCACCATC
CGAGGGCCACTACTATGGTATGGA
CACCCTCGGTCACTCTGTTCCCGCCC
TGTCTTCATCTTCCCGCCATCTGAT
CGTCTGGGGCCAAGGGACCACGGT
TCCTCTGAGGAGCTTCAAGCCAACAA
GAGCAGTTGAAATCTGGAACTGCC
CACCGTGTCCTCAGCCTCCACCAAG
GGCCACACTGGTGTGTCTCATCAGTG
TCTGTTGTGTGCCTGCTGAATAACT
GGCCCATCGGTCTTCCCCCTGGCAC
ACTTCTACCCGGGAGCCGTGACAGTG
TCTATCCCAGAGAGGCCAAAGTAC
CCTCCTCCAAGAGCACCTCTGGGG
GCCTGGAAGGCAGATAGCAGCCCCG
AGTGGAAGGTGGATAACGCCCTCC
GCACAGCGGCCCTGGGCTGCCTGG
TCAAGGCGGGAGTGGAAACCACCAC
AATCGGGTAACTCCCAGGAGAGTG
TCAAGGACTACTTCCCCGAACCGG
ACCCTCCAAACAAAGCAACAACAAG
TCACAGAGCAGGACAGCAAGGACA
TGACGGTGTCGTGGAACTCAGGCG
TACGCGGCCGAAAGCTATCTGAGCCT
GCACCTACAGCCTCAAGAGCACCC
CCCTGACCAGCGGCGTGCACACCT
GACGCCTGAGCAGTGGAAGTCCCAC
TGACGCTGAGCAAAGCAGACTACG
TCCCGGCTGTCCTACAGTCCTCAGG
AGAAGCTACAGCTGCCAGGTCACGC
AGAAACACAAAGTCTACGCCTGCG
ACTCTACTCCCTCAAGAGCGTGGTG
ATGAAGGGAGCACCGTGGAGAAGAC
AAGTCACCCATCAGGGCCTGAGCT
ACCGTGCCCTCCAGCAGCTTGGGC
AGTGGCCCCTACAGAATGTTCA
CGCCCGTCACAAAGAGCTTCAACA
ACCCAGACCTACATCTGCAACGTG
(SEQ ID NO: 539)
GGGGAGAGTGT
AATCACAAGCCCAGCAACACCAAG
(SEQ ID NO: 540)
GTGGACAAGAAAGTTGAGCCCAAA
TCTTGTGACAAAACTCACACATGCC
CACCGTGCCCAGCACCTGAACTCCT
GGGGGGACCGTCAGTCTTCCTCTTC
CCCCCAAAACCCAAGGACACCCTC
ATGATCTCCCGGACCCCTGAGGTC
ACATGCGTGGTGGTGGACGTGAGC
CACGAAGACCCTGAGGTCAAGTTC
AACTGGTACGTGGACGGCGTGGAG
GTGCATAATGCCAAGACAAAGCCG
TGCGAGGAGCAGTACGGCAGCACG
TACCGTTGCGTCAGCGTCCTCACCG
TCCTGCACCAGGACTGGCTGAATG
GCAAGGAGTACAAGTGCAAGGTGT
CCAACAAAGCCCTCCCAGCCCCCA
TCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGG
TGTACACCCTGCCCCCATCCCGGGA
GGAGATGACCAAGAACCAGGTCAG
CCTGACCTGCCTGGTCAAAGGCTTC
TATCCCAGCGACATCGCCGTGGAG
TGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCC
GTGCTGGACTCCGACGGCTCCTTCT
TCCTCTATAGCAAGCTCACCGTGGA
CAAGAGCAGGTGGCAGCAGGGGA
ACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACAC
GCAGAAGAGCCTCTCCCTGTCTCCG
GGTGGTGGCGGATCGGGAGGTGGC
GGATCCCAGGTGCAGCTGGTGGAG
TCTGGGGGAGGCTTGGTCAAGCCT
GGAGGGTCCCTGAGACTCTCCTGT
GCAGCCTCTGGATTCACCTTCAGTG
ACTACTACATGAGCTGGATCCGCC
AGGCTCCAGGGAAGGGGCTGGAGT
GGATTTCATACATTAGTAGCAGTG
AAAGTATCATCTATTACGTAGACTC
TGTGAAGGGCCGATTCACCATCTCC
AGGGACAACGCCAAGAACTCACTG
TATCTGCAAATGAACAGCCTGAGA
GCCGAGGACACGGCCGTGTATTAC
TGTGCGAGAGATGTTGGGAGCCAC
TTTGACTACTGGGGCCAGGGAACC
CTGGTCACCGTGTCCTCAGCAAGC
ACGAAGGGGCCGTCCGTATTTCCG
CTTGCGCCCTCGTCGAAGTCAACTT
CGGGAGGGACCGCGGCACTTGGCT
GTCTTGTCAAAGATTACTTCCCTGA
GCCAGTGACAGTCAGCTGGAATTC
CGGTGCCCTCACGTCAGGAGTACA
TACATTCCCTGCGGTATTGCAGTCC
TCCGGACTCTACTCCCTGGAGTCGG
TGGTAACGGTGCCCAGCTCCAGCTT
GGGGACCCAGACGTACATTTGTAA
CGTGAATCACAAACCAAGCAATAC
TAAGGTAGATAAGAAAGTAGAACC
GAAGAGCTGC
(SEQ ID NO: 541)
AA
QAVPTQPSSLSASPGASASLTCTLRSGI
DIQMTQSPSSVSASVGDRVTITCRAS
QVQLVESGGGVVQPGRSLRLSCAAS
NVGSSRIYWYQQKPGSPPQFLLRYTSD
QDISRWLAWYQQKPGKAPKLLISAA
GFTFSSHGMHWVRQPPGKGLEWVA
SDKLQGSGVPSRFSGSKDASANAGLLL
SRLQSGVPSRFSGSGSGTDFTLTISSL
VIWYDGSNEYYGDSVKGRFTISRDN
ISGLQSEDEADYYCMIWHSSAVVFGG
QPEDFAIYYCQQAKSFPRTFGQGTKV
SKNTLYLQMNSLRVEDTAVYYCTRG
GTKLTVLGQPKAAPSVTLFPPSSEELQ
EIKRTVAAPSVFIFPPSDEQLKSGTAS
GGHWNYEGHYYGMDVWGQGTTVT
ANKATLVCLISDFYPGAVTVAWKADS
VVCLLNNFYPREAKVQWKVDNALQ
VSSASTKGPSVFPLAPSSKSTSGGTA
SPVKAGVETTTPSKQSNNKYAAESYLS
SGNSQESVTEQDSKDSTYSLKSTLTL
ALGCLVKDYFPEPVTVSWNSGALTS
LTPEQWKSHRSYSCQVTHEGSTVEKT
SKADYEKHKVYACEVTHQGLSSPVT
GVHTFPAVLQSSGLYSLKSVVTVPSS
VAPTECS
KSFNRGEC
SLGTQTYICNVNHKPSNTKVDKKVE
(SEQ ID NO: 542)
(SEQ ID NO: 543)
PKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSH
EDPEVKFNWYVDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNG
KEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCL
VKGFYPSDIAVEWESNGQPENNYKT
TPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSL
SPGGGGSGGGGSQVQLVESGGGLVK
PGGSLRLSCAASGFTFSDYYMSWIRQ
APGKGLEWISYISSSESIIYYVDSVKG
RFTISRDNAKNSLYLQMNSLRAEDT
AVYYCARDVGSHFDYWGQGTLVTV
SSASTKGPSVFPLAPSSKSTSGGTAAL
GCLVKDYFPEPVTVSWNSGALTSGV
HTFPAVLQSSGLYSLESVVTVPSSSL
GTQTYICNVNHKPSNTKVDKKVEPK
SC
(SEQ ID NO: 544)
iPS:
21-
[hu anti-
NA
CAGGCTGTGCCGACTCAGCCCTCTTC
GACATTGTGATGACTCAGTCTCCAG
CAGGTGCAGTTGGTGGAGTCTGGG
576333
230_33H9_IgG_
<hu CD40> 21-230_
CCTCTCTGCATCTCCTGGAGCATCAG
ACTCCCTGGCTGTGTCTCTGGGCGA
GGAGGCGTGGTCCAGCCTGGGAGG
21-
33H9VH]::huIgG1zSEFL2*GK-
CCAGTCTCACCTGCACCTTACGCAGT
GAGGGCCACCATCAACTGCAAGTC
TCCCTGAGACTCTCCTGTGCAGCGT
233_7G11__Fab
K::(G4S)2::[hu anti-
GGCATCAATGTTGGTTCCTCCAGGAT
CAGCCAGAGTGTTTTATACAGCTCC
CTGGATTCACCTTCAGTAGCCATGG
<hu Mesothelin>
CTATTGGTACCAGCAGAAGCCAGGG
AACAATAAGAACTACTTAGCTTGG
CATGCACTGGGTCCGCCAACCTCC
7G11VH]::huIgG1z-
AGTCCTCCCCAGTTTCTCCTGAGGTA
TACCAGCAGAAACCAGGACAGCCT
AGGCAAGGGGCTGGAGTGGGTGGC
CH1-E::EPKSC + [anti-
CACATCAGACTCAGATAAATTGCAG
CCTAAGCTGCTCATTTACTGGGCAT
AGTTATCTGGTATGATGGAAGTAA
<hu CD40>
GGCTCTGGAGTCCCCAGCCGCTTCTC
CTACCCGAGAATCCGGGGTCCCTG
TGAATACTATGGAGACTCCGTGAA
21-230_33H9VL]::huLLC2-
TGGATCCAAAGATGCTTCGGCCAATG
ACCGATTCAGTGGCAGCGGGTCTG
GGGCCGATTCACCATCTCCAGAGA
E + [anti-
CAGGACTTTTACTCATCTCTGGGCTC
GGACAGATTTCACTCTCACCATCAG
CAATTCCAAGAACACGCTGTATCT
<hu Mesothelin>
CAGTCTGAGGATGAGGCTGACTATTA
CAGCCTGCAGGCTGAAGATGTGGC
GCAAATGAACAGCCTGAGAGTCGA
7G11VL]::huKLC-
CTGTATGATTTGGCACAGCAGCGCTG
AGTTTATTACTGTCAGCAATATTAT
GGACACGGCTGTGTATTACTGTAC
S176K (IgG-Fab);
TGGTATTCGGCGGAGGGACCAAACT
AGTACTCCTCCGACGTTCGGCCAA
GAGAGGGGGGGGCCACTGGAACTA
LMRID: SS-30874
GACCGTCCTAGGTCAGCCCAAGGCTG
GGGACCAAGGTGGAGATCAAACGG
CGAGGGCCACTACTATGGTATGGA
CACCCTCGGTCACTCTGTTCCCGCCC
ACGGTGGCTGCACCATCTGTCTTCA
CGTCTGGGGCCAAGGGACCACGGT
TCCTCTGAGGAGCTTCAAGCCAACAA
TCTTCCCGCCATCTGATGAGCAGTT
CACCGTGTCCTCAGCCTCCACCAAG
GGCCACACTGGTGTGTCTCATCAGTG
GAAATCTGGAACTGCCTCTGTTGTG
GGCCCATCGGTCTTCCCCCTGGCAC
ACTTCTACCCGGGAGCCGTGACAGTG
TGCCTGCTGAATAACTTCTATCCCA
CCTCCTCCAAGAGCACCTCTGGGG
GCCTGGAAGGCAGATAGCAGCCCCG
GAGAGGCCAAAGTACAGTGGAAGG
GCACAGCGGCCCTGGGCTGCCTGG
TCAAGGCGGGAGTGGAAACCACCAC
TGGATAACGCCCTCCAATCGGGTA
TCAAGGACTACTTCCCCGAACCGG
ACCCTCCAAACAAAGCAACAACAAG
ACTCCCAGGAGAGTGTCACAGAGC
TGACGGTGTCGTGGAACTCAGGCG
TACGCGGCCGAAAGCTATCTGAGCCT
AGGACAGCAAGGACAGCACCTACA
CCCTGACCAGCGGCGTGCACACCT
GACGCCTGAGCAGTGGAAGTCCCAC
GCCTCAAGAGCACCCTGACGCTGA
TCCCGGCTGTCCTACAGTCCTCAGG
AGAAGCTACAGCTGCCAGGTCACGC
GCAAAGCAGACTACGAGAAACACA
ACTCTACTCCCTCAAGAGCGTGGTG
ATGAAGGGAGCACCGTGGAGAAGAC
AAGTCTACGCCTGCGAAGTCACCC
ACCGTGCCCTCCAGCAGCTTGGGC
AGTGGCCCCTACAGAATGTTCA
ATCAGGGCCTGAGCTCGCCCGTCA
ACCCAGACCTACATCTGCAACGTG
(SEQ ID NO: 545)
CAAAGAGCTTCAACAGGGGAGAGT
AATCACAAGCCCAGCAACACCAAG
GT
GTGGACAAGAAAGTTGAGCCCAAA
(SEQ ID NO: 546)
TCTTGTGACAAAACTCACACATGCC
CACCGTGCCCAGCACCTGAACTCCT
GGGGGGACCGTCAGTCTTCCTCTTC
CCCCCAAAACCCAAGGACACCCTC
ATGATCTCCCGGACCCCTGAGGTC
ACATGCGTGGTGGTGGACGTGAGC
CACGAAGACCCTGAGGTCAAGTTC
AACTGGTACGTGGACGGCGTGGAG
GTGCATAATGCCAAGACAAAGCCG
TGCGAGGAGCAGTACGGCAGCACG
TACCGTTGCGTCAGCGTCCTCACCG
TCCTGCACCAGGACTGGCTGAATG
GCAAGGAGTACAAGTGCAAGGTGT
CCAACAAAGCCCTCCCAGCCCCCA
TCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGG
TGTACACCCTGCCCCCATCCCGGGA
GGAGATGACCAAGAACCAGGTCAG
CCTGACCTGCCTGGTCAAAGGCTTC
TATCCCAGCGACATCGCCGTGGAG
TGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCC
GTGCTGGACTCCGACGGCTCCTTCT
TCCTCTATAGCAAGCTCACCGTGGA
CAAGAGCAGGTGGCAGCAGGGGA
ACGTCTTCTCATGCTCCGTGATGCA
TGAGGCTCTGCACAACCACTACAC
GCAGAAGAGCCTCTCCCTGTCTCCG
GGTGGTGGCGGATCGGGAGGTGGC
GGATCCGAGGTGCAGCTGGTCGAG
TCTGGAGGAGGCTTGATCCAGCCT
GGGGGGTCCCTGAGACTCTCCTGT
GCAGTCTCTGGGTTCACCGTCAGTA
GCAAGTTCATGACCTGGGTCCGCC
AGGCTCCAGGGAAGGGGCTGGAGT
GGGTGTCAGTTATTTATAGCGGTGG
TAAGACATACTACGCAGACTCCGT
GAAGGGCCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTA
TCTTCAAATGAACAGCCTGAGAGC
CGAGGACACGGCCGTGTATTACTG
TGCGAGAGATAGCGGTGGCTGGGG
GTACTTTGACTACTGGGGCCAGGG
AACCCTGGTCACCGTGTCCTCAGCA
AGCACGAAGGGGCCGTCCGTATTT
CCGCTTGCGCCCTCGTCGAAGTCAA
CTTCGGGAGGGACCGCGGCACTTG
GCTGTCTTGTCAAAGATTACTTCCC
TGAGCCAGTGACAGTCAGCTGGAA
TTCCGGTGCCCTCACGTCAGGAGTA
CATACATTCCCTGCGGTATTGCAGT
CCTCCGGACTCTACTCCCTGGAGTC
GGTGGTAACGGTGCCCAGCTCCAG
CTTGGGGACCCAGACGTACATTTGT
AACGTGAATCACAAACCAAGCAAT
ACTAAGGTAGATAAGAAAGTAGAA
CCGAAGAGCTGC
(SEQ ID NO: 547)
AA
QAVPTQPSSLSASPGASASLTCTLRSGI
DIVMTQSPDSLAVSLGERATINCKSS
QVQLVESGGGVVQPGRSLRLSCAAS
NVGSSRIYWYQQKPGSPPQFLLRYTSD
QSVLYSSNNKNYLAWYQQKPGQPP
GFTFSSHGMHWVRQPPGKGLEWVA
SDKLQGSGVPSRFSGSKDASANAGLLL
KLLIYWASTRESGVPDRFSGSGSGTD
VIWYDGSNEYYGDSVKGRFTISRDN
ISGLQSEDEADYYCMIWHSSAVVFGG
FTLTISSLQAEDVAVYYCQQYYSTPP
SKNTLYLQMNSLRVEDTAVYYCTRG
GTKLTVLGQPKAAPSVTLFPPSSEELQ
TFGQGTKVEIKRTVAAPSVFIFPPSDE
GGHWNYEGHYYGMDVWGQGTTVT
ANKATLVCLISDFYPGAVTVAWKADS
QLKSGTASVVCLLNNFYPREAKVQW
VSSASTKGPSVFPLAPSSKSTSGGTA
SPVKAGVETTTPSKQSNNKYAAESYLS
KVDNALQSGNSQESVTEQDSKDSTY
ALGCLVKDYFPEPVTVSWNSGALTS
LTPEQWKSHRSYSCQVTHEGSTVEKT
SLKSTLTLSKADYEKHKVYACEVTH
GVHTFPAVLQSSGLYSLKSVVTVPSS
VAPTECS
QGLSSPVTKSFNRGEC
SLGTQTYICNVNHKPSNTKVDKKVE
(SEQ ID NO: 548)
(SEQ ID NO: 549)
PKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSH
EDPEVKFNWYVDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNG
KEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCL
VKGFYPSDIAVEWESNGQPENNYKT
TPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSL
SPGGGGSGGGGSEVQLVESGGGLIQP
GGSLRLSCAVSGFTVSSKFMTWVRQ
APGKGLEWVSVIYSGGKTYYADSVK
GRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDSGGWGYFDYWGQGTL
VTVSSASTKGPSVFPLAPSSKSTSGGT
AALGCLVKDYFPEPVTVSWNSGALT
SGVHTFPAVLQSSGLYSLESVVTVPS
SSLGTQTYICNVNHKPSNTKVDKKV
EPKSC
(SEQ ID NO: 550)
iPS:
21-
[hu anti-
NA
CAGTCTGCCCTGACTCAGCCTCGCTC
CAGTCAGTGTTGACGCAGCCGCCC
CAGGTGCAGCTGGTGGAGTCTGGG
576336
230_35F11_IgG_
<hu CD40> 21-230_
AGTGTCCGGGAGCCCTGGACAGTCA
TCAGTGTCTGGGGCCCCAGGGCAG
GGAGGCGTGGTCCAGCCTGGGAGG
21-
35F11VH]::huIgG1zSEFL2*GK-
GTCACCATCTCCTGCACTGGAACCAG
AGGGTCACCATCTCCTGCACTGGG
TCCCTGAGACTCTCCTGTGCAGCGT
233_4G12__Fab
K::(G4S)2::[hu anti-
CAGTGATGTTGGTGGTTATATCTTTG
AGCAGCTCCAACATCGGGGCAGGT
CTGGATTCACCCTCAGTAGCTATGG
<hu Mesothelin>
TCTCCTGGTACCAACAACACCCAGGC
TATGATGTTCACTGGTACCAGCAG
CATGCACTGGGTCCGCCAGGCTCC
4G12VH]::huIgG1z-
AAAGCCCCCAAACTCATGATTTATGA
GTTCCAGGAACAGCCCCCAAACTC
AGGCAAGGGGCTGGAGTGGGTGGC
CH1-E::EPKSC + [anti-
TGTCAGTAAGCGGCCCTCTGGGGTCC
CTCATCTATGGTAACAGCAAGCGG
AGTTATCTGGTATGATGGAAGTAA
<hu CD40>
CTGATCGCTTCTCTGGCTCCAAGTCT
CCCTCAGGGGTCCCTGACCGATTCT
TAAATACTATGCAGACTCCGTGAA
21-230_35F11VL]::huLLC2-
GTCAACACGGCCTCCCTGACCATCTC
CTGGCTCCAAGTCTGGCACCTCAGC
GGGCCGAGTCACCATCTCCAGAGA
E + [anti-
TGGGCTCCAGGCTGAGGATGAGACT
CTCCCTGGCCATCACTGGGCTCCAG
CAATTCCAAGAACACGCTGTATCT
<hu Mesothelin>
GATTATTACTGCTGCTCATATGCAGG
GCTGAGGATGAGGCTGATTATTAC
GCAAATGAATAGCCTGAGAGCCGA
4G12VL]::huLLC2-
CAACTACACTTATGTCTTCGGAACTG
TGCCAGTCCTATGACAGCAGCCTG
GGACACGGCTGTGTATTACTGTAC
K (IgG-Fab);
GGACCAAGGTCACCGTCCTAGGTCA
GGTGGTTGGGTGTTCGGCGGAGGG
GAGAGATGGCCGGAACTACGTCTA
LMRID: SS-30875
GCCCAAGGCTGCACCCTCGGTCACTC
ACCAAGCTGACCGTCCTACAGCCC
CTTTGACAACTGGGGCCAGGGAAC
TGTTCCCGCCCTCCTCTGAGGAGCTT
AAGGCTGCACCCTCGGTCACTCTGT
CCTGGTCACCGTGTCCTCAGCCTCC
CAAGCCAACAAGGCCACACTGGTGT
TCCCGCCCTCCTCTGAGGAGCTTCA
ACCAAGGGCCCATCGGTCTTCCCCC
GTCTCATCAGTGACTTCTACCCGGGA
AGCCAACAAGGCCACACTGGTGTG
TGGCACCCTCCTCCAAGAGCACCTC
GCCGTGACAGTGGCCTGGAAGGCAG
TCTCATCAGTGACTTCTACCCGGGA
TGGGGGCACAGCGGCCCTGGGCTG
ATAGCAGCCCCGTCAAGGCGGGAGT
GCCGTGACAGTGGCCTGGAAGGCA
CCTGGTCAAGGACTACTTCCCCGA
GGAAACCACCACACCCTCCAAACAA
GATAGCAGCCCCGTCAAGGCGGGA
ACCGGTGACGGTGTCGTGGAACTC
AGCAACAACAAGTACGCGGCCGAAA
GTGGAAACCACCACACCCTCCAAA
AGGCGCCCTGACCAGCGGCGTGCA
GCTATCTGAGCCTGACGCCTGAGCAG
CAAAGCAACAACAAGTACGCGGCC
CACCTTCCCGGCTGTCCTACAGTCC
TGGAAGTCCCACAGAAGCTACAGCT
AAGAGCTATCTGAGCCTGACGCCT
TCAGGACTCTACTCCCTCAAGAGC
GCCAGGTCACGCATGAAGGGAGCAC
GAGCAGTGGAAGTCCCACAGAAGC
GTGGTGACCGTGCCCTCCAGCAGC
CGTGGAGAAGACAGTGGCCCCTACA
TACAGCTGCCAGGTCACGCATGAA
TTGGGCACCCAGACCTACATCTGC
GAATGTTCA
GGGAGCACCGTGGAGAAGACAGTG
AACGTGAATCACAAGCCCAGCAAC
(SEQ ID NO: 551)
GCCCCTACAGAATGTTCA
ACCAAGGTGGACAAGAAAGTTGAG
(SEQ ID NO: 552)
CCCAAATCTTGTGACAAAACTCAC
ACATGCCCACCGTGCCCAGCACCT
GAACTCCTGGGGGGACCGTCAGTC
TTCCTCTTCCCCCCAAAACCCAAGG
ACACCCTCATGATCTCCCGGACCCC
TGAGGTCACATGCGTGGTGGTGGA
CGTGAGCCACGAAGACCCTGAGGT
CAAGTTCAACTGGTACGTGGACGG
CGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGG
CAGCACGTACCGTTGCGTCAGCGT
CCTCACCGTCCTGCACCAGGACTG
GCTGAATGGCAAGGAGTACAAGTG
CAAGGTGTCCAACAAAGCCCTCCC
AGCCCCCATCGAGAAAACCATCTC
CAAAGCCAAAGGGCAGCCCCGAGA
ACCACAGGTGTACACCCTGCCCCC
ATCCCGGGAGGAGATGACCAAGAA
CCAGGTCAGCCTGACCTGCCTGGTC
AAAGGCTTCTATCCCAGCGACATC
GCCGTGGAGTGGGAGAGCAATGGG
CAGCCGGAGAACAACTACAAGACC
ACGCCTCCCGTGCTGGACTCCGAC
GGCTCCTTCTTCCTCTATAGCAAGC
TCACCGTGGACAAGAGCAGGTGGC
AGCAGGGGAACGTCTTCTCATGCT
CCGTGATGCATGAGGCTCTGCACA
ACCACTACACGCAGAAGAGCCTCT
CCCTGTCTCCGGGTGGTGGCGGATC
GGGAGGTGGCGGATCCCAGGTGCA
GCTGCAGGAGTCGGGCCCAGGACT
GGTGAAGCCTTCGGAAACCCTGTC
CCTCACCTGCACTGTCTCTGGTGGC
TCCATCAGCAGTAGTAGTTACTACT
GGGGCTGGATCAGGCAGCCCCCAG
GGAAGGGGCTGGAGTGGATTGGGA
GTATCTATTATAGTGGGATCACCAA
CTACAACCCGTCCCTCAAGAGTCG
AGTCACCATCTCCGTAGACACGTCC
AAGAACCAGTTCTCCCTGAAGCTG
AGTTCTGTGACCGCCGCAGACACG
GCCGTGTATTACTGTGCGAGATCCA
GTAACTACGATGCTTTTGATATCTG
GGGCCAAGGGACAATGGTCACCGT
GTCCTCAGCAAGCACGAAGGGGCC
GTCCGTATTTCCGCTTGCGCCCTCG
TCGAAGTCAACTTCGGGAGGGACC
GCGGCACTTGGCTGTCTTGTCAAAG
ATTACTTCCCTGAGCCAGTGACAGT
CAGCTGGAATTCCGGTGCCCTCAC
GTCAGGAGTACATACATTCCCTGC
GGTATTGCAGTCCTCCGGACTCTAC
TCCCTGGAGTCGGTGGTAACGGTG
CCCAGCTCCAGCTTGGGGACCCAG
ACGTACATTTGTAACGTGAATCAC
AAACCAAGCAATACTAAGGTAGAT
AAGAAAGTAGAACCGAAGAGCTGC
(SEQ ID NO: 553)
AA
QSALTQPRSVSGSPGQSVTISCTGTSSD
QSVLTQPPSVSGAPGQRVTISCTGSSS
QVQLVESGGGVVQPGRSLRLSCAAS
VGGYIFVSWYQQHPGKAPKLMIYDVS
NIGAGYDVHWYQQVPGTAPKLLIYG
GFTLSSYGMHWVRQAPGKGLEWVA
KRPSGVPDRFSGSKSVNTASLTISGLQA
NSKRPSGVPDRFSGSKSGTSASLAIT
VIWYDGSNKYYADSVKGRVTISRDN
EDETDYYCCSYAGNYTYVFGTGTKVT
GLQAEDEADYYCQSYDSSLGGWVF
SKNTLYLQMNSLRAEDTAVYYCTRD
VLGQPKAAPSVTLFPPSSEELQANKAT
GGGTKLTVLQPKAAPSVTLFPPSSEE
GRNYVYFDNWGQGTLVTVSSASTK
LVCLISDFYPGAVTVAWKADSSPVKA
LQANKATLVCLISDFYPGAVTVAWK
GPSVFPLAPSSKSTSGGTAALGCLVK
GVETTTPSKQSNNKYAAESYLSLTPEQ
ADSSPVKAGVETTTPSKQSNNKYAA
DYFPEPVTVSWNSGALTSGVHTFPA
WKSHRSYSCQVTHEGSTVEKTVAPTE
KSYLSLTPEQWKSHRSYSCQVTHEG
VLQSSGLYSLKSVVTVPSSSLGTQTY
CS
STVEKTVAPTECS
ICNVNHKPSNTKVDKKVEPKSCDKT
(SEQ ID NO: 554)
(SEQ ID NO: 555)
HTCPPCPAPELLGGPSVFLFPPKPKDT
LMISRTPEVTCVVVDVSHEDPEVKFN
WYVDGVEVHNAKTKPCEEQYGSTY
RCVSVLTVLHQDWLNGKEYKCKVS
NKALPAPIEKTISKAKGQPREPQVYT
LPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSD
GSFFLYSKLTVDKSRWQQGNVFSCS
VMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLQESGPGLVKPSETLSLTC
TVSGGSISSSSYYWGWIRQPPGKGLE
WIGSIYYSGITNYNPSLKSRVTISVDT
SKNQFSLKLSSVTAADTAVYYCARS
SNYDAFDIWGQGTMVTVSSASTKGP
SVFPLAPSSKSTSGGTAALGCLVKDY
FPEPVTVSWNSGALTSGVHTFPAVL
QSSGLYSLESVVTVPSSSLGTQTYICN
VNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 556)
iPS:
21-
[hu anti-
NA
CAGTCTGCCCTGACTCAGCCTCGCTC
GACATTCAGATGACCCAGTCTCCAT
CAGGTGCAGCTGGTGGAGTCTGGG
576341
230_35F11_IgG_
<hu CD40> 21-230_
AGTGTCCGGGAGCCCTGGACAGTCA
CTTCCGTGTCTGCATCTGTAGGGGA
GGAGGCGTGGTCCAGCCTGGGAGG
21-
35F11VH]::huIgG1zSEFL2*GK-
GTCACCATCTCCTGCACTGGAACCAG
CAGAGTCACCATCACTTGTCGGGC
TCCCTGAGACTCTCCTGTGCAGCGT
233_4H6__Fab
K::(G4S)2::[hu anti-
CAGTGATGTTGGTGGTTATATCTTTG
GAGTCAGGGTATTACCAGGTGGTT
CTGGATTCACCCTCAGTAGCTATGG
<hu Mesothelin>
TCTCCTGGTACCAACAACACCCAGGC
AGCCTGGTATCAGCAGAAACCAGG
CATGCACTGGGTCCGCCAGGCTCC
4H6VH]::huIgG1z-
AAAGCCCCCAAACTCATGATTTATGA
GAAAGCCCCTAAGCTCCTGATCTAT
AGGCAAGGGGCTGGAGTGGGTGGC
CH1-E::EPKSC + [anti-
TGTCAGTAAGCGGCCCTCTGGGGTCC
GCTGCATCCGTTTTGCAAAGTGGG
AGTTATCTGGTATGATGGAAGTAA
<hu CD40>
CTGATCGCTTCTCTGGCTCCAAGTCT
GTCCCATCAAGGTTCAGCGGCAGT
TAAATACTATGCAGACTCCGTGAA
21-230_35F11VL]::huLLC2-
GTCAACACGGCCTCCCTGACCATCTC
GGATCTGGGACAGATTTCACTCTCA
GGGCCGAGTCACCATCTCCAGAGA
E + [anti-
TGGGCTCCAGGCTGAGGATGAGACT
CCATCAGCAGCCTGCAGCCTGAAG
CAATTCCAAGAACACGCTGTATCT
<hu Mesothelin>
GATTATTACTGCTGCTCATATGCAGG
ATTTTGCAACTTACTATTGTCAACA
GCAAATGAATAGCCTGAGAGCCGA
4H6VL]::huKLC-
CAACTACACTTATGTCTTCGGAACTG
GTCTAACAGTTTCCCTCGGACGTTC
GGACACGGCTGTGTATTACTGTAC
S176K (IgG-Fab);
GGACCAAGGTCACCGTCCTAGGTCA
GGCCAAGGGACCAAGGTGGAAATC
GAGAGATGGCCGGAACTACGTCTA
LMRID: SS-30876
GCCCAAGGCTGCACCCTCGGTCACTC
AAACGGACGGTGGCTGCACCATCT
CTTTGACAACTGGGGCCAGGGAAC
TGTTCCCGCCCTCCTCTGAGGAGCTT
GTCTTCATCTTCCCGCCATCTGATG
CCTGGTCACCGTGTCCTCAGCCTCC
CAAGCCAACAAGGCCACACTGGTGT
AGCAGTTGAAATCTGGAACTGCCT
ACCAAGGGCCCATCGGTCTTCCCCC
GTCTCATCAGTGACTTCTACCCGGGA
CTGTTGTGTGCCTGCTGAATAACTT
TGGCACCCTCCTCCAAGAGCACCTC
GCCGTGACAGTGGCCTGGAAGGCAG
CTATCCCAGAGAGGCCAAAGTACA
TGGGGGCACAGCGGCCCTGGGCTG
ATAGCAGCCCCGTCAAGGCGGGAGT
GTGGAAGGTGGATAACGCCCTCCA
CCTGGTCAAGGACTACTTCCCCGA
GGAAACCACCACACCCTCCAAACAA
ATCGGGTAACTCCCAGGAGAGTGT
ACCGGTGACGGTGTCGTGGAACTC
AGCAACAACAAGTACGCGGCCGAAA
CACAGAGCAGGACAGCAAGGACA
AGGCGCCCTGACCAGCGGCGTGCA
GCTATCTGAGCCTGACGCCTGAGCAG
GCACCTACAGCCTCAAGAGCACCC
CACCTTCCCGGCTGTCCTACAGTCC
TGGAAGTCCCACAGAAGCTACAGCT
TGACGCTGAGCAAAGCAGACTACG
TCAGGACTCTACTCCCTCAAGAGC
GCCAGGTCACGCATGAAGGGAGCAC
AGAAACACAAAGTCTACGCCTGCG
GTGGTGACCGTGCCCTCCAGCAGC
CGTGGAGAAGACAGTGGCCCCTACA
AAGTCACCCATCAGGGCCTGAGCT
TTGGGCACCCAGACCTACATCTGC
GAATGTTCA
CGCCCGTCACAAAGAGCTTCAACA
AACGTGAATCACAAGCCCAGCAAC
(SEQ ID NO: 557)
GGGGAGAGTGT
ACCAAGGTGGACAAGAAAGTTGAG
(SEQ ID NO: 558)
CCCAAATCTTGTGACAAAACTCAC
ACATGCCCACCGTGCCCAGCACCT
GAACTCCTGGGGGGACCGTCAGTC
TTCCTCTTCCCCCCAAAACCCAAGG
ACACCCTCATGATCTCCCGGACCCC
TGAGGTCACATGCGTGGTGGTGGA
CGTGAGCCACGAAGACCCTGAGGT
CAAGTTCAACTGGTACGTGGACGG
CGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGG
CAGCACGTACCGTTGCGTCAGCGT
CCTCACCGTCCTGCACCAGGACTG
GCTGAATGGCAAGGAGTACAAGTG
CAAGGTGTCCAACAAAGCCCTCCC
AGCCCCCATCGAGAAAACCATCTC
CAAAGCCAAAGGGCAGCCCCGAGA
ACCACAGGTGTACACCCTGCCCCC
ATCCCGGGAGGAGATGACCAAGAA
CCAGGTCAGCCTGACCTGCCTGGTC
AAAGGCTTCTATCCCAGCGACATC
GCCGTGGAGTGGGAGAGCAATGGG
CAGCCGGAGAACAACTACAAGACC
ACGCCTCCCGTGCTGGACTCCGAC
GGCTCCTTCTTCCTCTATAGCAAGC
TCACCGTGGACAAGAGCAGGTGGC
AGCAGGGGAACGTCTTCTCATGCT
CCGTGATGCATGAGGCTCTGCACA
ACCACTACACGCAGAAGAGCCTCT
CCCTGTCTCCGGGTGGTGGCGGATC
GGGAGGTGGCGGATCCCAGGTGCA
GCTGGTCGAGTCTGGGGGAGGCTT
GGTCAAGCCTGGAGGGTCCCTGAG
ACTCTCCTGTGCAGCCTCTGGATTC
ACCTTCAGTGACTACTACATGACCT
GGATCAGGCAGGCTCCAGGGAAGG
GGCTGGAGTGGATTTCATACATTA
GTAGTAGTGGTAGTACCATCTACTA
CGCAGACTCTGTGAAGGGCCGATT
CACCATCTCCAGGGACAACGCCAA
GAACTCACTGTATCTGCAAATGAA
CAGCCTGAGAGCCGAGGACACGGC
CGTGTATTACTGTGCGAGAGATCG
GAACTCCCACTTTGACTATTGGGGC
CAGGGAACCCTGGTCACCGTGTCC
TCAGCAAGCACGAAGGGGCCGTCC
GTATTTCCGCTTGCGCCCTCGTCGA
AGTCAACTTCGGGAGGGACCGCGG
CACTTGGCTGTCTTGTCAAAGATTA
CTTCCCTGAGCCAGTGACAGTCAG
CTGGAATTCCGGTGCCCTCACGTCA
GGAGTACATACATTCCCTGCGGTAT
TGCAGTCCTCCGGACTCTACTCCCT
GGAGTCGGTGGTAACGGTGCCCAG
CTCCAGCTTGGGGACCCAGACGTA
CATTTGTAACGTGAATCACAAACC
AAGCAATACTAAGGTAGATAAGAA
AGTAGAACCGAAGAGCTGC
(SEQ ID NO: 559)
AA
QSALTQPRSVSGSPGQSVTISCTGTSSD
DIQMTQSPSSVSASVGDRVTITCRAS
QVQLVESGGGVVQPGRSLRLSCAAS
VGGYIFVSWYQQHPGKAPKLMIYDVS
QGITRWLAWYQQKPGKAPKLLIYAA
GFTLSSYGMHWVRQAPGKGLEWVA
KRPSGVPDRFSGSKSVNTASLTISGLQA
SVLQSGVPSRFSGSGSGTDFTLTISSL
VIWYDGSNKYYADSVKGRVTISRDN
EDETDYYCCSYAGNYTYVFGTGTKVT
QPEDFATYYCQQSNSFPRTFGQGTK
SKNTLYLQMNSLRAEDTAVYYCTRD
VLGQPKAAPSVTLFPPSSEELQANKAT
VEIKRTVAAPSVFIFPPSDEQLKSGTA
GRNYVYFDNWGQGTLVTVSSASTK
LVCLISDFYPGAVTVAWKADSSPVKA
SVVCLLNNFYPREAKVQWKVDNAL
GPSVFPLAPSSKSTSGGTAALGCLVK
GVETTTPSKQSNNKYAAESYLSLTPEQ
QSGNSQESVTEQDSKDSTYSLKSTLT
DYFPEPVTVSWNSGALTSGVHTFPA
WKSHRSYSCQVTHEGSTVEKTVAPTE
LSKADYEKHKVYACEVTHQGLSSPV
VLQSSGLYSLKSVVTVPSSSLGTQTY
CS
TKSFNRGEC
ICNVNHKPSNTKVDKKVEPKSCDKT
(SEQ ID NO: 560)
(SEQ ID NO: 561)
HTCPPCPAPELLGGPSVFLFPPKPKDT
LMISRTPEVTCVVVDVSHEDPEVKFN
WYVDGVEVHNAKTKPCEEQYGSTY
RCVSVLTVLHQDWLNGKEYKCKVS
NKALPAPIEKTISKAKGQPREPQVYT
LPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSD
GSFFLYSKLTVDKSRWQQGNVFSCS
VMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLVESGGGLVKPGGSLRLS
CAASGFTFSDYYMTWIRQAPGKGLE
WISYISSSGSTIYYADSVKGRFTISRD
NAKNSLYLQMNSLRAEDTAVYYCA
RDRNSHFDYWGQGTLVTVSSASTKG
PSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAV
LQSSGLYSLESVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 562)
iPS:
21-
[hu anti-
NA
CAGTCTGCCCTGACTCAGCCTCGCTC
GACATCCAGATGACCCAGTCTCCA
CAGGTGCAGCTGGTGGAGTCTGGG
576344
230_35F11_IgG_
<hu CD40> 21-230_
AGTGTCCGGGAGCCCTGGACAGTCA
TCTTCCGTGTCTGCTTCTGTCGGAG
GGAGGCGTGGTCCAGCCTGGGAGG
21-
35F11VH]::huIgG1zSEFL2*GK-
GTCACCATCTCCTGCACTGGAACCAG
ACAGAGTCACCATCACTTGTCGGG
TCCCTGAGACTCTCCTGTGCAGCGT
233_6F4__Fab
K::(G4S)2::[hu anti-
CAGTGATGTTGGTGGTTATATCTTTG
CGAGTCAGGATATTAGCAGGTGGT
CTGGATTCACCCTCAGTAGCTATGG
<hu Mesothelin>
TCTCCTGGTACCAACAACACCCAGGC
TAGCCTGGTATCAGCAGAAACCAG
CATGCACTGGGTCCGCCAGGCTCC
6F4VH]::huIgG1z-
AAAGCCCCCAAACTCATGATTTATGA
GGAAAGCCCCTAAGCTCCTGATTTC
AGGCAAGGGGCTGGAGTGGGTGGC
CH1-E::EPKSC + [anti-
TGTCAGTAAGCGGCCCTCTGGGGTCC
TGCTGCATCCAGATTGCAAAGTGG
AGTTATCTGGTATGATGGAAGTAA
<hu CD40>
CTGATCGCTTCTCTGGCTCCAAGTCT
AGTCCCATCAAGGTTCAGCGGCAG
TAAATACTATGCAGACTCCGTGAA
21-230_35F11VL]::huLLC2-
GTCAACACGGCCTCCCTGACCATCTC
TGGATCTGGGACAGATTTCACTCTC
GGGCCGAGTCACCATCTCCAGAGA
E + [anti-
TGGGCTCCAGGCTGAGGATGAGACT
ACCATCAGCAGCCTGCAGCCTGAA
CAATTCCAAGAACACGCTGTATCT
<hu Mesothelin>
GATTATTACTGCTGCTCATATGCAGG
GATTTTGCAATTTACTATTGTCAAC
GCAAATGAATAGCCTGAGAGCCGA
6F4VL]::huKLC-
CAACTACACTTATGTCTTCGGAACTG
AGGCTAAAAGTTTTCCTCGGACGTT
GGACACGGCTGTGTATTACTGTAC
S176K (IgG-Fab);
GGACCAAGGTCACCGTCCTAGGTCA
CGGCCAAGGGACCAAGGTGGAAAT
GAGAGATGGCCGGAACTACGTCTA
LMRID: SS-30877
GCCCAAGGCTGCACCCTCGGTCACTC
CAAACGGACGGTGGCTGCACCATC
CTTTGACAACTGGGGCCAGGGAAC
TGTTCCCGCCCTCCTCTGAGGAGCTT
TGTCTTCATCTTCCCGCCATCTGAT
CCTGGTCACCGTGTCCTCAGCCTCC
CAAGCCAACAAGGCCACACTGGTGT
GAGCAGTTGAAATCTGGAACTGCC
ACCAAGGGCCCATCGGTCTTCCCCC
GTCTCATCAGTGACTTCTACCCGGGA
TCTGTTGTGTGCCTGCTGAATAACT
TGGCACCCTCCTCCAAGAGCACCTC
GCCGTGACAGTGGCCTGGAAGGCAG
TCTATCCCAGAGAGGCCAAAGTAC
TGGGGGCACAGCGGCCCTGGGCTG
ATAGCAGCCCCGTCAAGGCGGGAGT
AGTGGAAGGTGGATAACGCCCTCC
CCTGGTCAAGGACTACTTCCCCGA
GGAAACCACCACACCCTCCAAACAA
AATCGGGTAACTCCCAGGAGAGTG
ACCGGTGACGGTGTCGTGGAACTC
AGCAACAACAAGTACGCGGCCGAAA
TCACAGAGCAGGACAGCAAGGACA
AGGCGCCCTGACCAGCGGCGTGCA
GCTATCTGAGCCTGACGCCTGAGCAG
GCACCTACAGCCTCAAGAGCACCC
CACCTTCCCGGCTGTCCTACAGTCC
TGGAAGTCCCACAGAAGCTACAGCT
TGACGCTGAGCAAAGCAGACTACG
TCAGGACTCTACTCCCTCAAGAGC
GCCAGGTCACGCATGAAGGGAGCAC
AGAAACACAAAGTCTACGCCTGCG
GTGGTGACCGTGCCCTCCAGCAGC
CGTGGAGAAGACAGTGGCCCCTACA
AAGTCACCCATCAGGGCCTGAGCT
TTGGGCACCCAGACCTACATCTGC
GAATGTTCA
CGCCCGTCACAAAGAGCTTCAACA
AACGTGAATCACAAGCCCAGCAAC
(SEQ ID NO: 563)
GGGGAGAGTGT
ACCAAGGTGGACAAGAAAGTTGAG
(SEQ ID NO: 564)
CCCAAATCTTGTGACAAAACTCAC
ACATGCCCACCGTGCCCAGCACCT
GAACTCCTGGGGGGACCGTCAGTC
TTCCTCTTCCCCCCAAAACCCAAGG
ACACCCTCATGATCTCCCGGACCCC
TGAGGTCACATGCGTGGTGGTGGA
CGTGAGCCACGAAGACCCTGAGGT
CAAGTTCAACTGGTACGTGGACGG
CGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGG
CAGCACGTACCGTTGCGTCAGCGT
CCTCACCGTCCTGCACCAGGACTG
GCTGAATGGCAAGGAGTACAAGTG
CAAGGTGTCCAACAAAGCCCTCCC
AGCCCCCATCGAGAAAACCATCTC
CAAAGCCAAAGGGCAGCCCCGAGA
ACCACAGGTGTACACCCTGCCCCC
ATCCCGGGAGGAGATGACCAAGAA
CCAGGTCAGCCTGACCTGCCTGGTC
AAAGGCTTCTATCCCAGCGACATC
GCCGTGGAGTGGGAGAGCAATGGG
CAGCCGGAGAACAACTACAAGACC
ACGCCTCCCGTGCTGGACTCCGAC
GGCTCCTTCTTCCTCTATAGCAAGC
TCACCGTGGACAAGAGCAGGTGGC
AGCAGGGGAACGTCTTCTCATGCT
CCGTGATGCATGAGGCTCTGCACA
ACCACTACACGCAGAAGAGCCTCT
CCCTGTCTCCGGGTGGTGGCGGATC
GGGAGGTGGCGGATCCCAGGTGCA
GCTGGTGGAGTCTGGGGGAGGCTT
GGTCAAGCCTGGAGGGTCCCTGAG
ACTCTCCTGTGCAGCCTCTGGATTC
ACCTTCAGTGACTACTACATGAGCT
GGATCCGCCAGGCTCCAGGGAAGG
GGCTGGAGTGGATTTCATACATTA
GTAGCAGTGAAAGTATCATCTATT
ACGTAGACTCTGTGAAGGGCCGAT
TCACCATCTCCAGGGACAACGCCA
AGAACTCACTGTATCTGCAAATGA
ACAGCCTGAGAGCCGAGGACACGG
CCGTGTATTACTGTGCGAGAGATGT
TGGGAGCCACTTTGACTACTGGGG
CCAGGGAACCCTGGTCACCGTGTC
CTCAGCAAGCACGAAGGGGCCGTC
CGTATTTCCGCTTGCGCCCTCGTCG
AAGTCAACTTCGGGAGGGACCGCG
GCACTTGGCTGTCTTGTCAAAGATT
ACTTCCCTGAGCCAGTGACAGTCA
GCTGGAATTCCGGTGCCCTCACGTC
AGGAGTACATACATTCCCTGCGGT
ATTGCAGTCCTCCGGACTCTACTCC
CTGGAGTCGGTGGTAACGGTGCCC
AGCTCCAGCTTGGGGACCCAGACG
TACATTTGTAACGTGAATCACAAA
CCAAGCAATACTAAGGTAGATAAG
AAAGTAGAACCGAAGAGCTGC
(SEQ ID NO: 565)
AA
QSALTQPRSVSGSPGQSVTISCTGTSSD
DIQMTQSPSSVSASVGDRVTITCRAS
QVQLVESGGGVVQPGRSLRLSCAAS
VGGYIFVSWYQQHPGKAPKLMIYDVS
QDISRWLAWYQQKPGKAPKLLISAA
GFTLSSYGMHWVRQAPGKGLEWVA
KRPSGVPDRFSGSKSVNTASLTISGLQA
SRLQSGVPSRFSGSGSGTDFTLTISSL
VIWYDGSNKYYADSVKGRVTISRDN
EDETDYYCCSYAGNYTYVFGTGTKVT
QPEDFAIYYCQQAKSFPRTFGQGTKV
SKNTLYLQMNSLRAEDTAVYYCTRD
VLGQPKAAPSVTLFPPSSEELQANKAT
EIKRTVAAPSVFIFPPSDEQLKSGTAS
GRNYVYFDNWGQGTLVTVSSASTK
LVCLISDFYPGAVTVAWKADSSPVKA
VVCLLNNFYPREAKVQWKVDNALQ
GPSVFPLAPSSKSTSGGTAALGCLVK
GVETTTPSKQSNNKYAAESYLSLTPEQ
SGNSQESVTEQDSKDSTYSLKSTLTL
DYFPEPVTVSWNSGALTSGVHTFPA
WKSHRSYSCQVTHEGSTVEKTVAPTE
SKADYEKHKVYACEVTHQGLSSPVT
VLQSSGLYSLKSVVTVPSSSLGTQTY
CS
KSFNRGEC
ICNVNHKPSNTKVDKKVEPKSCDKT
(SEQ ID NO: 566)
(SEQ ID NO: 567)
HTCPPCPAPELLGGPSVFLFPPKPKDT
LMISRTPEVTCVVVDVSHEDPEVKFN
WYVDGVEVHNAKTKPCEEQYGSTY
RCVSVLTVLHQDWLNGKEYKCKVS
NKALPAPIEKTISKAKGQPREPQVYT
LPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSD
GSFFLYSKLTVDKSRWQQGNVFSCS
VMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLVESGGGLVKPGGSLRLS
CAASGFTFSDYYMSWIRQAPGKGLE
WISYISSSESIIYYVDSVKGRFTISRDN
AKNSLYLQMNSLRAEDTAVYYCAR
DVGSHFDYWGQGTLVTVSSASTKGP
SVFPLAPSSKSTSGGTAALGCLVKDY
FPEPVTVSWNSGALTSGVHTFPAVL
QSSGLYSLESVVTVPSSSLGTQTYICN
VNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 568)
iPS:
21-
[hu anti-
NA
CAGTCTGCCCTGACTCAGCCTCGCTC
GACATTGTGATGACTCAGTCTCCAG
CAGGTGCAGCTGGTGGAGTCTGGG
576347
230_35F11_IgG_
<hu CD40> 21-230_
AGTGTCCGGGAGCCCTGGACAGTCA
ACTCCCTGGCTGTGTCTCTGGGCGA
GGAGGCGTGGTCCAGCCTGGGAGG
21-
35F11VH]::huIgG1zSEFL2*GK-
GTCACCATCTCCTGCACTGGAACCAG
GAGGGCCACCATCAACTGCAAGTC
TCCCTGAGACTCTCCTGTGCAGCGT
233_7G11__Fab
K::(G4S)2::[hu anti-
CAGTGATGTTGGTGGTTATATCTTTG
CAGCCAGAGTGTTTTATACAGCTCC
CTGGATTCACCCTCAGTAGCTATGG
<hu Mesothelin>
TCTCCTGGTACCAACAACACCCAGGC
AACAATAAGAACTACTTAGCTTGG
CATGCACTGGGTCCGCCAGGCTCC
7G11VH]::huIgG1z-
AAAGCCCCCAAACTCATGATTTATGA
TACCAGCAGAAACCAGGACAGCCT
AGGCAAGGGGCTGGAGTGGGTGGC
CH1-E::EPKSC + [anti-
TGTCAGTAAGCGGCCCTCTGGGGTCC
CCTAAGCTGCTCATTTACTGGGCAT
AGTTATCTGGTATGATGGAAGTAA
<hu CD40>
CTGATCGCTTCTCTGGCTCCAAGTCT
CTACCCGAGAATCCGGGGTCCCTG
TAAATACTATGCAGACTCCGTGAA
21-230_35F11VL]::huLLC2-
GTCAACACGGCCTCCCTGACCATCTC
ACCGATTCAGTGGCAGCGGGTCTG
GGGCCGAGTCACCATCTCCAGAGA
E + [anti-
TGGGCTCCAGGCTGAGGATGAGACT
GGACAGATTTCACTCTCACCATCAG
CAATTCCAAGAACACGCTGTATCT
<hu Mesothelin>
GATTATTACTGCTGCTCATATGCAGG
CAGCCTGCAGGCTGAAGATGTGGC
GCAAATGAATAGCCTGAGAGCCGA
7G11VL]::huKLC-
CAACTACACTTATGTCTTCGGAACTG
AGTTTATTACTGTCAGCAATATTAT
GGACACGGCTGTGTATTACTGTAC
S176K (IgG-Fab);
GGACCAAGGTCACCGTCCTAGGTCA
AGTACTCCTCCGACGTTCGGCCAA
GAGAGATGGCCGGAACTACGTCTA
LMRID: SS-30878
GCCCAAGGCTGCACCCTCGGTCACTC
GGGACCAAGGTGGAGATCAAACGG
CTTTGACAACTGGGGCCAGGGAAC
TGTTCCCGCCCTCCTCTGAGGAGCTT
ACGGTGGCTGCACCATCTGTCTTCA
CCTGGTCACCGTGTCCTCAGCCTCC
CAAGCCAACAAGGCCACACTGGTGT
TCTTCCCGCCATCTGATGAGCAGTT
ACCAAGGGCCCATCGGTCTTCCCCC
GTCTCATCAGTGACTTCTACCCGGGA
GAAATCTGGAACTGCCTCTGTTGTG
TGGCACCCTCCTCCAAGAGCACCTC
GCCGTGACAGTGGCCTGGAAGGCAG
TGCCTGCTGAATAACTTCTATCCCA
TGGGGGCACAGCGGCCCTGGGCTG
ATAGCAGCCCCGTCAAGGCGGGAGT
GAGAGGCCAAAGTACAGTGGAAGG
CCTGGTCAAGGACTACTTCCCCGA
GGAAACCACCACACCCTCCAAACAA
TGGATAACGCCCTCCAATCGGGTA
ACCGGTGACGGTGTCGTGGAACTC
AGCAACAACAAGTACGCGGCCGAAA
ACTCCCAGGAGAGTGTCACAGAGC
AGGCGCCCTGACCAGCGGCGTGCA
GCTATCTGAGCCTGACGCCTGAGCAG
AGGACAGCAAGGACAGCACCTACA
CACCTTCCCGGCTGTCCTACAGTCC
TGGAAGTCCCACAGAAGCTACAGCT
GCCTCAAGAGCACCCTGACGCTGA
TCAGGACTCTACTCCCTCAAGAGC
GCCAGGTCACGCATGAAGGGAGCAC
GCAAAGCAGACTACGAGAAACACA
GTGGTGACCGTGCCCTCCAGCAGC
CGTGGAGAAGACAGTGGCCCCTACA
AAGTCTACGCCTGCGAAGTCACCC
TTGGGCACCCAGACCTACATCTGC
GAATGTTCA
ATCAGGGCCTGAGCTCGCCCGTCA
AACGTGAATCACAAGCCCAGCAAC
(SEQ ID NO: 569)
CAAAGAGCTTCAACAGGGGAGAGT
ACCAAGGTGGACAAGAAAGTTGAG
GT
CCCAAATCTTGTGACAAAACTCAC
(SEQ ID NO: 570)
ACATGCCCACCGTGCCCAGCACCT
GAACTCCTGGGGGGACCGTCAGTC
TTCCTCTTCCCCCCAAAACCCAAGG
ACACCCTCATGATCTCCCGGACCCC
TGAGGTCACATGCGTGGTGGTGGA
CGTGAGCCACGAAGACCCTGAGGT
CAAGTTCAACTGGTACGTGGACGG
CGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGG
CAGCACGTACCGTTGCGTCAGCGT
CCTCACCGTCCTGCACCAGGACTG
GCTGAATGGCAAGGAGTACAAGTG
CAAGGTGTCCAACAAAGCCCTCCC
AGCCCCCATCGAGAAAACCATCTC
CAAAGCCAAAGGGCAGCCCCGAGA
ACCACAGGTGTACACCCTGCCCCC
ATCCCGGGAGGAGATGACCAAGAA
CCAGGTCAGCCTGACCTGCCTGGTC
AAAGGCTTCTATCCCAGCGACATC
GCCGTGGAGTGGGAGAGCAATGGG
CAGCCGGAGAACAACTACAAGACC
ACGCCTCCCGTGCTGGACTCCGAC
GGCTCCTTCTTCCTCTATAGCAAGC
TCACCGTGGACAAGAGCAGGTGGC
AGCAGGGGAACGTCTTCTCATGCT
CCGTGATGCATGAGGCTCTGCACA
ACCACTACACGCAGAAGAGCCTCT
CCCTGTCTCCGGGTGGTGGCGGATC
GGGAGGTGGCGGATCCGAGGTGCA
GCTGGTCGAGTCTGGAGGAGGCTT
GATCCAGCCTGGGGGGTCCCTGAG
ACTCTCCTGTGCAGTCTCTGGGTTC
ACCGTCAGTAGCAAGTTCATGACC
TGGGTCCGCCAGGCTCCAGGGAAG
GGGCTGGAGTGGGTGTCAGTTATTT
ATAGCGGTGGTAAGACATACTACG
CAGACTCCGTGAAGGGCCGATTCA
CCATCTCCAGAGACAATTCCAAGA
ACACGCTGTATCTTCAAATGAACA
GCCTGAGAGCCGAGGACACGGCCG
TGTATTACTGTGCGAGAGATAGCG
GTGGCTGGGGGTACTTTGACTACTG
GGGCCAGGGAACCCTGGTCACCGT
GTCCTCAGCAAGCACGAAGGGGCC
GTCCGTATTTCCGCTTGCGCCCTCG
TCGAAGTCAACTTCGGGAGGGACC
GCGGCACTTGGCTGTCTTGTCAAAG
ATTACTTCCCTGAGCCAGTGACAGT
CAGCTGGAATTCCGGTGCCCTCAC
GTCAGGAGTACATACATTCCCTGC
GGTATTGCAGTCCTCCGGACTCTAC
TCCCTGGAGTCGGTGGTAACGGTG
CCCAGCTCCAGCTTGGGGACCCAG
ACGTACATTTGTAACGTGAATCAC
AAACCAAGCAATACTAAGGTAGAT
AAGAAAGTAGAACCGAAGAGCTGC
(SEQ ID NO: 571)
AA
QSALTQPRSVSGSPGQSVTISCTGTSSD
DIVMTQSPDSLAVSLGERATINCKSS
QVQLVESGGGVVQPGRSLRLSCAAS
VGGYIFVSWYQQHPGKAPKLMIYDVS
QSVLYSSNNKNYLAWYQQKPGQPP
GFTLSSYGMHWVRQAPGKGLEWVA
KRPSGVPDRFSGSKSVNTASLTISGLQA
KLLIYWASTRESGVPDRFSGSGSGTD
VIWYDGSNKYYADSVKGRVTISRDN
EDETDYYCCSYAGNYTYVFGTGTKVT
FTLTISSLQAEDVAVYYCQQYYSTPP
SKNTLYLQMNSLRAEDTAVYYCTRD
VLGQPKAAPSVTLFPPSSEELQANKAT
TFGQGTKVEIKRTVAAPSVFIFPPSDE
GRNYVYFDNWGQGTLVTVSSASTK
LVCLISDFYPGAVTVAWKADSSPVKA
QLKSGTASVVCLLNNFYPREAKVQW
GPSVFPLAPSSKSTSGGTAALGCLVK
GVETTTPSKQSNNKYAAESYLSLTPEQ
KVDNALQSGNSQESVTEQDSKDSTY
DYFPEPVTVSWNSGALTSGVHTFPA
WKSHRSYSCQVTHEGSTVEKTVAPTE
SLKSTLTLSKADYEKHKVYACEVTH
VLQSSGLYSLKSVVTVPSSSLGTQTY
CS
QGLSSPVTKSFNRGEC
ICNVNHKPSNTKVDKKVEPKSCDKT
(SEQ ID NO: 572)
(SEQ ID NO: 573)
HTCPPCPAPELLGGPSVFLFPPKPKDT
LMISRTPEVTCVVVDVSHEDPEVKFN
WYVDGVEVHNAKTKPCEEQYGSTY
RCVSVLTVLHQDWLNGKEYKCKVS
NKALPAPIEKTISKAKGQPREPQVYT
LPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSD
GSFFLYSKLTVDKSRWQQGNVFSCS
VMHEALHNHYTQKSLSLSPGGGGSG
GGGSEVQLVESGGGLIQPGGSLRLSC
AVSGFTVSSKFMTWVRQAPGKGLE
WVSVIYSGGKTYYADSVKGRFTISR
DNSKNTLYLQMNSLRAEDTAVYYC
ARDSGGWGYFDYWGQGTLVTVSSA
STKGPSVFPLAPSSKSTSGGTAALGC
LVKDYFPEPVTVSWNSGALTSGVHT
FPAVLQSSGLYSLESVVTVPSSSLGT
QTYICNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 574)
iPS:
21-
[hu anti-
NA
GAAATTGTGTTGACGCAGTCTCCAGG
CAGTCAGTGTTGACGCAGCCGCCC
CAGGTACAGCTGCAACAGTCAGGT
576350
230_36F3_IgG_
<hu CD40> 21-230_
CACCCTGTCTTTGTCTCCAGGGGAAA
TCAGTGTCTGGGGCCCCAGGGCAG
CCAGGACTGGTGAAGCCCTCGCAG
21-
36F3VH]::huIgG1zSEFL2*GK-
GAGCCACCCTCTCCTGCAGGGCCAGT
AGGGTCACCATCTCCTGCACTGGG
ACCCTCTCACTCACCTGTGCCATCT
233_4G12__Fab
K::(G4S)2::[hu anti-
CAGAGTGTTAGCAGCAACTACTTAGC
AGCAGCTCCAACATCGGGGCAGGT
CCGGGGACAGTGTCTCTAGCAGCC
<hu Mesothelin>
CTGGTACCAACAGAAACCTGGCCAG
TATGATGTTCACTGGTACCAGCAG
GTACTGCTTGGAACTGGATCAGGC
4G12VH]::huIgG1z-
GCTCCCAGGGCCCTTATCTATGCTGC
GTTCCAGGAACAGCCCCCAAACTC
AGTCCCCATCGAGAGGCCTTGAGT
CH1-E::EPKSC + [anti-
ATCCAACAGGGCCGCTGGCATCTCAG
CTCATCTATGGTAACAGCAAGCGG
GGCTGGGAAGGACATACTACAGGT
<hu CD40>
ACAGGTTCAGTGGCAGTGGGTCTGG
CCCTCAGGGGTCCCTGACCGATTCT
CCAAGTGGTATCATGATTATTCAGT
21-230_36F3VL]::huKLC-
GACAGACTTCACTCTCACCATCAGCA
CTGGCTCCAAGTCTGGCACCTCAGC
ATCTGTGAAAAGTCGAATCACCAT
S176E + [anti-
GACTGGAGCCTGAAGATTTTGCAGTG
CTCCCTGGCCATCACTGGGCTCCAG
CGACCCAGACACATCCAAGAACCA
<hu Mesothelin>
TATTTCTGTCAGCAGTATGGTAGCTC
GCTGAGGATGAGGCTGATTATTAC
GTTCTCCCTGCAGCTGAACTCTGTG
4G12VL]::huLLC2-
ACCGCTCACTTTCGGCGGAGGGACTA
TGCCAGTCCTATGACAGCAGCCTG
ACTCCCGAGGACACGGCTGTTTATT
K (IgG-Fab);
AGGTGGAGATCAAACGAACGGTGGC
GGTGGTTGGGTGTTCGGCGGAGGG
ATTGTGCAAGAGGGGCTGCTCCCTT
LMRID: SS-30879
TGCACCATCTGTCTTCATCTTCCCGCC
ACCAAGCTGACCGTCCTACAGCCC
TGACTACTGGGGCCAGGGAACCCT
ATCTGATGAGCAGTTGAAATCTGGAA
AAGGCTGCACCCTCGGTCACTCTGT
GGTCACCGTGTCCTCAGCCTCCACC
CTGCCTCTGTTGTGTGCCTGCTGAAT
TCCCGCCCTCCTCTGAGGAGCTTCA
AAGGGCCCATCGGTCTTCCCCCTGG
AACTTCTATCCCAGAGAGGCCAAAGT
AGCCAACAAGGCCACACTGGTGTG
CACCCTCCTCCAAGAGCACCTCTGG
ACAGTGGAAGGTGGATAACGCCCTC
TCTCATCAGTGACTTCTACCCGGGA
GGGCACAGCGGCCCTGGGCTGCCT
CAATCGGGTAACTCCCAGGAGAGTG
GCCGTGACAGTGGCCTGGAAGGCA
GGTCAAGGACTACTTCCCCGAACC
TCACAGAGCAGGACAGCAAGGACAG
GATAGCAGCCCCGTCAAGGCGGGA
GGTGACGGTGTCGTGGAACTCAGG
CACCTACAGCCTCGAAAGCACCCTGA
GTGGAAACCACCACACCCTCCAAA
CGCCCTGACCAGCGGCGTGCACAC
CGCTGAGCAAAGCAGACTACGAGAA
CAAAGCAACAACAAGTACGCGGCC
CTTCCCGGCTGTCCTACAGTCCTCA
ACACAAAGTCTACGCCTGCGAAGTC
AAGAGCTATCTGAGCCTGACGCCT
GGACTCTACTCCCTCAAGAGCGTG
ACCCATCAGGGCCTGAGCTCGCCCGT
GAGCAGTGGAAGTCCCACAGAAGC
GTGACCGTGCCCTCCAGCAGCTTG
CACAAAGAGCTTCAACAGGGGAGAG
TACAGCTGCCAGGTCACGCATGAA
GGCACCCAGACCTACATCTGCAAC
TGT
GGGAGCACCGTGGAGAAGACAGTG
GTGAATCACAAGCCCAGCAACACC
(SEQ ID NO: 575)
GCCCCTACAGAATGTTCA
AAGGTGGACAAGAAAGTTGAGCCC
(SEQ ID NO: 576)
AAATCTTGTGACAAAACTCACACA
TGCCCACCGTGCCCAGCACCTGAA
CTCCTGGGGGGACCGTCAGTCTTCC
TCTTCCCCCCAAAACCCAAGGACA
CCCTCATGATCTCCCGGACCCCTGA
GGTCACATGCGTGGTGGTGGACGT
GAGCCACGAAGACCCTGAGGTCAA
GTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAA
GCCGTGCGAGGAGCAGTACGGCAG
CACGTACCGTTGCGTCAGCGTCCTC
ACCGTCCTGCACCAGGACTGGCTG
AATGGCAAGGAGTACAAGTGCAAG
GTGTCCAACAAAGCCCTCCCAGCC
CCCATCGAGAAAACCATCTCCAAA
GCCAAAGGGCAGCCCCGAGAACCA
CAGGTGTACACCCTGCCCCCATCCC
GGGAGGAGATGACCAAGAACCAG
GTCAGCCTGACCTGCCTGGTCAAA
GGCTTCTATCCCAGCGACATCGCCG
TGGAGTGGGAGAGCAATGGGCAGC
CGGAGAACAACTACAAGACCACGC
CTCCCGTGCTGGACTCCGACGGCTC
CTTCTTCCTCTATAGCAAGCTCACC
GTGGACAAGAGCAGGTGGCAGCAG
GGGAACGTCTTCTCATGCTCCGTGA
TGCATGAGGCTCTGCACAACCACT
ACACGCAGAAGAGCCTCTCCCTGT
CTCCGGGTGGTGGCGGATCGGGAG
GTGGCGGATCCCAGGTGCAGCTGC
AGGAGTCGGGCCCAGGACTGGTGA
AGCCTTCGGAAACCCTGTCCCTCAC
CTGCACTGTCTCTGGTGGCTCCATC
AGCAGTAGTAGTTACTACTGGGGC
TGGATCAGGCAGCCCCCAGGGAAG
GGGCTGGAGTGGATTGGGAGTATC
TATTATAGTGGGATCACCAACTAC
AACCCGTCCCTCAAGAGTCGAGTC
ACCATCTCCGTAGACACGTCCAAG
AACCAGTTCTCCCTGAAGCTGAGTT
CTGTGACCGCCGCAGACACGGCCG
TGTATTACTGTGCGAGATCCAGTAA
CTACGATGCTTTTGATATCTGGGGC
CAAGGGACAATGGTCACCGTGTCC
TCAGCAAGCACGAAGGGGCCGTCC
GTATTTCCGCTTGCGCCCTCGTCGA
AGTCAACTTCGGGAGGGACCGCGG
CACTTGGCTGTCTTGTCAAAGATTA
CTTCCCTGAGCCAGTGACAGTCAG
CTGGAATTCCGGTGCCCTCACGTCA
GGAGTACATACATTCCCTGCGGTAT
TGCAGTCCTCCGGACTCTACTCCCT
GGAGTCGGTGGTAACGGTGCCCAG
CTCCAGCTTGGGGACCCAGACGTA
CATTTGTAACGTGAATCACAAACC
AAGCAATACTAAGGTAGATAAGAA
AGTAGAACCGAAGAGCTGC
(SEQ ID NO: 577)
AA
EIVLTQSPGTLSLSPGERATLSCRASQS
QSVLTQPPSVSGAPGQRVTISCTGSSS
QVQLQQSGPGLVKPSQTLSLTCAISG
VSSNYLAWYQQKPGQAPRALIYAASN
NIGAGYDVHWYQQVPGTAPKLLIYG
DSVSSSRTAWNWIRQSPSRGLEWLG
RAAGISDRFSGSGSGTDFTLTISRLEPE
NSKRPSGVPDRFSGSKSGTSASLAIT
RTYYRSKWYHDYSVSVKSRITIDPDT
DFAVYFCQQYGSSPLTFGGGTKVEIKR
GLQAEDEADYYCQSYDSSLGGWVF
SKNQFSLQLNSVTPEDTAVYYCARG
TVAAPSVFIFPPSDEQLKSGTASVVCLL
GGGTKLTVLQPKAAPSVTLFPPSSEE
AAPFDYWGQGTLVTVSSASTKGPSV
NNFYPREAKVQWKVDNALQSGNSQES
LQANKATLVCLISDFYPGAVTVAWK
FPLAPSSKSTSGGTAALGCLVKDYFP
VTEQDSKDSTYSLESTLTLSKADYEKH
ADSSPVKAGVETTTPSKQSNNKYAA
EPVTVSWNSGALTSGVHTFPAVLQS
KVYACEVTHQGLSSPVTKSFNRGEC
KSYLSLTPEQWKSHRSYSCQVTHEG
SGLYSLKSVVTVPSSSLGTQTYICNV
(SEQ ID NO: 578)
STVEKTVAPTECS
NHKPSNTKVDKKVEPKSCDKTHTCP
(SEQ ID NO: 579)
PCPAPELLGGPSVFLFPPKPKDTLMIS
RTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPCEEQYGSTYRCVS
VLTVLHQDWLNGKEYKCKVSNKAL
PAPIEKTISKAKGQPREPQVYTLPPSR
EEMTKNQVSLTCLVKGFYPSDIAVE
WESNGQPENNYKTTPPVLDSDGSFF
LYSKLTVDKSRWQQGNVFSCSVMH
EALHNHYTQKSLSLSPGGGGSGGGG
SQVQLQESGPGLVKPSETLSLTCTVS
GGSISSSSYYWGWIRQPPGKGLEWIG
SIYYSGITNYNPSLKSRVTISVDTSKN
QFSLKLSSVTAADTAVYYCARSSNY
DAFDIWGQGTMVTVSSASTKGPSVF
PLAPSSKSTSGGTAALGCLVKDYFPE
PVTVSWNSGALTSGVHTFPAVLQSS
GLYSLESVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSC
(SEQ ID NO: 580)
iPS:
21-
[hu anti-
NA
GAAATTGTGTTGACGCAGTCTCCAGG
GACATTCAGATGACCCAGTCTCCAT
CAGGTACAGCTGCAACAGTCAGGT
576355
230_36F3_IgG_
<hu CD40> 21-230_
CACCCTGTCTTTGTCTCCAGGGGAAA
CTTCCGTGTCTGCATCTGTAGGGGA
CCAGGACTGGTGAAGCCCTCGCAG
21-
36F3VH]::huIgG1zSEFL2*GK-
GAGCCACCCTCTCCTGCAGGGCCAGT
CAGAGTCACCATCACTTGTCGGGC
ACCCTCTCACTCACCTGTGCCATCT
233_4H6__Fab
K::(G4S)2::[hu anti-
CAGAGTGTTAGCAGCAACTACTTAGC
GAGTCAGGGTATTACCAGGTGGTT
CCGGGGACAGTGTCTCTAGCAGCC
<hu Mesothelin>
CTGGTACCAACAGAAACCTGGCCAG
AGCCTGGTATCAGCAGAAACCAGG
GTACTGCTTGGAACTGGATCAGGC
4H6VH]::huIgG1z-
GCTCCCAGGGCCCTTATCTATGCTGC
GAAAGCCCCTAAGCTCCTGATCTAT
AGTCCCCATCGAGAGGCCTTGAGT
CH1-E::EPKSC + [anti-
ATCCAACAGGGCCGCTGGCATCTCAG
GCTGCATCCGTTTTGCAAAGTGGG
GGCTGGGAAGGACATACTACAGGT
<hu CD40>
ACAGGTTCAGTGGCAGTGGGTCTGG
GTCCCATCAAGGTTCAGCGGCAGT
CCAAGTGGTATCATGATTATTCAGT
21-230_36F3VL]::huKLC-
GACAGACTTCACTCTCACCATCAGCA
GGATCTGGGACAGATTTCACTCTCA
ATCTGTGAAAAGTCGAATCACCAT
S176E + [anti-
GACTGGAGCCTGAAGATTTTGCAGTG
CCATCAGCAGCCTGCAGCCTGAAG
CGACCCAGACACATCCAAGAACCA
<hu Mesothelin>
TATTTCTGTCAGCAGTATGGTAGCTC
ATTTTGCAACTTACTATTGTCAACA
GTTCTCCCTGCAGCTGAACTCTGTG
4H6VL]::huKLC-
ACCGCTCACTTTCGGCGGAGGGACTA
GTCTAACAGTTTCCCTCGGACGTTC
ACTCCCGAGGACACGGCTGTTTATT
S176K (IgG-Fab);
AGGTGGAGATCAAACGAACGGTGGC
GGCCAAGGGACCAAGGTGGAAATC
ATTGTGCAAGAGGGGCTGCTCCCTT
LMRID: SS-30880
TGCACCATCTGTCTTCATCTTCCCGCC
AAACGGACGGTGGCTGCACCATCT
TGACTACTGGGGCCAGGGAACCCT
ATCTGATGAGCAGTTGAAATCTGGAA
GTCTTCATCTTCCCGCCATCTGATG
GGTCACCGTGTCCTCAGCCTCCACC
CTGCCTCTGTTGTGTGCCTGCTGAAT
AGCAGTTGAAATCTGGAACTGCCT
AAGGGCCCATCGGTCTTCCCCCTGG
AACTTCTATCCCAGAGAGGCCAAAGT
CTGTTGTGTGCCTGCTGAATAACTT
CACCCTCCTCCAAGAGCACCTCTGG
ACAGTGGAAGGTGGATAACGCCCTC
CTATCCCAGAGAGGCCAAAGTACA
GGGCACAGCGGCCCTGGGCTGCCT
CAATCGGGTAACTCCCAGGAGAGTG
GTGGAAGGTGGATAACGCCCTCCA
GGTCAAGGACTACTTCCCCGAACC
TCACAGAGCAGGACAGCAAGGACAG
ATCGGGTAACTCCCAGGAGAGTGT
GGTGACGGTGTCGTGGAACTCAGG
CACCTACAGCCTCGAAAGCACCCTGA
CACAGAGCAGGACAGCAAGGACA
CGCCCTGACCAGCGGCGTGCACAC
CGCTGAGCAAAGCAGACTACGAGAA
GCACCTACAGCCTCAAGAGCACCC
CTTCCCGGCTGTCCTACAGTCCTCA
ACACAAAGTCTACGCCTGCGAAGTC
TGACGCTGAGCAAAGCAGACTACG
GGACTCTACTCCCTCAAGAGCGTG
ACCCATCAGGGCCTGAGCTCGCCCGT
AGAAACACAAAGTCTACGCCTGCG
GTGACCGTGCCCTCCAGCAGCTTG
CACAAAGAGCTTCAACAGGGGAGAG
AAGTCACCCATCAGGGCCTGAGCT
GGCACCCAGACCTACATCTGCAAC
TGT
CGCCCGTCACAAAGAGCTTCAACA
GTGAATCACAAGCCCAGCAACACC
(SEQ ID NO: 581)
GGGGAGAGTGT
AAGGTGGACAAGAAAGTTGAGCCC
(SEQ ID NO: 582)
AAATCTTGTGACAAAACTCACACA
TGCCCACCGTGCCCAGCACCTGAA
CTCCTGGGGGGACCGTCAGTCTTCC
TCTTCCCCCCAAAACCCAAGGACA
CCCTCATGATCTCCCGGACCCCTGA
GGTCACATGCGTGGTGGTGGACGT
GAGCCACGAAGACCCTGAGGTCAA
GTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAA
GCCGTGCGAGGAGCAGTACGGCAG
CACGTACCGTTGCGTCAGCGTCCTC
ACCGTCCTGCACCAGGACTGGCTG
AATGGCAAGGAGTACAAGTGCAAG
GTGTCCAACAAAGCCCTCCCAGCC
CCCATCGAGAAAACCATCTCCAAA
GCCAAAGGGCAGCCCCGAGAACCA
CAGGTGTACACCCTGCCCCCATCCC
GGGAGGAGATGACCAAGAACCAG
GTCAGCCTGACCTGCCTGGTCAAA
GGCTTCTATCCCAGCGACATCGCCG
TGGAGTGGGAGAGCAATGGGCAGC
CGGAGAACAACTACAAGACCACGC
CTCCCGTGCTGGACTCCGACGGCTC
CTTCTTCCTCTATAGCAAGCTCACC
GTGGACAAGAGCAGGTGGCAGCAG
GGGAACGTCTTCTCATGCTCCGTGA
TGCATGAGGCTCTGCACAACCACT
ACACGCAGAAGAGCCTCTCCCTGT
CTCCGGGTGGTGGCGGATCGGGAG
GTGGCGGATCCCAGGTGCAGCTGG
TCGAGTCTGGGGGAGGCTTGGTCA
AGCCTGGAGGGTCCCTGAGACTCT
CCTGTGCAGCCTCTGGATTCACCTT
CAGTGACTACTACATGACCTGGAT
CAGGCAGGCTCCAGGGAAGGGGCT
GGAGTGGATTTCATACATTAGTAGT
AGTGGTAGTACCATCTACTACGCA
GACTCTGTGAAGGGCCGATTCACC
ATCTCCAGGGACAACGCCAAGAAC
TCACTGTATCTGCAAATGAACAGC
CTGAGAGCCGAGGACACGGCCGTG
TATTACTGTGCGAGAGATCGGAAC
TCCCACTTTGACTATTGGGGCCAGG
GAACCCTGGTCACCGTGTCCTCAGC
AAGCACGAAGGGGCCGTCCGTATT
TCCGCTTGCGCCCTCGTCGAAGTCA
ACTTCGGGAGGGACCGCGGCACTT
GGCTGTCTTGTCAAAGATTACTTCC
CTGAGCCAGTGACAGTCAGCTGGA
ATTCCGGTGCCCTCACGTCAGGAGT
ACATACATTCCCTGCGGTATTGCAG
TCCTCCGGACTCTACTCCCTGGAGT
CGGTGGTAACGGTGCCCAGCTCCA
GCTTGGGGACCCAGACGTACATTT
GTAACGTGAATCACAAACCAAGCA
ATACTAAGGTAGATAAGAAAGTAG
AACCGAAGAGCTGC
(SEQ ID NO: 583)
AA
EIVLTQSPGTLSLSPGERATLSCRASQS
DIQMTQSPSSVSASVGDRVTITCRAS
QVQLQQSGPGLVKPSQTLSLTCAISG
VSSNYLAWYQQKPGQAPRALIYAASN
QGITRWLAWYQQKPGKAPKLLIYAA
DSVSSSRTAWNWIRQSPSRGLEWLG
RAAGISDRFSGSGSGTDFTLTISRLEPE
SVLQSGVPSRFSGSGSGTDFTLTISSL
RTYYRSKWYHDYSVSVKSRITIDPDT
DFAVYFCQQYGSSPLTFGGGTKVEIKR
QPEDFATYYCQQSNSFPRTFGQGTK
SKNQFSLQLNSVTPEDTAVYYCARG
TVAAPSVFIFPPSDEQLKSGTASVVCLL
VEIKRTVAAPSVFIFPPSDEQLKSGTA
AAPFDYWGQGTLVTVSSASTKGPSV
NNFYPREAKVQWKVDNALQSGNSQES
SVVCLLNNFYPREAKVQWKVDNAL
FPLAPSSKSTSGGTAALGCLVKDYFP
VTEQDSKDSTYSLESTLTLSKADYEKH
QSGNSQESVTEQDSKDSTYSLKSTLT
EPVTVSWNSGALTSGVHTFPAVLQS
KVYACEVTHQGLSSPVTKSFNRGEC
LSKADYEKHKVYACEVTHQGLSSPV
SGLYSLKSVVTVPSSSLGTQTYICNV
(SEQ ID NO: 584)
TKSFNRGEC
NHKPSNTKVDKKVEPKSCDKTHTCP
(SEQ ID NO: 585)
PCPAPELLGGPSVFLFPPKPKDTLMIS
RTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPCEEQYGSTYRCVS
VLTVLHQDWLNGKEYKCKVSNKAL
PAPIEKTISKAKGQPREPQVYTLPPSR
EEMTKNQVSLTCLVKGFYPSDIAVE
WESNGQPENNYKTTPPVLDSDGSFF
LYSKLTVDKSRWQQGNVFSCSVMH
EALHNHYTQKSLSLSPGGGGSGGGG
SQVQLVESGGGLVKPGGSLRLSCAA
SGFTFSDYYMTWIRQAPGKGLEWIS
YISSSGSTIYYADSVKGRFTISRDNAK
NSLYLQMNSLRAEDTAVYYCARDR
NSHFDYWGQGTLVTVSSASTKGPSV
FPLAPSSKSTSGGTAALGCLVKDYFP
EPVTVSWNSGALTSGVHTFPAVLQS
SGLYSLESVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSC
(SEQ ID NO: 586)
iPS:
21-
[hu anti-
NA
GAAATTGTGTTGACGCAGTCTCCAGG
GACATCCAGATGACCCAGTCTCCA
CAGGTACAGCTGCAACAGTCAGGT
576358
230_36F3_IgG_
<hu CD40> 21-230_
CACCCTGTCTTTGTCTCCAGGGGAAA
TCTTCCGTGTCTGCTTCTGTCGGAG
CCAGGACTGGTGAAGCCCTCGCAG
21-
36F3VH]::huIgG1zSEFL2*GK-
GAGCCACCCTCTCCTGCAGGGCCAGT
ACAGAGTCACCATCACTTGTCGGG
ACCCTCTCACTCACCTGTGCCATCT
233_6F4__Fab
K::(G4S)2::[hu anti-
CAGAGTGTTAGCAGCAACTACTTAGC
CGAGTCAGGATATTAGCAGGTGGT
CCGGGGACAGTGTCTCTAGCAGCC
<hu Mesothelin>
CTGGTACCAACAGAAACCTGGCCAG
TAGCCTGGTATCAGCAGAAACCAG
GTACTGCTTGGAACTGGATCAGGC
6F4VH]::huIgG1z-
GCTCCCAGGGCCCTTATCTATGCTGC
GGAAAGCCCCTAAGCTCCTGATTTC
AGTCCCCATCGAGAGGCCTTGAGT
CH1-E::EPKSC + [anti-
ATCCAACAGGGCCGCTGGCATCTCAG
TGCTGCATCCAGATTGCAAAGTGG
GGCTGGGAAGGACATACTACAGGT
<hu CD40>
ACAGGTTCAGTGGCAGTGGGTCTGG
AGTCCCATCAAGGTTCAGCGGCAG
CCAAGTGGTATCATGATTATTCAGT
21-230_36F3VL]::huKLC-
GACAGACTTCACTCTCACCATCAGCA
TGGATCTGGGACAGATTTCACTCTC
ATCTGTGAAAAGTCGAATCACCAT
S176E + [anti-
GACTGGAGCCTGAAGATTTTGCAGTG
ACCATCAGCAGCCTGCAGCCTGAA
CGACCCAGACACATCCAAGAACCA
<hu Mesothelin>
TATTTCTGTCAGCAGTATGGTAGCTC
GATTTTGCAATTTACTATTGTCAAC
GTTCTCCCTGCAGCTGAACTCTGTG
6F4VL]::huKLC-
ACCGCTCACTTTCGGCGGAGGGACTA
AGGCTAAAAGTTTTCCTCGGACGTT
ACTCCCGAGGACACGGCTGTTTATT
S176K (IgG-Fab);
AGGTGGAGATCAAACGAACGGTGGC
CGGCCAAGGGACCAAGGTGGAAAT
ATTGTGCAAGAGGGGCTGCTCCCTT
LMRID: SS-30881
TGCACCATCTGTCTTCATCTTCCCGCC
CAAACGGACGGTGGCTGCACCATC
TGACTACTGGGGCCAGGGAACCCT
ATCTGATGAGCAGTTGAAATCTGGAA
TGTCTTCATCTTCCCGCCATCTGAT
GGTCACCGTGTCCTCAGCCTCCACC
CTGCCTCTGTTGTGTGCCTGCTGAAT
GAGCAGTTGAAATCTGGAACTGCC
AAGGGCCCATCGGTCTTCCCCCTGG
AACTTCTATCCCAGAGAGGCCAAAGT
TCTGTTGTGTGCCTGCTGAATAACT
CACCCTCCTCCAAGAGCACCTCTGG
ACAGTGGAAGGTGGATAACGCCCTC
TCTATCCCAGAGAGGCCAAAGTAC
GGGCACAGCGGCCCTGGGCTGCCT
CAATCGGGTAACTCCCAGGAGAGTG
AGTGGAAGGTGGATAACGCCCTCC
GGTCAAGGACTACTTCCCCGAACC
TCACAGAGCAGGACAGCAAGGACAG
AATCGGGTAACTCCCAGGAGAGTG
GGTGACGGTGTCGTGGAACTCAGG
CACCTACAGCCTCGAAAGCACCCTGA
TCACAGAGCAGGACAGCAAGGACA
CGCCCTGACCAGCGGCGTGCACAC
CGCTGAGCAAAGCAGACTACGAGAA
GCACCTACAGCCTCAAGAGCACCC
CTTCCCGGCTGTCCTACAGTCCTCA
ACACAAAGTCTACGCCTGCGAAGTC
TGACGCTGAGCAAAGCAGACTACG
GGACTCTACTCCCTCAAGAGCGTG
ACCCATCAGGGCCTGAGCTCGCCCGT
AGAAACACAAAGTCTACGCCTGCG
GTGACCGTGCCCTCCAGCAGCTTG
CACAAAGAGCTTCAACAGGGGAGAG
AAGTCACCCATCAGGGCCTGAGCT
GGCACCCAGACCTACATCTGCAAC
TGT
CGCCCGTCACAAAGAGCTTCAACA
GTGAATCACAAGCCCAGCAACACC
(SEQ ID NO: 587)
GGGGAGAGTGT
AAGGTGGACAAGAAAGTTGAGCCC
(SEQ ID NO: 588)
AAATCTTGTGACAAAACTCACACA
TGCCCACCGTGCCCAGCACCTGAA
CTCCTGGGGGGACCGTCAGTCTTCC
TCTTCCCCCCAAAACCCAAGGACA
CCCTCATGATCTCCCGGACCCCTGA
GGTCACATGCGTGGTGGTGGACGT
GAGCCACGAAGACCCTGAGGTCAA
GTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAA
GCCGTGCGAGGAGCAGTACGGCAG
CACGTACCGTTGCGTCAGCGTCCTC
ACCGTCCTGCACCAGGACTGGCTG
AATGGCAAGGAGTACAAGTGCAAG
GTGTCCAACAAAGCCCTCCCAGCC
CCCATCGAGAAAACCATCTCCAAA
GCCAAAGGGCAGCCCCGAGAACCA
CAGGTGTACACCCTGCCCCCATCCC
GGGAGGAGATGACCAAGAACCAG
GTCAGCCTGACCTGCCTGGTCAAA
GGCTTCTATCCCAGCGACATCGCCG
TGGAGTGGGAGAGCAATGGGCAGC
CGGAGAACAACTACAAGACCACGC
CTCCCGTGCTGGACTCCGACGGCTC
CTTCTTCCTCTATAGCAAGCTCACC
GTGGACAAGAGCAGGTGGCAGCAG
GGGAACGTCTTCTCATGCTCCGTGA
TGCATGAGGCTCTGCACAACCACT
ACACGCAGAAGAGCCTCTCCCTGT
CTCCGGGTGGTGGCGGATCGGGAG
GTGGCGGATCCCAGGTGCAGCTGG
TGGAGTCTGGGGGAGGCTTGGTCA
AGCCTGGAGGGTCCCTGAGACTCT
CCTGTGCAGCCTCTGGATTCACCTT
CAGTGACTACTACATGAGCTGGAT
CCGCCAGGCTCCAGGGAAGGGGCT
GGAGTGGATTTCATACATTAGTAG
CAGTGAAAGTATCATCTATTACGTA
GACTCTGTGAAGGGCCGATTCACC
ATCTCCAGGGACAACGCCAAGAAC
TCACTGTATCTGCAAATGAACAGC
CTGAGAGCCGAGGACACGGCCGTG
TATTACTGTGCGAGAGATGTTGGG
AGCCACTTTGACTACTGGGGCCAG
GGAACCCTGGTCACCGTGTCCTCA
GCAAGCACGAAGGGGCCGTCCGTA
TTTCCGCTTGCGCCCTCGTCGAAGT
CAACTTCGGGAGGGACCGCGGCAC
TTGGCTGTCTTGTCAAAGATTACTT
CCCTGAGCCAGTGACAGTCAGCTG
GAATTCCGGTGCCCTCACGTCAGG
AGTACATACATTCCCTGCGGTATTG
CAGTCCTCCGGACTCTACTCCCTGG
AGTCGGTGGTAACGGTGCCCAGCT
CCAGCTTGGGGACCCAGACGTACA
TTTGTAACGTGAATCACAAACCAA
GCAATACTAAGGTAGATAAGAAAG
TAGAACCGAAGAGCTGC
(SEQ ID NO: 589)
AA
EIVLTQSPGTLSLSPGERATLSCRASQS
DIQMTQSPSSVSASVGDRVTITCRAS
QVQLQQSGPGLVKPSQTLSLTCAISG
VSSNYLAWYQQKPGQAPRALIYAASN
QDISRWLAWYQQKPGKAPKLLISAA
DSVSSSRTAWNWIRQSPSRGLEWLG
RAAGISDRFSGSGSGTDFTLTISRLEPE
SRLQSGVPSRFSGSGSGTDFTLTISSL
RTYYRSKWYHDYSVSVKSRITIDPDT
DFAVYFCQQYGSSPLTFGGGTKVEIKR
QPEDFAIYYCQQAKSFPRTFGQGTKV
SKNQFSLQLNSVTPEDTAVYYCARG
TVAAPSVFIFPPSDEQLKSGTASVVCLL
EIKRTVAAPSVFIFPPSDEQLKSGTAS
AAPFDYWGQGTLVTVSSASTKGPSV
NNFYPREAKVQWKVDNALQSGNSQES
VVCLLNNFYPREAKVQWKVDNALQ
FPLAPSSKSTSGGTAALGCLVKDYFP
VTEQDSKDSTYSLESTLTLSKADYEKH
SGNSQESVTEQDSKDSTYSLKSTLTL
EPVTVSWNSGALTSGVHTFPAVLQS
KVYACEVTHQGLSSPVTKSFNRGEC
SKADYEKHKVYACEVTHQGLSSPVT
SGLYSLKSVVTVPSSSLGTQTYICNV
(SEQ ID NO: 590)
KSFNRGEC
NHKPSNTKVDKKVEPKSCDKTHTCP
(SEQ ID NO: 591)
PCPAPELLGGPSVFLFPPKPKDTLMIS
RTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPCEEQYGSTYRCVS
VLTVLHQDWLNGKEYKCKVSNKAL
PAPIEKTISKAKGQPREPQVYTLPPSR
EEMTKNQVSLTCLVKGFYPSDIAVE
WESNGQPENNYKTTPPVLDSDGSFF
LYSKLTVDKSRWQQGNVFSCSVMH
EALHNHYTQKSLSLSPGGGGSGGGG
SQVQLVESGGGLVKPGGSLRLSCAA
SGFTFSDYYMSWIRQAPGKGLEWIS
YISSSESIIYYVDSVKGRFTISRDNAK
NSLYLQMNSLRAEDTAVYYCARDV
GSHFDYWGQGTLVTVSSASTKGPSV
FPLAPSSKSTSGGTAALGCLVKDYFP
EPVTVSWNSGALTSGVHTFPAVLQS
SGLYSLESVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSC
(SEQ ID NO: 592)
iPS:
21-
[hu anti-
NA
GAAATTGTGTTGACGCAGTCTCCAGG
GACATTGTGATGACTCAGTCTCCAG
CAGGTACAGCTGCAACAGTCAGGT
576361
230_36F3_IgG_
<hu CD40> 21-230_
CACCCTGTCTTTGTCTCCAGGGGAAA
ACTCCCTGGCTGTGTCTCTGGGCGA
CCAGGACTGGTGAAGCCCTCGCAG
21-
36F3VH]::huIgG1zSEFL2*GK-
GAGCCACCCTCTCCTGCAGGGCCAGT
GAGGGCCACCATCAACTGCAAGTC
ACCCTCTCACTCACCTGTGCCATCT
233_7G11__Fab
K::(G4S)2::[hu anti-
CAGAGTGTTAGCAGCAACTACTTAGC
CAGCCAGAGTGTTTTATACAGCTCC
CCGGGGACAGTGTCTCTAGCAGCC
<hu Mesothelin>
CTGGTACCAACAGAAACCTGGCCAG
AACAATAAGAACTACTTAGCTTGG
GTACTGCTTGGAACTGGATCAGGC
7G11VH]::huIgG1z-
GCTCCCAGGGCCCTTATCTATGCTGC
TACCAGCAGAAACCAGGACAGCCT
AGTCCCCATCGAGAGGCCTTGAGT
CH1-E::EPKSC + [anti-
ATCCAACAGGGCCGCTGGCATCTCAG
CCTAAGCTGCTCATTTACTGGGCAT
GGCTGGGAAGGACATACTACAGGT
<hu CD40>
ACAGGTTCAGTGGCAGTGGGTCTGG
CTACCCGAGAATCCGGGGTCCCTG
CCAAGTGGTATCATGATTATTCAGT
21-230_36F3VL]::huKLC-
GACAGACTTCACTCTCACCATCAGCA
ACCGATTCAGTGGCAGCGGGTCTG
ATCTGTGAAAAGTCGAATCACCAT
S176E + [anti-
GACTGGAGCCTGAAGATTTTGCAGTG
GGACAGATTTCACTCTCACCATCAG
CGACCCAGACACATCCAAGAACCA
<hu Mesothelin>
TATTTCTGTCAGCAGTATGGTAGCTC
CAGCCTGCAGGCTGAAGATGTGGC
GTTCTCCCTGCAGCTGAACTCTGTG
7G11VL]::huKLC-
ACCGCTCACTTTCGGCGGAGGGACTA
AGTTTATTACTGTCAGCAATATTAT
ACTCCCGAGGACACGGCTGTTTATT
S176K (IgG-Fab);
AGGTGGAGATCAAACGAACGGTGGC
AGTACTCCTCCGACGTTCGGCCAA
ATTGTGCAAGAGGGGCTGCTCCCTT
LMRID: SS-30882
TGCACCATCTGTCTTCATCTTCCCGCC
GGGACCAAGGTGGAGATCAAACGG
TGACTACTGGGGCCAGGGAACCCT
ATCTGATGAGCAGTTGAAATCTGGAA
ACGGTGGCTGCACCATCTGTCTTCA
GGTCACCGTGTCCTCAGCCTCCACC
CTGCCTCTGTTGTGTGCCTGCTGAAT
TCTTCCCGCCATCTGATGAGCAGTT
AAGGGCCCATCGGTCTTCCCCCTGG
AACTTCTATCCCAGAGAGGCCAAAGT
GAAATCTGGAACTGCCTCTGTTGTG
CACCCTCCTCCAAGAGCACCTCTGG
ACAGTGGAAGGTGGATAACGCCCTC
TGCCTGCTGAATAACTTCTATCCCA
GGGCACAGCGGCCCTGGGCTGCCT
CAATCGGGTAACTCCCAGGAGAGTG
GAGAGGCCAAAGTACAGTGGAAGG
GGTCAAGGACTACTTCCCCGAACC
TCACAGAGCAGGACAGCAAGGACAG
TGGATAACGCCCTCCAATCGGGTA
GGTGACGGTGTCGTGGAACTCAGG
CACCTACAGCCTCGAAAGCACCCTGA
ACTCCCAGGAGAGTGTCACAGAGC
CGCCCTGACCAGCGGCGTGCACAC
CGCTGAGCAAAGCAGACTACGAGAA
AGGACAGCAAGGACAGCACCTACA
CTTCCCGGCTGTCCTACAGTCCTCA
ACACAAAGTCTACGCCTGCGAAGTC
GCCTCAAGAGCACCCTGACGCTGA
GGACTCTACTCCCTCAAGAGCGTG
ACCCATCAGGGCCTGAGCTCGCCCGT
GCAAAGCAGACTACGAGAAACACA
GTGACCGTGCCCTCCAGCAGCTTG
CACAAAGAGCTTCAACAGGGGAGAG
AAGTCTACGCCTGCGAAGTCACCC
GGCACCCAGACCTACATCTGCAAC
TGT
ATCAGGGCCTGAGCTCGCCCGTCA
GTGAATCACAAGCCCAGCAACACC
(SEQ ID NO: 593)
CAAAGAGCTTCAACAGGGGAGAGT
AAGGTGGACAAGAAAGTTGAGCCC
GT
AAATCTTGTGACAAAACTCACACA
(SEQ ID NO: 594)
TGCCCACCGTGCCCAGCACCTGAA
CTCCTGGGGGGACCGTCAGTCTTCC
TCTTCCCCCCAAAACCCAAGGACA
CCCTCATGATCTCCCGGACCCCTGA
GGTCACATGCGTGGTGGTGGACGT
GAGCCACGAAGACCCTGAGGTCAA
GTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAA
GCCGTGCGAGGAGCAGTACGGCAG
CACGTACCGTTGCGTCAGCGTCCTC
ACCGTCCTGCACCAGGACTGGCTG
AATGGCAAGGAGTACAAGTGCAAG
GTGTCCAACAAAGCCCTCCCAGCC
CCCATCGAGAAAACCATCTCCAAA
GCCAAAGGGCAGCCCCGAGAACCA
CAGGTGTACACCCTGCCCCCATCCC
GGGAGGAGATGACCAAGAACCAG
GTCAGCCTGACCTGCCTGGTCAAA
GGCTTCTATCCCAGCGACATCGCCG
TGGAGTGGGAGAGCAATGGGCAGC
CGGAGAACAACTACAAGACCACGC
CTCCCGTGCTGGACTCCGACGGCTC
CTTCTTCCTCTATAGCAAGCTCACC
GTGGACAAGAGCAGGTGGCAGCAG
GGGAACGTCTTCTCATGCTCCGTGA
TGCATGAGGCTCTGCACAACCACT
ACACGCAGAAGAGCCTCTCCCTGT
CTCCGGGTGGTGGCGGATCGGGAG
GTGGCGGATCCGAGGTGCAGCTGG
TCGAGTCTGGAGGAGGCTTGATCC
AGCCTGGGGGGTCCCTGAGACTCT
CCTGTGCAGTCTCTGGGTTCACCGT
CAGTAGCAAGTTCATGACCTGGGT
CCGCCAGGCTCCAGGGAAGGGGCT
GGAGTGGGTGTCAGTTATTTATAGC
GGTGGTAAGACATACTACGCAGAC
TCCGTGAAGGGCCGATTCACCATCT
CCAGAGACAATTCCAAGAACACGC
TGTATCTTCAAATGAACAGCCTGA
GAGCCGAGGACACGGCCGTGTATT
ACTGTGCGAGAGATAGCGGTGGCT
GGGGGTACTTTGACTACTGGGGCC
AGGGAACCCTGGTCACCGTGTCCT
CAGCAAGCACGAAGGGGCCGTCCG
TATTTCCGCTTGCGCCCTCGTCGAA
GTCAACTTCGGGAGGGACCGCGGC
ACTTGGCTGTCTTGTCAAAGATTAC
TTCCCTGAGCCAGTGACAGTCAGCT
GGAATTCCGGTGCCCTCACGTCAG
GAGTACATACATTCCCTGCGGTATT
GCAGTCCTCCGGACTCTACTCCCTG
GAGTCGGTGGTAACGGTGCCCAGC
TCCAGCTTGGGGACCCAGACGTAC
ATTTGTAACGTGAATCACAAACCA
AGCAATACTAAGGTAGATAAGAAA
GTAGAACCGAAGAGCTGC
(SEQ ID NO: 595)
AA
EIVLTQSPGTLSLSPGERATLSCRASQS
DIVMTQSPDSLAVSLGERATINCKSS
QVQLQQSGPGLVKPSQTLSLTCAISG
VSSNYLAWYQQKPGQAPRALIYAASN
QSVLYSSNNKNYLAWYQQKPGQPP
DSVSSSRTAWNWIRQSPSRGLEWLG
RAAGISDRFSGSGSGTDFTLTISRLEPE
KLLIYWASTRESGVPDRFSGSGSGTD
RTYYRSKWYHDYSVSVKSRITIDPDT
DFAVYFCQQYGSSPLTFGGGTKVEIKR
FTLTISSLQAEDVAVYYCQQYYSTPP
SKNQFSLQLNSVTPEDTAVYYCARG
TVAAPSVFIFPPSDEQLKSGTASVVCLL
TFGQGTKVEIKRTVAAPSVFIFPPSDE
AAPFDYWGQGTLVTVSSASTKGPSV
NNFYPREAKVQWKVDNALQSGNSQES
QLKSGTASVVCLLNNFYPREAKVQW
FPLAPSSKSTSGGTAALGCLVKDYFP
VTEQDSKDSTYSLESTLTLSKADYEKH
KVDNALQSGNSQESVTEQDSKDSTY
EPVTVSWNSGALTSGVHTFPAVLQS
KVYACEVTHQGLSSPVTKSFNRGEC
SLKSTLTLSKADYEKHKVYACEVTH
SGLYSLKSVVTVPSSSLGTQTYICNV
(SEQ ID NO: 596)
QGLSSPVTKSFNRGEC
NHKPSNTKVDKKVEPKSCDKTHTCP
(SEQ ID NO: 597)
PCPAPELLGGPSVFLFPPKPKDTLMIS
RTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPCEEQYGSTYRCVS
VLTVLHQDWLNGKEYKCKVSNKAL
PAPIEKTISKAKGQPREPQVYTLPPSR
EEMTKNQVSLTCLVKGFYPSDIAVE
WESNGQPENNYKTTPPVLDSDGSFF
LYSKLTVDKSRWQQGNVFSCSVMH
EALHNHYTQKSLSLSPGGGGSGGGG
SEVQLVESGGGLIQPGGSLRLSCAVS
GFTVSSKFMTWVRQAPGKGLEWVS
VIYSGGKTYYADSVKGRFTISRDNSK
NTLYLQMNSLRAEDTAVYYCARDS
GGWGYFDYWGQGTLVTVSSASTKG
PSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAV
LQSSGLYSLESVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 598)
iPS:
21-
[hu anti-
NA
TCCTATGAGCTGACTCAGCCACCCTC
CAGTCAGTGTTGACGCAGCCGCCC
CAGGTGCAGTTGGTGGAGTCTGGG
576364
230_37A6_IgG_
<hu CD40> 21-230_
AGTGTCCGTGTCCCCAGGACAGACA
TCAGTGTCTGGGGCCCCAGGGCAG
GGAGGCTTAGTCAAGCCTGGAGGG
21-
37A6VH]::huIgG1zSEFL2*GK-
GCCAGCATCACCTGCTCTGGAGAAA
AGGGTCACCATCTCCTGCACTGGG
TCCCTGAGACTCTCCTGTGCAGCCT
233_4G12__Fab
K::(G4S)2::[hu anti-
GGTTGGGAAATAAATATATTTGCTGG
AGCAGCTCCAACATCGGGGCAGGT
CTGAATTCACCTTCAGTGACTACTA
<hu Mesothelin>
TATCAGCAGAAGCCAGGCCAGTCCC
TATGATGTTCACTGGTACCAGCAG
CATGAGCTGGATCCGCCAGGCTCC
4G12VH]::huIgG1z-
CTGTTCTGGTCATCTATCAAGATTTC
GTTCCAGGAACAGCCCCCAAACTC
AGGGAAGGGGCTGGAGTGGGTTTC
CH1-E::EPKSC + [anti-
AAGCGGCCCTCAGGGATCCCTGAGC
CTCATCTATGGTAACAGCAAGCGG
ATATATTAGTCGAAGTGGTGATAC
<hu CD40>
GATTCTCTGGCTCCAACTCTGGGATC
CCCTCAGGGGTCCCTGACCGATTCT
CATCTACTACGCAGACTCTGTGAA
21-230_37A6VL]::huLLC2-
ACAGCCACTCTGACCATCAGCGGGA
CTGGCTCCAAGTCTGGCACCTCAGC
GGGCCGATTCACCATCTCCAGGGA
E + [anti-
CCCAGGCTATGGATGAGGCTGACTAT
CTCCCTGGCCATCACTGGGCTCCAG
CAACGCCAAGAACTCACTGTATCT
<hu Mesothelin>
TACTGTCAGGCGTGGGACAGCAGAA
GCTGAGGATGAGGCTGATTATTAC
GCAAATGAATGGCCTGCGAGCCGA
4G12VL]::huLLC2-
CTGTGGTATTCGGCGGAGGGACCAA
TGCCAGTCCTATGACAGCAGCCTG
AGACACGGCCGTGTATTACTGTGC
K (IgG-Fab);
GCTGACCGTCCTAGGTCAGCCCAAGG
GGTGGTTGGGTGTTCGGCGGAGGG
GAGAGACTTAGCAGCAGGTGCTAC
LMRID: SS-30883
CTGCACCCTCGGTCACTCTGTTCCCG
ACCAAGCTGACCGTCCTACAGCCC
AGGGGGCCTTGACTGCTGGGGCCA
CCCTCCTCTGAGGAGCTTCAAGCCAA
AAGGCTGCACCCTCGGTCACTCTGT
GGGAACCCTGGTCACCGTGTCCTC
CAAGGCCACACTGGTGTGTCTCATCA
TCCCGCCCTCCTCTGAGGAGCTTCA
AGCCTCCACCAAGGGCCCATCGGT
GTGACTTCTACCCGGGAGCCGTGACA
AGCCAACAAGGCCACACTGGTGTG
CTTCCCCCTGGCACCCTCCTCCAAG
GTGGCCTGGAAGGCAGATAGCAGCC
TCTCATCAGTGACTTCTACCCGGGA
AGCACCTCTGGGGGCACAGCGGCC
CCGTCAAGGCGGGAGTGGAAACCAC
GCCGTGACAGTGGCCTGGAAGGCA
CTGGGCTGCCTGGTCAAGGACTAC
CACACCCTCCAAACAAAGCAACAAC
GATAGCAGCCCCGTCAAGGCGGGA
TTCCCCGAACCGGTGACGGTGTCGT
AAGTACGCGGCCGAAAGCTATCTGA
GTGGAAACCACCACACCCTCCAAA
GGAACTCAGGCGCCCTGACCAGCG
GCCTGACGCCTGAGCAGTGGAAGTC
CAAAGCAACAACAAGTACGCGGCC
GCGTGCACACCTTCCCGGCTGTCCT
CCACAGAAGCTACAGCTGCCAGGTC
AAGAGCTATCTGAGCCTGACGCCT
ACAGTCCTCAGGACTCTACTCCCTC
ACGCATGAAGGGAGCACCGTGGAGA
GAGCAGTGGAAGTCCCACAGAAGC
AAGAGCGTGGTGACCGTGCCCTCC
AGACAGTGGCCCCTACAGAATGTTCA
TACAGCTGCCAGGTCACGCATGAA
AGCAGCTTGGGCACCCAGACCTAC
(SEQ ID NO: 599)
GGGAGCACCGTGGAGAAGACAGTG
ATCTGCAACGTGAATCACAAGCCC
GCCCCTACAGAATGTTCA
AGCAACACCAAGGTGGACAAGAAA
(SEQ ID NO: 600)
GTTGAGCCCAAATCTTGTGACAAA
ACTCACACATGCCCACCGTGCCCA
GCACCTGAACTCCTGGGGGGACCG
TCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCC
GGACCCCTGAGGTCACATGCGTGG
TGGTGGACGTGAGCCACGAAGACC
CTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATG
CCAAGACAAAGCCGTGCGAGGAGC
AGTACGGCAGCACGTACCGTTGCG
TCAGCGTCCTCACCGTCCTGCACCA
GGACTGGCTGAATGGCAAGGAGTA
CAAGTGCAAGGTGTCCAACAAAGC
CCTCCCAGCCCCCATCGAGAAAAC
CATCTCCAAAGCCAAAGGGCAGCC
CCGAGAACCACAGGTGTACACCCT
GCCCCCATCCCGGGAGGAGATGAC
CAAGAACCAGGTCAGCCTGACCTG
CCTGGTCAAAGGCTTCTATCCCAGC
GACATCGCCGTGGAGTGGGAGAGC
AATGGGCAGCCGGAGAACAACTAC
AAGACCACGCCTCCCGTGCTGGAC
TCCGACGGCTCCTTCTTCCTCTATA
GCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCT
CATGCTCCGTGATGCATGAGGCTCT
GCACAACCACTACACGCAGAAGAG
CCTCTCCCTGTCTCCGGGTGGTGGC
GGATCGGGAGGTGGCGGATCCCAG
GTGCAGCTGCAGGAGTCGGGCCCA
GGACTGGTGAAGCCTTCGGAAACC
CTGTCCCTCACCTGCACTGTCTCTG
GTGGCTCCATCAGCAGTAGTAGTT
ACTACTGGGGCTGGATCAGGCAGC
CCCCAGGGAAGGGGCTGGAGTGGA
TTGGGAGTATCTATTATAGTGGGAT
CACCAACTACAACCCGTCCCTCAA
GAGTCGAGTCACCATCTCCGTAGA
CACGTCCAAGAACCAGTTCTCCCTG
AAGCTGAGTTCTGTGACCGCCGCA
GACACGGCCGTGTATTACTGTGCG
AGATCCAGTAACTACGATGCTTTTG
ATATCTGGGGCCAAGGGACAATGG
TCACCGTGTCCTCAGCAAGCACGA
AGGGGCCGTCCGTATTTCCGCTTGC
GCCCTCGTCGAAGTCAACTTCGGG
AGGGACCGCGGCACTTGGCTGTCT
TGTCAAAGATTACTTCCCTGAGCCA
GTGACAGTCAGCTGGAATTCCGGT
GCCCTCACGTCAGGAGTACATACA
TTCCCTGCGGTATTGCAGTCCTCCG
GACTCTACTCCCTGGAGTCGGTGGT
AACGGTGCCCAGCTCCAGCTTGGG
GACCCAGACGTACATTTGTAACGT
GAATCACAAACCAAGCAATACTAA
GGTAGATAAGAAAGTAGAACCGAA
GAGCTGC
(SEQ ID NO: 601)
AA
SYELTQPPSVSVSPGQTASITCSGERLG
QSVLTQPPSVSGAPGQRVTISCTGSSS
QVQLVESGGGLVKPGGSLRLSCAAS
NKYICWYQQKPGQSPVLVIYQDFKRPS
NIGAGYDVHWYQQVPGTAPKLLIYG
EFTFSDYYMSWIRQAPGKGLEWVSY
GIPERFSGSNSGITATLTISGTQAMDEA
NSKRPSGVPDRFSGSKSGTSASLAIT
ISRSGDTIYYADSVKGRFTISRDNAK
DYYCQAWDSRTVVFGGGTKLTVLGQP
GLQAEDEADYYCQSYDSSLGGWVF
NSLYLQMNGLRAEDTAVYYCARDL
KAAPSVTLFPPSSEELQANKATLVCLIS
GGGTKLTVLQPKAAPSVTLFPPSSEE
AAGATGGLDCWGQGTLVTVSSAST
DFYPGAVTVAWKADSSPVKAGVETTT
LQANKATLVCLISDFYPGAVTVAWK
KGPSVFPLAPSSKSTSGGTAALGCLV
PSKQSNNKYAAESYLSLTPEQWKSHRS
ADSSPVKAGVETTTPSKQSNNKYAA
KDYFPEPVTVSWNSGALTSGVHTFP
YSCQVTHEGSTVEKTVAPTECS
KSYLSLTPEQWKSHRSYSCQVTHEG
AVLQSSGLYSLKSVVTVPSSSLGTQT
(SEQ ID NO: 602)
STVEKTVAPTECS
YICNVNHKPSNTKVDKKVEPKSCDK
(SEQ ID NO: 603)
THTCPPCPAPELLGGPSVFLFPPKPKD
TLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPCEEQYGST
YRCVSVLTVLHQDWLNGKEYKCKV
SNKALPAPIEKTISKAKGQPREPQVY
TLPPSREEMTKNQVSLTCLVKGFYPS
DIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGS
GGGGSQVQLQESGPGLVKPSETLSLT
CTVSGGSISSSSYYWGWIRQPPGKGL
EWIGSIYYSGITNYNPSLKSRVTISVD
TSKNQFSLKLSSVTAADTAVYYCAR
SSNYDAFDIWGQGTMVTVSSASTKG
PSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAV
LQSSGLYSLESVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 604)
iPS:
21-
[hu anti-
NA
TCCTATGAGCTGACTCAGCCACCCTC
GACATTCAGATGACCCAGTCTCCAT
CAGGTGCAGTTGGTGGAGTCTGGG
576369
230_37A6_IgG_
<hu CD40> 21-230_
AGTGTCCGTGTCCCCAGGACAGACA
CTTCCGTGTCTGCATCTGTAGGGGA
GGAGGCTTAGTCAAGCCTGGAGGG
21-
37A6VH]::huIgG1zSEFL2*GK-
GCCAGCATCACCTGCTCTGGAGAAA
CAGAGTCACCATCACTTGTCGGGC
TCCCTGAGACTCTCCTGTGCAGCCT
233_4H6__Fab
K::(G4S)2::[hu anti-
GGTTGGGAAATAAATATATTTGCTGG
GAGTCAGGGTATTACCAGGTGGTT
CTGAATTCACCTTCAGTGACTACTA
<hu Mesothelin>
TATCAGCAGAAGCCAGGCCAGTCCC
AGCCTGGTATCAGCAGAAACCAGG
CATGAGCTGGATCCGCCAGGCTCC
4H6VH]::huIgG1z-
CTGTTCTGGTCATCTATCAAGATTTC
GAAAGCCCCTAAGCTCCTGATCTAT
AGGGAAGGGGCTGGAGTGGGTTTC
CH1-E::EPKSC + [anti-
AAGCGGCCCTCAGGGATCCCTGAGC
GCTGCATCCGTTTTGCAAAGTGGG
ATATATTAGTCGAAGTGGTGATAC
<hu CD40>
GATTCTCTGGCTCCAACTCTGGGATC
GTCCCATCAAGGTTCAGCGGCAGT
CATCTACTACGCAGACTCTGTGAA
21-230_37A6VL]::huLLC2-
ACAGCCACTCTGACCATCAGCGGGA
GGATCTGGGACAGATTTCACTCTCA
GGGCCGATTCACCATCTCCAGGGA
E + [anti-
CCCAGGCTATGGATGAGGCTGACTAT
CCATCAGCAGCCTGCAGCCTGAAG
CAACGCCAAGAACTCACTGTATCT
<hu Mesothelin>
TACTGTCAGGCGTGGGACAGCAGAA
ATTTTGCAACTTACTATTGTCAACA
GCAAATGAATGGCCTGCGAGCCGA
4H6VL]::huKLC-
CTGTGGTATTCGGCGGAGGGACCAA
GTCTAACAGTTTCCCTCGGACGTTC
AGACACGGCCGTGTATTACTGTGC
S176K (IgG-Fab);
GCTGACCGTCCTAGGTCAGCCCAAGG
GGCCAAGGGACCAAGGTGGAAATC
GAGAGACTTAGCAGCAGGTGCTAC
LMRID: SS-30884
CTGCACCCTCGGTCACTCTGTTCCCG
AAACGGACGGTGGCTGCACCATCT
AGGGGGCCTTGACTGCTGGGGCCA
CCCTCCTCTGAGGAGCTTCAAGCCAA
GTCTTCATCTTCCCGCCATCTGATG
GGGAACCCTGGTCACCGTGTCCTC
CAAGGCCACACTGGTGTGTCTCATCA
AGCAGTTGAAATCTGGAACTGCCT
AGCCTCCACCAAGGGCCCATCGGT
GTGACTTCTACCCGGGAGCCGTGACA
CTGTTGTGTGCCTGCTGAATAACTT
CTTCCCCCTGGCACCCTCCTCCAAG
GTGGCCTGGAAGGCAGATAGCAGCC
CTATCCCAGAGAGGCCAAAGTACA
AGCACCTCTGGGGGCACAGCGGCC
CCGTCAAGGCGGGAGTGGAAACCAC
GTGGAAGGTGGATAACGCCCTCCA
CTGGGCTGCCTGGTCAAGGACTAC
CACACCCTCCAAACAAAGCAACAAC
ATCGGGTAACTCCCAGGAGAGTGT
TTCCCCGAACCGGTGACGGTGTCGT
AAGTACGCGGCCGAAAGCTATCTGA
CACAGAGCAGGACAGCAAGGACA
GGAACTCAGGCGCCCTGACCAGCG
GCCTGACGCCTGAGCAGTGGAAGTC
GCACCTACAGCCTCAAGAGCACCC
GCGTGCACACCTTCCCGGCTGTCCT
CCACAGAAGCTACAGCTGCCAGGTC
TGACGCTGAGCAAAGCAGACTACG
ACAGTCCTCAGGACTCTACTCCCTC
ACGCATGAAGGGAGCACCGTGGAGA
AGAAACACAAAGTCTACGCCTGCG
AAGAGCGTGGTGACCGTGCCCTCC
AGACAGTGGCCCCTACAGAATGTTCA
AAGTCACCCATCAGGGCCTGAGCT
AGCAGCTTGGGCACCCAGACCTAC
(SEQ ID NO: 605)
CGCCCGTCACAAAGAGCTTCAACA
ATCTGCAACGTGAATCACAAGCCC
GGGGAGAGTGT
AGCAACACCAAGGTGGACAAGAAA
(SEQ ID NO: 606)
GTTGAGCCCAAATCTTGTGACAAA
ACTCACACATGCCCACCGTGCCCA
GCACCTGAACTCCTGGGGGGACCG
TCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCC
GGACCCCTGAGGTCACATGCGTGG
TGGTGGACGTGAGCCACGAAGACC
CTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATG
CCAAGACAAAGCCGTGCGAGGAGC
AGTACGGCAGCACGTACCGTTGCG
TCAGCGTCCTCACCGTCCTGCACCA
GGACTGGCTGAATGGCAAGGAGTA
CAAGTGCAAGGTGTCCAACAAAGC
CCTCCCAGCCCCCATCGAGAAAAC
CATCTCCAAAGCCAAAGGGCAGCC
CCGAGAACCACAGGTGTACACCCT
GCCCCCATCCCGGGAGGAGATGAC
CAAGAACCAGGTCAGCCTGACCTG
CCTGGTCAAAGGCTTCTATCCCAGC
GACATCGCCGTGGAGTGGGAGAGC
AATGGGCAGCCGGAGAACAACTAC
AAGACCACGCCTCCCGTGCTGGAC
TCCGACGGCTCCTTCTTCCTCTATA
GCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCT
CATGCTCCGTGATGCATGAGGCTCT
GCACAACCACTACACGCAGAAGAG
CCTCTCCCTGTCTCCGGGTGGTGGC
GGATCGGGAGGTGGCGGATCCCAG
GTGCAGCTGGTCGAGTCTGGGGGA
GGCTTGGTCAAGCCTGGAGGGTCC
CTGAGACTCTCCTGTGCAGCCTCTG
GATTCACCTTCAGTGACTACTACAT
GACCTGGATCAGGCAGGCTCCAGG
GAAGGGGCTGGAGTGGATTTCATA
CATTAGTAGTAGTGGTAGTACCATC
TACTACGCAGACTCTGTGAAGGGC
CGATTCACCATCTCCAGGGACAAC
GCCAAGAACTCACTGTATCTGCAA
ATGAACAGCCTGAGAGCCGAGGAC
ACGGCCGTGTATTACTGTGCGAGA
GATCGGAACTCCCACTTTGACTATT
GGGGCCAGGGAACCCTGGTCACCG
TGTCCTCAGCAAGCACGAAGGGGC
CGTCCGTATTTCCGCTTGCGCCCTC
GTCGAAGTCAACTTCGGGAGGGAC
CGCGGCACTTGGCTGTCTTGTCAAA
GATTACTTCCCTGAGCCAGTGACA
GTCAGCTGGAATTCCGGTGCCCTCA
CGTCAGGAGTACATACATTCCCTGC
GGTATTGCAGTCCTCCGGACTCTAC
TCCCTGGAGTCGGTGGTAACGGTG
CCCAGCTCCAGCTTGGGGACCCAG
ACGTACATTTGTAACGTGAATCAC
AAACCAAGCAATACTAAGGTAGAT
AAGAAAGTAGAACCGAAGAGCTGC
(SEQ ID NO: 607)
AA
SYELTQPPSVSVSPGQTASITCSGERLG
DIQMTQSPSSVSASVGDRVTITCRAS
QVQLVESGGGLVKPGGSLRLSCAAS
NKYICWYQQKPGQSPVLVIYQDFKRPS
QGITRWLAWYQQKPGKAPKLLIYAA
EFTFSDYYMSWIRQAPGKGLEWVSY
GIPERFSGSNSGITATLTISGTQAMDEA
SVLQSGVPSRFSGSGSGTDFTLTISSL
ISRSGDTIYYADSVKGRFTISRDNAK
DYYCQAWDSRTVVFGGGTKLTVLGQP
QPEDFATYYCQQSNSFPRTFGQGTK
NSLYLQMNGLRAEDTAVYYCARDL
KAAPSVTLFPPSSEELQANKATLVCLIS
VEIKRTVAAPSVFIFPPSDEQLKSGTA
AAGATGGLDCWGQGTLVTVSSAST
DFYPGAVTVAWKADSSPVKAGVETTT
SVVCLLNNFYPREAKVQWKVDNAL
KGPSVFPLAPSSKSTSGGTAALGCLV
PSKQSNNKYAAESYLSLTPEQWKSHRS
QSGNSQESVTEQDSKDSTYSLKSTLT
KDYFPEPVTVSWNSGALTSGVHTFP
YSCQVTHEGSTVEKTVAPTECS
LSKADYEKHKVYACEVTHQGLSSPV
AVLQSSGLYSLKSVVTVPSSSLGTQT
(SEQ ID NO: 608)
TKSFNRGEC
YICNVNHKPSNTKVDKKVEPKSCDK
(SEQ ID NO: 609)
THTCPPCPAPELLGGPSVFLFPPKPKD
TLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPCEEQYGST
YRCVSVLTVLHQDWLNGKEYKCKV
SNKALPAPIEKTISKAKGQPREPQVY
TLPPSREEMTKNQVSLTCLVKGFYPS
DIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGS
GGGGSQVQLVESGGGLVKPGGSLRL
SCAASGFTFSDYYMTWIRQAPGKGL
EWISYISSSGSTIYYADSVKGRFTISR
DNAKNSLYLQMNSLRAEDTAVYYC
ARDRNSHFDYWGQGTLVTVSSASTK
GPSVFPLAPSSKSTSGGTAALGCLVK
DYFPEPVTVSWNSGALTSGVHTFPA
VLQSSGLYSLESVVTVPSSSLGTQTYI
CNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 610)
iPS:
21-
[hu anti-
NA
TCCTATGAGCTGACTCAGCCACCCTC
GACATCCAGATGACCCAGTCTCCA
CAGGTGCAGTTGGTGGAGTCTGGG
576372
230_37A6_IgG_
<hu CD40> 21-230_
AGTGTCCGTGTCCCCAGGACAGACA
TCTTCCGTGTCTGCTTCTGTCGGAG
GGAGGCTTAGTCAAGCCTGGAGGG
21-
37A6VH]::huIgG1zSEFL2*GK-
GCCAGCATCACCTGCTCTGGAGAAA
ACAGAGTCACCATCACTTGTCGGG
TCCCTGAGACTCTCCTGTGCAGCCT
233_6F4__Fab
K::(G4S)2::[hu anti-
GGTTGGGAAATAAATATATTTGCTGG
CGAGTCAGGATATTAGCAGGTGGT
CTGAATTCACCTTCAGTGACTACTA
<hu Mesothelin>
TATCAGCAGAAGCCAGGCCAGTCCC
TAGCCTGGTATCAGCAGAAACCAG
CATGAGCTGGATCCGCCAGGCTCC
6F4VH]::huIgG1z-
CTGTTCTGGTCATCTATCAAGATTTC
GGAAAGCCCCTAAGCTCCTGATTTC
AGGGAAGGGGCTGGAGTGGGTTTC
CH1-E::EPKSC + [anti-
AAGCGGCCCTCAGGGATCCCTGAGC
TGCTGCATCCAGATTGCAAAGTGG
ATATATTAGTCGAAGTGGTGATAC
<hu CD40>
GATTCTCTGGCTCCAACTCTGGGATC
AGTCCCATCAAGGTTCAGCGGCAG
CATCTACTACGCAGACTCTGTGAA
21-230_37A6VL]::huLLC2-
ACAGCCACTCTGACCATCAGCGGGA
TGGATCTGGGACAGATTTCACTCTC
GGGCCGATTCACCATCTCCAGGGA
E + [anti-
CCCAGGCTATGGATGAGGCTGACTAT
ACCATCAGCAGCCTGCAGCCTGAA
CAACGCCAAGAACTCACTGTATCT
<hu Mesothelin>
TACTGTCAGGCGTGGGACAGCAGAA
GATTTTGCAATTTACTATTGTCAAC
GCAAATGAATGGCCTGCGAGCCGA
6F4VL]::huKLC-
CTGTGGTATTCGGCGGAGGGACCAA
AGGCTAAAAGTTTTCCTCGGACGTT
AGACACGGCCGTGTATTACTGTGC
S176K (IgG-Fab);
GCTGACCGTCCTAGGTCAGCCCAAGG
CGGCCAAGGGACCAAGGTGGAAAT
GAGAGACTTAGCAGCAGGTGCTAC
LMRID: SS-30885
CTGCACCCTCGGTCACTCTGTTCCCG
CAAACGGACGGTGGCTGCACCATC
AGGGGGCCTTGACTGCTGGGGCCA
CCCTCCTCTGAGGAGCTTCAAGCCAA
TGTCTTCATCTTCCCGCCATCTGAT
GGGAACCCTGGTCACCGTGTCCTC
CAAGGCCACACTGGTGTGTCTCATCA
GAGCAGTTGAAATCTGGAACTGCC
AGCCTCCACCAAGGGCCCATCGGT
GTGACTTCTACCCGGGAGCCGTGACA
TCTGTTGTGTGCCTGCTGAATAACT
CTTCCCCCTGGCACCCTCCTCCAAG
GTGGCCTGGAAGGCAGATAGCAGCC
TCTATCCCAGAGAGGCCAAAGTAC
AGCACCTCTGGGGGCACAGCGGCC
CCGTCAAGGCGGGAGTGGAAACCAC
AGTGGAAGGTGGATAACGCCCTCC
CTGGGCTGCCTGGTCAAGGACTAC
CACACCCTCCAAACAAAGCAACAAC
AATCGGGTAACTCCCAGGAGAGTG
TTCCCCGAACCGGTGACGGTGTCGT
AAGTACGCGGCCGAAAGCTATCTGA
TCACAGAGCAGGACAGCAAGGACA
GGAACTCAGGCGCCCTGACCAGCG
GCCTGACGCCTGAGCAGTGGAAGTC
GCACCTACAGCCTCAAGAGCACCC
GCGTGCACACCTTCCCGGCTGTCCT
CCACAGAAGCTACAGCTGCCAGGTC
TGACGCTGAGCAAAGCAGACTACG
ACAGTCCTCAGGACTCTACTCCCTC
ACGCATGAAGGGAGCACCGTGGAGA
AGAAACACAAAGTCTACGCCTGCG
AAGAGCGTGGTGACCGTGCCCTCC
AGACAGTGGCCCCTACAGAATGTTCA
AAGTCACCCATCAGGGCCTGAGCT
AGCAGCTTGGGCACCCAGACCTAC
(SEQ ID NO: 611)
CGCCCGTCACAAAGAGCTTCAACA
ATCTGCAACGTGAATCACAAGCCC
GGGGAGAGTGT
AGCAACACCAAGGTGGACAAGAAA
(SEQ ID NO: 612)
GTTGAGCCCAAATCTTGTGACAAA
ACTCACACATGCCCACCGTGCCCA
GCACCTGAACTCCTGGGGGGACCG
TCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCC
GGACCCCTGAGGTCACATGCGTGG
TGGTGGACGTGAGCCACGAAGACC
CTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATG
CCAAGACAAAGCCGTGCGAGGAGC
AGTACGGCAGCACGTACCGTTGCG
TCAGCGTCCTCACCGTCCTGCACCA
GGACTGGCTGAATGGCAAGGAGTA
CAAGTGCAAGGTGTCCAACAAAGC
CCTCCCAGCCCCCATCGAGAAAAC
CATCTCCAAAGCCAAAGGGCAGCC
CCGAGAACCACAGGTGTACACCCT
GCCCCCATCCCGGGAGGAGATGAC
CAAGAACCAGGTCAGCCTGACCTG
CCTGGTCAAAGGCTTCTATCCCAGC
GACATCGCCGTGGAGTGGGAGAGC
AATGGGCAGCCGGAGAACAACTAC
AAGACCACGCCTCCCGTGCTGGAC
TCCGACGGCTCCTTCTTCCTCTATA
GCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCT
CATGCTCCGTGATGCATGAGGCTCT
GCACAACCACTACACGCAGAAGAG
CCTCTCCCTGTCTCCGGGTGGTGGC
GGATCGGGAGGTGGCGGATCCCAG
GTGCAGCTGGTGGAGTCTGGGGGA
GGCTTGGTCAAGCCTGGAGGGTCC
CTGAGACTCTCCTGTGCAGCCTCTG
GATTCACCTTCAGTGACTACTACAT
GAGCTGGATCCGCCAGGCTCCAGG
GAAGGGGCTGGAGTGGATTTCATA
CATTAGTAGCAGTGAAAGTATCAT
CTATTACGTAGACTCTGTGAAGGG
CCGATTCACCATCTCCAGGGACAA
CGCCAAGAACTCACTGTATCTGCA
AATGAACAGCCTGAGAGCCGAGGA
CACGGCCGTGTATTACTGTGCGAG
AGATGTTGGGAGCCACTTTGACTA
CTGGGGCCAGGGAACCCTGGTCAC
CGTGTCCTCAGCAAGCACGAAGGG
GCCGTCCGTATTTCCGCTTGCGCCC
TCGTCGAAGTCAACTTCGGGAGGG
ACCGCGGCACTTGGCTGTCTTGTCA
AAGATTACTTCCCTGAGCCAGTGA
CAGTCAGCTGGAATTCCGGTGCCCT
CACGTCAGGAGTACATACATTCCCT
GCGGTATTGCAGTCCTCCGGACTCT
ACTCCCTGGAGTCGGTGGTAACGG
TGCCCAGCTCCAGCTTGGGGACCC
AGACGTACATTTGTAACGTGAATC
ACAAACCAAGCAATACTAAGGTAG
ATAAGAAAGTAGAACCGAAGAGCT
GC
(SEQ ID NO: 613)
AA
SYELTQPPSVSVSPGQTASITCSGERLG
DIQMTQSPSSVSASVGDRVTITCRAS
QVQLVESGGGLVKPGGSLRLSCAAS
NKYICWYQQKPGQSPVLVIYQDFKRPS
QDISRWLAWYQQKPGKAPKLLISAA
EFTFSDYYMSWIRQAPGKGLEWVSY
GIPERFSGSNSGITATLTISGTQAMDEA
SRLQSGVPSRFSGSGSGTDFTLTISSL
ISRSGDTIYYADSVKGRFTISRDNAK
DYYCQAWDSRTVVFGGGTKLTVLGQP
QPEDFAIYYCQQAKSFPRTFGQGTKV
NSLYLQMNGLRAEDTAVYYCARDL
KAAPSVTLFPPSSEELQANKATLVCLIS
EIKRTVAAPSVFIFPPSDEQLKSGTAS
AAGATGGLDCWGQGTLVTVSSAST
DFYPGAVTVAWKADSSPVKAGVETTT
VVCLLNNFYPREAKVQWKVDNALQ
KGPSVFPLAPSSKSTSGGTAALGCLV
PSKQSNNKYAAESYLSLTPEQWKSHRS
SGNSQESVTEQDSKDSTYSLKSTLTL
KDYFPEPVTVSWNSGALTSGVHTFP
YSCQVTHEGSTVEKTVAPTECS
SKADYEKHKVYACEVTHQGLSSPVT
AVLQSSGLYSLKSVVTVPSSSLGTQT
(SEQ ID NO: 614)
KSFNRGEC
YICNVNHKPSNTKVDKKVEPKSCDK
(SEQ ID NO: 615)
THTCPPCPAPELLGGPSVFLFPPKPKD
TLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPCEEQYGST
YRCVSVLTVLHQDWLNGKEYKCKV
SNKALPAPIEKTISKAKGQPREPQVY
TLPPSREEMTKNQVSLTCLVKGFYPS
DIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGS
GGGGSQVQLVESGGGLVKPGGSLRL
SCAASGFTFSDYYMSWIRQAPGKGL
EWISYISSSESIIYYVDSVKGRFTISRD
NAKNSLYLQMNSLRAEDTAVYYCA
RDVGSHFDYWGQGTLVTVSSASTKG
PSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAV
LQSSGLYSLESVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 616)
iPS:
21-
[hu anti-
NA
TCCTATGAGCTGACTCAGCCACCCTC
GACATTGTGATGACTCAGTCTCCAG
CAGGTGCAGTTGGTGGAGTCTGGG
576375
230_37A6_IgG_
<hu CD40> 21-230_
AGTGTCCGTGTCCCCAGGACAGACA
ACTCCCTGGCTGTGTCTCTGGGCGA
GGAGGCTTAGTCAAGCCTGGAGGG
21-
37A6VH]::huIgG1zSEFL2*GK-
GCCAGCATCACCTGCTCTGGAGAAA
GAGGGCCACCATCAACTGCAAGTC
TCCCTGAGACTCTCCTGTGCAGCCT
233_7G11__Fab
K::(G4S)2::[hu anti-
GGTTGGGAAATAAATATATTTGCTGG
CAGCCAGAGTGTTTTATACAGCTCC
CTGAATTCACCTTCAGTGACTACTA
<hu Mesothelin>
TATCAGCAGAAGCCAGGCCAGTCCC
AACAATAAGAACTACTTAGCTTGG
CATGAGCTGGATCCGCCAGGCTCC
7G11VH]::huIgG1z-
CTGTTCTGGTCATCTATCAAGATTTC
TACCAGCAGAAACCAGGACAGCCT
AGGGAAGGGGCTGGAGTGGGTTTC
CH1-E::EPKSC + [anti-
AAGCGGCCCTCAGGGATCCCTGAGC
CCTAAGCTGCTCATTTACTGGGCAT
ATATATTAGTCGAAGTGGTGATAC
<hu CD40>
GATTCTCTGGCTCCAACTCTGGGATC
CTACCCGAGAATCCGGGGTCCCTG
CATCTACTACGCAGACTCTGTGAA
21-230_37A6VL]::huLLC2-
ACAGCCACTCTGACCATCAGCGGGA
ACCGATTCAGTGGCAGCGGGTCTG
GGGCCGATTCACCATCTCCAGGGA
E + [anti-
CCCAGGCTATGGATGAGGCTGACTAT
GGACAGATTTCACTCTCACCATCAG
CAACGCCAAGAACTCACTGTATCT
<hu Mesothelin>
TACTGTCAGGCGTGGGACAGCAGAA
CAGCCTGCAGGCTGAAGATGTGGC
GCAAATGAATGGCCTGCGAGCCGA
7G11VL]::huKLC-
CTGTGGTATTCGGCGGAGGGACCAA
AGTTTATTACTGTCAGCAATATTAT
AGACACGGCCGTGTATTACTGTGC
S176K (IgG-Fab);
GCTGACCGTCCTAGGTCAGCCCAAGG
AGTACTCCTCCGACGTTCGGCCAA
GAGAGACTTAGCAGCAGGTGCTAC
LMRID: SS-30886
CTGCACCCTCGGTCACTCTGTTCCCG
GGGACCAAGGTGGAGATCAAACGG
AGGGGGCCTTGACTGCTGGGGCCA
CCCTCCTCTGAGGAGCTTCAAGCCAA
ACGGTGGCTGCACCATCTGTCTTCA
GGGAACCCTGGTCACCGTGTCCTC
CAAGGCCACACTGGTGTGTCTCATCA
TCTTCCCGCCATCTGATGAGCAGTT
AGCCTCCACCAAGGGCCCATCGGT
GTGACTTCTACCCGGGAGCCGTGACA
GAAATCTGGAACTGCCTCTGTTGTG
CTTCCCCCTGGCACCCTCCTCCAAG
GTGGCCTGGAAGGCAGATAGCAGCC
TGCCTGCTGAATAACTTCTATCCCA
AGCACCTCTGGGGGCACAGCGGCC
CCGTCAAGGCGGGAGTGGAAACCAC
GAGAGGCCAAAGTACAGTGGAAGG
CTGGGCTGCCTGGTCAAGGACTAC
CACACCCTCCAAACAAAGCAACAAC
TGGATAACGCCCTCCAATCGGGTA
TTCCCCGAACCGGTGACGGTGTCGT
AAGTACGCGGCCGAAAGCTATCTGA
ACTCCCAGGAGAGTGTCACAGAGC
GGAACTCAGGCGCCCTGACCAGCG
GCCTGACGCCTGAGCAGTGGAAGTC
AGGACAGCAAGGACAGCACCTACA
GCGTGCACACCTTCCCGGCTGTCCT
CCACAGAAGCTACAGCTGCCAGGTC
GCCTCAAGAGCACCCTGACGCTGA
ACAGTCCTCAGGACTCTACTCCCTC
ACGCATGAAGGGAGCACCGTGGAGA
GCAAAGCAGACTACGAGAAACACA
AAGAGCGTGGTGACCGTGCCCTCC
AGACAGTGGCCCCTACAGAATGTTCA
AAGTCTACGCCTGCGAAGTCACCC
AGCAGCTTGGGCACCCAGACCTAC
(SEQ ID NO: 617)
ATCAGGGCCTGAGCTCGCCCGTCA
ATCTGCAACGTGAATCACAAGCCC
CAAAGAGCTTCAACAGGGGAGAGT
AGCAACACCAAGGTGGACAAGAAA
GT
GTTGAGCCCAAATCTTGTGACAAA
(SEQ ID NO: 618)
ACTCACACATGCCCACCGTGCCCA
GCACCTGAACTCCTGGGGGGACCG
TCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCC
GGACCCCTGAGGTCACATGCGTGG
TGGTGGACGTGAGCCACGAAGACC
CTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATG
CCAAGACAAAGCCGTGCGAGGAGC
AGTACGGCAGCACGTACCGTTGCG
TCAGCGTCCTCACCGTCCTGCACCA
GGACTGGCTGAATGGCAAGGAGTA
CAAGTGCAAGGTGTCCAACAAAGC
CCTCCCAGCCCCCATCGAGAAAAC
CATCTCCAAAGCCAAAGGGCAGCC
CCGAGAACCACAGGTGTACACCCT
GCCCCCATCCCGGGAGGAGATGAC
CAAGAACCAGGTCAGCCTGACCTG
CCTGGTCAAAGGCTTCTATCCCAGC
GACATCGCCGTGGAGTGGGAGAGC
AATGGGCAGCCGGAGAACAACTAC
AAGACCACGCCTCCCGTGCTGGAC
TCCGACGGCTCCTTCTTCCTCTATA
GCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCT
CATGCTCCGTGATGCATGAGGCTCT
GCACAACCACTACACGCAGAAGAG
CCTCTCCCTGTCTCCGGGTGGTGGC
GGATCGGGAGGTGGCGGATCCGAG
GTGCAGCTGGTCGAGTCTGGAGGA
GGCTTGATCCAGCCTGGGGGGTCC
CTGAGACTCTCCTGTGCAGTCTCTG
GGTTCACCGTCAGTAGCAAGTTCAT
GACCTGGGTCCGCCAGGCTCCAGG
GAAGGGGCTGGAGTGGGTGTCAGT
TATTTATAGCGGTGGTAAGACATA
CTACGCAGACTCCGTGAAGGGCCG
ATTCACCATCTCCAGAGACAATTCC
AAGAACACGCTGTATCTTCAAATG
AACAGCCTGAGAGCCGAGGACACG
GCCGTGTATTACTGTGCGAGAGAT
AGCGGTGGCTGGGGGTACTTTGAC
TACTGGGGCCAGGGAACCCTGGTC
ACCGTGTCCTCAGCAAGCACGAAG
GGGCCGTCCGTATTTCCGCTTGCGC
CCTCGTCGAAGTCAACTTCGGGAG
GGACCGCGGCACTTGGCTGTCTTGT
CAAAGATTACTTCCCTGAGCCAGT
GACAGTCAGCTGGAATTCCGGTGC
CCTCACGTCAGGAGTACATACATTC
CCTGCGGTATTGCAGTCCTCCGGAC
TCTACTCCCTGGAGTCGGTGGTAAC
GGTGCCCAGCTCCAGCTTGGGGAC
CCAGACGTACATTTGTAACGTGAA
TCACAAACCAAGCAATACTAAGGT
AGATAAGAAAGTAGAACCGAAGA
GCTGC
(SEQ ID NO: 619)
AA
SYELTQPPSVSVSPGQTASITCSGERLG
DIVMTQSPDSLAVSLGERATINCKSS
QVQLVESGGGLVKPGGSLRLSCAAS
NKYICWYQQKPGQSPVLVIYQDFKRPS
QSVLYSSNNKNYLAWYQQKPGQPP
EFTFSDYYMSWIRQAPGKGLEWVSY
GIPERFSGSNSGITATLTISGTQAMDEA
KLLIYWASTRESGVPDRFSGSGSGTD
ISRSGDTIYYADSVKGRFTISRDNAK
DYYCQAWDSRTVVFGGGTKLTVLGQP
FTLTISSLQAEDVAVYYCQQYYSTPP
NSLYLQMNGLRAEDTAVYYCARDL
KAAPSVTLFPPSSEELQANKATLVCLIS
TFGQGTKVEIKRTVAAPSVFIFPPSDE
AAGATGGLDCWGQGTLVTVSSAST
DFYPGAVTVAWKADSSPVKAGVETTT
QLKSGTASVVCLLNNFYPREAKVQW
KGPSVFPLAPSSKSTSGGTAALGCLV
PSKQSNNKYAAESYLSLTPEQWKSHRS
KVDNALQSGNSQESVTEQDSKDSTY
KDYFPEPVTVSWNSGALTSGVHTFP
YSCQVTHEGSTVEKTVAPTECS
SLKSTLTLSKADYEKHKVYACEVTH
AVLQSSGLYSLKSVVTVPSSSLGTQT
(SEQ ID NO: 620)
QGLSSPVTKSFNRGEC
YICNVNHKPSNTKVDKKVEPKSCDK
(SEQ ID NO: 621)
THTCPPCPAPELLGGPSVFLFPPKPKD
TLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPCEEQYGST
YRCVSVLTVLHQDWLNGKEYKCKV
SNKALPAPIEKTISKAKGQPREPQVY
TLPPSREEMTKNQVSLTCLVKGFYPS
DIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGS
GGGGSEVQLVESGGGLIQPGGSLRLS
CAVSGFTVSSKFMTWVRQAPGKGLE
WVSVIYSGGKTYYADSVKGRFTISR
DNSKNTLYLQMNSLRAEDTAVYYC
ARDSGGWGYFDYWGQGTLVTVSSA
STKGPSVFPLAPSSKSTSGGTAALGC
LVKDYFPEPVTVSWNSGALTSGVHT
FPAVLQSSGLYSLESVVTVPSSSLGT
QTYICNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 622)
iPS:
21-
[hu anti-
NA
CAGTCTGCCCTGACTCAGCCTGCCTC
CAGTCAGTGTTGACGCAGCCGCCC
CAGGTGCAGCTGGTGCAGTCTGGG
576378
230_392_IgG_
<hu CD40> 21-230_
CGTGTCTGGGAGCCCTGGACAGTCGA
TCAGTGTCTGGGGCCCCAGGGCAG
ACTGAGGTGAAGAAGCCTGGGGCC
21-
39C2VH]::huIgG1zSEFL2*GK-
TCACCATCTCCTGCACTGGAACCAGC
AGGGTCACCATCTCCTGCACTGGG
TCAGTGAAGGTGTCCTGCAAGGCT
233_4G12__Fab
K::(G4S)2::[hu anti-
AGTGATGTTGGGAATTATAACCTTGT
AGCAGCTCCAACATCGGGGCAGGT
TCTGGATACACCTTCCCCGGCTACT
<hu Mesothelin>
CTCCTGGTACCAACAGCACCCAGGCA
TATGATGTTCACTGGTACCAGCAG
ATATGCACTGGGTGCGACAGGCCC
4G12VH]::huIgG1z-
AAGCCCCCAAACTCATGATTTATGAG
GTTCCAGGAACAGCCCCCAAACTC
CTGGACAGGGGCTTGAGTGGATGG
CH1-E::EPKSC + [anti-
GTCAATAGGCGGCCCTCAGGGGTTTC
CTCATCTATGGTAACAGCAAGCGG
GATGGATCAACCCTGACAGTGGTG
<hu CD40>
TAATCGCTTCTCTGGCTCCAAGTCTG
CCCTCAGGGGTCCCTGACCGATTCT
GCACAAAGTATACACAGAAGTTTC
21-230_39C2VL]::huLLC2-
GCAACACGGCCTCCCTGACAATCTCT
CTGGCTCCAAGTCTGGCACCTCAGC
AGGGCAGGGTCACCTTGACCAGGG
E + [anti-
GGGCTCCAGGCTGAGGACGAGGCTG
CTCCCTGGCCATCACTGGGCTCCAG
ACGCGTCCGTCAGCACAGCCTACA
<hu Mesothelin>
AATATTACTGCTGCTCATATGCAGGT
GCTGAGGATGAGGCTGATTATTAC
TTGACCTGAACAGGCTGAGATCTG
4G12VL]::huLLC-
AGAGACACTTTCGTGGTGTTCGGCGG
TGCCAGTCCTATGACAGCAGCCTG
ACGACACGGCCGTATATTACTGTG
K (IgG-Fab);
AGGGACCAAGCTGACCGTCCTAGGT
GGTGGTTGGGTGTTCGGCGGAGGG
CGAGAGAGAGGTGTAGGACTACCA
LMRID: SS-30887
CAGCCCAAGGCTGCACCCTCGGTCAC
ACCAAGCTGACCGTCCTACAGCCC
ACTGCTATTTGGACTACTGGGGCCA
TCTGTTCCCGCCCTCCTCTGAGGAGC
AAGGCTGCACCCTCGGTCACTCTGT
GGGAAGTCTGGTCACCGTGTCCTC
TTCAAGCCAACAAGGCCACACTGGT
TCCCGCCCTCCTCTGAGGAGCTTCA
AGCCTCCACCAAGGGCCCATCGGT
GTGTCTCATCAGTGACTTCTACCCGG
AGCCAACAAGGCCACACTGGTGTG
CTTCCCCCTGGCACCCTCCTCCAAG
GAGCCGTGACAGTGGCCTGGAAGGC
TCTCATCAGTGACTTCTACCCGGGA
AGCACCTCTGGGGGCACAGCGGCC
AGATAGCAGCCCCGTCAAGGCGGGA
GCCGTGACAGTGGCCTGGAAGGCA
CTGGGCTGCCTGGTCAAGGACTAC
GTGGAAACCACCACACCCTCCAAAC
GATAGCAGCCCCGTCAAGGCGGGA
TTCCCCGAACCGGTGACGGTGTCGT
AAAGCAACAACAAGTACGCGGCCGA
GTGGAAACCACCACACCCTCCAAA
GGAACTCAGGCGCCCTGACCAGCG
AAGCTATCTGAGCCTGACGCCTGAGC
CAAAGCAACAACAAGTACGCGGCC
GCGTGCACACCTTCCCGGCTGTCCT
AGTGGAAGTCCCACAGAAGCTACAG
AAGAGCTATCTGAGCCTGACGCCT
ACAGTCCTCAGGACTCTACTCCCTC
CTGCCAGGTCACGCATGAAGGGAGC
GAGCAGTGGAAGTCCCACAGAAGC
AAGAGCGTGGTGACCGTGCCCTCC
ACCGTGGAGAAGACAGTGGCCCCTA
TACAGCTGCCAGGTCACGCATGAA
AGCAGCTTGGGCACCCAGACCTAC
CAGAATGTTCA
GGGAGCACCGTGGAGAAGACAGTG
ATCTGCAACGTGAATCACAAGCCC
(SEQ ID NO: 623)
GCCCCTACAGAATGTTCA
AGCAACACCAAGGTGGACAAGAAA
(SEQ ID NO: 624)
GTTGAGCCCAAATCTTGTGACAAA
ACTCACACATGCCCACCGTGCCCA
GCACCTGAACTCCTGGGGGGACCG
TCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCC
GGACCCCTGAGGTCACATGCGTGG
TGGTGGACGTGAGCCACGAAGACC
CTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATG
CCAAGACAAAGCCGTGCGAGGAGC
AGTACGGCAGCACGTACCGTTGCG
TCAGCGTCCTCACCGTCCTGCACCA
GGACTGGCTGAATGGCAAGGAGTA
CAAGTGCAAGGTGTCCAACAAAGC
CCTCCCAGCCCCCATCGAGAAAAC
CATCTCCAAAGCCAAAGGGCAGCC
CCGAGAACCACAGGTGTACACCCT
GCCCCCATCCCGGGAGGAGATGAC
CAAGAACCAGGTCAGCCTGACCTG
CCTGGTCAAAGGCTTCTATCCCAGC
GACATCGCCGTGGAGTGGGAGAGC
AATGGGCAGCCGGAGAACAACTAC
AAGACCACGCCTCCCGTGCTGGAC
TCCGACGGCTCCTTCTTCCTCTATA
GCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCT
CATGCTCCGTGATGCATGAGGCTCT
GCACAACCACTACACGCAGAAGAG
CCTCTCCCTGTCTCCGGGTGGTGGC
GGATCGGGAGGTGGCGGATCCCAG
GTGCAGCTGCAGGAGTCGGGCCCA
GGACTGGTGAAGCCTTCGGAAACC
CTGTCCCTCACCTGCACTGTCTCTG
GTGGCTCCATCAGCAGTAGTAGTT
ACTACTGGGGCTGGATCAGGCAGC
CCCCAGGGAAGGGGCTGGAGTGGA
TTGGGAGTATCTATTATAGTGGGAT
CACCAACTACAACCCGTCCCTCAA
GAGTCGAGTCACCATCTCCGTAGA
CACGTCCAAGAACCAGTTCTCCCTG
AAGCTGAGTTCTGTGACCGCCGCA
GACACGGCCGTGTATTACTGTGCG
AGATCCAGTAACTACGATGCTTTTG
ATATCTGGGGCCAAGGGACAATGG
TCACCGTGTCCTCAGCAAGCACGA
AGGGGCCGTCCGTATTTCCGCTTGC
GCCCTCGTCGAAGTCAACTTCGGG
AGGGACCGCGGCACTTGGCTGTCT
TGTCAAAGATTACTTCCCTGAGCCA
GTGACAGTCAGCTGGAATTCCGGT
GCCCTCACGTCAGGAGTACATACA
TTCCCTGCGGTATTGCAGTCCTCCG
GACTCTACTCCCTGGAGTCGGTGGT
AACGGTGCCCAGCTCCAGCTTGGG
GACCCAGACGTACATTTGTAACGT
GAATCACAAACCAAGCAATACTAA
GGTAGATAAGAAAGTAGAACCGAA
GAGCTGC
(SEQ ID NO: 625)
AA
QSALTQPASVSGSPGQSITISCTGTSSD
QSVLTQPPSVSGAPGQRVTISCTGSSS
QVQLVQSGTEVKKPGASVKVSCKAS
VGNYNLVSWYQQHPGKAPKLMIYEV
NIGAGYDVHWYQQVPGTAPKLLIYG
GYTFPGYYMHWVRQAPGQGLEWM
NRRPSGVSNRFSGSKSGNTASLTISGLQ
NSKRPSGVPDRFSGSKSGTSASLAIT
GWINPDSGGTKYTQKFQGRVTLTRD
AEDEAEYYCCSYAGRDTFVVFGGGTK
GLQAEDEADYYCQSYDSSLGGWVF
ASVSTAYIDLNRLRSDDTAVYYCAR
LTVLGQPKAAPSVTLFPPSSEELQANK
GGGTKLTVLQPKAAPSVTLFPPSSEE
ERCRTTNCYLDYWGQGSLVTVSSAS
ATLVCLISDFYPGAVTVAWKADSSPVK
LQANKATLVCLISDFYPGAVTVAWK
TKGPSVFPLAPSSKSTSGGTAALGCL
AGVETTTPSKQSNNKYAAESYLSLTPE
ADSSPVKAGVETTTPSKQSNNKYAA
VKDYFPEPVTVSWNSGALTSGVHTF
QWKSHRSYSCQVTHEGSTVEKTVAPT
KSYLSLTPEQWKSHRSYSCQVTHEG
PAVLQSSGLYSLKSVVTVPSSSLGTQ
ECS
STVEKTVAPTECS
TYICNVNHKPSNTKVDKKVEPKSCD
(SEQ ID NO: 626)
(SEQ ID NO: 627)
KTHTCPPCPAPELLGGPSVFLFPPKPK
DTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPCEEQYG
STYRCVSVLTVLHQDWLNGKEYKC
KVSNKALPAPIEKTISKAKGQPREPQ
VYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVL
DSDGSFFLYSKLTVDKSRWQQGNVF
SCSVMHEALHNHYTQKSLSLSPGGG
GSGGGGSQVQLQESGPGLVKPSETLS
LTCTVSGGSISSSSYYWGWIRQPPGK
GLEWIGSIYYSGITNYNPSLKSRVTIS
VDTSKNQFSLKLSSVTAADTAVYYC
ARSSNYDAFDIWGQGTMVTVSSAST
KGPSVFPLAPSSKSTSGGTAALGCLV
KDYFPEPVTVSWNSGALTSGVHTFP
AVLQSSGLYSLESVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 628)
iPS:
21-
[hu anti-
NA
CAGTCTGCCCTGACTCAGCCTGCCTC
GACATTCAGATGACCCAGTCTCCAT
CAGGTGCAGCTGGTGCAGTCTGGG
576383
230_392_IgG_
<hu CD40> 21-230_
CGTGTCTGGGAGCCCTGGACAGTCGA
CTTCCGTGTCTGCATCTGTAGGGGA
ACTGAGGTGAAGAAGCCTGGGGCC
21-
39C2VH]::huIgG1zSEFL2*GK-
TCACCATCTCCTGCACTGGAACCAGC
CAGAGTCACCATCACTTGTCGGGC
TCAGTGAAGGTGTCCTGCAAGGCT
233_4H6__Fab
K::(G4S)2::[hu
AGTGATGTTGGGAATTATAACCTTGT
GAGTCAGGGTATTACCAGGTGGTT
TCTGGATACACCTTCCCCGGCTACT
anti-<hu Mesothelin>
CTCCTGGTACCAACAGCACCCAGGCA
AGCCTGGTATCAGCAGAAACCAGG
ATATGCACTGGGTGCGACAGGCCC
4H6VH]::huIgG1z-
AAGCCCCCAAACTCATGATTTATGAG
GAAAGCCCCTAAGCTCCTGATCTAT
CTGGACAGGGGCTTGAGTGGATGG
CH1-E::EPKSC + [anti-
GTCAATAGGCGGCCCTCAGGGGTTTC
GCTGCATCCGTTTTGCAAAGTGGG
GATGGATCAACCCTGACAGTGGTG
<hu CD40>
TAATCGCTTCTCTGGCTCCAAGTCTG
GTCCCATCAAGGTTCAGCGGCAGT
GCACAAAGTATACACAGAAGTTTC
21-230_39C2VL]::huLLC2-
GCAACACGGCCTCCCTGACAATCTCT
GGATCTGGGACAGATTTCACTCTCA
AGGGCAGGGTCACCTTGACCAGGG
E + [anti-
GGGCTCCAGGCTGAGGACGAGGCTG
CCATCAGCAGCCTGCAGCCTGAAG
ACGCGTCCGTCAGCACAGCCTACA
<hu Mesothelin>
AATATTACTGCTGCTCATATGCAGGT
ATTTTGCAACTTACTATTGTCAACA
TTGACCTGAACAGGCTGAGATCTG
4H6VL]::huKLC-
AGAGACACTTTCGTGGTGTTCGGCGG
GTCTAACAGTTTCCCTCGGACGTTC
ACGACACGGCCGTATATTACTGTG
S176K (IgG-Fab);
AGGGACCAAGCTGACCGTCCTAGGT
GGCCAAGGGACCAAGGTGGAAATC
CGAGAGAGAGGTGTAGGACTACCA
LMRID: SS-30888
CAGCCCAAGGCTGCACCCTCGGTCAC
AAACGGACGGTGGCTGCACCATCT
ACTGCTATTTGGACTACTGGGGCCA
TCTGTTCCCGCCCTCCTCTGAGGAGC
GTCTTCATCTTCCCGCCATCTGATG
GGGAAGTCTGGTCACCGTGTCCTC
TTCAAGCCAACAAGGCCACACTGGT
AGCAGTTGAAATCTGGAACTGCCT
AGCCTCCACCAAGGGCCCATCGGT
GTGTCTCATCAGTGACTTCTACCCGG
CTGTTGTGTGCCTGCTGAATAACTT
CTTCCCCCTGGCACCCTCCTCCAAG
GAGCCGTGACAGTGGCCTGGAAGGC
CTATCCCAGAGAGGCCAAAGTACA
AGCACCTCTGGGGGCACAGCGGCC
AGATAGCAGCCCCGTCAAGGCGGGA
GTGGAAGGTGGATAACGCCCTCCA
CTGGGCTGCCTGGTCAAGGACTAC
GTGGAAACCACCACACCCTCCAAAC
ATCGGGTAACTCCCAGGAGAGTGT
TTCCCCGAACCGGTGACGGTGTCGT
AAAGCAACAACAAGTACGCGGCCGA
CACAGAGCAGGACAGCAAGGACA
GGAACTCAGGCGCCCTGACCAGCG
AAGCTATCTGAGCCTGACGCCTGAGC
GCACCTACAGCCTCAAGAGCACCC
GCGTGCACACCTTCCCGGCTGTCCT
AGTGGAAGTCCCACAGAAGCTACAG
TGACGCTGAGCAAAGCAGACTACG
ACAGTCCTCAGGACTCTACTCCCTC
CTGCCAGGTCACGCATGAAGGGAGC
AGAAACACAAAGTCTACGCCTGCG
AAGAGCGTGGTGACCGTGCCCTCC
ACCGTGGAGAAGACAGTGGCCCCTA
AAGTCACCCATCAGGGCCTGAGCT
AGCAGCTTGGGCACCCAGACCTAC
CAGAATGTTCA
CGCCCGTCACAAAGAGCTTCAACA
ATCTGCAACGTGAATCACAAGCCC
(SEQ ID NO: 629)
GGGGAGAGTGT
AGCAACACCAAGGTGGACAAGAAA
(SEQ ID NO: 630)
GTTGAGCCCAAATCTTGTGACAAA
ACTCACACATGCCCACCGTGCCCA
GCACCTGAACTCCTGGGGGGACCG
TCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCC
GGACCCCTGAGGTCACATGCGTGG
TGGTGGACGTGAGCCACGAAGACC
CTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATG
CCAAGACAAAGCCGTGCGAGGAGC
AGTACGGCAGCACGTACCGTTGCG
TCAGCGTCCTCACCGTCCTGCACCA
GGACTGGCTGAATGGCAAGGAGTA
CAAGTGCAAGGTGTCCAACAAAGC
CCTCCCAGCCCCCATCGAGAAAAC
CATCTCCAAAGCCAAAGGGCAGCC
CCGAGAACCACAGGTGTACACCCT
GCCCCCATCCCGGGAGGAGATGAC
CAAGAACCAGGTCAGCCTGACCTG
CCTGGTCAAAGGCTTCTATCCCAGC
GACATCGCCGTGGAGTGGGAGAGC
AATGGGCAGCCGGAGAACAACTAC
AAGACCACGCCTCCCGTGCTGGAC
TCCGACGGCTCCTTCTTCCTCTATA
GCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCT
CATGCTCCGTGATGCATGAGGCTCT
GCACAACCACTACACGCAGAAGAG
CCTCTCCCTGTCTCCGGGTGGTGGC
GGATCGGGAGGTGGCGGATCCCAG
GTGCAGCTGGTCGAGTCTGGGGGA
GGCTTGGTCAAGCCTGGAGGGTCC
CTGAGACTCTCCTGTGCAGCCTCTG
GATTCACCTTCAGTGACTACTACAT
GACCTGGATCAGGCAGGCTCCAGG
GAAGGGGCTGGAGTGGATTTCATA
CATTAGTAGTAGTGGTAGTACCATC
TACTACGCAGACTCTGTGAAGGGC
CGATTCACCATCTCCAGGGACAAC
GCCAAGAACTCACTGTATCTGCAA
ATGAACAGCCTGAGAGCCGAGGAC
ACGGCCGTGTATTACTGTGCGAGA
GATCGGAACTCCCACTTTGACTATT
GGGGCCAGGGAACCCTGGTCACCG
TGTCCTCAGCAAGCACGAAGGGGC
CGTCCGTATTTCCGCTTGCGCCCTC
GTCGAAGTCAACTTCGGGAGGGAC
CGCGGCACTTGGCTGTCTTGTCAAA
GATTACTTCCCTGAGCCAGTGACA
GTCAGCTGGAATTCCGGTGCCCTCA
CGTCAGGAGTACATACATTCCCTGC
GGTATTGCAGTCCTCCGGACTCTAC
TCCCTGGAGTCGGTGGTAACGGTG
CCCAGCTCCAGCTTGGGGACCCAG
ACGTACATTTGTAACGTGAATCAC
AAACCAAGCAATACTAAGGTAGAT
AAGAAAGTAGAACCGAAGAGCTGC
(SEQ ID NO: 631)
AA
QSALTQPASVSGSPGQSITISCTGTSSD
DIQMTQSPSSVSASVGDRVTITCRAS
QVQLVQSGTEVKKPGASVKVSCKAS
VGNYNLVSWYQQHPGKAPKLMIYEV
QGITRWLAWYQQKPGKAPKLLIYAA
GYTFPGYYMHWVRQAPGQGLEWM
NRRPSGVSNRFSGSKSGNTASLTISGLQ
SVLQSGVPSRFSGSGSGTDFTLTISSL
GWINPDSGGTKYTQKFQGRVTLTRD
AEDEAEYYCCSYAGRDTFVVFGGGTK
QPEDFATYYCQQSNSFPRTFGQGTK
ASVSTAYIDLNRLRSDDTAVYYCAR
LTVLGQPKAAPSVTLFPPSSEELQANK
VEIKRTVAAPSVFIFPPSDEQLKSGTA
ERCRTTNCYLDYWGQGSLVTVSSAS
ATLVCLISDFYPGAVTVAWKADSSPVK
SVVCLLNNFYPREAKVQWKVDNAL
TKGPSVFPLAPSSKSTSGGTAALGCL
AGVETTTPSKQSNNKYAAESYLSLTPE
QSGNSQESVTEQDSKDSTYSLKSTLT
VKDYFPEPVTVSWNSGALTSGVHTF
QWKSHRSYSCQVTHEGSTVEKTVAPT
LSKADYEKHKVYACEVTHQGLSSPV
PAVLQSSGLYSLKSVVTVPSSSLGTQ
ECS
TKSFNRGEC
TYICNVNHKPSNTKVDKKVEPKSCD
(SEQ ID NO: 632)
(SEQ ID NO: 633)
KTHTCPPCPAPELLGGPSVFLFPPKPK
DTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPCEEQYG
STYRCVSVLTVLHQDWLNGKEYKC
KVSNKALPAPIEKTISKAKGQPREPQ
VYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVL
DSDGSFFLYSKLTVDKSRWQQGNVF
SCSVMHEALHNHYTQKSLSLSPGGG
GSGGGGSQVQLVESGGGLVKPGGSL
RLSCAASGFTFSDYYMTWIRQAPGK
GLEWISYISSSGSTIYYADSVKGRFTI
SRDNAKNSLYLQMNSLRAEDTAVY
YCARDRNSHFDYWGQGTLVTVSSAS
TKGPSVFPLAPSSKSTSGGTAALGCL
VKDYFPEPVTVSWNSGALTSGVHTF
PAVLQSSGLYSLESVVTVPSSSLGTQ
TYICNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 634)
iPS:
21-
[hu anti-
NA
CAGTCTGCCCTGACTCAGCCTGCCTC
GACATCCAGATGACCCAGTCTCCA
CAGGTGCAGCTGGTGCAGTCTGGG
576386
230_392_IgG_
<hu CD40> 21-230_
CGTGTCTGGGAGCCCTGGACAGTCGA
TCTTCCGTGTCTGCTTCTGTCGGAG
ACTGAGGTGAAGAAGCCTGGGGCC
21-
39C2VH]::huIgG1zSEFL2*GK-
TCACCATCTCCTGCACTGGAACCAGC
ACAGAGTCACCATCACTTGTCGGG
TCAGTGAAGGTGTCCTGCAAGGCT
233_6F4__Fab
K::(G4S)2::[hu
AGTGATGTTGGGAATTATAACCTTGT
CGAGTCAGGATATTAGCAGGTGGT
TCTGGATACACCTTCCCCGGCTACT
anti-<hu Mesothelin>
CTCCTGGTACCAACAGCACCCAGGCA
TAGCCTGGTATCAGCAGAAACCAG
ATATGCACTGGGTGCGACAGGCCC
6F4VH]::huIgG1z-
AAGCCCCCAAACTCATGATTTATGAG
GGAAAGCCCCTAAGCTCCTGATTTC
CTGGACAGGGGCTTGAGTGGATGG
CH1-E::EPKSC + [anti-
GTCAATAGGCGGCCCTCAGGGGTTTC
TGCTGCATCCAGATTGCAAAGTGG
GATGGATCAACCCTGACAGTGGTG
<hu CD40>
TAATCGCTTCTCTGGCTCCAAGTCTG
AGTCCCATCAAGGTTCAGCGGCAG
GCACAAAGTATACACAGAAGTTTC
21-230_39C2VL]::huLLC2-
GCAACACGGCCTCCCTGACAATCTCT
TGGATCTGGGACAGATTTCACTCTC
AGGGCAGGGTCACCTTGACCAGGG
E + [anti-
GGGCTCCAGGCTGAGGACGAGGCTG
ACCATCAGCAGCCTGCAGCCTGAA
ACGCGTCCGTCAGCACAGCCTACA
<hu Mesothelin>
AATATTACTGCTGCTCATATGCAGGT
GATTTTGCAATTTACTATTGTCAAC
TTGACCTGAACAGGCTGAGATCTG
6F4VL]::huKLC-
AGAGACACTTTCGTGGTGTTCGGCGG
AGGCTAAAAGTTTTCCTCGGACGTT
ACGACACGGCCGTATATTACTGTG
S176K (IgG-Fab);
AGGGACCAAGCTGACCGTCCTAGGT
CGGCCAAGGGACCAAGGTGGAAAT
CGAGAGAGAGGTGTAGGACTACCA
LMRID: SS-30889
CAGCCCAAGGCTGCACCCTCGGTCAC
CAAACGGACGGTGGCTGCACCATC
ACTGCTATTTGGACTACTGGGGCCA
TCTGTTCCCGCCCTCCTCTGAGGAGC
TGTCTTCATCTTCCCGCCATCTGAT
GGGAAGTCTGGTCACCGTGTCCTC
TTCAAGCCAACAAGGCCACACTGGT
GAGCAGTTGAAATCTGGAACTGCC
AGCCTCCACCAAGGGCCCATCGGT
GTGTCTCATCAGTGACTTCTACCCGG
TCTGTTGTGTGCCTGCTGAATAACT
CTTCCCCCTGGCACCCTCCTCCAAG
GAGCCGTGACAGTGGCCTGGAAGGC
TCTATCCCAGAGAGGCCAAAGTAC
AGCACCTCTGGGGGCACAGCGGCC
AGATAGCAGCCCCGTCAAGGCGGGA
AGTGGAAGGTGGATAACGCCCTCC
CTGGGCTGCCTGGTCAAGGACTAC
GTGGAAACCACCACACCCTCCAAAC
AATCGGGTAACTCCCAGGAGAGTG
TTCCCCGAACCGGTGACGGTGTCGT
AAAGCAACAACAAGTACGCGGCCGA
TCACAGAGCAGGACAGCAAGGACA
GGAACTCAGGCGCCCTGACCAGCG
AAGCTATCTGAGCCTGACGCCTGAGC
GCACCTACAGCCTCAAGAGCACCC
GCGTGCACACCTTCCCGGCTGTCCT
AGTGGAAGTCCCACAGAAGCTACAG
TGACGCTGAGCAAAGCAGACTACG
ACAGTCCTCAGGACTCTACTCCCTC
CTGCCAGGTCACGCATGAAGGGAGC
AGAAACACAAAGTCTACGCCTGCG
AAGAGCGTGGTGACCGTGCCCTCC
ACCGTGGAGAAGACAGTGGCCCCTA
AAGTCACCCATCAGGGCCTGAGCT
AGCAGCTTGGGCACCCAGACCTAC
CAGAATGTTCA
CGCCCGTCACAAAGAGCTTCAACA
ATCTGCAACGTGAATCACAAGCCC
(SEQ ID NO: 635)
GGGGAGAGTGT
AGCAACACCAAGGTGGACAAGAAA
(SEQ ID NO: 636)
GTTGAGCCCAAATCTTGTGACAAA
ACTCACACATGCCCACCGTGCCCA
GCACCTGAACTCCTGGGGGGACCG
TCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCC
GGACCCCTGAGGTCACATGCGTGG
TGGTGGACGTGAGCCACGAAGACC
CTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATG
CCAAGACAAAGCCGTGCGAGGAGC
AGTACGGCAGCACGTACCGTTGCG
TCAGCGTCCTCACCGTCCTGCACCA
GGACTGGCTGAATGGCAAGGAGTA
CAAGTGCAAGGTGTCCAACAAAGC
CCTCCCAGCCCCCATCGAGAAAAC
CATCTCCAAAGCCAAAGGGCAGCC
CCGAGAACCACAGGTGTACACCCT
GCCCCCATCCCGGGAGGAGATGAC
CAAGAACCAGGTCAGCCTGACCTG
CCTGGTCAAAGGCTTCTATCCCAGC
GACATCGCCGTGGAGTGGGAGAGC
AATGGGCAGCCGGAGAACAACTAC
AAGACCACGCCTCCCGTGCTGGAC
TCCGACGGCTCCTTCTTCCTCTATA
GCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCT
CATGCTCCGTGATGCATGAGGCTCT
GCACAACCACTACACGCAGAAGAG
CCTCTCCCTGTCTCCGGGTGGTGGC
GGATCGGGAGGTGGCGGATCCCAG
GTGCAGCTGGTGGAGTCTGGGGGA
GGCTTGGTCAAGCCTGGAGGGTCC
CTGAGACTCTCCTGTGCAGCCTCTG
GATTCACCTTCAGTGACTACTACAT
GAGCTGGATCCGCCAGGCTCCAGG
GAAGGGGCTGGAGTGGATTTCATA
CATTAGTAGCAGTGAAAGTATCAT
CTATTACGTAGACTCTGTGAAGGG
CCGATTCACCATCTCCAGGGACAA
CGCCAAGAACTCACTGTATCTGCA
AATGAACAGCCTGAGAGCCGAGGA
CACGGCCGTGTATTACTGTGCGAG
AGATGTTGGGAGCCACTTTGACTA
CTGGGGCCAGGGAACCCTGGTCAC
CGTGTCCTCAGCAAGCACGAAGGG
GCCGTCCGTATTTCCGCTTGCGCCC
TCGTCGAAGTCAACTTCGGGAGGG
ACCGCGGCACTTGGCTGTCTTGTCA
AAGATTACTTCCCTGAGCCAGTGA
CAGTCAGCTGGAATTCCGGTGCCCT
CACGTCAGGAGTACATACATTCCCT
GCGGTATTGCAGTCCTCCGGACTCT
ACTCCCTGGAGTCGGTGGTAACGG
TGCCCAGCTCCAGCTTGGGGACCC
AGACGTACATTTGTAACGTGAATC
ACAAACCAAGCAATACTAAGGTAG
ATAAGAAAGTAGAACCGAAGAGCT
GC
(SEQ ID NO: 637)
AA
QSALTQPASVSGSPGQSITISCTGTSSD
DIQMTQSPSSVSASVGDRVTITCRAS
QVQLVQSGTEVKKPGASVKVSCKAS
VGNYNLVSWYQQHPGKAPKLMIYEV
QDISRWLAWYQQKPGKAPKLLISAA
GYTFPGYYMHWVRQAPGQGLEWM
NRRPSGVSNRFSGSKSGNTASLTISGLQ
SRLQSGVPSRFSGSGSGTDFTLTISSL
GWINPDSGGTKYTQKFQGRVTLTRD
AEDEAEYYCCSYAGRDTFVVFGGGTK
QPEDFAIYYCQQAKSFPRTFGQGTKV
ASVSTAYIDLNRLRSDDTAVYYCAR
LTVLGQPKAAPSVTLFPPSSEELQANK
EIKRTVAAPSVFIFPPSDEQLKSGTAS
ERCRTTNCYLDYWGQGSLVTVSSAS
ATLVCLISDFYPGAVTVAWKADSSPVK
VVCLLNNFYPREAKVQWKVDNALQ
TKGPSVFPLAPSSKSTSGGTAALGCL
AGVETTTPSKQSNNKYAAESYLSLTPE
SGNSQESVTEQDSKDSTYSLKSTLTL
VKDYFPEPVTVSWNSGALTSGVHTF
QWKSHRSYSCQVTHEGSTVEKTVAPT
SKADYEKHKVYACEVTHQGLSSPVT
PAVLQSSGLYSLKSVVTVPSSSLGTQ
ECS
KSFNRGEC
TYICNVNHKPSNTKVDKKVEPKSCD
(SEQ ID NO: 638)
(SEQ ID NO: 639)
KTHTCPPCPAPELLGGPSVFLFPPKPK
DTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPCEEQYG
STYRCVSVLTVLHQDWLNGKEYKC
KVSNKALPAPIEKTISKAKGQPREPQ
VYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVL
DSDGSFFLYSKLTVDKSRWQQGNVF
SCSVMHEALHNHYTQKSLSLSPGGG
GSGGGGSQVQLVESGGGLVKPGGSL
RLSCAASGFTFSDYYMSWIRQAPGK
GLEWISYISSSESIIYYVDSVKGRFTIS
RDNAKNSLYLQMNSLRAEDTAVYY
CARDVGSHFDYWGQGTLVTVSSAST
KGPSVFPLAPSSKSTSGGTAALGCLV
KDYFPEPVTVSWNSGALTSGVHTFP
AVLQSSGLYSLESVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 640)
iPS:
21-
[hu anti-
NA
CAGTCTGCCCTGACTCAGCCTGCCTC
GACATTGTGATGACTCAGTCTCCAG
CAGGTGCAGCTGGTGCAGTCTGGG
576389
230_392_IgG_
<hu CD40> 21-230_
CGTGTCTGGGAGCCCTGGACAGTCGA
ACTCCCTGGCTGTGTCTCTGGGCGA
ACTGAGGTGAAGAAGCCTGGGGCC
21-
39C2VH]::huIgG1zSEFL2*GK-
TCACCATCTCCTGCACTGGAACCAGC
GAGGGCCACCATCAACTGCAAGTC
TCAGTGAAGGTGTCCTGCAAGGCT
233_7G11__Fab
K::(G4S)2::[hu anti-
AGTGATGTTGGGAATTATAACCTTGT
CAGCCAGAGTGTTTTATACAGCTCC
TCTGGATACACCTTCCCCGGCTACT
<hu Mesothelin>
CTCCTGGTACCAACAGCACCCAGGCA
AACAATAAGAACTACTTAGCTTGG
ATATGCACTGGGTGCGACAGGCCC
7G11VH]::huIgG1z-
AAGCCCCCAAACTCATGATTTATGAG
TACCAGCAGAAACCAGGACAGCCT
CTGGACAGGGGCTTGAGTGGATGG
CH1-E::EPKSC + [anti-
GTCAATAGGCGGCCCTCAGGGGTTTC
CCTAAGCTGCTCATTTACTGGGCAT
GATGGATCAACCCTGACAGTGGTG
<hu CD40>
TAATCGCTTCTCTGGCTCCAAGTCTG
CTACCCGAGAATCCGGGGTCCCTG
GCACAAAGTATACACAGAAGTTTC
21-230_39C2VL]::huLLC2-
GCAACACGGCCTCCCTGACAATCTCT
ACCGATTCAGTGGCAGCGGGTCTG
AGGGCAGGGTCACCTTGACCAGGG
E + [anti-
GGGCTCCAGGCTGAGGACGAGGCTG
GGACAGATTTCACTCTCACCATCAG
ACGCGTCCGTCAGCACAGCCTACA
<hu Mesothelin>
AATATTACTGCTGCTCATATGCAGGT
CAGCCTGCAGGCTGAAGATGTGGC
TTGACCTGAACAGGCTGAGATCTG
7G11VL]::huKLC-
AGAGACACTTTCGTGGTGTTCGGCGG
AGTTTATTACTGTCAGCAATATTAT
ACGACACGGCCGTATATTACTGTG
S176K (IgG-Fab);
AGGGACCAAGCTGACCGTCCTAGGT
AGTACTCCTCCGACGTTCGGCCAA
CGAGAGAGAGGTGTAGGACTACCA
LMRID: SS-30890
CAGCCCAAGGCTGCACCCTCGGTCAC
GGGACCAAGGTGGAGATCAAACGG
ACTGCTATTTGGACTACTGGGGCCA
TCTGTTCCCGCCCTCCTCTGAGGAGC
ACGGTGGCTGCACCATCTGTCTTCA
GGGAAGTCTGGTCACCGTGTCCTC
TTCAAGCCAACAAGGCCACACTGGT
TCTTCCCGCCATCTGATGAGCAGTT
AGCCTCCACCAAGGGCCCATCGGT
GTGTCTCATCAGTGACTTCTACCCGG
GAAATCTGGAACTGCCTCTGTTGTG
CTTCCCCCTGGCACCCTCCTCCAAG
GAGCCGTGACAGTGGCCTGGAAGGC
TGCCTGCTGAATAACTTCTATCCCA
AGCACCTCTGGGGGCACAGCGGCC
AGATAGCAGCCCCGTCAAGGCGGGA
GAGAGGCCAAAGTACAGTGGAAGG
CTGGGCTGCCTGGTCAAGGACTAC
GTGGAAACCACCACACCCTCCAAAC
TGGATAACGCCCTCCAATCGGGTA
TTCCCCGAACCGGTGACGGTGTCGT
AAAGCAACAACAAGTACGCGGCCGA
ACTCCCAGGAGAGTGTCACAGAGC
GGAACTCAGGCGCCCTGACCAGCG
AAGCTATCTGAGCCTGACGCCTGAGC
AGGACAGCAAGGACAGCACCTACA
GCGTGCACACCTTCCCGGCTGTCCT
AGTGGAAGTCCCACAGAAGCTACAG
GCCTCAAGAGCACCCTGACGCTGA
ACAGTCCTCAGGACTCTACTCCCTC
CTGCCAGGTCACGCATGAAGGGAGC
GCAAAGCAGACTACGAGAAACACA
AAGAGCGTGGTGACCGTGCCCTCC
ACCGTGGAGAAGACAGTGGCCCCTA
AAGTCTACGCCTGCGAAGTCACCC
AGCAGCTTGGGCACCCAGACCTAC
CAGAATGTTCA
ATCAGGGCCTGAGCTCGCCCGTCA
ATCTGCAACGTGAATCACAAGCCC
(SEQ ID NO: 641)
CAAAGAGCTTCAACAGGGGAGAGT
AGCAACACCAAGGTGGACAAGAAA
GT
GTTGAGCCCAAATCTTGTGACAAA
(SEQ ID NO: 642)
ACTCACACATGCCCACCGTGCCCA
GCACCTGAACTCCTGGGGGGACCG
TCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCC
GGACCCCTGAGGTCACATGCGTGG
TGGTGGACGTGAGCCACGAAGACC
CTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATG
CCAAGACAAAGCCGTGCGAGGAGC
AGTACGGCAGCACGTACCGTTGCG
TCAGCGTCCTCACCGTCCTGCACCA
GGACTGGCTGAATGGCAAGGAGTA
CAAGTGCAAGGTGTCCAACAAAGC
CCTCCCAGCCCCCATCGAGAAAAC
CATCTCCAAAGCCAAAGGGCAGCC
CCGAGAACCACAGGTGTACACCCT
GCCCCCATCCCGGGAGGAGATGAC
CAAGAACCAGGTCAGCCTGACCTG
CCTGGTCAAAGGCTTCTATCCCAGC
GACATCGCCGTGGAGTGGGAGAGC
AATGGGCAGCCGGAGAACAACTAC
AAGACCACGCCTCCCGTGCTGGAC
TCCGACGGCTCCTTCTTCCTCTATA
GCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCT
CATGCTCCGTGATGCATGAGGCTCT
GCACAACCACTACACGCAGAAGAG
CCTCTCCCTGTCTCCGGGTGGTGGC
GGATCGGGAGGTGGCGGATCCGAG
GTGCAGCTGGTCGAGTCTGGAGGA
GGCTTGATCCAGCCTGGGGGGTCC
CTGAGACTCTCCTGTGCAGTCTCTG
GGTTCACCGTCAGTAGCAAGTTCAT
GACCTGGGTCCGCCAGGCTCCAGG
GAAGGGGCTGGAGTGGGTGTCAGT
TATTTATAGCGGTGGTAAGACATA
CTACGCAGACTCCGTGAAGGGCCG
ATTCACCATCTCCAGAGACAATTCC
AAGAACACGCTGTATCTTCAAATG
AACAGCCTGAGAGCCGAGGACACG
GCCGTGTATTACTGTGCGAGAGAT
AGCGGTGGCTGGGGGTACTTTGAC
TACTGGGGCCAGGGAACCCTGGTC
ACCGTGTCCTCAGCAAGCACGAAG
GGGCCGTCCGTATTTCCGCTTGCGC
CCTCGTCGAAGTCAACTTCGGGAG
GGACCGCGGCACTTGGCTGTCTTGT
CAAAGATTACTTCCCTGAGCCAGT
GACAGTCAGCTGGAATTCCGGTGC
CCTCACGTCAGGAGTACATACATTC
CCTGCGGTATTGCAGTCCTCCGGAC
TCTACTCCCTGGAGTCGGTGGTAAC
GGTGCCCAGCTCCAGCTTGGGGAC
CCAGACGTACATTTGTAACGTGAA
TCACAAACCAAGCAATACTAAGGT
AGATAAGAAAGTAGAACCGAAGA
GCTGC
(SEQ ID NO: 643)
AA
QSALTQPASVSGSPGQSITISCTGTSSD
DIVMTQSPDSLAVSLGERATINCKSS
QVQLVQSGTEVKKPGASVKVSCKAS
VGNYNLVSWYQQHPGKAPKLMIYEV
QSVLYSSNNKNYLAWYQQKPGQPP
GYTFPGYYMHWVRQAPGQGLEWM
NRRPSGVSNRFSGSKSGNTASLTISGLQ
KLLIYWASTRESGVPDRFSGSGSGTD
GWINPDSGGTKYTQKFQGRVTLTRD
AEDEAEYYCCSYAGRDTFVVFGGGTK
FTLTISSLQAEDVAVYYCQQYYSTPP
ASVSTAYIDLNRLRSDDTAVYYCAR
LTVLGQPKAAPSVTLFPPSSEELQANK
TFGQGTKVEIKRTVAAPSVFIFPPSDE
ERCRTTNCYLDYWGQGSLVTVSSAS
ATLVCLISDFYPGAVTVAWKADSSPVK
QLKSGTASVVCLLNNFYPREAKVQW
TKGPSVFPLAPSSKSTSGGTAALGCL
AGVETTTPSKQSNNKYAAESYLSLTPE
KVDNALQSGNSQESVTEQDSKDSTY
VKDYFPEPVTVSWNSGALTSGVHTF
QWKSHRSYSCQVTHEGSTVEKTVAPT
SLKSTLTLSKADYEKHKVYACEVTH
PAVLQSSGLYSLKSVVTVPSSSLGTQ
ECS
QGLSSPVTKSFNRGEC
TYICNVNHKPSNTKVDKKVEPKSCD
(SEQ ID NO: 644)
(SEQ ID NO: 645)
KTHTCPPCPAPELLGGPSVFLFPPKPK
DTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPCEEQYG
STYRCVSVLTVLHQDWLNGKEYKC
KVSNKALPAPIEKTISKAKGQPREPQ
VYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVL
DSDGSFFLYSKLTVDKSRWQQGNVF
SCSVMHEALHNHYTQKSLSLSPGGG
GSGGGGSEVQLVESGGGLIQPGGSLR
LSCAVSGFTVSSKFMTWVRQAPGKG
LEWVSVIYSGGKTYYADSVKGRFTIS
RDNSKNTLYLQMNSLRAEDTAVYY
CARDSGGWGYFDYWGQGTLVTVSS
ASTKGPSVFPLAPSSKSTSGGTAALG
CLVKDYFPEPVTVSWNSGALTSGVH
TFPAVLQSSGLYSLESVVTVPSSSLGT
QTYICNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 646)
TABLE 27B
MSLN-CD40 IgG-Fab
iPS:
21-233_4G12_IgG_21-
[hu anti-
NA
CAGTCAGTGTTGACGCAGCCGCCCTC
GACATCCAGATGACCCAGTCTCCATC
CAGGTGCAGCTGCAGGAGTCGGGCC
576118
230_4G7_Fab
<hu Mesothelin>
AGTGTCTGGGGCCCCAGGGCAGAGG
CTCCCTGTCTGCATCTGTAGGAGACA
CAGGACTGGTGAAGCCTTCGGAAAC
4G12VH]::huIgG1zSEFL2*GK-
GTCACCATCTCCTGCACTGGGAGCAG
TTCTCACCATCACTTGCCGGGCAAGT
CCTGTCCCTCACCTGCACTGTCTCTG
K::(G4S)2:[hu anti-
CTCCAACATCGGGGCAGGTTATGAT
CAGAACATTACCACCTATTTAAATTG
GTGGCTCCATCAGCAGTAGTAGTTAC
<huCD40>
GTTCACTGGTACCAGCAGGTTCCAGG
GTATCAGCAGAAACCAGGGAAAGCC
TACTGGGGCTGGATCAGGCAGCCCC
21-230_4G7VH]::huIgG1z-
AACAGCCCCCAAACTCCTCATCTATG
CCTAACCTCCTGATCTCTGCTGCATC
CAGGGAAGGGGCTGGAGTGGATTGG
CH1-E::EPKSC + [anti-
GTAACAGCAAGCGGCCCTCAGGGGT
CCGTTTGCGAAGTGGGGTCCCATCAA
GAGTATCTATTATAGTGGGATCACCA
<hu Mesothelin>
CCCTGACCGATTCTCTGGCTCCAAGT
GGTTCAGTGGCAGTGGATCTGGGAC
ACTACAACCCGTCCCTCAAGAGTCG
4G12VL]::huLLC2-E +
CTGGCACCTCAGCCTCCCTGGCCATC
AGATTTCACTCTCACCATCAGCAGTC
AGTCACCATCTCCGTAGACACGTCCA
[anti-<huCD40>
ACTGGGCTCCAGGCTGAGGATGAGG
TGCAACCTGTAGATTTTACAACTTTC
AGAACCAGTTCTCCCTGAAGCTGAGT
21-230_4G7VL]::huKLC-
CTGATTATTACTGCCAGTCCTATGAC
TACTGTCAACAGACTTTCACTACCCC
TCTGTGACCGCCGCAGACACGGCCG
S176K(IgG-Fab): LMRID:
AGCAGCCTGGGTGGTTGGGTGTTCG
GTGGACGTTCGGCCAAGGGACCAAG
TGTATTACTGTGCGAGGCCCAGTAAC
SS-30819
GCGGAGGGACCAAGCTGACCGTCCT
GTGGAGATCAAACGAACGGTGGCTG
TACGATGCTTTTGATATCTGGGGCCA
ACAGCCCAAGGCTGCACCCTCGGTC
CACCATCTGTCTTCATCTTCCCGCCA
AGGGACAATGGTCACCGTGTCCTCA
ACTCTGTTCCCGCCCTCCTCTGAGGA
TCTGATGAGCAGTTGAAATCTGGAA
GCCTCCACCAAGGGCCCATCGGTCTT
GCTTCAAGCCAACAAGGCCACACTG
CTGCCTCTGTTGTGTGCCTGCTGAAT
CCCCCTGGCACCCTCCTCCAAGAGCA
GTGTGTCTCATCAGTGACTTCTACCC
AACTTCTATCCCAGAGAGGCCAAAG
CCTCTGGGGGCACAGCGGCCCTGGG
GGGAGCCGTGACAGTGGCCTGGAAG
TACAGTGGAAGGTGGATAACGCCCT
CTGCCTGGTCAAGGACTACTTCCCCG
GCAGATAGCAGCCCCGTCAAGGCGG
CCAATCGGGTAACTCCCAGGAGAGT
AACCGGTGACGGTGTCGTGGAACTC
GAGTGGAAACCACCACACCCTCCAA
GTCACAGAGCAGGACAGCAAGGACA
AGGCGCCCTGACCAGCGGCGTGCAC
ACAAAGCAACAACAAGTACGCGGCC
GCACCTACAGCCTCAAGAGCACCCT
ACCTTCCCGGCTGTCCTACAGTCCTC
GAAAGCTATCTGAGCCTGACGCCTG
GACGCTGAGCAAAGCAGACTACGAG
AGGACTCTACTCCCTCAAGAGCGTG
AGCAGTGGAAGTCCCACAGAAGCTA
AAACACAAAGTCTACGCCTGCGAAG
GTGACCGTGCCCTCCAGCAGCTTGGG
CAGCTGCCAGGTCACGCATGAAGGG
TCACCCATCAGGGCCTGAGCTCGCCC
CACCCAGACCTACATCTGCAACGTG
AGCACCGTGGAGAAGACAGTGGCCC
GTCACAAAGAGCTTCAACAGGGGAG
AATCACAAGCCCAGCAACACCAAGG
CTACAGAATGTTCA
AGTGT
TGGACAAGAAAGTTGAGCCCAAATC
(SEQ ID NO: 647)
(SEQ ID NO: 648)
TTGTGACAAAACTCACACATGCCCAC
CGTGCCCAGCACCTGAACTCCTGGG
GGGACCGTCAGTCTTCCTCTTCCCCC
CAAAACCCAAGGACACCCTCATGAT
CTCCCGGACCCCTGAGGTCACATGCG
TGGTGGTGGACGTGAGCCACGAAGA
CCCTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGTGCGAGGAGCAG
TACGGCAGCACGTACCGTTGCGTCA
GCGTCCTCACCGTCCTGCACCAGGAC
TGGCTGAATGGCAAGGAGTACAAGT
GCAAGGTGTCCAACAAAGCCCTCCC
AGCCCCCATCGAGAAAACCATCTCC
AAAGCCAAAGGGCAGCCCCGAGAAC
CACAGGTGTACACCCTGCCCCCATCC
CGGGAGGAGATGACCAAGAACCAGG
TCAGCCTGACCTGCCTGGTCAAAGGC
TTCTATCCCAGCGACATCGCCGTGGA
GTGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCCG
TGCTGGACTCCGACGGCTCCTTCTTC
CTCTATAGCAAGCTCACCGTGGACA
AGAGCAGGTGGCAGCAGGGGAACGT
CTTCTCATGCTCCGTGATGCATGAGG
CTCTGCACAACCACTACACGCAGAA
GAGCCTCTCCCTGTCTCCGGGTGGTG
GCGGATCGGGAGGTGGCGGATCCCA
GGTGCAGCTGGTGCAGTCTGGGGCT
GAGGTGAAGAAGCCTGGGGCCTCAG
TGAAGGTGTCCTGCAAGGCTTCTGGA
TACACCTTCGCCGGCTACTATATGCA
CTGGGTGCGACAGGCCCCTGGACAA
GGGCTTGAGTGGATGGGATGGATCA
ACCCTGACAGTGGAGGCACAAACTT
TGCACAGCAGTTTCAGGGCAGGGTC
ACCATGACCAGGGATACGTCCATCA
GCACAGCCTACATGGAGGTGAGCAG
GCTGAGATCTGACGACACGGCCGTG
TTTTACTGTGCGAGAGAGAAGATCA
CTATGACTGGTATTTACTTTGACTAT
TGGGGCCAGGGAACCCTGGTCACCG
TGTCCTCAGCAAGCACGAAGGGGCC
GTCCGTATTTCCGCTTGCGCCCTCGT
CGAAGTCAACTTCGGGAGGGACCGC
GGCACTTGGCTGTCTTGTCAAAGATT
ACTTCCCTGAGCCAGTGACAGTCAGC
TGGAATTCCGGTGCCCTCACGTCAGG
AGTACATACATTCCCTGCGGTATTGC
AGTCCTCCGGACTCTACTCCCTGGAG
TCGGTGGTAACGGTGCCCAGCTCCA
GCTTGGGGACCCAGACGTACATTTGT
AACGTGAATCACAAACCAAGCAATA
CTAAGGTAGATAAGAAAGTAGAACC
GAAGAGCTGC
(SEQ ID NO: 649)
AA
QSVLTQPPSVSGAPGQRVTISCTGSSSN
DIQMTQSPSSLSASVGDILTITCRASQN
QVQLQESGPGLVKPSETLSLTCTVSGG
IGAGYDVHWYQQVPGTAPKLLIYGNS
ITTYLNWYQQKPGKAPNLLISAASRLRS
SISSSSYYWGWIRQPPGKGLEWIGSIYY
KRPSGVPDRFSGSKSGTSASLAITGLQ
GVPSRFSGSGSGTDFTLTISSLQPVDFT
SGITNYNPSLKSRVTISVDTSKNQFSLK
AEDEADYYCQSYDSSLGGWVFGGGT
TFYCQQTFTTPWTFGQGTKVEIKRTVA
LSSVTAADTAVYYCARPSNYDAFDIW
KLTVLQPKAAPSVTLFPPSSEELQANK
APSVFIFPPSDEQLKSGTASVVCLLNNF
GQGTMVTVSSASTKGPSVFPLAPSSKS
ATLVCLISDFYPGAVTVAWKADSSPV
YPREAKVQWKVDNALQSGNSQESVTE
TSGGTAALGCLVKDYFPEPVTVSWNS
KAGVETTTPSKQSNNKYAAESYLSLTP
QDSKDSTYSLKSTLTLSKADYEKHKV
GALTSGVHTFPAVLQSSGLYSLKSVVT
EQWKSHRSYSCQVTHEGSTVEKTVAP
YACEVTHQGLSSPVTKSFNRGEC
VPSSSLGTQTYICNVNHKPSNTKVDKK
TECS
(SEQ ID NO: 651)
VEPKSCDKTHTCPPCPAPELLGGPSVF
(SEQ ID NO: 650)
LFPPKPKDTLMISRTPEVTCVVVDVSH
EDPEVKFNWYVDGVEVHNAKTKPCE
EQYGSTYRCVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPRE
PQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLVQSGAEVKKPGASVKVSC
KASGYTFAGYYMHWVRQAPGQGLE
WMGWINPDSGGTNFAQQFQGRVTMT
RDTSISTAYMEVSRLRSDDTAVFYCAR
EKITMTGIYFDYWGQGTLVTVSSASTK
GPSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAVLQ
SSGLYSLESVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSC
(SEQ ID NO: 652)
iSP:
21-233_4G12_IgG_21-
[hu anti-
NA
CAGTCAGTGTTGACGCAGCCGCCCTC
GACATCCAGATGACCCAGTCTCCATC
CAGGTGCAGCTGCAGGAGTCGGGCC
576125
230_29H10_Fab
<hu Mesothelin>
AGTGTCTGGGGCCCCAGGGCAGAGG
CTCACTGTCTGCATCTGTAGGAGACA
CAGGACTGGTGAAGCCTTCGGAAAC
4G12VH]::huIgG1zSEFL2*GK-
GTCACCATCTCCTGCACTGGGAGCAG
GAGTCACCATCACCTGTCGGGCGAG
CCTGTCCCTCACCTGCACTGTCTCTG
K::(G4S)2:[hu anti-<huCD40>
CTCCAACATCGGGGCAGGTTATGAT
TCAGGACATTAGCAATAATTTAGCCT
GTGGCTCCATCAGCAGTAGTAGTTAC
21-230_29H10VH]::huIgG1z-
GTTCACTGGTACCAGCAGGTTCCAGG
GGTTTCAGCAGAAACCAGGGAAACC
TACTGGGGCTGGATCAGGCAGCCCC
CH1-E::EPKSC +
AACAGCCCCCAAACTCCTCATCTATG
CCCTAAGTCCCTGATGTATGCTGCAT
CAGGGAAGGGGCTGGAGTGGATTGG
[anti-<hu Mesothelin>
GTAACAGCAAGCGGCCCTCAGGGGT
CCAGTTTGCACAGTGGAGTCCCATCA
GAGTATCTATTATAGTGGGATCACCA
4G12VL]::huLLC2-E +
CCCTGACCGATTCTCTGGCTCCAAGT
ACGTTCAGCGGCAGTGGATCTGGGA
ACTACAACCCGTCCCTCAAGAGTCG
[anti-<huCD40>
CTGGCACCTCAGCCTCCCTGGCCATC
CAGATTTCACTTTCACCATCAGCAGC
AGTCACCATCTCCGTAGACACGTCCA
21-230_29H10VL]::huKLC-
ACTGGGCTCCAGGCTGAGGATGAGG
CTGCAGCCTGAAGATTTTGCAACTTA
AGAACCAGTTCTCCCTGAAGCTGAGT
S176K(IgG-Fab); LMRID:
CTGATTATTACTGCCAGTCCTATGAC
TTACTGCCAACAGTATAATAGTTACC
TCTGTGACCGCCGCAGACACGGCCG
SS-30820
AGCAGCCTGGGTGGTTGGGTGTTCG
CTCTCACTTTCGGCGGAGGGACCAA
TGTATTACTGTGCGAGGCCCAGTAAC
GCGGAGGGACCAAGCTGACCGTCCT
GGTGGAGATCAGACGAACGGTGGCT
TACGATGCTTTTGATATCTGGGGCCA
ACAGCCCAAGGCTGCACCCTCGGTC
GCACCATCTGTCTTCATCTTCCCGCC
AGGGACAATGGTCACCGTGTCCTCA
ACTCTGTTCCCGCCCTCCTCTGAGGA
ATCTGATGAGCAGTTGAAATCTGGA
GCCTCCACCAAGGGCCCATCGGTCTT
GCTTCAAGCCAACAAGGCCACACTG
ACTGCCTCTGTTGTGTGCCTGCTGAA
CCCCCTGGCACCCTCCTCCAAGAGCA
GTGTGTCTCATCAGTGACTTCTACCC
TAACTTCTATCCCAGAGAGGCCAAA
CCTCTGGGGGCACAGCGGCCCTGGG
GGGAGCCGTGACAGTGGCCTGGAAG
GTACAGTGGAAGGTGGATAACGCCC
CTGCCTGGTCAAGGACTACTTCCCCG
GCAGATAGCAGCCCCGTCAAGGCGG
TCCAATCGGGTAACTCCCAGGAGAG
AACCGGTGACGGTGTCGTGGAACTC
GAGTGGAAACCACCACACCCTCCAA
TGTCACAGAGCAGGACAGCAAGGAC
AGGCGCCCTGACCAGCGGCGTGCAC
ACAAAGCAACAACAAGTACGCGGCC
AGCACCTACAGCCTCAAGAGCACCC
ACCTTCCCGGCTGTCCTACAGTCCTC
GAAAGCTATCTGAGCCTGACGCCTG
TGACGCTGAGCAAAGCAGACTACGA
AGGACTCTACTCCCTCAAGAGCGTG
AGCAGTGGAAGTCCCACAGAAGCTA
GAAACACAAAGTCTACGCCTGCGAA
GTGACCGTGCCCTCCAGCAGCTTGGG
CAGCTGCCAGGTCACGCATGAAGGG
GTCACCCATCAGCGCCTGAGCTCGCC
CACCCAGACCTACATCTGCAACGTG
AGCACCGTGGAGAAGACAGTGGCCC
CGTCACAAAGAGCTTCAACAGGGGA
AATCACAAGCCCAGCAACACCAAGG
CTACAGAATGTTCA
GAGTGT
TGGACAAGAAAGTTGAGCCCAAATC
(SEQ ID NO: 653)
(SEQ ID NO: 654)
TTGTGACAAAACTCACACATGCCCAC
CGTGCCCAGCACCTGAACTCCTGGG
GGGACCGTCAGTCTTCCTCTTCCCCC
CAAAACCCAAGGACACCCTCATGAT
CTCCCGGACCCCTGAGGTCACATGCG
TGGTGGTGGACGTGAGCCACGAAGA
CCCTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGTGCGAGGAGCAG
TACGGCAGCACGTACCGTTGCGTCA
GCGTCCTCACCGTCCTGCACCAGGAC
TGGCTGAATGGCAAGGAGTACAAGT
GCAAGGTGTCCAACAAAGCCCTCCC
AGCCCCCATCGAGAAAACCATCTCC
AAAGCCAAAGGGCAGCCCCGAGAAC
CACAGGTGTACACCCTGCCCCCATCC
CGGGAGGAGATGACCAAGAACCAGG
TCAGCCTGACCTGCCTGGTCAAAGGC
TTCTATCCCAGCGACATCGCCGTGGA
GTGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCCG
TGCTGGACTCCGACGGCTCCTTCTTC
CTCTATAGCAAGCTCACCGTGGACA
AGAGCAGGTGGCAGCAGGGGAACGT
CTTCTCATGCTCCGTGATGCATGAGG
CTCTGCACAACCACTACACGCAGAA
GAGCCTCTCCCTGTCTCCGGGTGGTG
GCGGATCGGGAGGTGGCGGATCCCA
GGTGCAACTGGTGCAGTCTGGGGCT
GAGGTGACGAAGCCTGGGGCCTCAG
TGAAGGTGTCCTGCAAGGCTTCTGGA
TACACCTTCGCCGGCTACTATATGCA
CTGGGTGCGACAGGCCCCTGGACAA
GGGCTTGAGTGGATGGGATGGATCA
ACCCTCACAGTGGTGGCACAAACTA
TGCACAGAAGTTTCAGGACAGGGTC
ACCATGACCAGGGACACGTCCATCA
ACACAGCCTACATGGAACTGAGCAG
GCTGAGATCTGACGACACGGCCGTG
TATTACTGTGCGAGAGAACGTATTTC
TATGGTTCGGGGAGTCGGGCACAAC
TGGTTCGCCCCCTGGGGCCAGGGAA
CCCTGGTCACCGTGTCCTCAGCAAGC
ACGAAGGGGCCGTCCGTATTTCCGCT
TGCGCCCTCGTCGAAGTCAACTTCGG
GAGGGACCGCGGCACTTGGCTGTCTT
GTCAAAGATTACTTCCCTGAGCCAGT
GACAGTCAGCTGGAATTCCGGTGCC
CTCACGTCAGGAGTACATACATTCCC
TGCGGTATTGCAGTCCTCCGGACTCT
ACTCCCTGGAGTCGGTGGTAACGGT
GCCCAGCTCCAGCTTGGGGACCCAG
ACGTACATTTGTAACGTGAATCACAA
ACCAAGCAATACTAAGGTAGATAAG
AAAGTAGAACCGAAGAGCTGC
(SEQ ID NO: 655)
AA
QSVLTQPPSVSGAPGQRVTISCTGSSSN
DIQMTQSPSSLSASVGDRVTITCRASQ
QVQLQESGPGLVKPSETLSLTCTVSGG
IGAGYDVHWYQQVPGTAPKLLIYGNS
DISNNLAWFQQKPGKPPKSLMYAASS
SISSSSYYWGWIRQPPGKGLEWIGSIYY
KRPSGVPDRFSGSKSGTSASLAITGLQ
LHSGVPSTFSGSGSGTDFTFTISSLQPE
SGITNYNPSLKSRVTISVDTSKNQFSLK
AEDEADYYCQSYDSSLGGWVFGGGT
DFATYYCQQYNSYPLTFGGGTKVEIRR
LSSVTAADTAVYYCARPSNYDAFDIW
KLTVLQPKAAPSVTLFPPSSEELQANK
TVAAPSVFIFPPSDEQLKSGTASVVCLL
GQGTMVTVSSASTKGPSVFPLAPSSKS
ATLVCLISDFYPGAVTVAWKADSSPV
NNFYPREAKVQWKVDNALQSGNSQE
TSGGTAALGCLVKDYFPEPVTVSWNS
KAGVETTTPSKQSNNKYAAESYLSLTP
SVTEQDSKDSTYSLKSTLTLSKADYEK
GALTSGVHTFPAVLQSSGLYSLKSVVT
EQWKSHRSYSCQVTHEGSTVEKTVAP
HKVYACEVTHQGLSSPVTKSFNRGEC
VPSSSLGTQTYICNVNHKPSNTKVDKK
TECS
(SEQ ID NO: 657)
VEPKSCDKTHTCPPCPAPELLGGPSVF
(SEQ ID NO: 656)
LFPPKPKDTLMISRTPEVTCVVVDVSH
EDPEVKFNWYVDGVEVHNAKTKPCE
EQYGSTYRCVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPRE
PQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLVQSGAEVTKPGASVKVSC
KASGYTFAGYYMHWVRQAPGQGLE
WMGWINPHSGGTNYAQKFQDRVTMT
RDTSINTAYMELSRLRSDDTAVYYCA
RERISMVRGVGHNWFAPWGQGTLVT
VSSASTKGPSVFPLAPSSKSTSGGTAAL
GCLVKDYFPEPVTVSWNSGALTSGVH
TFPAVLQSSGLYSLESVVTVPSSSLGTQ
TYICNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 658)
iPS:
21-233_4G12_IgG_21-
[hu anti-
NA
CAGTCAGTGTTGACGCAGCCGCCCTC
CAGTCTGCCCTGACTCAGCCTGCCTC
CAGGTGCAGCTGCAGGAGTCGGGCC
576130
230_30A12_Fab
<hu Mesothelin>
AGTGTCTGGGGCCCCAGGGCAGAGG
CGTGTCTGGGAGCCCTGGACAGTCG
CAGGACTGGTGAAGCCTTCGGAAAC
4G12VH]::huIgG1zSEFL2*GK-
GTCACCATCTCCTGCACTGGGAGCAG
ATCACCATCTCCTGCACTGGAACCAG
CCTGTCCCTCACCTGCACTGTCTCTG
K::(G4S)2:[hu anti-<huCD40>
CTCCAACATCGGGGCAGGTTATGAT
CAGTGATGTTGGGAATTATAACCTTG
GTGGCTCCATCAGCAGTAGTAGTTAC
21-230_30A12VH]::huIgG1z-
GTTCACTGGTACCAGCAGGTTCCAGG
TCTCCTGGTACCAACAGCACCCAGGC
TACTGGGGCTGGATCAGGCAGCCCC
CH1-E::EPKSC +
AACAGCCCCCAAACTCCTCATCTATG
AAAGCCCCCAAACTCATGATTTTTGA
CAGGGAAGGGGCTGGAGTGGATTGG
[anti-<hu Mesothelin>
GTAACAGCAAGCGGCCCTCAGGGGT
GGTCAATCAGCGGCCCTCAGGGGTTT
GAGTATCTATTATAGTGGGATCACCA
4G12VL]::huLLC2-E +
CCCTGACCGATTCTCTGGCTCCAAGT
CTAATCGCTTCTCTGGCTCCAAGTCT
ACTACAACCCGTCCCTCAAGAGTCG
[anti-<huCD40>
CTGGCACCTCAGCCTCCCTGGCCATC
GGCACCACGGCCTCCCTGACAATCTC
AGTCACCATCTCCGTAGACACGTCCA
21-230_30A12VL]::huLLC2-
ACTGGGCTCCAGGCTGAGGATGAGG
TGGGCTCCAGGCTGCGGACGAGGCT
AGAACCAGTTCTCCCTGAAGCTGAGT
K(IgG-Fab); LMRID:
CTGATTATTACTGCCAGTCCTATGAC
GATTATTTCTGCTGCTCATATACAAC
TCTGTGACCGCCGCAGACACGGCCG
SS-30821
AGCAGCCTGGGTGGTTGGGTGTTCG
TAGTAGCACTTATGTGATCTTCGGCG
TGTATTACTGTGCGAGGCCCAGTAAC
GCGGAGGGACCAAGCTGACCGTCCT
GAGGGACCAAGCTGACCGTCCTAGG
TACGATGCTTTTGATATCTGGGGCCA
ACAGCCCAAGGCTGCACCCTCGGTC
TCAGCCCAAGGCTGCACCCTCGGTCA
AGGGACAATGGTCACCGTGTCCTCA
ACTCTGTTCCCGCCCTCCTCTGAGGA
CTCTGTTCCCGCCCTCCTCTGAGGAG
GCCTCCACCAAGGGCCCATCGGTCTT
GCTTCAAGCCAACAAGGCCACACTG
CTTCAAGCCAACAAGGCCACACTGG
CCCCCTGGCACCCTCCTCCAAGAGCA
GTGTGTCTCATCAGTGACTTCTACCC
TGTGTCTCATCAGTGACTTCTACCCG
CCTCTGGGGGCACAGCGGCCCTGGG
GGGAGCCGTGACAGTGGCCTGGAAG
GGAGCCGTGACAGTGGCCTGGAAGG
CTGCCTGGTCAAGGACTACTTCCCCG
GCAGATAGCAGCCCCGTCAAGGCGG
CAGATAGCAGCCCCGTCAAGGCGGG
AACCGGTGACGGTGTCGTGGAACTC
GAGTGGAAACCACCACACCCTCCAA
AGTGGAAACCACCACACCCTCCAAA
AGGCGCCCTGACCAGCGGCGTGCAC
ACAAAGCAACAACAAGTACGCGGCC
CAAAGCAACAACAAGTACGCGGCCA
ACCTTCCCGGCTGTCCTACAGTCCTC
GAAAGCTATCTGAGCCTGACGCCTG
AGAGCTATCTGAGCCTGACGCCTGA
AGGACTCTACTCCCTCAAGAGCGTG
AGCAGTGGAAGTCCCACAGAAGCTA
GCAGTGGAAGTCCCACAGAAGCTAC
GTGACCGTGCCCTCCAGCAGCTTGGG
CAGCTGCCAGGTCACGCATGAAGGG
AGCTGCCAGGTCACGCATGAAGGGA
CACCCAGACCTACATCTGCAACGTG
AGCACCGTGGAGAAGACAGTGGCCC
GCACCGTGGAGAAGACAGTGGCCCC
AATCACAAGCCCAGCAACACCAAGG
CTACAGAATGTTCA
TACAGAATGTTCA
TGGACAAGAAAGTTGAGCCCAAATC
(SEQ ID NO: 659)
(SEQ ID NO: 660)
TTGTGACAAAACTCACACATGCCCAC
CGTGCCCAGCACCTGAACTCCTGGG
GGGACCGTCAGTCTTCCTCTTCCCCC
CAAAACCCAAGGACACCCTCATGAT
CTCCCGGACCCCTGAGGTCACATGCG
TGGTGGTGGACGTGAGCCACGAAGA
CCCTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGTGCGAGGAGCAG
TACGGCAGCACGTACCGTTGCGTCA
GCGTCCTCACCGTCCTGCACCAGGAC
TGGCTGAATGGCAAGGAGTACAAGT
GCAAGGTGTCCAACAAAGCCCTCCC
AGCCCCCATCGAGAAAACCATCTCC
AAAGCCAAAGGGCAGCCCCGAGAAC
CACAGGTGTACACCCTGCCCCCATCC
CGGGAGGAGATGACCAAGAACCAGG
TCAGCCTGACCTGCCTGGTCAAAGGC
TTCTATCCCAGCGACATCGCCGTGGA
GTGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCCG
TGCTGGACTCCGACGGCTCCTTCTTC
CTCTATAGCAAGCTCACCGTGGACA
AGAGCAGGTGGCAGCAGGGGAACGT
CTTCTCATGCTCCGTGATGCATGAGG
CTCTGCACAACCACTACACGCAGAA
GAGCCTCTCCCTGTCTCCGGGTGGTG
GCGGATCGGGAGGTGGCGGATCCGA
GGTGCAGCTGCTGGAGTCTGGGGGA
GGCTTGGTACAGCCTGGGGGGTCCCT
GAGACTCTCCTGTGCAGCCTCTGGAT
TCACCTTTAGTAGAAATGCCATGAGT
TGGGTCCGCCAGGCTCCAGGGAAGG
GGCTGGAGTGGGTGTCAGCTACTGG
TGGTAGTGGTATTAGCACATACTACG
CAGACTCCGTGAAGGGCCGGTTCAC
CATCTCCAGAGACAATTCCAAGAAC
ACGCTGTATCTGCAAATGAACAGTCT
GAGAGCCGAGGACACGGCCGTATAT
TACTGTGCGAGAGGTTATAGCAACA
GCTGGTGGTACTTTGACTACTGGGGC
CAGGGAACCCTGGTCACCGTGTCCTC
AGCAAGCACGAAGGGGCCGTCCGTA
TTTCCGCTTGCGCCCTCGTCGAAGTC
AACTTCGGGAGGGACCGCGGCACTT
GGCTGTCTTGTCAAAGATTACTTCCC
TGAGCCAGTGACAGTCAGCTGGAAT
TCCGGTGCCCTCACGTCAGGAGTACA
TACATTCCCTGCGGTATTGCAGTCCT
CCGGACTCTACTCCCTGGAGTCGGTG
GTAACGGTGCCCAGCTCCAGCTTGG
GGACCCAGACGTACATTTGTAACGT
GAATCACAAACCAAGCAATACTAAG
GTAGATAAGAAAGTAGAACCGAAGA
GCTGC
(SEQ ID NO: 661)
AA
QSVLTQPPSVSGAPGQRVTISCTGSSSN
QSALTQPASVSGSPGQSITISCTGTSSD
QVQLQESGPGLVKPSETLSLTCTVSGG
IGAGYDVHWYQQVPGTAPKLLIYGNS
VGNYNLVSWYQQHPGKAPKLMIFEV
SISSSSYYWGWIRQPPGKGLEWIGSIYY
KRPSGVPDRFSGSKSGTSASLAITGLQ
NQRPSGVSNRFSGSKSGTTASLTISGLQ
SGITNYNPSLKSRVTISVDTSKNQFSLK
AEDEADYYCQSYDSSLGGWVFGGGT
AADEADYFCCSYTTSSTYVIFGGGTKL
LSSVTAADTAVYYCARPSNYDAFDIW
KLTVLQPKAAPSVTLFPPSSEELQANK
TVLGQPKAAPSVTLFPPSSEELQANKA
GQGTMVTVSSASTKGPSVFPLAPSSKS
ATLVCLISDFYPGAVTVAWKADSSPV
TLVCLISDFYPGAVTVAWKADSSPVK
TSGGTAALGCLVKDYFPEPVTVSWNS
KAGVETTTPSKQSNNKYAAESYLSLTP
AGVETTTPSKQSNNKYAAKSYLSLTPE
GALTSGVHTFPAVLQSSGLYSLKSVVT
EQWKSHRSYSCQVTHEGSTVEKTVAP
QWKSHRSYSCQVTHEGSTVEKTVAPT
VPSSSLGTQTYICNVNHKPSNTKVDKK
TECS
ECS
VEPKSCDKTHTCPPCPAPELLGGPSVF
(SEQ ID NO: 662)
(SEQ ID NO: 663)
LFPPKPKDTLMISRTPEVTCVVVDVSH
EDPEVKFNWYVDGVEVHNAKTKPCE
EQYGSTYRCVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPRE
PQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGSG
GGGSEVQLLESGGGLVQPGGSLRLSC
AASGFTFSRNAMSWVRQAPGKGLEW
VSATGGSGISTYYADSVKGRFTISRDN
SKNTLYLQMNSLRAEDTAVYYCARG
YSNSWWYFDYWGQGTLVTVSSASTK
GPSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAVLQ
SSGLYSLESVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSC
(SEQ ID NO: 664)
iPS:
21-233_4G12_IgG_21-
[hu anti-
NA
CAGTCAGTGTTGACGCAGCCGCCCTC
GACATCCAGATGACCCAGTCTCCATC
CAGGTGCAGCTGCAGGAGTCGGGCC
576135
230_33H6_Fab
<hu Mesothelin>
AGTGTCTGGGGCCCCAGGGCAGAGG
CTCCCTGTCTGCATCTGTAGGAGACA
CAGGACTGGTGAAGCCTTCGGAAAC
4G12VH]::huIgG1zSEFL2*GK-
GTCACCATCTCCTGCACTGGGAGCAG
GAGTCACCATCACTTGCCGGGCAGG
CCTGTCCCTCACCTGCACTGTCTCTG
K::(G4S)2:[hu anti-<huCD40>
CTCCAACATCGGGGCAGGTTATGAT
TCAGAACATTAGCAGGCATTTAAATT
GTGGCTCCATCAGCAGTAGTAGTTAC
21-230_33H6VH]::huIgG1z-
GTTCACTGGTACCAGCAGGTTCCAGG
GGTATCAGCAGAATCCAGGGAAAGC
TACTGGGGCTGGATCAGGCAGCCCC
CH1-E::EPKSC +
AACAGCCCCCAAACTCCTCATCTATG
CCCTAAGGTCCTGATCCATCCTGCAT
CAGGGAAGGGGCTGGAGTGGATTGG
[anti-<hu Mesothelin>
GTAACAGCAAGCGGCCCTCAGGGGT
CCAGTTTGCCAAGTGGGGTCCCGTCA
GAGTATCTATTATAGTGGGATCACCA
4G12VL]::huLLC2-E +
CCCTGACCGATTCTCTGGCTCCAAGT
AGGTTCAGTGGCAGTGGATCTGGGA
ACTACAACCCGTCCCTCAAGAGTCG
[anti-<huCD40>
CTGGCACCTCAGCCTCCCTGGCCATC
CAGATTTCAGTCTTACCATCAGCAGT
AGTCACCATCTCCGTAGACACGTCCA
21-230_33H6VL]::
ACTGGGCTCCAGGCTGAGGATGAGG
CTGCAACCTGAAGATTTTGGAACTTA
AGAACCAGTTCTCCCTGAAGCTGAGT
huKLC-
CTGATTATTACTGCCAGTCCTATGAC
CTTCTGTCAACAGAGTTACAGTACCC
TCTGTGACCGCCGCAGACACGGCCG
S176K(IgG-Fab);
AGCAGCCTGGGTGGTTGGGTGTTCG
CTCCCACTTTCGGCGGAGGGACCAA
TGTATTACTGTGCGAGGCCCAGTAAC
LMRID: SS-30822
GCGGAGGGACCAAGCTGACCGTCCT
GGTGGAGCTCAAACGAACGGTGGCT
TACGATGCTTTTGATATCTGGGGCCA
ACAGCCCAAGGCTGCACCCTCGGTC
GCACCATCTGTCTTCATCTTCCCGCC
AGGGACAATGGTCACCGTGTCCTCA
ACTCTGTTCCCGCCCTCCTCTGAGGA
ATCTGATGAGCAGTTGAAATCTGGA
GCCTCCACCAAGGGCCCATCGGTCTT
GCTTCAAGCCAACAAGGCCACACTG
ACTGCCTCTGTTGTGTGCCTGCTGAA
CCCCCTGGCACCCTCCTCCAAGAGCA
GTGTGTCTCATCAGTGACTTCTACCC
TAACTTCTATCCCAGAGAGGCCAAA
CCTCTGGGGGCACAGCGGCCCTGGG
GGGAGCCGTGACAGTGGCCTGGAAG
GTACAGTGGAAGGTGGATAACGCCC
CTGCCTGGTCAAGGACTACTTCCCCG
GCAGATAGCAGCCCCGTCAAGGCGG
TCCAATCGGGTAACTCCCAGGAGAG
AACCGGTGACGGTGTCGTGGAACTC
GAGTGGAAACCACCACACCCTCCAA
TGTCACAGAGCAGGACAGCAAGGAC
AGGCGCCCTGACCAGCGGCGTGCAC
ACAAAGCAACAACAAGTACGCGGCC
AGCACCTACAGCCTCAAGAGCACCC
ACCTTCCCGGCTGTCCTACAGTCCTC
GAAAGCTATCTGAGCCTGACGCCTG
TGACGCTGAGCAAAGCAGACTACGA
AGGACTCTACTCCCTCAAGAGCGTG
AGCAGTGGAAGTCCCACAGAAGCTA
GAAACACAAAGTCTACGCCTGCGAA
GTGACCGTGCCCTCCAGCAGCTTGGG
CAGCTGCCAGGTCACGCATGAAGGG
GTCACCCATCAGGGCCTGAGCTCGCC
CACCCAGACCTACATCTGCAACGTG
AGCACCGTGGAGAAGACAGTGGCCC
CGTCACAAAGAGCTTCAACAGGGGA
AATCACAAGCCCAGCAACACCAAGG
CTACAGAATGTTCA
GAGTGT
TGGACAAGAAAGTTGAGCCCAAATC
(SEQ ID NO: 665)
(SEQ ID NO: 666)
TTGTGACAAAACTCACACATGCCCAC
CGTGCCCAGCACCTGAACTCCTGGG
GGGACCGTCAGTCTTCCTCTTCCCCC
CAAAACCCAAGGACACCCTCATGAT
CTCCCGGACCCCTGAGGTCACATGCG
TGGTGGTGGACGTGAGCCACGAAGA
CCCTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGTGCGAGGAGCAG
TACGGCAGCACGTACCGTTGCGTCA
GCGTCCTCACCGTCCTGCACCAGGAC
TGGCTGAATGGCAAGGAGTACAAGT
GCAAGGTGTCCAACAAAGCCCTCCC
AGCCCCCATCGAGAAAACCATCTCC
AAAGCCAAAGGGCAGCCCCGAGAAC
CACAGGTGTACACCCTGCCCCCATCC
CGGGAGGAGATGACCAAGAACCAGG
TCAGCCTGACCTGCCTGGTCAAAGGC
TTCTATCCCAGCGACATCGCCGTGGA
GTGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCCG
TGCTGGACTCCGACGGCTCCTTCTTC
CTCTATAGCAAGCTCACCGTGGACA
AGAGCAGGTGGCAGCAGGGGAACGT
CTTCTCATGCTCCGTGATGCATGAGG
CTCTGCACAACCACTACACGCAGAA
GAGCCTCTCCCTGTCTCCGGGTGGTG
GCGGATCGGGAGGTGGCGGATCCCA
GGTGCAACTGGTGCAGTCTGGGGCT
GAAGTGAAGAAGCCTGGGGCCTCAG
TGAAGGTGTCCTGCAAGGCTTCTGGA
TACACCTTCCCCGGCTACTATATGTA
CTGGTTGCGACAGGCCCCTGGACAA
GGACTTGAGTGGATGGGATGGATCA
ACCCTGACAGTGGTGACACAAACTA
TGCACAGAAGTTTCAGGGCAGGGTC
ACCATGACCAGGGACACGTCCATCA
GCACAGCCTTTATGGAGCTGAGCAG
GCTGAGATCAGACGACACGGCCGTG
TATTACTGTGCGAGAGAGAAGCCCA
GATATTTTGACTCCTTCTACTACTAC
CTTATGGACGTCTGGGGCCAAGGGA
CCACGGTCACCGTGTCCTCAGCAAGC
ACGAAGGGGCCGTCCGTATTTCCGCT
TGCGCCCTCGTCGAAGTCAACTTCGG
GAGGGACCGCGGCACTTGGCTGTCTT
GTCAAAGATTACTTCCCTGAGCCAGT
GACAGTCAGCTGGAATTCCGGTGCC
CTCACGTCAGGAGTACATACATTCCC
TGCGGTATTGCAGTCCTCCGGACTCT
ACTCCCTGGAGTCGGTGGTAACGGT
GCCCAGCTCCAGCTTGGGGACCCAG
ACGTACATTTGTAACGTGAATCACAA
ACCAAGCAATACTAAGGTAGATAAG
AAAGTAGAACCGAAGAGCTGC
(SEQ ID NO: 667)
AA
QSVLTQPPSVSGAPGQRVTISCTGSSSN
DIQMTQSPSSLSASVGDRVTITCRAGQ
QVQLQESGPGLVKPSETLSLTCTVSGG
IGAGYDVHWYQQVPGTAPKLLIYGNS
NISRHLNWYQQNPGKAPKVLIHPASSL
SISSSSYYWGWIRQPPGKGLEWIGSIYY
KRPSGVPDRFSGSKSGTSASLAITGLQ
PSGVPSRFSGSGSGTDFSLTISSLQPED
SGITNYNPSLKSRVTISVDTSKNQFSLK
AEDEADYYCQSYDSSLGGWVFGGGT
FGTYFCQQSYSTPPTFGGGTKVELKRTV
LSSVTAADTAVYYCARPSNYDAFDIW
KLTVLQPKAAPSVTLFPPSSEELQANK
AAPSVFIFPPSDEQLKSGTASVVCLLNN
GQGTMVTVSSASTKGPSVFPLAPSSKS
ATLVCLISDFYPGAVTVAWKADSSPV
FYPREAKVQWKVDNALQSGNSQESVT
TSGGTAALGCLVKDYFPEPVTVSWNS
KAGVETTTPSKQSNNKYAAESYLSLTP
EQDSKDSTYSLKSTLTLSKADYEKHK
GALTSGVHTFPAVLQSSGLYSLKSVVT
EQWKSHRSYSCQVTHEGSTVEKTVAP
VYACEVTHQGLSSPVTKSFNRGEC
VPSSSLGTQTYICNVNHKPSNTKVDKK
TECS
(SEQ ID NO: 669)
VEPKSCDKTHTCPPCPAPELLGGPSVF
(SEQ ID NO: 668)
LFPPKPKDTLMISRTPEVTCVVVDVSH
EDPEVKFNWYVDGVEVHNAKTKPCE
EQYGSTYRCVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPRE
PQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLVQSGAEVKKPGASVKVSC
KASGYTFPGYYMYWLRQAPGQGLEW
MGWINPDSGDTNYAQKFQGRVTMTR
DTSISTAFMELSRLRSDDTAVYYCARE
KPRYFDSFYYYLMDVWGQGTTVTVSS
ASTKGPSVFPLAPSSKSTSGGTAALGC
LVKDYFPEPVTVSWNSGALTSGVHTFP
AVLQSSGLYSLESVVTVPSSSLGTQTYI
CNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 670)
iPS:
21-233_4G12_IgG2_21-
[hu anti-
NA
CAGTCAGTGTTGACGCAGCCGCCCTC
CAGGCTGTGCCGACTCAGCCCTCTTC
CAGGTGCAGCTGCAGGAGTCGGGCC
576140
2302_33H92_Fab
<hu Mesothelin>4G12VH]::
AGTGTCTGGGGCCCCAGGGCAGAGG
CCTCTCTGCATCTCCTGGAGCATCAG
CAGGACTGGTGAAGCCTTCGGAAAC
huIgG1zSEFL2*GK-
GTCACCATCTCCTGCACTGGGAGCAG
CCAGTCTCACCTGCACCTTACGCAGT
CCTGTCCCTCACCTGCACTGTCTCTG
K::(G4S)2::
CTCCAACATCGGGGCAGGTTATGAT
GGCATCAATGTTGGTTCCTCCAGGAT
GTGGCTCCATCAGCAGTAGTAGTTAC
[hu anti-<huCD40>
GTTCACTGGTACCAGCAGGTTCCAGG
CTATTGGTACCAGCAGAAGCCAGGG
TACTGGGGCTGGATCAGGCAGCCCC
21-230_33H9VH]::
AACAGCCCCCAAACTCCTCATCTATG
AGTCCTCCCCAGTTTCTCCTGAGGTA
CAGGGAAGGGGCTGGAGTGGATTGG
huIgG1z-CH1-
GTAACAGCAAGCGGCCCTCAGGGGT
CACATCAGACTCAGATAAATTGCAG
GAGTATCTATTATAGTGGGATCACCA
E::EPKSC +
CCCTGACCGATTCTCTGGCTCCAAGT
GGCTCTGGAGTCCCCAGCCGCTTCTC
ACTACAACCCGTCCCTCAAGAGTCG
[anti-<hu Mesothelin>
CTGGCACCTCAGCCTCCCTGGCCATC
TGGATCCAAAGATGCTTCGGCCAAT
AGTCACCATCTCCGTAGACACGTCCA
4G12VL::huLLC2-E +
ACTGGGCTCCAGGCTGAGGATGAGG
GCAGGACTTTTACTCATCTCTGGGCT
AGAACCAGTTCTCCCTGAAGCTGAGT
[anti-<huCD40>
CTGATTATTACTGCCAGTCCTATGAC
CCAGTCTGAGGATGAGGCTGACTATT
TCTGTGACCGCCGCAGACACGGCCG
21-230_33H9VL]::
AGCAGCCTGGGTGGTTGGGTGTTCG
ACTGTATGATTTGGCACAGCAGCGCT
TGTATTACTGTGCGAGGCCCAGTAAC
huLLC2-K(IgG-Fab);
GCGGAGGGACCAAGCTGACCGTCCT
GTGGTATTCGGCGGAGGGACCAAAC
TACGATGCTTTTGATATCTGGGGCCA
LMRID: SS-30823
ACAGCCCAAGGCTGCACCCTCGGTC
TGACCGTCCTAGGTCAGCCCAAGGCT
AGGGACAATGGTCACCGTGTCCTCA
ACTCTGTTCCCGCCCTCCTCTGAGGA
GCACCCTCGGTCACTCTGTTCCCGCC
GCCTCCACCAAGGGCCCATCGGTCTT
GCTTCAAGCCAACAAGGCCACACTG
CTCCTCTGAGGAGCTTCAAGCCAACA
CCCCCTGGCACCCTCCTCCAAGAGCA
GTGTGTCTCATCAGTGACTTCTACCC
AGGCCACACTGGTGTGTCTCATCAGT
CCTCTGGGGGCACAGCGGCCCTGGG
GGGAGCCGTGACAGTGGCCTGGAAG
GACTTCTACCCGGGAGCCGTGACAG
CTGCCTGGTCAAGGACTACTTCCCCG
GCAGATAGCAGCCCCGTCAAGGCGG
TGGCCTGGAAGGCAGATAGCAGCCC
AACCGGTGACGGTGTCGTGGAACTC
GAGTGGAAACCACCACACCCTCCAA
CGTCAAGGCGGGAGTGGAAACCACC
AGGCGCCCTGACCAGCGGCGTGCAC
ACAAAGCAACAACAAGTACGCGGCC
ACACCCTCCAAACAAAGCAACAACA
ACCTTCCCGGCTGTCCTACAGTCCTC
GAAAGCTATCTGAGCCTGACGCCTG
AGTACGCGGCCAAGAGCTATCTGAG
AGGACTCTACTCCCTCAAGAGCGTG
AGCAGTGGAAGTCCCACAGAAGCTA
CCTGACGCCTGAGCAGTGGAAGTCC
GTGACCGTGCCCTCCAGCAGCTTGGG
CAGCTGCCAGGTCACGCATGAAGGG
CACAGAAGCTACAGCTGCCAGGTCA
CACCCAGACCTACATCTGCAACGTG
AGCACCGTGGAGAAGACAGTGGCCC
CGCATGAAGGGAGCACCGTGGAGAA
AATCACAAGCCCAGCAACACCAAGG
CTACAGAATGTTCA
GACAGTGGCCCCTACAGAATGTTCA
TGGACAAGAAAGTTGAGCCCAAATC
(SEQ ID NO: 671)
(SEQ ID NO: 672)
TTGTGACAAAACTCACACATGCCCAC
CGTGCCCAGCACCTGAACTCCTGGG
GGGACCGTCAGTCTTCCTCTTCCCCC
CAAAACCCAAGGACACCCTCATGAT
CTCCCGGACCCCTGAGGTCACATGCG
TGGTGGTGGACGTGAGCCACGAAGA
CCCTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGTGCGAGGAGCAG
TACGGCAGCACGTACCGTTGCGTCA
GCGTCCTCACCGTCCTGCACCAGGAC
TGGCTGAATGGCAAGGAGTACAAGT
GCAAGGTGTCCAACAAAGCCCTCCC
AGCCCCCATCGAGAAAACCATCTCC
AAAGCCAAAGGGCAGCCCCGAGAAC
CACAGGTGTACACCCTGCCCCCATCC
CGGGAGGAGATGACCAAGAACCAGG
TCAGCCTGACCTGCCTGGTCAAAGGC
TTCTATCCCAGCGACATCGCCGTGGA
GTGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCCG
TGCTGGACTCCGACGGCTCCTTCTTC
CTCTATAGCAAGCTCACCGTGGACA
AGAGCAGGTGGCAGCAGGGGAACGT
CTTCTCATGCTCCGTGATGCATGAGG
CTCTGCACAACCACTACACGCAGAA
GAGCCTCTCCCTGTCTCCGGGTGGTG
GCGGATCGGGAGGTGGCGGATCCCA
GGTGCAGTTGGTGGAGTCTGGGGGA
GGCGTGGTCCAGCCTGGGAGGTCCC
TGAGACTCTCCTGTGCAGCGTCTGGA
TTCACCTTCAGTAGCCATGGCATGCA
CTGGGTCCGCCAACCTCCAGGCAAG
GGGCTGGAGTGGGTGGCAGTTATCT
GGTATGATGGAAGTAATGAATACTA
TGGAGACTCCGTGAAGGGCCGATTC
ACCATCTCCAGAGACAATTCCAAGA
ACACGCTGTATCTGCAAATGAACAG
CCTGAGAGTCGAGGACACGGCTGTG
TATTACTGTACGAGAGGGGGGGGCC
ACTGGAACTACGAGGGCCACTACTA
TGGTATGGACGTCTGGGGCCAAGGG
ACCACGGTCACCGTGTCCTCAGCAA
GCACGAAGGGGCCGTCCGTATTTCC
GCTTGCGCCCTCGTCGAAGTCAACTT
CGGGAGGGACCGCGGCACTTGGCTG
TCTTGTCAAAGATTACTTCCCTGAGC
CAGTGACAGTCAGCTGGAATTCCGG
TGCCCTCACGTCAGGAGTACATACAT
TCCCTGCGGTATTGCAGTCCTCCGGA
CTCTACTCCCTGGAGTCGGTGGTAAC
GGTGCCCAGCTCCAGCTTGGGGACC
CAGACGTACATTTGTAACGTGAATCA
CAAACCAAGCAATACTAAGGTAGAT
AAGAAAGTAGAACCGAAGAGCTGC
(SEQ ID NO: 673)
AA
QSVLTQPPSVSGAPGQRVTISCTGSSSN
QAVPTQPSSLSASPGASASLTCTLRSGI
QVQLQESGPGLVKPSETLSLTCTVSGG
IGAGYDVHWYQQVPGTAPKLLIYGNS
NVGSSRIYWYQQKPGSPPQFLLRYTSD
SISSSSYYWGWIRQPPGKGLEWIGSIYY
KRPSGVPDRFSGSKSGTSASLAITGLQ
SDKLQGSGVPSRFSGSKDASANAGLLL
SGITNYNPSLKSRVTISVDTSKNQFSLK
AEDEADYYCQSYDSSLGGWVFGGGT
ISGLQSEDEADYYCMIWHSSAVVFGG
LSSVTAADTAVYYCARPSNYDAFDIW
KLTVLQPKAAPSVTLFPPSSEELQANK
GTKLTVLGQPKAAPSVTLFPPSSEELQ
GQGTMVTVSSASTKGPSVFPLAPSSKS
ATLVCLISDFYPGAVTVAWKADSSPV
ANKATLVCLISDFYPGAVTVAWKADS
TSGGTAALGCLVKDYFPEPVTVSWNS
KAGVETTTPSKQSNNKYAAESYLSLTP
SPVKAGVETTTPSKQSNNKYAAKSYL
GALTSGVHTFPAVLQSSGLYSLKSVVT
EQWKSHRSYSCQVTHEGSTVEKTVAP
SLTPEQWKSHRSYSCQVTHEGSTVEKT
VPSSSLGTQTYICNVNHKPSNTKVDKK
TECS
VAPTECS
VEPKSCDKTHTCPPCPAPELLGGPSVF
(SEQ ID NO: 674)
(SEQ ID NO: 675)
LFPPKPKDTLMISRTPEVTCVVVDVSH
EDPEVKFNWYVDGVEVHNAKTKPCE
EQYGSTYRCVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPRE
PQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLVESGGGVVQPGRSLRLSC
AASGFTFSSHGMHWVRQPPGKGLEW
VAVIWYDGSNEYYGDSVKGRFTISRD
NSKNTLYLQMNSLRVEDTAVYYCTRG
GGHWNYEGHYYGMDVWGQGTTVTV
SSASTKGPSVFPLAPSSKSTSGGTAALG
CLVKDYFPEPVTVSWNSGALTSGVHT
FPAVLQSSGLYSLESVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 676)
iPS:
21-233_4G12_IgG_21-
[hu anti-
NA
CAGTCAGTGTTGACGCAGCCGCCCTC
CAGTCTGCCCTGACTCAGCCTCGCTC
CAGGTGCAGCTGCAGGAGTCGGGCC
576145
230_35F11_Fab
<hu Mesothelin>
AGTGTCTGGGGCCCCAGGGCAGAGG
AGTGTCCGGGAGCCCTGGACAGTCA
CAGGACTGGTGAAGCCTTCGGAAAC
4G12VH]::huIgG1zSEFL2*GK-
GTCACCATCTCCTGCACTGGGAGCAG
GTCACCATCTCCTGCACTGGAACCAG
CCTGTCCCTCACCTGCACTGTCTCTG
K::(G4S)2:[hu anti-<huCD40>
CTCCAACATCGGGGCAGGTTATGAT
CAGTGATGTTGGTGGTTATATCTTTG
GTGGCTCCATCAGCAGTAGTAGTTAC
21-230_35F11VH]::huIgG1z-
GTTCACTGGTACCAGCAGGTTCCAGG
TCTCCTGGTACCAACAACACCCAGGC
TACTGGGGCTGGATCAGGCAGCCCC
CH1-E::EPKSC +
AACAGCCCCCAAACTCCTCATCTATG
AAAGCCCCCAAACTCATGATTTATGA
CAGGGAAGGGGCTGGAGTGGATTGG
[anti-<hu Mesothelin>
GTAACAGCAAGCGGCCCTCAGGGGT
TGTCAGTAAGCGGCCCTCTGGGGTCC
GAGTATCTATTATAGTGGGATCACCA
4G12VL]::huLLC2-E +
CCCTGACCGATTCTCTGGCTCCAAGT
CTGATCGCTTCTCTGGCTCCAAGTCT
ACTACAACCCGTCCCTCAAGAGTCG
[anti-<huCD40>
CTGGCACCTCAGCCTCCCTGGCCATC
GTCAACACGGCCTCCCTGACCATCTC
AGTCACCATCTCCGTAGACACGTCCA
21-230_35F11VL]::huLLC2-
ACTGGGCTCCAGGCTGAGGATGAGG
TGGGCTCCAGGCTGAGGATGAGACT
AGAACCAGTTCTCCCTGAAGCTGAGT
K(IgG-Fab); LMRID:
CTGATTATTACTGCCAGTCCTATGAC
GATTATTACTGCTGCTCATATGCAGG
TCTGTGACCGCCGCAGACACGGCCG
SS-30824
AGCAGCCTGGGTGGTTGGGTGTTCG
CAACTACACTTATGTCTTCGGAACTG
TGTATTACTGTGCGAGGCCCAGTAAC
GCGGAGGGACCAAGCTGACCGTCCT
GGACCAAGGTCACCGTCCTAGGTCA
TACGATGCTTTTGATATCTGGGGCCA
ACAGCCCAAGGCTGCACCCTCGGTC
GCCCAAGGCTGCACCCTCGGTCACTC
AGGGACAATGGTCACCGTGTCCTCA
ACTCTGTTCCCGCCCTCCTCTGAGGA
TGTTCCCGCCCTCCTCTGAGGAGCTT
GCCTCCACCAAGGGCCCATCGGTCTT
GCTTCAAGCCAACAAGGCCACACTG
CAAGCCAACAAGGCCACACTGGTGT
CCCCCTGGCACCCTCCTCCAAGAGCA
GTGTGTCTCATCAGTGACTTCTACCC
GTCTCATCAGTGACTTCTACCCGGGA
CCTCTGGGGGCACAGCGGCCCTGGG
GGGAGCCGTGACAGTGGCCTGGAAG
GCCGTGACAGTGGCCTGGAAGGCAG
CTGCCTGGTCAAGGACTACTTCCCCG
GCAGATAGCAGCCCCGTCAAGGCGG
ATAGCAGCCCCGTCAAGGCGGGAGT
AACCGGTGACGGTGTCGTGGAACTC
GAGTGGAAACCACCACACCCTCCAA
GGAAACCACCACACCCTCCAAACAA
AGGCGCCCTGACCAGCGGCGTGCAC
ACAAAGCAACAACAAGTACGCGGCC
AGCAACAACAAGTACGCGGCCAAGA
ACCTTCCCGGCTGTCCTACAGTCCTC
GAAAGCTATCTGAGCCTGACGCCTG
GCTATCTGAGCCTGACGCCTGAGCA
AGGACTCTACTCCCTCAAGAGCGTG
AGCAGTGGAAGTCCCACAGAAGCTA
GTGGAAGTCCCACAGAAGCTACAGC
GTGACCGTGCCCTCCAGCAGCTTGGG
CAGCTGCCAGGTCACGCATGAAGGG
TGCCAGGTCACGCATGAAGGGAGCA
CACCCAGACCTACATCTGCAACGTG
AGCACCGTGGAGAAGACAGTGGCCC
CCGTGGAGAAGACAGTGGCCCCTAC
AATCACAAGCCCAGCAACACCAAGG
CTACAGAATGTTCA
AGAATGTTCA
TGGACAAGAAAGTTGAGCCCAAATC
(SEQ ID NO: 677)
(SEQ ID NO: 678)
TTGTGACAAAACTCACACATGCCCAC
CGTGCCCAGCACCTGAACTCCTGGG
GGGACCGTCAGTCTTCCTCTTCCCCC
CAAAACCCAAGGACACCCTCATGAT
CTCCCGGACCCCTGAGGTCACATGCG
TGGTGGTGGACGTGAGCCACGAAGA
CCCTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGTGCGAGGAGCAG
TACGGCAGCACGTACCGTTGCGTCA
GCGTCCTCACCGTCCTGCACCAGGAC
TGGCTGAATGGCAAGGAGTACAAGT
GCAAGGTGTCCAACAAAGCCCTCCC
AGCCCCCATCGAGAAAACCATCTCC
AAAGCCAAAGGGCAGCCCCGAGAAC
CACAGGTGTACACCCTGCCCCCATCC
CGGGAGGAGATGACCAAGAACCAGG
TCAGCCTGACCTGCCTGGTCAAAGGC
TTCTATCCCAGCGACATCGCCGTGGA
GTGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCCG
TGCTGGACTCCGACGGCTCCTTCTTC
CTCTATAGCAAGCTCACCGTGGACA
AGAGCAGGTGGCAGCAGGGGAACGT
CTTCTCATGCTCCGTGATGCATGAGG
CTCTGCACAACCACTACACGCAGAA
GAGCCTCTCCCTGTCTCCGGGTGGTG
GCGGATCGGGAGGTGGCGGATCCCA
GGTGCAGCTGGTGGAGTCTGGGGGA
GGCGTGGTCCAGCCTGGGAGGTCCC
TGAGACTCTCCTGTGCAGCGTCTGGA
TTCACCCTCAGTAGCTATGGCATGCA
CTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCAGTTATCT
GGTATGATGGAAGTAATAAATACTA
TGCAGACTCCGTGAAGGGCCGAGTC
ACCATCTCCAGAGACAATTCCAAGA
ACACGCTGTATCTGCAAATGAATAG
CCTGAGAGCCGAGGACACGGCTGTG
TATTACTGTACGAGAGATGGCCGGA
ACTACGTCTACTTTGACAACTGGGGC
CAGGGAACCCTGGTCACCGTGTCCTC
AGCAAGCACGAAGGGGCCGTCCGTA
TTTCCGCTTGCGCCCTCGTCGAAGTC
AACTTCGGGAGGGACCGCGGCACTT
GGCTGTCTTGTCAAAGATTACTTCCC
TGAGCCAGTGACAGTCAGCTGGAAT
TCCGGTGCCCTCACGTCAGGAGTACA
TACATTCCCTGCGGTATTGCAGTCCT
CCGGACTCTACTCCCTGGAGTCGGTG
GTAACGGTGCCCAGCTCCAGCTTGG
GGACCCAGACGTACATTTGTAACGT
GAATCACAAACCAAGCAATACTAAG
GTAGATAAGAAAGTAGAACCGAAGA
GCTGC
(SEQ ID NO: 679)
AA
QSVLTQPPSVSGAPGQRVTISCTGSSSN
QSALTQPRSVSGSPGQSVTISCTGTSS
QVQLQESGPGLVKPSETLSLTCTVSGG
IGAGYDVHWYQQVPGTAPKLLIYGNS
DVGGYIFVSWYQQHPGKAPKLMIYDVS
SISSSSYYWGWIRQPPGKGLEWIGSIYY
KRPSGVPDRFSGSKSGTSASLAITGLQ
KRPSGVPDRFSGSKSVNTASLTISGLQ
SGITNYNPSLKSRVTISVDTSKNQFSLK
AEDEADYYCQSYDSSLGGWVFGGGT
AEDETDYYCCSYAGNYTYVFGTGTKV
LSSVTAADTAVYYCARPSNYDAFDIW
KLTVLQPKAAPSVTLFPPSSEELQANK
TVLGQPKAAPSVTLFPPSSEELQANKA
GQGTMVTVSSASTKGPSVFPLAPSSKS
ATLVCLISDFYPGAVTVAWKADSSPV
TLVCLISDFYPGAVTVAWKADSSPVK
TSGGTAALGCLVKDYFPEPVTVSWNS
KAGVETTTPSKQSNNKYAAESYLSLTP
AGVETTTPSKQSNNKYAAKSYLSLTPE
GALTSGVHTFPAVLQSSGLYSLKSVVT
EQWKSHRSYSCQVTHEGSTVEKTVAP
QWKSHRSYSCQVTHEGSTVEKTVAPT
VPSSSLGTQTYICNVNHKPSNTKVDKK
TECS
ECS
VEPKSCDKTHTCPPCPAPELLGGPSVF
(SEQ ID NO: 680)
(SEQ ID NO: 681)
LFPPKPKDTLMISRTPEVTCVVVDVSH
EDPEVKFNWYVDGVEVHNAKTKPCE
EQYGSTYRCVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPRE
PQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLVESGGGVVQPGRSLRLSC
AASGFTLSSYGMHWVRQAPGKGLEW
VAVIWYDGSNKYYADSVKGRVTISRD
NSKNTLYLQMNSLRAEDTAVYYCTRD
GRNYVYFDNWGQGTLVTVSSASTKGP
SVFPLAPSSKSTSGGTAALGCLVKDYF
PEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLESVVTVPSSSLGTQTYICNVNH
KPSNTKVDKKVEPKSC
(SEQ ID NO: 682)
iPS:
21-233_4G12_IgG_21-
[hu anti-<hu Mesothelin>
NA
CAGTCAGTGTTGACGCAGCCGCCCTC
GAAATTGTGTTGACGCAGTCTCCAGG
CAGGTGCAGCTGCAGGAGTCGGGCC
576150
230_36F3_Fab
4G12VH]::huIgG1zSEFL2*GK-
AGTGTCTGGGGCCCCAGGGCAGAGG
CACCCTGTCTTTGTCTCCAGGGGAAA
CAGGACTGGTGAAGCCTTCGGAAAC
K::(G4S)2::[hu anti-
GTCACCATCTCCTGCACTGGGAGCAG
GAGCCACCCTCTCCTGCAGGGCCAGT
CCTGTCCCTCACCTGCACTGTCTCTG
<huCD40>
CTCCAACATCGGGGCAGGTTATGAT
CAGAGTGTTAGCAGCAACTACTTAG
GTGGCTCCATCAGCAGTAGTAGTTAC
21-230_36F3VH]::huIgG1z-
GTTCACTGGTACCAGCAGGTTCCAGG
CCTGGTACCAACAGAAACCTGGCCA
TACTGGGGCTGGATCAGGCAGCCCC
CH1-E::EPKSC + [anti-
AACAGCCCCCAAACTCCTCATCTATG
GGCTCCCAGGGCCCTTATCTATGCTG
CAGGGAAGGGGCTGGAGTGGATTGG
<huMesotheline>4G12VL]::
GTAACAGCAAGCGGCCCTCAGGGGT
CATCCAACAGGGCCGCTGGCATCTC
GAGTATCTATTATAGTGGGATCACCA
huLLC2-E +
CCCTGACCGATTCTCTGGCTCCAAGT
AGACAGGTTCAGTGGCAGTGGGTCT
ACTACAACCCGTCCCTCAAGAGTCG
[anti-<huCD40>
CTGGCACCTCAGCCTCCCTGGCCATC
GGGACAGACTTCACTCTCACCATCAG
AGTCACCATCTCCGTAGACACGTCCA
21-230_36F3VL]::
ACTGGGCTCCAGGCTGAGGATGAGG
CAGACTGGAGCCTGAAGATTTTGCA
AGAACCAGTTCTCCCTGAAGCTGAGT
huKLC-S176K(IgG-
CTGATTATTACTGCCAGTCCTATGAC
GTGTATTTCTGTCAGCAGTATGGTAG
TCTGTGACCGCCGCAGACACGGCCG
Fab); LMRID:
AGCAGCCTGGGTGGTTGGGTGTTCG
CTCACCGCTCACTTTCGGCGGAGGGA
TGTATTACTGTGCGAGGCCCAGTAAC
SS-30825
GCGGAGGGACCAAGCTGACCGTCCT
CTAAGGTGGAGATCAAACGAACGGT
TACGATGCTTTTGATATCTGGGGCCA
ACAGCCCAAGGCTGCACCCTCGGTC
GGCTGCACCATCTGTCTTCATCTTCC
AGGGACAATGGTCACCGTGTCCTCA
ACTCTGTTCCCGCCCTCCTCTGAGGA
CGCCATCTGATGAGCAGTTGAAATCT
GCCTCCACCAAGGGCCCATCGGTCTT
GCTTCAAGCCAACAAGGCCACACTG
GGAACTGCCTCTGTTGTGTGCCTGCT
CCCCCTGGCACCCTCCTCCAAGAGCA
GTGTGTCTCATCAGTGACTTCTACCC
GAATAACTTCTATCCCAGAGAGGCC
CCTCTGGGGGCACAGCGGCCCTGGG
GGGAGCCGTGACAGTGGCCTGGAAG
AAAGTACAGTGGAAGGTGGATAACG
CTGCCTGGTCAAGGACTACTTCCCCG
GCAGATAGCAGCCCCGTCAAGGCGG
CCCTCCAATCGGGTAACTCCCAGGA
AACCGGTGACGGTGTCGTGGAACTC
GAGTGGAAACCACCACACCCTCCAA
GAGTGTCACAGAGCAGGACAGCAAG
AGGCGCCCTGACCAGCGGCGTGCAC
ACAAAGCAACAACAAGTACGCGGCC
GACAGCACCTACAGCCTCAAGAGCA
ACCTTCCCGGCTGTCCTACAGTCCTC
GAAAGCTATCTGAGCCTGACGCCTG
CCCTGACGCTGAGCAAAGCAGACTA
AGGACTCTACTCCCTCAAGAGCGTG
AGCAGTGGAAGTCCCACAGAAGCTA
CGAGAAACACAAAGTCTACGCCTGC
GTGACCGTGCCCTCCAGCAGCTTGGG
CAGCTGCCAGGTCACGCATGAAGGG
GAAGTCACCCATCAGGGCCTGAGCT
CACCCAGACCTACATCTGCAACGTG
AGCACCGTGGAGAAGACAGTGGCCC
CGCCCGTCACAAAGAGCTTCAACAG
AATCACAAGCCCAGCAACACCAAGG
CTACAGAATGTTCA
GGGAGAGTGT
TGGACAAGAAAGTTGAGCCCAAATC
(SEQ ID NO: 683)
(SEQ ID NO: 684)
TTGTGACAAAACTCACACATGCCCAC
CGTGCCCAGCACCTGAACTCCTGGG
GGGACCGTCAGTCTTCCTCTTCCCCC
CAAAACCCAAGGACACCCTCATGAT
CTCCCGGACCCCTGAGGTCACATGCG
TGGTGGTGGACGTGAGCCACGAAGA
CCCTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGTGCGAGGAGCAG
TACGGCAGCACGTACCGTTGCGTCA
GCGTCCTCACCGTCCTGCACCAGGAC
TGGCTGAATGGCAAGGAGTACAAGT
GCAAGGTGTCCAACAAAGCCCTCCC
AGCCCCCATCGAGAAAACCATCTCC
AAAGCCAAAGGGCAGCCCCGAGAAC
CACAGGTGTACACCCTGCCCCCATCC
CGGGAGGAGATGACCAAGAACCAGG
TCAGCCTGACCTGCCTGGTCAAAGGC
TTCTATCCCAGCGACATCGCCGTGGA
GTGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCCG
TGCTGGACTCCGACGGCTCCTTCTTC
CTCTATAGCAAGCTCACCGTGGACA
AGAGCAGGTGGCAGCAGGGGAACGT
CTTCTCATGCTCCGTGATGCATGAGG
CTCTGCACAACCACTACACGCAGAA
GAGCCTCTCCCTGTCTCCGGGTGGTG
GCGGATCGGGAGGTGGCGGATCCCA
GGTACAGCTGCAACAGTCAGGTCCA
GGACTGGTGAAGCCCTCGCAGACCC
TCTCACTCACCTGTGCCATCTCCGGG
GACAGTGTCTCTAGCAGCCGTACTGC
TTGGAACTGGATCAGGCAGTCCCCAT
CGAGAGGCCTTGAGTGGCTGGGAAG
GACATACTACAGGTCCAAGTGGTAT
CATGATTATTCAGTATCTGTGAAAAG
TCGAATCACCATCGACCCAGACACA
TCCAAGAACCAGTTCTCCCTGCAGCT
GAACTCTGTGACTCCCGAGGACACG
GCTGTTTATTATTGTGCAAGAGGGGC
TGCTCCCTTTGACTACTGGGGCCAGG
GAACCCTGGTCACCGTGTCCTCAGCA
AGCACGAAGGGGCCGTCCGTATTTC
CGCTTGCGCCCTCGTCGAAGTCAACT
TCGGGAGGGACCGCGGCACTTGGCT
GTCTTGTCAAAGATTACTTCCCTGAG
CCAGTGACAGTCAGCTGGAATTCCG
GTGCCCTCACGTCAGGAGTACATAC
ATTCCCTGCGGTATTGCAGTCCTCCG
GACTCTACTCCCTGGAGTCGGTGGTA
ACGGTGCCCAGCTCCAGCTTGGGGA
CCCAGACGTACATTTGTAACGTGAAT
CACAAACCAAGCAATACTAAGGTAG
ATAAGAAAGTAGAACCGAAGAGCTG
C
(SEQ ID NO: 685)
AA
QSVLTQPPSVSGAPGQRVTISCTGSSSN
EIVLTQSPGTLSLSPGERATLSCRASQS
QVQLQESGPGLVKPSETLSLTCTVSGG
IGAGYDVHWYQQVPGTAPKLLIYGNS
VSSNYLAWYQQKPGQAPRALIYAASN
SISSSSYYWGWIRQPPGKGLEWIGSIYY
KRPSGVPDRFSGSKSGTSASLAITGLQ
RAAGISDRFSGSGSGTDFTLTISRLEPE
SGITNYNPSLKSRVTISVDTSKNQFSLK
AEDEADYYCQSYDSSLGGWVFGGGT
DFAVYFCQQYGSSPLTFGGGTKVEIKR
LSSVTAADTAVYYCARPSNYDAFDIW
KLTVLQPKAAPSVTLFPPSSEELQANK
TVAAPSVFIFPPSDEQLKSGTASVVCLL
GQGTMVTVSSASTKGPSVFPLAPSSKS
ATLVCLISDFYPGAVTVAWKADSSPV
NNFYPREAKVQWKVDNALQSGNSQE
TSGGTAALGCLVKDYFPEPVTVSWNS
KAGVETTTPSKQSNNKYAAESYLSLTP
SVTEQDSKDSTYSLKSTLTLSKADYEK
GALTSGVHTFPAVLQSSGLYSLKSVVT
EQWKSHRSYSCQVTHEGSTVEKTVAP
HKVYACEVTHQGLSSPVTKSFNRGEC
VPSSSLGTQTYICNVNHKPSNTKVDKK
TECS
(SEQ ID NO: 687)
VEPKSCDKTHTCPPCPAPELLGGPSVF
(SEQ ID NO: 686)
LFPPKPKDTLMISRTPEVTCVVVDVSH
EDPEVKFNWYVDGVEVHNAKTKPCE
EQYGSTYRCVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPRE
PQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLQQSGPGLVKPSQTLSLTC
AISGDSVSSSRTAWNWIRQSPSRGLEW
LGRTYYRSKWYHDYSVSVKSRITIDPD
TSKNQFSLQLNSVTPEDTAVYYCARG
AAPFDYWGQGTLVTVSSASTKGPSVF
PLAPSSKSTSGGTAALGCLVKDYFPEP
VTVSWNSGALTSGVHTFPAVLQSSGL
YSLESVVTVPSSSLGTQTYICNVNHKP
SNTKVDKKVEPKSC
(SEQ ID NO: 688)
iPS:
21-233_4G12_IgG_21-
[hu anti-<hu Mesothelin>
NA
CAGTCAGTGTTGACGCAGCCGCCCTC
TCCTATGAGCTGACTCAGCCACCCTC
CAGGTGCAGCTGCAGGAGTCGGGCC
576155
230_37A6_Fab
4G12VH]::huIgG1zSEFL2*GK-
AGTGTCTGGGGCCCCAGGGCAGAGG
AGTGTCCGTGTCCCCAGGACAGACA
CAGGACTGGTGAAGCCTTCGGAAAC
K::(G4S)2::[hu anti-
GTCACCATCTCCTGCACTGGGAGCAG
GCCAGCATCACCTGCTCTGGAGAAA
CCTGTCCCTCACCTGCACTGTCTCTG
<huCD40>21-230_37A6VH]::
CTCCAACATCGGGGCAGGTTATGAT
GGTTGGGAAATAAATATATTTGCTGG
GTGGCTCCATCAGCAGTAGTAGTTAC
huIgG1z-CH1-E::EPKSC +
GTTCACTGGTACCAGCAGGTTCCAGG
TATCAGCAGAAGCCAGGCCAGTCCC
TACTGGGGCTGGATCAGGCAGCCCC
[anti-<hu Mesothelin>
AACAGCCCCCAAACTCCTCATCTATG
CTGTTCTGGTCATCTATCAAGATTTC
CAGGGAAGGGGCTGGAGTGGATTGG
4G12VL]::huLLC2-E +
GTAACAGCAAGCGGCCCTCAGGGGT
AAGCGGCCCTCAGGGATCCCTGAGC
GAGTATCTATTATAGTGGGATCACCA
[anti-<huCD40>
CCCTGACCGATTCTCTGGCTCCAAGT
GATTCTCTGGCTCCAACTCTGGGATC
ACTACAACCCGTCCCTCAAGAGTCG
21-230_37A6VL]::
CTGGCACCTCAGCCTCCCTGGCCATC
ACAGCCACTCTGACCATCAGCGGGA
AGTCACCATCTCCGTAGACACGTCCA
huLLC2-K(IgG-
ACTGGGCTCCAGGCTGAGGATGAGG
CCCAGGCTATGGATGAGGCTGACTA
AGAACCAGTTCTCCCTGAAGCTGAGT
Fab); LMRID:
CTGATTATTACTGCCAGTCCTATGAC
TTACTGTCAGGCGTGGGACAGCAGA
TCTGTGACCGCCGCAGACACGGCCG
SS-30826
AGCAGCCTGGGTGGTTGGGTGTTCG
ACTGTGGTATTCGGCGGAGGGACCA
TGTATTACTGTGCGAGGCCCAGTAAC
GCGGAGGGACCAAGCTGACCGTCCT
AGCTGACCGTCCTAGGTCAGCCCAA
TACGATGCTTTTGATATCTGGGGCCA
ACAGCCCAAGGCTGCACCCTCGGTC
GGCTGCACCCTCGGTCACTCTGTTCC
AGGGACAATGGTCACCGTGTCCTCA
ACTCTGTTCCCGCCCTCCTCTGAGGA
CGCCCTCCTCTGAGGAGCTTCAAGCC
GCCTCCACCAAGGGCCCATCGGTCTT
GCTTCAAGCCAACAAGGCCACACTG
AACAAGGCCACACTGGTGTGTCTCAT
CCCCCTGGCACCCTCCTCCAAGAGCA
GTGTGTCTCATCAGTGACTTCTACCC
CAGTGACTTCTACCCGGGAGCCGTG
CCTCTGGGGGCACAGCGGCCCTGGG
GGGAGCCGTGACAGTGGCCTGGAAG
ACAGTGGCCTGGAAGGCAGATAGCA
CTGCCTGGTCAAGGACTACTTCCCCG
GCAGATAGCAGCCCCGTCAAGGCGG
GCCCCGTCAAGGCGGGAGTGGAAAC
AACCGGTGACGGTGTCGTGGAACTC
GAGTGGAAACCACCACACCCTCCAA
CACCACACCCTCCAAACAAAGCAAC
AGGCGCCCTGACCAGCGGCGTGCAC
ACAAAGCAACAACAAGTACGCGGCC
AACAAGTACGCGGCCAAGAGCTATC
ACCTTCCCGGCTGTCCTACAGTCCTC
GAAAGCTATCTGAGCCTGACGCCTG
TGAGCCTGACGCCTGAGCAGTGGAA
AGGACTCTACTCCCTCAAGAGCGTG
AGCAGTGGAAGTCCCACAGAAGCTA
GTCCCACAGAAGCTACAGCTGCCAG
GTGACCGTGCCCTCCAGCAGCTTGGG
CAGCTGCCAGGTCACGCATGAAGGG
GTCACGCATGAAGGGAGCACCGTGG
CACCCAGACCTACATCTGCAACGTG
AGCACCGTGGAGAAGACAGTGGCCC
AGAAGACAGTGGCCCCTACAGAATG
AATCACAAGCCCAGCAACACCAAGG
CTACAGAATGTTCA
TTCA
TGGACAAGAAAGTTGAGCCCAAATC
(SEQ ID NO: 689)
(SEQ ID NO: 690)
TTGTGACAAAACTCACACATGCCCAC
CGTGCCCAGCACCTGAACTCCTGGG
GGGACCGTCAGTCTTCCTCTTCCCCC
CAAAACCCAAGGACACCCTCATGAT
CTCCCGGACCCCTGAGGTCACATGCG
TGGTGGTGGACGTGAGCCACGAAGA
CCCTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGTGCGAGGAGCAG
TACGGCAGCACGTACCGTTGCGTCA
GCGTCCTCACCGTCCTGCACCAGGAC
TGGCTGAATGGCAAGGAGTACAAGT
GCAAGGTGTCCAACAAAGCCCTCCC
AGCCCCCATCGAGAAAACCATCTCC
AAAGCCAAAGGGCAGCCCCGAGAAC
CACAGGTGTACACCCTGCCCCCATCC
CGGGAGGAGATGACCAAGAACCAGG
TCAGCCTGACCTGCCTGGTCAAAGGC
TTCTATCCCAGCGACATCGCCGTGGA
GTGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCCG
TGCTGGACTCCGACGGCTCCTTCTTC
CTCTATAGCAAGCTCACCGTGGACA
AGAGCAGGTGGCAGCAGGGGAACGT
CTTCTCATGCTCCGTGATGCATGAGG
CTCTGCACAACCACTACACGCAGAA
GAGCCTCTCCCTGTCTCCGGGTGGTG
GCGGATCGGGAGGTGGCGGATCCCA
GGTGCAGTTGGTGGAGTCTGGGGGA
GGCTTAGTCAAGCCTGGAGGGTCCCT
GAGACTCTCCTGTGCAGCCTCTGAAT
TCACCTTCAGTGACTACTACATGAGC
TGGATCCGCCAGGCTCCAGGGAAGG
GGCTGGAGTGGGTTTCATATATTAGT
CGAAGTGGTGATACCATCTACTACGC
AGACTCTGTGAAGGGCCGATTCACC
ATCTCCAGGGACAACGCCAAGAACT
CACTGTATCTGCAAATGAATGGCCTG
CGAGCCGAAGACACGGCCGTGTATT
ACTGTGCGAGAGACTTAGCAGCAGG
TGCTACAGGGGGCCTTGACTGCTGG
GGCCAGGGAACCCTGGTCACCGTGT
CCTCAGCAAGCACGAAGGGGCCGTC
CGTATTTCCGCTTGCGCCCTCGTCGA
AGTCAACTTCGGGAGGGACCGCGGC
ACTTGGCTGTCTTGTCAAAGATTACT
TCCCTGAGCCAGTGACAGTCAGCTG
GAATTCCGGTGCCCTCACGTCAGGA
GTACATACATTCCCTGCGGTATTGCA
GTCCTCCGGACTCTACTCCCTGGAGT
CGGTGGTAACGGTGCCCAGCTCCAG
CTTGGGGACCCAGACGTACATTTGTA
ACGTGAATCACAAACCAAGCAATAC
TAAGGTAGATAAGAAAGTAGAACCG
AAGAGCTGC
(SEQ ID NO: 691)
AA
QSVLTQPPSVSGAPGQRVTISCTGSSSN
SYELTQPPSVSVSPGQTASITCSGERLG
QVQLQESGPGLVKPSETLSLTCTVSGG
IGAGYDVHWYQQVPGTAPKLLIYGNS
NKYICWYQQKPGQSPVLVIYQDFKRPS
SISSSSYYWGWIRQPPGKGLEWIGSIYY
KRPSGVPDRFSGSKSGTSASLAITGLQ
GIPERFSGSNSGITATLTISGTQAMDEA
SGITNYNPSLKSRVTISVDTSKNQFSLK
AEDEADYYCQSYDSSLGGWVFGGGT
DYYCQAWDSRTVVFGGGTKLTVLGQ
LSSVTAADTAVYYCARPSNYDAFDIW
KLTVLQPKAAPSVTLFPPSSEELQANK
PKAAPSVTLFPPSSEELQANKATLVCLI
GQGTMVTVSSASTKGPSVFPLAPSSKS
ATLVCLISDFYPGAVTVAWKADSSPV
SDFYPGAVTVAWKADSSPVKAGVETT
TSGGTAALGCLVKDYFPEPVTVSWNS
KAGVETTTPSKQSNNKYAAESYLSLTP
TPSKQSNNKYAAKSYLSLTPEQWKSH
GALTSGVHTFPAVLQSSGLYSLKSVVT
EQWKSHRSYSCQVTHEGSTVEKTVAP
RSYSCQVTHEGSTVEKTVAPTECS
VPSSSLGTQTYICNVNHKPSNTKVDKK
TECS
(SEQ ID NO: 693)
VEPKSCDKTHTCPPCPAPELLGGPSVF
(SEQ ID NO: 692)
LFPPKPKDTLMISRTPEVTCVVVDVSH
EDPEVKFNWYVDGVEVHNAKTKPCE
EQYGSTYRCVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPRE
PQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLVESGGGLVKPGGSLRLSC
AASEFTFSDYYMSWIRQAPGKGLEWV
SYISRSGDTIYYADSVKGRFTISRDNAK
NSLYLQMNGLRAEDTAVYYCARDLA
AGATGGLDCWGQGTLVTVSSASTKGP
SVFPLAPSSKSTSGGTAALGCLVKDYF
PEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLESVVTVPSSSLGTQTYICNVNH
KPSNTKVDKKVEPKSC
(SEQ ID NO: 694)
iPS:
21-233_4G12_IgG_21-
[hu anti-<hu Mesothelin>
NA
CAGTCAGTGTTGACGCAGCCGCCCTC
CAGTCTGCCCTGACTCAGCCTGCCTC
CAGGTGCAGCTGCAGGAGTCGGGCC
576160
230_39C2_Fab
4G12VH]::huIgG1zSEFL2*GK-
AGTGTCTGGGGCCCCAGGGCAGAGG
CGTGTCTGGGAGCCCTGGACAGTCG
CAGGACTGGTGAAGCCTTCGGAAAC
K::(G4S)2::[hu anti-
GTCACCATCTCCTGCACTGGGAGCAG
ATCACCATCTCCTGCACTGGAACCAG
CCTGTCCCTCACCTGCACTGTCTCTG
<huCD40>21-230_39C2VH]::
CTCCAACATCGGGGCAGGTTATGAT
CAGTGATGTTGGGAATTATAACCTTG
GTGGCTCCATCAGCAGTAGTAGTTAC
huIgG1z-CH1-E::EPKSC +
GTTCACTGGTACCAGCAGGTTCCAGG
TCTCCTGGTACCAACAGCACCCAGGC
TACTGGGGCTGGATCAGGCAGCCCC
[anti-<hu Mesothelin>
AACAGCCCCCAAACTCCTCATCTATG
AAAGCCCCCAAACTCATGATTTATGA
CAGGGAAGGGGCTGGAGTGGATTGG
4G12VL]::huLLC2-E +
GTAACAGCAAGCGGCCCTCAGGGGT
GGTCAATAGGCGGCCCTCAGGGGTT
GAGTATCTATTATAGTGGGATCACCA
[anti-<huCD40>
CCCTGACCGATTCTCTGGCTCCAAGT
TCTAATCGCTTCTCTGGCTCCAAGTC
ACTACAACCCGTCCCTCAAGAGTCG
21-230_39C2VL]::
CTGGCACCTCAGCCTCCCTGGCCATC
TGGCAACACGGCCTCCCTGACAATCT
AGTCACCATCTCCGTAGACACGTCCA
huLLC2-K(IgG-
ACTGGGCTCCAGGCTGAGGATGAGG
CTGGGCTCCAGGCTGAGGACGAGGC
AGAACCAGTTCTCCCTGAAGCTGAGT
Fab); LMRID:
CTGATTATTACTGCCAGTCCTATGAC
TGAATATTACTGCTGCTCATATGCAG
TCTGTGACCGCCGCAGACACGGCCG
SS-30827
AGCAGCCTGGGTGGTTGGGTGTTCG
GTAGAGACACTTTCGTGGTGTTCGGC
TGTATTACTGTGCGAGGCCCAGTAAC
GCGGAGGGACCAAGCTGACCGTCCT
GGAGGGACCAAGCTGACCGTCCTAG
TACGATGCTTTTGATATCTGGGGCCA
ACAGCCCAAGGCTGCACCCTCGGTC
GTCAGCCCAAGGCTGCACCCTCGGTC
AGGGACAATGGTCACCGTGTCCTCA
ACTCTGTTCCCGCCCTCCTCTGAGGA
ACTCTGTTCCCGCCCTCCTCTGAGGA
GCCTCCACCAAGGGCCCATCGGTCTT
GCTTCAAGCCAACAAGGCCACACTG
GCTTCAAGCCAACAAGGCCACACTG
CCCCCTGGCACCCTCCTCCAAGAGCA
GTGTGTCTCATCAGTGACTTCTACCC
GTGTGTCTCATCAGTGACTTCTACCC
CCTCTGGGGGCACAGCGGCCCTGGG
GGGAGCCGTGACAGTGGCCTGGAAG
GGGAGCCGTGACAGTGGCCTGGAAG
CTGCCTGGTCAAGGACTACTTCCCCG
GCAGATAGCAGCCCCGTCAAGGCGG
GCAGATAGCAGCCCCGTCAAGGCGG
AACCGGTGACGGTGTCGTGGAACTC
GAGTGGAAACCACCACACCCTCCAA
GAGTGGAAACCACCACACCCTCCAA
AGGCGCCCTGACCAGCGGCGTGCAC
ACAAAGCAACAACAAGTACGCGGCC
ACAAAGCAACAACAAGTACGCGGCC
ACCTTCCCGGCTGTCCTACAGTCCTC
GAAAGCTATCTGAGCCTGACGCCTG
AAGAGCTATCTGAGCCTGACGCCTG
AGGACTCTACTCCCTCAAGAGCGTG
AGCAGTGGAAGTCCCACAGAAGCTA
AGCAGTGGAAGTCCCACAGAAGCTA
GTGACCGTGCCCTCCAGCAGCTTGGG
CAGCTGCCAGGTCACGCATGAAGGG
CAGCTGCCAGGTCACGCATGAAGGG
CACCCAGACCTACATCTGCAACGTG
AGCACCGTGGAGAAGACAGTGGCCC
AGCACCGTGGAGAAGACAGTGGCCC
AATCACAAGCCCAGCAACACCAAGG
CTACAGAATGTTCA
CTACAGAATGTTCA
TGGACAAGAAAGTTGAGCCCAAATC
(SEQ ID NO: 695)
(SEQ ID NO: 696)
TTGTGACAAAACTCACACATGCCCAC
CGTGCCCAGCACCTGAACTCCTGGG
GGGACCGTCAGTCTTCCTCTTCCCCC
CAAAACCCAAGGACACCCTCATGAT
CTCCCGGACCCCTGAGGTCACATGCG
TGGTGGTGGACGTGAGCCACGAAGA
CCCTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGTGCGAGGAGCAG
TACGGCAGCACGTACCGTTGCGTCA
GCGTCCTCACCGTCCTGCACCAGGAC
TGGCTGAATGGCAAGGAGTACAAGT
GCAAGGTGTCCAACAAAGCCCTCCC
AGCCCCCATCGAGAAAACCATCTCC
AAAGCCAAAGGGCAGCCCCGAGAAC
CACAGGTGTACACCCTGCCCCCATCC
CGGGAGGAGATGACCAAGAACCAGG
TCAGCCTGACCTGCCTGGTCAAAGGC
TTCTATCCCAGCGACATCGCCGTGGA
GTGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCCG
TGCTGGACTCCGACGGCTCCTTCTTC
CTCTATAGCAAGCTCACCGTGGACA
AGAGCAGGTGGCAGCAGGGGAACGT
CTTCTCATGCTCCGTGATGCATGAGG
CTCTGCACAACCACTACACGCAGAA
GAGCCTCTCCCTGTCTCCGGGTGGTG
GCGGATCGGGAGGTGGCGGATCCCA
GGTGCAGCTGGTGCAGTCTGGGACT
GAGGTGAAGAAGCCTGGGGCCTCAG
TGAAGGTGTCCTGCAAGGCTTCTGGA
TACACCTTCCCCGGCTACTATATGCA
CTGGGTGCGACAGGCCCCTGGACAG
GGGCTTGAGTGGATGGGATGGATCA
ACCCTGACAGTGGTGGCACAAAGTA
TACACAGAAGTTTCAGGGCAGGGTC
ACCTTGACCAGGGACGCGTCCGTCA
GCACAGCCTACATTGACCTGAACAG
GCTGAGATCTGACGACACGGCCGTA
TATTACTGTGCGAGAGAGAGGTGTA
GGACTACCAACTGCTATTTGGACTAC
TGGGGCCAGGGAAGTCTGGTCACCG
TGTCCTCAGCAAGCACGAAGGGGCC
GTCCGTATTTCCGCTTGCGCCCTCGT
CGAAGTCAACTTCGGGAGGGACCGC
GGCACTTGGCTGTCTTGTCAAAGATT
ACTTCCCTGAGCCAGTGACAGTCAGC
TGGAATTCCGGTGCCCTCACGTCAGG
AGTACATACATTCCCTGCGGTATTGC
AGTCCTCCGGACTCTACTCCCTGGAG
TCGGTGGTAACGGTGCCCAGCTCCA
GCTTGGGGACCCAGACGTACATTTGT
AACGTGAATCACAAACCAAGCAATA
CTAAGGTAGATAAGAAAGTAGAACC
GAAGAGCTGC
(SEQ ID NO: 697)
AA
QSVLTQPPSVSGAPGQRVTISCTGSSSN
QSALTQPASVSGSPGQSITISCTGTSSD
QVQLQESGPGLVKPSETLSLTCTVSGG
IGAGYDVHWYQQVPGTAPKLLIYGNS
VGNYNLVSWYQQHPGKAPKLMIYEV
SISSSSYYWGWIRQPPGKGLEWIGSIYY
KRPSGVPDRFSGSKSGTSASLAITGLQ
NRRPSGVSNRFSGSKSGNTASLTISGLQ
SGITNYNPSLKSRVTISVDTSKNQFSLK
AEDEADYYCQSYDSSLGGWVFGGGT
AEDEAEYYCCSYAGRDTFVVFGGGTK
LSSVTAADTAVYYCARPSNYDAFDIW
KLTVLQPKAAPSVTLFPPSSEELQANK
LTVLGQPKAAPSVTLFPPSSEELQANK
GQGTMVTVSSASTKGPSVFPLAPSSKS
ATLVCLISDFYPGAVTVAWKADSSPV
ATLVCLISDFYPGAVTVAWKADSSPV
TSGGTAALGCLVKDYFPEPVTVSWNS
KAGVETTTPSKQSNNKYAAESYLSLTP
KAGVETTTPSKQSNNKYAAKSYLSLTP
GALTSGVHTFPAVLQSSGLYSLKSVVT
EQWKSHRSYSCQVTHEGSTVEKTVAP
EQWKSHRSYSCQVTHEGSTVEKTVAP
VPSSSLGTQTYICNVNHKPSNTKVDKK
TECS
TECS
VEPKSCDKTHTCPPCPAPELLGGPSVF
(SEQ ID NO: 698)
(SEQ ID NO: 699)
LFPPKPKDTLMISRTPEVTCVVVDVSH
EDPEVKFNWYVDGVEVHNAKTKPCE
EQYGSTYRCVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPRE
PQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLVQSGTEVKKPGASVKVSC
KASGYTFPGYYMHWVRQAPGQGLEW
MGWINPDSGGTKYTQKFQGRVTLTRD
ASVSTAYIDLNRLRSDDTAVYYCARE
RCRTTNCYLDYWGQGSLVTVSSASTK
GPSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAVLQ
SSGLYSLESVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSC
(SEQ ID NO: 700)
iPS:
21-233_4H6_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATTCAGATGACCCAGTCTCCATC
GACATCCAGATGACCCAGTCTCCATC
CAGGTGCAGCTGGTCGAGTCTGGGG
576165
230_4G7_Fab
4H6VH]::huIgG1zSEFL2*GK-
TTCCGTGTCTGCATCTGTAGGGGACA
CTCCCTGTCTGCATCTGTAGGAGACA
GAGGCTTGGTCAAGCCTGGAGGGTC
K::(G4S)2::[hu anti-
GAGTCACCATCACTTGTCGGGCGAGT
TTCTCACCATCACTTGCCGGGCAAGT
CCTGAGACTCTCCTGTGCAGCCTCTG
<huCD40>21-230_4G7VH]::
CAGGGTATTACCAGGTGGTTAGCCTG
CAGAACATTACCACCTATTTAAATTG
GATTCACCTTCAGTGACTACTACATG
huIgG1z-CH1-E::EPKSC +
GTATCAGCAGAAACCAGGGAAAGCC
GTATCAGCAGAAACCAGGGAAAGCC
ACCTGGATCAGGCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CCTAAGCTCCTGATCTATGCTGCATC
CCTAACCTCCTGATCTCTGCTGCATC
AGGGGCTGGAGTGGATTTCATACATT
4H6VL]::huKLC-S176E +
CGTTTTGCAAAGTGGGGTCCCATCAA
CCGTTTGCGAAGTGGGGTCCCATCAA
AGTAGTAGTGGTAGTACCATCTACTA
[anti-<huCD40>
GGTTCAGCGGCAGTGGATCTGGGAC
GGTTCAGTGGCAGTGGATCTGGGAC
CGCAGACTCTGTGAAGGGCCGATTC
21-230_4G7VL]::
AGATTTCACTCTCACCATCAGCAGCC
AGATTTCACTCTCACCATCAGCAGTC
ACCATCTCCAGGGACAACGCCAAGA
huKLC-S176K(IgG-
TGCAGCCTGAAGATTTTGCAACTTAC
TGCAACCTGTAGATTTTACAACTTTC
ACTCACTGTATCTGCAAATGAACAGC
Fab); LMRID:
TATTGTCAACAGTCTAACAGTTTCCC
TACTGTCAACAGACTTTCACTACCCC
CTGAGAGCCGAGGACACGGCCGTGT
SS-30828
TCGGACGTTCGGCCAAGGGACCAAG
GTGGACGTTCGGCCAAGGGACCAAG
ATTACTGTGCGAGAGATCGGAACTC
GTGGAAATCAAACGGACGGTGGCTG
GTGGAGATCAAACGAACGGTGGCTG
CCACTTTGACTATTGGGGCCAGGGA
CACCATCTGTCTTCATCTTCCCGCCA
CACCATCTGTCTTCATCTTCCCGCCA
ACCCTGGTCACCGTGTCCTCAGCCTC
TCTGATGAGCAGTTGAAATCTGGAA
TCTGATGAGCAGTTGAAATCTGGAA
CACCAAGGGCCCATCGGTCTTCCCCC
CTGCCTCTGTTGTGTGCCTGCTGAAT
CTGCCTCTGTTGTGTGCCTGCTGAAT
TGGCACCCTCCTCCAAGAGCACCTCT
AACTTCTATCCCAGAGAGGCCAAAG
AACTTCTATCCCAGAGAGGCCAAAG
GGGGGCACAGCGGCCCTGGGCTGCC
TACAGTGGAAGGTGGATAACGCCCT
TACAGTGGAAGGTGGATAACGCCCT
TGGTCAAGGACTACTTCCCCGAACCG
CCAATCGGGTAACTCCCAGGAGAGT
CCAATCGGGTAACTCCCAGGAGAGT
GTGACGGTGTCGTGGAACTCAGGCG
GTCACAGAGCAGGACAGCAAGGACA
GTCACAGAGCAGGACAGCAAGGACA
CCCTGACCAGCGGCGTGCACACCTTC
GCACCTACAGCCTCGAAAGCACCCT
GCACCTACAGCCTCAAGAGCACCCT
CCGGCTGTCCTACAGTCCTCAGGACT
GACGCTGAGCAAAGCAGACTACGAG
GACGCTGAGCAAAGCAGACTACGAG
CTACTCCCTCAAGAGCGTGGTGACCG
AAACACAAAGTCTACGCCTGCGAAG
AAACACAAAGTCTACGCCTGCGAAG
TGCCCTCCAGCAGCTTGGGCACCCAG
TCACCCATCAGGGCCTGAGCTCGCCC
TCACCCATCAGGGCCTGAGCTCGCCC
ACCTACATCTGCAACGTGAATCACA
GTCACAAAGAGCTTCAACAGGGGAG
GTCACAAAGAGCTTCAACAGGGGAG
AGCCCAGCAACACCAAGGTGGACAA
AGTGT
AGTGT
GAAAGTTGAGCCCAAATCTTGTGAC
(SEQ ID NO: 701)
(SEQ ID NO: 702)
AAAACTCACACATGCCCACCGTGCC
CAGCACCTGAACTCCTGGGGGGACC
GTCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGT
GGACGTGAGCCACGAAGACCCTGAG
GTCAAGTTCAACTGGTACGTGGACG
GCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGC
AGCACGTACCGTTGCGTCAGCGTCCT
CACCGTCCTGCACCAGGACTGGCTG
AATGGCAAGGAGTACAAGTGCAAGG
TGTCCAACAAAGCCCTCCCAGCCCCC
ATCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGGT
GTACACCCTGCCCCCATCCCGGGAG
GAGATGACCAAGAACCAGGTCAGCC
TGACCTGCCTGGTCAAAGGCTTCTAT
CCCAGCGACATCGCCGTGGAGTGGG
AGAGCAATGGGCAGCCGGAGAACAA
CTACAAGACCACGCCTCCCGTGCTGG
ACTCCGACGGCTCCTTCTTCCTCTAT
AGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTGC
ACAACCACTACACGCAGAAGAGCCT
CTCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCCAGGTGCA
GCTGGTGCAGTCTGGGGCTGAGGTG
AAGAAGCCTGGGGCCTCAGTGAAGG
TGTCCTGCAAGGCTTCTGGATACACC
TTCGCCGGCTACTATATGCACTGGGT
GCGACAGGCCCCTGGACAAGGGCTT
GAGTGGATGGGATGGATCAACCCTG
ACAGTGGAGGCACAAACTTTGCACA
GCAGTTTCAGGGCAGGGTCACCATG
ACCAGGGATACGTCCATCAGCACAG
CCTACATGGAGGTGAGCAGGCTGAG
ATCTGACGACACGGCCGTGTTTTACT
GTGCGAGAGAGAAGATCACTATGAC
TGGTATTTACTTTGACTATTGGGGCC
AGGGAACCCTGGTCACCGTGTCCTCA
GCAAGCACGAAGGGGCCGTCCGTAT
TTCCGCTTGCGCCCTCGTCGAAGTCA
ACTTCGGGAGGGACCGCGGCACTTG
GCTGTCTTGTCAAAGATTACTTCCCT
GAGCCAGTGACAGTCAGCTGGAATT
CCGGTGCCCTCACGTCAGGAGTACAT
ACATTCCCTGCGGTATTGCAGTCCTC
CGGACTCTACTCCCTGGAGTCGGTGG
TAACGGTGCCCAGCTCCAGCTTGGG
GACCCAGACGTACATTTGTAACGTG
AATCACAAACCAAGCAATACTAAGG
TAGATAAGAAAGTAGAACCGAAGAG
CTGC
(SEQ ID NO: 703)
AA
DIQMTQSPSSVSASVGDRVTITCRASQ
DIQMTQSPSSLSASVGDILTITCRASQ
QVQLVESGGGLVKPGGSLRLSCAASG
GITRWLAWYQQKPGKAPKLLIYAASV
NITTYLNWYQQKPGKAPNLLISAASRL
FTFSDYYMTWIRQAPGKGLEWISYISS
LQSGVPSRFSGSGSGTDFTLTISSLQPE
RSGVPSRFSGSGSGTDFTLTISSLQPV
SGSTIYYADSVKGRFTISRDNAKNSLY
DFATYYCQQSNSFPRTFGQGTKVEIKR
DFTTFYCQQTFTTPWTFGQGTKVEIKR
LQMNSLRAEDTAVYYCARDRNSHFD
TVAAPSVFIFPPSDEQLKSGTASVVCLL
TVAAPSVFIFPPSDEQLKSGTASVVCL
YWGQGTLVTVSSASTKGPSVFPLAPSS
NNFYPREAKVQWKVDNALQSGNSQE
LNNFYPREAKVQWKVDNALQSGNSQES
KSTSGGTAALGCLVKDYFPEPVTVSW
SVTEQDSKDSTYSLESTLTLSKADYEK
VTEQDSKDSTYSLKSTLTLSKADYEKH
NSGALTSGVHTFPAVLQSSGLYSLKSV
HKVYACEVTHQGLSSPVTKSFNRGEC
KVYACEVTHQGLSSPVTKSFNRGEC
VTVPSSSLGTQTYICNVNHKPSNTKVD
(SEQ ID NO: 704)
(SEQ ID NO: 705)
KKVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDV
SHEDPEVKFNWYVDGVEVHNAKTKP
CEEQYGSTYRCVSVLTVLHQDWLNGK
EYKCKVSNKALPAPIEKTISKAKGQPR
EPQVYTLPPSREEMTKNQVSLTCLVKG
FYPSDIAVEWESNGQPENNYKTTPPVL
DSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGS
GGGGSQVQLVQSGAEVKKPGASVKVS
CKASGYTFAGYYMHWVRQAPGQGLE
WMGWINPDSGGTNFAQQFQGRVTMT
RDTSISTAYMEVSRLRSDDTAVFYCAR
EKITMTGIYFDYWGQGTLVTVSSASTK
GPSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAVLQ
SSGLYSLESVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSC
(SEQ ID NO: 706)
iPS:
21-233_4H6_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATTCAGATGACCCAGTCTCCATC
GACATCCAGATGACCCAGTCTCCATC
CAGGTGCAGCTGGTCGAGTCTGGGG
576171
230_29H10_Fab
4H6VH]::huIgG1zSEFL2*GK-
TTCCGTGTCTGCATCTGTAGGGGACA
CTCACTGTCTGCATCTGTAGGAGACA
GAGGCTTGGTCAAGCCTGGAGGGTC
K::(G4S)2::[hu anti-
GAGTCACCATCACTTGTCGGGCGAGT
GAGTCACCATCACCTGTCGGGCGAG
CCTGAGACTCTCCTGTGCAGCCTCTG
<huCD40>21-230_29H10VH]::
CAGGGTATTACCAGGTGGTTAGCCTG
TCAGGACATTAGCAATAATTTAGCCT
GATTCACCTTCAGTGACTACTACATG
huIgG1z-CH1-E::EPKSC +
GTATCAGCAGAAACCAGGGAAAGCC
GGTTTCAGCAGAAACCAGGGAAACC
ACCTGGATCAGGCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CCTAAGCTCCTGATCTATGCTGCATC
CCCTAAGTCCCTGATGTATGCTGCAT
AGGGGCTGGAGTGGATTTCATACATT
4H6VL]::huKLC-S176E +
CGTTTTGCAAAGTGGGGTCCCATCAA
CCAGTTTGCACAGTGGAGTCCCATCA
AGTAGTAGTGGTAGTACCATCTACTA
[anti-<huCD40>
GGTTCAGCGGCAGTGGATCTGGGAC
ACGTTCAGCGGCAGTGGATCTGGGA
CGCAGACTCTGTGAAGGGCCGATTC
21-230_29H10VL]::
AGATTTCACTCTCACCATCAGCAGCC
CAGATTTCACTTTCACCATCAGCAGC
ACCATCTCCAGGGACAACGCCAAGA
huKLC-S176K(IgG-
TGCAGCCTGAAGATTTTGCAACTTAC
CTGCAGCCTGAAGATTTTGCAACTTA
ACTCACTGTATCTGCAAATGAACAGC
Fab); LMRID:
TATTGTCAACAGTCTAACAGTTTCCC
TTACTGCCAACAGTATAATAGTTACC
CTGAGAGCCGAGGACACGGCCGTGT
SS-30829
TCGGACGTTCGGCCAAGGGACCAAG
CTCTCACTTTCGGCGGAGGGACCAA
ATTACTGTGCGAGAGATCGGAACTC
GTGGAAATCAAACGGACGGTGGCTG
GGTGGAGATCAGACGAACGGTGGCT
CCACTTTGACTATTGGGGCCAGGGA
CACCATCTGTCTTCATCTTCCCGCCA
GCACCATCTGTCTTCATCTTCCCGCC
ACCCTGGTCACCGTGTCCTCAGCCTC
TCTGATGAGCAGTTGAAATCTGGAA
ATCTGATGAGCAGTTGAAATCTGGA
CACCAAGGGCCCATCGGTCTTCCCCC
CTGCCTCTGTTGTGTGCCTGCTGAAT
ACTGCCTCTGTTGTGTGCCTGCTGAA
TGGCACCCTCCTCCAAGAGCACCTCT
AACTTCTATCCCAGAGAGGCCAAAG
TAACTTCTATCCCAGAGAGGCCAAA
GGGGGCACAGCGGCCCTGGGCTGCC
TACAGTGGAAGGTGGATAACGCCCT
GTACAGTGGAAGGTGGATAACGCCC
TGGTCAAGGACTACTTCCCCGAACCG
CCAATCGGGTAACTCCCAGGAGAGT
TCCAATCGGGTAACTCCCAGGAGAG
GTGACGGTGTCGTGGAACTCAGGCG
GTCACAGAGCAGGACAGCAAGGACA
TGTCACAGAGCAGGACAGCAAGGAC
CCCTGACCAGCGGCGTGCACACCTTC
GCACCTACAGCCTCGAAAGCACCCT
AGCACCTACAGCCTCAAGAGCACCC
CCGGCTGTCCTACAGTCCTCAGGACT
GACGCTGAGCAAAGCAGACTACGAG
TGACGCTGAGCAAAGCAGACTACGA
CTACTCCCTCAAGAGCGTGGTGACCG
AAACACAAAGTCTACGCCTGCGAAG
GAAACACAAAGTCTACGCCTGCGAA
TGCCCTCCAGCAGCTTGGGCACCCAG
TCACCCATCAGGGCCTGAGCTCGCCC
GTCACCCATCAGGGCCTGAGCTCGCC
ACCTACATCTGCAACGTGAATCACA
GTCACAAAGAGCTTCAACAGGGGAG
CGTCACAAAGAGCTTCAACAGGGGA
AGCCCAGCAACACCAAGGTGGACAA
AGTGT
GAGTGT
GAAAGTTGAGCCCAAATCTTGTGAC
(SEQ ID NO: 707)
(SEQ ID NO: 708)
AAAACTCACACATGCCCACCGTGCC
CAGCACCTGAACTCCTGGGGGGACC
GTCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGT
GGACGTGAGCCACGAAGACCCTGAG
GTCAAGTTCAACTGGTACGTGGACG
GCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGC
AGCACGTACCGTTGCGTCAGCGTCCT
CACCGTCCTGCACCAGGACTGGCTG
AATGGCAAGGAGTACAAGTGCAAGG
TGTCCAACAAAGCCCTCCCAGCCCCC
ATCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGGT
GTACACCCTGCCCCCATCCCGGGAG
GAGATGACCAAGAACCAGGTCAGCC
TGACCTGCCTGGTCAAAGGCTTCTAT
CCCAGCGACATCGCCGTGGAGTGGG
AGAGCAATGGGCAGCCGGAGAACAA
CTACAAGACCACGCCTCCCGTGCTGG
ACTCCGACGGCTCCTTCTTCCTCTAT
AGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTGC
ACAACCACTACACGCAGAAGAGCCT
CTCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCCAGGTGCA
ACTGGTGCAGTCTGGGGCTGAGGTG
ACGAAGCCTGGGGCCTCAGTGAAGG
TGTCCTGCAAGGCTTCTGGATACACC
TTCGCCGGCTACTATATGCACTGGGT
GCGACAGGCCCCTGGACAAGGGCTT
GAGTGGATGGGATGGATCAACCCTC
ACAGTGGTGGCACAAACTATGCACA
GAAGTTTCAGGACAGGGTCACCATG
ACCAGGGACACGTCCATCAACACAG
CCTACATGGAACTGAGCAGGCTGAG
ATCTGACGACACGGCCGTGTATTACT
GTGCGAGAGAACGTATTTCTATGGTT
CGGGGAGTCGGGCACAACTGGTTCG
CCCCCTGGGGCCAGGGAACCCTGGT
CACCGTGTCCTCAGCAAGCACGAAG
GGGCCGTCCGTATTTCCGCTTGCGCC
CTCGTCGAAGTCAACTTCGGGAGGG
ACCGCGGCACTTGGCTGTCTTGTCAA
AGATTACTTCCCTGAGCCAGTGACAG
TCAGCTGGAATTCCGGTGCCCTCACG
TCAGGAGTACATACATTCCCTGCGGT
ATTGCAGTCCTCCGGACTCTACTCCC
TGGAGTCGGTGGTAACGGTGCCCAG
CTCCAGCTTGGGGACCCAGACGTAC
ATTTGTAACGTGAATCACAAACCAA
GCAATACTAAGGTAGATAAGAAAGT
AGAACCGAAGAGCTGC
(SEQ ID NO: 709)
AA
DIQMTQSPSSVSASVGDRVTITCRASQ
DIQMTQSPSSLSASVGDRVTITCRASQ
QVQL VESGGGLVKPGGSLRLSCAASG
GITRWLAWYQQKPGKAPKLLIYAASV
DISNNLAWFQQKPGKPPKSLMYAASS
FTFSDYYMTWIRQAPGKGLEWISYISS
LQSGVPSRFSGSGSGTDFTLTISSLQPE
LHSGVPSTFSGSGSGTDFTFTISSLQPE
SGSTIYYADSVKGRFTISRDNAKNSLY
DFATYYCQQSNSFPRTFGQGTKVEIKR
DFATYYCQQYNSYPLTFGGGTKVEIRR
LQMNSLRAEDTAVYYCARDRNSHFD
TVAAPSVFIFPPSDEQLKSGTASVVCLL
TVAAPSVFIFPPSDEQLKSGTASVVCLL
YWGQGTLVTVSSASTKGPSVFPLAPSS
NNFYPREAKVQWKVDNALQSGNSQE
NNFYPREAKVQWKVDNALQSGNSQE
KSTSGGTAALGCLVKDYFPEPVTVSW
SVTEQDSKDSTYSLESTLTLSKADYEK
SVTEQDSKDSTYSLKSTLTLSKADYEK
NSGALTSGVHTFPAVLQSSGLYSLKSV
HKVYACEVTHQGLSSPVTKSFNRGEC
HKVYACEVTHQGLSSPVTKSFNRGEC
VTVPSSSLGTQTYICNVNHKPSNTKVD
(SEQ ID NO: 710)
(SEQ ID NO: 711)
KKVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDV
SHEDPEVKFNWYVDGVEVHNAKTKP
CEEQYGSTYRCVSVLTVLHQDWLNGK
EYKCKVSNKALPAPIEKTISKAKGQPR
EPQVYTLPPSREEMTKNQVSLTCLVKG
FYPSDIAVEWESNGQPENNYKTTPPVL
DSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGS
GGGGSQVQLVQSGAEVTKPGASVKVS
CKASGYTFAGYYMHWVRQAPGQGLE
WMGWINPHSGGTNYAQKFQDRVTMT
RDTSINTAYMELSRLRSDDTAVYYCA
RERISMVRGVGHNWFAPWGQGTLVT
VSSASTKGPSVFPLAPSSKSTSGGTAAL
GCLVKDYFPEPVTVSWNSGALTSGVH
TFPAVLQSSGLYSLESVVTVPSSSLGTQ
TYICNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 712)
iPS:
21-233_4H6_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATTCAGATGACCCAGTCTCCATC
CAGTCTGCCCTGACTCAGCCTGCCTC
CAGGTGCAGCTGGTCGAGTCTGGGG
576174
230_30A12_Fab
4H6VH]::huIgG1zSEFL2*GK-
TTCCGTGTCTGCATCTGTAGGGGACA
CGTGTCTGGGAGCCCTGGACAGTCG
GAGGCTTGGTCAAGCCTGGAGGGTC
K::(G4S)2::[hu anti-
GAGTCACCATCACTTGTCGGGCGAGT
ATCACCATCTCCTGCACTGGAACCAG
CCTGAGACTCTCCTGTGCAGCCTCTG
<huCD40>21-230_30A12VH]::
CAGGGTATTACCAGGTGGTTAGCCTG
CAGTGATGTTGGGAATTATAACCTTG
GATTCACCTTCAGTGACTACTACATG
huIgG1z-CH1-E::EPKSC +
GTATCAGCAGAAACCAGGGAAAGCC
TCTCCTGGTACCAACAGCACCCAGGC
ACCTGGATCAGGCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CCTAAGCTCCTGATCTATGCTGCATC
AAAGCCCCCAAACTCATGATTTTTGA
AGGGGCTGGAGTGGATTTCATACATT
4H6VL]::huKLC-S176E +
CGTTTTGCAAAGTGGGGTCCCATCAA
GGTCAATCAGCGGCCCTCAGGGGTTT
AGTAGTAGTGGTAGTACCATCTACTA
[anti-<huCD40>
GGTTCAGCGGCAGTGGATCTGGGAC
CTAATCGCTTCTCTGGCTCCAAGTCT
CGCAGACTCTGTGAAGGGCCGATTC
21-230_30A12VL]::
AGATTTCACTCTCACCATCAGCAGCC
GGCACCACGGCCTCCCTGACAATCTC
ACCATCTCCAGGGACAACGCCAAGA
huLLC2-K(IgG-
TGCAGCCTGAAGATTTTGCAACTTAC
TGGGCTCCAGGCTGCGGACGAGGCT
ACTCACTGTATCTGCAAATGAACAGC
Fab); LMRID:
TATTGTCAACAGTCTAACAGTTTCCC
GATTATTTCTGCTGCTCATATACAAC
CTGAGAGCCGAGGACACGGCCGTGT
SS-30830
TCGGACGTTCGGCCAAGGGACCAAG
TAGTAGCACTTATGTGATCTTCGGCG
ATTACTGTGCGAGAGATCGGAACTC
GTGGAAATCAAACGGACGGTGGCTG
GAGGGACCAAGCTGACCGTCCTAGG
CCACTTTGACTATTGGGGCCAGGGA
CACCATCTGTCTTCATCTTCCCGCCA
TCAGCCCAAGGCTGCACCCTCGGTCA
ACCCTGGTCACCGTGTCCTCAGCCTC
TCTGATGAGCAGTTGAAATCTGGAA
CTCTGTTCCCGCCCTCCTCTGAGGAG
CACCAAGGGCCCATCGGTCTTCCCCC
CTGCCTCTGTTGTGTGCCTGCTGAAT
CTTCAAGCCAACAAGGCCACACTGG
TGGCACCCTCCTCCAAGAGCACCTCT
AACTTCTATCCCAGAGAGGCCAAAG
TGTGTCTCATCAGTGACTTCTACCCG
GGGGGCACAGCGGCCCTGGGCTGCC
TACAGTGGAAGGTGGATAACGCCCT
GGAGCCGTGACAGTGGCCTGGAAGG
TGGTCAAGGACTACTTCCCCGAACCG
CCAATCGGGTAACTCCCAGGAGAGT
CAGATAGCAGCCCCGTCAAGGCGGG
GTGACGGTGTCGTGGAACTCAGGCG
GTCACAGAGCAGGACAGCAAGGACA
AGTGGAAACCACCACACCCTCCAAA
CCCTGACCAGCGGCGTGCACACCTTC
GCACCTACAGCCTCGAAAGCACCCT
CAAAGCAACAACAAGTACGCGGCCA
CCGGCTGTCCTACAGTCCTCAGGACT
GACGCTGAGCAAAGCAGACTACGAG
AGAGCTATCTGAGCCTGACGCCTGA
CTACTCCCTCAAGAGCGTGGTGACCG
AAACACAAAGTCTACGCCTGCGAAG
GCACTGGAAGTCCCACAGAAGCTAC
TGCCCTCCAGCAGCTTGGGCACCCAG
TCACCCATCAGGGCCTGAGCTCGCCC
AGCTGCCAGGTCACGCATCAAGGGA
ACCTACATCTGCAACGTGAATCACA
GTCACAAAGAGCTTCAACAGGGGAG
GCACCGTGGAGAAGACAGTGGCCCC
AGCCCAGCAACACCAAGGTGGACAA
AGTGT
TACAGAATGTTCA
GAAAGTTGAGCCCAAATCTTGTGAC
(SEQ ID NO: 713)
(SEQ ID NO: 714)
AAAACTCACACATGCCCACCGTGCC
CAGCACCTGAACTCCTGGGGGGACC
GTCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGT
GGACGTGAGCCACGAAGACCCTGAG
GTCAAGTTCAACTGGTACGTGGACG
GCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGC
AGCACGTACCGTTGCGTCAGCGTCCT
CACCGTCCTGCACCAGGACTGGCTG
AATGGCAAGGAGTACAAGTGCAAGG
TGTCCAACAAAGCCCTCCCAGCCCCC
ATCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGGT
GTACACCCTGCCCCCATCCCGGGAG
GAGATGACCAAGAACCAGGTCAGCC
TGACCTGCCTGGTCAAAGGCTTCTAT
CCCAGCGACATCGCCGTGGAGTGGG
AGAGCAATGGGCAGCCGGAGAACAA
CTACAAGACCACGCCTCCCGTGCTGG
ACTCCGACGGCTCCTTCTTCCTCTAT
AGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTGC
ACAACCACTACACGCAGAAGAGCCT
CTCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCGAGGTGCA
GCTGCTGGAGTCTGGGGGAGGCTTG
GTACAGCCTGGGGGGTCCCTGAGAC
TCTCCTGTGCAGCCTCTGGATTCACC
TTTAGTAGAAATGCCATGAGTTGGGT
CCGCCAGGCTCCAGGGAAGGGGCTG
GAGTGGGTGTCAGCTACTGGTGGTA
GTGGTATTAGCACATACTACGCAGA
CTCCGTGAAGGGCCGGTTCACCATCT
CCAGAGACAATTCCAAGAACACGCT
GTATCTGCAAATGAACAGTCTGAGA
GCCGAGGACACGGCCGTATATTACT
GTGCGAGAGGTTATAGCAACAGCTG
GTGGTACTTTGACTACTGGGGCCAGG
GAACCCTGGTCACCGTGTCCTCAGCA
AGCACGAAGGGGCCGTCCGTATTTC
CGCTTGCGCCCTCGTCGAAGTCAACT
TCGGGAGGGACCGCGGCACTTGGCT
GTCTTGTCAAAGATTACTTCCCTGAG
CCAGTGACAGTCAGCTGGAATTCCG
GTGCCCTCACGTCAGGAGTACATAC
ATTCCCTGCGGTATTGCAGTCCTCCG
GACTCTACTCCCTGGAGTCGGTGGTA
ACGGTGCCCAGCTCCAGCTTGGGGA
CCCAGACGTACATTTGTAACGTGAAT
CACAAACCAAGCAATACTAAGGTAG
ATAAGAAAGTAGAACCGAAGAGCTG
C
(SEQ ID NO: 715)
AA
DIQMTQSPSSVSASVGDRVTITCRASQ
QSALTQPASVSGSPGQSITISCTGTSSD
QVQLVESGGGLVKPGGSLRLSCAASG
GITRWLAWYQQKPGKAPKLLIYAASV
VGNYNLVSWYQQHPGKAPKLMIFEV
FTFSDYYMTWIRQAPGKGLEWISYISS
LQSGVPSRFSGSGSGTDFTLTISSLQPE
NQRPSGVSNRFSGSKSGTTASLTISGLQ
SGSTIYYADSVKGRFTISRDNAKNSLY
DFATYYCQQSNSFPRTFGQGTKVEIKR
AADEADYFCCSYTTSSTYVIFGGGTKL
LQMNSLRAEDTAVYYCARDRNSHFD
TVAAPSVFIFPPSDEQLKSGTASVVCLL
TVLGQPKAAPSVTLFPPSSEELQANKA
YWGQGTLVTVSSASTKGPSVFPLAPSS
NNFYPREAKVQWKVDNALQSGNSQE
TLVCLISDFYPGAVTVAWKADSSPVK
KSTSGGTAALGCLVKDYFPEPVTVSW
SVTEQDSKDSTYSLESTLTLSKADYEK
AGVETTTPSKQSNNKYAAKSYLSLTPE
NSGALTSGVHTFPAVLQSSGLYSLKSV
HKVYACEVTHQGLSSPVTKSFNRGEC
QWKSHRSYSCQVTHEGSTVEKTVAPT
VTVPSSSLGTQTYICNVNHKPSNTKVD
(SEQ ID NO: 716)
ECS
KKVEPKSCDKTHTCPPCPAPELLGGPS
(SEQ ID NO: 717)
VFLFPPKPKDTLMISRTPEVTCVVVDV
SHEDPEVKFNWYVDGVEVHNAKTKP
CEEQYGSTYRCVSVLTVLHQDWLNGK
EYKCKVSNKALPAPIEKTISKAKGQPR
EPQVYTLPPSREEMTKNQVSLTCLVKG
FYPSDIAVEWESNGQPENNYKTTPPVL
DSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGS
GGGGSEVQLLESGGGLVQPGGSLRLS
CAASGFTFSRNAMSWVRQAPGKGLE
WVSATGGSGISTYYADSVKGRFTISRD
NSKNTLYLQMNSLRAEDTAVYYCAR
GYSNSWWYFDYWGQGTLVTVSSAST
KGPSVFPLAPSSKSTSGGTAALGCLVK
DYFPEPVTVSWNSGALTSGVHTFPAVL
QSSGLYSLESVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSC
(SEQ ID NO: 718)
iPS:
21-233_4H6_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATTCAGATGACCCAGTCTCCATC
GACATCCAGATGACCCAGTCTCCATC
CAGGTGCAGCTGGTCGAGTCTGGGG
576177
230_33H6_Fab
4H6VH]::huIgG1zSEFL2*GK-
TTCCGTGTCTGCATCTGTAGGGGACA
CTCCCTGTCTGCATCTGTAGGAGACA
GAGGCTTGGTCAAGCCTGGAGGGTC
K::(G4S)2::[hu anti-
GAGTCACCATCACTTGTCGGGCGAGT
GAGTCACCATCACTTGCCGGGCAGG
CCTGAGACTCTCCTGTGCAGCCTCTG
<huCD40>21-230_33H6VH]::
CAGGGTATTACCAGGTGGTTAGCCTG
TCAGAACATTAGCAGGCATTTAAATT
GATTCACCTTCAGTGACTACTACATG
huIgG1z-CH1-E::EPKSC +
GTATCAGCAGAAACCAGGGAAAGCC
GGTATCAGCAGAATCCAGGGAAAGC
ACCTGGATCAGGCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CCTAAGCTCCTGATCTATGCTGCATC
CCCTAAGGTCCTGATCCATCCTGCAT
AGGGGCTGGAGTGGATTTCATACATT
4H6VL]::huKLC-S176E +
CGTTTTGCAAAGTGGGGTCCCATCAA
CCAGTTTGCCAAGTGGGGTCCCGTCA
AGTAGTAGTGGTAGTACCATCTACTA
[anti-<huCD40>
GGTTCAGCGGCAGTGGATCTGGGAC
AGGTTCAGTGGCAGTGGATCTGGGA
CGCAGACTCTGTGAAGGGCCGATTC
21-230_33H6VL]::
AGATTTCACTCTCACCATCAGCAGCC
CAGATTTCAGTCTTACCATCAGCAGT
ACCATCTCCAGGGACAACGCCAAGA
huKLC-S176K(IgG-
TGCAGCCTGAAGATTTTGCAACTTAC
CTGCAACCTGAAGATTTTGGAACTTA
ACTCACTGTATCTGCAAATGAACAGC
Fab); LMRID:
TATTGTCAACAGTCTAACAGTTTCCC
CTTCTGTCAACAGAGTTACAGTACCC
CTGAGAGCCGAGGACACGGCCGTGT
SS-30831
TCGGACGTTCGGCCAAGGGACCAAG
CTCCCACTTTCGGCGGAGGGACCAA
ATTACTGTGCGAGAGATCGGAACTC
GTGGAAATCAAACGGACGGTGGCTG
GGTGGAGCTCAAACGAACGGTGGCT
CCACTTTGACTATTGGGGCCAGGGA
CACCATCTGTCTTCATCTTCCCGCCA
GCACCATCTGTCTTCATCTTCCCGCC
ACCCTGGTCACCGTGTCCTCAGCCTC
TCTGATGAGCAGTTGAAATCTGGAA
ATCTGATGAGCAGTTGAAATCTGGA
CACCAAGGGCCCATCGGTCTTCCCCC
CTGCCTCTGTTGTGTGCCTGCTGAAT
ACTGCCTCTGTTGTGTGCCTGCTGAA
TGGCACCCTCCTCCAAGAGCACCTCT
AACTTCTATCCCAGAGAGGCCAAAG
TAACTTCTATCCCAGAGAGGCCAAA
GGGGGCACAGCGGCCCTGGGCTGCC
TACAGTGGAAGGTGGATAACGCCCT
GTACAGTGGAAGGTGGATAACGCCC
TGGTCAAGGACTACTTCCCCGAACCG
CCAATCGGGTAACTCCCAGGAGAGT
TCCAATCGGGTAACTCCCAGGAGAG
GTGACGGTGTCGTGGAACTCAGGCG
GTCACAGAGCAGGACAGCAAGGACA
TGTCACAGAGCAGGACAGCAAGGAC
CCCTGACCAGCGGCGTGCACACCTTC
GCACCTACAGCCTCGAAAGCACCCT
AGCACCTACAGCCTCAAGAGCACCC
CCGGCTGTCCTACAGTCCTCAGGACT
GACGCTGAGCAAAGCAGACTACGAG
TGACGCTGAGCAAAGCAGACTACGA
CTACTCCCTCAAGAGCGTGGTGACCG
AAACACAAAGTCTACGCCTGCGAAG
GAAACACAAAGTCTACGCCTGCGAA
TGCCCTCCAGCAGCTTGGGCACCCAG
TCACCCATCAGGGCCTGAGCTCGCCC
GTCACCCATCAGGGCCTGAGCTCGCC
ACCTACATCTGCAACGTGAATCACA
GTCACAAAGAGCTTCAACAGGGGAG
CGTCACAAAGAGCTTCAACAGGGGA
AGCCCAGCAACACCAAGGTGGACAA
AGTGT
GAGTGT
GAAAGTTGAGCCCAAATCTTGTGAC
(SEQ ID NO: 719)
(SEQ ID NO: 720)
AAAACTCACACATGCCCACCGTGCC
CAGCACCTGAACTCCTGGGGGGACC
GTCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGT
GGACGTGAGCCACGAAGACCCTGAG
GTCAAGTTCAACTGGTACGTGGACG
GCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGC
AGCACGTACCGTTGCGTCAGCGTCCT
CACCGTCCTGCACCAGGACTGGCTG
AATGGCAAGGAGTACAAGTGCAAGG
TGTCCAACAAAGCCCTCCCAGCCCCC
ATCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGGT
GTACACCCTGCCCCCATCCCGGGAG
GAGATGACCAAGAACCAGGTCAGCC
TGACCTGCCTGGTCAAAGGCTTCTAT
CCCAGCGACATCGCCGTGGAGTGGG
AGAGCAATGGGCAGCCGGAGAACAA
CTACAAGACCACGCCTCCCGTGCTGG
ACTCCGACGGCTCCTTCTTCCTCTAT
AGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTGC
ACAACCACTACACGCAGAAGAGCCT
CTCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCCAGGTGCA
ACTGGTGCAGTCTGGGGCTGAAGTG
AAGAAGCCTGGGGCCTCAGTGAAGG
TGTCCTGCAAGGCTTCTGGATACACC
TTCCCCGGCTACTATATGTACTGGTT
GCGACAGGCCCCTGGACAAGGACTT
GAGTGGATGGGATGGATCAACCCTG
ACAGTGGTGACACAAACTATGCACA
GAAGTTTCAGGGCAGGGTCACCATG
ACCAGGGACACGTCCATCAGCACAG
CCTTTATGGAGCTGAGCAGGCTGAG
ATCAGACGACACGGCCGTGTATTACT
GTGCGAGAGAGAAGCCCAGATATTT
TGACTCCTTCTACTACTACCTTATGG
ACGTCTGGGGCCAAGGGACCACGGT
CACCGTGTCCTCAGCAAGCACGAAG
GGGCCGTCCGTATTTCCGCTTGCGCC
CTCGTCGAAGTCAACTTCGGGAGGG
ACCGCGGCACTTGGCTGTCTTGTCAA
AGATTACTTCCCTGAGCCAGTGACAG
TCAGCTGGAATTCCGGTGCCCTCACG
TCAGGAGTACATACATTCCCTGCGGT
ATTGCAGTCCTCCGGACTCTACTCCC
TGGAGTCGGTGGTAACGGTGCCCAG
CTCCAGCTTGGGGACCCAGACGTAC
ATTTGTAACGTGAATCACAAACCAA
GCAATACTAAGGTAGATAAGAAAGT
AGAACCGAAGAGCTGC
(SEQ ID NO: 721)
AA
DIQMTQSPSSVSASVGDRVTITCRASQ
DIQMTQSPSSLSASVGDRVTITCRAGQ
QVQLVESGGGLVKPGGSLRLSCAASG
GITRWLAWYQQKPGKAPKLLIYAASV
NISRHLNWYQQNPGKAPKVLIHPASSL
FTFSDYYMTWIRQAPGKGLEWISYISS
LQSGVPSRFSGSGSGTDFTLTISSLQPE
PSGVPSRFSGSGSGTDFSLTISSLQPED
SGSTIYYADSVKGRFTISRDNAKNSLY
DFATYYCQQSNSFPRTFGQGTKVEIKR
FGTYFCQQSYSTPPTFGGGTKVELKRTV
LQMNSLRAEDTAVYYCARDRNSHFD
TVAAPSVFIFPPSDEQLKSGTASVVCLL
AAPSVFIFPPSDEQLKSGTASVVCLLNN
YWGQGTLVTVSSASTKGPSVFPLAPSS
NNFYPREAKVQWKVDNALQSGNSQE
FYPREAKVQWKVDNALQSGNSQESVT
KSTSGGTAALGCLVKDYFPEPVTVSW
SVTEQDSKDSTYSLESTLTLSKADYEK
EQDSKDSTYSLKSTLTLSKADYEKHK
NSGALTSGVHTFPAVLQSSGLYSLKSV
HKVYACEVTHQGLSSPVTKSFNRGEC
VYACEVTHQGLSSPVTKSFNRGEC
VTVPSSSLGTQTYICNVNHKPSNTKVD
(SEQ ID NO: 722)
(SEQ ID NO: 723)
KKVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDV
SHEDPEVKFNWYVDGVEVHNAKTKP
CEEQYGSTYRCVSVLTVLHQDWLNGK
EYKCKVSNKALPAPIEKTISKAKGQPR
EPQVYTLPPSREEMTKNQVSLTCLVKG
FYPSDIAVEWESNGQPENNYKTTPPVL
DSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGS
GGGGSQVQLVQSGAEVKKPGASVKVS
CKASGYTFPGYYMYWLRQAPGQGLE
WMGWINPDSGDTNYAQKFQGRVTMT
RDTSISTAFMELSRLRSDDTAVYYCAR
EKPRYFDSFYYYLMDVWGQGTTVTVS
SASTKGPSVFPLAPSSKSTSGGTAALG
CLVKDYFPEPVTVSWNSGALTSGVHT
FPAVLQSSGLYSLESVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 724)
iPS:
21-233_4H6_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATTCAGATGACCCAGTCTCCATC
CAGGCTGTGCCGACTCAGCCCTCTTC
CAGGTGCAGCTGGTCGAGTCTGGGG
576180
230_33H9_Fab
4H6VH]::huIgG1zSEFL2*GK-
TTCCGTGTCTGCATCTGTAGGGGACA
CCTCTCTGCATCTCCTGGAGCATCAG
GAGGCTTGGTCAAGCCTGGAGGGTC
K::(G4S)2::[hu anti-
GAGTCACCATCACTTGTCGGGCGAGT
CCAGTCTCACCTGCACCTTACGCAGT
CCTGAGACTCTCCTGTGCAGCCTCTG
<huCD40>21-230_33H9VH]::
CAGGGTATTACCAGGTGGTTAGCCTG
GGCATCAATGTTGGTTCCTCCAGGAT
GATTCACCTTCAGTGACTACTACATG
huIgG1z-CH1-E::EPKSC +
GTATCAGCAGAAACCAGGGAAAGCC
CTATTGGTACCAGCAGAAGCCAGGG
ACCTGGATCAGGCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CCTAAGCTCCTGATCTATGCTGCATC
AGTCCTCCCCAGTTTCTCCTGAGGTA
AGGGGCTGGAGTGGATTTCATACATT
4H6VL]::huKLC-S176E +
CGTTTTGCAAAGTGGGGTCCCATCAA
CACATCAGACTCAGATAAATTGCAG
AGTAGTAGTGGTAGTACCATCTACTA
[anti-<huCD40>
GGTTCAGCGGCAGTGGATCTGGGAC
GGCTCTGGAGTCCCCAGCCGCTTCTC
CGCAGACTCTGTGAAGGGCCGATTC
21-230_33H9VL]::
AGATTTCACTCTCACCATCAGCAGCC
TGGATCCAAAGATGCTTCGGCCAAT
ACCATCTCCAGGGACAACGCCAAGA
huLLC2-K(IgG-
TGCAGCCTGAAGATTTTGCAACTTAC
GCAGGACTTTTACTCATCTCTGGGCT
ACTCACTGTATCTGCAAATGAACAGC
Fab); LMRID:
TATTGTCAACAGTCTAACAGTTTCCC
CCAGTCTGAGGATGAGGCTGACTATT
CTGAGAGCCGAGGACACGGCCGTGT
SS-30832
TCGGACGTTCGGCCAAGGGACCAAG
ACTGTATGATTTGGCACAGCAGCGCT
ATTACTGTGCGAGAGATCGGAACTC
GTGGAAATCAAACGGACGGTGGCTG
GTGGTATTCGGCGGAGGGACCAAAC
CCACTTTGACTATTGGGGCCAGGGA
CACCATCTGTCTTCATCTTCCCGCCA
TGACCGTCCTAGGTCAGCCCAAGGCT
ACCCTGGTCACCGTGTCCTCAGCCTC
TCTGATGAGCAGTTGAAATCTGGAA
GCACCCTCGGTCACTCTGTTCCCGCC
CACCAAGGGCCCATCGGTCTTCCCCC
CTGCCTCTGTTGTGTGCCTGCTGAAT
CTCCTCTGAGGAGCTTCAAGCCAACA
TGGCACCCTCCTCCAAGAGCACCTCT
AACTTCTATCCCAGAGAGGCCAAAG
AGGCCACACTGGTGTGTCTCATCAGT
GGGGGCACAGCGGCCCTGGGCTGCC
TACAGTGGAAGGTGGATAACGCCCT
GACTTCTACCCGGGAGCCGTGACAG
TGGTCAAGGACTACTTCCCCGAACCG
CCAATCGGGTAACTCCCAGGAGAGT
TGGCCTGGAAGGCAGATAGCAGCCC
GTGACGGTGTCGTGGAACTCAGGCG
GTCACAGAGCAGGACAGCAAGGACA
CGTCAAGGCGGGAGTGGAAACCACC
CCCTGACCAGCGGCGTGCACACCTTC
GCACCTACAGCCTCGAAAGCACCCT
ACACCCTCCAAACAAAGCAACAACA
CCGGCTGTCCTACAGTCCTCAGGACT
GACGCTGAGCAAAGCAGACTACGAG
AGTACGCGGCCAAGAGCTATCTGAG
CTACTCCCTCAAGAGCGTGGTGACCG
AAACACAAAGTCTACGCCTGCGAAG
CCTGACGCCTGAGCAGTGGAAGTCC
TGCCCTCCAGCAGCTTGGGCACCCAG
TCACCCATCAGGGCCTGAGCTCGCCC
CACAGAAGCTACAGCTGCCAGGTCA
ACCTACATCTGCAACGTGAATCACA
GTCACAAAGAGCTTCAACAGGGGAG
CGCATGAAGGGAGCACCGTGGAGAA
AGCCCAGCAACACCAAGGTGGACAA
AGTGT
GACAGTGGCCCCTACAGAATGTTCA
GAAAGTTGAGCCCAAATCTTGTGAC
(SEQ ID NO: 725)
(SEQ ID NO: 726)
AAAACTCACACATGCCCACCGTGCC
CAGCACCTGAACTCCTGGGGGGACC
GTCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGT
GGACGTGAGCCACGAAGACCCTGAG
GTCAAGTTCAACTGGTACGTGGACG
GCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGC
AGCACGTACCGTTGCGTCAGCGTCCT
CACCGTCCTGCACCAGGACTGGCTG
AATGGCAAGGAGTACAAGTGCAAGG
TGTCCAACAAAGCCCTCCCAGCCCCC
ATCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGGT
GTACACCCTGCCCCCATCCCGGGAG
GAGATGACCAAGAACCAGGTCAGCC
TGACCTGCCTGGTCAAAGGCTTCTAT
CCCAGCGACATCGCCGTGGAGTGGG
AGAGCAATGGGCAGCCGGAGAACAA
CTACAAGACCACGCCTCCCGTGCTGG
ACTCCGACGGCTCCTTCTTCCTCTAT
AGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTGC
ACAACCACTACACGCAGAAGAGCCT
CTCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCCAGGTGCA
GTTGGTGGAGTCTGGGGGAGGCGTG
GTCCAGCCTGGGAGGTCCCTGAGAC
TCTCCTGTGCAGCGTCTGGATTCACC
TTCAGTAGCCATGGCATGCACTGGGT
CCGCCAACCTCCAGGCAAGGGGCTG
GAGTGGGTGGCAGTTATCTGGTATG
ATGGAAGTAATGAATACTATGGAGA
CTCCGTGAAGGGCCGATTCACCATCT
CCAGAGACAATTCCAAGAACACGCT
GTATCTGCAAATGAACAGCCTGAGA
GTCGAGGACACGGCTGTGTATTACTG
TACGAGAGGGGGGGGCCACTGGAAC
TACGAGGGCCACTACTATGGTATGG
ACGTCTGGGGCCAAGGGACCACGGT
CACCGTGTCCTCAGCAAGCACGAAG
GGGCCGTCCGTATTTCCGCTTGCGCC
CTCGTCGAAGTCAACTTCGGGAGGG
ACCGCGGCACTTGGCTGTCTTGTCAA
AGATTACTTCCCTGAGCCAGTGACAG
TCAGCTGGAATTCCGGTGCCCTCACG
TCAGGAGTACATACATTCCCTGCGGT
ATTGCAGTCCTCCGGACTCTACTCCC
TGGAGTCGGTGGTAACGGTGCCCAG
CTCCAGCTTGGGGACCCAGACGTAC
ATTTGTAACGTGAATCACAAACCAA
GCAATACTAAGGTAGATAAGAAAGT
AGAACCGAAGAGCTGC
(SEQ ID NO: 727)
AA
DIQMTQSPSSVSASVGDRVTITCRASQ
QAVPTQPSSLSASPGASASLTCTLRSGI
QVQLVESGGGLVKPGGSLRLSCAASG
GITRWLAWYQQKPGKAPKLLIYAASV
NVGSSRIYWYQQKPGSPPQFLLRYTSD
FTFSDYYMTWIRQAPGKGLEWISYISS
LQSGVPSRFSGSGSGTDFTLTISSLQPE
SDKLQGSGVPSRFSGSKDASANAGLLL
SGSTIYYADSVKGRFTISRDNAKNSLY
DFATYYCQQSNSFPRTFGQGTKVEIKR
ISGLQSEDEADYYCMIWHSSAVVFGG
LQMNSLRAEDTAVYYCARDRNSHFD
TVAAPSVFIFPPSDEQLKSGTASVVCLL
GTKLTVLGQPKAAPSVTLFPPSSEELQ
YWGQGTLVTVSSASTKGPSVFPLAPSS
NNFYPREAKVQWKVDNALQSGNSQE
ANKATLVCLISDFYPGAVTVAWKADS
KSTSGGTAALGCLVKDYFPEPVTVSW
SVTEQDSKDSTYSLESTLTLSKADYEK
SPVKAGVETTTPSKQSNNKYAAKSYL
NSGALTSGVHTFPAVLQSSGLYSLKSV
HKVYACEVTHQGLSSPVTKSFNRGEC
SLTPEQWKSHRSYSCQVTHEGSTVEKT
VTVPSSSLGTQTYICNVNHKPSNTKVD
(SEQ ID NO: 728)
VAPTECS
KKVEPKSCDKTHTCPPCPAPELLGGPS
(SEQ ID NO: 729)
VFLFPPKPKDTLMISRTPEVTCVVVDV
SHEDPEVKFNWYVDGVEVHNAKTKP
CEEQYGSTYRCVSVLTVLHQDWLNGK
EYKCKVSNKALPAPIEKTISKAKGQPR
EPQVYTLPPSREEMTKNQVSLTCLVKG
FYPSDIAVEWESNGQPENNYKTTPPVL
DSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGS
GGGGSQVQLVESGGGVVQPGRSLRLS
CAASGFTFSSHGMHWVRQPPGKGLE
WVAVIWYDGSNEYYGDSVKGRFTISR
DNSKNTLYLQMNSLRVEDTAVYYCTR
GGGHWNYEGHYYGMDVWGQGTTVT
VSSASTKGPSVFPLAPSSKSTSGGTAAL
GCLVKDYFPEPVTVSWNSGALTSGVH
TFPAVLQSSGLYSLESVVTVPSSSLGTQ
TYICNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 730)
iPS:
21-233_4H6_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATTCAGATGACCCAGTCTCCATC
CAGTCTGCCCTGACTCAGCCTCGCTC
CAGGTGCAGCTGGTCGAGTCTGGGG
576183
230_35F11_Fab
4H6VH]::huIgG1zSEFL2*GK-
TTCCGTGTCTGCATCTGTAGGGGACA
AGTGTCCGGGAGCCCTGGACAGTCA
GAGGCTTGGTCAAGCCTGGAGGGTC
K::(G4S)2::[hu anti-
GAGTCACCATCACTTGTCGGGCGAGT
GTCACCATCTCCTGCACTGGAACCAG
CCTGAGACTCTCCTGTGCAGCCTCTG
<huCD40>21-230_35F11VH]::
CAGGGTATTACCAGGTGGTTAGCCTG
CAGTGATGTTGGTGGTTATATCTTTG
GATTCACCTTCAGTGACTACTACATG
huIgG1z-CH1-E::EPKSC +
GTATCAGCAGAAACCAGGGAAAGCC
TCTCCTGGTACCAACAACACCCAGGC
ACCTGGATCAGGCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CCTAAGCTCCTGATCTATGCTGCATC
AAAGCCCCCAAACTCATGATTTATGA
AGGGGCTGGAGTGGATTTCATACATT
4H6VL]::huKLC-S176E +
CGTTTTGCAAAGTGGGGTCCCATCAA
TGTCAGTAAGCGGCCCTCTGGGGTCC
AGTAGTAGTGGTAGTACCATCTACTA
[anti-<huCD40>
GGTTCAGCGGCAGTGGATCTGGGAC
CTGATCGCTTCTCTGGCTCCAAGTCT
CGCAGACTCTGTGAAGGGCCGATTC
21-230_35F11VL]::
AGATTTCACTCTCACCATCAGCAGCC
GTCAACACGGCCTCCCTGACCATCTC
ACCATCTCCAGGGACAACGCCAAGA
huLLC2-K(IgG-
TGCAGCCTGAAGATTTTGCAACTTAC
TGGGCTCCAGGCTGAGGATGAGACT
ACTCACTGTATCTGCAAATGAACAGC
Fab); LMRID:
TATTGTCAACAGTCTAACAGTTTCCC
GATTATTACTGCTGCTCATATGCAGG
CTGAGAGCCGAGGACACGGCCGTGT
SS-30833
TCGGACGTTCGGCCAAGGGACCAAG
CAACTACACTTATGTCTTCGGAACTG
ATTACTGTGCGAGAGATCGGAACTC
GTGGAAATCAAACGGACGGTGGCTG
GGACCAAGGTCACCGTCCTAGGTCA
CCACTTTGACTATTGGGGCCAGGGA
CACCATCTGTCTTCATCTTCCCGCCA
GCCCAAGGCTGCACCCTCGGTCACTC
ACCCTGGTCACCGTGTCCTCAGCCTC
TCTGATGAGCAGTTGAAATCTGGAA
TGTTCCCGCCCTCCTCTGAGGAGCTT
CACCAAGGGCCCATCGGTCTTCCCCC
CTGCCTCTGTTGTGTGCCTGCTGAAT
CAACCCAACAAGGCCACACTGGTGT
TGGCACCCTCCTCCAAGAGCACCTCT
AACTTCTATCCCAGAGAGGCCAAAG
GTCTCATCAGTGACTTCTACCCGGGA
GGGGGCACAGCGGCCCTGGGCTGCC
TACAGTGGAAGGTGGATAACGCCCT
GCCGTGACAGTGGCCTGGAAGGCAG
TGGTCAAGGACTACTTCCCCGAACCG
CCAATCGGGTAACTCCCAGGAGAGT
ATAGCAGCCCCGTCAAGGCGGGAGT
GTGACGGTGTCGTGGAACTCAGGCG
GTCACAGAGCAGGACAGCAAGGACA
GGAAACCACCACACCCTCCAAACAA
CCCTGACCAGCGGCGTGCACACCTTC
GCACCTACAGCCTCGAAAGCACCCT
AGCAACAACAAGTACGCGGCCAAGA
CCGGCTGTCCTACAGTCCTCAGGACT
GACGCTGAGCAAAGCAGACTACGAG
GCTATCTGAGCCTGACGCCTGAGCA
CTACTCCCTCAAGAGCGTGGTGACCG
AAACACAAAGTCTACGCCTGCGAAG
GTGGAAGTCCCACAGAAGCTACAGC
TGCCCTCCAGCAGCTTGGGCACCCAG
TCACCCATCAGGGCCTGAGCTCGCCC
TGCCAGGTCACGCATGAAGGGAGCA
ACCTACATCTGCAACGTGAATCACA
GTCACAAAGAGCTTCAACAGGGGAG
CCGTGGAGAAGACAGTGGCCCCTAC
AGCCCAGCAACACCAAGGTGGACAA
AGTGT
AGAATGTTCA
GAAAGTTGAGCCCAAATCTTGTGAC
(SEQ ID NO: 731)
(SEQ ID NO: 732)
AAAACTCACACATGCCCACCGTGCC
CAGCACCTGAACTCCTGGGGGGACC
GTCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGT
GGACGTGAGCCACGAAGACCCTGAG
GTCAAGTTCAACTGGTACGTGGACG
GCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGC
AGCACGTACCGTTGCGTCAGCGTCCT
CACCGTCCTGCACCAGGACTGGCTG
AATGGCAAGGAGTACAAGTGCAAGG
TGTCCAACAAAGCCCTCCCAGCCCCC
ATCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGGT
GTACACCCTGCCCCCATCCCGGGAG
GAGATGACCAAGAACCAGGTCAGCC
TGACCTGCCTGGTCAAAGGCTTCTAT
CCCAGCGACATCGCCGTGGAGTGGG
AGAGCAATGGGCAGCCGGAGAACAA
CTACAAGACCACGCCTCCCGTGCTGG
ACTCCGACGGCTCCTTCTTCCTCTAT
AGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTGC
ACAACCACTACACGCAGAAGAGCCT
CTCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCCAGGTGCA
GCTGGTGGAGTCTGGGGGAGGCGTG
GTCCAGCCTGGGAGGTCCCTGAGAC
TCTCCTGTGCAGCGTCTGGATTCACC
CTCAGTAGCTATGGCATGCACTGGGT
CCGCCAGGCTCCAGGCAAGGGGCTG
GAGTGGGTGGCAGTTATCTGGTATG
ATGGAAGTAATAAATACTATGCAGA
CTCCGTGAAGGGCCGAGTCACCATCT
CCAGAGACAATTCCAAGAACACGCT
GTATCTGCAAATGAATAGCCTGAGA
GCCGAGGACACGGCTGTGTATTACT
GTACGAGAGATGGCCGGAACTACGT
CTACTTTGACAACTGGGGCCAGGGA
ACCCTGGTCACCGTGTCCTCAGCAAG
CACGAAGGGGCCGTCCGTATTTCCGC
TTGCGCCCTCGTCGAAGTCAACTTCG
GGAGGGACCGCGGCACTTGGCTGTC
TTGTCAAAGATTACTTCCCTGAGCCA
GTGACAGTCAGCTGGAATTCCGGTG
CCCTCACGTCAGGAGTACATACATTC
CCTGCGGTATTGCAGTCCTCCGGACT
CTACTCCCTGGAGTCGGTGGTAACGG
TGCCCAGCTCCAGCTTGGGGACCCA
GACGTACATTTGTAACGTGAATCACA
AACCAAGCAATACTAAGGTAGATAA
GAAAGTAGAACCGAAGAGCTGC
(SEQ ID NO: 733)
AA
DIQMTQSPSSVSASVGDRVTITCRASQ
QSALTQPRSVSGSPGQSVTISCTGTSSD
QVQLVESGGGLVKPGGSLRLSCAASG
GITRWLAWYQQKPGKAPKLLIYAASV
VGGYIFVSWYQQHPGKAPKLMIYDVS
FTFSDYYMTWIRQAPGKGLEWISYISS
LQSGVPSRFSGSGSGTDFTLTISSLQPE
KRPSGVPDRFSGSKSVNTASLTISGLQ
SGSTIYYADSVKGRFTISRDNAKNSLY
DFATYYCQQSNSFPRTFGQGTKVEIKR
AEDETDYYCCSYAGNYTYVFGTGTKV
LQMNSLRAEDTAVYYCARDRNSHFD
TVAAPSVFIFPPSDEQLKSGTASVVCLL
TVLGQPKAAPSVTLFPPSSEELQANKA
YWGQGTLVTVSSASTKGPSVFPLAPSS
NNFYPREAKVQWKVDNALQSGNSQE
TLVCLISDFYPGAVTVAWKADSSPVK
KSTSGGTAALGCLVKDYFPEPVTVSW
SVTEQDSKDSTYSLESTLTLSKADYEK
AGVETTTPSKQSNNKYAAKSYLSLTPE
NSGALTSGVHTFPAVLQSSGLYSLKSV
HKVYACEVTHQGLSSPVTKSFNRGEC
QWKSHRSYSCQVTHEGSTVEKTVAPT
VTVPSSSLGTQTYICNVNHKPSNTKVD
(SEQ ID NO: 734)
ECS
KKVEPKSCDKTHTCPPCPAPELLGGPS
(SEQ ID NO: 735)
VFLFPPKPKDTLMISRTPEVTCVVVDV
SHEDPEVKFNWYVDGVEVHNAKTKP
CEEQYGSTYRCVSVLTVLHQDWLNGK
EYKCKVSNKALPAPIEKTISKAKGQPR
EPQVYTLPPSREEMTKNQVSLTCLVKG
FYPSDIAVEWESNGQPENNYKTTPPVL
DSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGS
GGGGSQVQLVESGGGVVQPGRSLRLS
CAASGFTLSSYGMHWVRQAPGKGLE
WVAVIWYDGSNKYYADSVKGRVTISR
DNSKNTLYLQMNSLRAEDTAVYYCTR
DGRNYVYFDNWGQGTLVTVSSASTK
GPSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAVLQ
SSGLYSLESVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSC
(SEQ ID NO: 736)
iPS:
21-233_4H6_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATTCAGATGACCCAGTCTCCATC
GAAATTGTGTTGACGCAGTCTCCAGG
CAGGTGCAGCTGGTCGAGTCTGGGG
576186
230_36F3_Fab
4H6VH]::huIgG1zSEFL2*GK-
TTCCGTGTCTGCATCTGTAGGGGACA
CACCCTGTCTTTGTCTCCAGGGGAAA
GAGGCTTGGTCAAGCCTGGAGGGTC
K::(G4S)2::[hu anti-
GAGTCACCATCACTTGTCGGGCGAGT
GAGCCACCCTCTCCTGCAGGGCCAGT
CCTGAGACTCTCCTGTGCAGCCTCTG
<huCD40>21-230_36F3VH]::
CAGGGTATTACCAGGTGGTTAGCCTG
CAGAGTGTTAGCAGCAACTACTTAG
GATTCACCTTCAGTGACTACTACATG
huIgG1z-CH1-E::EPKSC +
GTATCAGCAGAAACCAGGGAAAGCC
CCTGGTACCAACAGAAACCTGGCCA
ACCTGGATCAGGCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CCTAAGCTCCTGATCTATGCTGCATC
GGCTCCCAGGGCCCTTATCTATGCTG
AGGGGCTGGAGTGGATTTCATACATT
4H6VL]::huKLC-S176E +
CGTTTTGCAAAGTGGGGTCCCATCAA
CATCCAACAGGGCCGCTGGCATCTC
AGTAGTAGTGGTAGTACCATCTACTA
[anti-<huCD40>
GGTTCAGCGGCAGTGGATCTGGGAC
AGACAGGTTCAGTGGCAGTGGGTCT
CGCAGACTCTGTGAAGGGCCGATTC
21-230_36F3VL]::
AGATTTCACTCTCACCATCAGCAGCC
GGGACAGACTTCACTCTCACCATCAG
ACCATCTCCAGGGACAACGCCAAGA
huKLC-S176K(IgG-
TGCAGCCTGAAGATTTTGCAACTTAC
CAGACTGGAGCCTGAAGATTTTGCA
ACTCACTGTATCTGCAAATGAACAGC
Fab); LMRID:
TATTGTCAACAGTCTAACAGTTTCCC
GTGTATTTCTGTCAGCAGTATGGTAG
CTGAGAGCCGAGGACACGGCCGTGT
SS-30834
TCGGACGTTCGGCCAAGGGACCAAG
CTCACCGCTCACTTTCGGCGGAGGGA
ATTACTGTGCGAGAGATCGGAACTC
GTGGAAATCAAACGGACGGTGGCTG
CTAAGGTGGAGATCAAACGAACGGT
CCACTTTGACTATTGGGGCCAGGGA
CACCATCTGTCTTCATCTTCCCGCCA
GGCTGCACCATCTGTCTTCATCTTCC
ACCCTGGTCACCGTGTCCTCAGCCTC
TCTGATGAGCAGTTGAAATCTGGAA
CGCCATCTGATGAGCAGTTGAAATCT
CACCAAGGGCCCATCGGTCTTCCCCC
CTGCCTCTGTTGTGTGCCTGCTGAAT
GGAACTGCCTCTGTTGTGTGCCTGCT
TGGCACCCTCCTCCAAGAGCACCTCT
AACTTCTATCCCAGAGAGGCCAAAG
GAATAACTTCTATCCCAGAGAGGCC
GGGGGCACAGCGGCCCTGGGCTGCC
TACAGTGGAAGGTGGATAACGCCCT
AAAGTACAGTGGAAGGTGGATAACG
TGGTCAAGGACTACTTCCCCGAACCG
CCAATCGGGTAACTCCCAGGAGAGT
CCCTCCAATCGGGTAACTCCCAGGA
GTGACGGTGTCGTGGAACTCAGGCG
GTCACAGAGCAGGACAGCAAGGACA
GAGTGTCACAGAGCAGGACAGCAAG
CCCTGACCAGCGGCGTGCACACCTTC
GCACCTACAGCCTCGAAAGCACCCT
GACAGCACCTACAGCCTCAAGAGCA
CCGGCTGTCCTACAGTCCTCAGGACT
GACGCTGAGCAAAGCAGACTACGAG
CCCTGACGCTGAGCAAAGCAGACTA
CTACTCCCTCAAGAGCGTGGTGACCG
AAACACAAAGTCTACGCCTGCGAAG
CGAGAAACACAAAGTCTACGCCTGC
TGCCCTCCAGCAGCTTGGGCACCCAG
TCACCCATCAGGGCCTGAGCTCGCCC
GAAGTCACCCATCAGGGCCTGAGCT
ACCTACATCTGCAACGTGAATCACA
GTCACAAAGAGCTTCAACAGGGGAG
CGCCCGTCACAAAGAGCTTCAACAG
AGCCCAGCAACACCAAGGTGGACAA
AGTGT
GGGAGAGTGT
GAAAGTTGAGCCCAAATCTTGTGAC
(SEQ ID NO: 737)
(SEQ ID NO: 738)
AAAACTCACACATGCCCACCGTGCC
CAGCACCTGAACTCCTGGGGGGACC
GTCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGT
GGACGTGAGCCACGAAGACCCTGAG
GTCAAGTTCAACTGGTACGTGGACG
GCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGC
AGCACGTACCGTTGCGTCAGCGTCCT
CACCGTCCTGCACCAGGACTGGCTG
AATGGCAAGGAGTACAAGTGCAAGG
TGTCCAACAAAGCCCTCCCAGCCCCC
ATCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGGT
GTACACCCTGCCCCCATCCCGGGAG
GAGATGACCAAGAACCAGGTCAGCC
TGACCTGCCTGGTCAAAGGCTTCTAT
CCCAGCGACATCGCCGTGGAGTGGG
AGAGCAATGGGCAGCCGGAGAACAA
CTACAAGACCACGCCTCCCGTGCTGG
ACTCCGACGGCTCCTTCTTCCTCTAT
AGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTGC
ACAACCACTACACGCAGAAGAGCCT
CTCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCCAGGTACA
GCTGCAACAGTCAGGTCCAGGACTG
GTGAAGCCCTCGCAGACCCTCTCACT
CACCTGTGCCATCTCCGGGGACAGTG
TCTCTAGCAGCCGTACTGCTTGGAAC
TGGATCAGGCAGTCCCCATCGAGAG
GCCTTGAGTGGCTGGGAAGGACATA
CTACAGGTCCAAGTGGTATCATGATT
ATTCAGTATCTGTGAAAAGTCGAATC
ACCATCGACCCAGACACATCCAAGA
ACCAGTTCTCCCTGCAGCTGAACTCT
GTGACTCCCGAGGACACGGCTGTTTA
TTATTGTGCAAGAGGGGCTGCTCCCT
TTGACTACTGGGGCCAGGGAACCCT
GGTCACCGTGTCCTCAGCAAGCACG
AAGGGGCCGTCCGTATTTCCGCTTGC
GCCCTCGTCGAAGTCAACTTCGGGA
GGGACCGCGGCACTTGGCTGTCTTGT
CAAAGATTACTTCCCTGAGCCAGTGA
CAGTCAGCTGGAATTCCGGTGCCCTC
ACGTCAGGAGTACATACATTCCCTGC
GGTATTGCAGTCCTCCGGACTCTACT
CCCTGGAGTCGGTGGTAACGGTGCC
CAGCTCCAGCTTGGGGACCCAGACG
TACATTTGTAACGTGAATCACAAACC
AAGCAATACTAAGGTAGATAAGAAA
GTAGAACCGAAGAGCTGC
(SEQ ID NO: 739)
AA
DIQMTQSPSSVSASVGDRVTITCRASQ
EIVLTQSPGTLSLSPGERATLSCRASQS
QVQLVESGGGLVKPGGSLRLSCAASG
GITRWLAWYQQKPGKAPKLLIYAASV
VSSNYLAWYQQKPGQAPRALIYAASN
FTFSDYYMTWIRQAPGKGLEWISYISS
LQSGVPSRFSGSGSGTDFTLTISSLQPE
RAAGISDRFSGSGSGTDFTLTISRLEPE
SGSTIYYADSVKGRFTISRDNAKNSLY
DFATYYCQQSNSFPRTFGQGTKVEIKR
DFAVYFCQQYGSSPLTFGGGTKVEIKR
LQMNSLRAEDTAVYYCARDRNSHFD
TVAAPSVFIFPPSDEQLKSGTASVVCLL
TVAAPSVFIFPPSDEQLKSGTASVVCLL
YWGQGTLVTVSSASTKGPSVFPLAPSS
NNFYPREAKVQWKVDNALQSGNSQE
NNFYPREAKVQWKVDNALQSGNSQE
KSTSGGTAALGCLVKDYFPEPVTVSW
SVTEQDSKDSTYSLESTLTLSKADYEK
SVTEQDSKDSTYSLKSTLTLSKADYEK
NSGALTSGVHTFPAVLQSSGLYSLKSV
HKVYACEVTHQGLSSPVTKSFNRGEC
HKVYACEVTHQGLSSPVTKSFNRGEC
VTVPSSSLGTQTYICNVNHKPSNTKVD
(SEQ ID NO: 740)
(SEQ ID NO: 741)
KKVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDV
SHEDPEVKFNWYVDGVEVHNAKTKP
CEEQYGSTYRCVSVLTVLHQDWLNGK
EYKCKVSNKALPAPIEKTISKAKGQPR
EPQVYTLPPSREEMTKNQVSLTCLVKG
FYPSDIAVEWESNGQPENNYKTTPPVL
DSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGS
GGGGSQVQLQQSGPGLVKPSQTLSLT
CAISGDSVSSSRTAWNWIRQSPSRGLE
WLGRTYYRSKWYHDYSVSVKSRITID
PDTSKNQFSLQLNSVTPEDTAVYYCAR
GAAPFDYWGQGTLVTVSSASTKGPSV
FPLAPSSKSTSGGTAALGCLVKDYFPE
PVTVSWNSGALTSGVHTFPAVLQSSGL
YSLESVVTVPSSSLGTQTYICNVNHKP
SNTKVDKKVEPKSC
(SEQ ID NO: 742)
iPS:
21-233_4H6_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATTCAGATGACCCAGTCTCCATC
TCCTATGAGCTGACTCAGCCACCCTC
CAGGTGCAGCTGGTCGAGTCTGGGG
576189
230_37A6_Fab
4H6VH]::huIgG1zSEFL2*GK-
TTCCGTGTCTGCATCTGTAGGGGACA
AGTGTCCGTGTCCCCAGGACAGACA
GAGGCTTGGTCAAGCCTGGAGGGTC
K::(G4S)2::[hu anti-
GAGTCACCATCACTTGTCGGGCGAGT
GCCAGCATCACCTGCTCTGGAGAAA
CCTGAGACTCTCCTGTGCAGCCTCTG
<huCD40>21-230_37A6VH]::
CAGGGTATTACCAGGTGGTTAGCCTG
GGTTGGGAAATAAATATATTTGCTGG
GATTCACCTTCAGTGACTACTACATG
huIgG1z-CH1-E::EPKSC +
GTATCAGCAGAAACCAGGGAAAGCC
TATCAGCAGAAGCCAGGCCAGTCCC
ACCTGGATCAGGCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CCTAAGCTCCTGATCTATGCTGCATC
CTGTTCTGGTCATCTATCAAGATTTC
AGGGGCTGGAGTGGATTTCATACATT
4H6VL]::huKLC-S176E +
CGTTTTGCAAAGTGGGGTCCCATCAA
AAGCGGCCCTCAGGGATCCCTGAGC
AGTAGTAGTGGTAGTACCATCTACTA
[anti-<huCD40>
GGTTCAGCGGCAGTGGATCTGGGAC
GATTCTCTGGCTCCAACTCTGGGATC
CGCAGACTCTGTGAAGGGCCGATTC
21-230_37A6VL]::
AGATTTCACTCTCACCATCAGCAGCC
ACAGCCACTCTGACCATCAGCGGGA
ACCATCTCCAGGGACAACGCCAAGA
huLLC2-K(IgG-
TGCAGCCTGAAGATTTTGCAACTTAC
CCCAGGCTATGGATGAGGCTGACTA
ACTCACTGTATCTGCAAATGAACAGC
Fab); LMRID:
TATTGTCAACAGTCTAACAGTTTCCC
TTACTGTCAGGCGTGGGACAGCAGA
CTGAGAGCCGAGGACACGGCCGTGT
SS-30835
TCGGACGTTCGGCCAAGGGACCAAG
ACTGTGGTATTCGGCGGAGGGACCA
ATTACTGTGCGAGAGATCGGAACTC
GTGGAAATCAAACGGACGGTGGCTG
AGCTGACCGTCCTAGGTCAGCCCAA
CCACTTTGACTATTGGGGCCAGGGA
CACCATCTGTCTTCATCTTCCCGCCA
GGCTGCACCCTCGGTCACTCTGTTCC
ACCCTGGTCACCGTGTCCTCAGCCTC
TCTGATGAGCAGTTGAAATCTGGAA
CGCCCTCCTCTGAGGAGCTTCAAGCC
CACCAAGGGCCCATCGGTCTTCCCCC
CTGCCTCTGTTGTGTGCCTGCTGAAT
AACAAGGCCACACTGGTGTGTCTCAT
TGGCACCCTCCTCCAAGAGCACCTCT
AACTTCTATCCCAGAGAGGCCAAAG
CAGTGACTTCTACCCGGGAGCCGTG
GGGGGCACAGCGGCCCTGGGCTGCC
TACAGTGGAAGGTGGATAACGCCCT
ACAGTGGCCTGGAAGGCAGATAGCA
TGGTCAAGGACTACTTCCCCGAACCG
CCAATCGGGTAACTCCCAGGAGAGT
GCCCCGTCAAGGCGGGAGTGGAAAC
GTGACGGTGTCGTGGAACTCAGGCG
GTCACAGAGCAGGACAGCAAGGACA
CACCACACCCTCCAAACAAAGCAAC
CCCTGACCAGCGGCGTGCACACCTTC
GCACCTACAGCCTCGAAAGCACCCT
AACAAGTACGCGGCCAAGAGCTATC
CCGGCTGTCCTACAGTCCTCAGGACT
GACGCTGAGCAAAGCAGACTACGAG
TGAGCCTGACGCCTGAGCAGTGGAA
CTACTCCCTCAAGAGCGTGGTGACCG
AAACACAAAGTCTACGCCTGCGAAG
GTCCCACAGAAGCTACAGCTGCCAG
TGCCCTCCAGCAGCTTGGGCACCCAG
TCACCCATCAGGGCCTGAGCTCGCCC
GTCACGCATGAAGGGAGCACCGTGG
ACCTACATCTGCAACGTGAATCACA
GTCACAAAGAGCTTCAACAGGGGAG
AGAAGACAGTGGCCCCTACAGAATG
AGCCCAGCAACACCAAGGTGGACAA
AGTGT
TTCA
GAAAGTTGAGCCCAAATCTTGTGAC
(SEQ ID NO: 743)
(SEQ ID NO: 744)
AAAACTCACACATGCCCACCGTGCC
CAGCACCTGAACTCCTGGGGGGACC
GTCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGT
GGACGTGAGCCACGAAGACCCTGAG
GTCAAGTTCAACTGGTACGTGGACG
GCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGC
AGCACGTACCGTTGCGTCAGCGTCCT
CACCGTCCTGCACCAGGACTGGCTG
AATGGCAAGGAGTACAAGTGCAAGG
TGTCCAACAAAGCCCTCCCAGCCCCC
ATCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGGT
GTACACCCTGCCCCCATCCCGGGAG
GAGATGACCAAGAACCAGGTCAGCC
TGACCTGCCTGGTCAAAGGCTTCTAT
CCCAGCGACATCGCCGTGGAGTGGG
AGAGCAATGGGCAGCCGGAGAACAA
CTACAAGACCACGCCTCCCGTGCTGG
ACTCCGACGGCTCCTTCTTCCTCTAT
AGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTGC
ACAACCACTACACGCAGAAGAGCCT
CTCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCCAGGTGCA
GTTGGTGGAGTCTGGGGGAGGCTTA
GTCAAGCCTGGAGGGTCCCTGAGAC
TCTCCTGTGCAGCCTCTGAATTCACC
TTCAGTGACTACTACATGAGCTGGAT
CCGCCAGGCTCCAGGGAAGGGGCTG
GAGTGGGTTTCATATATTAGTCGAAG
TGGTGATACCATCTACTACGCAGACT
CTGTGAAGGGCCGATTCACCATCTCC
AGGGACAACGCCAAGAACTCACTGT
ATCTGCAAATGAATGGCCTGCGAGC
CGAAGACACGGCCGTGTATTACTGT
GCGAGAGACTTAGCAGCAGGTGCTA
CAGGGGGCCTTGACTGCTGGGGCCA
GGGAACCCTGGTCACCGTGTCCTCAG
CAAGCACGAAGGGGCCGTCCGTATT
TCCGCTTGCGCCCTCGTCGAAGTCAA
CTTCGGGAGGGACCGCGGCACTTGG
CTGTCTTGTCAAAGATTACTTCCCTG
AGCCAGTGACAGTCAGCTGGAATTC
CGGTGCCCTCACGTCAGGAGTACAT
ACATTCCCTGCGGTATTGCAGTCCTC
CGGACTCTACTCCCTGGAGTCGGTGG
TAACGGTGCCCAGCTCCAGCTTGGG
GACCCAGACGTACATTTGTAACGTG
AATCACAAACCAAGCAATACTAAGG
TAGATAAGAAAGTAGAACCGAAGAG
CTGC
(SEQ ID NO: 745)
AA
DIQMTQSPSSVSASVGDRVTITCRASQ
SYELTQPPSVSVSPGQTASITCSGERLG
QVQLVESGGGLVKPGGSLRLSCAASG
GITRWLAWYQQKPGKAPKLLIYAASV
NKYICWYQQKPGQSPVLVIYQDFKRPS
FTFSDYYMTWIRQAPGKGLEWISYISS
LQSGVPSRFSGSGSGTDFTLTISSLQPE
GIPERFSGSNSGITATLTISGTQAMDEA
SGSTIYYADSVKGRFTISRDNAKNSLY
DFATYYCQQSNSFPRTFGQGTKVEIKR
DYYCQAWDSRTVVFGGGTKLTVLGQ
LQMNSLRAEDTAVYYCARDRNSHFD
TVAAPSVFIFPPSDEQLKSGTASVVCLL
PKAAPSVTLFPPSSEELQANKATLVCLI
YWGQGTLVTVSSASTKGPSVFPLAPSS
NNFYPREAKVQWKVDNALQSGNSQE
SDFYPGAVTVAWKADSSPVKAGVETT
KSTSGGTAALGCLVKDYFPEPVTVSW
SVTEQDSKDSTYSLESTLTLSKADYEK
TPSKQSNNKYAAKSYLSLTPEQWKSH
NSGALTSGVHTFPAVLQSSGLYSLKSV
HKVYACEVTHQGLSSPVTKSFNRGEC
RSYSCQVTHEGSTVEKTVAPTECS
VTVPSSSLGTQTYICNVNHKPSNTKVD
(SEQ ID NO: 746)
(SEQ ID NO: 747)
KKVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDV
SHEDPEVKFNWYVDGVEVHNAKTKP
CEEQYGSTYRCVSVLTVLHQDWLNGK
EYKCKVSNKALPAPIEKTISKAKGQPR
EPQVYTLPPSREEMTKNQVSLTCLVKG
FYPSDIAVEWESNGQPENNYKTTPPVL
DSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGS
GGGGSQVQLVESGGGLVKPGGSLRLS
CAASEFTFSDYYMSWIRQAPGKGLEW
VSYISRSGDTIYYADSVKGRFTISRDNA
KNSLYLQMNGLRAEDTAVYYCARDL
AAGATGGLDCWGQGTLVTVSSASTK
GPSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAVLQ
SSGLYSLESVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSC
(SEQ ID NO: 748)
iPS:
21-233_4H6_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATCCAGATGACCCAGTCTCCATC
CAGTCTGCCCTGACTCAGCCTGCCTC
CAGGTGCAGCTGGTCGAGTCTGGGG
576192
230_39C2_Fab
4H6VH]::huIgG1zSEFL2*GK-
TTCCGTGTCTGCTTCTGTCGGAGACA
CGTGTCTGGGAGCCCTGGACAGTCG
GAGGCTTGGTCAAGCCTGGAGGGTC
K::(G4S)2::[hu anti-
GAGTCACCATCACTTGTCGGGCGAGT
ATCACCATCTCCTGCACTGGAACCAG
CCTGAGACTCTCCTGTGCAGCCTCTG
<huCD40>21-230_39C2VH]::
CAGGATATTAGCAGGTGGTTAGCCT
CAGTGATGTTGGGAATTATAACCTTG
GATTCACCTTCAGTGACTACTACATG
huIgG1z-CH1-E::EPKSC +
GGTATCAGCAGAAACCAGGGAAAGC
TCTCCTGGTACCAACAGCACCCAGGC
ACCTGGATCAGGCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CCCTAAGCTCCTGATTTCTGCTGCAT
AAAGCCCCCAAACTCATGATTTATGA
AGGGGCTGGAGTGGATTTCATACATT
4H6VL]::huKLC-S176E +
CCAGATTGCAAAGTGGAGTCCCATC
GGTCAATAGGCGGCCCTCAGGGGTT
AGTAGTAGTGGTAGTACCATCTACTA
[anti-<huCD40>
AAGGTTCAGCGGCAGTGGATCTGGG
TCTAATCGCTTCTCTGGCTCCAAGTC
CGCAGACTCTGTGAAGGGCCGATTC
21-230_39C2VL]::
ACAGATTTCACTCTCACCATCAGCAG
TGGCAACACGGCCTCCCTGACAATCT
ACCATCTCCAGGGACAACGCCAAGA
huLLC2-K(IgG-
CCTGCAGCCTGAAGATTTTGCAATTT
CTGGGCTCCAGGCTGAGGACGAGGC
ACTCACTGTATCTGCAAATGAACAGC
Fab); LMRID:
ACTATTGTCAACAGGCTAAAAGTTTT
TGAATATTACTGCTGCTCATATGCAG
CTGAGAGCCGAGGACACGGCCGTGT
SS-30836
CCTCGGACGTTCGGCCAAGGGACCA
GTAGAGACACTTTCGTGGTGTTCGGC
ATTACTGTGCGAGAGATCGGAACTC
AGGTGGAAATCAAACGGACGGTGGC
GGAGGGACCAAGCTGACCGTCCTAG
CCACTTTGACTATTGGGGCCAGGGA
TGCACCATCTGTCTTCATCTTCCCGC
GTCAGCCCAAGGCTGCACCCTCGGTC
ACCCTGGTCACCGTGTCCTCAGCCTC
CATCTGATGAGCAGTTGAAATCTGG
ACTCTGTTCCCGCCCTCCTCTGAGGA
CACCAAGGGCCCATCGGTCTTCCCCC
AACTGCCTCTGTTGTGTGCCTGCTGA
GCTTCAAGCCAACAAGGCCACACTG
TGGCACCCTCCTCCAAGAGCACCTCT
ATAACTTCTATCCCAGAGAGGCCAA
GTGTGTCTCATCAGTGACTTCTACCC
GGGGGCACAGCGGCCCTGGGCTGCC
AGTACAGTGGAAGGTGGATAACGCC
GGGAGCCGTGACAGTGGCCTGGAAG
TGGTCAAGGACTACTTCCCCGAACCG
CTCCAATCGGGTAACTCCCAGGAGA
GCAGATAGCAGCCCCGTCAAGGCGG
GTGACGGTGTCGTGGAACTCAGGCG
GTGTCACAGAGCAGGACAGCAAGGA
GAGTGGAAACCACCACACCCTCCAA
CCCTGACCAGCGGCGTGCACACCTTC
CAGCACCTACAGCCTCGAAAGCACC
ACAAAGCAACAACAAGTACGCGGCC
CCGGCTGTCCTACAGTCCTCAGGACT
CTGACGCTGAGCAAAGCAGACTACG
AAGAGCTATCTGAGCCTGACGCCTG
CTACTCCCTCAAGAGCGTGGTGACCG
AGAAACACAAAGTCTACGCCTGCGA
AGCAGTGGAAGTCCCACAGAAGCTA
TGCCCTCCAGCAGCTTGGGCACCCAG
AGTCACCCATCAGGGCCTGAGCTCG
CAGCTGCCAGGTCACGCATGAAGGG
ACCTACATCTGCAACGTGAATCACA
CCCGTCACAAAGAGCTTCAACAGGG
AGCACCGTGGAGAAGACAGTGGCCC
AGCCCAGCAACACCAAGGTGGACAA
GAGAGTGT
CTACAGAATGTTCA
GAAAGTTGAGCCCAAATCTTGTGAC
(SEQ ID NO: 749)
(SEQ ID NO: 750)
AAAACTCACACATGCCCACCGTGCC
CAGCACCTGAACTCCTGGGGGGACC
GTCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGT
GGACGTGAGCCACGAAGACCCTGAG
GTCAAGTTCAACTGGTACGTGGACG
GCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGC
AGCACGTACCGTTGCGTCAGCGTCCT
CACCGTCCTGCACCAGGACTGGCTG
AATGGCAAGGAGTACAAGTGCAAGG
TGTCCAACAAAGCCCTCCCAGCCCCC
ATCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGGT
GTACACCCTGCCCCCATCCCGGGAG
GAGATGACCAAGAACCAGGTCAGCC
TGACCTGCCTGGTCAAAGGCTTCTAT
CCCAGCGACATCGCCGTGGAGTGGG
AGAGCAATGGGCAGCCGGAGAACAA
CTACAAGACCACGCCTCCCGTGCTGG
ACTCCGACGGCTCCTTCTTCCTCTAT
AGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTGC
ACAACCACTACACGCAGAAGAGCCT
CTCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCCAGGTGCA
GCTGGTGCAGTCTGGGACTGAGGTG
AAGAAGCCTGGGGCCTCAGTGAAGG
TGTCCTGCAAGGCTTCTGGATACACC
TTCCCCGGCTACTATATGCACTGGGT
GCGACAGGCCCCTGGACAGGGGCTT
GAGTGGATGGGATGGATCAACCCTG
ACAGTGGTGGCACAAAGTATACACA
GAAGTTTCAGGGCAGGGTCACCTTG
ACCAGGGACGCGTCCGTCAGCACAG
CCTACATTGACCTGAACAGGCTGAG
ATCTGACGACACGGCCGTATATTACT
GTGCGAGAGAGAGGTGTAGGACTAC
CAACTGCTATTTGGACTACTGGGGCC
AGGGAAGTCTGGTCACCGTGTCCTCA
GCAAGCACGAAGGGGCCGTCCGTAT
TTCCGCTTGCGCCCTCGTCGAAGTCA
ACTTCGGGAGGGACCGCGGCACTTG
GCTGTCTTGTCAAAGATTACTTCCCT
GAGCCAGTGACAGTCAGCTGGAATT
CCGGTGCCCTCACGTCAGGAGTACAT
ACATTCCCTGCGGTATTGCAGTCCTC
CGGACTCTACTCCCTGGAGTCGGTGG
TAACGGTGCCCAGCTCCAGCTTGGG
GACCCAGACGTACATTTGTAACGTG
AATCACAAACCAAGCAATACTAAGG
TAGATAAGAAAGTAGAACCGAAGAG
CTGC
(SEQ ID NO: 751)
AA
DISRWLAWYQQKPGKAPKLLISAASR
VGNYNLVSWYQQHPGKAPKLMIYEV
FTFSDYYMTWIRQAPGKGLEWISYISS
LQSGVPSRFSGSGSGTDFTLTISSLQPE
NRRPSGVSNRFSGSKSGNTASLTISGLQ
SGSTIYYADSVKGRFTISRDNAKNSLY
DFAIYYCQQAKSFPRTFGQGTKVEIKR
AEDEAEYYCCSYAGRDTFVVFGGGTK
LQMNSLRAEDTAVYYCARDRNSHFD
TVAAPSVFIFPPSDEQLKSGTASVVCLL
LTVLGQPKAAPSVTLFPPSSEELQANK
YWGQGTLVTVSSASTKGPSVFPLAPSS
NNFYPREAKVQWKVDNALQSGNSQE
ATLVCLISDFYPGAVTVAWKADSSPV
KSTSGGTAALGCLVKDYFPEPVTVSW
SVTEQDSKDSTYSLESTLTLSKADYEK
KAGVETTTPSKQSNNKYAAKSYLSLTP
NSGALTSGVHTFPAVLQSSGLYSLKSV
HKVYACEVTHQGLSSPVTKSFNRGEC
EQWKSHRSYSCQVTHEGSTVEKTVAP
VTVPSSSLGTQTYICNVNHKPSNTKVD
(SEQ ID NO: 752)
TECS
KKVEPKSCDKTHTCPPCPAPELLGGPS
(SEQ ID NO: 753)
VFLFPPKPKDTLMISRTPEVTCVVVDV
SHEDPEVKFNWYVDGVEVHNAKTKP
CEEQYGSTYRCVSVLTVLHQDWLNGK
EYKCKVSNKALPAPIEKTISKAKGQPR
EPQVYTLPPSREEMTKNQVSLTCLVKG
FYPSDIAVEWESNGQPENNYKTTPPVL
DSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGS
GGGGSQVQLVQSGTEVKKPGASVKVS
CKASGYTFPGYYMHWVRQAPGQGLE
WMGWINPDSGGTKYTQKFQGRVTLT
RDASVSTAYIDLNRLRSDDTAVYYCA
RERCRTTNCYLDYWGQGSLVTVSSAS
TKGPSVFPLAPSSKSTSGGTAALGCLV
KDYFPEPVTVSWNSGALTSGVHTFPA
VLQSSGLYSLESVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 754)
iPS:
21-233_6F4_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATCCAGATGACCCAGTCTCCATC
GACATCCAGATGACCCAGTCTCCATC
CAGGTGCAGCTGGTGGAGTCTGGGG
576198
230_4G7_Fab
6F4VH]::huIgG1zSEFL2*GK-
TTCCGTGTCTGCTTCTGTCGGAGACA
CTCCCTGTCTGCATCTGTAGGAGACA
GAGGCTTGGTCAAGCCTGGAGGGTC
K::(G4S)2::[hu anti-
GAGTCACCATCACTTGTCGGGCGAGT
TTCTCACCATCACTTGCCGGGCAAGT
CCTGAGACTCTCCTGTGCAGCCTCTG
<huCD40>21-230_4G7VH]::
CAGGATATTAGCAGGTGGTTAGCCT
CAGAACATTACCACCTATTTAAATTG
GATTCACCTTCAGTGACTACTACATG
huIgG1z-CH1-E::EPKSC +
GGTATCAGCAGAAACCAGGGAAAGC
GTATCAGCAGAAACCAGGGAAAGCC
AGCTGGATCCGCCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CCCTAAGCTCCTGATTTCTGCTGCAT
CCTAACCTCCTGATCTCTGCTGCATC
AGGGGCTGGAGTGGATTTCATACATT
6F4VL]::huKLC-S176E +
CCAGATTGCAAAGTGGAGTCCCATC
CCGTTTGCGAAGTGGGGTCCCATCAA
AGTAGCAGTGAAAGTATCATCTATTA
[anti-<huCD40>
AAGGTTCAGCGGCAGTGGATCTGGG
GGTTCAGTGGCAGTGGATCTGGGAC
CGTAGACTCTGTGAAGGGCCGATTC
21-230_4G7VL]::
ACAGATTTCACTCTCACCATCAGCAG
AGATTTCACTCTCACCATCAGCAGTC
ACCATCTCCAGGGACAACGCCAAGA
huKLC-S176K(IgG-
CCTGCAGCCTGAAGATTTTGCAATTT
TGCAACCTGTAGATTTTACAACTTTC
ACTCACTGTATCTGCAAATGAACAGC
Fab); LMRID:
ACTATTGTCAACAGGCTAAAAGTTTT
TACTGTCAACAGACTTTCACTACCCC
CTGAGAGCCGAGGACACGGCCGTGT
SS-30837
CCTCGGACGTTCGGCCAAGGGACCA
GTGGACGTTCGGCCAAGGGACCAAG
ATTACTGTGCGAGAGATGTTGGGAG
AGGTGGAAATCAAACGGACGGTGGC
GTGGAGATCAAACGAACGGTGGCTG
CCACTTTGACTACTGGGGCCAGGGA
TGCACCATCTGTCTTCATCTTCCCGC
CACCATCTGTCTTCATCTTCCCGCCA
ACCCTGGTCACCGTGTCCTCAGCCTC
CATCTGATGAGCAGTTGAAATCTGG
TCTGATGAGCAGTTGAAATCTGGAA
CACCAAGGGCCCATCGGTCTTCCCCC
AACTGCCTCTGTTGTGTGCCTGCTGA
CTGCCTCTGTTGTGTGCCTGCTGAAT
TGGCACCCTCCTCCAAGAGCACCTCT
ATAACTTCTATCCCAGAGAGGCCAA
AACTTCTATCCCAGAGAGGCCAAAG
GGGGGCACAGCGGCCCTGGGCTGCC
AGTACAGTGGAAGGTGGATAACGCC
TACAGTGGAAGGTGGATAACGCCCT
TGGTCAAGGACTACTTCCCCGAACCG
CTCCAATCGGGTAACTCCCAGGAGA
CCAATCGGGTAACTCCCAGGAGAGT
GTGACGGTGTCGTGGAACTCAGGCG
GTGTCACAGAGCAGGACAGCAAGGA
GTCACAGAGCAGGACAGCAAGGACA
CCCTGACCAGCGGCGTGCACACCTTC
CAGCACCTACAGCCTCGAAAGCACC
GCACCTACAGCCTCAAGAGCACCCT
CCGGCTGTCCTACAGTCCTCAGGACT
CTGACGCTGAGCAAAGCAGACTACG
GACGCTGAGCAAAGCAGACTACGAG
CTACTCCCTCAAGAGCGTGGTGACCG
AGAAACACAAAGTCTACGCCTGCGA
AAACACAAAGTCTACGCCTGCGAAG
TGCCCTCCAGCAGCTTGGGCACCCAG
AGTCACCCATCAGGGCCTGAGCTCG
TCACCCATCAGGGCCTGAGCTCGCCC
ACCTACATCTGCAACGTGAATCACA
CCCGTCACAAAGAGCTTCAACAGGG
GTCACAAAGAGCTTCAACAGGGGAG
AGCCCAGCAACACCAAGGTGGACAA
GAGAGTGT
AGTGT
GAAAGTTGAGCCCAAATCTTGTGAC
(SEQ ID NO: 755)
(SEQ ID NO: 756)
AAAACTCACACATGCCCACCGTGCC
CAGCACCTGAACTCCTGGGGGGACC
GTCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGT
GGACGTGAGCCACGAAGACCCTGAG
GTCAAGTTCAACTGGTACGTGGACG
GCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGC
AGCACGTACCGTTGCGTCAGCGTCCT
CACCGTCCTGCACCAGGACTGGCTG
AATGGCAAGGAGTACAAGTGCAAGG
TGTCCAACAAAGCCCTCCCAGCCCCC
ATCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGGT
GTACACCCTGCCCCCATCCCGGGAG
GAGATGACCAAGAACCAGGTCAGCC
TGACCTGCCTGGTCAAAGGCTTCTAT
CCCAGCGACATCGCCGTGGAGTGGG
AGAGCAATGGGCAGCCGGAGAACAA
CTACAAGACCACGCCTCCCGTGCTGG
ACTCCGACGGCTCCTTCTTCCTCTAT
AGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTGC
ACAACCACTACACGCAGAAGAGCCT
CTCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCCAGGTGCA
GCTGGTGCAGTCTGGGGCTGAGGTG
AAGAAGCCTGGGGCCTCAGTGAAGG
TGTCCTGCAAGGCTTCTGGATACACC
TTCGCCGGCTACTATATGCACTGGGT
GCGACAGGCCCCTGGACAAGGGCTT
GAGTGGATGGGATGGATCAACCCTG
ACAGTGGAGGCACAAACTTTGCACA
GCAGTTTCAGGGCAGGGTCACCATG
ACCAGGGATACGTCCATCAGCACAG
CCTACATGGAGGTGAGCAGGCTGAG
ATCTGACGACACGGCCGTGTTTTACT
GTGCGAGAGAGAAGATCACTATGAC
TGGTATTTACTTTGACTATTGGGGCC
AGGGAACCCTGGTCACCGTGTCCTCA
GCAAGCACGAAGGGGCCGTCCGTAT
TTCCGCTTGCGCCCTCGTCGAAGTCA
ACTTCGGGAGGGACCGCGGCACTTG
GCTGTCTTGTCAAAGATTACTTCCCT
GAGCCAGTGACAGTCAGCTGGAATT
CCGGTGCCCTCACGTCAGGAGTACAT
ACATTCCCTGCGGTATTGCAGTCCTC
CGGACTCTACTCCCTGGAGTCGGTGG
TAACGGTGCCCAGCTCCAGCTTGGG
GACCCAGACGTACATTTGTAACGTG
AATCACAAACCAAGCAATACTAAGG
TAGATAAGAAAGTAGAACCGAAGAG
CTGC
(SEQ ID NO: 757)
AA
DIQMTQSPSSVSASVGDRVTITCRASQ
DIQMTQSPSSLSASVGDILTITCRASQN
QVQLVESGGGLVKPGGSLRLSCAASG
DISRWLAWYQQKPGKAPKLLISAASR
ITTYLNWYQQKPGKAPNLLISAASRLRS
FTFSDYYMSWIRQAPGKGLEWISYISS
LQSGVPSRFSGSGSGTDFTLTISSLQPE
GVPSRFSGSGSGTDFTLTISSLQPVDFT
SESIIYYVDSVKGRFTISRDNAKNSLYL
DFAIYYCQQAKSFPRTFGQGTKVEIKR
TFYCQQTFTTPWTFGQGTKVEIKRTVA
QMNSLRAEDTAVYYCARDVGSHFDY
TVAAPSVFIFPPSDEQLKSGTASVVCLL
APSVFIFPPSDEQLKSGTASVVCLLNNF
WGQGTLVTVSSASTKGPSVFPLAPSSK
NNFYPREAKVQWKVDNALQSGNSQE
YPREAKVQWKVDNALQSGNSQESVTE
STSGGTAALGCLVKDYFPEPVTVSWN
SVTEQDSKDSTYSLESTLTLSKADYEK
QDSKDSTYSLKSTLTLSKADYEKHKV
SGALTSGVHTFPAVLQSSGLYSLKSVV
HKVYACEVTHQGLSSPVTKSFNRGEC
YACEVTHQGLSSPVTKSFNRGEC
TVPSSSLGTQTYICNVNHKPSNTKVDK
(SEQ ID NO: 758)
(SEQ ID NO: 759)
KVEPKSCDKTHTCPPCPAPELLGGPSV
FLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVKFNWYVDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPRE
PQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLVQSGAEVKKPGASVKVSC
KASGYTFAGYYMHWVRQAPGQGLE
WMGWINPDSGGTNFAQQFQGRVTMT
RDTSISTAYMEVSRLRSDDTAVFYCAR
EKITMTGIYFDYWGQGTLVTVSSASTK
GPSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAVLQ
SSGLYSLESVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSC
(SEQ ID NO: 760)
iPS:
21-233_6F4_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATCCAGATGACCCAGTCTCCATC
GACATCCAGATGACCCAGTCTCCATC
CAGGTGCAGCTGGTGGAGTCTGGGG
576201
230_29H10_Fab
6F4VH]::huIgG1zSEFL2*GK-
TTCCGTGTCTGCTTCTGTCGGAGACA
CTCACTGTCTGCATCTGTAGGAGACA
GAGGCTTGGTCAAGCCTGGAGGGTC
K::(G4S)2::[hu anti-
GAGTCACCATCACTTGTCGGGCGAGT
GAGTCACCATCACCTGTCGGGCGAG
CCTGAGACTCTCCTGTGCAGCCTCTG
<huCD40>21-230_29H10VH]::
CAGGATATTAGCAGGTGGTTAGCCT
TCAGGACATTAGCAATAATTTAGCCT
GATTCACCTTCAGTGACTACTACATG
huIgG1z-CH1-E::EPKSC +
GGTATCAGCAGAAACCAGGGAAAGC
GGTTTCAGCAGAAACCAGGGAAACC
AGCTGGATCCGCCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CCCTAAGCTCCTGATTTCTGCTGCAT
CCCTAAGTCCCTGATGTATGCTGCAT
AGGGGCTGGAGTGGATTTCATACATT
6F4VL]::huKLC-S176E +
CCAGATTGCAAAGTGGAGTCCCATC
CCAGTTTGCACAGTGGAGTCCCATCA
AGTAGCAGTGAAAGTATCATCTATTA
[anti-<huCD40>
AAGGTTCAGCGGCAGTGGATCTGGG
ACGTTCAGCGGCAGTGGATCTGGGA
CGTAGACTCTGTGAAGGGCCGATTC
21-230_29H10VL]::
ACAGATTTCACTCTCACCATCAGCAG
CAGATTTCACTTTCACCATCAGCAGC
ACCATCTCCAGGGACAACGCCAAGA
huKLC-S176K(IgG-
CCTGCAGCCTGAAGATTTTGCAATTT
CTGCAGCCTGAAGATTTTGCAACTTA
ACTCACTGTATCTGCAAATGAACAGC
Fab); LMRID:
ACTATTGTCAACAGGCTAAAAGTTTT
TTACTGCCAACAGTATAATAGTTACC
CTGAGAGCCGAGGACACGGCCGTGT
SS-30838
CCTCGGACGTTCGGCCAAGGGACCA
CTCTCACTTTCGGCGGAGGGACCAA
ATTACTGTGCGAGAGATGTTGGGAG
AGGTGGAAATCAAACGGACGGTGGC
GGTGGAGATCAGACGAACGGTGGCT
CCACTTTGACTACTGGGGCCAGGGA
TGCACCATCTGTCTTCATCTTCCCGC
GCACCATCTGTCTTCATCTTCCCGCC
ACCCTGGTCACCGTGTCCTCAGCCTC
CATCTGATGAGCAGTTGAAATCTGG
ATCTGATGAGCAGTTGAAATCTGGA
CACCAAGGGCCCATCGGTCTTCCCCC
AACTGCCTCTGTTGTGTGCCTGCTGA
ACTGCCTCTGTTGTGTGCCTGCTGAA
TGGCACCCTCCTCCAAGAGCACCTCT
ATAACTTCTATCCCAGAGAGGCCAA
TAACTTCTATCCCAGAGAGGCCAAA
GGGGGCACAGCGGCCCTGGGCTGCC
AGTACAGTGGAAGGTGGATAACGCC
GTACAGTGGAAGGTGGATAACGCCC
TGGTCAAGGACTACTTCCCCGAACCG
CTCCAATCGGGTAACTCCCAGGAGA
TCCAATCGGGTAACTCCCAGGAGAG
GTGACGGTGTCGTGGAACTCAGGCG
GTGTCACAGAGCAGGACAGCAAGGA
TGTCACAGAGCAGGACAGCAAGGAC
CCCTGACCAGCGGCGTGCACACCTTC
CAGCACCTACAGCCTCGAAAGCACC
AGCACCTACAGCCTCAAGAGCACCC
CCGGCTGTCCTACAGTCCTCAGGACT
CTGACGCTGAGCAAAGCAGACTACG
TGACGCTGAGCAAAGCAGACTACGA
CTACTCCCTCAAGAGCGTGGTGACCG
AGAAACACAAAGTCTACGCCTGCGA
GAAACACAAAGTCTACGCCTGCGAA
TGCCCTCCAGCAGCTTGGGCACCCAG
AGTCACCCATCAGGGCCTGAGCTCG
GTCACCCATCAGGGCCTGAGCTCGCC
ACCTACATCTGCAACGTGAATCACA
CCCGTCACAAAGAGCTTCAACAGGG
CGTCACAAAGAGCTTCAACAGGGGA
AGCCCAGCAACACCAAGGTGGACAA
GAGAGTGT
GAGTGT
GAAAGTTGAGCCCAAATCTTGTGAC
(SEQ ID NO: 761)
(SEQ ID NO: 762)
AAAACTCACACATGCCCACCGTGCC
CAGCACCTGAACTCCTGGGGGGACC
GTCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGT
GGACGTGAGCCACGAAGACCCTGAG
GTCAAGTTCAACTGGTACGTGGACG
GCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGC
AGCACGTACCGTTGCGTCAGCGTCCT
CACCGTCCTGCACCAGGACTGGCTG
AATGGCAAGGAGTACAAGTGCAAGG
TGTCCAACAAAGCCCTCCCAGCCCCC
ATCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGGT
GTACACCCTGCCCCCATCCCGGGAG
GAGATGACCAAGAACCAGGTCAGCC
TGACCTGCCTGGTCAAAGGCTTCTAT
CCCAGCGACATCGCCGTGGAGTGGG
AGAGCAATGGGCAGCCGGAGAACAA
CTACAAGACCACGCCTCCCGTGCTGG
ACTCCGACGGCTCCTTCTTCCTCTAT
AGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTGC
ACAACCACTACACGCAGAAGAGCCT
CTCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCCAGGTGCA
ACTGGTGCAGTCTGGGGCTGAGGTG
ACGAAGCCTGGGGCCTCAGTGAAGG
TGTCCTGCAAGGCTTCTGGATACACC
TTCGCCGGCTACTATATGCACTGGGT
GCGACAGGCCCCTGGACAAGGGCTT
GAGTGGATGGGATGGATCAACCCTC
ACAGTGGTGGCACAAACTATGCACA
GAAGTTTCAGGACAGGGTCACCATG
ACCAGGGACACGTCCATCAACACAG
CCTACATGGAACTGAGCAGGCTGAG
ATCTGACGACACGGCCGTGTATTACT
GTGCGAGAGAACGTATTTCTATGGTT
CGGGGAGTCGGGCACAACTGGTTCG
CCCCCTGGGGCCAGGGAACCCTGGT
CACCGTGTCCTCAGCAAGCACGAAG
GGGCCGTCCGTATTTCCGCTTGCGCC
CTCGTCGAAGTCAACTTCGGGAGGG
ACCGCGGCACTTGGCTGTCTTGTCAA
AGATTACTTCCCTGAGCCAGTGACAG
TCAGCTGGAATTCCGGTGCCCTCACG
TCAGGAGTACATACATTCCCTGCGGT
ATTGCAGTCCTCCGGACTCTACTCCC
TGGAGTCGGTGGTAACGGTGCCCAG
CTCCAGCTTGGGGACCCAGACGTAC
ATTTGTAACGTGAATCACAAACCAA
GCAATACTAAGGTAGATAAGAAAGT
AGAACCGAAGAGCTGC
(SEQ ID NO: 763)
AA
DIQMTQSPSSVSASVGDRVTITCRASQ
DIQMTQSPSSLSASVGDRVTITCRASQ
QVQLVESGGGLVKPGGSLRLSCAASG
DISRWLAWYQQKPGKAPKLLISAASR
DISNNLAWFQQKPGKPPKSLMYAASS
FTFSDYYMSWIRQAPGKGLEWISYISS
LQSGVPSRFSGSGSGTDFTLTISSLQPE
LHSGVPSTFSGSGSGTDFTFTISSLQPE
SESIIYYVDSVKGRFTISRDNAKNSLYL
DFAIYYCQQAKSFPRTFGQGTKVEIKR
DFATYYCQQYNSYPLTFGGGTKVEIRR
QMNSLRAEDTAVYYCARDVGSHFDY
TVAAPSVFIFPPSDEQLKSGTASVVCLL
TVAAPSVFIFPPSDEQLKSGTASVVCLL
WGQGTLVTVSSASTKGPSVFPLAPSSK
NNFYPREAKVQWKVDNALQSGNSQE
NNFYPREAKVQWKVDNALQSGNSQE
STSGGTAALGCLVKDYFPEPVTVSWN
SVTEQDSKDSTYSLESTLTLSKADYEK
SVTEQDSKDSTYSLKSTLTLSKADYEK
SGALTSGVHTFPAVLQSSGLYSLKSVV
HKVYACEVTHQGLSSPVTKSFNRGEC
HKVYACEVTHQGLSSPVTKSFNRGEC
TVPSSSLGTQTYICNVNHKPSNTKVDK
(SEQ ID NO: 764)
(SEQ ID NO: 765)
KVEPKSCDKTHTCPPCPAPELLGGPSV
FLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVKFNWYVDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPRE
PQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLVQSGAEVTKPGASVKVSC
KASGYTFAGYYMHWVRQAPGQGLE
WMGWINPHSGGTNYAQKFQDRVTMT
RDTSINTAYMELSRLRSDDTAVYYCA
RERISMVRGVGHNWFAPWGQGTLVT
VSSASTKGPSVFPLAPSSKSTSGGTAAL
GCLVKDYFPEPVTVSWNSGALTSGVH
TFPAVLQSSGLYSLESVVTVPSSSLGTQ
TYICNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 766)
iPS:
21-233_6F4_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATCCAGATGACCCAGTCTCCATC
CAGTCTGCCCTGACTCAGCCTGCCTC
CAGGTGCAGCTGGTGGAGTCTGGGG
576204
230_30A12_Fab
6F4VH]::huIgG1zSEFL2*GK-
TTCCGTGTCTGCTTCTGTCGGAGACA
CGTGTCTGGGAGCCCTGGACAGTCG
GAGGCTTGGTCAAGCCTGGAGGGTC
K::(G4S)2::[hu anti-
GAGTCACCATCACTTGTCGGGCGAGT
ATCACCATCTCCTGCACTGGAACCAG
CCTGAGACTCTCCTGTGCAGCCTCTG
<huCD40>21-230_30A12VH]::
CAGGATATTAGCAGGTGGTTAGCCT
CAGTGATGTTGGGAATTATAACCTTG
GATTCACCTTCAGTGACTACTACATG
huIgG1z-CH1-E::EPKSC +
GGTATCAGCAGAAACCAGGGAAAGC
TCTCCTGGTACCAACAGCACCCAGGC
AGCTGGATCCGCCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CCCTAAGCTCCTGATTTCTGCTGCAT
AAAGCCCCCAAACTCATGATTTTTGA
AGGGGCTGGAGTGGATTTCATACATT
6F4VL]::huKLC-S176E +
CCAGATTGCAAAGTGGAGTCCCATC
GGTCAATCAGCGGCCCTCAGGGGTTT
AGTAGCAGTGAAAGTATCATCTATTA
[anti-<huCD40>
AAGGTTCAGCGGCAGTGGATCTGGG
CTAATCGCTTCTCTGGCTCCAAGTCT
CGTAGACTCTGTGAAGGGCCGATTC
21-230_30A12VL]::
ACAGATTTCACTCTCACCATCAGCAG
GGCACCACGGCCTCCCTGACAATCTC
ACCATCTCCAGGGACAACGCCAAGA
huLLC2-K(IgG-
CCTGCAGCCTGAAGATTTTGCAATTT
TGGGCTCCAGGCTGCGGACGAGGCT
ACTCACTGTATCTGCAAATGAACAGC
Fab); LMRID:
ACTATTGTCAACAGGCTAAAAGTTTT
GATTATTTCTGCTGCTCATATACAAC
CTGAGAGCCGAGGACACGGCCGTGT
SS-30839
CCTCGGACGTTCGGCCAAGGGACCA
TAGTAGCACTTATGTGATCTTCGGCG
ATTACTGTGCGAGAGATGTTGGGAG
AGGTGGAAATCAAACGGACGGTGGC
GAGGGACCAAGCTGACCGTCCTAGG
CCACTTTGACTACTGGGGCCAGGGA
TGCACCATCTGTCTTCATCTTCCCGC
TCAGCCCAAGGCTGCACCCTCGGTCA
ACCCTGGTCACCGTGTCCTCAGCCTC
CATCTGATGAGCAGTTGAAATCTGG
CTCTGTTCCCGCCCTCCTCTGAGGAG
CACCAAGGGCCCATCGGTCTTCCCCC
AACTGCCTCTGTTGTGTGCCTGCTGA
CTTCAAGCCAACAAGGCCACACTGG
TGGCACCCTCCTCCAAGAGCACCTCT
ATAACTTCTATCCCAGAGAGGCCAA
TGTGTCTCATCAGTGACTTCTACCCG
GGGGGCACAGCGGCCCTGGGCTGCC
AGTACAGTGGAAGGTGGATAACGCC
GGAGCCGTGACAGTGGCCTGGAAGG
TGGTCAAGGACTACTTCCCCGAACCG
CTCCAATCGGGTAACTCCCAGGAGA
CAGATAGCAGCCCCGTCAAGGCGGG
GTGACGGTGTCGTGGAACTCAGGCG
GTGTCACAGAGCAGGACAGCAAGGA
AGTGGAAACCACCACACCCTCCAAA
CCCTGACCAGCGGCGTGCACACCTTC
CAGCACCTACAGCCTCGAAAGCACC
CAAAGCAACAACAAGTACGCGGCCA
CCGGCTGTCCTACAGTCCTCAGGACT
CTGACGCTGAGCAAAGCAGACTACG
AGAGCTATCTGAGCCTGACGCCTGA
CTACTCCCTCAAGAGCGTGGTGACCG
AGAAACACAAAGTCTACGCCTGCGA
GCACTGGAAGTCCCACAGAAGCTAC
TGCCCTCCAGCAGCTTGGGCACCCAG
AGTCACCCATCAGGGCCTGAGCTCG
AGCTGCCAGGTCACGCATCAAGGGA
ACCTACATCTGCAACGTGAATCACA
CCCGTCACAAAGAGCTTCAACAGGG
GCACCGTGGAGAAGACAGTGGCCCC
AGCCCAGCAACACCAAGGTGGACAA
GAGAGTGT
TACAGAATGTTCA
GAAAGTTGAGCCCAAATCTTGTGAC
(SEQ ID NO: 767)
(SEQ ID NO: 768)
AAAACTCACACATGCCCACCGTGCC
CAGCACCTGAACTCCTGGGGGGACC
GTCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGT
GGACGTGAGCCACGAAGACCCTGAG
GTCAAGTTCAACTGGTACGTGGACG
GCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGC
AGCACGTACCGTTGCGTCAGCGTCCT
CACCGTCCTGCACCAGGACTGGCTG
AATGGCAAGGAGTACAAGTGCAAGG
TGTCCAACAAAGCCCTCCCAGCCCCC
ATCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGGT
GTACACCCTGCCCCCATCCCGGGAG
GAGATGACCAAGAACCAGGTCAGCC
TGACCTGCCTGGTCAAAGGCTTCTAT
CCCAGCGACATCGCCGTGGAGTGGG
AGAGCAATGGGCAGCCGGAGAACAA
CTACAAGACCACGCCTCCCGTGCTGG
ACTCCGACGGCTCCTTCTTCCTCTAT
AGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTGC
ACAACCACTACACGCAGAAGAGCCT
CTCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCGAGGTGCA
GCTGCTGGAGTCTGGGGGAGGCTTG
GTACAGCCTGGGGGGTCCCTGAGAC
TCTCCTGTGCAGCCTCTGGATTCACC
TTTAGTAGAAATGCCATGAGTTGGGT
CCGCCAGGCTCCAGGGAAGGGGCTG
GAGTGGGTGTCAGCTACTGGTGGTA
GTGGTATTAGCACATACTACGCAGA
CTCCGTGAAGGGCCGGTTCACCATCT
CCAGAGACAATTCCAAGAACACGCT
GTATCTGCAAATGAACAGTCTGAGA
GCCGAGGACACGGCCGTATATTACT
GTGCGAGAGGTTATAGCAACAGCTG
GTGGTACTTTGACTACTGGGGCCAGG
GAACCCTGGTCACCGTGTCCTCAGCA
AGCACGAAGGGGCCGTCCGTATTTC
CGCTTGCGCCCTCGTCGAAGTCAACT
TCGGGAGGGACCGCGGCACTTGGCT
GTCTTGTCAAAGATTACTTCCCTGAG
CCAGTGACAGTCAGCTGGAATTCCG
GTGCCCTCACGTCAGGAGTACATAC
ATTCCCTGCGGTATTGCAGTCCTCCG
GACTCTACTCCCTGGAGTCGGTGGTA
ACGGTGCCCAGCTCCAGCTTGGGGA
CCCAGACGTACATTTGTAACGTGAAT
CACAAACCAAGCAATACTAAGGTAG
ATAAGAAAGTAGAACCGAAGAGCTG
C
(SEQ ID NO: 769)
AA
DIQMTQSPSSVSASVGDRVTITCRASQ
QSALTQPASVSGSPGQSITISCTGTSSD
QVQLVESGGGLVKPGGSLRLSCAASG
DISRWLAWYQQKPGKAPKLLISAASR
VGNYNLVSWYQQHPGKAPKLMIFEV
FTFSDYYMSWIRQAPGKGLEWISYISS
LQSGVPSRFSGSGSGTDFTLTISSLQPE
NQRPSGVSNRFSGSKSGTTASLTISGLQ
SESIIYYVDSVKGRFTISRDNAKNSLYL
DFAIYYCQQAKSFPRTFGQGTKVEIKR
AADEADYFCCSYTTSSTYVIFGGGTKL
QMNSLRAEDTAVYYCARDVGSHFDY
TVAAPSVFIFPPSDEQLKSGTASVVCLL
TVLGQPKAAPSVTLFPPSSEELQANKA
WGQGTLVTVSSASTKGPSVFPLAPSSK
NNFYPREAKVQWKVDNALQSGNSQE
TLVCLISDFYPGAVTVAWKADSSPVK
STSGGTAALGCLVKDYFPEPVTVSWN
SVTEQDSKDSTYSLESTLTLSKADYEK
AGVETTTPSKQSNNKYAAKSYLSLTPE
SGALTSGVHTFPAVLQSSGLYSLKSVV
HKVYACEVTHQGLSSPVTKSFNRGEC
QWKSHRSYSCQVTHEGSTVEKTVAPT
TVPSSSLGTQTYICNVNHKPSNTKVDK
(SEQ ID NO: 770)
ECS
KVEPKSCDKTHTCPPCPAPELLGGPSV
(SEQ ID NO: 771)
FLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVKFNWYVDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPRE
PQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGSG
GGGSEVQLLESGGGLVQPGGSLRLSC
AASGFTFSRNAMSWVRQAPGKGLEW
VSATGGSGISTYYADSVKGRFTISRDN
SKNTLYLQMNSLRAEDTAVYYCARG
YSNSWWYFDYWGQGTLVTVSSASTK
GPSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAVLQ
SSGLYSLESVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSC
(SEQ ID NO: 772)
iPS:
21-233_6F4_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATCCAGATGACCCAGTCTCCATC
GACATCCAGATGACCCAGTCTCCATC
CAGGTGCAGCTGGTGGAGTCTGGGG
576207
230_33H6_Fab
6F4VH]::huIgG1zSEFL2*GK-
TTCCGTGTCTGCTTCTGTCGGAGACA
CTCCCTGTCTGCATCTGTAGGAGACA
GAGGCTTGGTCAAGCCTGGAGGGTC
K::(G4S)2::[hu anti-
GAGTCACCATCACTTGTCGGGCGAGT
GAGTCACCATCACTTGCCGGGCAGG
CCTGAGACTCTCCTGTGCAGCCTCTG
<huCD40>21-230_33H6VH]::
CAGGATATTAGCAGGTGGTTAGCCT
TCAGAACATTAGCAGGCATTTAAATT
GATTCACCTTCAGTGACTACTACATG
huIgG1z-CH1-E::EPKSC +
GGTATCAGCAGAAACCAGGGAAAGC
GGTATCAGCAGAATCCAGGGAAAGC
AGCTGGATCCGCCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CCCTAAGCTCCTGATTTCTGCTGCAT
CCCTAAGGTCCTGATCCATCCTGCAT
AGGGGCTGGAGTGGATTTCATACATT
6F4VL]::huKLC-S176E +
CCAGATTGCAAAGTGGAGTCCCATC
CCAGTTTGCCAAGTGGGGTCCCGTCA
AGTAGCAGTGAAAGTATCATCTATTA
[anti-<huCD40>
AAGGTTCAGCGGCAGTGGATCTGGG
AGGTTCAGTGGCAGTGGATCTGGGA
CGTAGACTCTGTGAAGGGCCGATTC
21-230_33H6VL]::
ACAGATTTCACTCTCACCATCAGCAG
CAGATTTCAGTCTTACCATCAGCAGT
ACCATCTCCAGGGACAACGCCAAGA
huKLC-S176K(IgG-
CCTGCAGCCTGAAGATTTTGCAATTT
CTGCAACCTGAAGATTTTGGAACTTA
ACTCACTGTATCTGCAAATGAACAGC
Fab); LMRID:
ACTATTGTCAACAGGCTAAAAGTTTT
CTTCTGTCAACAGAGTTACAGTACCC
CTGAGAGCCGAGGACACGGCCGTGT
SS-30840
CCTCGGACGTTCGGCCAAGGGACCA
CTCCCACTTTCGGCGGAGGGACCAA
ATTACTGTGCGAGAGATGTTGGGAG
AGGTGGAAATCAAACGGACGGTGGC
GGTGGAGCTCAAACGAACGGTGGCT
CCACTTTGACTACTGGGGCCAGGGA
TGCACCATCTGTCTTCATCTTCCCGC
GCACCATCTGTCTTCATCTTCCCGCC
ACCCTGGTCACCGTGTCCTCAGCCTC
CATCTGATGAGCAGTTGAAATCTGG
ATCTGATGAGCAGTTGAAATCTGGA
CACCAAGGGCCCATCGGTCTTCCCCC
AACTGCCTCTGTTGTGTGCCTGCTGA
ACTGCCTCTGTTGTGTGCCTGCTGAA
TGGCACCCTCCTCCAAGAGCACCTCT
ATAACTTCTATCCCAGAGAGGCCAA
TAACTTCTATCCCAGAGAGGCCAAA
GGGGGCACAGCGGCCCTGGGCTGCC
AGTACAGTGGAAGGTGGATAACGCC
GTACAGTGGAAGGTGGATAACGCCC
TGGTCAAGGACTACTTCCCCGAACCG
CTCCAATCGGGTAACTCCCAGGAGA
TCCAATCGGGTAACTCCCAGGAGAG
GTGACGGTGTCGTGGAACTCAGGCG
GTGTCACAGAGCAGGACAGCAAGGA
TGTCACAGAGCAGGACAGCAAGGAC
CCCTGACCAGCGGCGTGCACACCTTC
CAGCACCTACAGCCTCGAAAGCACC
AGCACCTACAGCCTCAAGAGCACCC
CCGGCTGTCCTACAGTCCTCAGGACT
CTGACGCTGAGCAAAGCAGACTACG
TGACGCTGAGCAAAGCAGACTACGA
CTACTCCCTCAAGAGCGTGGTGACCG
AGAAACACAAAGTCTACGCCTGCGA
GAAACACAAAGTCTACGCCTGCGAA
TGCCCTCCAGCAGCTTGGGCACCCAG
AGTCACCCATCAGGGCCTGAGCTCG
GTCACCCATCAGGGCCTGAGCTCGCC
ACCTACATCTGCAACGTGAATCACA
CCCGTCACAAAGAGCTTCAACAGGG
CGTCACAAAGAGCTTCAACAGGGGA
AGCCCAGCAACACCAAGGTGGACAA
GAGAGTGT
GAGTGT
GAAAGTTGAGCCCAAATCTTGTGAC
(SEQ ID NO: 773)
(SEQ ID NO: 774)
AAAACTCACACATGCCCACCGTGCC
CAGCACCTGAACTCCTGGGGGGACC
GTCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGT
GGACGTGAGCCACGAAGACCCTGAG
GTCAAGTTCAACTGGTACGTGGACG
GCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGC
AGCACGTACCGTTGCGTCAGCGTCCT
CACCGTCCTGCACCAGGACTGGCTG
AATGGCAAGGAGTACAAGTGCAAGG
TGTCCAACAAAGCCCTCCCAGCCCCC
ATCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGGT
GTACACCCTGCCCCCATCCCGGGAG
GAGATGACCAAGAACCAGGTCAGCC
TGACCTGCCTGGTCAAAGGCTTCTAT
CCCAGCGACATCGCCGTGGAGTGGG
AGAGCAATGGGCAGCCGGAGAACAA
CTACAAGACCACGCCTCCCGTGCTGG
ACTCCGACGGCTCCTTCTTCCTCTAT
AGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTGC
ACAACCACTACACGCAGAAGAGCCT
CTCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCCAGGTGCA
ACTGGTGCAGTCTGGGGCTGAAGTG
AAGAAGCCTGGGGCCTCAGTGAAGG
TGTCCTGCAAGGCTTCTGGATACACC
TTCCCCGGCTACTATATGTACTGGTT
GCGACAGGCCCCTGGACAAGGACTT
GAGTGGATGGGATGGATCAACCCTG
ACAGTGGTGACACAAACTATGCACA
GAAGTTTCAGGGCAGGGTCACCATG
ACCAGGGACACGTCCATCAGCACAG
CCTTTATGGAGCTGAGCAGGCTGAG
ATCAGACGACACGGCCGTGTATTACT
GTGCGAGAGAGAAGCCCAGATATTT
TGACTCCTTCTACTACTACCTTATGG
ACGTCTGGGGCCAAGGGACCACGGT
CACCGTGTCCTCAGCAAGCACGAAG
GGGCCGTCCGTATTTCCGCTTGCGCC
CTCGTCGAAGTCAACTTCGGGAGGG
ACCGCGGCACTTGGCTGTCTTGTCAA
AGATTACTTCCCTGAGCCAGTGACAG
TCAGCTGGAATTCCGGTGCCCTCACG
TCAGGAGTACATACATTCCCTGCGGT
ATTGCAGTCCTCCGGACTCTACTCCC
TGGAGTCGGTGGTAACGGTGCCCAG
CTCCAGCTTGGGGACCCAGACGTAC
ATTTGTAACGTGAATCACAAACCAA
GCAATACTAAGGTAGATAAGAAAGT
AGAACCGAAGAGCTGC
(SEQ ID NO: 775)
AA
DIQMTQSPSSVSASVGDRVTITCRASQ
DIQMTQSPSSLSASVGDRVTITCRAGQ
QVQL VESGGGLVKPGGSLRLSCAASG
DISRWLAWYQQKPGKAPKLLISAASR
NISRHLNWYQQNPGKAPKVLIHPASSL
FTFSDYYMSWIRQAPGKGLEWISYISS
LQSGVPSRFSGSGSGTDFTLTISSLQPE
PSGVPSRFSGSGSGTDFSLTISSLQPED
SESIIYYVDSVKGRFTISRDNAKNSLYL
DFAIYYCQQAKSFPRTFGQGTKVEIKR
FGTYFCQQSYSTPPTFGGGTKVELKRTV
QMNSLRAEDTAVYYCARDVGSHFDY
TVAAPSVFIFPPSDEQLKSGTASVVCLL
AAPSVFIFPPSDEQLKSGTASVVCLLNN
WGQGTLVTVSSASTKGPSVFPLAPSSK
NNFYPREAKVQWKVDNALQSGNSQE
FYPREAKVQWKVDNALQSGNSQESVT
STSGGTAALGCLVKDYFPEPVTVSWN
SVTEQDSKDSTYSLESTLTLSKADYEK
EQDSKDSTYSLKSTLTLSKADYEKHK
SGALTSGVHTFPAVLQSSGLYSLKSVV
HKVYACEVTHQGLSSPVTKSFNRGEC
VYACEVTHQGLSSPVTKSFNRGEC
TVPSSSLGTQTYICNVNHKPSNTKVDK
(SEQ ID NO: 776)
(SEQ ID NO: 777)
KVEPKSCDKTHTCPPCPAPELLGGPSV
FLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVKFNWYVDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPRE
PQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLVQSGAEVKKPGASVKVSC
KASGYTFPGYYMYWLRQAPGQGLEW
MGWINPDSGDTNYAQKFQGRVTMTR
DTSISTAFMELSRLRSDDTAVYYCARE
KPRYFDSFYYYLMDVWGQGTTVTVSS
ASTKGPSVFPLAPSSKSTSGGTAALGC
LVKDYFPEPVTVSWNSGALTSGVHTFP
AVLQSSGLYSLESVVTVPSSSLGTQTYI
CNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 778)
iPS:
21-233_6F4_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATCCAGATGACCCAGTCTCCATC
CAGCCTGTGCCGACTCAGCCCTCTTC
CAGGTGCAGCTGGTGGAGTCTGGGG
576210
230_33H9_Fab
6F4VH]::huIgG1zSEFL2*GK-
TTCCGTGTCTGCTTCTGTCGGAGACA
CCTCTCTGCATCTCCTGGAGCATCAG
GAGGCTTGGTCAAGCCTGGAGGGTC
K::(G4S)2::[hu anti-
GAGTCACCATCACTTGTCGGGCGAGT
CCAGTCTCACCTGCACCTTACGCAGT
CCTGAGACTCTCCTGTGCAGCCTCTG
<huCD40>21-230_33H9VH]::
CAGGATATTAGCAGGTGGTTAGCCT
GGCATCAATGTTGGTTCCTCCAGGAT
GATTCACCTTCAGTGACTACTACATG
huIgG1z-CH1-E::EPKSC +
GGTATCAGCAGAAACCAGGGAAAGC
CTATTGGTACCAGCAGAACCCAGGG
AGCTGGATCCGCCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CCCTAAGCTCCTGATTTCTGCTGCAT
AGTCCTCCCCAGTTTCTCCTGAGGTA
AGGGGCTGGAGTGGATTTCATACATT
6F4VL]::huKLC-S176E +
CCAGATTGCAAAGTGGAGTCCCATC
CACATCAGACTCAGATAAATTGCAG
AGTAGCAGTGAAAGTATCATCTATTA
[anti-<huCD40>
AAGGTTCAGCGGCAGTGGATCTGGG
GGCTCTGGAGTCCCCAGCCGCTTCTC
CGTAGACTCTGTGAAGGGCCGATTC
21-230_33H9VL]::
ACAGATTTCACTCTCACCATCAGCAG
TGGATCCAAAGATGCTTCGGCCAAT
ACCATCTCCAGGGACAACGCCAAGA
huLLC2-K(IgG-
CCTGCAGCCTGAAGATTTTGCAATTT
GCACGACTTTTACTCATCTCTGGGCT
ACTCACTGTATCTGCAAATGAACAGC
Fab); LMRID:
ACTATTGTCAACAGGCTAAAAGTTTT
CCAGTCTGAGGATGAGGCTGACTATT
CTGAGAGCCGAGGACACGGCCGTGT
SS-30841
CCTCGGACGTTCGGCCAAGGGACCA
ACTGTATGATTTGGCACAGCAGCGCT
ATTACTGTGCGAGAGATGTTGGGAG
AGGTGGAAATCAAACGGACGGTGGC
GTGGTATTCGGCGGAGGGACCAAAC
CCACTTTGACTACTGGGGCCAGGGA
TGCACCATCTGTCTTCATCTTCCCGC
TGACCGTCCTAGGTCAGCCCAAGGCT
ACCCTGGTCACCGTGTCCTCAGCCTC
CATCTGATGAGCAGTTGAAATCTGG
GCACCCTCGGTCACTCTGTTCCCGCC
CACCAAGGGCCCATCGGTCTTCCCCC
AACTGCCTCTGTTGTGTGCCTGCTGA
CTCCTCTGAGGAGCTTCAAGCCAACA
TGGCACCCTCCTCCAAGAGCACCTCT
ATAACTTCTATCCCAGAGAGGCCAA
AGGCCACACTGGTGTGTCTCATCAGT
GGGGGCACAGCGGCCCTGGGCTGCC
AGTACAGTGGAAGGTGGATAACGCC
GACTICTACCCGGGAGCCGTGACAG
TGGTCAAGGACTACTTCCCCGAACCG
CTCCAATCGGGTAACTCCCAGGAGA
TGGCCTGGAAGGCAGATAGCAGCCC
GTGACGGTGTCGTGGAACTCAGGCG
GTGTCACAGAGCAGGACAGCAAGGA
CGTCAAGGCGGGAGTGGAAACCACC
CCCTGACCAGCGGCGTGCACACCTTC
CAGCACCTACAGCCTCGAAAGCACC
ACACCCTCCAAACAAAGCAACAACA
CCGGCTGTCCTACAGTCCTCAGGACT
CTGACGCTGAGCAAAGCAGACTACG
AGTACGCGGCCAAGAGCTATCTGAG
CTACTCCCTCAAGAGCGTGGTGACCG
AGAAACACAAAGTCTACGCCTGCGA
CCTGACGCCTGAGCAGTGGAAGTCC
TGCCCTCCAGCAGCTTGGGCACCCAG
AGTCACCCATCAGGGCCTGAGCTCG
CACAGAAGCTACAGCTGCCAGGTCA
ACCTACATCTGCAACGTGAATCACA
CCCGTCACAAAGAGCTTCAACAGGG
CGCATGAAGGGAGCACCGTGGAGAA
AGCCCAGCAACACCAAGGTGGACAA
GAGAGTGT
GACAGTGGCCCCTACAGAATGTTCA
GAAAGTTGAGCCCAAATCTTGTGAC
(SEQ ID NO: 779)
(SEQ ID NO: 780)
AAAACTCACACATGCCCACCGTGCC
CAGCACCTGAACTCCTGGGGGGACC
GTCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGT
GGACGTGAGCCACGAAGACCCTGAG
GTCAAGTTCAACTGGTACGTGGACG
GCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGC
AGCACGTACCGTTGCGTCAGCGTCCT
CACCGTCCTGCACCAGGACTGGCTG
AATGGCAAGGAGTACAAGTGCAAGG
TGTCCAACAAAGCCCTCCCAGCCCCC
ATCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGGT
GTACACCCTGCCCCCATCCCGGGAG
GAGATGACCAAGAACCAGGTCAGCC
TGACCTGCCTGGTCAAAGGCTTCTAT
CCCAGCGACATCGCCGTGGAGTGGG
AGAGCAATGGGCAGCCGGAGAACAA
CTACAAGACCACGCCTCCCGTGCTGG
ACTCCGACGGCTCCTTCTTCCTCTAT
AGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTGC
ACAACCACTACACGCAGAAGAGCCT
CTCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCCAGGTGCA
GTTGGTGGAGTCTGGGGGAGGCGTG
GTCCAGCCTGGGAGGTCCCTGAGAC
TCTCCTGTGCAGCGTCTGGATTCACC
TTCAGTAGCCATGGCATGCACTGGGT
CCGCCAACCTCCAGGCAAGGGGCTG
GAGTGGGTGGCAGTTATCTGGTATG
ATGGAAGTAATGAATACTATGGAGA
CTCCGTGAAGGGCCGATTCACCATCT
CCAGAGACAATTCCAAGAACACGCT
GTATCTGCAAATGAACAGCCTGAGA
GTCGAGGACACGGCTGTGTATTACTG
TACGAGAGGGGGGGGCCACTGGAAC
TACGAGGGCCACTACTATGGTATGG
ACGTCTGGGGCCAAGGGACCACGGT
CACCGTGTCCTCAGCAAGCACGAAG
GGGCCGTCCGTATTTCCGCTTGCGCC
CTCGTCGAAGTCAACTTCGGGAGGG
ACCGCGGCACTTGGCTGTCTTGTCAA
AGATTACTTCCCTGAGCCAGTGACAG
TCAGCTGGAATTCCGGTGCCCTCACG
TCAGGAGTACATACATTCCCTGCGGT
ATTGCAGTCCTCCGGACTCTACTCCC
TGGAGTCGGTGGTAACGGTGCCCAG
CTCCAGCTTGGGGACCCAGACGTAC
ATTTGTAACGTGAATCACAAACCAA
GCAATACTAAGGTAGATAAGAAAGT
AGAACCGAAGAGCTGC
(SEQ ID NO: 781)
AA
DIQMTQSPSSVSASVGDRVTITCRASQ
QAVPTQPSSLSASPGASASLTCTLRSGI
QVQL VESGGGLVKPGGSLRLSCAASG
DISRWLAWYQQKPGKAPKLLISAASR
NVGSSRIYWYQQKPGSPPQFLLRYTSD
FTFSDYYMSWIRQAPGKGLEWISYISS
LQSGVPSRFSGSGSGTDFTLTISSLQPE
SDKLQGSGVPSRFSGSKDASANAGLLL
SESIIYYVDSVKGRFTISRDNAKNSLYL
DFAIYYCQQAKSFPRTFGQGTKVEIKR
ISGLQSEDEADYYCMIWHSSAVVFGG
QMNSLRAEDTAVYYCARDVGSHFDY
TVAAPSVFIFPPSDEQLKSGTASVVCLL
GTKLTVLGQPKAAPSVTLFPPSSEELQ
WGQGTLVTVSSASTKGPSVFPLAPSSK
NNFYPREAKVQWKVDNALQSGNSQE
ANKATLVCLISDFYPGAVTVAWKADS
STSGGTAALGCLVKDYFPEPVTVSWN
SVTEQDSKDSTYSLESTLTLSKADYEK
SPVKAGVETTTPSKQSNNKYAAKSYL
SGALTSGVHTFPAVLQSSGLYSLKSVV
HKVYACEVTHQGLSSPVTKSFNRGEC
SLTPEQWKSHRSYSCQVTHEGSTVEKT
TVPSSSLGTQTYICNVNHKPSNTKVDK
(SEQ ID NO: 782)
VAPTECS
KVEPKSCDKTHTCPPCPAPELLGGPSV
(SEQ ID NO: 783)
FLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVKFNWYVDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPRE
PQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLVESGGGVVQPGRSLRLSC
AASGFTFSSHGMHWVRQPPGKGLEW
VAVIWYDGSNEYYGDSVKGRFTISRD
NSKNTLYLQMNSLRVEDTAVYYCTRG
GGHWNYEGHYYGMDVWGQGTTVTV
SSASTKGPSVFPLAPSSKSTSGGTAALG
CLVKDYFPEPVTVSWNSGALTSGVHT
FPAVLQSSGLYSLESVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 784)
iPS:
21-233_6F4_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATCCAGATGACCCAGTCTCCATC
CAGTCTGCCCTGACTCAGCCTCGCTC
CAGGTGCAGCTGGTGGAGTCTGGGG
576213
230_35F11_Fab
6F4VH]::huIgG1zSEFL2*GK-
TTCCGTGTCTGCTTCTGTCGGAGACA
AGTGTCCGGGAGCCCTGGACAGTCA
GAGGCTTGGTCAAGCCTGGAGGGTC
K::(G4S)2::[hu anti-
GAGTCACCATCACTTGTCGGGCGAGT
GTCACCATCTCCTGCACTGGAACCAG
CCTGAGACTCTCCTGTGCAGCCTCTG
<huCD40>21-230_35F11VH]::
CAGGATATTAGCAGGTGGTTAGCCT
CAGTGATGTTGGTGGTTATATCTTTG
GATTCACCTTCAGTGACTACTACATG
huIgG1z-CH1-E::EPKSC +
GGTATCAGCAGAAACCAGGGAAAGC
TCTCCTGGTACCAACAACACCCAGGC
AGCTGGATCCGCCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CCCTAAGCTCCTGATTTCTGCTGCAT
AAAGCCCCCAAACTCATGATTTATGA
AGGGGCTGGAGTGGATTTCATACATT
6F4VL]::huKLC-S176E +
CCAGATTGCAAAGTGGAGTCCCATC
TGTCAGTAAGCGGCCCTCTGGGGTCC
AGTAGCAGTGAAAGTATCATCTATTA
[anti-<huCD40>
AAGGTTCAGCGGCAGTGGATCTGGG
CTGATCGCTTCTCTGGCTCCAAGTCT
CGTAGACTCTGTGAAGGGCCGATTC
21-230_35F11VL]::
ACAGATTTCACTCTCACCATCAGCAG
GTCAACACGGCCTCCCTGACCATCTC
ACCATCTCCAGGGACAACGCCAAGA
huLLC2-K(IgG-
CCTGCAGCCTGAAGATTTTGCAATTT
TGGGCTCCAGGCTGAGGATGAGACT
ACTCACTGTATCTGCAAATGAACAGC
Fab); LMRID:
ACTATTGTCAACAGGCTAAAAGTTTT
GATTATTACTGCTGCTCATATGCAGG
CTGAGAGCCGAGGACACGGCCGTGT
SS-30842
CCTCGGACGTTCGGCCAAGGGACCA
CAACTACACTTATGTCTTCGGAACTG
ATTACTGTGCGAGAGATGTTGGGAG
AGGTGGAAATCAAACGGACGGTGGC
GGACCAAGGTCACCGTCCTAGGTCA
CCACTTTGACTACTGGGGCCAGGGA
TGCACCATCTGTCTTCATCTTCCCGC
GCCCAAGGCTGCACCCTCGGTCACTC
ACCCTGGTCACCGTGTCCTCAGCCTC
CATCTGATGAGCAGTTGAAATCTGG
TGTTCCCGCCCTCCTCTGAGGAGCTT
CACCAAGGGCCCATCGGTCTTCCCCC
AACTGCCTCTGTTGTGTGCCTGCTGA
CAACCCAACAAGGCCACACTGGTGT
TGGCACCCTCCTCCAAGAGCACCTCT
ATAACTTCTATCCCAGAGAGGCCAA
GTCTCATCAGTGACTTCTACCCGGGA
GGGGGCACAGCGGCCCTGGGCTGCC
AGTACAGTGGAAGGTGGATAACGCC
GCCGTGACAGTGGCCTGGAAGGCAG
TGGTCAAGGACTACTTCCCCGAACCG
CTCCAATCGGGTAACTCCCAGGAGA
ATAGCAGCCCCGTCAAGGCGGGAGT
GTGACGGTGTCGTGGAACTCAGGCG
GTGTCACAGAGCAGGACAGCAAGGA
GGAAACCACCACACCCTCCAAACAA
CCCTGACCAGCGGCGTGCACACCTTC
CAGCACCTACAGCCTCGAAAGCACC
AGCAACAACAAGTACGCGGCCAAGA
CCGGCTGTCCTACAGTCCTCAGGACT
CTGACGCTGAGCAAAGCAGACTACG
GCTATCTGAGCCTGACGCCTGAGCA
CTACTCCCTCAAGAGCGTGGTGACCG
AGAAACACAAAGTCTACGCCTGCGA
GTGGAAGTCCCACAGAAGCTACAGC
TGCCCTCCAGCAGCTTGGGCACCCAG
AGTCACCCATCAGGGCCTGAGCTCG
TGCCAGGTCACGCATGAAGGGAGCA
ACCTACATCTGCAACGTGAATCACA
CCCGTCACAAAGAGCTTCAACAGGG
CCGTGGAGAAGACAGTGGCCCCTAC
AGCCCAGCAACACCAAGGTGGACAA
GAGAGTGT
AGAATGTTCA
GAAAGTTGAGCCCAAATCTTGTGAC
(SEQ ID NO: 785)
(SEQ ID NO: 786)
AAAACTCACACATGCCCACCGTGCC
CAGCACCTGAACTCCTGGGGGGACC
GTCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGT
GGACGTGAGCCACGAAGACCCTGAG
GTCAAGTTCAACTGGTACGTGGACG
GCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGC
AGCACGTACCGTTGCGTCAGCGTCCT
CACCGTCCTGCACCAGGACTGGCTG
AATGGCAAGGAGTACAAGTGCAAGG
TGTCCAACAAAGCCCTCCCAGCCCCC
ATCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGGT
GTACACCCTGCCCCCATCCCGGGAG
GAGATGACCAAGAACCAGGTCAGCC
TGACCTGCCTGGTCAAAGGCTTCTAT
CCCAGCGACATCGCCGTGGAGTGGG
AGAGCAATGGGCAGCCGGAGAACAA
CTACAAGACCACGCCTCCCGTGCTGG
ACTCCGACGGCTCCTTCTTCCTCTAT
AGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTGC
ACAACCACTACACGCAGAAGAGCCT
CTCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCCAGGTGCA
GCTGGTGGAGTCTGGGGGAGGCGTG
GTCCAGCCTGGGAGGTCCCTGAGAC
TCTCCTGTGCAGCGTCTGGATTCACC
CTCAGTAGCTATGGCATGCACTGGGT
CCGCCAGGCTCCAGGCAAGGGGCTG
GAGTGGGTGGCAGTTATCTGGTATG
ATGGAAGTAATAAATACTATGCAGA
CTCCGTGAAGGGCCGAGTCACCATCT
CCAGAGACAATTCCAAGAACACGCT
GTATCTGCAAATGAATAGCCTGAGA
GCCGAGGACACGGCTGTGTATTACT
GTACGAGAGATGGCCGGAACTACGT
CTACTTTGACAACTGGGGCCAGGGA
ACCCTGGTCACCGTGTCCTCAGCAAG
CACGAAGGGGCCGTCCGTATTTCCGC
TTGCGCCCTCGTCGAAGTCAACTTCG
GGAGGGACCGCGGCACTTGGCTGTC
TTGTCAAAGATTACTTCCCTGAGCCA
GTGACAGTCAGCTGGAATTCCGGTG
CCCTCACGTCAGGAGTACATACATTC
CCTGCGGTATTGCAGTCCTCCGGACT
CTACTCCCTGGAGTCGGTGGTAACGG
TGCCCAGCTCCAGCTTGGGGACCCA
GACGTACATTTGTAACGTGAATCACA
AACCAAGCAATACTAAGGTAGATAA
GAAAGTAGAACCGAAGAGCTGC
(SEQ ID NO: 787)
AA
DIQMTQSPSSVSASVGDRVTITCRASQ
QSALTQPRSVSGSPGQSVTISCTGTSSD
QVQLVESGGGLVKPGGSLRLSCAASG
DISRWLAWYQQKPGKAPKLLISAASR
VGGYIFVSWYQQHPGKAPKLMIYDVS
FTFSDYYMSWIRQAPGKGLEWISYISS
LQSGVPSRFSGSGSGTDFTLTISSLQPE
KRPSGVPDRFSGSKSVNTASLTISGLQ
SESIIYYVDSVKGRFTISRDNAKNSLYL
DFAIYYCQQAKSFPRTFGQGTKVEIKR
AEDETDYYCCSYAGNYTYVFGTGTKV
QMNSLRAEDTAVYYCARDVGSHFDY
TVAAPSVFIFPPSDEQLKSGTASVVCLL
TVLGQPKAAPSVTLFPPSSEELQANKA
WGQGTLVTVSSASTKGPSVFPLAPSSK
NNFYPREAKVQWKVDNALQSGNSQE
TLVCLISDFYPGAVTVAWKADSSPVK
STSGGTAALGCLVKDYFPEPVTVSWN
SVTEQDSKDSTYSLESTLTLSKADYEK
AGVETTTPSKQSNNKYAAKSYLSLTPE
SGALTSGVHTFPAVLQSSGLYSLKSVV
HKVYACEVTHQGLSSPVTKSFNRGEC
QWKSHRSYSCQVTHEGSTVEKTVAPT
TVPSSSLGTQTYICNVNHKPSNTKVDK
(SEQ ID NO: 788)
ECS
KVEPKSCDKTHTCPPCPAPELLGGPSV
(SEQ ID NO: 789)
FLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVKFNWYVDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPRE
PQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLVESGGGVVQPGRSLRLSC
AASGFTLSSYGMHWVRQAPGKGLEW
VAVIWYDGSNKYYADSVKGRVTISRD
NSKNTLYLQMNSLRAEDTAVYYCTRD
GRNYVYFDNWGQGTLVTVSSASTKGP
SVFPLAPSSKSTSGGTAALGCLVKDYF
PEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLESVVTVPSSSLGTQTYICNVNH
KPSNTKVDKKVEPKSC
(SEQ ID NO: 790)
iPS:
21-233_6F4_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATCCAGATGACCCAGTCTCCATC
GAAATTGTGTTGACGCAGTCTCCAGG
CAGGTGCAGCTGGTGGAGTCTGGGG
576216
230_36F3_Fab
6F4VH]::huIgG1zSEFL2*GK-
TTCCGTGTCTGCTTCTGTCGGAGACA
CACCCTGTCTTTGTCTCCAGGGGAAA
GAGGCTTGGTCAAGCCTGGAGGGTC
K::(G4S)2::[hu anti-
GAGTCACCATCACTTGTCGGGCGAGT
GAGCCACCCTCTCCTGCAGGGCCAGT
CCTGAGACTCTCCTGTGCAGCCTCTG
<huCD40>21-230_36F3VH]::
CAGGATATTAGCAGGTGGTTAGCCT
CAGAGTGTTAGCAGCAACTACTTAG
GATTCACCTTCAGTGACTACTACATG
huIgG1z-CH1-E::EPKSC +
GGTATCAGCAGAAACCAGGGAAAGC
CCTGGTACCAACAGAAACCTGGCCA
AGCTGGATCCGCCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CCCTAAGCTCCTGATTTCTGCTGCAT
GGCTCCCAGGGCCCTTATCTATGCTG
AGGGGCTGGAGTGGATTTCATACATT
6F4VL]::huKLC-S176E +
CCAGATTGCAAAGTGGAGTCCCATC
CATCCAACAGGGCCGCTGGCATCTC
AGTAGCAGTGAAAGTATCATCTATTA
[anti-<huCD40>
AAGGTTCAGCGGCAGTGGATCTGGG
AGACAGGTTCAGTGGCAGTGGGTCT
CGTAGACTCTGTGAAGGGCCGATTC
21-230_36F3VL]::
ACAGATTTCACTCTCACCATCAGCAG
GGGACAGACTTCACTCTCACCATCAG
ACCATCTCCAGGGACAACGCCAAGA
huKLC-S176K(IgG-
CCTGCAGCCTGAAGATTTTGCAATTT
CAGACTGGAGCCTGAAGATTTTGCA
ACTCACTGTATCTGCAAATGAACAGC
Fab); LMRID:
ACTATTGTCAACAGGCTAAAAGTTTT
GTGTATTTCTGTCAGCAGTATGGTAG
CTGAGAGCCGAGGACACGGCCGTGT
SS-30843
CCTCGGACGTTCGGCCAAGGGACCA
CTCACCGCTCACTTTCGGCGGAGGGA
ATTACTGTGCGAGAGATGTTGGGAG
AGGTGGAAATCAAACGGACGGTGGC
CTAAGGTGGAGATCAAACGAACGGT
CCACTTTGACTACTGGGGCCAGGGA
TGCACCATCTGTCTTCATCTTCCCGC
GGCTGCACCATCTGTCTTCATCTTCC
ACCCTGGTCACCGTGTCCTCAGCCTC
CATCTGATGAGCAGTTGAAATCTGG
CGCCATCTGATGAGCAGTTGAAATCT
CACCAAGGGCCCATCGGTCTTCCCCC
AACTGCCTCTGTTGTGTGCCTGCTGA
GGAACTGCCTCTGTTGTGTGCCTGCT
TGGCACCCTCCTCCAAGAGCACCTCT
ATAACTTCTATCCCAGAGAGGCCAA
GAATAACTTCTATCCCAGAGAGGCC
GGGGGCACAGCGGCCCTGGGCTGCC
AGTACAGTGGAAGGTGGATAACGCC
AAAGTACAGTGGAAGGTGGATAACG
TGGTCAAGGACTACTTCCCCGAACCG
CTCCAATCGGGTAACTCCCAGGAGA
CCCTCCAATCGGGTAACTCCCAGGA
GTGACGGTGTCGTGGAACTCAGGCG
GTGTCACAGAGCAGGACAGCAAGGA
GAGTGTCACAGAGCAGGACAGCAAG
CCCTGACCAGCGGCGTGCACACCTTC
CAGCACCTACAGCCTCGAAAGCACC
GACAGCACCTACAGCCTCAAGAGCA
CCGGCTGTCCTACAGTCCTCAGGACT
CTGACGCTGAGCAAAGCAGACTACG
CCCTGACGCTGAGCAAAGCAGACTA
CTACTCCCTCAAGAGCGTGGTGACCG
AGAAACACAAAGTCTACGCCTGCGA
CGACAAACACAAAGTCTACGCCTGC
TGCCCTCCAGCAGCTTGGGCACCCAG
AGTCACCCATCAGGGCCTGAGCTCG
GAAGTCACCCATCAGGGCCTGAGCT
ACCTACATCTGCAACGTGAATCACA
CCCGTCACAAAGAGCTTCAACAGGG
CGCCCGTCACAAAGAGCTTCAACAG
AGCCCAGCAACACCAAGGTGGACAA
GAGAGTGT
GGGAGAGTGT
GAAAGTTGAGCCCAAATCTTGTGAC
(SEQ ID NO: 791)
(SEQ ID NO: 792)
AAAACTCACACATGCCCACCGTGCC
CAGCACCTGAACTCCTGGGGGGACC
GTCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGT
GGACGTGAGCCACGAAGACCCTGAG
GTCAAGTTCAACTGGTACGTGGACG
GCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGC
AGCACGTACCGTTGCGTCAGCGTCCT
CACCGTCCTGCACCAGGACTGGCTG
AATGGCAAGGAGTACAAGTGCAAGG
TGTCCAACAAAGCCCTCCCAGCCCCC
ATCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGGT
GTACACCCTGCCCCCATCCCGGGAG
GAGATGACCAAGAACCAGGTCAGCC
TGACCTGCCTGGTCAAAGGCTTCTAT
CCCAGCGACATCGCCGTGGAGTGGG
AGAGCAATGGGCAGCCGGAGAACAA
CTACAAGACCACGCCTCCCGTGCTGG
ACTCCGACGGCTCCTTCTTCCTCTAT
AGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTGC
ACAACCACTACACGCAGAAGAGCCT
CTCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCCAGGTACA
GCTGCAACAGTCAGGTCCAGGACTG
GTGAAGCCCTCGCAGACCCTCTCACT
CACCTGTGCCATCTCCGGGGACAGTG
TCTCTAGCAGCCGTACTGCTTGGAAC
TGGATCAGGCAGTCCCCATCGAGAG
GCCTTGAGTGGCTGGGAAGGACATA
CTACAGGTCCAAGTGGTATCATGATT
ATTCAGTATCTGTGAAAAGTCGAATC
ACCATCGACCCAGACACATCCAAGA
ACCAGTTCTCCCTGCAGCTGAACTCT
GTGACTCCCGAGGACACGGCTGTTTA
TTATTGTGCAAGAGGGGCTGCTCCCT
TTGACTACTGGGGCCAGGGAACCCT
GGTCACCGTGTCCTCAGCAAGCACG
AAGGGGCCGTCCGTATTTCCGCTTGC
GCCCTCGTCGAAGTCAACTTCGGGA
GGGACCGCGGCACTTGGCTGTCTTGT
CAAAGATTACTTCCCTGAGCCAGTGA
CAGTCAGCTGGAATTCCGGTGCCCTC
ACGTCAGGAGTACATACATTCCCTGC
GGTATTGCAGTCCTCCGGACTCTACT
CCCTGGAGTCGGTGGTAACGGTGCC
CAGCTCCAGCTTGGGGACCCAGACG
TACATTTGTAACGTGAATCACAAACC
AAGCAATACTAAGGTAGATAAGAAA
GTAGAACCGAAGAGCTGC
(SEQ ID NO: 793)
AA
DIQMTQSPSSVSASVGDRVTITCRASQ
EIVLTQSPGTLSLSPGERATLSCRASQS
QVQLVESGGGLVKPGGSLRLSCAASG
DISRWLAWYQQKPGKAPKLLISAASR
VSSNYLAWYQQKPGQAPRALIYAASN
FTFSDYYMSWIRQAPGKGLEWISYISS
LQSGVPSRFSGSGSGTDFTLTISSLQPE
RAAGISDRFSGSGSGTDFTLTISRLEPE
SESIIYYVDSVKGRFTISRDNAKNSLYL
DFAIYYCQQAKSFPRTFGQGTKVEIKR
DFAVYFCQQYGSSPLTFGGGTKVEIKR
QMNSLRAEDTAVYYCARDVGSHFDY
TVAAPSVFIFPPSDEQLKSGTASVVCLL
TVAAPSVFIFPPSDEQLKSGTASVVCLL
WGQGTLVTVSSASTKGPSVFPLAPSSK
NNFYPREAKVQWKVDNALQSGNSQE
NNFYPREAKVQWKVDNALQSGNSQE
STSGGTAALGCLVKDYFPEPVTVSWN
SVTEQDSKDSTYSLESTLTLSKADYEK
SVTEQDSKDSTYSLKSTLTLSKADYEK
SGALTSGVHTFPAVLQSSGLYSLKSVV
HKVYACEVTHQGLSSPVTKSFNRGEC
HKVYACEVTHQGLSSPVTKSFNRGEC
TVPSSSLGTQTYICNVNHKPSNTKVDK
(SEQ ID NO: 794)
(SEQ ID NO: 795)
KVEPKSCDKTHTCPPCPAPELLGGPSV
FLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVKFNWYVDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPRE
PQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLQQSGPGLVKPSQTLSLTC
AISGDSVSSSRTAWNWIRQSPSRGLEW
LGRTYYRSKWYHDYSVSVKSRITIDPD
TSKNQFSLQLNSVTPEDTAVYYCARG
AAPFDYWGQGTLVTVSSASTKGPSVF
PLAPSSKSTSGGTAALGCLVKDYFPEP
VTVSWNSGALTSGVHTFPAVLQSSGL
YSLESVVTVPSSSLGTQTYICNVNHKP
SNTKVDKKVEPKSC
(SEQ ID NO: 796)
iPS:
21-233_6F4_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATCCAGATGACCCAGTCTCCATC
TCCTATGAGCTGACTCAGCCACCCTC
CAGGTGCAGCTGGTGGAGTCTGGGG
576219
230_37A6_Fab
6F4VH]::huIgG1zSEFL2*GK-
TTCCGTGTCTGCTTCTGTCGGAGACA
AGTGTCCGTGTCCCCAGGACAGACA
GAGGCTTGGTCAAGCCTGGAGGGTC
K::(G4S)2::[hu anti-
GAGTCACCATCACTTGTCGGGCGAGT
GCCAGCATCACCTGCTCTGGAGAAA
CCTGAGACTCTCCTGTGCAGCCTCTG
<huCD40>21-230_37A6VH]::
CAGGATATTAGCAGGTGGTTAGCCT
GGTTGGGAAATAAATATATTTGCTGG
GATTCACCTTCAGTGACTACTACATG
huIgG1z-CH1-E::EPKSC +
GGTATCAGCAGAAACCAGGGAAAGC
TATCAGCAGAAGCCAGGCCAGTCCC
AGCTGGATCCGCCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CCCTAAGCTCCTGATTTCTGCTGCAT
CTGTTCTGGTCATCTATCAAGATTTC
AGGGGCTGGAGTGGATTTCATACATT
6F4VL]::huKLC-S176E +
CCAGATTGCAAAGTGGAGTCCCATC
AAGCGGCCCTCAGGGATCCCTGAGC
AGTAGCAGTGAAAGTATCATCTATTA
[anti-<huCD40>
AAGGTTCAGCGGCAGTGGATCTGGG
GATTCTCTGGCTCCAACTCTGGGATC
CGTAGACTCTGTGAAGGGCCGATTC
21-230_37A6VL]::
ACAGATTTCACTCTCACCATCAGCAG
ACAGCCACTCTGACCATCAGCGGGA
ACCATCTCCAGGGACAACGCCAAGA
huLLC2-K(IgG-
CCTGCAGCCTGAAGATTTTGCAATTT
CCCAGGCTATGGATGAGGCTGACTA
ACTCACTGTATCTGCAAATGAACAGC
Fab); LMRID:
ACTATTGTCAACAGGCTAAAAGTTTT
TTACTGTCAGGCGTGGGACAGCAGA
CTGAGAGCCGAGGACACGGCCGTGT
SS-30844
CCTCGGACGTTCGGCCAAGGGACCA
ACTGTGGTATTCGGCGGAGGGACCA
ATTACTGTGCGAGAGATGTTGGGAG
AGGTGGAAATCAAACGGACGGTGGC
AGCTGACCGTCCTAGGTCAGCCCAA
CCACTTTGACTACTGGGGCCAGGGA
TGCACCATCTGTCTTCATCTTCCCGC
GGCTGCACCCTCGGTCACTCTGTTCC
ACCCTGGTCACCGTGTCCTCAGCCTC
CATCTGATGAGCAGTTGAAATCTGG
CGCCCTCCTCTGAGGAGCTTCAAGCC
CACCAAGGGCCCATCGGTCTTCCCCC
AACTGCCTCTGTTGTGTGCCTGCTGA
AACAAGGCCACACTGGTGTGTCTCAT
TGGCACCCTCCTCCAAGAGCACCTCT
ATAACTTCTATCCCAGAGAGGCCAA
CAGTGACTTCTACCCGGGAGCCGTG
GGGGGCACAGCGGCCCTGGGCTGCC
AGTACAGTGGAAGGTGGATAACGCC
ACAGTGGCCTGGAAGGCAGATAGCA
TGGTCAAGGACTACTTCCCCGAACCG
CTCCAATCGGGTAACTCCCAGGAGA
GCCCCGTCAAGGCGGGAGTGGAAAC
GTGACGGTGTCGTGGAACTCAGGCG
GTGTCACAGAGCAGGACAGCAAGGA
CACCACACCCTCCAAACAAAGCAAC
CCCTGACCAGCGGCGTGCACACCTTC
CAGCACCTACAGCCTCGAAAGCACC
AACAAGTACGCGGCCAAGAGCTATC
CCGGCTGTCCTACAGTCCTCAGGACT
CTGACGCTGAGCAAAGCAGACTACG
TGAGCCTGACGCCTGAGCAGTGGAA
CTACTCCCTCAAGAGCGTGGTGACCG
AGAAACACAAAGTCTACGCCTGCGA
GTCCCACAGAAGCTACAGCTGCCAG
TGCCCTCCAGCAGCTTGGGCACCCAG
AGTCACCCATCAGGGCCTGAGCTCG
GTCACGCATGAAGGGAGCACCGTGG
ACCTACATCTGCAACGTGAATCACA
CCCGTCACAAAGAGCTTCAACAGGG
AGAAGACAGTGGCCCCTACAGAATG
AGCCCAGCAACACCAAGGTGGACAA
GAGAGTGT
TTCA
GAAAGTTGAGCCCAAATCTTGTGAC
(SEQ ID NO: 797)
(SEQ ID NO: 798)
AAAACTCACACATGCCCACCGTGCC
CAGCACCTGAACTCCTGGGGGGACC
GTCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGT
GGACGTGAGCCACGAAGACCCTGAG
GTCAAGTTCAACTGGTACGTGGACG
GCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGC
AGCACGTACCGTTGCGTCAGCGTCCT
CACCGTCCTGCACCAGGACTGGCTG
AATGGCAAGGAGTACAAGTGCAAGG
TGTCCAACAAAGCCCTCCCAGCCCCC
ATCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGGT
GTACACCCTGCCCCCATCCCGGGAG
GAGATGACCAAGAACCAGGTCAGCC
TGACCTGCCTGGTCAAAGGCTTCTAT
CCCAGCGACATCGCCGTGGAGTGGG
AGAGCAATGGGCAGCCGGAGAACAA
CTACAAGACCACGCCTCCCGTGCTGG
ACTCCGACGGCTCCTTCTTCCTCTAT
AGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTGC
ACAACCACTACACGCAGAAGAGCCT
CTCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCCAGGTGCA
GTTGGTGGAGTCTGGGGGAGGCTTA
GTCAAGCCTGGAGGGTCCCTGAGAC
TCTCCTGTGCAGCCTCTGAATTCACC
TTCAGTGACTACTACATGAGCTGGAT
CCGCCAGGCTCCAGGGAAGGGGCTG
GAGTGGGTTTCATATATTAGTCGAAG
TGGTGATACCATCTACTACGCAGACT
CTGTGAAGGGCCGATTCACCATCTCC
AGGGACAACGCCAAGAACTCACTGT
ATCTGCAAATGAATGGCCTGCGAGC
CGAAGACACGGCCGTGTATTACTGT
GCGAGAGACTTAGCAGCAGGTGCTA
CAGGGGGCCTTGACTGCTGGGGCCA
GGGAACCCTGGTCACCGTGTCCTCAG
CAAGCACGAAGGGGCCGTCCGTATT
TCCGCTTGCGCCCTCGTCGAAGTCAA
CTTCGGGAGGGACCGCGGCACTTGG
CTGTCTTGTCAAAGATTACTTCCCTG
AGCCAGTGACAGTCAGCTGGAATTC
CGGTGCCCTCACGTCAGGAGTACAT
ACATTCCCTGCGGTATTGCAGTCCTC
CGGACTCTACTCCCTGGAGTCGGTGG
TAACGGTGCCCAGCTCCAGCTTGGG
GACCCAGACGTACATTTGTAACGTG
AATCACAAACCAAGCAATACTAAGG
TAGATAAGAAAGTAGAACCGAAGAG
CTGC
(SEQ ID NO: 799)
AA
DIQMTQSPSSVSASVGDRVTITCRASQ
SYELTQPPSVSVSPGQTASITCSGERLG
QVQLVESGGGLVKPGGSLRLSCAASG
DISRWLAWYQQKPGKAPKLLISAASR
NKYICWYQQKPGQSPVLVIYQDFKRPS
FTFSDYYMSWIRQAPGKGLEWISYISS
LQSGVPSRFSGSGSGTDFTLTISSLQPE
GIPERFSGSNSGITATLTISGTQAMDEA
SESIIYYVDSVKGRFTISRDNAKNSLYL
DFAIYYCQQAKSFPRTFGQGTKVEIKR
DYYCQAWDSRTVVFGGGTKLTVLGQ
QMNSLRAEDTAVYYCARDVGSHFDY
TVAAPSVFIFPPSDEQLKSGTASVVCLL
PKAAPSVTLFPPSSEELQANKATLVCLI
WGQGTLVTVSSASTKGPSVFPLAPSSK
NNFYPREAKVQWKVDNALQSGNSQE
SDFYPGAVTVAWKADSSPVKAGVETT
STSGGTAALGCLVKDYFPEPVTVSWN
SVTEQDSKDSTYSLESTLTLSKADYEK
TPSKQSNNKYAAKSYLSLTPEQWKSH
SGALTSGVHTFPAVLQSSGLYSLKSVV
HKVYACEVTHQGLSSPVTKSFNRGEC
RSYSCQVTHEGSTVEKTVAPTECS
TVPSSSLGTQTYICNVNHKPSNTKVDK
(SEQ ID NO: 800)
(SEQ ID NO: 801)
KVEPKSCDKTHTCPPCPAPELLGGPSV
FLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVKFNWYVDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPRE
PQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLVESGGGLVKPGGSLRLSC
AASEFTFSDYYMSWIRQAPGKGLEWV
SYISRSGDTIYYADSVKGRFTISRDNAK
NSLYLQMNGLRAEDTAVYYCARDLA
AGATGGLDCWGQGTLVTVSSASTKGP
SVFPLAPSSKSTSGGTAALGCLVKDYF
PEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLESVVTVPSSSLGTQTYICNVNH
KPSNTKVDKKVEPKSC
(SEQ ID NO: 802)
iPS:
21-233_6F4_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATTGTGATGACTCAGTCTCCAGA
CAGTCTGCCCTGACTCAGCCTGCCTC
CAGGTGCAGCTGGTGGAGTCTGGGG
576222
230_39C2_Fab
6F4VH]::huIgG1zSEFL2*GK-
CTCCCTGGCTGTGTCTCTGGGCGAGA
CGTGTCTGGGAGCCCTGGACAGTCG
GAGGCTTGGTCAAGCCTGGAGGGTC
K::(G4S)2::[hu anti-
GGGCCACCATCAACTGCAAGTCCAG
ATCACCATCTCCTGCACTGGAACCAG
CCTGAGACTCTCCTGTGCAGCCTCTG
<huCD40>21-230_39C2VH]::
CCAGAGTGTTTTATACAGCTCCAACA
CAGTGATGTTGGGAATTATAACCTTG
GATTCACCTTCAGTGACTACTACATG
huIgG1z-CH1-E::EPKSC +
ATAAGAACTACTTAGCTTGGTACCAG
TCTCCTGGTACCAACAGCACCCAGGC
AGCTGGATCCGCCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CAGAAACCAGGACAGCCTCCTAAGC
AAAGCCCCCAAACTCATGATTTATGA
AGGGGCTGGAGTGGATTTCATACATT
7G11VL]::huKLC-S176E +
TGCTCATTTACTGGGCATCTACCCGA
GGTCAATAGGCGGCCCTCAGGGGTT
AGTAGCAGTGAAAGTATCATCTATTA
[anti-<huCD40>
GAATCCGGGGTCCCTGACCGATTCA
TCTAATCGCTTCTCTGGCTCCAAGTC
CGTAGACTCTGTGAAGGGCCGATTC
21-230_39C2VL]::
GTGGCAGCGGGTCTGGGACAGATTT
TGGCAACACGGCCTCCCTGACAATCT
ACCATCTCCAGGGACAACGCCAAGA
huLLC2-K(IgG-
CACTCTCACCATCAGCAGCCTGCAGG
CTGGGCTCCAGGCTGAGGACGAGGC
ACTCACTGTATCTGCAAATGAACAGC
Fab); LMRID:
CTGAAGATGTGGCAGTTTATTACTGT
TGAATATTACTGCTGCTCATATGCAG
CTGAGAGCCGAGGACACGGCCGTGT
SS-30845
CAGCAATATTATAGTACTCCTCCGAC
GTAGAGACACTTTCGTGGTGTTCGGC
ATTACTGTGCGAGAGATGTTGGGAG
GTTCGGCCAAGGGACCAAGGTGGAG
GGAGGGACCAAGCTGACCGTCCTAG
CCACTTTGACTACTGGGGCCAGGGA
ATCAAACGGACGGTGGCTGCACCAT
GTCAGCCCAAGGCTGCACCCTCGGTC
ACCCTGGTCACCGTGTCCTCAGCCTC
CTGTCTTCATCTTCCCGCCATCTGAT
ACTCTGTTCCCGCCCTCCTCTGAGGA
CACCAAGGGCCCATCGGTCTTCCCCC
GAGCAGTTGAAATCTGGAACTGCCT
GCTTCAAGCCAACAAGGCCACACTG
TGGCACCCTCCTCCAAGAGCACCTCT
CTGTTGTGTGCCTGCTGAATAACTTC
GTGTGTCTCATCAGTGACTTCTACCC
GGGGGCACAGCGGCCCTGGGCTGCC
TATCCCAGAGAGGCCAAAGTACAGT
GGGAGCCGTGACAGTGGCCTGGAAG
TGGTCAAGGACTACTTCCCCGAACCG
GGAAGGTGGATAACGCCCTCCAATC
GCAGATAGCAGCCCCGTCAAGGCGG
GTGACGGTGTCGTGGAACTCAGGCG
GGGTAACTCCCAGGAGAGTGTCACA
GAGTGGAAACCACCACACCCTCCAA
CCCTGACCAGCGGCGTGCACACCTTC
GAGCAGGACAGCAAGGACAGCACCT
ACAAAGCAACAACAAGTACGCGGCC
CCGGCTGTCCTACAGTCCTCAGGACT
ACAGCCTCGAAAGCACCCTGACGCT
AAGAGCTATCTGAGCCTGACGCCTG
CTACTCCCTCAAGAGCGTGGTGACCG
GAGCAAAGCAGACTACGAGAAACAC
AGCAGTGGAAGTCCCACAGAAGCTA
TGCCCTCCAGCAGCTTGGGCACCCAG
AAAGTCTACGCCTGCGAAGTCACCC
CAGCTGCCAGGTCACGCATGAAGGG
ACCTACATCTGCAACGTGAATCACA
ATCAGGGCCTGAGCTCGCCCGTCAC
AGCACCGTGGAGAAGACAGTGGCCC
AGCCCAGCAACACCAAGGTGGACAA
AAAGAGCTTCAACAGGGGAGAGTGT
CTACAGAATGTTCA
GAAAGTTGAGCCCAAATCTTGTGAC
(SEQ ID NO: 803)
(SEQ ID NO: 804)
AAAACTCACACATGCCCACCGTGCC
CAGCACCTGAACTCCTGGGGGGACC
GTCAGTCTTCCTCTTCCCCCCAAAAC
CCAAGGACACCCTCATGATCTCCCGG
ACCCCTGAGGTCACATGCGTGGTGGT
GGACGTGAGCCACGAAGACCCTGAG
GTCAAGTTCAACTGGTACGTGGACG
GCGTGGAGGTGCATAATGCCAAGAC
AAAGCCGTGCGAGGAGCAGTACGGC
AGCACGTACCGTTGCGTCAGCGTCCT
CACCGTCCTGCACCAGGACTGGCTG
AATGGCAAGGAGTACAAGTGCAAGG
TGTCCAACAAAGCCCTCCCAGCCCCC
ATCGAGAAAACCATCTCCAAAGCCA
AAGGGCAGCCCCGAGAACCACAGGT
GTACACCCTGCCCCCATCCCGGGAG
GAGATGACCAAGAACCAGGTCAGCC
TGACCTGCCTGGTCAAAGGCTTCTAT
CCCAGCGACATCGCCGTGGAGTGGG
AGAGCAATGGGCAGCCGGAGAACAA
CTACAAGACCACGCCTCCCGTGCTGG
ACTCCGACGGCTCCTTCTTCCTCTAT
AGCAAGCTCACCGTGGACAAGAGCA
GGTGGCAGCAGGGGAACGTCTTCTC
ATGCTCCGTGATGCATGAGGCTCTGC
ACAACCACTACACGCAGAAGAGCCT
CTCCCTGTCTCCGGGTGGTGGCGGAT
CGGGAGGTGGCGGATCCCAGGTGCA
GCTGGTGCAGTCTGGGACTGAGGTG
AAGAAGCCTGGGGCCTCAGTGAAGG
TGTCCTGCAAGGCTTCTGGATACACC
TTCCCCGGCTACTATATGCACTGGGT
GCGACAGGCCCCTGGACAGGGGCTT
GAGTGGATGGGATGGATCAACCCTG
ACAGTGGTGGCACAAAGTATACACA
GAAGTTTCAGGGCAGGGTCACCTTG
ACCAGGGACGCGTCCGTCAGCACAG
CCTACATTGACCTGAACAGGCTGAG
ATCTGACGACACGGCCGTATATTACT
GTGCGAGAGAGAGGTGTAGGACTAC
CAACTGCTATTTGGACTACTGGGGCC
AGGGAAGTCTGGTCACCGTGTCCTCA
GCAAGCACGAAGGGGCCGTCCGTAT
TTCCGCTTGCGCCCTCGTCGAAGTCA
ACTTCGGGAGGGACCGCGGCACTTG
GCTGTCTTGTCAAAGATTACTTCCCT
GAGCCAGTGACAGTCAGCTGGAATT
CCGGTGCCCTCACGTCAGGAGTACAT
ACATTCCCTGCGGTATTGCAGTCCTC
CGGACTCTACTCCCTGGAGTCGGTGG
TAACGGTGCCCAGCTCCAGCTTGGG
GACCCAGACGTACATTTGTAACGTG
AATCACAAACCAAGCAATACTAAGG
TAGATAAGAAAGTAGAACCGAAGAG
CTGC
(SEQ ID NO: 805)
AA
DIVMTQSPDSLAVSLGERATINCKSSQ
QSALTQPASVSGSPGQSITISCTGTSSD
QVQLVESGGGLVKPGGSLRLSCAASG
SVLYSSNNKNYLAWYQQKPGQPPKLL
VGNYNLVSWYQQHPGKAPKLMIYEV
FTFSDYYMSWIRQAPGKGLEWISYISS
IYWASTRESGVPDRFSGSGSGTDFTLTI
NRRPSGVSNRFSGSKSGNTASLTISGLQ
SESIIYYVDSVKGRFTISRDNAKNSLYL
SSLQAEDVAVYYCQQYYSTPPTFGQG
AEDEAEYYCCSYAGRDTFVVFGGGTK
QMNSLRAEDTAVYYCARDVGSHFDY
TKVEIKRTVAAPSVFIFPPSDEQLKSGT
LTVLGQPKAAPSVTLFPPSSEELQANK
WGQGTLVTVSSASTKGPSVFPLAPSSK
ASVVCLLNNFYPREAKVQWKVDNAL
ATLVCLISDFYPGAVTVAWKADSSPV
STSGGTAALGCLVKDYFPEPVTVSWN
QSGNSQESVTEQDSKDSTYSLESTLTL
KAGVETTTPSKQSNNKYAAKSYLSLTP
SGALTSGVHTFPAVLQSSGLYSLKSVV
SKADYEKHKVYACEVTHQGLSSPVTK
EQWKSHRSYSCQVTHEGSTVEKTVAP
TVPSSSLGTQTYICNVNHKPSNTKVDK
SFNRGEC
TECS
KVEPKSCDKTHTCPPCPAPELLGGPSV
(SEQ ID NO: 806)
(SEQ ID NO: 807)
FLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVKFNWYVDGVEVHNAKTKPC
EEQYGSTYRCVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPRE
PQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGGGGSG
GGGSQVQLVQSGTEVKKPGASVKVSC
KASGYTFPGYYMHWVRQAPGQGLEW
MGWINPDSGGTKYTQKFQGRVTLTRD
ASVSTAYIDLNRLRSDDTAVYYCARE
RCRTTNCYLDYWGQGSLVTVSSASTK
GPSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAVLQ
SSGLYSLESVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSC
(SEQ ID NO: 808)
iPS:
21-233_7G11_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATTGTGATGACTCAGTCTCCAGA
GACATCCAGATGACCCAGTCTCCATC
GAGGTGCAGCTGGTCGAGTCTGGAG
576228
230_4G7_Fab
7G11VH]::huIgG1zSEFL2*GK-
CTCCCTGGCTGTGTCTCTGGGCGAGA
CTCCCTGTCTGCATCTGTAGGAGACA
GAGGCTTGATCCAGCCTGGGGGGTC
K::(G4S)2::[hu anti-
GGGCCACCATCAACTGCAAGTCCAG
TTCTCACCATCACTTGCCGGGCAAGT
CCTGAGACTCTCCTGTGCAGTCTCTG
<huCD40>21-230_4G7VH]::
CCAGAGTGTTTTATACAGCTCCAACA
CAGAACATTACCACCTATTTAAATTG
GGTTCACCGTCAGTAGCAAGTTCATG
huIgG1z-CH1-E::EPKSC +
ATAAGAACTACTTAGCTTGGTACCAG
GTATCAGCAGAAACCAGGGAAAGCC
ACCTGGGTCCGCCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CAGAAACCAGGACAGCCTCCTAAGC
CCTAACCTCCTGATCTCTGCTGCATC
AGGGGCTGGAGTGGGTGTCAGTTAT
7G11VL]::huKLC-S176E +
TGCTCATTTACTGGGCATCTACCCGA
CCGTTTGCGAAGTGGGGTCCCATCAA
TTATAGCGGTGGTAAGACATACTAC
[anti-<huCD40>
GAATCCGGGGTCCCTGACCGATTCA
GGTTCAGTGGCAGTGGATCTGGGAC
GCAGACTCCGTGAAGGGCCGATTCA
21-230_4G7VL]::
GTGGCAGCGGGTCTGGGACAGATTT
AGATTTCACTCTCACCATCAGCAGTC
CCATCTCCAGAGACAATTCCAAGAA
huKLC-S176K(IgG-
CACTCTCACCATCAGCAGCCTGCAGG
TGCAACCTGTAGATTTTACAACTTTC
CACGCTGTATCTTCAAATGAACAGCC
Fab); LMRID:
CTGAAGATGTGGCAGTTTATTACTGT
TACTGTCAACAGACTTTCACTACCCC
TGAGAGCCGAGGACACGGCCGTGTA
SS-30846
CAGCAATATTATAGTACTCCTCCGAC
GTGGACGTTCGGCCAAGGGACCAAG
TTACTGTGCGAGAGATAGCGGTGGC
GTTCGGCCAAGGGACCAAGGTGGAG
GTGGAGATCAAACGAACGGTGGCTG
TGGGGGTACTTTGACTACTGGGGCCA
ATCAAACGGACGGTGGCTGCACCAT
CACCATCTGTCTTCATCTTCCCGCCA
GGGAACCCTGGTCACCGTGTCCTCAG
CTGTCTTCATCTTCCCGCCATCTGAT
TCTGATGAGCAGTTGAAATCTGGAA
CCTCCACCAAGGGCCCATCGGTCTTC
GAGCAGTTGAAATCTGGAACTGCCT
CTGCCTCTGTTGTGTGCCTGCTGAAT
CCCCTGGCACCCTCCTCCAAGAGCAC
CTGTTGTGTGCCTGCTGAATAACTTC
AACTTCTATCCCAGAGAGGCCAAAG
CTCTGGGGGCACAGCGGCCCTGGGC
TATCCCAGAGAGGCCAAAGTACAGT
TACAGTGGAAGGTGGATAACGCCCT
TGCCTGGTCAAGGACTACTTCCCCGA
GGAAGGTGGATAACGCCCTCCAATC
CCAATCGGGTAACTCCCAGGAGAGT
ACCGGTGACGGTGTCGTGGAACTCA
GGGTAACTCCCAGGAGAGTGTCACA
GTCACAGAGCAGGACAGCAAGGACA
GGCGCCCTGACCAGCGGCGTGCACA
GAGCAGGACAGCAAGGACAGCACCT
GCACCTACAGCCTCAAGAGCACCCT
CCTTCCCGGCTGTCCTACAGTCCTCA
ACAGCCTCGAAAGCACCCTGACGCT
GACGCTGAGCAAAGCAGACTACGAG
GGACTCTACTCCCTCAAGAGCGTGGT
GAGCAAAGCAGACTACGAGAAACAC
AAACACAAAGTCTACGCCTGCGAAG
GACCGTGCCCTCCAGCAGCTTGGGC
AAAGTCTACGCCTGCGAAGTCACCC
TCACCCATCAGGGCCTGAGCTCGCCC
ACCCAGACCTACATCTGCAACGTGA
ATCAGGGCCTGAGCTCGCCCGTCAC
GTCACAAAGAGCTTCAACAGGGGAG
ATCACAAGCCCAGCAACACCAAGGT
AAAGAGCTTCAACAGGGGAGAGTGT
AGTGT
GGACAAGAAAGTTGAGCCCAAATCT
(SEQ ID NO: 809)
(SEQ ID NO: 810)
TGTGACAAAACTCACACATGCCCAC
CGTGCCCAGCACCTGAACTCCTGGG
GGGACCGTCAGTCTTCCTCTTCCCCC
CAAAACCCAAGGACACCCTCATGAT
CTCCCGGACCCCTGAGGTCACATGCG
TGGTGGTGGACGTGAGCCACGAAGA
CCCTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGTGCGAGGAGCAG
TACGGCAGCACGTACCGTTGCGTCA
GCGTCCTCACCGTCCTGCACCAGGAC
TGGCTGAATGGCAAGGAGTACAAGT
GCAAGGTGTCCAACAAAGCCCTCCC
AGCCCCCATCGAGAAAACCATCTCC
AAAGCCAAAGGGCAGCCCCGAGAAC
CACAGGTGTACACCCTGCCCCCATCC
CGGGAGGAGATGACCAAGAACCAGG
TCAGCCTGACCTGCCTGGTCAAAGGC
TTCTATCCCAGCGACATCGCCGTGGA
GTGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCCG
TGCTGGACTCCGACGGCTCCTTCTTC
CTCTATAGCAAGCTCACCGTGGACA
AGAGCAGGTGGCAGCAGGGGAACGT
CTTCTCATGCTCCGTGATGCATGAGG
CTCTGCACAACCACTACACGCAGAA
GAGCCTCTCCCTGTCTCCGGGTGGTG
GCGGATCGGGAGGTGGCGGATCCCA
GGTGCAGCTGGTGCAGTCTGGGGCT
GAGGTGAAGAAGCCTGGGGCCTCAG
TGAAGGTGTCCTGCAAGGCTTCTGGA
TACACCTTCGCCGGCTACTATATGCA
CTGGGTGCGACAGGCCCCTGGACAA
GGGCTTGAGTGGATGGGATGGATCA
ACCCTGACAGTGGAGGCACAAACTT
TGCACAGCAGTTTCAGGGCAGGGTC
ACCATGACCAGGGATACGTCCATCA
GCACAGCCTACATGGAGGTGAGCAG
GCTGAGATCTGACGACACGGCCGTG
TTTTACTGTGCGAGAGAGAAGATCA
CTATGACTGGTATTTACTTTGACTAT
TGGGGCCAGGGAACCCTGGTCACCG
TGTCCTCAGCAAGCACGAAGGGGCC
GTCCGTATTTCCGCTTGCGCCCTCGT
CGAAGTCAACTTCGGGAGGGACCGC
GGCACTTGGCTGTCTTGTCAAAGATT
ACTTCCCTGAGCCAGTGACAGTCAGC
TGGAATTCCGGTGCCCTCACGTCAGG
AGTACATACATTCCCTGCGGTATTGC
AGTCCTCCGGACTCTACTCCCTGGAG
TCGGTGGTAACGGTGCCCAGCTCCA
GCTTGGGGACCCAGACGTACATTTGT
AACGTGAATCACAAACCAAGCAATA
CTAAGGTAGATAAGAAAGTAGAACC
GAAGAGCTGC
(SEQ ID NO: 811)
AA
DIVMTQSPDSLAVSLGERATINCKSSQ
DIQMTQSPSSLSASVGDILTITCRASQN
EVQLVESGGGLIQPGGSLRLSCAVSGF
SVLYSSNNKNYLAWYQQKPGQPPKLL
ITTYLNWYQQKPGKAPNLLISAASRLRS
TVSSKFMTWVRQAPGKGLEWVSVIYS
IYWASTRESGVPDRFSGSGSGTDFTLTI
GVPSRFSGSGSGTDFTLTISSLQPVDFT
GGKTYYADSVKGRFTISRDNSKNTLY
SSLQAEDVAVYYCQQYYSTPPTFGQG
TFYCQQTFTTPWTFGQGTKVEIKRTVA
LQMNSLRAEDTAVYYCARDSGGWGY
TKVEIKRTVAAPSVFIFPPSDEQLKSGT
APSVFIFPPSDEQLKSGTASVVCLLNNF
FDYWGQGTLVTVSSASTKGPSVFPLAP
ASVVCLLNNFYPREAKVQWKVDNAL
YPREAKVQWKVDNALQSGNSQESVTE
SSKSTSGGTAALGCLVKDYFPEPVTVS
QSGNSQESVTEQDSKDSTYSLESTLTL
QDSKDSTYSLKSTLTLSKADYEKHKV
WNSGALTSGVHTFPAVLQSSGLYSLKS
SKADYEKHKVYACEVTHQGLSSPVTK
YACEVTHQGLSSPVTKSFNRGEC
VVTVPSSSLGTQTYICNVNHKPSNTKV
SFNRGEC
(SEQ ID NO: 813)
DKKVEPKSCDKTHTCPPCPAPELLGGP
(SEQ ID NO: 812)
SVFLFPPKPKDTLMISRTPEVTCVVVD
VSHEDPEVKFNWYVDGVEVHNAKTK
PCEEQYGSTYRCVSVLTVLHQDWLNG
KEYKCKVSNKALPAPIEKTISKAKGQP
REPQVYTLPPSREEMTKNQVSLTCLVK
GFYPSDIAVEWESNGQPENNYKTTPPV
LDSDGSFFLYSKLTVDKSRWQQGNVF
SCSVMHEALHNHYTQKSLSLSPGGGG
SGGGGSQVQLVQSGAEVKKPGASVKV
SCKASGYTFAGYYMHWVRQAPGQGL
EWMGWINPDSGGTNFAQQFQGRVTM
TRDTSISTAYMEVSRLRSDDTAVFYCA
REKITMTGIYFDYWGQGTLVTVSSAST
KGPSVFPLAPSSKSTSGGTAALGCLVK
DYFPEPVTVSWNSGALTSGVHTFPAVL
QSSGLYSLESVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSC
(SEQ ID NO: 814)
iPS:
21-233_7G11_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATTGTGATGACTCAGTCTCCAGA
GACATCCAGATGACCCAGTCTCCATC
GAGGTGCAGCTGGTCGAGTCTGGAG
576231
230_29H10_Fab
7G11VH]::huIgG1zSEFL2*GK-
CTCCCTGGCTGTGTCTCTGGGCGAGA
CTCACTGTCTGCATCTGTAGGAGACA
GAGGCTTGATCCAGCCTGGGGGGTC
K::(G4S)2::[hu anti-
GGGCCACCATCAACTGCAAGTCCAG
GAGTCACCATCACCTGTCGGGCGAG
CCTGAGACTCTCCTGTGCAGTCTCTG
<huCD40>21-230_29H10VH]::
CCAGAGTGTTTTATACAGCTCCAACA
TCAGGACATTAGCAATAATTTAGCCT
GGTTCACCGTCAGTAGCAAGTTCATG
huIgG1z-CH1-E::EPKSC +
ATAAGAACTACTTAGCTTGGTACCAG
GGTTTCAGCAGAAACCAGGGAAACC
ACCTGGGTCCGCCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CAGAAACCAGGACAGCCTCCTAAGC
CCCTAAGTCCCTGATGTATGCTGCAT
AGGGGCTGGAGTGGGTGTCAGTTAT
7G11VL]::huKLC-S176E +
TGCTCATTTACTGGGCATCTACCCGA
CCAGTTTGCACAGTGGAGTCCCATCA
TTATAGCGGTGGTAAGACATACTAC
[anti-<huCD40>
GAATCCGGGGTCCCTGACCGATTCA
ACGTTCAGCGGCAGTGGATCTGGGA
GCAGACTCCGTGAAGGGCCGATTCA
21-230_29H10VL]::
GTGGCAGCGGGTCTGGGACAGATTT
CAGATTTCACTTTCACCATCAGCAGC
CCATCTCCAGAGACAATTCCAAGAA
huKLC-S176K(IgG-
CACTCTCACCATCAGCAGCCTGCAGG
CTGCAGCCTGAAGATTTTGCAACTTA
CACGCTGTATCTTCAAATGAACAGCC
Fab); LMRID:
CTGAAGATGTGGCAGTTTATTACTGT
TTACTGCCAACAGTATAATAGTTACC
TGAGAGCCGAGGACACGGCCGTGTA
SS-30847
CAGCAATATTATAGTACTCCTCCGAC
CTCTCACTTTCGGCGGAGGGACCAA
TTACTGTGCGAGAGATAGCGGTGGC
GTTCGGCCAAGGGACCAAGGTGGAG
GGTGGAGATCAGACGAACGGTGGCT
TGGGGGTACTTTGACTACTGGGGCCA
ATCAAACGGACGGTGGCTGCACCAT
GCACCATCTGTCTTCATCTTCCCGCC
GGGAACCCTGGTCACCGTGTCCTCAG
CTGTCTTCATCTTCCCGCCATCTGAT
ATCTGATGAGCAGTTGAAATCTGGA
CCTCCACCAAGGGCCCATCGGTCTTC
GAGCAGTTGAAATCTGGAACTGCCT
ACTGCCTCTGTTGTGTGCCTGCTGAA
CCCCTGGCACCCTCCTCCAAGAGCAC
CTGTTGTGTGCCTGCTGAATAACTTC
TAACTTCTATCCCAGAGAGGCCAAA
CTCTGGGGGCACAGCGGCCCTGGGC
TATCCCAGAGAGGCCAAAGTACAGT
GTACAGTGGAAGGTGGATAACGCCC
TGCCTGGTCAAGGACTACTTCCCCGA
GGAAGGTGGATAACGCCCTCCAATC
TCCAATCGGGTAACTCCCAGGAGAG
ACCGGTGACGGTGTCGTGGAACTCA
GGGTAACTCCCAGGAGAGTGTCACA
TGTCACAGAGCAGGACAGCAAGGAC
GGCGCCCTGACCAGCGGCGTGCACA
GAGCAGGACAGCAAGCACAGCACCT
AGCACCTACAGCCTCAAGAGCACCC
CCTTCCCGGCTGTCCTACAGTCCTCA
ACAGCCTCGAAAGCACCCTGACGCT
TGACGCTGAGCAAAGCAGACTACGA
GGACTCTACTCCCTCAAGAGCGTGGT
GAGCAAAGCAGACTACGAGAAACAC
GAAACACAAAGTCTACGCCTGCGAA
GACCGTGCCCTCCAGCAGCTTGGGC
AAAGTCTACGCCTGCGAAGTCACCC
GTCACCCATCAGGGCCTGAGCTCGCC
ACCCAGACCTACATCTGCAACGTGA
ATCAGGGCCTGAGCTCGCCCGTCAC
CGTCACAAAGAGCTTCAACAGGGGA
ATCACAAGCCCAGCAACACCAAGGT
AAAGAGCTTCAACAGGGGAGAGTGT
GAGTGT
GGACAAGAAAGTTGAGCCCAAATCT
(SEQ ID NO: 815)
(SEQ ID NO: 816)
TGTGACAAAACTCACACATGCCCAC
CGTGCCCAGCACCTGAACTCCTGGG
GGGACCGTCAGTCTTCCTCTTCCCCC
CAAAACCCAAGGACACCCTCATGAT
CTCCCGGACCCCTGAGGTCACATGCG
TGGTGGTGGACGTGAGCCACGAAGA
CCCTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGTGCGAGGAGCAG
TACGGCAGCACGTACCGTTGCGTCA
GCGTCCTCACCGTCCTGCACCAGGAC
TGGCTGAATGGCAAGGAGTACAAGT
GCAAGGTGTCCAACAAAGCCCTCCC
AGCCCCCATCGAGAAAACCATCTCC
AAAGCCAAAGGGCAGCCCCGAGAAC
CACAGGTGTACACCCTGCCCCCATCC
CGGGAGGAGATGACCAAGAACCAGG
TCAGCCTGACCTGCCTGGTCAAAGGC
TTCTATCCCAGCGACATCGCCGTGGA
GTGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCCG
TGCTGGACTCCGACGGCTCCTTCTTC
CTCTATAGCAAGCTCACCGTGGACA
AGAGCAGGTGGCAGCAGGGGAACGT
CTTCTCATGCTCCGTGATGCATGAGG
CTCTGCACAACCACTACACGCAGAA
GAGCCTCTCCCTGTCTCCGGGTGGTG
GCGGATCGGGAGGTGGCGGATCCCA
GGTGCAACTGGTGCAGTCTGGGGCT
GAGGTGACGAAGCCTGGGGCCTCAG
TGAAGGTGTCCTGCAAGGCTTCTGGA
TACACCTTCGCCGGCTACTATATGCA
CTGGGTGCGACAGGCCCCTGGACAA
GGGCTTGAGTGGATGGGATGGATCA
ACCCTCACAGTGGTGGCACAAACTA
TGCACAGAAGTTTCAGGACAGGGTC
ACCATGACCAGGGACACGTCCATCA
ACACAGCCTACATGGAACTGAGCAG
GCTGAGATCTGACGACACGGCCGTG
TATTACTGTGCGAGAGAACGTATTTC
TATGGTTCGGGGAGTCGGGCACAAC
TGGTTCGCCCCCTGGGGCCAGGGAA
CCCTGGTCACCGTGTCCTCAGCAAGC
ACGAAGGGGCCGTCCGTATTTCCGCT
TGCGCCCTCGTCGAAGTCAACTTCGG
GAGGGACCGCGGCACTTGGCTGTCTT
GTCAAAGATTACTTCCCTGAGCCAGT
GACAGTCAGCTGGAATTCCGGTGCC
CTCACGTCAGGAGTACATACATTCCC
TGCGGTATTGCAGTCCTCCGGACTCT
ACTCCCTGGAGTCGGTGGTAACGGT
GCCCAGCTCCAGCTTGGGGACCCAG
ACGTACATTTGTAACGTGAATCACAA
ACCAAGCAATACTAAGGTAGATAAG
AAAGTAGAACCGAAGAGCTGC
(SEQ ID NO: 817)
AA
DIVMTQSPDSLAVSLGERATINCKSSQ
DIQMTQSPSSLSASVGDRVTITCRASQ
EVQLVESGGGLIQPGGSLRLSCAVSGF
SVLYSSNNKNYLAWYQQKPGQPPKLL
DISNNLAWFQQKPGKPPKSLMYAASS
TVSSKFMTWVRQAPGKGLEWVSVIYS
IYWASTRESGVPDRFSGSGSGTDFTLTI
LHSGVPSTFSGSGSGTDFTFTISSLQPE
GGKTYYADSVKGRFTISRDNSKNTLY
SSLQAEDVAVYYCQQYYSTPPTFGQG
DFATYYCQQYNSYPLTFGGGTKVEIRR
LQMNSLRAEDTAVYYCARDSGGWGY
TKVEIKRTVAAPSVFIFPPSDEQLKSGT
TVAAPSVFIFPPSDEQLKSGTASVVCLL
FDYWGQGTLVTVSSASTKGPSVFPLAP
ASVVCLLNNFYPREAKVQWKVDNAL
NNFYPREAKVQWKVDNALQSGNSQE
SSKSTSGGTAALGCLVKDYFPEPVTVS
QSGNSQESVTEQDSKDSTYSLESTLTL
SVTEQDSKDSTYSLKSTLTLSKADYEK
WNSGALTSGVHTFPAVLQSSGLYSLKS
SKADYEKHKVYACEVTHQGLSSPVTK
HKVYACEVTHQGLSSPVTKSFNRGEC
VVTVPSSSLGTQTYICNVNHKPSNTKV
SFNRGEC
(SEQ ID NO: 819)
DKKVEPKSCDKTHTCPPCPAPELLGGP
(SEQ ID NO: 818)
SVFLFPPKPKDTLMISRTPEVTCVVVD
VSHEDPEVKFNWYVDGVEVHNAKTK
PCEEQYGSTYRCVSVLTVLHQDWLNG
KEYKCKVSNKALPAPIEKTISKAKGQP
REPQVYTLPPSREEMTKNQVSLTCLVK
GFYPSDIAVEWESNGQPENNYKTTPPV
LDSDGSFFLYSKLTVDKSRWQQGNVF
SCSVMHEALHNHYTQKSLSLSPGGGG
SGGGGSQVQLVQSGAEVTKPGASVKV
SCKASGYTFAGYYMHWVRQAPGQGL
EWMGWINPHSGGTNYAQKFQDRVTM
TRDTSINTAYMELSRLRSDDTAVYYC
ARERISMVRGVGHNWFAPWGQGTLV
TVSSASTKGPSVFPLAPSSKSTSGGTAA
LGCLVKDYFPEPVTVSWNSGALTSGV
HTFPAVLQSSGLYSLESVVTVPSSSLGT
QTYICNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 820)
iPS:
21-233_7G11_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATTGTGATGACTCAGTCTCCAGA
CAGTCTGCCCTGACTCAGCCTGCCTC
GAGGTGCAGCTGGTCGAGTCTGGAG
576234
230_30A12_Fab
7G11VH]::huIgG1zSEFL2*GK-
CTCCCTGGCTGTGTCTCTGGGCGAGA
CGTGTCTGGGAGCCCTGGACAGTCG
GAGGCTTGATCCAGCCTGGGGGGTC
K::(G4S)2::[hu anti-
GGGCCACCATCAACTGCAAGTCCAG
ATCACCATCTCCTGCACTGGAACCAG
CCTGAGACTCTCCTGTGCAGTCTCTG
<huCD40>21-230_30A12VH]::
CCAGAGTGTTTTATACAGCTCCAACA
CAGTGATGTTGGGAATTATAACCTTG
GGTTCACCGTCAGTAGCAAGTTCATG
huIgG1z-CH1-E::EPKSC +
ATAAGAACTACTTAGCTTGGTACCAG
TCTCCTGGTACCAACAGCACCCAGGC
ACCTGGGTCCGCCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CAGAAACCAGGACAGCCTCCTAAGC
AAAGCCCCCAAACTCATGATTTTTGA
AGGGGCTGGAGTGGGTGTCAGTTAT
7G11VL]::huKLC-S176E +
TGCTCATTTACTGGGCATCTACCCGA
GGTCAATCAGCGGCCCTCAGGGGTTT
TTATAGCGGTGGTAAGACATACTAC
[anti-<huCD40>
GAATCCGGGGTCCCTGACCGATTCA
CTAATCGCTTCTCTGGCTCCAAGTCT
GCAGACTCCGTGAAGGGCCGATTCA
21-230_30A12VL]::
GTGGCAGCGGGTCTGGGACAGATTT
GGCACCACGGCCTCCCTGACAATCTC
CCATCTCCAGAGACAATTCCAAGAA
huLLC2-K(IgG-
CACTCTCACCATCAGCAGCCTGCAGG
TGGGCTCCAGGCTGCGGACGAGGCT
CACGCTGTATCTTCAAATGAACAGCC
Fab); LMRID:
CTGAAGATGTGGCAGTTTATTACTGT
GATTATTTCTGCTGCTCATATACAAC
TGAGAGCCGAGGACACGGCCGTGTA
SS-30848
CAGCAATATTATAGTACTCCTCCGAC
TAGTAGCACTTATGTGATCTTCGGCG
TTACTGTGCGAGAGATAGCGGTGGC
GTTCGGCCAAGGGACCAAGGTGGAG
GAGGGACCAAGCTGACCGTCCTAGG
TGGGGGTACTTTGACTACTGGGGCCA
ATCAAACGGACGGTGGCTGCACCAT
TCAGCCCAAGGCTGCACCCTCGGTCA
GGGAACCCTGGTCACCGTGTCCTCAG
CTGTCTTCATCTTCCCGCCATCTGAT
CTCTGTTCCCGCCCTCCTCTGAGGAG
CCTCCACCAAGGGCCCATCGGTCTTC
GAGCAGTTGAAATCTGGAACTGCCT
CTTCAAGCCAACAAGGCCACACTGG
CCCCTGGCACCCTCCTCCAAGAGCAC
CTGTTGTGTGCCTGCTGAATAACTTC
TGTGTCTCATCAGTGACTTCTACCCG
CTCTGGGGGCACAGCGGCCCTGGGC
TATCCCAGAGAGGCCAAAGTACAGT
GGAGCCGTGACAGTGGCCTGGAAGG
TGCCTGGTCAAGGACTACTTCCCCGA
GGAAGGTGGATAACGCCCTCCAATC
CAGATAGCAGCCCCGTCAAGGCGGG
ACCGGTGACGGTGTCGTGGAACTCA
GGGTAACTCCCAGGAGAGTGTCACA
AGTGGAAACCACCACACCCTCCAAA
GGCGCCCTGACCAGCGGCGTGCACA
GAGCAGGACAGCAAGCACAGCACCT
CAAAGCAACAACAAGTACGCGGCCA
CCTTCCCGGCTGTCCTACAGTCCTCA
ACAGCCTCGAAAGCACCCTGACGCT
AGAGCTATCTGAGCCTGACGCCTGA
GGACTCTACTCCCTCAAGAGCGTGGT
GAGCAAAGCAGACTACGAGAAACAC
GCACTGGAAGTCCCACAGAAGCTAC
GACCGTGCCCTCCAGCAGCTTGGGC
AAAGTCTACGCCTGCGAAGTCACCC
AGCTGCCAGGTCACGCATCAAGGGA
ACCCAGACCTACATCTGCAACGTGA
ATCAGGGCCTGAGCTCGCCCGTCAC
GCACCGTGGAGAAGACAGTGGCCCC
ATCACAAGCCCAGCAACACCAAGGT
AAAGAGCTTCAACAGGGGAGAGTGT
TACAGAATGTTCA
GGACAAGAAAGTTGAGCCCAAATCT
(SEQ ID NO: 821)
(SEQ ID NO: 822)
TGTGACAAAACTCACACATGCCCAC
CGTGCCCAGCACCTGAACTCCTGGG
GGGACCGTCAGTCTTCCTCTTCCCCC
CAAAACCCAAGGACACCCTCATGAT
CTCCCGGACCCCTGAGGTCACATGCG
TGGTGGTGGACGTGAGCCACGAAGA
CCCTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGTGCGAGGAGCAG
TACGGCAGCACGTACCGTTGCGTCA
GCGTCCTCACCGTCCTGCACCAGGAC
TGGCTGAATGGCAAGGAGTACAAGT
GCAAGGTGTCCAACAAAGCCCTCCC
AGCCCCCATCGAGAAAACCATCTCC
AAAGCCAAAGGGCAGCCCCGAGAAC
CACAGGTGTACACCCTGCCCCCATCC
CGGGAGGAGATGACCAAGAACCAGG
TCAGCCTGACCTGCCTGGTCAAAGGC
TTCTATCCCAGCGACATCGCCGTGGA
GTGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCCG
TGCTGGACTCCGACGGCTCCTTCTTC
CTCTATAGCAAGCTCACCGTGGACA
AGAGCAGGTGGCAGCAGGGGAACGT
CTTCTCATGCTCCGTGATGCATGAGG
CTCTGCACAACCACTACACGCAGAA
GAGCCTCTCCCTGTCTCCGGGTGGTG
GCGGATCGGGAGGTGGCGGATCCGA
GGTGCAGCTGCTGGAGTCTGGGGGA
GGCTTGGTACAGCCTGGGGGGTCCCT
GAGACTCTCCTGTGCAGCCTCTGGAT
TCACCTTTAGTAGAAATGCCATGAGT
TGGGTCCGCCAGGCTCCAGGGAAGG
GGCTGGAGTGGGTGTCAGCTACTGG
TGGTAGTGGTATTAGCACATACTACG
CAGACTCCGTGAAGGGCCGGTTCAC
CATCTCCAGAGACAATTCCAAGAAC
ACGCTGTATCTGCAAATGAACAGTCT
GAGAGCCGAGGACACGGCCGTATAT
TACTGTGCGAGAGGTTATAGCAACA
GCTGGTGGTACTTTGACTACTGGGGC
CAGGGAACCCTGGTCACCGTGTCCTC
AGCAAGCACGAAGGGGCCGTCCGTA
TTTCCGCTTGCGCCCTCGTCGAAGTC
AACTTCGGGAGGGACCGCGGCACTT
GGCTGTCTTGTCAAAGATTACTTCCC
TGAGCCAGTGACAGTCAGCTGGAAT
TCCGGTGCCCTCACGTCAGGAGTACA
TACATTCCCTGCGGTATTGCAGTCCT
CCGGACTCTACTCCCTGGAGTCGGTG
GTAACGGTGCCCAGCTCCAGCTTGG
GGACCCAGACGTACATTTGTAACGT
GAATCACAAACCAAGCAATACTAAG
GTAGATAAGAAAGTAGAACCGAAGA
GCTGC
(SEQ ID NO: 823)
AA
DIVMTQSPDSLAVSLGERATINCKSSQ
QSALTQPASVSGSPGQSITISCTGTSSD
EVQLVESGGGLIQPGGSLRLSCAVSGF
SVLYSSNNKNYLAWYQQKPGQPPKLL
VGNYNLVSWYQQHPGKAPKLMIFEV
TVSSKFMTWVRQAPGKGLEWVSVIYS
IYWASTRESGVPDRFSGSGSGTDFTLTI
NQRPSGVSNRFSGSKSGTTASLTISGLQ
GGKTYYADSVKGRFTISRDNSKNTLY
SSLQAEDVAVYYCQQYYSTPPTFGQG
AADEADYFCCSYTTSSTYVIFGGGTKL
LQMNSLRAEDTAVYYCARDSGGWGY
TKVEIKRTVAAPSVFIFPPSDEQLKSGT
TVLGQPKAAPSVTLFPPSSEELQANKA
FDYWGQGTLVTVSSASTKGPSVFPLAP
ASVVCLLNNFYPREAKVQWKVDNAL
TLVCLISDFYPGAVTVAWKADSSPVK
SSKSTSGGTAALGCLVKDYFPEPVTVS
QSGNSQESVTEQDSKDSTYSLESTLTL
AGVETTTPSKQSNNKYAAKSYLSLTPE
WNSGALTSGVHTFPAVLQSSGLYSLKS
SKADYEKHKVYACEVTHQGLSSPVTK
QWKSHRSYSCQVTHEGSTVEKTVAPT
VVTVPSSSLGTQTYICNVNHKPSNTKV
SFNRGEC
ECS
DKKVEPKSCDKTHTCPPCPAPELLGGP
(SEQ ID NO: 824)
(SEQ ID NO: 825)
SVFLFPPKPKDTLMISRTPEVTCVVVD
VSHEDPEVKFNWYVDGVEVHNAKTK
PCEEQYGSTYRCVSVLTVLHQDWLNG
KEYKCKVSNKALPAPIEKTISKAKGQP
REPQVYTLPPSREEMTKNQVSLTCLVK
GFYPSDIAVEWESNGQPENNYKTTPPV
LDSDGSFFLYSKLTVDKSRWQQGNVF
SCSVMHEALHNHYTQKSLSLSPGGGG
SGGGGSEVQLLESGGGLVQPGGSLRLS
CAASGFTFSRNAMSWVRQAPGKGLE
WVSATGGSGISTYYADSVKGRFTISRD
NSKNTLYLQMNSLRAEDTAVYYCAR
GYSNSWWYFDYWGQGTLVTVSSAST
KGPSVFPLAPSSKSTSGGTAALGCLVK
DYFPEPVTVSWNSGALTSGVHTFPAVL
QSSGLYSLESVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSC
(SEQ ID NO: 826)
iPS:
21-233_7G11_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATTGTGATGACTCAGTCTCCAGA
GACATCCAGATGACCCAGTCTCCATC
GAGGTGCAGCTGGTCGAGTCTGGAG
576237
230_33H6_Fab
7G11VH]::huIgG1zSEFL2*GK-
CTCCCTGGCTGTGTCTCTGGGCGAGA
CTCCCTGTCTGCATCTGTAGGAGACA
GAGGCTTGATCCAGCCTGGGGGGTC
K::(G4S)2::[hu anti-
GGGCCACCATCAACTGCAAGTCCAG
GAGTCACCATCACTTGCCGGGCAGG
CCTGAGACTCTCCTGTGCAGTCTCTG
<huCD40>21-230_33H6VH]::
CCAGAGTGTTTTATACAGCTCCAACA
TCAGAACATTAGCAGGCATTTAAATT
GGTTCACCGTCAGTAGCAAGTTCATG
huIgG1z-CH1-E::EPKSC +
ATAAGAACTACTTAGCTTGGTACCAG
GGTATCAGCAGAATCCAGGGAAAGC
ACCTGGGTCCGCCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CAGAAACCAGGACAGCCTCCTAAGC
CCCTAAGGTCCTGATCCATCCTGCAT
AGGGGCTGGAGTGGGTGTCAGTTAT
7G11VL]::huKLC-S176E +
TGCTCATTTACTGGGCATCTACCCGA
CCAGTTTGCCAAGTGGGGTCCCGTCA
TTATAGCGGTGGTAAGACATACTAC
[anti-<huCD40>
GAATCCGGGGTCCCTGACCGATTCA
AGGTTCAGTGGCAGTGGATCTGGGA
GCAGACTCCGTGAAGGGCCGATTCA
21-230_33H6VL]::
GTGGCAGCGGGTCTGGGACAGATTT
CAGATTTCAGTCTTACCATCAGCAGT
CCATCTCCAGAGACAATTCCAAGAA
huKLC-S176K(IgG-
CACTCTCACCATCAGCAGCCTGCAGG
CTGCAACCTGAAGATTTTGGAACTTA
CACGCTGTATCTTCAAATGAACAGCC
Fab); LMRID:
CTGAAGATGTGGCAGTTTATTACTGT
CTTCTGTCAACAGAGTTACAGTACCC
TGAGAGCCGAGGACACGGCCGTGTA
SS-30849
CAGCAATATTATAGTACTCCTCCGAC
CTCCCACTTTCGGCGGAGGGACCAA
TTACTGTGCGAGAGATAGCGGTGGC
GTTCGGCCAAGGGACCAAGGTGGAG
GGTGGAGCTCAAACGAACGGTGGCT
TGGGGGTACTTTGACTACTGGGGCCA
ATCAAACGGACGGTGGCTGCACCAT
GCACCATCTGTCTTCATCTTCCCGCC
GGGAACCCTGGTCACCGTGTCCTCAG
CTGTCTTCATCTTCCCGCCATCTGAT
ATCTGATGAGCAGTTGAAATCTGGA
CCTCCACCAAGGGCCCATCGGTCTTC
GAGCAGTTGAAATCTGGAACTGCCT
ACTGCCTCTGTTGTGTGCCTGCTGAA
CCCCTGGCACCCTCCTCCAAGAGCAC
CTGTTGTGTGCCTGCTGAATAACTTC
TAACTTCTATCCCAGAGAGGCCAAA
CTCTGGGGGCACAGCGGCCCTGGGC
TATCCCAGAGAGGCCAAAGTACAGT
GTACAGTGGAAGGTGGATAACGCCC
TGCCTGGTCAAGGACTACTTCCCCGA
GGAAGGTGGATAACGCCCTCCAATC
TCCAATCGGGTAACTCCCAGGAGAG
ACCGGTGACGGTGTCGTGGAACTCA
GGGTAACTCCCAGGAGAGTGTCACA
TGTCACAGAGCAGGACAGCAAGGAC
GGCGCCCTGACCAGCGGCGTGCACA
GAGCAGGACAGCAAGGACAGCACCT
AGCACCTACAGCCTCAAGAGCACCC
CCTTCCCGGCTGTCCTACAGTCCTCA
ACAGCCTCGAAAGCACCCTGACGCT
TGACGCTGAGCAAAGCAGACTACGA
GGACTCTACTCCCTCAAGAGCGTGGT
GAGCAAAGCAGACTACGAGAAACAC
GAAACACAAAGTCTACGCCTGCGAA
GACCGTGCCCTCCAGCAGCTTGGGC
AAAGTCTACGCCTGCGAAGTCACCC
GTCACCCATCAGGGCCTGAGCTCGCC
ACCCAGACCTACATCTGCAACGTGA
ATCAGGGCCTGAGCTCGCCCGTCAC
CGTCACAAAGAGCTTCAACAGGGGA
ATCACAAGCCCAGCAACACCAAGGT
AAAGAGCTTCAACAGGGGAGAGTGT
GAGTGT
GGACAAGAAAGTTGAGCCCAAATCT
(SEQ ID NO: 827)
(SEQ ID NO: 828)
TGTGACAAAACTCACACATGCCCAC
CGTGCCCAGCACCTGAACTCCTGGG
GGGACCGTCAGTCTTCCTCTTCCCCC
CAAAACCCAAGGACACCCTCATGAT
CTCCCGGACCCCTGAGGTCACATGCG
TGGTGGTGGACGTGAGCCACGAAGA
CCCTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGTGCGAGGAGCAG
TACGGCAGCACGTACCGTTGCGTCA
GCGTCCTCACCGTCCTGCACCAGGAC
TGGCTGAATGGCAAGGAGTACAAGT
GCAAGGTGTCCAACAAAGCCCTCCC
AGCCCCCATCGAGAAAACCATCTCC
AAAGCCAAAGGGCAGCCCCGAGAAC
CACAGGTGTACACCCTGCCCCCATCC
CGGGAGGAGATGACCAAGAACCAGG
TCAGCCTGACCTGCCTGGTCAAAGGC
TTCTATCCCAGCGACATCGCCGTGGA
GTGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCCG
TGCTGGACTCCGACGGCTCCTTCTTC
CTCTATAGCAAGCTCACCGTGGACA
AGAGCAGGTGGCAGCAGGGGAACGT
CTTCTCATGCTCCGTGATGCATGAGG
CTCTGCACAACCACTACACGCAGAA
GAGCCTCTCCCTGTCTCCGGGTGGTG
GCGGATCGGGAGGTGGCGGATCCCA
GGTGCAACTGGTGCAGTCTGGGGCT
GAAGTGAAGAAGCCTGGGGCCTCAG
TGAAGGTGTCCTGCAAGGCTTCTGGA
TACACCTTCCCCGGCTACTATATGTA
CTGGTTGCGACAGGCCCCTGGACAA
GGACTTGAGTGGATGGGATGGATCA
ACCCTGACAGTGGTGACACAAACTA
TGCACAGAAGTTTCAGGGCAGGGTC
ACCATGACCAGGGACACGTCCATCA
GCACAGCCTTTATGGAGCTGAGCAG
GCTGAGATCAGACGACACGGCCGTG
TATTACTGTGCGAGAGAGAAGCCCA
GATATTTTGACTCCTTCTACTACTAC
CTTATGGACGTCTGGGGCCAAGGGA
CCACGGTCACCGTGTCCTCAGCAAGC
ACGAAGGGGCCGTCCGTATTTCCGCT
TGCGCCCTCGTCGAAGTCAACTTCGG
GAGGGACCGCGGCACTTGGCTGTCTT
GTCAAAGATTACTTCCCTGAGCCAGT
GACAGTCAGCTGGAATTCCGGTGCC
CTCACGTCAGGAGTACATACATTCCC
TGCGGTATTGCAGTCCTCCGGACTCT
ACTCCCTGGAGTCGGTGGTAACGGT
GCCCAGCTCCAGCTTGGGGACCCAG
ACGTACATTTGTAACGTGAATCACAA
ACCAAGCAATACTAAGGTAGATAAG
AAAGTAGAACCGAAGAGCTGC
(SEQ ID NO: 829)
AA
DIVMTQSPDSLAVSLGERATINCKSSQ
DIQMTQSPSSLSASVGDRVTITCRAGQ
EVQLVESGGGLIQPGGSLRLSCAVSGF
SVLYSSNNKNYLAWYQQKPGQPPKLL
NISRHLNWYQQNPGKAPKVLIHPASSL
TVSSKFMTWVRQAPGKGLEWVSVIYS
IYWASTRESGVPDRFSGSGSGTDFTLTI
PSGVPSRFSGSGSGTDFSLTISSLQPED
GGKTYYADSVKGRFTISRDNSKNTLY
SSLQAEDVAVYYCQQYYSTPPTFGQG
FGTYFCQQSYSTPPTFGGGTKVELKRTV
LQMNSLRAEDTAVYYCARDSGGWGY
TKVEIKRTVAAPSVFIFPPSDEQLKSGT
AAPSVFIFPPSDEQLKSGTASVVCLLNN
FDYWGQGTLVTVSSASTKGPSVFPLAP
ASVVCLLNNFYPREAKVQWKVDNAL
FYPREAKVQWKVDNALQSGNSQESVT
SSKSTSGGTAALGCLVKDYFPEPVTVS
QSGNSQESVTEQDSKDSTYSLESTLTL
EQDSKDSTYSLKSTLTLSKADYEKHK
WNSGALTSGVHTFPAVLQSSGLYSLKS
SKADYEKHKVYACEVTHQGLSSPVTK
VYACEVTHQGLSSPVTKSFNRGEC
VVTVPSSSLGTQTYICNVNHKPSNTKV
SFNRGEC
(SEQ ID NO: 831)
DKKVEPKSCDKTHTCPPCPAPELLGGP
(SEQ ID NO: 830)
SVFLFPPKPKDTLMISRTPEVTCVVVD
VSHEDPEVKFNWYVDGVEVHNAKTK
PCEEQYGSTYRCVSVLTVLHQDWLNG
KEYKCKVSNKALPAPIEKTISKAKGQP
REPQVYTLPPSREEMTKNQVSLTCLVK
GFYPSDIAVEWESNGQPENNYKTTPPV
LDSDGSFFLYSKLTVDKSRWQQGNVF
SCSVMHEALHNHYTQKSLSLSPGGGG
SGGGGSQVQLVQSGAEVKKPGASVKV
SCKASGYTFPGYYMYWLRQAPGQGL
EWMGWINPDSGDTNYAQKFQGRVTM
TRDTSISTAFMELSRLRSDDTAVYYCA
REKPRYFDSFYYYLMDVWGQGTTVT
VSSASTKGPSVFPLAPSSKSTSGGTAAL
GCLVKDYFPEPVTVSWNSGALTSGVH
TFPAVLQSSGLYSLESVVTVPSSSLGTQ
TYICNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 832)
iPS:
21-233_7G11_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATTGTGATGACTCAGTCTCCAGA
CAGGCTGTGCCGACTCAGCCCTCTTC
GAGGTGCAGCTGGTCGAGTCTGGAG
576240
230_33H9_Fab
7G11VH]::huIgG1zSEFL2*GK-
CTCCCTGGCTGTGTCTCTGGGCGAGA
CCTCTCTGCATCTCCTGGAGCATCAG
GAGGCTTGATCCAGCCTGGGGGGTC
K::(G4S)2::[hu anti-
GGGCCACCATCAACTGCAAGTCCAG
CCAGTCTCACCTGCACCTTACGCAGT
CCTGAGACTCTCCTGTGCAGTCTCTG
<huCD40>21-230_33H9VH]::
CCAGAGTGTTTTATACAGCTCCAACA
GGCATCAATGTTGGTTCCTCCAGGAT
GGTTCACCGTCAGTAGCAAGTTCATG
huIgG1z-CH1-E::EPKSC +
ATAAGAACTACTTAGCTTGGTACCAG
CTATTGGTACCAGCAGAAGCCAGGG
ACCTGGGTCCGCCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CAGAAACCAGGACAGCCTCCTAAGC
AGTCCTCCCCAGTTTCTCCTGAGGTA
AGGGGCTGGAGTGGGTGTCAGTTAT
7G11VL]::huKLC-S176E +
TGCTCATTTACTGGGCATCTACCCGA
CACATCAGACTCAGATAAATTGCAG
TTATAGCGGTGGTAAGACATACTAC
[anti-<huCD40>
GAATCCGGGGTCCCTGACCGATTCA
GGCTCTGGAGTCCCCAGCCGCTTCTC
GCAGACTCCGTGAAGGGCCGATTCA
21-230_33H9VL]::
GTGGCAGCGGGTCTGGGACAGATTT
TGGATCCAAAGATGCTTCGGCCAAT
CCATCTCCAGAGACAATTCCAAGAA
huLLC2-K(IgG-
CACTCTCACCATCAGCAGCCTGCAGG
GCAGGACTTTTACTCATCTCTGGGCT
CACGCTGTATCTTCAAATGAACAGCC
Fab); LMRID:
CTGAAGATGTGGCAGTTTATTACTGT
CCAGTCTGAGGATGAGGCTGACTATT
TGAGAGCCGAGGACACGGCCGTGTA
SS-30850
CAGCAATATTATAGTACTCCTCCGAC
ACTGTATGATTTGGCACAGCAGCGCT
TTACTGTGCGAGAGATAGCGGTGGC
GTTCGGCCAAGGGACCAAGGTGGAG
GTGGTATTCGGCGGAGGGACCAAAC
TGGGGGTACTTTGACTACTGGGGCCA
ATCAAACGGACGGTGGCTGCACCAT
TGACCGTCCTAGGTCAGCCCAAGGCT
GGGAACCCTGGTCACCGTGTCCTCAG
CTGTCTTCATCTTCCCGCCATCTGAT
GCACCCTCGGTCACTCTGTTCCCGCC
CCTCCACCAAGGGCCCATCGGTCTTC
GAGCAGTTGAAATCTGGAACTGCCT
CTCCTCTGAGGAGCTTCAAGCCAACA
CCCCTGGCACCCTCCTCCAAGAGCAC
CTGTTGTGTGCCTGCTGAATAACTTC
AGGCCACACTGGTGTGTCTCATCAGT
CTCTGGGGGCACAGCGGCCCTGGGC
TATCCCAGAGAGGCCAAAGTACAGT
GACTTCTACCCGGGAGCCGTGACAG
TGCCTGGTCAAGGACTACTTCCCCGA
GGAAGGTGGATAACGCCCTCCAATC
TGGCCTGGAAGGCAGATAGCAGCCC
ACCGGTGACGGTGTCGTGGAACTCA
GGGTAACTCCCAGGAGAGTGTCACA
CGTCAAGGCGGGAGTGGAAACCACC
GGCGCCCTGACCAGCGGCGTGCACA
GAGCAGGACAGCAAGGACAGCACCT
ACACCCTCCAAACAAAGCAACAACA
CCTTCCCGGCTGTCCTACAGTCCTCA
ACAGCCTCGAAAGCACCCTGACGCT
AGTACGCGGCCAAGAGCTATCTGAG
GGACTCTACTCCCTCAAGAGCGTGGT
GAGCAAAGCAGACTACGAGAAACAC
CCTGACGCCTGAGCAGTGGAAGTCC
GACCGTGCCCTCCAGCAGCTTGGGC
AAAGTCTACGCCTGCGAAGTCACCC
CACAGAAGCTACAGCTGCCAGGTCA
ACCCAGACCTACATCTGCAACGTGA
ATCAGGGCCTGAGCTCGCCCGTCAC
CGCATGAAGGGAGCACCGTGGAGAA
ATCACAAGCCCAGCAACACCAAGGT
AAAGAGCTTCAACAGGGGAGAGTGT
GACAGTGGCCCCTACAGAATGTTCA
GGACAAGAAAGTTGAGCCCAAATCT
(SEQ ID NO: 833)
(SEQ ID NO: 834)
TGTGACAAAACTCACACATGCCCAC
CGTGCCCAGCACCTGAACTCCTGGG
GGGACCGTCAGTCTTCCTCTTCCCCC
CAAAACCCAAGGACACCCTCATGAT
CTCCCGGACCCCTGAGGTCACATGCG
TGGTGGTGGACGTGAGCCACGAAGA
CCCTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGTGCGAGGAGCAG
TACGGCAGCACGTACCGTTGCGTCA
GCGTCCTCACCGTCCTGCACCAGGAC
TGGCTGAATGGCAAGGAGTACAAGT
GCAAGGTGTCCAACAAAGCCCTCCC
AGCCCCCATCGAGAAAACCATCTCC
AAAGCCAAAGGGCAGCCCCGAGAAC
CACAGGTGTACACCCTGCCCCCATCC
CGGGAGGAGATGACCAAGAACCAGG
TCAGCCTGACCTGCCTGGTCAAAGGC
TTCTATCCCAGCGACATCGCCGTGGA
GTGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCCG
TGCTGGACTCCGACGGCTCCTTCTTC
CTCTATAGCAAGCTCACCGTGGACA
AGAGCAGGTGGCAGCAGGGGAACGT
CTTCTCATGCTCCGTGATGCATGAGG
CTCTGCACAACCACTACACGCAGAA
GAGCCTCTCCCTGTCTCCGGGTGGTG
GCGGATCGGGAGGTGGCGGATCCCA
GGTGCAGTTGGTGGAGTCTGGGGGA
GGCGTGGTCCAGCCTGGGAGGTCCC
TGAGACTCTCCTGTGCAGCGTCTGGA
TTCACCTTCAGTAGCCATGGCATGCA
CTGGGTCCGCCAACCTCCAGGCAAG
GGGCTGGAGTGGGTGGCAGTTATCT
GGTATGATGGAAGTAATGAATACTA
TGGAGACTCCGTGAAGGGCCGATTC
ACCATCTCCAGAGACAATTCCAAGA
ACACGCTGTATCTGCAAATGAACAG
CCTGAGAGTCGAGGACACGGCTGTG
TATTACTGTACGAGAGGGGGGGGCC
ACTGGAACTACGAGGGCCACTACTA
TGGTATGGACGTCTGGGGCCAAGGG
ACCACGGTCACCGTGTCCTCAGCAA
GCACGAAGGGGCCGTCCGTATTTCC
GCTTGCGCCCTCGTCGAAGTCAACTT
CGGGAGGGACCGCGGCACTTGGCTG
TCTTGTCAAAGATTACTTCCCTGAGC
CAGTGACAGTCAGCTGGAATTCCGG
TGCCCTCACGTCAGGAGTACATACAT
TCCCTGCGGTATTGCAGTCCTCCGGA
CTCTACTCCCTGGAGTCGGTGGTAAC
GGTGCCCAGCTCCAGCTTGGGGACC
CAGACGTACATTTGTAACGTGAATCA
CAAACCAAGCAATACTAAGGTAGAT
AAGAAAGTAGAACCGAAGAGCTGC
(SEQ ID NO: 835)
AA
DIVMTQSPDSLAVSLGERATINCKSSQ
QAVPTQPSSLSASPGASASLTCTLRSGI
EVQLVESGGGLIQPGGSLRLSCAVSGF
SVLYSSNNKNYLAWYQQKPGQPPKLL
NVGSSRIYWYQQKPGSPPQFLLRYTSD
TVSSKFMTWVRQAPGKGLEWVSVIYS
IYWASTRESGVPDRFSGSGSGTDFTLTI
SDKLQGSGVPSRFSGSKDASANAGLLL
GGKTYYADSVKGRFTISRDNSKNTLY
SSLQAEDVAVYYCQQYYSTPPTFGQG
ISGLQSEDEADYYCMIWHSSAVVFGG
LQMNSLRAEDTAVYYCARDSGGWGY
TKVEIKRTVAAPSVFIFPPSDEQLKSGT
GTKLTVLGQPKAAPSVTLFPPSSEELQ
FDYWGQGTLVTVSSASTKGPSVFPLAP
ASVVCLLNNFYPREAKVQWKVDNAL
ANKATLVCLISDFYPGAVTVAWKADS
SSKSTSGGTAALGCLVKDYFPEPVTVS
QSGNSQESVTEQDSKDSTYSLESTLTL
SPVKAGVETTTPSKQSNNKYAAKSYL
WNSGALTSGVHTFPAVLQSSGLYSLKS
SKADYEKHKVYACEVTHQGLSSPVTK
SLTPEQWKSHRSYSCQVTHEGSTVEKT
VVTVPSSSLGTQTYICNVNHKPSNTKV
SFNRGEC
VAPTECS
DKKVEPKSCDKTHTCPPCPAPELLGGP
(SEQ ID NO: 836)
(SEQ ID NO: 837)
SVFLFPPKPKDTLMISRTPEVTCVVVD
VSHEDPEVKFNWYVDGVEVHNAKTK
PCEEQYGSTYRCVSVLTVLHQDWLNG
KEYKCKVSNKALPAPIEKTISKAKGQP
REPQVYTLPPSREEMTKNQVSLTCLVK
GFYPSDIAVEWESNGQPENNYKTTPPV
LDSDGSFFLYSKLTVDKSRWQQGNVF
SCSVMHEALHNHYTQKSLSLSPGGGG
SGGGGSQVQLVESGGGVVQPGRSLRL
SCAASGFTFSSHGMHWVRQPPGKGLE
WVAVIWYDGSNEYYGDSVKGRFTISR
DNSKNTLYLQMNSLRVEDTAVYYCTR
GGGHWNYEGHYYGMDVWGQGTTVT
VSSASTKGPSVFPLAPSSKSTSGGTAAL
GCLVKDYFPEPVTVSWNSGALTSGVH
TFPAVLQSSGLYSLESVVTVPSSSLGTQ
TYICNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 838)
iPS:
21-233_7G11_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATTGTGATGACTCAGTCTCCAGA
CAGTCTGCCCTGACTCAGCCTCGCTC
GAGGTGCAGCTGGTCGAGTCTGGAG
576243
230_35F11_Fab
7G11VH]::huIgG1zSEFL2*GK-
CTCCCTGGCTGTGTCTCTGGGCGAGA
AGTGTCCGGGAGCCCTGGACAGTCA
GAGGCTTGATCCAGCCTGGGGGGTC
K::(G4S)2::[hu anti-
GGGCCACCATCAACTGCAAGTCCAG
GTCACCATCTCCTGCACTGGAACCAG
CCTGAGACTCTCCTGTGCAGTCTCTG
<huCD40>21-230_35F11VH]::
CCAGAGTGTTTTATACAGCTCCAACA
CAGTGATGTTGGTGGTTATATCTTTG
GGTTCACCGTCAGTAGCAAGTTCATG
huIgG1z-CH1-E::EPKSC +
ATAAGAACTACTTAGCTTGGTACCAG
TCTCCTGGTACCAACAACACCCAGGC
ACCTGGGTCCGCCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CAGAAACCAGGACAGCCTCCTAAGC
AAAGCCCCCAAACTCATGATTTATGA
AGGGGCTGGAGTGGGTGTCAGTTAT
7G11VL]::huKLC-S176E +
TGCTCATTTACTGGGCATCTACCCGA
TGTCAGTAAGCGGCCCTCTGGGGTCC
TTATAGCGGTGGTAAGACATACTAC
[anti-<huCD40>
GAATCCGGGGTCCCTGACCGATTCA
CTGATCGCTTCTCTGGCTCCAAGTCT
GCAGACTCCGTGAAGGGCCGATTCA
21-230_35F11VL]::
GTGGCAGCGGGTCTGGGACAGATTT
GTCAACACGGCCTCCCTGACCATCTC
CCATCTCCAGAGACAATTCCAAGAA
huLLC2-K(IgG-
CACTCTCACCATCAGCAGCCTGCAGG
TGGGCTCCAGGCTGAGGATGAGACT
CACGCTGTATCTTCAAATGAACAGCC
Fab); LMRID:
CTGAAGATGTGGCAGTTTATTACTGT
GATTATTACTGCTGCTCATATGCAGG
TGAGAGCCGAGGACACGGCCGTGTA
SS-30851
CAGCAATATTATAGTACTCCTCCGAC
CAACTACACTTATGTCTTCGGAACTG
TTACTGTGCGAGAGATAGCGGTGGC
GTTCGGCCAAGGGACCAAGGTGGAG
GGACCAAGGTCACCGTCCTAGGTCA
TGGGGGTACTTTGACTACTGGGGCCA
ATCAAACGGACGGTGGETGCACCAT
GCCCAAGGCTGCACCCTCGGTCACTC
GGGAACCCTGGTCACCGTGTCCTCAG
CTGTCTTCATCTTCCCGCCATCTGAT
TGTTCCCGCCCTCCTCTGAGGAGCTT
CCTCCACCAAGGGCCCATCGGTCTTC
GAGCAGTTGAAATCTGGAACTGCCT
CAACCCAACAAGGCCACACTGGTGT
CCCCTGGCACCCTCCTCCAAGAGCAC
CTGTTGTGTGCCTGCTGAATAACTTC
GTCTCATCAGTGACTTCTACCCGGGA
CTCTGGGGGCACAGCGGCCCTGGGC
TATCCCAGAGAGGCCAAAGTACAGT
GCCGTGACAGTGGCCTGGAAGGCAG
TGCCTGGTCAAGGACTACTTCCCCGA
GGAAGGTGGATAACGCCCTCCAATC
ATAGCAGCCCCGTCAAGGCGGGAGT
ACCGGTGACGGTGTCGTGGAACTCA
GGGTAACTCCCAGGAGAGTGTCACA
GGAAACCACCACACCCTCCAAACAA
GGCGCCCTGACCAGCGGCGTGCACA
GAGCAGGACAGCAAGCACAGCACCT
AGCAACAACAAGTACGCGGCCAAGA
CCTTCCCGGCTGTCCTACAGTCCTCA
ACAGCCTCGAAAGCACCCTGACGCT
GCTATCTGAGCCTGACGCCTGAGCA
GGACTCTACTCCCTCAAGAGCGTGGT
GAGCAAAGCAGACTACGAGAAACAC
GTGGAAGTCCCACAGAAGCTACAGC
GACCGTGCCCTCCAGCAGCTTGGGC
AAAGTCTACGCCTGCGAAGTCACCC
TGCCAGGTCACGCATGAAGGGAGCA
ACCCAGACCTACATCTGCAACGTGA
ATCAGGGCCTGAGCTCGCCCGTCAC
CCGTGGAGAAGACAGTGGCCCCTAC
ATCACAAGCCCAGCAACACCAAGGT
AAAGAGCTTCAACAGGGGAGAGTGT
AGAATGTTCA
GGACAAGAAAGTTGAGCCCAAATCT
(SEQ ID NO: 839)
(SEQ ID NO: 840)
TGTGACAAAACTCACACATGCCCAC
CGTGCCCAGCACCTGAACTCCTGGG
GGGACCGTCAGTCTTCCTCTTCCCCC
CAAAACCCAAGGACACCCTCATGAT
CTCCCGGACCCCTGAGGTCACATGCG
TGGTGGTGGACGTGAGCCACGAAGA
CCCTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGTGCGAGGAGCAG
TACGGCAGCACGTACCGTTGCGTCA
GCGTCCTCACCGTCCTGCACCAGGAC
TGGCTGAATGGCAAGGAGTACAAGT
GCAAGGTGTCCAACAAAGCCCTCCC
AGCCCCCATCGAGAAAACCATCTCC
AAAGCCAAAGGGCAGCCCCGAGAAC
CACAGGTGTACACCCTGCCCCCATCC
CGGGAGGAGATGACCAAGAACCAGG
TCAGCCTGACCTGCCTGGTCAAAGGC
TTCTATCCCAGCGACATCGCCGTGGA
GTGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCCG
TGCTGGACTCCGACGGCTCCTTCTTC
CTCTATAGCAAGCTCACCGTGGACA
AGAGCAGGTGGCAGCAGGGGAACGT
CTTCTCATGCTCCGTGATGCATGAGG
CTCTGCACAACCACTACACGCAGAA
GAGCCTCTCCCTGTCTCCGGGTGGTG
GCGGATCGGGAGGTGGCGGATCCCA
GGTGCAGCTGGTGGAGTCTGGGGGA
GGCGTGGTCCAGCCTGGGAGGTCCC
TGAGACTCTCCTGTGCAGCGTCTGGA
TTCACCCTCAGTAGCTATGGCATGCA
CTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCAGTTATCT
GGTATGATGGAAGTAATAAATACTA
TGCAGACTCCGTGAAGGGCCGAGTC
ACCATCTCCAGAGACAATTCCAAGA
ACACGCTGTATCTGCAAATGAATAG
CCTGAGAGCCGAGGACACGGCTGTG
TATTACTGTACGAGAGATGGCCGGA
ACTACGTCTACTTTGACAACTGGGGC
CAGGGAACCCTGGTCACCGTGTCCTC
AGCAAGCACGAAGGGGCCGTCCGTA
TTTCCGCTTGCGCCCTCGTCGAAGTC
AACTTCGGGAGGGACCGCGGCACTT
GGCTGTCTTGTCAAAGATTACTTCCC
TGAGCCAGTGACAGTCAGCTGGAAT
TCCGGTGCCCTCACGTCAGGAGTACA
TACATTCCCTGCGGTATTGCAGTCCT
CCGGACTCTACTCCCTGGAGTCGGTG
GTAACGGTGCCCAGCTCCAGCTTGG
GGACCCAGACGTACATTTGTAACGT
GAATCACAAACCAAGCAATACTAAG
GTAGATAAGAAAGTAGAACCGAAGA
GCTGC
(SEQ ID NO: 841)
AA
DIVMTQSPDSLAVSLGERATINCKSSQ
QSALTQPRSVSGSPGQSVTISCTGTSSD
EVQLVESGGGLIQPGGSLRLSCAVSGF
SVLYSSNNKNYLAWYQQKPGQPPKLL
VGGYIFVSWYQQHPGKAPKLMIYDVS
TVSSKFMTWVRQAPGKGLEWVSVIYS
IYWASTRESGVPDRFSGSGSGTDFTLTI
KRPSGVPDRFSGSKSVNTASLTISGLQ
GGKTYYADSVKGRFTISRDNSKNTLY
SSLQAEDVAVYYCQQYYSTPPTFGQG
AEDETDYYCCSYAGNYTYVFGTGTKV
LQMNSLRAEDTAVYYCARDSGGWGY
TKVEIKRTVAAPSVFIFPPSDEQLKSGT
TVLGQPKAAPSVTLFPPSSEELQANKA
FDYWGQGTLVTVSSASTKGPSVFPLAP
ASVVCLLNNFYPREAKVQWKVDNAL
TLVCLISDFYPGAVTVAWKADSSPVK
SSKSTSGGTAALGCLVKDYFPEPVTVS
QSGNSQESVTEQDSKDSTYSLESTLTL
AGVETTTPSKQSNNKYAAKSYLSLTPE
WNSGALTSGVHTFPAVLQSSGLYSLKS
SKADYEKHKVYACEVTHQGLSSPVTK
QWKSHRSYSCQVTHEGSTVEKTVAPT
VVTVPSSSLGTQTYICNVNHKPSNTKV
SFNRGEC
ECS
DKKVEPKSCDKTHTCPPCPAPELLGGP
(SEQ ID NO: 842)
(SEQ ID NO: 843)
SVFLFPPKPKDTLMISRTPEVTCVVVD
VSHEDPEVKFNWYVDGVEVHNAKTK
PCEEQYGSTYRCVSVLTVLHQDWLNG
KEYKCKVSNKALPAPIEKTISKAKGQP
REPQVYTLPPSREEMTKNQVSLTCLVK
GFYPSDIAVEWESNGQPENNYKTTPPV
LDSDGSFFLYSKLTVDKSRWQQGNVF
SCSVMHEALHNHYTQKSLSLSPGGGG
SGGGGSQVQLVESGGGVVQPGRSLRL
SCAASGFTLSSYGMHWVRQAPGKGLE
WVAVIWYDGSNKYYADSVKGRVTISR
DNSKNTLYLQMNSLRAEDTAVYYCTR
DGRNYVYFDNWGQGTLVTVSSASTK
GPSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAVLQ
SSGLYSLESVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSC
(SEQ ID NO: 844)
iPS:
21-233_7G11_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATTGTGATGACTCAGTCTCCAGA
GAAATTGTGTTGACGCAGTCTCCAGG
GAGGTGCAGCTGGTCGAGTCTGGAG
576246
230_36F3_Fab
7G11VH]::huIgG1zSEFL2*GK-
CTCCCTGGCTGTGTCTCTGGGCGAGA
CACCCTGTCTTTGTCTCCAGGGGAAA
GAGGCTTGATCCAGCCTGGGGGGTC
K::(G4S)2::[hu anti-
GGGCCACCATCAACTGCAAGTCCAG
GAGCCACCCTCTCCTGCAGGGCCAGT
CCTGAGACTCTCCTGTGCAGTCTCTG
<huCD40>21-230_36F3VH]::
CCAGAGTGTTTTATACAGCTCCAACA
CAGAGTGTTAGCAGCAACTACTTAG
GGTTCACCGTCAGTAGCAAGTTCATG
huIgG1z-CH1-E::EPKSC +
ATAAGAACTACTTAGCTTGGTACCAG
CCTGGTACCAACAGAAACCTGGCCA
ACCTGGGTCCGCCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CAGAAACCAGGACAGCCTCCTAAGC
GGCTCCCAGGGCCCTTATCTATGCTG
AGGGGCTGGAGTGGGTGTCAGTTAT
7G11VL]::huKLC-S176E +
TGCTCATTTACTGGGCATCTACCCGA
CATCCAACAGGGCCGCTGGCATCTC
TTATAGCGGTGGTAAGACATACTAC
[anti-<huCD40>
GAATCCGGGGTCCCTGACCGATTCA
AGACAGGTTCAGTGGCAGTGGGTCT
GCAGACTCCGTGAAGGGCCGATTCA
21-230_36F3VL]::
GTGGCAGCGGGTCTGGGACAGATTT
GGGACAGACTTCACTCTCACCATCAG
CCATCTCCAGAGACAATTCCAAGAA
huKLC-S176K(IgG-
CACTCTCACCATCAGCAGCCTGCAGG
CAGACTGGAGCCTGAAGATTTTGCA
CACGCTGTATCTTCAAATGAACAGCC
Fab); LMRID:
CTGAAGATGTGGCAGTTTATTACTGT
GTGTATTTCTGTCAGCAGTATGGTAG
TGAGAGCCGAGGACACGGCCGTGTA
SS-30852
CAGCAATATTATAGTACTCCTCCGAC
CTCACCGCTCACTTTCGGCGGAGGGA
TTACTGTGCGAGAGATAGCGGTGGC
GTTCGGCCAAGGGACCAAGGTGGAG
CTAAGGTGGAGATCAAACGAACGGT
TGGGGGTACTTTGACTACTGGGGCCA
ATCAAACGGACGGTGGCTGCACCAT
GGCTGCACCATCTGTCTTCATCTTCC
GGGAACCCTGGTCACCGTGTCCTCAG
CTGTCTTCATCTTCCCGCCATCTGAT
CGCCATCTGATGAGCAGTTGAAATCT
CCTCCACCAAGGGCCCATCGGTCTTC
GAGCAGTTGAAATCTGGAACTGCCT
GGAACTGCCTCTGTTGTGTGCCTGCT
CCCCTGGCACCCTCCTCCAAGAGCAC
CTGTTGTGTGCCTGCTGAATAACTTC
GAATAACTTCTATCCCAGAGAGGCC
CTCTGGGGGCACAGCGGCCCTGGGC
TATCCCAGAGAGGCCAAAGTACAGT
AAAGTACAGTGGAAGGTGGATAACG
TGCCTGGTCAAGGACTACTTCCCCGA
GGAAGGTGGATAACGCCCTCCAATC
CCCTCCAATCGGGTAACTCCCAGGA
ACCGGTGACGGTGTCGTGGAACTCA
GGGTAACTCCCAGGAGAGTGTCACA
GAGTGTCACAGAGCAGGACAGCAAG
GGCGCCCTGACCAGCGGCGTGCACA
GAGCAGGACAGCAAGGACAGCACCT
GACAGCACCTACAGCCTCAAGAGCA
CCTTCCCGGCTGTCCTACAGTCCTCA
ACAGCCTCGAAAGCACCCTGACGCT
CCCTGACGCTGAGCAAAGCAGACTA
GGACTCTACTCCCTCAAGAGCGTGGT
GAGCAAAGCAGACTACGAGAAACAC
CGAGAAACACAAAGTCTACGCCTGC
GACCGTGCCCTCCAGCAGCTTGGGC
AAAGTCTACGCCTGCGAAGTCACCC
GAAGTCACCCATCAGGGCCTGAGCT
ACCCAGACCTACATCTGCAACGTGA
ATCAGGGCCTGAGCTCGCCCGTCAC
CGCCCGTCACAAAGAGCTTCAACAG
ATCACAAGCCCAGCAACACCAAGGT
AAAGAGCTTCAACAGGGGAGAGTGT
GGGAGAGTGT
GGACAAGAAAGTTGAGCCCAAATCT
(SEQ ID NO: 845)
(SEQ ID NO: 846)
TGTGACAAAACTCACACATGCCCAC
CGTGCCCAGCACCTGAACTCCTGGG
GGGACCGTCAGTCTTCCTCTTCCCCC
CAAAACCCAAGGACACCCTCATGAT
CTCCCGGACCCCTGAGGTCACATGCG
TGGTGGTGGACGTGAGCCACGAAGA
CCCTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGTGCGAGGAGCAG
TACGGCAGCACGTACCGTTGCGTCA
GCGTCCTCACCGTCCTGCACCAGGAC
TGGCTGAATGGCAAGGAGTACAAGT
GCAAGGTGTCCAACAAAGCCCTCCC
AGCCCCCATCGAGAAAACCATCTCC
AAAGCCAAAGGGCAGCCCCGAGAAC
CACAGGTGTACACCCTGCCCCCATCC
CGGGAGGAGATGACCAAGAACCAGG
TCAGCCTGACCTGCCTGGTCAAAGGC
TTCTATCCCAGCGACATCGCCGTGGA
GTGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCCG
TGCTGGACTCCGACGGCTCCTTCTTC
CTCTATAGCAAGCTCACCGTGGACA
AGAGCAGGTGGCAGCAGGGGAACGT
CTTCTCATGCTCCGTGATGCATGAGG
CTCTGCACAACCACTACACGCAGAA
GAGCCTCTCCCTGTCTCCGGGTGGTG
GCGGATCGGGAGGTGGCGGATCCCA
GGTACAGCTGCAACAGTCAGGTCCA
GGACTGGTGAAGCCCTCGCAGACCC
TCTCACTCACCTGTGCCATCTCCGGG
GACAGTGTCTCTAGCAGCCGTACTGC
TTGGAACTGGATCAGGCAGTCCCCAT
CGAGAGGCCTTGAGTGGCTGGGAAG
GACATACTACAGGTCCAAGTGGTAT
CATGATTATTCAGTATCTGTGAAAAG
TCGAATCACCATCGACCCAGACACA
TCCAAGAACCAGTTCTCCCTGCAGCT
GAACTCTGTGACTCCCGAGGACACG
GCTGTTTATTATTGTGCAAGAGGGGC
TGCTCCCTTTGACTACTGGGGCCAGG
GAACCCTGGTCACCGTGTCCTCAGCA
AGCACGAAGGGGCCGTCCGTATTTC
CGCTTGCGCCCTCGTCGAAGTCAACT
TCGGGAGGGACCGCGGCACTTGGCT
GTCTTGTCAAAGATTACTTCCCTGAG
CCAGTGACAGTCAGCTGGAATTCCG
GTGCCCTCACGTCAGGAGTACATAC
ATTCCCTGCGGTATTGCAGTCCTCCG
GACTCTACTCCCTGGAGTCGGTGGTA
ACGGTGCCCAGCTCCAGCTTGGGGA
CCCAGACGTACATTTGTAACGTGAAT
CACAAACCAAGCAATACTAAGGTAG
ATAAGAAAGTAGAACCGAAGAGCTG
C
(SEQ ID NO: 847)
AA
DIVMTQSPDSLAVSLGERATINCKSSQ
EIVLTQSPGTLSLSPGERATLSCRASQS
EVQLVESGGGLIQPGGSLRLSCAVSGF
SVLYSSNNKNYLAWYQQKPGQPPKLL
VSSNYLAWYQQKPGQAPRALIYAASN
TVSSKFMTWVRQAPGKGLEWVSVIYS
IYWASTRESGVPDRFSGSGSGTDFTLTI
RAAGISDRFSGSGSGTDFTLTISRLEPE
GGKTYYADSVKGRFTISRDNSKNTLY
SSLQAEDVAVYYCQQYYSTPPTFGQG
DFAVYFCQQYGSSPLTFGGGTKVEIKR
LQMNSLRAEDTAVYYCARDSGGWGY
TKVEIKRTVAAPSVFIFPPSDEQLKSGT
TVAAPSVFIFPPSDEQLKSGTASVVCLL
FDYWGQGTLVTVSSASTKGPSVFPLAP
ASVVCLLNNFYPREAKVQWKVDNAL
NNFYPREAKVQWKVDNALQSGNSQE
SSKSTSGGTAALGCLVKDYFPEPVTVS
QSGNSQESVTEQDSKDSTYSLESTLTL
SVTEQDSKDSTYSLKSTLTLSKADYEK
WNSGALTSGVHTFPAVLQSSGLYSLKS
SKADYEKHKVYACEVTHQGLSSPVTK
HKVYACEVTHQGLSSPVTKSFNRGEC
VVTVPSSSLGTQTYICNVNHKPSNTKV
SFNRGEC
(SEQ ID NO: 849)
DKKVEPKSCDKTHTCPPCPAPELLGGP
(SEQ ID NO: 848)
SVFLFPPKPKDTLMISRTPEVTCVVVD
VSHEDPEVKFNWYVDGVEVHNAKTK
PCEEQYGSTYRCVSVLTVLHQDWLNG
KEYKCKVSNKALPAPIEKTISKAKGQP
REPQVYTLPPSREEMTKNQVSLTCLVK
GFYPSDIAVEWESNGQPENNYKTTPPV
LDSDGSFFLYSKLTVDKSRWQQGNVF
SCSVMHEALHNHYTQKSLSLSPGGGG
SGGGGSQVQLQQSGPGLVKPSQTLSLT
CAISGDSVSSSRTAWNWIRQSPSRGLE
WLGRTYYRSKWYHDYSVSVKSRITID
PDTSKNQFSLQLNSVTPEDTAVYYCAR
GAAPFDYWGQGTLVTVSSASTKGPSV
FPLAPSSKSTSGGTAALGCLVKDYFPE
PVTVSWNSGALTSGVHTFPAVLQSSGL
YSLESVVTVPSSSLGTQTYICNVNHKP
SNTKVDKKVEPKSC
(SEQ ID NO: 850)
iPS:
21-233_7G11_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATTGTGATGACTCAGTCTCCAGA
TCCTATGAGCTGACTCAGCCACCCTC
GAGGTGCAGCTGGTCGAGTCTGGAG
576249
230_37A6_Fab
7G11VH]::huIgG1zSEFL2*GK-
CTCCCTGGCTGTGTCTCTGGGCGAGA
AGTGTCCGTGTCCCCAGGACAGACA
GAGGCTTGATCCAGCCTGGGGGGTC
K::(G4S)2::[hu anti-
GGGCCACCATCAACTGCAAGTCCAG
GCCAGCATCACCTGCTCTGGAGAAA
CCTGAGACTCTCCTGTGCAGTCTCTG
<huCD40>21-230_37A6VH]::
CCAGAGTGTTTTATACAGCTCCAACA
GGTTGGGAAATAAATATATTTGCTGG
GGTTCACCGTCAGTAGCAAGTTCATG
huIgG1z-CH1-E::EPKSC +
ATAAGAACTACTTAGCTTGGTACCAG
TATCAGCAGAAGCCAGGCCAGTCCC
ACCTGGGTCCGCCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CAGAAACCAGGACAGCCTCCTAAGC
CTGTTCTGGTCATCTATCAAGATTTC
AGGGGCTGGAGTGGGTGTCAGTTAT
7G11VL]::huKLC-S176E +
TGCTCATTTACTGGGCATCTACCCGA
AAGCGGCCCTCAGGGATCCCTGAGC
TTATAGCGGTGGTAAGACATACTAC
[anti-<huCD40>
GAATCCGGGGTCCCTGACCGATTCA
GATTCTCTGGCTCCAACTCTGGGATC
GCAGACTCCGTGAAGGGCCGATTCA
21-230_37A6VL]::
GTGGCAGCGGGTCTGGGACAGATTT
ACAGCCACTCTGACCATCAGCGGGA
CCATCTCCAGAGACAATTCCAAGAA
huLLC2-K(IgG-
CACTCTCACCATCAGCAGCCTGCAGG
CCCAGGCTATGGATGAGGCTGACTA
CACGCTGTATCTTCAAATGAACAGCC
Fab); LMRID:
CTGAAGATGTGGCAGTTTATTACTGT
TTACTGTCAGGCGTGGGACAGCAGA
TGAGAGCCGAGGACACGGCCGTGTA
SS-30853
CAGCAATATTATAGTACTCCTCCGAC
ACTGTGGTATTCGGCGGAGGGACCA
TTACTGTGCGAGAGATAGCGGTGGC
GTTCGGCCAAGGGACCAAGGTGGAG
AGCTGACCGTCCTAGGTCAGCCCAA
TGGGGGTACTTTGACTACTGGGGCCA
ATCAAACGGACGGTGGCTGCACCAT
GGCTGCACCCTCGGTCACTCTGTTCC
GGGAACCCTGGTCACCGTGTCCTCAG
CTGTCTTCATCTTCCCGCCATCTGAT
CGCCCTCCTCTGAGGAGCTTCAAGCC
CCTCCACCAAGGGCCCATCGGTCTTC
GAGCAGTTGAAATCTGGAACTGCCT
AACAAGGCCACACTGGTGTGTCTCAT
CCCCTGGCACCCTCCTCCAAGAGCAC
CTGTTGTGTGCCTGCTGAATAACTTC
CAGTGACTTCTACCCGGGAGCCGTG
CTCTGGGGGCACAGCGGCCCTGGGC
TATCCCAGAGAGGCCAAAGTACAGT
ACAGTGGCCTGGAAGGCAGATAGCA
TGCCTGGTCAAGGACTACTTCCCCGA
GGAAGGTGGATAACGCCCTCCAATC
GCCCCGTCAAGGCGGGAGTGGAAAC
ACCGGTGACGGTGTCGTGGAACTCA
GGGTAACTCCCAGGAGAGTGTCACA
CACCACACCCTCCAAACAAAGCAAC
GGCGCCCTGACCAGCGGCGTGCACA
GAGCAGGACAGCAAGGACAGCACCT
AACAAGTACGCGGCCAAGAGCTATC
CCTTCCCGGCTGTCCTACAGTCCTCA
ACAGCCTCGAAAGCACCCTGACGCT
TGAGCCTGACGCCTGAGCAGTGGAA
GGACTCTACTCCCTCAAGAGCGTGGT
GAGCAAAGCAGACTACGAGAAACAC
GTCCCACAGAAGCTACAGCTGCCAG
GACCGTGCCCTCCAGCAGCTTGGGC
AAAGTCTACGCCTGCGAAGTCACCC
GTCACGCATGAAGGGAGCACCGTGG
ACCCAGACCTACATCTGCAACGTGA
ATCAGGGCCTGAGCTCGCCCGTCAC
AGAAGACAGTGGCCCCTACAGAATG
ATCACAAGCCCAGCAACACCAAGGT
AAAGAGCTTCAACAGGGGAGAGTGT
TTCA
GGACAAGAAAGTTGAGCCCAAATCT
(SEQ ID NO: 851)
(SEQ ID NO: 852)
TGTGACAAAACTCACACATGCCCAC
CGTGCCCAGCACCTGAACTCCTGGG
GGGACCGTCAGTCTTCCTCTTCCCCC
CAAAACCCAAGGACACCCTCATGAT
CTCCCGGACCCCTGAGGTCACATGCG
TGGTGGTGGACGTGAGCCACGAAGA
CCCTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGTGCGAGGAGCAG
TACGGCAGCACGTACCGTTGCGTCA
GCGTCCTCACCGTCCTGCACCAGGAC
TGGCTGAATGGCAAGGAGTACAAGT
GCAAGGTGTCCAACAAAGCCCTCCC
AGCCCCCATCGAGAAAACCATCTCC
AAAGCCAAAGGGCAGCCCCGAGAAC
CACAGGTGTACACCCTGCCCCCATCC
CGGGAGGAGATGACCAAGAACCAGG
TCAGCCTGACCTGCCTGGTCAAAGGC
TTCTATCCCAGCGACATCGCCGTGGA
GTGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCCG
TGCTGGACTCCGACGGCTCCTTCTTC
CTCTATAGCAAGCTCACCGTGGACA
AGAGCAGGTGGCAGCAGGGGAACGT
CTTCTCATGCTCCGTGATGCATGAGG
CTCTGCACAACCACTACACGCAGAA
GAGCCTCTCCCTGTCTCCGGGTGGTG
GCGGATCGGGAGGTGGCGGATCCCA
GGTGCAGTTGGTGGAGTCTGGGGGA
GGCTTAGTCAAGCCTGGAGGGTCCCT
GAGACTCTCCTGTGCAGCCTCTGAAT
TCACCTTCAGTGACTACTACATGAGC
TGGATCCGCCAGGCTCCAGGGAAGG
GGCTGGAGTGGGTTTCATATATTAGT
CGAAGTGGTGATACCATCTACTACGC
AGACTCTGTGAAGGGCCGATTCACC
ATCTCCAGGGACAACGCCAAGAACT
CACTGTATCTGCAAATGAATGGCCTG
CGAGCCGAAGACACGGCCGTGTATT
ACTGTGCGAGAGACTTAGCAGCAGG
TGCTACAGGGGGCCTTGACTGCTGG
GGCCAGGGAACCCTGGTCACCGTGT
CCTCAGCAAGCACGAAGGGGCCGTC
CGTATTTCCGCTTGCGCCCTCGTCGA
AGTCAACTTCGGGAGGGACCGCGGC
ACTTGGCTGTCTTGTCAAAGATTACT
TCCCTGAGCCAGTGACAGTCAGCTG
GAATTCCGGTGCCCTCACGTCAGGA
GTACATACATTCCCTGCGGTATTGCA
GTCCTCCGGACTCTACTCCCTGGAGT
CGGTGGTAACGGTGCCCAGCTCCAG
CTTGGGGACCCAGACGTACATTTGTA
ACGTGAATCACAAACCAAGCAATAC
TAAGGTAGATAAGAAAGTAGAACCG
AAGAGCTGC
(SEQ ID NO: 853)
AA
DIVMTQSPDSLAVSLGERATINCKSSQ
SYELTQPPSVSVSPGQTASITCSGERLG
EVQLVESGGGLIQPGGSLRLSCAVSGF
SVLYSSNNKNYLAWYQQKPGQPPKLL
NKYICWYQQKPGQSPVLVIYQDFKRPS
TVSSKFMTWVRQAPGKGLEWVSVIYS
IYWASTRESGVPDRFSGSGSGTDFTLTI
GIPERFSGSNSGITATLTISGTQAMDEA
GGKTYYADSVKGRFTISRDNSKNTLY
SSLQAEDVAVYYCQQYYSTPPTFGQG
DYYCQAWDSRTVVFGGGTKLTVLGQ
LQMNSLRAEDTAVYYCARDSGGWGY
TKVEIKRTVAAPSVFIFPPSDEQLKSGT
PKAAPSVTLFPPSSEELQANKATLVCLI
FDYWGQGTLVTVSSASTKGPSVFPLAP
ASVVCLLNNFYPREAKVQWKVDNAL
SDFYPGAVTVAWKADSSPVKAGVETT
SSKSTSGGTAALGCLVKDYFPEPVTVS
QSGNSQESVTEQDSKDSTYSLESTLTL
TPSKQSNNKYAAKSYLSLTPEQWKSH
WNSGALTSGVHTFPAVLQSSGLYSLKS
SKADYEKHKVYACEVTHQGLSSPVTK
RSYSCQVTHEGSTVEKTVAPTECS
VVTVPSSSLGTQTYICNVNHKPSNTKV
SFNRGEC
(SEQ ID NO: 855)
DKKVEPKSCDKTHTCPPCPAPELLGGP
(SEQ ID NO: 854)
SVFLFPPKPKDTLMISRTPEVTCVVVD
VSHEDPEVKFNWYVDGVEVHNAKTK
PCEEQYGSTYRCVSVLTVLHQDWLNG
KEYKCKVSNKALPAPIEKTISKAKGQP
REPQVYTLPPSREEMTKNQVSLTCLVK
GFYPSDIAVEWESNGQPENNYKTTPPV
LDSDGSFFLYSKLTVDKSRWQQGNVF
SCSVMHEALHNHYTQKSLSLSPGGGG
SGGGGSQVQLVESGGGLVKPGGSLRL
SCAASEFTFSDYYMSWIRQAPGKGLE
WVSYISRSGDTIYYADSVKGRFTISRD
NAKNSLYLQMNGLRAEDTAVYYCAR
DLAAGATGGLDCWGQGTLVTVSSAST
KGPSVFPLAPSSKSTSGGTAALGCLVK
DYFPEPVTVSWNSGALTSGVHTFPAVL
QSSGLYSLESVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSC
(SEQ ID NO: 856)
iPS:
21-233_7G11_IgG_21-
[hu anti-<hu Mesothelin>
NA
GACATTGTGATGACTCAGTCTCCAGA
CAGTCTGCCCTGACTCAGCCTGCCTC
GAGGTGCAGCTGGTCGAGTCTGGAG
576253
230_39C2_Fab
7G11VH]::huIgG1zSEFL2*GK-
CTCCCTGGCTGTGTCTCTGGGCGAGA
CGTGTCTGGGAGCCCTGGACAGTCG
GAGGCTTGATCCAGCCTGGGGGGTC
K::(G4S)2::[hu anti-
GGGCCACCATCAACTGCAAGTCCAG
ATCACCATCTCCTGCACTGGAACCAG
CCTGAGACTCTCCTGTGCAGTCTCTG
<huCD40>21-230_39C2VH]::
CCAGAGTGTTTTATACAGCTCCAACA
CAGTGATGTTGGGAATTATAACCTTG
GGTTCACCGTCAGTAGCAAGTTCATG
huIgG1z-CH1-E::EPKSC +
ATAAGAACTACTTAGCTTGGTACCAG
TCTCCTGGTACCAACAGCACCCAGGC
ACCTGGGTCCGCCAGGCTCCAGGGA
[anti-<hu Mesothelin>
CAGAAACCAGGACAGCCTCCTAAGC
AAAGCCCCCAAACTCATGATTTATGA
AGGGGCTGGAGTGGGTGTCAGTTAT
7G11VL]::huKLC-S176E +
TGCTCATTTACTGGGCATCTACCCGA
GGTCAATAGGCGGCCCTCAGGGGTT
TTATAGCGGTGGTAAGACATACTAC
[anti-<huCD40>
GAATCCGGGGTCCCTGACCGATTCA
TCTAATCGCTTCTCTGGCTCCAAGTC
GCAGACTCCGTGAAGGGCCGATTCA
21-230_39C2VL]::
GTGGCAGCGGGTCTGGGACAGATTT
TGGCAACACGGCCTCCCTGACAATCT
CCATCTCCAGAGACAATTCCAAGAA
huLLC2-K(IgG-
CACTCTCACCATCAGCAGCCTGCAGG
CTGGGCTCCAGGCTGAGGACGAGGC
CACGCTGTATCTTCAAATGAACAGCC
Fab); LMRID:
CTGAAGATGTGGCAGTTTATTACTGT
TGAATATTACTGCTGCTCATATGCAG
TGAGAGCCGAGGACACGGCCGTGTA
SS-30854
CAGCAATATTATAGTACTCCTCCGAC
GTAGAGACACTTTCGTGGTGTTCGGC
TTACTGTGCGAGAGATAGCGGTGGC
GTTCGGCCAAGGGACCAAGGTGGAG
GGAGGGACCAAGCTGACCGTCCTAG
TGGGGGTACTTTGACTACTGGGGCCA
ATCAAACGGACGGTGGCTGCACCAT
GTCAGCCCAAGGCTGCACCCTCGGTC
GGGAACCCTGGTCACCGTGTCCTCAG
CTGTCTTCATCTTCCCGCCATCTGAT
ACTCTGTTCCCGCCCTCCTCTGAGGA
CCTCCACCAAGGGCCCATCGGTCTTC
GAGCAGTTGAAATCTGGAACTGCCT
GCTTCAAGCCAACAAGGCCACACTG
CCCCTGGCACCCTCCTCCAAGAGCAC
CTGTTGTGTGCCTGCTGAATAACTTC
GTGTGTCTCATCAGTGACTTCTACCC
CTCTGGGGGCACAGCGGCCCTGGGC
TATCCCAGAGAGGCCAAAGTACAGT
GGGAGCCGTGACAGTGGCCTGGAAG
TGCCTGGTCAAGGACTACTTCCCCGA
GGAAGGTGGATAACGCCCTCCAATC
GCAGATAGCAGCCCCGTCAAGGCGG
ACCGGTGACGGTGTCGTGGAACTCA
GGGTAACTCCCAGGAGAGTGTCACA
GAGTGGAAACCACCACACCCTCCAA
GGCGCCCTGACCAGCGGCGTGCACA
GAGCAGGACAGCAAGGACAGCACCT
ACAAAGCAACAACAAGTACGCGGCC
CCTTCCCGGCTGTCCTACAGTCCTCA
ACAGCCTCGAAAGCACCCTGACGCT
AAGAGCTATCTGAGCCTGACGCCTG
GGACTCTACTCCCTCAAGAGCGTGGT
GAGCAAAGCAGACTACGAGAAACAC
AGCAGTGGAAGTCCCACAGAAGCTA
GACCGTGCCCTCCAGCAGCTTGGGC
AAAGTCTACGCCTGCGAAGTCACCC
CAGCTGCCAGGTCACGCATGAAGGG
ACCCAGACCTACATCTGCAACGTGA
ATCAGGGCCTGAGCTCGCCCGTCAC
AGCACCGTGGAGAAGACAGTGGCCC
ATCACAAGCCCAGCAACACCAAGGT
AAAGAGCTTCAACAGGGGAGAGTGT
CTACAGAATGTTCA
GGACAAGAAAGTTGAGCCCAAATCT
(SEQ ID NO: 857)
(SEQ ID NO: 858)
TGTGACAAAACTCACACATGCCCAC
CGTGCCCAGCACCTGAACTCCTGGG
GGGACCGTCAGTCTTCCTCTTCCCCC
CAAAACCCAAGGACACCCTCATGAT
CTCCCGGACCCCTGAGGTCACATGCG
TGGTGGTGGACGTGAGCCACGAAGA
CCCTGAGGTCAAGTTCAACTGGTACG
TGGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGTGCGAGGAGCAG
TACGGCAGCACGTACCGTTGCGTCA
GCGTCCTCACCGTCCTGCACCAGGAC
TGGCTGAATGGCAAGGAGTACAAGT
GCAAGGTGTCCAACAAAGCCCTCCC
AGCCCCCATCGAGAAAACCATCTCC
AAAGCCAAAGGGCAGCCCCGAGAAC
CACAGGTGTACACCCTGCCCCCATCC
CGGGAGGAGATGACCAAGAACCAGG
TCAGCCTGACCTGCCTGGTCAAAGGC
TTCTATCCCAGCGACATCGCCGTGGA
GTGGGAGAGCAATGGGCAGCCGGAG
AACAACTACAAGACCACGCCTCCCG
TGCTGGACTCCGACGGCTCCTTCTTC
CTCTATAGCAAGCTCACCGTGGACA
AGAGCAGGTGGCAGCAGGGGAACGT
CTTCTCATGCTCCGTGATGCATGAGG
CTCTGCACAACCACTACACGCAGAA
GAGCCTCTCCCTGTCTCCGGGTGGTG
GCGGATCGGGAGGTGGCGGATCCCA
GGTGCAGCTGGTGCAGTCTGGGACT
GAGGTGAAGAAGCCTGGGGCCTCAG
TGAAGGTGTCCTGCAAGGCTTCTGGA
TACACCTTCCCCGGCTACTATATGCA
CTGGGTGCGACAGGCCCCTGGACAG
GGGCTTGAGTGGATGGGATGGATCA
ACCCTGACAGTGGTGGCACAAAGTA
TACACAGAAGTTTCAGGGCAGGGTC
ACCTTGACCAGGGACGCGTCCGTCA
GCACAGCCTACATTGACCTGAACAG
GCTGAGATCTGACGACACGGCCGTA
TATTACTGTGCGAGAGAGAGGTGTA
GGACTACCAACTGCTATTTGGACTAC
TGGGGCCAGGGAAGTCTGGTCACCG
TGTCCTCAGCAAGCACGAAGGGGCC
GTCCGTATTTCCGCTTGCGCCCTCGT
CGAAGTCAACTTCGGGAGGGACCGC
GGCACTTGGCTGTCTTGTCAAAGATT
ACTTCCCTGAGCCAGTGACAGTCAGC
TGGAATTCCGGTGCCCTCACGTCAGG
AGTACATACATTCCCTGCGGTATTGC
AGTCCTCCGGACTCTACTCCCTGGAG
TCGGTGGTAACGGTGCCCAGCTCCA
GCTTGGGGACCCAGACGTACATTTGT
AACGTGAATCACAAACCAAGCAATA
CTAAGGTAGATAAGAAAGTAGAACC
GAAGAGCTGC
(SEQ ID NO: 859)
AA
DIVMTQSPDSLAVSLGERATINCKSSQ
QSALTQPASVSGSPGQSITISCTGTSSD
EVQLVESGGGLIQPGGSLRLSCAVSGF
SVLYSSNNKNYLAWYQQKPGQPPKLL
VGNYNLVSWYQQHPGKAPKLMIYEV
TVSSKFMTWVRQAPGKGLEWVSVIYS
IYWASTRESGVPDRFSGSGSGTDFTLTI
NRRPSGVSNRFSGSKSGNTASLTISGLQ
GGKTYYADSVKGRFTISRDNSKNTLY
SSLQAEDVAVYYCQQYYSTPPTFGQG
AEDEAEYYCCSYAGRDTFVVFGGGTK
LQMNSLRAEDTAVYYCARDSGGWGY
TKVEIKRTVAAPSVFIFPPSDEQLKSGT
LTVLGQPKAAPSVTLFPPSSEELQANK
FDYWGQGTLVTVSSASTKGPSVFPLAP
ASVVCLLNNFYPREAKVQWKVDNAL
ATLVCLISDFYPGAVTVAWKADSSPV
SSKSTSGGTAALGCLVKDYFPEPVTVS
QSGNSQESVTEQDSKDSTYSLESTLTL
KAGVETTTPSKQSNNKYAAKSYLSLTP
WNSGALTSGVHTFPAVLQSSGLYSLKS
SKADYEKHKVYACEVTHQGLSSPVTK
EQWKSHRSYSCQVTHEGSTVEKTVAP
VVTVPSSSLGTQTYICNVNHKPSNTKV
SFNRGEC
TECS
DKKVEPKSCDKTHTCPPCPAPELLGGP
(SEQ ID NO: 860)
(SEQ ID NO: 861)
SVFLFPPKPKDTLMISRTPEVTCVVVD
VSHEDPEVKFNWYVDGVEVHNAKTK
PCEEQYGSTYRCVSVLTVLHQDWLNG
KEYKCKVSNKALPAPIEKTISKAKGQP
REPQVYTLPPSREEMTKNQVSLTCLVK
GFYPSDIAVEWESNGQPENNYKTTPPV
LDSDGSFFLYSKLTVDKSRWQQGNVF
SCSVMHEALHNHYTQKSLSLSPGGGG
SGGGGSQVQLVQSGTEVKKPGASVKV
SCKASGYTFPGYYMHWVRQAPGQGL
EWMGWINPDSGGTKYTQKFQGRVTL
TRDASVSTAYIDLNRLRSDDTAVYYC
ARERCRTTNCYLDYWGQGSLVTVSSA
STKGPSVFPLAPSSKSTSGGTAALGCL
VKDYFPEPVTVSWNSGALTSGVHTFP
AVLQSSGLYSLESVVTVPSSSLGTQTYI
CNVNHKPSNTKVDKKVEPKSC
(SEQ ID NO: 862)
Kappa CL
(SEQ ID NO: 863)
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ
WKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
KHKVYACEVTHQGLSSPVTKSFNRGEC
(SEQ ID NO: 926)
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ
WKVDNALQSGNSQESVTEQDSKDSTYSLESTLTLSKADYE
KHKVYACEVTHQGLSSPVTKSFNRGEC
(SEQ ID NO: 927)
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ
WKVDNALQSGNSQESVTEQDSKDSTYSLKSTLTLSKADYE
KHKVYACEVTHQGLSSPVTKSFNRGEC
Lambda CL
(SEQ ID NO: 864)
GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTV
AWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWK
SHRSYSCQVTHEGSTVEKTVAPTECS
(SEQ ID NO: 928)
GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTV
AWKADSSPVKAGVETTTPSKQSNNKYAAKSYLSLTPEQWK
SHRSYSCQVTHEGSTVEKTVAPTECS
(SEQ ID NO: 929)
GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTV
AWKADSSPVKAGVETTTPSKQSNNKYAAESYLSLTPEQWK
SHRSYSCQVTHEGSTVEKTVAPTECS
Common CH1-hinge-CH2-CH3
(SEQ ID NO: 865)
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS
WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG
PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW
YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGK
EYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE
MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV
LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYT
QKSLSLSPGK
Common CH1-hinge-CH2-CH3 (K590G)
(SEQ ID NO: 866)
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS
WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG
PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW
YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGK
EYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE
MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV
LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYT
QKSLSLSPGG
(SEQ ID NO: 867)
GGSGGGGS
(SEQ ID NO: 868)
GGGGSGGGGS
(SEQ ID NO: 889)
GGGGSGGGGSGGGGS
(SEQ ID NO: 890)
GGGGSGGGGSGGGGSGGGGS
(SEQ ID NO: 891)
GGGGQGGGGQ
(SEQ ID NO: 892)
GGGGQGGGGQGGGGQ
(SEQ ID NO: 893)
GGGGQGGGGQGGGGQGGGGQ
(SEQ ID NO: 894)
MDMRVPAQLLGLLLLWLRGARC
(SEQ ID NO: 895)
MAWALLLLTLLTQGTGSWA
(SEQ ID NO: 896)
MTCSPLLLTLLIHCTGSWA
(SEQ ID NO: 897)
MEAPAQLLFLLLLWLPDTTG
(SEQ ID NO: 898)
MEWTWRVLFLVAAATGAHS
(SEQ ID NO: 899)
METPAQLLFLLLLWLPDTTG
(SEQ ID NO: 900)
METPAQLLFLLLLWLPDTTG
(SEQ ID NO: 901)
MKHLWFFLLLVAAPRWVLS
(SEQ ID NO: 902)
MEWSWVFLFFLSVTTGVHS
Human MSLN v2 NM 013404
(SEQ ID NO: 903)
MALPTARPLLGSCGTPALGSLLFLLFSLGWVQPSRTLAGE
TGQEAAPLDGVLANPPNISSLSPRQLLGFPCAEVSGLSTE
RVRELAVALAQKNVKLSTEQLRCLAHRLSEPPEDLDALPL
DLLLFLNPDAFSGPQACTRFFSRITKANVDLLPRGAPERQ
RLLPAALACWGVRGSLLSEADVRALGGLACDLPGRFVAES
AEVLLPRLVSCPGPLDQDQQEAARAALQGGGPPYGPPSTW
SVSTMDALRGLLPVLGQPIIRSIPQGIVAAWRQRSSRDPS
WRQPERILRPRFRREVEKTACPSGKKAREIDESLIFYKKW
ELEACVDAALLATQMDRVNAIPFTYEQLDVLKHKLDELYP
QGYPESVIQHLGYLFLKMSPEDIRKWNVTSLETLKALLEV
NKGHEMSPQAPRRPLPQVATLIDRFVKGRGQLDKDTLDTL
TAFYPGYLCSLSPEELSSVPPSSIWAVRPQDLDTCDPRQL
DVLYPKARLAFQNMNGSEYFVKIQSFLGGAPTEDLKALSQ
QNVSMDLATFMKLRTDAVLPLTVAEVQKLLGPHVEGLKAE
ERHRPVRDWILRQRQDDLDTLGLGLQGGIPNGYLVLDLSM
QEALSGTPCLLGPGPVLTVLALLLASTLA
Human MSLN v6 AY743922
(SEQ ID NO: 904)
MALPTARPLLGSCGTPALGSLLFLLFSLGWVQPSRTLAGE
TGQEAAPLDGVLANPPNISSLSPRQLLGFPCAEVSGLSTE
RVRELAVALAQKNVKLSTEQLRCLAHRLSEPPEDLDALPL
DLLLFLNPDAFSGPQACTHFFSRITKANVDLLPRGAPERQ
RLLPAALACWGVRGSLLSEADVRALGGLACDLPGRFVAES
AEVLLPRLVSCPGPLDQDQQEAARAALQGGGPPYGPPSTW
SVSTMDALRGLLPVLGQPIIRSIPQGIVAAWRQRSSRDPS
WRQPERILRPRFRREVEKTACPSGKKAREIDESLIFYKKW
ELEACVDAALLATQMDRVNAIPFTYEQLDVLKHKLDELYP
QGYPESVIQHLGYLFLKMSPEDIRKWNVTSLETLKALLEV
NKGHEMSPQVATLIDRFVKGRGQLDKDTLDTLTAFYPGYL
CSLSPEELSSVPPSSIWAVRPQDLDTCDPRQLDVLYPKAR
LAFQNMNGSEYFVKIQSFLGGAPTEDLKALSQQNVSMDLA
TFMKLRTDAVLPLTVAEVQKLLGPHVEGLKAEERHRPVRD
WILRQRQDDLDTLGLGLQGGIPNGYLVLDLSVQEALSGTP
CLLGPGPVLTVLALLLASTLA
cyno MSLN macaque v1 LMR C52457
(SEQ ID NO: 905)
MALPMARPLSGSCGTPALGSLLFLLFSLGWVQPSRVLAGE
TRQEAAPLDGILTNAPDIASLSPRQLLGFTCVEVSGLSTE
LVQELAVALGQKNVKLSAEQLRCLAHRLSEPPEDLDALPL
DLLLFLNPDAFSGPQACTHFFSRVAKANVDLLPRGAPERQ
RLLPAALTCWGVRGSLLSEADVRALGGLACDLPGRFVAES
AEWLPRLVRCLGPLDQDQQEAARAALQRGGPPYGPPSTWS
ISTLDDLQSLLPVLGQPVIHSIPQGILAAWRQRSSRDPSW
QQPEQTVLRPRFRRDVERTTCPPEKEVHEIDENLIFYKKR
ELEACVDAALLAAQMDRVDAIPFTYEQLDVLKHKLDELYP
QGYPESVIRHLGHLFLKMSPEDIRKWNVTSLETLKALLKV
SKGHEMSAQVATLIDRVWGRGQLDKDTADTLTAFCPGCLC
SLSPERLSSVPPSVIGAVRPQDLDTCGPRQLDVLYPKARL
AFQNMSGSEYFVKIRPFLGGAPTEDLKALSQQNVSMDLAT
FMKLRREAVLPLTVAEVQKLLGPHVEGLKVEEQHSPVRDW
ILKQRQDDLDTLGLGLQGGIPNGYLILDLSVREALSGTPC
LLGPGPVLTILALLLASTLA
Kappa CL S176E
(SEQ ID NO: 906)
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ
WKVDNALQSGNSQESVTEQDSKDSTYSLESTLTLSKADYE
KHKVYACEVTHQGLSSPVTKSFNRGEC
Kappa CL S176K
(SEQ ID NO: 907)
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ
WKVDNALQSGNSQESVTEQDSKDSTYSLKSTLTLSKADYE
KHKVYACEVTHQGLSSPVTKSFNRGEC
Lambda CL S176K
(SEQ ID NO: 908)
GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTV
AWKADSSPVKAGVETTTPSKQSNNKYAAKSYLSLTPEQWK
SHRSYSCQVTHEGSTVEKTVAPTECS
Lambda CL S176E
(SEQ ID NO: 909)
GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTV
AWKADSSPVKAGVETTTPSKQSNNKYAAESYLSLTPEQWK
SHRSYSCQVTHEGSTVEKTVAPTECS
> XM_005590816.2 (without N-terminal
11 aa) cyno Mesothelin
(SEQ ID NO: 910)
MALPMARPLSGSCGTPALGSLLFLLFSLGWVQPSRVLAGE
TRQEAAPLDGILTNAPDIASLSPRQLLGFTCVEVSGLSTE
LVQELAVALGQKNVKLSAEQLRCLAHRLSEPPEDLDALPL
DLLLFLNPDAFSGPQACTHFFSRVAKANVDLLPRGAPERQ
RLLPAALTCWGVRGSLLSEADVRALGGLACDLPGRFVAES
AEVVLPRLVRCLGPLDQDQQEAARAALQRGGPPYGPPSTW
SISTLDDLQSLLPVLGQPVIHSIPQGILAAWRQRSSRDPS
WQQPEQTVLRPRFRRDVERTTCPPEKEVHEIDESLIFYKK
RELEACVDAALLAAQMDRVDAIPFTYEQLDVLKHKLDELY
PQGYPESVIRHLGHLFLKMSPEDIRKWNVTSLETLKALLK
VSKGHEMSAQVATLIDRVVVGRGQLDKDTADTLTAFCPGC
LCSLSPERLSSVPPSIIGAVRPQDLDTCGPRQLDVLYPKA
RLAFQNMSGSEYFVKIRPFLGGAPTEDLKALSQQNVSMDL
ATFMKLRREAVLPLSVAEVQKLLGPHVEGLKVEEQHSPVR
DWILKQRQDDLDTLGLGLQGGIPNGYLILDLSVREALSGT
PCLLGPGPVLTVLALLLASTLA
>XP_005569274.1 PREDICTED: tumor necrosis
factor receptor superfamily member 5
isoform X1 [Macaca fascicularis]
(SEQ ID NO: 911)
MVRLPLQCVLWGCLLTAVYPEPPTACREKQYLINSQCCSL
CQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETRCHQH
KYCDPNLGLRVQQKGTSETDTICTCEEGLHCTSESCESCV
PHRSCLPGFGVKQIATGVSDTICEPCPVGFFSNVSSAFEK
CRPWTSCETKDLVVQQAGTNKTDVVCGPQDRQRALVVIPI
CLGILFVILLLVLVFISESSEKVAKKPNDKVPHPKQEPQE
INFPDDLPGSNPAAPVQETLHGCQPVTQEDGKESRISVQE
RQ
Common CH1-hinge-CH2-CH3 (S176K)
(SEQ ID NO: 912)
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS
WNSGALTSGVHTFPAVLQSSGLYSLKSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG
PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW
YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGK
EYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE
MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV
LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYT
QKSLSLSPGG
Common CH1-hinge-CH2-CH3 (S176E)
(SEQ ID NO: 913)
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS
WNSGALTSGVHTFPAVLQSSGLYSLESVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG
PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW
YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGK
EYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE
MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV
LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYT
QKSLSLSPGG
Common CHI-hinge-CH2-CH3 (S176K/K590G)
(SEQ ID NO: 914)
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS
WNSGALTSGVHTFPAVLQSSGLYSLKSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG
PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW
YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGK
EYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE
MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV
LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYT
QKSLSLSPGK
Common CH1-hinge-CH2-CH3 (S176E/K590G)
(SEQ ID NO: 915)
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS
WNSGALTSGVHTFPAVLQSSGLYSLESVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG
PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW
YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGK
EYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE
MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV
LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYT
QKSLSLSPGKInventors (6)
- Xin YuFoster City, CA, US
- Jackson EgenSan Mateo, CA, US
- Fernando GarcesSherman Oaks, CA, US
- Shunsuke TakenakaVancouver, CA
- AeRyon KimFoster City, CA, US
- Deepali SawantNewark, CA, US
Assignees (1)
- Amgen Inc.Thousand Oaks, CA, US
CPC (15)
C07K16/2878A61K2039/505A61P35/04C07K16/30C07K2317/31C07K2317/33C07K2317/35C07K2317/522C07K2317/524C07K2317/526C07K2317/53C07K2317/565C07K2317/622C07K2317/75C07K2317/92
IPC (4)
A61K39/00A61P35/04C07K16/28C07K16/30
Backward citations (39)
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Source: ipg260428.zip (2026-04-28)