Compositions and methods for binding to covalent peptide conjugates

Abstract

Provided are compositions and methods comprising a binding partner that specifically binds to a peptide conjugate / MHC complex, wherein the peptide conjugate / MHC complex comprises a peptide conjugate formed by a covalent reaction between a targeted covalent inhibitor and a peptide. The binding partner is provided as an antibody or antibody derivative that specifically binds to the peptide conjugate / MHC complex described herein.

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims priority and benefit of U.S. Provisional Patent Application No. 63 / 509,472, filed on 21 June 2023, and U.S. Provisional Patent Application No. 63 / 637,558, filed on 23 April 2024, each of which is incorporated herein by reference in its entirety.

[0002] Description of federally funded research and development. This invention was made with government support under CA016087 and CA267362, granted by the National Institutes of Health. The government has certain rights in this invention. [Background technology]

[0003] There is a continuing unmet need for drugs that can bind to targets, including drugs that covalently bind to proteins or peptides. In particular, there is a need to improve the effectiveness of targeted therapies, as well as a need to increase the immunogenicity of tumors, and a need to increase the effectiveness of cancer immunotherapy driven by the loss of intracellular oncogenes and tumor suppressor genes. This disclosure relates to these needs. [Overview of the project]

[0004] This disclosure provides compositions and methods comprising binding partners that specifically bind to target sites on proteins or peptides containing covalently bound molecules. This disclosure illustrates this approach using binding partners in the form of numerous antibodies and antibody derivatives that specifically bind to proteins and peptides covalently modified by molecular binding, the molecules being exemplified by various drugs. Furthermore, this disclosure demonstrates that binding partners that specifically bind to peptides covalently modified by the binding of small molecule drugs are specific to the described covalently modified peptides when presented in the context of human leukocyte antigens (HLA), where HLA is a representative example of the major histocompatibility complex (MHC). Thus, binding partners specific to peptide-drug conjugates in HLA complexes are demonstrated. This disclosure also provides binding partners specific to two different drug-peptide / MHC complexes. This disclosure includes polynucleotides encoding the described binding partners and cells modified to express the binding partners. This disclosure includes diagnostic, prophylactic, and therapeutic approaches using the binding partners.

[0005] In one embodiment, the disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain has a dissociation constant (K) up to about 100 nM to a first peptide conjugate / MHC complex. D ) and (ii) a maximum of approximately 100 nM of K into the second peptide conjugate / MHC complex. Dare combined, and the first peptide conjugate / MHC complex comprises: (a) a first peptide conjugate, wherein the first peptide conjugate of the first peptide conjugate / MHC complex is a first peptide covalently bound to a first targeted covalent inhibitor or a fragment thereof, and (b) a first MHC; the second peptide conjugate / MHC complex comprises: (a) a second peptide conjugate, wherein the second peptide conjugate of the second peptide conjugate / MHC complex is a second peptide covalently bound to a second targeted covalent inhibitor or a fragment thereof, and (b) a second MHC, wherein the first targeted covalent inhibitor is different from the second targeted covalent inhibitor.

[0006] In some embodiments, the antigen-binding domain binds to (i) the first peptide conjugate / MHC complex with a dissociation constant (K D ) of up to about 50 nM and / or (ii) the second peptide conjugate / MHC complex with a K D of up to about 50 nM. In some embodiments, the antigen-binding domain binds to (i) the first peptide conjugate / MHC complex with a dissociation constant (K D ) of up to about 10 nM and / or (ii) the second peptide conjugate / MHC complex with a K D of up to about 10 nM. In some embodiments, the antigen-binding domain binds to (i) the first peptide conjugate / MHC complex with a dissociation constant (K D ) of up to about 5 nM and / or (ii) the second peptide conjugate / MHC complex with a K D of up to about 5 nM.

[0007] In some embodiments, the first targeted covalent inhibitor is a covalent inhibitor of a RAS protein and the second targeted covalent inhibitor is a covalent inhibitor of a RAS protein. In some embodiments, the first targeted covalent inhibitor is KRAS G12CThe second targeted covalent inhibitor is KRAS G12C It is a covalent inhibitor. In some embodiments, (i) the first targeted covalent inhibitor is adagrasib and the second targeted covalent inhibitor is sotrasib, (ii) the first targeted covalent inhibitor is adagrasib and the second targeted covalent inhibitor is divalasib, or (iii) the first targeted covalent inhibitor is divalasib and the second targeted covalent inhibitor is sotrasib.

[0008] In some embodiments, the antigen-binding domain is (i) conjugated to a free first targeted covalent inhibitor with a dissociation constant (K) D (ii) Does not bind at less than 200 nM, or K is added to the first peptide. D (iii) K does not bind at less than 200 nM, or does not form a complex with MHC in the free first peptide conjugate. D (iv) No binding occurs at less than 200 nM, or any combination of the above.

[0009] In some embodiments, the antigen-binding domain binds to the first peptide conjugate / MHC complex with greater affinity than the first peptide, the free first targeted covalent inhibitor, and / or the free first peptide conjugate. In some embodiments, the affinity of the antigen-binding domain to the first peptide conjugate / MHC complex is 100 to 10,000 times greater than the affinity of the antigen-binding domain to the first peptide or the free first targeted covalent inhibitor. In some embodiments, the antigen-binding domain does not bind to the complex of the first peptide and the first MHC in a detectable manner, in which case the first peptide is not covalently bound to the first targeted covalent inhibitor or its fragment. In some embodiments, the antigen-binding domain does not bind to the free first targeted covalent inhibitor in a detectable manner. In some embodiments, the antigen-binding domain binds to the free first peptide conjugate with respect to the dissociation constant (K) of the antibody or the antigen-binding fragment relative to the first peptide conjugate / MHC complex. D ) at least 2.5 times K D They are joined together.

[0010] In some embodiments, the antigen-binding domain is (i) conjugated to a free second targeted covalent inhibitor with a dissociation constant (K) D (ii) Does not bind at less than 200 nM, or K is added to the second peptide. D (iii) K does not bind at less than 200 nM, or does not form a complex with the MHC in the free second peptide conjugate. D (iv) No binding occurs at less than 200 nM, or any combination of the above.

[0011] In some embodiments, the antigen-binding domain binds to the second peptide conjugate / MHC complex with greater affinity than to the second peptide, the free second targeted covalent inhibitor, and / or the free second peptide conjugate.

[0012] In some embodiments, the affinity of the antigen-binding domain to the second peptide conjugate / MHC complex is 100 to 10,000 times greater than the affinity of the antigen-binding domain to the second peptide or the free second targeted covalent inhibitor. In some embodiments, the antigen-binding domain does not bind to the complex of the second peptide and the second MHC in a detectable manner, in which case the second peptide is not covalently bound to the second targeted covalent inhibitor or its fragment. In some embodiments, the antigen-binding domain does not bind to the free second targeted covalent inhibitor in a detectable manner. In some embodiments, the antigen-binding domain binds to the free second peptide conjugate, and the dissociation constant (K) of the antibody or the antigen-binding fragment to the second peptide conjugate / MHC complex is D ) at least 2.5 times K D They are joined together.

[0013] In some embodiments, the first peptide and the second peptide contain the same amino acid sequence. In some embodiments, the first peptide and the second peptide consist of the same amino acid sequence. In some embodiments, the first peptide or the second peptide contains the amino acid sequence VVVGACGVGK. In some embodiments, the first peptide and the second peptide contain different amino acid sequences. In some embodiments, the first peptide and the second peptide contain a common continuous amino acid sequence that is at least 3, 4, 5, 6, 7, 8, or 9 amino acid lengths. In some embodiments, the first peptide and / or the second peptide contain the amino acid sequence VVVGACGVGK, VVGACGVGK, or KLVVVGACGV. In some embodiments, the first MHC or the second MHC is encoded by an HLA, where the HLA is HLA-A*02:01, HLA-A*03:01, or HLA-A*11:01.

[0014] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain is bound to a peptide conjugate / MHC complex, the peptide conjugate of the peptide conjugate / MHC complex is a targeted covalent inhibitor or a fragment thereof and a peptide covalently bound to MHC, and the antigen-binding domain provides the peptide conjugate / MHC complex with a dissociation constant (K) up to approximately 50 nM. D The targeted covalent inhibitor is adagrab, which binds via ).

[0015] In some embodiments, the peptide conjugate / MHC complex is a first peptide conjugate / MHC complex comprising a first peptide conjugate comprising a first peptide and a first targeted covalent inhibitor or fragment thereof, wherein the antigen-binding domain is further bound to a second peptide conjugate / MHC complex, the second peptide conjugate / MHC complex comprising (a) a second peptide conjugate, wherein the second peptide conjugate of the second peptide conjugate / MHC complex is a second peptide covalently bound to a second targeted covalent inhibitor or fragment thereof, and (b) a second MHC.

[0016] In some embodiments, the antigen-binding domain is configured to contain up to approximately 50 nM of K to the second peptide conjugate / MHC complex. D It binds via (i) a dissociation constant (K) up to about 10 nM to the first peptide conjugate / MHC complex. D ) and (ii) the second peptide conjugate / MHC complex with up to approximately 10 nM of K D It binds via (i) a dissociation constant (K) up to about 5 nM to the first peptide conjugate / MHC complex. D ) and (ii) the second peptide conjugate / MHC complex with up to approximately 5 nM of K D They are joined together.

[0017] In some embodiments, the second targeted covalent inhibitor is sotrasib or divalasib. In some embodiments, the antigen-binding domain is a free first targeted covalent inhibitor with a dissociation constant (K D ) Does not bind at concentrations less than 200 nM. In some embodiments, the antigen-binding domain binds to the first peptide conjugate / MHC complex with greater affinity than to the first peptide or the free first targeted covalent inhibitor. In some embodiments, the affinity of the antigen-binding domain to the first peptide conjugate / MHC complex is 100 to 10,000 times greater than the affinity of the antigen-binding domain to the first peptide or the free first targeted covalent inhibitor.

[0018] In some embodiments, the antigen-binding domain does not bind to the complex of the first peptide and the first MHC in a detectable manner, in which case the first peptide is not covalently bound to the first targeted covalent inhibitor or its fragment. In some embodiments, the antigen-binding domain does not bind to the free first targeted covalent inhibitor in a detectable manner. In some embodiments, the antigen-binding domain binds to the free first peptide conjugate, with respect to the dissociation constant (K) of the antibody or antigen-binding fragment for the first peptide conjugate / MHC complex. D ) at least 2.5 times K D They are joined together.

[0019] In some embodiments, the antigen-binding domain is configured to release a second targeted covalent inhibitor with a dissociation constant (K). D) Does not bind at concentrations less than 200 nM. In some embodiments, the antigen-binding domain binds to the second peptide conjugate / MHC complex with greater affinity than to the second peptide or the free second targeted covalent inhibitor. In some embodiments, the affinity of the antigen-binding domain to the second peptide conjugate / MHC complex is 100 to 10,000 times greater than the affinity of the antigen-binding domain to the second peptide or the free second targeted covalent inhibitor.

[0020] In some embodiments, the antigen-binding domain does not bind to the complex of the second peptide and the second MHC in a detectable manner, in which case the second peptide is not covalently bound to the second targeted covalent inhibitor or its fragment. In some embodiments, the antigen-binding domain does not bind to the free second targeted covalent inhibitor in a detectable manner. In some embodiments, the antigen-binding domain binds to the free second peptide conjugate, and the dissociation constant (K) of the antibody or antigen-binding fragment to the second peptide conjugate / MHC complex is D ) at least 2.5 times K D They are joined together.

[0021] In some embodiments, the first peptide and the second peptide contain the same amino acid sequence. In some embodiments, the first peptide and the second peptide consist of the same amino acid sequence. In some embodiments, the first peptide or the second peptide contains the amino acid sequence VVVGACGVGK. In some embodiments, the first peptide and the second peptide contain different amino acid sequences. In some embodiments, the first peptide or the second peptide contains the amino acid sequence VVVGACGVGK, VVGACGVGK, or KLVVVGACGV. In some embodiments, the MHC or the second MHC is an HLA, and the HLA is HLA-A*02:01, HLA-A*03:01, or HLA-A*11:01.

[0022] In some embodiments, the first peptide or the second peptide comprises a nucleophilic or electrophilic residue, which comprises cysteine, aspartic acid, arginine, serine, or tyrosine. In some embodiments, the first peptide or the second peptide comprises a cysteine ​​residue. In some embodiments, the first peptide conjugate is formed by a covalent reaction between the first targeted covalent inhibitor and the cysteine ​​residue of the first peptide. In some embodiments, the second peptide conjugate is formed by a covalent reaction between the second targeted covalent inhibitor and the cysteine ​​residue of the second peptide.

[0023] In some embodiments, the first peptide or the second peptide is a segment of a cancer-related protein, and optionally, the protein is encoded by a gene that has been mutated in cancer. In some embodiments, the first peptide or the second peptide is a segment of an enzyme, and the first targeted covalent inhibitor or the second targeted covalent inhibitor is an inhibitor of the enzyme. In some embodiments, the enzyme is a kinase or a GTPase.

[0024] In some embodiments, the first peptide or the second peptide is KRAS or derived from KRAS. G12C KRAS G12D , or KRAS G12R The segment includes (i) tricomplex KRAS G12C Inhibitors or KRAS G12C Degradation-inducing factor, (ii) Tricomplex KRAS G12D Inhibitors or KRAS G12D Degradation-inducing factors, or (iii) tricomplex KRAS G12R Inhibitors or KRAS G12R It is a degradation-inducing factor.

[0025] In some embodiments, the first peptide conjugate or the second peptide conjugate comprises a compound selected from the group consisting of compounds (1), (2), and (3). [ka] In this case, the compound is covalently bonded to a cysteine ​​residue of the peptide, and the peptide comprises the amino acid sequence VVVGACGVGK, VVGACGVGK, or KLVVVGACGV. In some embodiments, the peptide comprises the amino acid sequence VVVGACGVGK or VVGACGVGK, and the MHC is HLA-A*03:01 or HLA-A*11:01. In some embodiments, the peptide comprises the amino acid sequence KLVVVGACGV, and the MHC is HLA-A*02:01. In some embodiments, the first peptide conjugate is adagracive and KRAS G12C It is formed by a covalent bonding reaction with a peptide. In some embodiments, the second peptide conjugate is formed by sotracib and KRAS G12C It is formed by a covalent bonding reaction with a peptide. In some embodiments, the second peptide conjugate is formed by divalasib and KRAS G12C It is formed by a covalent bonding reaction with peptides.

[0026] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), where (a) the VH is (i) an HC CDR1 comprising the amino acid sequence X1SX3X4SIH, where X1 is I, F, or V, X3 is S or Y, and X4 is S or Y; and (ii) the amino acid sequence X1ISX4X5X6X7X8TX 10 HC CDR2 containing YADSVKG, where X1 is S or Y, X4 is S or P, X5 is S or Y, X6 is S or Y, X7 is S or G, X8 is S or Y, X 10(iii) those which are S or Y, and (iii) amino acid sequence X N HC CDR3 containing X1X2DY, X N (i) the VL is an amino acid sequence selected from LWAS, FQWY, GYGW, GWYYL, YWYYM, YWYYL, GYYYPYY, SYYGFWQALW, SSRQYYHSQVEPPM, SGYYSSHWYLQSWYQ, and HYSEKWWGWYTMYID, where X1 is G or A and X2 is L or M, and / or (b) the VL is (i) LC CDR1 containing the amino acid sequence RASQSVSSAVA or a variant thereof containing 1 to 5 amino acid changes, (ii) LC CDR2 containing the amino acid sequence SASSLYS or a variant thereof containing 1 to 5 amino acid changes, and (iii) the amino acid sequence QQX3X4X5X6X7X8X9X 10 LC CDR3 containing T, where X3 is W, T, S, A or G, X4 is N, W, S, G, Y, D or K, X5 is W, Y, S, A or T, X6 is G, S, Y, L, W, E or D, X7 is W, S, H, Y, E, F or none, X8 is P, Q, S, W, E, L, G or none, X9 is L or P, X 10 This includes those that are I, L, F, or V.

[0027] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises (i) HC CDR1 comprising the amino acid sequence FSSSSIH or a variant thereof comprising 1 to 3 amino acid changes, (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) HC CDR3 comprising the amino acid sequence LWASGLDY, and / or the VL comprises (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T CDR3 includes those in which X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V.

[0028] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), where (a) the VH comprises (i) HC CDR1 comprising the amino acid sequence FSSSSIH or a variant thereof comprising 1 to 3 amino acid changes, (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) HC CDR3 comprising the amino acid sequence SYYGFWQALWALDY, and / or (b) the VL comprises (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T CDR3 includes those in which X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V.

[0029] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), where (a) the VH comprises (i) HC CDR1 comprising the amino acid sequence FSSSSIH or a variant thereof comprising 1 to 3 amino acid changes, (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) HC CDR3 comprising the amino acid sequence GYYYPYYAMDY, and / or (b) the VL comprises (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC CDR3 comprising the amino acid sequence QQX1X2X3X4YPX5T This includes CDR3s where X1 is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5 is I, L, or V.

[0030] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), where (a) the VH comprises (i) HC CDR1 comprising the amino acid sequence FSSSSIH or a variant thereof comprising 1 to 3 amino acid changes, (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) HC CDR3 comprising the amino acid sequence GYYYPYYAMDY, and / or (b) the VL comprises (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T CDR3 includes those in which X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V.

[0031] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), and (a) the VH comprises (i) HC CDR1 comprising the amino acid sequence FSSSSIH or a variant thereof comprising 1 to 3 amino acid changes, (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) HC CDR3 comprising the amino acid sequence X1X2X3X4X5MDY, where X1 is F or G, X2 is Q or Y, X3 is W or G, X4 is Y or W, and X5 is A or G, and / or (b) the VL comprises (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, and (ii) LC CDR1 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes. CDR2, and / or (iii) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T, wherein X1 is W, S, or A; X2 is N, W, S, or D; X3 is W, S, or Y; X4 is G, L, S, E, or Y; X5 is W, S, Y, E, or F; X6 is P, W, G, E, or Q; and X7 is I, F, or V.

[0032] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), where (a) the VH comprises (i) HC CDR1 comprising the amino acid sequence FSSSSIH or a variant thereof comprising 1 to 3 amino acid changes, (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) HC CDR3 comprising the amino acid sequence SGYYSSHWYLQSWYQAMDY, and / or (b) the VL comprises (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC CDR3 comprising the amino acid sequence QQX1X2X3X4YPX5T This includes CDR3s where X1 is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5 is I, L, or V.

[0033] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), where (a) the VH comprises (i) HC CDR1 comprising the amino acid sequence FSSSSIH or a variant thereof comprising 1 to 3 amino acid changes, (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) HC CDR3 comprising the amino acid sequence SGYYSSHWYLQSWYQAMDY, and / or (b) the VL comprises (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6T This includes CDR3s in which X1 is G or A, X2 is S or Y, X3 is S or Y, X4 is G, D, or S, X5 is P or L, and X6 is I or L.

[0034] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), where (a) the VH comprises (i) HC CDR1 comprising the amino acid sequence FSSSSIH or a variant thereof comprising 1 to 3 amino acid changes, (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) HC CDR3 comprising the amino acid sequence HYSEKWWGWYTMYIDAMDY, and / or (b) the VL comprises (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T CDR3 includes those in which X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V.

[0035] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), where (a) the VH comprises (i) HC CDR1 comprising the amino acid sequence FSSSSIH or a variant thereof comprising 1 to 3 amino acid changes, (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) HC CDR3 comprising the amino acid sequence X1WYYX2GMDY, where X1 is G or Y and X2 is M or L, and / or (b) the VL comprises (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC containing amino acids comprising the amino acid sequence QQX1X2X3X4YPX5T This includes CDR3s where X1 is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5 is I, L, or V.

[0036] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), and (a) the VH comprises (i) HC CDR1 comprising the amino acid sequence FSSSSIH or a variant thereof comprising 1 to 3 amino acid changes, (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) HC CDR3 comprising the amino acid sequence X1WYYX2GMDY, where X1 is G or Y and X2 is M or L, and / or (b) the VL comprises (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6T This includes CDR3s in which X1 is G or A, X2 is S or Y, X3 is S or Y, X4 is G, D, or S, X5 is P or L, and X6 is I or L.

[0037] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), and (a) the VH comprises (i) HC CDR1 comprising the amino acid sequence FSSSSIH or a variant thereof comprising 1 to 3 amino acid changes, (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) HC CDR3 comprising the amino acid sequence X1WYYX2GMDY, where X1 is G or Y and X2 is M or L, and / or (b) the VL comprises (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC CDR2 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T CDR3 includes those in which X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V.

[0038] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), where (a) the VH comprises (i) HC CDR1 comprising the amino acid sequence FSSSSIH or a variant thereof comprising 1 to 3 amino acid changes, (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) HC CDR3 comprising the amino acid sequence SSRQYYHSQVEPPMAMDY, and / or (b) the VL comprises (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC containing amino acids comprising the amino acid sequence QQX1X2X3X4YPX5T This includes CDR3s where X1 is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5 is I, L, or V.

[0039] In some embodiments, the antigen-binding domain is the amino acid sequences of HC CDR1, HC CDR2, and HC CDR3 of the VH amino acid sequence of a polypeptide selected from the group consisting of RM_001, RM_002, RM_003, RM_004, RM_005, RM_006, RM_007, RM_008, RM_009, RM_010, RM_011, RM_012, RM_013, RM_014, RM_015, RM_016, RM_017, RM_018, RM_019, RM_020, RM_021, RM_022, RM_023, RM_024, RM_025, RM_026, RM_027, RM_028, RM_029, RM_030, RM_031, and RM_032, and / or the amino acid sequences of LC CDR1, LC CDR1, LC CDR3 of the VL amino acid sequence. The amino acid sequences of CDR2 and LC CDR3, or variants thereof that include one to five amino acid changes in one or more of the amino acid sequences of said CDR.

[0040] In some embodiments, the antigen-binding domain is HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR1 of a polypeptide selected from the group consisting of RM_001, RM_002, RM_003, RM_004, RM_005, RM_006, RM_007, RM_008, RM_009, RM_010, RM_011, RM_012, RM_013, RM_014, RM_015, RM_016, RM_017, RM_018, RM_019, RM_020, RM_021, RM_022, RM_023, RM_024, RM_025, RM_026, RM_027, RM_028, RM_029, RM_030, RM_031, and RM_032. The amino acid sequence of CDR3, or a variant thereof containing one to five amino acid changes in one or more of the amino acid sequences of said CDR.

[0041] In some embodiments, the antigen-binding domain includes VH and / or VL amino acid sequences that are 90%, 95%, or 100% identical to the following VH and VL sequences: RM_001 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTISSSSIHWVRQAPGKGLEWVASISSYYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARLWASGLDYWGQGTLVTVSS RM_002 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSYYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARLWASGLDYWGQGTLVTVSS RM_003 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWWYGSPLFTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQALWALDYWGQGTLVTVSS RM_004 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWWYGSPLFTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQALWALDYWGQGTLVTVSS RM_005 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS RM_006 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISPYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS RM_007 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQTSWYHSLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS RM_008 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS RM_009 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS RM_010 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSWLYWLVTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISAD TSKNTAYLQMNSLRAEDTAVYYCARFQWYAMDYWGQGTLVTVSS RM_011 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTISSYSIHWVRQAPGKGLEWVAYISSYSGYTSYADSVKGRFTISAD TSKNTAYLQMNSLRAEDTAVYYCARGYGWGMDYWGQGTLVTVSS RM_012 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTISYSSIHWVRQAPGKGLEWVAYISSSSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSHWYLQSWYQAMDYWGQGTLVTVSS RM_013 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQASYGPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSHWYLQSWYQAMDYWGQGTLVTVSS RM_014 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWWSSSQLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYSSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARHYSEKWWGWYTMYIDAMDYWGQGTLVTVSS RM_015 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS RM_016 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS RM_017 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS RM_018 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS RM_019 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS RM_020 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS RM_021 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS RM_022 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS RM_023 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSYYEELITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS RM_024 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQAYSDPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS RM_025 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGSSSLLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS RM_026 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSGSYLLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS RM_027 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQADYEFGLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS RM_028 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS RM_029 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS RM_030 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSSSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS RM_031 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYSSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS RM_032 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGSSSLLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVAYISPYSGYTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYLGMDYWGQGTLVTVSS

[0042] In some embodiments, the polypeptide specifically binds to the first peptide conjugate / MHC complex and a T cell antigen. In some embodiments, the polypeptide specifically binds to the first peptide conjugate / MHC complex and human CD3. In some embodiments, the polypeptide specifically binds to the second peptide conjugate / MHC complex and a T cell antigen. In some embodiments, the polypeptide specifically binds to the second peptide conjugate / MHC complex and human CD3. In some embodiments, the polypeptide includes a heavy chain constant region selected from the group consisting of human IgM, IgG1, IgG2, IgG3, IgG4, IgA1, and IgA. In some embodiments, the heavy chain constant region includes one or more amino acid substitutions, deletions, or additions to the Fc region. In some embodiments, the polypeptide is conjugated with a detectable label, a chemotherapeutic agent, a radioisotope, or a toxin.

[0043] In some embodiments, the polypeptide is contained within a chimeric antigen receptor. In some embodiments, the polypeptide is expressed by T cells, killer macrophages, neutrophils, or natural killer cells.

[0044] In some embodiments, this disclosure provides polynucleotides encoding polypeptides described herein.

[0045] In some embodiments, the present disclosure provides polynucleotides encoding heavy-chain variable regions and / or light-chain variable regions of polypeptides described herein. In some embodiments, the polynucleotides are modified polynucleotides.

[0046] In some embodiments, this disclosure provides vectors comprising polynucleotides as described herein. In some embodiments, the vector is a viral vector. In some embodiments, the viral vector is an adenovirus vector, a lentivirus vector, a retrovirus vector, or an adeno-associated virus vector.

[0047] In some embodiments, the Disclosure provides a recombinant host cell comprising (a) a polynucleotide as described herein, (b) a vector as described herein, (c) a first polynucleotide encoding the VH or heavy chain of the polypeptide as described herein, and a second polynucleotide encoding the VL or light chain of the polypeptide as described herein, or (d) a first vector comprising a first polynucleotide encoding the VH or heavy chain of the polypeptide as described herein, and a second polynucleotide encoding the VL or light chain of the polypeptide as described herein.

[0048] In some embodiments, the present disclosure provides a pharmaceutical composition comprising a polypeptide as described herein, a polynucleotide as described herein, a vector as described herein, or a host cell as described herein, and a pharmaceutically acceptable carrier or excipient.

[0049] In some embodiments, the present disclosure provides a method for producing a polypeptide, the method comprising culturing a host cell described herein under suitable conditions such that the polynucleotide is expressed and its binding partner is produced.

[0050] In certain embodiments, the present disclosure provides eukaryotic cells comprising a polynucleotide or a vector as described herein, wherein the cells are optionally totipotent, pluripotent, or pluripotent stem cells, optionally having an induced pluripotent stem cell phenotype, or optionally being leukocytes, optionally CD4+ T cells, optionally CD8+ T cells, optionally γδ T cells, optionally natural killer cells, neutrophils, or macrophages.

[0051] In some embodiments, the present disclosure provides a method comprising administering a polypeptide, a polynucleotide, a vector, a pharmaceutical composition, or a cell as described herein to an individual in need.

[0052] In some embodiments, the Disclosure provides (a) an isolated peptide conjugate formed by a covalent reaction between a targeted covalent inhibitor and a peptide, and (b) a cell-free peptide conjugate / MHC complex comprising an MHC, wherein the targeted covalent inhibitor is sotrasib, adaglasib, or divalasib, and the MHC is an HLA, wherein the HLA is HLA-A*02:01, HLA-A*03:01, or HLA-A*11:01.

[0053] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), and (a) the VH comprises (i) an amino acid sequence X N HC CDR3 containing X1X2DY, X N teeth 、 (b) The VL is an amino acid sequence selected from LWAS, FQWY, GYGW, GWYYL, YWYYM, YWYYL, GYYYPYY, SYYGFWQALW, SSRQYYHSQVEPPM, SGYYSSHWYLQSWYQ, and HYSEKWWGWYTMYID, where X1 is G or A and X2 is L or M, and / or (b) the VL is (i) LC CDR1 containing the amino acid sequence RASQSVSSAVA or a variant thereof containing 1 to 5 amino acid changes, (ii) LC CDR2 containing the amino acid sequence SASSLYS or a variant thereof containing 1 to 5 amino acid changes, and (iii) the amino acid sequence QQX3X4X5X6X7X8X9X 10 LC CDR3 containing T, where X3 is W, T, S, A or G, X4 is N, W, S, G, Y, D or K, X5 is W, Y, S, A or T, X6 is G, S, Y, L, W, E or D, X7 is W, S, H, Y, E, F or none, X8 is P, Q, S, W, E, L, G or none, X9 is L or P, X 10This includes those which are I, L, F, or V. In some embodiments, the VH includes HC CDR1 containing the amino acid sequence X1SX3X4SIH, where X1 is I, F, or V, X3 is S or Y, and X4 is S or Y. In some embodiments, the VH includes the amino acid sequence X1ISX4X5X6X7X8TX 10 HC CDR2 containing YADSVKG, where X1 is S or Y, X4 is S or P, X5 is S or Y, X6 is S or Y, X7 is S or G, X8 is S or Y, X 10 is S or Y. In some embodiments, the VL includes LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VL includes LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes.

[0054] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), (a) the VH being (i) an HC CDR1 comprising the amino acid sequence X1SX3X4SIH, where X1 is I, F, or V, X3 is S or Y, and X4 is S or Y; (ii) an amino acid sequence X1ISX4X5X6X7X8TX 10 HC CDR2 containing YADSVKG, where X1 is S or Y, X4 is S or P, X5 is S or Y, X6 is S or Y, X7 is S or G, X8 is S or Y, X 10 (iii) those which are S or Y, and amino acid sequence X N HC CDR3 containing X1X2DY, X N(i) the VL is an amino acid sequence selected from LWAS, FQWY, GYGW, GWYYL, YWYYM, YWYYL, GYYYPYY, SYYGFWQALW, SSRQYYHSQVEPPM, SGYYSSHWYLQSWYQ, and HYSEKWWGWYTMYID, where X1 is G or A and X2 is L or M, and / or (b) the VL is (i) LC CDR1 containing the amino acid sequence RASQSVSSAVA or a variant thereof containing 1 to 5 amino acid changes, (ii) LC CDR2 containing the amino acid sequence SASSLYS or a variant thereof containing 1 to 5 amino acid changes, and (iii) the amino acid sequence QQX3X4X5X6X7X8X9X 10 LC CDR3 containing T, where X3 is W, T, S, A or G, X4 is N, W, S, G, Y, D or K, X5 is W, Y, S, A or T, X6 is G, S, Y, L, W, E or D, X7 is W, S, H, Y, E, F or none, X8 is P, Q, S, W, E, L, G or none, X9 is L or P, X 10 This includes those that are I, L, F, or V.

[0055] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3 (HC CDR3) sequence LWASGLDY (SEQ ID NO: 5).

[0056] In some embodiments, the VH includes the HC CDR2 sequence SISSYYGSTSYADSVKG (SEQ ID NO: 4). In some embodiments, the VH includes the HC CDR1 sequence ISSSSIH (SEQ ID NO: 3). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQWNWGWPLIT (SEQ ID NO: 8). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 7). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 6). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence ISSSSIH (SEQ ID NO: 3), the HC CDR2 sequence SISSYYGSTSYADSVKG (SEQ ID NO: 4), the HC CDR3 sequence LWASGLDY (SEQ ID NO: 5), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 6), the LC CDR2 sequence SASSLYS (SEQ ID NO: 7), and the LC CDR3 sequence QQWNWGWPLIT (SEQ ID NO: 8). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTISSSSIHWVRQAPGKGLEWVASISSYYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARLWASGLDYWGQGTLVTVSS (SEQ ID NO: 2). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV (Sequence ID 1).

[0057] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3 (HC CDR3) sequence LWASGLDY (SEQ ID NO: 13).

[0058] In some embodiments, the VH includes the HC CDR2 sequence SISSYYGSTSYADSVKG (SEQ ID NO: 12). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 11). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQWNWGWPLIT (SEQ ID NO: 16). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 15). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 14). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 11), the HC CDR2 sequence SISSYYGSTSYADSVKG (SEQ ID NO: 12), the HC CDR3 sequence LWASGLDY (SEQ ID NO: 13), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 14), the LC CDR2 sequence SASSLYS (SEQ ID NO: 15), and the LC CDR3 sequence QQWNWGWPLIT (SEQ ID NO: 16). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSYYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARLWASGLDYWGQGTLVTVSS (SEQ ID NO: 10). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV (Sequence ID 9).

[0059] In one embodiment, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence SYYGFWQALWALDY (SEQ ID NO: 21).

[0060] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 20). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 19). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQWWYGSPLFT (SEQ ID NO: 24). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 23). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 22). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 19), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 20), the HC CDR3 sequence SYYGFWQALWALDY (SEQ ID NO: 21), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 22), the LC CDR2 sequence SASSLYS (SEQ ID NO: 23), and the LC CDR3 sequence QQWWYGSPLFT (SEQ ID NO: 24). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQALWALDYWGQGTLVTVSS (SEQ ID NO: 18). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWWYGSPLFTFGQGTKVEIKRT (Sequence ID 17).

[0061] In one embodiment, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence SYYGFWQALWALDY (SEQ ID NO: 29).

[0062] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 28). In some embodiments, the VH includes the HC CDR1 sequence FSSYSIH (SEQ ID NO: 27). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQWWYGSPLFT (SEQ ID NO: 32). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 31). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 30). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSYSIH (SEQ ID NO: 27), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 28), the HC CDR3 sequence SYYGFWQALWALDY (SEQ ID NO: 29), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 30), the LC CDR2 sequence SASSLYS (SEQ ID NO: 31), and the LC CDR3 sequence QQWWYGSPLFT (SEQ ID NO: 32). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQALWALDYWGQGTLVTVSS (SEQ ID NO: 26). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWWYGSPLFTFGQGTKVEIKRT (SEQ ID NO: 25).

[0063] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence GYYYPYYAMDY (SEQ ID NO: 37).

[0064] In some embodiments, the VH includes the HC CDR2 sequence SISSYYGSTYYADSVKG (SEQ ID NO: 36). In some embodiments, the VH includes the HC CDR1 sequence FSYYSIH (SEQ ID NO: 35). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQGKTYYPIT (SEQ ID NO: 40). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 39). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 38). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSYYSIH (SEQ ID NO: 35), the HC CDR2 sequence SISSYYGSTYYADSVKG (SEQ ID NO: 36), the HC CDR3 sequence GYYYPYYAMDY (SEQ ID NO: 37), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 38), the LC CDR2 sequence SASSLYS (SEQ ID NO: 39), and the LC CDR3 sequence QQGKTYYPIT (SEQ ID NO: 40). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS (SEQ ID NO: 34). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV (Sequence ID 33).

[0065] In one embodiment, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence GYYYPYYAMDY (SEQ ID NO: 45).

[0066] In some embodiments, the VH includes the HC CDR2 sequence SISPYYGSTYYADSVKG (SEQ ID NO: 44). In some embodiments, the VH includes the HC CDR1 sequence FSYYSIH (SEQ ID NO: 43). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQGKTYYPIT (SEQ ID NO: 48). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 47). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 46). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSYYSIH (SEQ ID NO: 43), the HC CDR2 sequence SISPYYGSTYYADSVKG (SEQ ID NO: 44), the HC CDR3 sequence GYYYPYYAMDY (SEQ ID NO: 45), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 46), the LC CDR2 sequence SASSLYS (SEQ ID NO: 47), and the LC CDR3 sequence QQGKTYYPIT (SEQ ID NO: 48). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISPYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS (SEQ ID NO: 42). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV (SEQ ID NO: 41).

[0067] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence GYYYPYYAMDY (SEQ ID NO: 53).

[0068] In some embodiments, the VH includes the HC CDR2 sequence SISSYYGSTYYADSVKG (SEQ ID NO: 52). In some embodiments, the VH includes the HC CDR1 sequence FSYYSIH (SEQ ID NO: 51). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQTSWYHSLIT (SEQ ID NO: 56). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 55). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 54). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSYYSIH (SEQ ID NO: 51), the HC CDR2 sequence SISSYYGSTYYADSVKG (SEQ ID NO: 52), the HC CDR3 sequence GYYYPYYAMDY (SEQ ID NO: 53), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 54), the LC CDR2 sequence SASSLYS (SEQ ID NO: 55), and the LC CDR3 sequence QQTSWYHSLIT (SEQ ID NO: 56). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS (SEQ ID NO: 50). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQTSWYHSLITFGQGTKVEIKRTV (Sequence ID 49).

[0069] In one embodiment, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence GYYYPYYAMDY (SEQ ID NO: 61).

[0070] In some embodiments, the VH includes the HC CDR2 sequence SISSYYGSTYYADSVKG (SEQ ID NO: 60). In some embodiments, the VH includes the HC CDR1 sequence VSYYSIH (SEQ ID NO: 59). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQGKTYYPIT (SEQ ID NO: 64). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 63). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 62). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence VSYYSIH (SEQ ID NO: 59), the HC CDR2 sequence SISSYYGSTYYADSVKG (SEQ ID NO: 60), the HC CDR3 sequence GYYYPYYAMDY (SEQ ID NO: 61), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 62), the LC CDR2 sequence SASSLYS (SEQ ID NO: 63), and the LC CDR3 sequence QQGKTYYPIT (SEQ ID NO: 64). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS (SEQ ID NO: 58). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV (SEQ ID NO: 57).

[0071] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence GYYYPYYAMDY (SEQ ID NO: 69).

[0072] In some embodiments, the VH includes the HC CDR2 sequence SISSYYGSTYYADSVKG (SEQ ID NO: 68). In some embodiments, the VH includes the HC CDR1 sequence FSYYSIH (SEQ ID NO: 67). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSWWSYPLT (SEQ ID NO: 72). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 71). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 70). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSYYSIH (SEQ ID NO: 67), the HC CDR2 sequence SISSYYGSTYYADSVKG (SEQ ID NO: 68), the HC CDR3 sequence GYYYPYYAMDY (SEQ ID NO: 69), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 70), the LC CDR2 sequence SASSLYS (SEQ ID NO: 71), and the LC CDR3 sequence QQSWWSYPLT (SEQ ID NO: 72). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS (SEQ ID NO: 66). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (SEQ ID NO: 65).

[0073] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence FQWYAMDY (SEQ ID NO: 77).

[0074] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 76). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 75). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSWLYWLVT (SEQ ID NO: 80). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 79). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 78). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 75), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 76), the HC CDR3 sequence FQWYAMDY (SEQ ID NO: 77), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 78), the LC CDR2 sequence SASSLYS (SEQ ID NO: 79), and the LC CDR3 sequence QQSSWLYWLVT (SEQ ID NO: 80). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFQWYAMDYWGQGTLVTVSS (SEQ ID NO: 74). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWLVTFGQGTKVEIKRTV (SEQ ID NO: 73).

[0075] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3 (HC CDR3) sequence GYGWGMDY (SEQ ID NO: 85).

[0076] In some embodiments, the VH includes the HC CDR2 sequence YISSYSGYTSYADSVKG (SEQ ID NO: 84). In some embodiments, the VH includes the HC CDR1 sequence ISSYSIH (SEQ ID NO: 83). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQWNWGWPLIT (SEQ ID NO: 88). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 87). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 86). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence ISSYSIH (SEQ ID NO: 83), the HC CDR2 sequence YISSYSGYTSYADSVKG (SEQ ID NO: 84), the HC CDR3 sequence GYGWGMDY (SEQ ID NO: 85), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 86), the LC CDR2 sequence SASSLYS (SEQ ID NO: 87), and the LC CDR3 sequence QQWNWGWPLIT (SEQ ID NO: 88). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTISSYSIHWVRQAPGKGLEWVAYISSYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYGWGMDYWGQGTLVTVSS (SEQ ID NO: 82). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV (Sequence ID 81).

[0077] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence SGYYSSHWYLQSWYQAMDY (SEQ ID NO: 93).

[0078] In some embodiments, the VH includes the HC CDR2 sequence YISSSSGYTSYADSVKG (SEQ ID NO: 92). In some embodiments, the VH includes the HC CDR1 sequence ISYSSIH (SEQ ID NO: 91). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSAWYPVT (SEQ ID NO: 96). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 95). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 94). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence ISYSSIH (SEQ ID NO: 91), the HC CDR2 sequence YISSSSGYTSYADSVKG (SEQ ID NO: 92), the HC CDR3 sequence SGYYSSHWYLQSWYQAMDY (SEQ ID NO: 93), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 94), the LC CDR2 sequence SASSLYS (SEQ ID NO: 95), and the LC CDR3 sequence QQSSAWYPVT (SEQ ID NO: 96). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTISYSSIHWVRQAPGKGLEWVAYISSSSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSHWYLQSWYQAMDYWGQGTLVTVSS (SEQ ID NO: 90). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV (Sequence ID 89).

[0079] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence SGYYSSHWYLQSWYQAMDY (SEQ ID NO: 101).

[0080] In some embodiments, the VH includes the HC CDR2 sequence SISSYYGSTYYADSVKG (SEQ ID NO: 100). In some embodiments, the VH includes the HC CDR1 sequence FSYYSIH (SEQ ID NO: 99). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQASYGPIT (SEQ ID NO: 104). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 103). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 102). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSYYSIH (SEQ ID NO: 99), the HC CDR2 sequence SISSYYGSTYYADSVKG (SEQ ID NO: 100), the HC CDR3 sequence SGYYSSHWYLQSWYQAMDY (SEQ ID NO: 101), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 102), the LC CDR2 sequence SASSLYS (SEQ ID NO: 103), and the LC CDR3 sequence QQASYGPIT (SEQ ID NO: 104). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSHWYLQSWYQAMDYWGQGTLVTVSS (SEQ ID NO: 98). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASYGPITFGQGTKVEIKRTV (SEQ ID NO: 97).

[0081] In one embodiment, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence HYSEKWWGWYTMYIDAMDY (SEQ ID NO: 109).

[0082] In some embodiments, the VH includes the HC CDR2 sequence SISSYYGSTYYADSVKG (SEQ ID NO: 108). In some embodiments, the VH includes the HC CDR1 sequence VSYSSIH (SEQ ID NO: 107). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQWWSSSQLIT (SEQ ID NO: 112). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 111). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 110). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence VSYSSIH (SEQ ID NO: 107), the HC CDR2 sequence SISSYYGSTYYADSVKG (SEQ ID NO: 108), the HC CDR3 sequence HYSEKWWGWYTMYIDAMDY (SEQ ID NO: 109), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 110), the LC CDR2 sequence SASSLYS (SEQ ID NO: 111), and the LC CDR3 sequence QQWWSSSQLIT (SEQ ID NO: 112). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYSSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARHYSEKWWGWYTMYIDAMDYWGQGTLVTVSS (SEQ ID NO: 106). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWWSSSQLITFGQGTKVEIKRTV (Sequence ID 105).

[0083] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence GWYYLGMDY (SEQ ID NO: 117).

[0084] In some embodiments, the VH includes the HC CDR2 sequence YISPYSGYTSYADSVKG (SEQ ID NO: 116). In some embodiments, the VH includes the HC CDR1 sequence VSYYSIH (SEQ ID NO: 115). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQGKTYYPIT (SEQ ID NO: 120). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 119). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 118). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence VSYYSIH (SEQ ID NO: 115), the HC CDR2 sequence YISPYSGYTSYADSVKG (SEQ ID NO: 116), the HC CDR3 sequence GWYYLGMDY (SEQ ID NO: 117), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 118), the LC CDR2 sequence SASSLYS (SEQ ID NO: 119), and the LC CDR3 sequence QQGKTYYPIT (SEQ ID NO: 120). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS (SEQ ID NO: 114). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV (Sequence ID 113).

[0085] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence GWYYLGMDY (SEQ ID NO: 125).

[0086] In some embodiments, the VH includes the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 124). In some embodiments, the VH includes the HC CDR1 sequence VSSYSIH (SEQ ID NO: 123). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQGKTYYPIT (SEQ ID NO: 128). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 127). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 126). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence VSSYSIH (SEQ ID NO: 123), the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 124), the HC CDR3 sequence GWYYLGMDY (SEQ ID NO: 125), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 126), the LC CDR2 sequence SASSLYS (SEQ ID NO: 127), and the LC CDR3 sequence QQGKTYYPIT (SEQ ID NO: 128). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS (SEQ ID NO: 122). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV (Sequence ID 121).

[0087] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence GWYYLGMDY (SEQ ID NO: 133).

[0088] In some embodiments, the VH includes the HC CDR2 sequence YISPYSGYTSYADSVKG (SEQ ID NO: 132). In some embodiments, the VH includes the HC CDR1 sequence VSYYSIH (SEQ ID NO: 131). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSWWSYPLT (SEQ ID NO: 136). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 135). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 134). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence VSYYSIH (SEQ ID NO: 131), the HC CDR2 sequence YISPYSGYTSYADSVKG (SEQ ID NO: 132), the HC CDR3 sequence GWYYLGMDY (SEQ ID NO: 133), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 134), the LC CDR2 sequence SASSLYS (SEQ ID NO: 135), and the LC CDR3 sequence QQSWWSYPLT (SEQ ID NO: 136). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS (SEQ ID NO: 130). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (Sequence ID 129).

[0089] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence GWYYLGMDY (SEQ ID NO: 141).

[0090] In some embodiments, the VH includes the HC CDR2 sequence YISPYSGYTSYADSVKG (SEQ ID NO: 140). In some embodiments, the VH includes the HC CDR1 sequence VSSYSIH (SEQ ID NO: 139). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSWWSYPLT (SEQ ID NO: 144). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 143). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 142). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence VSSYSIH (SEQ ID NO: 139), the HC CDR2 sequence YISPYSGYTSYADSVKG (SEQ ID NO: 140), the HC CDR3 sequence GWYYLGMDY (SEQ ID NO: 141), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 142), the LC CDR2 sequence SASSLYS (SEQ ID NO: 143), and the LC CDR3 sequence QQSWWSYPLT (SEQ ID NO: 144). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS (SEQ ID NO: 138). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (Sequence ID 137).

[0091] In one embodiment, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence GWYYLGMDY (SEQ ID NO: 149).

[0092] In some embodiments, the VH includes the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 148). In some embodiments, the VH includes the HC CDR1 sequence FSSYSIH (SEQ ID NO: 147). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSWWSYPLT (SEQ ID NO: 152). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 151). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 150). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSYSIH (SEQ ID NO: 147), the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 148), the HC CDR3 sequence GWYYLGMDY (SEQ ID NO: 149), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 150), the LC CDR2 sequence SASSLYS (SEQ ID NO: 151), and the LC CDR3 sequence QQSWWSYPLT (SEQ ID NO: 152). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS (SEQ ID NO: 146). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (SEQ ID NO: 145).

[0093] In one embodiment, the disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence GWYYLGMDY (SEQ ID NO: 157).

[0094] In some embodiments, the VH includes the HC CDR2 sequence YISPYSGYTSYADSVKG (SEQ ID NO: 156). In some embodiments, the VH includes the HC CDR1 sequence VSYYSIH (SEQ ID NO: 155). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSAWYPVT (SEQ ID NO: 160). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 159). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 158). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence VSYYSIH (SEQ ID NO: 155), the HC CDR2 sequence YISPYSGYTSYADSVKG (SEQ ID NO: 156), the HC CDR3 sequence GWYYLGMDY (SEQ ID NO: 157), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 158), the LC CDR2 sequence SASSLYS (SEQ ID NO: 159), and the LC CDR3 sequence QQSSAWYPVT (SEQ ID NO: 160). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS (SEQ ID NO: 154). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV (SEQ ID NO: 153).

[0095] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence YWYYMGMDY (SEQ ID NO: 165).

[0096] In some embodiments, the VH includes the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 164). In some embodiments, the VH includes the HC CDR1 sequence VSSYSIH (SEQ ID NO: 163). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSWWSYPLT (SEQ ID NO: 168). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 167). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 166). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence VSSYSIH (SEQ ID NO: 163), the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 164), the HC CDR3 sequence YWYYMGMDY (SEQ ID NO: 165), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 166), the LC CDR2 sequence SASSLYS (SEQ ID NO: 167), and the LC CDR3 sequence QQSWWSYPLT (SEQ ID NO: 168). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS (SEQ ID NO: 162). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (Sequence ID 161).

[0097] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence YWYYMGMDY (SEQ ID NO: 173).

[0098] In some embodiments, the VH includes the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 172). In some embodiments, the VH includes the HC CDR1 sequence VSSYSIH (SEQ ID NO: 171). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSAWYPVT (SEQ ID NO: 176). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 175). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 174). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence VSSYSIH (SEQ ID NO: 171), the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 172), the HC CDR3 sequence YWYYMGMDY (SEQ ID NO: 173), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 174), the LC CDR2 sequence SASSLYS (SEQ ID NO: 175), and the LC CDR3 sequence QQSSAWYPVT (SEQ ID NO: 176). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS (SEQ ID NO: 170). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV (Sequence ID 169).

[0099] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence YWYYMGMDY (SEQ ID NO: 181).

[0100] In some embodiments, the VH includes the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 180). In some embodiments, the VH includes the HC CDR1 sequence VSSYSIH (SEQ ID NO: 179). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSYYEELIT (SEQ ID NO: 184). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 183). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 182). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence VSSYSIH (SEQ ID NO: 179), the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 180), the HC CDR3 sequence YWYYMGMDY (SEQ ID NO: 181), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 182), the LC CDR2 sequence SASSLYS (SEQ ID NO: 183), and the LC CDR3 sequence QQSSYYEELIT (SEQ ID NO: 184). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS (SEQ ID NO: 178). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSYYEELITFGQGTKVEIKRTV (Sequence ID 177).

[0101] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence YWYYMGMDY (SEQ ID NO: 189).

[0102] In some embodiments, the VH includes the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 188). In some embodiments, the VH includes the HC CDR1 sequence VSSYSIH (SEQ ID NO: 187). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQAYSDPLT (SEQ ID NO: 192). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 191). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 190). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence VSSYSIH (SEQ ID NO: 187), the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 188), the HC CDR3 sequence YWYYMGMDY (SEQ ID NO: 189), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 190), the LC CDR2 sequence SASSLYS (SEQ ID NO: 191), and the LC CDR3 sequence QQAYSDPLT (SEQ ID NO: 192). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS (SEQ ID NO: 186). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQAYSDPLTFGQGTKVEIKRTV (SEQ ID NO: 185).

[0103] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence YWYYMGMDY (SEQ ID NO: 197).

[0104] In some embodiments, the VH includes the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 196). In some embodiments, the VH includes the HC CDR1 sequence VSSYSIH (SEQ ID NO: 195). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQGSSSLLT (SEQ ID NO: 200). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 199). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 198). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence VSSYSIH (SEQ ID NO: 195), the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 196), the HC CDR3 sequence YWYYMGMDY (SEQ ID NO: 197), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 198), the LC CDR2 sequence SASSLYS (SEQ ID NO: 199), and the LC CDR3 sequence QQGSSSLLT (SEQ ID NO: 200). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS (SEQ ID NO: 194). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGSSSLLTFGQGTKVEIKRTV (Sequence ID 193).

[0105] In one embodiment, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence YWYYMGMDY (SEQ ID NO: 205).

[0106] In some embodiments, the VH includes the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 204). In some embodiments, the VH includes the HC CDR1 sequence VSSYSIH (SEQ ID NO: 203). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSGSYLLIT (SEQ ID NO: 208). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 207). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 206). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence VSSYSIH (SEQ ID NO: 203), the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 204), the HC CDR3 sequence YWYYMGMDY (SEQ ID NO: 205), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 206), the LC CDR2 sequence SASSLYS (SEQ ID NO: 207), and the LC CDR3 sequence QQSGSYLLIT (SEQ ID NO: 208). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS (SEQ ID NO: 202). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSGSYLLITFGQGTKVEIKRTV (Sequence ID 201).

[0107] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence YWYYMGMDY (SEQ ID NO: 213).

[0108] In some embodiments, the VH includes the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 212). In some embodiments, the VH includes the HC CDR1 sequence VSSYSIH (SEQ ID NO: 211). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQADYEFGLIT (SEQ ID NO: 216). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 215). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 214). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence VSSYSIH (SEQ ID NO: 211), the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 212), the HC CDR3 sequence YWYYMGMDY (SEQ ID NO: 213), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 214), the LC CDR2 sequence SASSLYS (SEQ ID NO: 215), and the LC CDR3 sequence QQADYEFGLIT (SEQ ID NO: 216). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS (SEQ ID NO: 210). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQADYEFGLITFGQGTKVEIKRTV (Sequence ID 209).

[0109] In one embodiment, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence SSRQYYHSQVEPPMAMDY (SEQ ID NO: 221).

[0110] In some embodiments, the VH includes the HC CDR2 sequence YISSSYGYTSYADSVKG (SEQ ID NO: 220). In some embodiments, the VH includes the HC CDR1 sequence FSSYSIH (SEQ ID NO: 219). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSWWSYPLT (SEQ ID NO: 224). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 223). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 222). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSYSIH (SEQ ID NO: 219), the HC CDR2 sequence YISSSYGYTSYADSVKG (SEQ ID NO: 220), the HC CDR3 sequence SSRQYYHSQVEPPMAMDY (SEQ ID NO: 221), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 222), the LC CDR2 sequence SASSLYS (SEQ ID NO: 223), and the LC CDR3 sequence QQSWWSYPLT (SEQ ID NO: 224). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS (SEQ ID NO: 218). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (SEQ ID NO: 217).

[0111] In one embodiment, the disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence SSRQYYHSQVEPPMAMDY (SEQ ID NO: 229).

[0112] In some embodiments, the VH includes the HC CDR2 sequence YISSSYGYTSYADSVKG (SEQ ID NO: 228). In some embodiments, the VH includes the HC CDR1 sequence FSYYSIH (SEQ ID NO: 227). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSWWSYPLT (SEQ ID NO: 232). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 231). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 230). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSYYSIH (SEQ ID NO: 227), the HC CDR2 sequence YISSSYGYTSYADSVKG (SEQ ID NO: 228), the HC CDR3 sequence SSRQYYHSQVEPPMAMDY (SEQ ID NO: 229), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 230), the LC CDR2 sequence SASSLYS (SEQ ID NO: 231), and the LC CDR3 sequence QQSWWSYPLT (SEQ ID NO: 232). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS (SEQ ID NO: 226). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (SEQ ID NO: 225).

[0113] In one embodiment, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence SSRQYYHSQVEPPMAMDY (SEQ ID NO: 237).

[0114] In some embodiments, the VH includes the HC CDR2 sequence YISSSYGYTSYADSVKG (SEQ ID NO: 236). In some embodiments, the VH includes the HC CDR1 sequence VSSSSIH (SEQ ID NO: 235). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSWWSYPLT (SEQ ID NO: 240). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 239). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 238). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence VSSSSIH (SEQ ID NO: 235), the HC CDR2 sequence YISSSYGYTSYADSVKG (SEQ ID NO: 236), the HC CDR3 sequence SSRQYYHSQVEPPMAMDY (SEQ ID NO: 237), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 238), the LC CDR2 sequence SASSLYS (SEQ ID NO: 239), and the LC CDR3 sequence QQSWWSYPLT (SEQ ID NO: 240). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSSSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS (SEQ ID NO: 234). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (SEQ ID NO: 233).

[0115] In one embodiment, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence SSRQYYHSQVEPPMAMDY (SEQ ID NO: 245).

[0116] In some embodiments, the VH includes the HC CDR2 sequence YISSSYGYTSYADSVKG (SEQ ID NO: 244). In some embodiments, the VH includes the HC CDR1 sequence VSYSSIH (SEQ ID NO: 243). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSWWSYPLT (SEQ ID NO: 248). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 247). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 246). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence VSYSSIH (SEQ ID NO: 243), the HC CDR2 sequence YISSSYGYTSYADSVKG (SEQ ID NO: 244), the HC CDR3 sequence SSRQYYHSQVEPPMAMDY (SEQ ID NO: 245), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 246), the LC CDR2 sequence SASSLYS (SEQ ID NO: 247), and the LC CDR3 sequence QQSWWSYPLT (SEQ ID NO: 248). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYSSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS (SEQ ID NO: 242). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (SEQ ID NO: 241).

[0117] In one embodiment, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3 (HC CDR3) sequence YWYYLGMDY (SEQ ID NO: 253).

[0118] In some embodiments, the VH includes the HC CDR2 sequence YISPYSGYTYYADSVKG (SEQ ID NO: 252). In some embodiments, the VH includes the HC CDR1 sequence VSSYSIH (SEQ ID NO: 251). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQGSSSLLT (SEQ ID NO: 256). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 255). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 254). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence VSSYSIH (SEQ ID NO: 251), the HC CDR2 sequence YISPYSGYTYYADSVKG (SEQ ID NO: 252), the HC CDR3 sequence YWYYLGMDY (SEQ ID NO: 253), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 254), the LC CDR2 sequence SASSLYS (SEQ ID NO: 255), and the LC CDR3 sequence QQGSSSLLT (SEQ ID NO: 256). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVAYISPYSGYTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYLGMDYWGQGTLVTVSS (SEQ ID NO: 250). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGSSSLLTFGQGTKVEIKRTV (SEQ ID NO: 249).

[0119] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein (a) the VH comprises (i) an HC CDR3 comprising the amino acid sequence LWASGLDY, and / or (b) the VL comprises (i) an LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T, where X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V.

[0120] In some embodiments, the VH comprises an HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes. In some embodiments, the VH comprises an HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VL comprises an LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VL comprises an LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VH comprises (a) an HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes, (b) an HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) an HC CDR3 comprising the amino acid sequence LWASGLDY. In some embodiments, the VL includes (a) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (b) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T, where X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V.

[0121] In some embodiments, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy-chain variable region (VH) and / or a light-chain variable region (VL), and (a) the VH comprises (i) an HC CDR3 comprising the amino acid sequence SYYGFWQALWALDY, and / or (b) the VL comprises (i) an LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T, where X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V. In some embodiments, the VH comprises an HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes. In some embodiments, the VH comprises an HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VL comprises an LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VL comprises an LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VH comprises (a) an HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes, (b) an HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) an HC CDR3 comprising the amino acid sequence SYYGFWQALWALDY.In some embodiments, the VL includes (a) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (b) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T, where X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V.

[0122] In some embodiments, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy-chain variable region (VH) and / or a light-chain variable region (VL), and (a) the VH comprises (i) an HC CDR3 comprising the amino acid sequence GYYYPYYAMDY, and / or (b) the VL comprises (i) an LC CDR3 comprising the amino acid sequence QQX1X2X3X4YPX5T, where X1 is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5 is I, L, or V. In some embodiments, the VH comprises an HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes. In some embodiments, the VH comprises an HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VL includes LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VL includes LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VH includes (a) HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes, (b) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) HC CDR3 comprising the amino acid sequence GYYYPYYAMDY. In some embodiments, the VL includes (a) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (b) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) LC CDR3 comprising the amino acid sequence QQX1X2X3X4YPX5T, where X1 is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5 is I, L, or V.

[0123] In some embodiments, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy-chain variable region (VH) and / or a light-chain variable region (VL), and (a) the VH comprises (i) an HC CDR3 comprising the amino acid sequence GYYYPYYAMDY, and / or (b) the VL comprises (i) an LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T, where X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V. In some embodiments, the VH comprises an HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes. In some embodiments, the VH comprises an HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VL comprises an LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VL comprises an LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VH comprises (a) an HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes, (b) an HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) an HC CDR3 comprising the amino acid sequence GYYYPYYAMDY.In some embodiments, the VL includes (a) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (b) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T, where X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V.

[0124] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), and (a) the VH comprises (i) an HC CDR3 comprising the amino acid sequence X1X2X3X4X5MDY, where X1 is F or G, X2 is Q or Y, X3 is W or G, X4 is Y or W, and X5 is A or G, and / or (b) the VL comprises (i) an LC comprising the amino acid sequence QQX1X2X3X4X5X6LX7T CDR3 includes a CDR3 in which X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V. In some embodiments, the VH includes an HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing 1 to 3 amino acid changes. In some embodiments, the VH includes an HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes. In some embodiments, the VL includes an LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes. In some embodiments, the VL includes an LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes. In some embodiments, the VH includes (a) HC CDR1 comprising the amino acid sequence FSSSSIH or a variant thereof comprising 1 to 3 amino acid changes, (b) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) HC CDR3 comprising the amino acid sequence X1X2X3X4X5MDY, where X1 is F or G, X2 is Q or Y, X3 is W or G, X4 is Y or W, and X5 is A or G.In some embodiments, the VL includes (a) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (b) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T, where X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V.

[0125] In some embodiments, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy-chain variable region (VH) and / or a light-chain variable region (VL), and (a) the VH comprises (i) an HC CDR3 comprising the amino acid sequence SGYYSSHWYLQSWYQAMDY, and / or (b) the VL comprises (i) an LC CDR3 comprising the amino acid sequence QQX1X2X3X4YPX5T, where X1 is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5 is I, L, or V. In some embodiments, the VH comprises an HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes. In some embodiments, the VH comprises an HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VL includes LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VL includes LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VH includes (a) HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes, (b) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) HC CDR3 comprising the amino acid sequence SGYYSSHWYLQSWYQAMDY.In some embodiments, the VL includes (a) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (b) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) LC CDR3 comprising the amino acid sequence QQX1X2X3X4YPX5T, where X1 is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5 is I, L, or V.

[0126] In some embodiments, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy-chain variable region (VH) and / or a light-chain variable region (VL), and (a) the VH comprises (i) an HC CDR3 comprising the amino acid sequence SGYYSSHWYLQSWYQAMDY, and / or (b) the VL comprises (i) an LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6T, where X1 is G or A, X2 is S or Y, X3 is S or Y, X4 is G, D, or S, X5 is P or L, and X6 is I or L. In some embodiments, the VH comprises an HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes. In some embodiments, the VH comprises an HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VL comprises an LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VL comprises an LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VH comprises (a) an HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes, (b) an HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) an HC CDR3 comprising the amino acid sequence SGYYSSHWYLQSWYQAMDY.In some embodiments, the VL includes (a) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (b) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6T, where X1 is G or A, X2 is S or Y, X3 is S or Y, X4 is G, D, or S, X5 is P or L, and X6 is I or L.

[0127] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein (a) the VH comprises (i) an HC CDR3 comprising the amino acid sequence HYSEKWWGWYTMYIDAMDY, and / or (b) the VL comprises (i) an LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T, where X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V. In some embodiments, the VH comprises an HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes. In some embodiments, the VH comprises an HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VL comprises an LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VL comprises an LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VH comprises (a) an HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes, (b) an HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) an HC CDR3 comprising the amino acid sequence HYSEKWWGWYTMYIDAMDY.In some embodiments, the VL includes (a) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (b) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T, where X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V.

[0128] In some embodiments, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy-chain variable region (VH) and / or a light-chain variable region (VL), and (a) the VH comprises (i) an HC CDR3 comprising the amino acid sequence X1WYYX2GMDY, where X1 is G or Y and X2 is M or L, and / or (b) the VL comprises (i) an LC CDR3 comprising the amino acid sequence QQX1X2X3X4YPX5T, where X1 is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5 is I, L, or V. In some embodiments, the VH comprises an HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes. In some embodiments, the VH comprises an HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VL comprises an LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VL comprises an LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VH comprises (a) an HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes, (b) an HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) an HC CDR3 comprising the amino acid sequence X1WYYX2GMDY, where X1 is G or Y, and X2 is M or L.In some embodiments, the VL includes (a) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (b) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) LC CDR3 comprising the amino acid sequence QQX1X2X3X4YPX5T, where X1 is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5 is I, L, or V.

[0129] In some embodiments, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy-chain variable region (VH) and / or a light-chain variable region (VL), and (a) the VH comprises (i) an HC CDR3 comprising the amino acid sequence X1WYYX2GMDY, where X1 is G or Y and X2 is M or L, and / or (b) the VL comprises (i) an LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6T, where X1 is G or A, X2 is S or Y, X3 is S or Y, X4 is G, D, or S, X5 is P or L, and X6 is I or L. In some embodiments, the VH comprises an HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes. In some embodiments, the VH comprises an HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VL comprises an LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VL comprises an LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VH comprises (a) an HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes, (b) an HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) an HC CDR3 comprising the amino acid sequence X1WYYX2GMDY, where X1 is G or Y, and X2 is M or L.In some embodiments, the VL includes (a) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (b) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6T, where X1 is G or A, X2 is S or Y, X3 is S or Y, X4 is G, D, or S, X5 is P or L, and X6 is I or L.

[0130] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), and (a) the VH comprises (i) an HC CDR3 comprising the amino acid sequence X1WYYX2GMDY, where X1 is G or Y and X2 is M or L, and / or (b) the VL comprises (i) an LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T, where X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V. In some embodiments, the VH comprises an HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof containing 1 to 3 amino acid changes. In some embodiments, the VH comprises an HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes. In some embodiments, the VL comprises an LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes. In some embodiments, the VL comprises an LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes. In some embodiments, the VH includes (a) HC CDR1 comprising the amino acid sequence FSSSSIH or a variant thereof comprising 1 to 3 amino acid changes, (b) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) HC CDR3 comprising the amino acid sequence X1WYYX2GMDY, where X1 is G or Y and X2 is M or L.In some embodiments, the VL includes (a) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (b) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T, where X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V.

[0131] In some embodiments, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy-chain variable region (VH) and / or a light-chain variable region (VL), and (a) the VH comprises (i) an HC CDR3 comprising the amino acid sequence SSRQYYHSQVEPPMAMDY, and / or (b) the VL comprises (i) an LC CDR3 comprising the amino acid sequence QQX1X2X3X4YPX5T, where X1 is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5 is I, L, or V. In some embodiments, the VH comprises an HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes. In some embodiments, the VH comprises an HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VL includes LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VL includes LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes. In some embodiments, the VH includes (a) HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes, (b) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) HC CDR3 comprising the amino acid sequence SSRQYYHSQVEPPMAMDY.In some embodiments, the VL includes (a) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (b) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (c) LC CDR3 comprising the amino acid sequence QQX1X2X3X4YPX5T, where X1 is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5 is I, L, or V.

[0132] In some embodiments, the antigen-binding domain binds to a peptide conjugate / MHC complex, wherein the peptide conjugate of the peptide conjugate / MHC complex is a targeted covalent inhibitor or a fragment thereof and a peptide covalently bound to an MHC. In some embodiments, the targeted covalent inhibitor is adaglacib, sotracib, or divalacib. In some embodiments, the peptide conjugate / MHC complex is a first peptide conjugate / MHC complex comprising a first peptide conjugate containing a first peptide and a first targeted covalent inhibitor or a fragment thereof, wherein the antigen-binding domain further binds to a second peptide conjugate / MHC complex, the second peptide conjugate / MHC complex comprising (a) a second peptide conjugate, wherein the second peptide conjugate of the second peptide conjugate / MHC complex is a second peptide covalently bound to a second targeted covalent inhibitor or a fragment thereof, and (b) a second MHC.

[0133] In some embodiments, the antigen-binding domain (i) provides the first peptide conjugate / MHC complex with a dissociation constant (K) up to approximately 50 nM. D ) and (ii) the second peptide conjugate / MHC complex with up to approximately 50 nM of K DIt binds via (i) a dissociation constant (K) up to about 10 nM to the first peptide conjugate / MHC complex. D ) and (ii) the second peptide conjugate / MHC complex with up to approximately 10 nM of K D It binds via (i) a dissociation constant (K) up to about 5 nM to the first peptide conjugate / MHC complex. D ) and (ii) the second peptide conjugate / MHC complex with up to approximately 5 nM of K D They are joined together.

[0134] In some embodiments, (i) the first targeted covalent inhibitor is adagrasib and the second targeted covalent inhibitor is sotrasib; (ii) the first targeted covalent inhibitor is adagrasib and the second targeted covalent inhibitor is divalasib; or (iii) the first targeted covalent inhibitor is divalasib and the second targeted covalent inhibitor is sotrasib.

[0135] In some embodiments, the antigen-binding domain is configured to release a first targeted covalent inhibitor with a dissociation constant (K D) Does not bind at concentrations less than 200 nM. In some embodiments, the antigen-binding domain binds to the first peptide conjugate / MHC complex with greater affinity than to the first peptide or the free first targeted covalent inhibitor. In some embodiments, the affinity of the antigen-binding domain to the first peptide conjugate / MHC complex is 100 to 10,000 times greater than the affinity of the antigen-binding domain to the first peptide or the free first targeted covalent inhibitor. In some embodiments, the antigen-binding domain does not bind to the complex of the first peptide and MHC in a detectable manner, in which case the first peptide is not covalently bound to the first targeted covalent inhibitor or its fragment. In some embodiments, the antigen-binding domain does not bind to the free first targeted covalent inhibitor in a detectable manner. In some embodiments, the antigen-binding domain binds to the free first peptide conjugate with a dissociation constant (K) of the antibody or the antigen-binding fragment to the first peptide conjugate / MHC complex. D ) at least 2.5 times K D It binds via a dissociation constant (K) to a free second targeted covalent inhibitor. In some embodiments, the antigen-binding domain is used to dissociate a second targeted covalent inhibitor. D ) Does not bind at concentrations below 200 nM.

[0136] In some embodiments, the antigen-binding domain binds to the second peptide conjugate / MHC complex with greater affinity than to the second peptide or the free second targeted covalent inhibitor. In some embodiments, the affinity of the antigen-binding domain to the second peptide conjugate / MHC complex is 100 to 10,000 times greater than the affinity of the antigen-binding domain to the second peptide or the free second targeted covalent inhibitor. In some embodiments, the antigen-binding domain does not bind to the complex of the second peptide and the second MHC in a detectable manner, in which case the second peptide is not covalently bound to the second targeted covalent inhibitor or its fragment. In some embodiments, the antigen-binding domain does not bind to the free second targeted covalent inhibitor in a detectable manner. In some embodiments, the antigen-binding domain binds to the free second peptide conjugate with a dissociation constant (K) of the antibody or antigen-binding fragment to the second peptide conjugate / MHC complex. D ) at least 2.5 times K D They are joined together.

[0137] In some embodiments, the first peptide and the second peptide contain the same amino acid sequence. In some embodiments, the first peptide and the second peptide consist of the same amino acid sequence. In some embodiments, the first peptide or the second peptide contains the amino acid sequence VVVGACGVGK. In some embodiments, the first peptide and the second peptide contain different amino acid sequences. In some embodiments, the first peptide or the second peptide contains the amino acid sequence VVVGACGVGK, VVGACGVGK, or KLVVVGACGV. In some embodiments, the MHC is HLA, and the HLA is HLA-A*02:01, HLA-A*03:01, or HLA-A*11:01.

[0138] In some embodiments, the first peptide or the second peptide is KRAS or derived from KRAS. G12C KRAS G12D , or KRAS G12R The segment includes. In some embodiments, the first peptide conjugate is a free first targeted covalent inhibitor and KRAS G12C Peptides, KRAS G12D Peptides, or KRAS G12R It is formed by a covalent bonding reaction with a peptide. In some embodiments, the second peptide conjugate is released with a second targeted covalent inhibitor and KRAS G12C Peptides, KRAS G12D Peptides, or KRAS G12R It is formed by a covalent bonding reaction with a peptide. In some embodiments, the free first targeted covalent inhibitor or the free second targeted covalent inhibitor is sotrasib, adaglasib, or divalasib. In some embodiments, the first peptide or the second peptide comprises the amino acid sequence VVVGACGVGK, VVGACGVGK, or KLVVVGACGV.

[0139] In some embodiments, the antigen-binding domain is (a) a first peptide conjugate / MHC complex containing VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex containing VVVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and (b) a first peptide conjugate containing VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 (c) It binds to the / MHC complex and a second peptide conjugate / MHC complex containing VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, or (c) a first peptide conjugate / MHC complex containing KLVVVGACGV conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01, and a second peptide conjugate / MHC complex containing KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

[0140] In some embodiments, the antigen-binding domain is (a) a first peptide conjugate / MHC complex containing VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex containing VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and (b) a first peptide conjugate containing VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 (c) It binds to the / MHC complex and a second peptide conjugate / MHC complex containing KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01, or (c) a first peptide conjugate / MHC complex containing VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex containing KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

[0141] In some embodiments, the antigen-binding domain is (a) a first peptide conjugate / MHC complex containing VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex containing VVVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01, and (b) a first peptide conjugate containing VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 (c) It binds to the / MHC complex and a second peptide conjugate / MHC complex containing VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01, or (c) a first peptide conjugate / MHC complex containing KLVVVGACGV conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01, and a second peptide conjugate / MHC complex containing KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

[0142] In some embodiments, the antigen-binding domain is (a) a first peptide conjugate / MHC complex containing VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex containing VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01, and (b) a first peptide conjugate containing VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 (c) It binds to the / MHC complex and a second peptide conjugate / MHC complex containing KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01, or (c) a first peptide conjugate / MHC complex containing VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex containing KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

[0143] In some embodiments, the antigen-binding domain is (a) a first peptide conjugate / MHC complex containing VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex containing VVVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01, and (b) a first peptide conjugate containing VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 (c) It binds to the / MHC complex and a second peptide conjugate / MHC complex containing VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01, or (c) a first peptide conjugate / MHC complex containing KLVVVGACGV conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01, and a second peptide conjugate / MHC complex containing KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

[0144] In some embodiments, the antigen-binding domain is (a) a first peptide conjugate / MHC complex containing VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex containing VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01, and (b) a first peptide conjugate containing VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 (c) It binds to the / MHC complex and a second peptide conjugate / MHC complex containing KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01, or (c) a first peptide conjugate / MHC complex containing VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex containing KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

[0145] In some embodiments, the antigen-binding domain is (a) a first peptide conjugate / MHC complex containing VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01, and a second peptide conjugate / MHC complex containing VVVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and (b) a first peptide conjugate containing VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01 (c) It binds to the / MHC complex and a second peptide conjugate / MHC complex containing VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, or (c) a first peptide conjugate / MHC complex containing KLVVVGACGV conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01, and a second peptide conjugate / MHC complex containing KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

[0146] In some embodiments, the antigen-binding domain is (a) a first peptide conjugate / MHC complex containing VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01, and a second peptide conjugate / MHC complex containing VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and (b) a first peptide conjugate containing VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01 (c) It binds to the / MHC complex and a second peptide conjugate / MHC complex containing KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01, or (c) a first peptide conjugate / MHC complex containing VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01, and a second peptide conjugate / MHC complex containing KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

[0147] In some embodiments, the first targeted covalent inhibitor or the second targeted covalent inhibitor is sotrasib, adagrasib, or diasib.

[0148] In some embodiments, the VH is linked to the VL via a linker array. In some embodiments, the linker array is (G4S) n or (S4G) nThis includes, in which case n is any integer from 1 to 10. In some embodiments, the linker comprises a glycine-serine-alanine linker G4SA3 or a glycine-serine linker (G4S)4. In some embodiments, the polypeptide is an intact antibody, a bispecific antibody, a multispecific antibody, an antigen-binding (Fab) fragment, a Fab' fragment, a (Fab')2 fragment, Fd, Fv, dAb, a single-domain fragment or a single monomer variable antibody domain, a single-chain diabody (scDb), a diabody (Db), a biaffinity retargeting (DART) molecule, a single-chain variable fragment (scFv), a bispecific T cell engager (BiTE), a bispecific killer cell engager (BiKE), a CrossMab, a triple-specific binding partner, a chimeric antigen receptor (CAR), a camelid antibody, a monobody (e.g., adonectin), a DARPin, an anticarin, an affibody, or an affimer. In some embodiments, the polypeptide comprises a monobody (e.g., adnectin), DARPin, antikalin, an affibody, or an affimer. In some embodiments, the polypeptide comprises a polypeptide chain comprising the antigen-binding domain. In some embodiments, the polypeptide chain further comprises a cytokine or a fragment thereof. In some embodiments, the cytokine comprises IL-2, IL-7, IL-15, IL-12, IL-18, IL-21, or interferon (IFN). In some embodiments, the cytokine comprises modified or mutated IL-2, IL-7, IL-15, IL-12, IL-18, IL-21, or IFN. In some embodiments, the polypeptide chain further comprises an agonist molecule. In some embodiments, the agonist molecule is a CD28 agonist or a 4-1BB agonist.

[0149] In some embodiments, the present disclosure provides a pharmaceutical composition comprising a polypeptide described herein and a pharmaceutically acceptable carrier, excipient, adjuvant, or diluent.

[0150] In some embodiments, the Disclosure provides a method for treating a subject in need of cancer treatment, in which the subject has been treated with a free targeted covalent inhibitor, and the method comprises administering to the subject a polypeptide or a pharmaceutical composition described herein. In some embodiments, the free targeted covalent inhibitor is sotrasib, adaglasib, or divalasib. In some embodiments, the subject is resistant to treatment with the free targeted covalent inhibitor.

[0151] In some embodiments, the Disclosure provides a method for treating a subject in need of cancer treatment, the method comprising administering to the subject a polypeptide or a pharmaceutical composition described herein. In some embodiments, the method further comprises co-administering a small molecule drug.

[0152] In some embodiments, the Disclosure provides a polypeptide or pharmaceutical composition described herein, and a method for administering the free targeted covalent inhibitor to a subject requiring administration of the free targeted covalent inhibitor, which is optionally sotrasib, adaglasib, or divalasib. In some embodiments, the polypeptide or pharmaceutical composition described herein is administered after or concurrently with the administration of the free targeted covalent inhibitor.

[0153] In one aspect, the present disclosure provides a method of producing a T cell receptor (TCR) that recognizes the first peptide conjugate / MHC complex or the second peptide conjugate / MHC complex described herein, the method comprising: (a) a plurality of candidate TCRs and the first peptide conjugate / MHC complex or the second peptide conjugate / MHC complex, and (b) identifying at least one TCR that binds to the first peptide conjugate / MHC complex or the second peptide conjugate / MHC complex. In some embodiments, the identification in (b) further comprises selecting or isolating the at least one TCR.

[0154] In some embodiments, the plurality of candidate TCRs are a plurality of soluble TCRs or a plurality of TCRs expressed on the cell surface of a plurality of cells. In some embodiments, the plurality of candidate TCRs are a plurality of TCRs expressed on the cell surface of the plurality of cells, and the identification in (b) comprises isolating or selecting a cell comprising the at least one TCR based on an activation marker of the cell. In some embodiments, the activation marker is a T cell activation marker. In some embodiments, the T cell activation marker is CD26, CD27, CD28, CD30, CD154, CD40L, CD134, CD25, CD44, CD69, CD137, PD-1 or KLRG1.

[0155] In one aspect, the present disclosure provides a T cell receptor (TCR) comprising at least one TCR of (b) of the method described herein. In some embodiments, the TCR is a soluble TCR. In some embodiments, the TCR is a bispecific TCR.

[0156] In some embodiments, the first peptide conjugate / MHC complex is different from the second peptide conjugate / MHC complex, and each of the first and second peptide conjugate / MHC complexes is independently of the formula X # X #+1 X #+2 X #+3 X #+4(X #+5 )X #+6 X #+7 X #+8 X #+9 、and X # X #+1 X #+2 X #+3 (X #+4 )X #+5 X #+6 X #+7 X #+8 X #+9 、and X # X #+1 X #+2 (X #+3 )X #+4 X #+5 X #+6 X #+7 X #+8 X #+9 、and X # X #+1 (X #+2 )X #+3 X #+4 X #+5 X #+6 X #+7 X #+8 X #+9 、and X #-1 X # X #+1 X #+2 X #+3 X #+4 (X #+5 )X #+6 X #+7 X #+8 X #+9 、and X #+1 X #+2 X #+3 X #+4 (X #+5 )X #+6 X #+7 X #+8 X #+9 are different peptides selected from the group consisting of peptides containing where the peptide conjugate of the first and second peptide conjugate / MHC complex is formed by a covalent reaction between the first targeted covalent inhibitor, the second targeted covalent inhibitor or a fragment thereof and the residues within the parentheses, and (b) the same MHC, and the polypeptide has a K of up to 100 nM for the first peptide conjugate / MHC complexD It binds to the second peptide conjugate / MHC complex and contains up to 100 nM of K D If the polypeptide binds or is in contact with the first peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis with background subtraction; if the polypeptide is in contact with the second peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis; or if the polypeptide is in contact with the first peptide conjugate / MHC complex, a maximum binding signal of at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction; if the polypeptide is in contact with the second peptide conjugate / MHC complex, a maximum binding signal of at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction, and the reference binding signal is X # X #+1 X #+2 X #+3 X #+4 (X #+5 )X #+6 X #+7 X #+8 X #+9 This is the maximum binding signal for polypeptides that bind to a specific target molecule.

[0157] In some embodiments, formula X # X #+1 X #+2 X #+3 X #+4 (X #+5 )X #+6 X #+7 X #+8 X #+9 is the formula X7X8X9X 10 X 11 X 12 X 13 X 14 X 15 X 16 X 12The polypeptide is covalently bound to the first targeted covalent inhibitor, the second targeted covalent inhibitor, or a fragment thereof. In some embodiments, the polypeptide is bound to the first peptide conjugate / MHC complex and the second peptide conjugate / MHC complex, and each of the first and second peptide conjugate / MHC complexes is of the formula X7X8X9X 10 X 11 X 12 X 13 X 14 X 15 X 16 A peptide comprising the same MHC, wherein the first peptide conjugate of the first peptide conjugate / MHC complex comprises the first targeted covalent inhibitor or a fragment thereof, and the X of the peptide. 12 Formed by a covalent bond reaction with the second peptide conjugate / MHC complex, the second peptide conjugate of the second targeted covalent inhibitor or a fragment thereof and the X of the peptide 13 The second targeted covalent inhibitor is formed by a covalent bonding reaction with the first targeted covalent inhibitor, and the polypeptide is the same as the first targeted covalent inhibitor, and the polypeptide is the same as the first peptide conjugate / MHC complex. D K is up to 100,000 times higher D The maximum wavelength shift of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum wavelength shift of the polypeptide bound to the first peptide conjugate / MHC complex, or the maximum binding signal of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum binding signal of the polypeptide bound to the first peptide conjugate / MHC complex.

[0158] In some embodiments, the polypeptide is bound to the first peptide conjugate / MHC complex and the second peptide conjugate / MHC complex, and each of the first and second peptide conjugate / MHC complexes is of the formula X7X8X9X 10 X 11 X 12 X 13 X 14 X 15 X 16 A peptide comprising the same MHC, wherein the first peptide conjugate of the first peptide conjugate / MHC complex comprises the first targeted covalent inhibitor or a fragment thereof, and X9, X 10 , X 11 , and X 12 Formed by a covalent bond reaction with a residue selected from the group consisting of, the second peptide conjugate of the second peptide conjugate / MHC complex is the second targeted covalent inhibitor or a fragment thereof and X 13 , X 14 , and X 15 The second targeted covalent inhibitor is formed by a covalent bond reaction with a residue selected from the group consisting of the following, and the polypeptide is the same as the first targeted covalent inhibitor, and the polypeptide is formed by a covalent bond reaction with the second peptide conjugate / MHC complex, with respect to the K of the polypeptide relative to the first peptide conjugate / MHC complex. D K is up to 100,000 times higher D The maximum wavelength shift of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum wavelength shift of the polypeptide bound to the first peptide conjugate / MHC complex, or the maximum binding signal of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum binding signal of the polypeptide bound to the first peptide conjugate / MHC complex.

[0159] In some embodiments, the polypeptide is bound to the first peptide conjugate / MHC complex and the second peptide conjugate / MHC complex, each of which is a peptide comprising formula ABC, where A comprises three or fewer residues having an N-terminal anchor residue, B comprises at least four but seven residues having residues covalently bound to the first targeted covalent inhibitor or fragment thereof or the second targeted covalent inhibitor or fragment thereof, and C comprises three or fewer residues having a C-terminal anchor residue, wherein the N-terminal anchor residue and the C-terminal anchor residue are MHC-bound and include the same MHC, and the residues covalently bound to the first targeted covalent inhibitor or fragment of the peptide in the first peptide conjugate / MHC complex are different from the residues covalently bound to the second targeted covalent inhibitor or fragment of the peptide in the second peptide conjugate / MHC complex, the polypeptide is bound to the first peptide conjugate / MHC complex with up to 100 nM of K D It binds to the second peptide conjugate / MHC complex, and up to 100 nM of K is added to the complex. D If the polypeptide binds or is in contact with the first peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis with background subtraction; if the polypeptide is in contact with the second peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis with background subtraction; or if the polypeptide is in contact with the first peptide conjugate / MHC complex, a maximum binding signal of at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction; if the polypeptide is in contact with the second peptide conjugate / MHC complex, a maximum binding signal of at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction, and the reference binding signal is X # X#+1 X #+2 X #+3 X #+4 (X #+5 )X #+6 X #+7 X #+8 X #+9 This is the maximum binding signal for polypeptides that bind to a specific target molecule.

[0160] In some embodiments, A includes two residues X7X8. In some embodiments, B includes seven residues X9X 10 X 11 X 12 X 13 X 14 X 15 Includes. In some embodiments, C is a single residue X 16 Includes.

[0161] In some embodiments, formula ABC is formula X7X8X9X 10 X 11 X 12 X 13 X 14 X 15 X 16 In some embodiments, the first peptide conjugate of the first peptide conjugate / MHC complex is the first targeted covalent inhibitor or a fragment thereof and the X of the peptide. 12 It is formed by a covalent bonding reaction with the second peptide conjugate / MHC complex. In some embodiments, the second peptide conjugate of the second peptide conjugate / MHC complex is formed by the second targeted covalent inhibitor or a fragment thereof and the X of the peptide. 13 The second targeted covalent inhibitor is formed by a covalent bonding reaction with the first targeted covalent inhibitor. In some embodiments, the polypeptide is bonded to the second peptide conjugate / MHC complex, and the polypeptide's K is bonded to the first peptide conjugate / MHC complex. D K is up to 100,000 times higher D They are joined together.

[0162] In some embodiments, the polypeptide has a K of the polypeptide relative to the first peptide conjugate / MHC complex. D K is up to 100,000 times higher D The residues that bind and covalently bind to the first targeted covalent inhibitor or fragment of the peptide of the first peptide conjugate / MHC complex are X9, X 10 , X 11 , and X 12 Selected from the group consisting of, the residue covalently bound to the second targeted covalent inhibitor or fragment of the peptide of the second peptide conjugate / MHC complex is X 13 , X 14 , and X 15 That is the case.

[0163] In some embodiments, the peptide is a RAS peptide. In some embodiments, the RAS peptide includes a mutation. In some embodiments, the mutation is G12C or G13C. In some embodiments, the RAS peptide includes a sequence selected from the group consisting of VVVGACGVGK, VVGACGVGK, and KLVVVGACGV. In some embodiments, the RAS peptide includes a sequence selected from the group consisting of VVVGAGCVGK, VVGAGCVGK, or KLVVVGAGCV. In some embodiments, the same MHC is selected from the group consisting of HLA-A*03:01, HLA-A*11:01, HLA-A*02:01, HLA-A*68:01, HLA-A*31:01, HLA-A*30:01, HLA-A*33:03, HLA-A*33:01, HLA-A*74:01, HLA-A*34:02, HLA-A*66:01, HLA-A*68:02, HLA-A*02:05, HLA-A*02:02, and HLA-A*02:06. In some embodiments, the targeted covalent inhibitor or fragment thereof comprises sotracib. In some embodiments, the peptide is a RAS peptide, and X 12 This is a mutation of G12C, and X 13 This is a mutation of G13C.

[0164] In some embodiments, the polypeptide is covalently bound to the first targeted covalent inhibitor or fragment thereof, with a first peptide conjugate / MHC complex having a G12C mutation Cys, up to 100 nM of K D The second peptide conjugate / MHC complex, which has a G13C mutation Cys covalently bound to the second targeted covalent inhibitor or fragment thereof, receives up to 100 nM of K D If the polypeptide binds or is in contact with the first peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis with background subtraction; if the polypeptide is in contact with the second peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis with background subtraction; or if the polypeptide is in contact with the first peptide conjugate / MHC complex, a maximum binding signal of at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction; if the polypeptide is in contact with the second peptide conjugate / MHC complex, a maximum binding signal of at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction, and the reference binding signal is X # X #+1 X #+2 X #+3 X #+4 X #+5 X #+6 X #+7 X #+8 X #+9 This is the maximum binding signal for polypeptides that bind to a specific target molecule.

[0165] In some embodiments, the polypeptide is linked to a second peptide conjugate / MHC complex having a G13C variant Cys covalently bound to the second targeted covalent inhibitor or fragment, and to the first peptide conjugate / MHC complex having a G12C variant Cys covalently bound to the first targeted covalent inhibitor or fragment. D K is up to 100,000 times higher D The maximum wavelength shift of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum wavelength shift of the polypeptide bound to the first peptide conjugate / MHC complex, or the maximum binding signal of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum binding signal of the polypeptide bound to the first peptide conjugate / MHC complex.

[0166] In some embodiments, the Disclosure comprises a polypeptide bound to a first peptide conjugate / MHC complex and a second peptide conjugate / MHC complex distinct from the first peptide conjugate / MHC complex, each of the first and second peptide conjugate / MHC complexes independently comprising formula X # X #+1 X #+2 X #+3 X #+4 (X #+5 )X #+6 X #+7 X #+8 X #+9 , and X # X #+1 X #+2 X #+3 (X #+4 )X #+5 X #+6 X #+7 X #+8 X #+9 , and X # X #+1 X #+2 (X #+3 )X #+4 X #+5 X#+6 X #+7 X #+8 X #+9 , and X # X #+1 (X #+2 )X #+3 X #+4 X #+5 X #+6 X #+7 X #+8 X #+9 , and X #-1 X # X #+1 X #+2 X #+3 X #+4 (X #+5 )X #+6 X #+7 X #+8 X #+9 , and X #+1 X #+2 X #+3 X #+4 (X #+5 )X #+6 X #+7 X #+8 X #+9 A different peptide selected from the group comprising peptides including, wherein the peptide conjugates of the first and second peptide conjugate / MHC complexes are formed by a covalent bond reaction between a targeted covalent inhibitor or a fragment thereof and the residue in parentheses, and (b) the same MHC, wherein the polypeptide contains up to 100 nM of K in the first peptide conjugate / MHC complex. D It binds to the second peptide conjugate / MHC complex and contains up to 100 nM of K DIf the polypeptide binds or is in contact with the first peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis with background subtraction; if the polypeptide is in contact with the second peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis with background subtraction; or if the polypeptide is in contact with the first peptide conjugate / MHC complex, a maximum binding signal of at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction; if the polypeptide is in contact with the second peptide conjugate / MHC complex, a maximum binding signal of at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction, and the reference binding signal is X # X #+1 X #+2 X #+3 X #+4 (X #+5 )X #+6 X #+7 X #+8 X #+9 This is the maximum binding signal for polypeptides that bind to a specific target molecule.

[0167] In some embodiments, each of the first and second peptide conjugate / MHC complexes independently comprises formula X # X #+1 X #+2 X #+3 X #+4 (X #+5 )X #+6 X #+7 X #+8 X #+9 , and X # X #+1 X #+2 X #+3 (X #+4 )X #+5 X #+6 X #+7 X #+8 X #+9 , and X # X #+1X #+2 (X #+3 )X #+4 X #+5 X #+6 X #+7 X #+8 X #+9 , and X # X #+1 (X #+2 )X #+3 X #+4 X #+5 X #+6 X #+7 X #+8 X #+9 It contains different peptides selected from the group consisting of peptides including the following.

[0168] In some embodiments, each of the first and second peptide conjugate / MHC complexes independently comprises a different peptide having an amino acid sequence selected from the group consisting of VVVGACGVGK, VVVGCGGVGK, VVVCAGGVGK, and VVCGAGGVGK.

[0169] In some embodiments, the Disclosure provides compositions that bind to a first peptide conjugate / MHC complex and a second peptide conjugate / MHC complex, each of which is of the formula X7X8X9X 10 X 11 X 12 X 13 X 14 X 15 X 16 A peptide comprising the same MHC, wherein the first peptide conjugate of the first peptide conjugate / MHC complex comprises a targeted covalent inhibitor or a fragment thereof, and X of the peptide. 12 Formed by a covalent bond reaction with the second peptide conjugate / MHC complex, the second peptide conjugate of the second peptide conjugate / MHC complex is formed with the same targeted covalent inhibitor or fragment thereof and the X of the peptide. 13 Formed by a covalent bonding reaction with the polypeptide, the polypeptide has a K in the second peptide conjugate / MHC complex relative to the first peptide conjugate / MHC complex. DK is up to 100,000 times higher D The maximum wavelength shift of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum wavelength shift of the polypeptide bound to the first peptide conjugate / MHC complex, or the maximum binding signal of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum binding signal of the polypeptide bound to the first peptide conjugate / MHC complex.

[0170] In some embodiments, the Disclosure provides compositions that bind to a first peptide conjugate / MHC complex and a second peptide conjugate / MHC complex, each of which is of the formula X7X8X9X 10 X 11 X 12 X 13 X 14 X 15 X 16 A peptide comprising the same MHC, wherein the first peptide conjugate of the first peptide conjugate / MHC complex comprises a targeted covalent inhibitor or a fragment thereof, and X9, X 10 , X 11 , and X 12 Formed by a covalent bond reaction with a residue selected from the group consisting of, the second peptide conjugate of the second peptide conjugate / MHC complex is formed with the same targeted covalent inhibitor or a fragment thereof, and X 13 , X 14 , and X 15 The polypeptide is formed by a covalent bond reaction with a residue selected from the group consisting of the following, and the polypeptide is bonded to the second peptide conjugate / MHC complex by the K of the polypeptide relative to the first peptide conjugate / MHC complex. D K is up to 100,000 times higher DThe maximum wavelength shift of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum wavelength shift of the polypeptide bound to the first peptide conjugate / MHC complex, or the maximum binding signal of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum binding signal of the polypeptide bound to the first peptide conjugate / MHC complex.

[0171] In some embodiments, the Disclosure provides compositions that bind to a first peptide conjugate / MHC complex and a second peptide conjugate / MHC complex, each of which is a peptide comprising formula ABC, where A comprises three or fewer residues having an N-terminal anchor residue, B comprises at least four but seven residues having residues covalently bound to a targeted covalent inhibitor or fragment thereof, and C comprises three or fewer residues having a C-terminal anchor residue, wherein the N-terminal and C-terminal anchor residues bind to MHC and include the same MHC, and the residues covalently bound to the targeted covalent inhibitor or fragment of the peptide in the first peptide conjugate / MHC complex are different from the residues covalently bound to the targeted covalent inhibitor or fragment of the peptide in the second peptide conjugate / MHC complex, and the polypeptide binds to the first peptide conjugate / MHC complex with up to 100 nM of K D It binds to the second peptide conjugate / MHC complex, and up to 100 nM of K is added to the complex. DIf the polypeptide binds or is in contact with the first peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis with background subtraction; if the polypeptide is in contact with the second peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis with background subtraction; or if the polypeptide is in contact with the first peptide conjugate / MHC complex, a maximum binding signal of at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction; if the polypeptide is in contact with the second peptide conjugate / MHC complex, a maximum binding signal of at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction, and the reference binding signal is X # X #+1 X #+2 X #+3 X #+4 (X #+5 )X #+6 X #+7 X #+8 X #+9 This is the maximum binding signal for polypeptides that bind to a specific target molecule.

[0172] In some embodiments, A includes two residues X7X8. In some embodiments, B includes seven residues X9X 10 X 11 X 12 X 13 X 14 X 15 Includes. In some embodiments, C is a single residue X 16 Includes. In some embodiments, formula ABC is formula X7X8X9X 10 X 11 X 12 X 13 X 14 X 15 X 16In some embodiments, the first peptide conjugate of the first peptide conjugate / MHC complex is the targeted covalent inhibitor or a fragment thereof and the peptide X 12 It is formed by a covalent bond reaction with the second peptide conjugate / MHC complex. In some embodiments, the second peptide conjugate of the second peptide conjugate / MHC complex is formed by the same targeted covalent inhibitor or fragment thereof and the X of the peptide. 13 It is formed by a covalent bonding reaction with [another entity].

[0173] In some embodiments, the polypeptide has a K of the polypeptide relative to the first peptide conjugate / MHC complex. D K is up to 100,000 times higher D They are joined together.

[0174] In some embodiments, the polypeptide has a K of the polypeptide relative to the first peptide conjugate / MHC complex. D K is up to 100,000 times higher D The residues that bind and covalently bind to the targeted covalent inhibitor or fragment of the peptide of the first peptide conjugate / MHC complex are X9, X 10 , X 11 , and X 12 Selected from the group consisting of, the residue covalently bound to the peptide of the second peptide conjugate / MHC complex or its fragment is X 13 , X 14 , and X 15 That is the case.

[0175] In some embodiments, the peptide is a RAS peptide. In some embodiments, the RAS peptide includes a mutation. In some embodiments, the mutation is G12C or G13C. In some embodiments, the RAS peptide includes a sequence selected from the group consisting of VVVGACGVGK, VVGACGVGK, and KLVVVGACGV. In some embodiments, the RAS peptide includes a sequence selected from the group consisting of VVVGAGCVGK, VVGAGCVGK, or KLVVVGAGCV. In some embodiments, the same MHC is selected from the group consisting of HLA-A*03:01, HLA-A*11:01, HLA-A*02:01, HLA-, HLA-A*68:01, HLA-A*31:01, HLA-A*30:01, HLA-A*33:03, HLA-A*33:01, HLA-A*74:01, HLA-A*34:02, HLA-A*66:01, HLA-A*68:02, HLA-A*02:05, HLA-A*02:02, and HLA-A*02:06. In some embodiments, the targeted covalent inhibitor or fragment thereof comprises sotracib. In some embodiments, the peptide is a RAS peptide, and X 12 This is a mutation of G12C, and X 13 This is a mutation of G13C.

[0176] In some embodiments, the polypeptide is combined with a first peptide conjugate / MHC complex having a G12C mutation Cys covalently bound to the targeted covalent inhibitor or a fragment thereof, with up to 100 nM of K D The second peptide conjugate / MHC complex, which has a G13C mutation Cys covalently bound to the targeted covalent inhibitor or its fragment, contains up to 100 nM of K DIf the polypeptide binds or is in contact with the first peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis with background subtraction; if the polypeptide is in contact with the second peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis with background subtraction; or if the polypeptide is in contact with the first peptide conjugate / MHC complex, a maximum binding signal of at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction; if the polypeptide is in contact with the second peptide conjugate / MHC complex, a maximum binding signal of at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction, and the reference binding signal is X # X #+1 X #+2 X #+3 X #+4 (X #+5 )X #+6 X #+7 X #+8 X #+9 This is the maximum binding signal for polypeptides that bind to a specific target molecule.

[0177] In some embodiments, the polypeptide is linked to a second peptide conjugate / MHC complex having a G13C variant Cys covalently bound to the targeted covalent inhibitor or fragment, and to the first peptide conjugate / MHC complex having a G12C variant Cys covalently bound to the targeted covalent inhibitor or fragment. D K is up to 100,000 times higher DThe maximum wavelength shift of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum wavelength shift of the polypeptide bound to the first peptide conjugate / MHC complex, or the maximum binding signal of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum binding signal of the polypeptide bound to the first peptide conjugate / MHC complex.

[0178] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), and (a) the VH comprises (i) an HC CDR3 comprising the amino acid sequence FX2X3X4AMDY, where X2 is Y, L, T, H, E, A, or R, X3 is D, V, L, E, H, T, or R, and X4 is L or Y (SEQ ID NO: 267), and / or (b) the VL comprises (i) the amino acid sequence QQX3SWLX7WX9X 10 LC CDR3 containing T, where X3 is A or S, X7 is Y or H, X9 is L, K, V, Y or I, and X 10 This includes those that are L, V, or I (Sequence ID 268).

[0179] In some embodiments, the VH is an HC CDR3 comprising the amino acid sequence FX2X3X4AMDY, where X2 is Q, Y, L, T, H, E, A, or R, X3 is W, D, V, L, E, H, T, or R, and X4 is L or Y.

[0180] In some embodiments, the VH comprises an HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof containing 1 to 3 amino acid changes. In some embodiments, the VH comprises an HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes. In some embodiments, the VL comprises an LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes. In some embodiments, the VL comprises an LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof containing 1 to 3 amino acid changes. In some embodiments, the VH includes HC CDR1 containing the amino acid sequence FSSSSIH or a variant thereof containing 1 to 3 amino acid changes, HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG or a variant thereof containing 1 to 5 amino acid changes, and / or HC CDR3 containing the amino acid sequence FX2X3X4AMDY, where X2 is Y, L, T, H, E, A, or R, X3 is D, V, L, E, H, T, or R, and X4 is L or Y. In some embodiments, the VL includes LC CDR1 containing the amino acid sequence RASQSVSSAVA or a variant thereof containing 1 to 5 amino acid changes, LC CDR2 containing the amino acid sequence SASSLYS or a variant thereof containing 1 to 3 amino acid changes, and / or the amino acid sequence QQX3SWLX7WX9X 10 LC CDR3 containing T, where X3 is A or S, X7 is Y or H, X9 is L, K, V, Y or I, and X 10 This includes those that are L, V, or I.

[0181] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3FYDLAMDY (SEQ ID NO: 273).

[0182] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 272). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 271). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLYWLIT (SEQ ID NO: 276). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 275). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 274). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 271), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 272), the HC CDR3 sequence FYDLAMDY (SEQ ID NO: 273), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 274), the LC CDR2 sequence SASSLYS (SEQ ID NO: 275), and the LC CDR3 sequence QQASWLYWLIT (SEQ ID NO: 276). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFYDLAMDYWGQGTLVTVSS (SEQ ID NO: 270). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWLITFGQGTKVEIK (SEQ ID NO: 269).

[0183] In some embodiments, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising the heavy chain complementarity-determining region 3FLDLAMDY (SEQ ID NO: 281). In some embodiments, the VH comprises the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 280). In some embodiments, the VH comprises the HC CDR1 sequence FSSSSIH (SEQ ID NO: 279). In some embodiments, the antigen-binding domain comprises a light chain variable region (VL) comprising the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLYWKIT (SEQ ID NO: 284). In some embodiments, the VL comprises the LC CDR2 sequence SASSLYS (SEQ ID NO: 283). In some embodiments, the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 282). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 279), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 280), the HC CDR3 sequence FLDLAMDY (SEQ ID NO: 281), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 282), the LC CDR2 sequence SASSLYS (SEQ ID NO: 283), and the LC CDR3 sequence QQASWLYWKIT (SEQ ID NO: 284). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFLDLAMDYWGQGTLVTVSS (SEQ ID NO: 278). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWKITFGQGTKVEIK (SEQ ID NO: 277).

[0184] In one embodiment, the disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3FTVLAMDY (SEQ ID NO: 289).

[0185] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 288). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 287). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLYWLIT (SEQ ID NO: 292). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 291). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 290). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 287), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 288), the HC CDR3 sequence FTVLAMDY (SEQ ID NO: 289), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 290), the LC CDR2 sequence SASSLYS (SEQ ID NO: 291), and the LC CDR3 sequence QQASWLYWLIT (SEQ ID NO: 292). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMDYWGQGTLVTVSS (SEQ ID NO: 286). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWLITFGQGTKVEIK (SEQ ID NO: 285).

[0186] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3FTVLAMDY (SEQ ID NO: 297).

[0187] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 296). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 295). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLYWKVT (SEQ ID NO: 300). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 299). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 298). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 295), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 296), the HC CDR3 sequence FTVLAMDY (SEQ ID NO: 297), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 297), the LC CDR2 sequence SASSLYS (SEQ ID NO: 298), and the LC CDR3 sequence QQASWLYWKVT (SEQ ID NO: 300). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMDYWGQGTLVTVSS (SEQ ID NO: 294). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWKVTFGQGTKVEIK (SEQ ID NO: 293).

[0188] In one embodiment, the disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3FTVLAMDY (SEQ ID NO: 305).

[0189] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 304). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 303). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLYWVIT (SEQ ID NO: 308). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 307). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 306). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 303), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 304), the HC CDR3 sequence FTVLAMDY (SEQ ID NO: 305), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 306), the LC CDR2 sequence SASSLYS (SEQ ID NO: 307), and the LC CDR3 sequence QQASWLYWVIT (SEQ ID NO: 308). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMDYWGQGTLVTVSS (SEQ ID NO: 302). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWVITFGQGTKVEIK (Sequence ID 301).

[0190] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3FHDLAMDY (SEQ ID NO: 313).

[0191] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 312). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 311). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLYWKIT (SEQ ID NO: 316). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 315). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 314). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 311), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 312), the HC CDR3 sequence FHDLAMDY (SEQ ID NO: 313), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 314), the LC CDR2 sequence SASSLYS (SEQ ID NO: 315), and the LC CDR3 sequence QQASWLYWKIT (SEQ ID NO: 316). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFHDLAMDYWGQGTLVTVSS (SEQ ID NO: 310). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWKITFGQGTKVEIK (SEQ ID NO: 309).

[0192] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3FHELAMDY (SEQ ID NO: 321).

[0193] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 320). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 319). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLYWLIT (SEQ ID NO: 324). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 323). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 322). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 319), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 320), the HC CDR3 sequence FHELAMDY (SEQ ID NO: 321), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 322), the LC CDR2 sequence SASSLYS (SEQ ID NO: 323), and the LC CDR3 sequence QQASWLYWLIT (SEQ ID NO: 324). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFHELAMDYWGQGTLVTVSS (SEQ ID NO: 318). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWLITFGQGTKVEIK (SEQ ID NO: 317).

[0194] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3FTVLAMDY (SEQ ID NO: 329).

[0195] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 328). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 327). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSWLYWKIT (SEQ ID NO: 332). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 331). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 330). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 327), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 328), the HC CDR3 sequence FTVLAMDY (SEQ ID NO: 329), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 330), the LC CDR2 sequence SASSLYS (SEQ ID NO: 331), and the LC CDR3 sequence QQSSWLYWKIT (SEQ ID NO: 332). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMDYWGQGTLVTVSS (SEQ ID NO: 326). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWKITFGQGTKVEIK (SEQ ID NO: 325).

[0196] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3FELLAMDY (SEQ ID NO: 337).

[0197] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 336). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 335). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSWLYWKIT (SEQ ID NO: 340). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 339). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 338). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 335), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 336), the HC CDR3 sequence FELLAMDY (SEQ ID NO: 337), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 338), the LC CDR2 sequence SASSLYS (SEQ ID NO: 339), and the LC CDR3 sequence QQSSWLYWKIT (SEQ ID NO: 340). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFELLAMDYWGQGTLVTVSS (SEQ ID NO: 334). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWKITFGQGTKVEIK (SEQ ID NO: 333).

[0198] In one embodiment, the disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3FTVLAMDY (SEQ ID NO: 345).

[0199] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 344). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 343). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSWLYWKVT (SEQ ID NO: 348). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 347). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 346). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 343), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 344), the HC CDR3 sequence FTVLAMDY (SEQ ID NO: 345), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 346), the LC CDR2 sequence SASSLYS (SEQ ID NO: 347), and the LC CDR3 sequence QQSSWLYWKVT (SEQ ID NO: 348). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMDYWGQGTLVTVSS (SEQ ID NO: 342). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWKVTFGQGTKVEIK (SEQ ID NO: 341).

[0200] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3FYDLAMDY (SEQ ID NO: 353).

[0201] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 352). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 351). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSWLYWKVT (SEQ ID NO: 356). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 355). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 354). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 351), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 352), the HC CDR3 sequence FYDLAMDY (SEQ ID NO: 353), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 354), the LC CDR2 sequence SASSLYS (SEQ ID NO: 355), and the LC CDR3 sequence QQSSWLYWKVT (SEQ ID NO: 356). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFYDLAMDYWGQGTLVTVSS (SEQ ID NO: 350). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWKVTFGQGTKVEIK (SEQ ID NO: 349).

[0202] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3FHELAMDY (SEQ ID NO: 361).

[0203] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 360). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 359). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLYWLIT (SEQ ID NO: 364). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 363). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 362). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 359), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 360), the HC CDR3 sequence FHELAMDY (SEQ ID NO: 361), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 362), the LC CDR2 sequence SASSLYS (SEQ ID NO: 363), and the LC CDR3 sequence QQASWLYWLIT (SEQ ID NO: 364). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFHELAMDYWGQGTLVTVSS (SEQ ID NO: 358). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWLITFGQGTKVEIK (SEQ ID NO: 357).

[0204] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3FTVLAMDY (SEQ ID NO: 369).

[0205] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 368). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 367). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLYWKVT (SEQ ID NO: 372). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 371). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 370). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 367), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 368), the HC CDR3 sequence FTVLAMDY (SEQ ID NO: 369), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 370), the LC CDR2 sequence SASSLYS (SEQ ID NO: 371), and the LC CDR3 sequence QQASWLYWKVT (SEQ ID NO: 372). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMDYWGQGTLVTVSS (SEQ ID NO: 366). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWKVTFGQGTKVEIK (SEQ ID NO: 365).

[0206] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3FYDLAMDY (SEQ ID NO: 377).

[0207] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 376). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 375). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSWLYWVIT (SEQ ID NO: 380). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 379). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 378). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 375), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 376), the HC CDR3 sequence FYDLAMDY (SEQ ID NO: 377), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 378), the LC CDR2 sequence SASSLYS (SEQ ID NO: 379), and the LC CDR3 sequence QQSSWLYWVIT (SEQ ID NO: 380). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFYDLAMDYWGQGTLVTVSS (SEQ ID NO: 374). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWVITFGQGTKVEIK (SEQ ID NO: 373).

[0208] In one embodiment, the disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3FHELAMDY (SEQ ID NO: 385).

[0209] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 384). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 383). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLYWLIT (SEQ ID NO: 388). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 387). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 386). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 383), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 384), the HC CDR3 sequence FHELAMDY (SEQ ID NO: 385), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 386), the LC CDR2 sequence SASSLYS (SEQ ID NO: 387), and the LC CDR3 sequence QQASWLYWLIT (SEQ ID NO: 388). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFHELAMDYWGQGTLVTVSS (SEQ ID NO: 382). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWLITFGQGTKVEIK (SEQ ID NO: 381).

[0210] In one embodiment, the disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3FAHLAMDY (SEQ ID NO: 393).

[0211] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 392). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 391). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSWLYWLIT (SEQ ID NO: 396). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 395). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 394). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 391), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 392), the HC CDR3 sequence FAHLAMDY (SEQ ID NO: 393), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 394), the LC CDR2 sequence SASSLYS (SEQ ID NO: 395), and the LC CDR3 sequence QQSSWLYWLIT (SEQ ID NO: 396). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFAHLAMDYWGQGTLVTVSS (SEQ ID NO: 390). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWLITFGQGTKVEIK (SEQ ID NO: 389).

[0212] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3FEDLAMDY (SEQ ID NO: 401).

[0213] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 400). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 399). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLYWYIT (SEQ ID NO: 404). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 403). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 402). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 399), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 400), the HC CDR3 sequence FEDLAMDY (SEQ ID NO: 401), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 402), the LC CDR2 sequence SASSLYS (SEQ ID NO: 403), and the LC CDR3 sequence QQASWLYWYIT (SEQ ID NO: 404). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFEDLAMDYWGQGTLVTVSS (SEQ ID NO: 398). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWYITFGQGTKVEIK (SEQ ID NO: 397).

[0214] In one embodiment, the disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3FRTLAMDY (SEQ ID NO: 409).

[0215] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 408). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 407). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSWLYWIIT (SEQ ID NO: 412). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 411). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 410). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 407), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 408), the HC CDR3 sequence FRTLAMDY (SEQ ID NO: 409), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 410), the LC CDR2 sequence SASSLYS (SEQ ID NO: 411), and the LC CDR3 sequence QQSSWLYWIIT (SEQ ID NO: 412). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFRTLAMDYWGQGTLVTVSS (SEQ ID NO: 406). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWIITFGQGTKVEIK (SEQ ID NO: 405).

[0216] In one embodiment, the disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3FTHYAMDY (SEQ ID NO: 417).

[0217] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 416). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 415). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSWLYWKIT (SEQ ID NO: 420). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 419). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 418). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 415), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 416), the HC CDR3 sequence FTHYAMDY (SEQ ID NO: 417), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 418), the LC CDR2 sequence SASSLYS (SEQ ID NO: 419), and the LC CDR3 sequence QQSSWLYWKIT (SEQ ID NO: 420). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFTHYAMDYWGQGTLVTVSS (SEQ ID NO: 414). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWKITFGQGTKVEIK (SEQ ID NO: 413).

[0218] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3FRLYAMDY (SEQ ID NO: 425).

[0219] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 424). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 423). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLHWKLT (SEQ ID NO: 428). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 427). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 426). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 423), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 424), the HC CDR3 sequence FRLYAMDY (SEQ ID NO: 425), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 426), the LC CDR2 sequence SASSLYS (SEQ ID NO: 427), and the LC CDR3 sequence QQASWLHWKLT (SEQ ID NO: 428). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFRLYAMDYWGQGTLVTVSS (SEQ ID NO: 422). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLHWKLTFGQGTKVEIK (SEQ ID NO: 421).

[0220] In one embodiment, the Disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region 3FHRLAMDY (SEQ ID NO: 433).

[0221] In some embodiments, the VH includes the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 432). In some embodiments, the VH includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 431). In some embodiments, the antigen-binding domain includes a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLHWKLT (SEQ ID NO: 436). In some embodiments, the VL includes the LC CDR2 sequence SASSLYS (SEQ ID NO: 435). In some embodiments, the VL includes the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 434). In some embodiments, the antigen-binding domain includes the HC CDR1 sequence FSSSSIH (SEQ ID NO: 431), the HC CDR2 sequence SISSSSGSTSYADSVKG (SEQ ID NO: 432), the HC CDR3 sequence FHRLAMDY (SEQ ID NO: 433), the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 434), the LC CDR2 sequence SASSLYS (SEQ ID NO: 435), and the LC CDR3 sequence QQASWLHWKLT (SEQ ID NO: 436). In some embodiments, the VH includes a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFHRLAMDYWGQGTLVTVSS (SEQ ID NO: 430). In some embodiments, the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLHWKLTFGQGTKVEIK (SEQ ID NO: 429).

[0222] As an example, the methods of the present disclosure include a method for treating an individual who has been administered a drug that forms a peptide-drug conjugate by administering a means for specifically binding the peptide-drug conjugate in a complex with an MCH. The means may bind to the peptide-drug conjugate in a complex with an MCH with an affinity greater than the affinity the means has for the free drug, or it may not bind to the free drug detectably. Methods using the means may be used in individuals requiring the means, including but not limited to cancer patients who may have a type of cancer that is resistant to the drug. As an example, the means may bind to two different peptide-drug conjugates present in different MHC complexes. [Brief explanation of the drawing]

[0223] [Figure 1] This demonstrates the binding of antibody clones to peptide conjugate / MHC complexes. Antibody clones were presented on the surface of yeast cells, and the binding of targets conjugated to fluorescently labeled streptavidin was detected using flow cytometry. [Figure 2A] This shows the binding properties of RM_010 Fab to peptide conjugate / MHC complexes. Biolayer interferometry (BLI) sensorgrams of interactions between the peptide conjugate / MHC complex and either sotrasib or adagrasib, and either HLA-A*03 or HLA-A*11 are shown. KD values ​​were estimated from the global fitting curve. [Figure 2B] This shows the binding properties of RM_010 Fab to peptide conjugate / MHC complexes. It also shows BLI sensorgrams of the interaction between RM_010 Fab and adagrasib-p7 / HLA-A*11 in the presence or absence of free adagrasib drug. [Figure 2C]This shows the binding properties of RM_010 Fab to peptide conjugate / MHC complexes. MHC binding is plotted as a function of free adagrasiv concentration. Binding signal intensity was normalized from values ​​without free adagrasiv and from a baseline of 0 nm. [Figure 3A] The results of the sotracib scan are shown. A schematic diagram of the method and scheme for residues within the panel is shown. Anchor residues are underlined in the sequence. [Figure 3B] The results of the sotrasib scan are shown. The BLI sensorgram of the binder to the tested soto-p7 / MHC complex immobilized on the sensor chip is shown. [Figure 3C] The results of the sotracib scan are shown. The binding signal of the Fab binder to the tested soto-p7 / MHC complex at 1200 seconds of measurement is shown (e.g., Bmax, shown as a vertical line in Figure 3B). [Figure 4] The results of the HLA scan are shown. A shows a schematic diagram of the modified soto-p7 peptide used in the HLA scan. Anchor residues are underlined, and sotracib-bound Cys are highlighted. B shows the BLI sensorgram of the binder to the soto-p7 / MHC complex tested. C shows the binding signal of the Fab binder to the soto-p7 / MHC complex tested at 1200 seconds of measurement (e.g., Bmax, shown as a vertical line in Figure 4B). [Figure 5A] The results of deep mutation scanning and analysis of the variable light (VL) chain region of the binding partner RM_010 are shown. Diversified residues (underlined) are indicated in the mutation scan. [Figure 5B] The results of deep mutation scanning and analysis of the variable light (VL) chain region of the binding partner RM_010 are shown. The enrichment of variants across the tested VL sites for adagrasib-p7 in complex with HLA-A*03 is also shown. [Figure 5C]The results of deep mutation scanning and analysis of the variable light (VL) chain region of the binding partner RM_010 are shown. The enrichment of variants across the tested VL sites for adagrasib-p7 in complex with HLA-A*11 is also shown. [Figure 6] The results of deep mutation scanning and analysis of the variable weight (VH) chain region of the binding partner RM_010 are shown. A shows the diversified residues (underlined) in the mutation scan. B shows the enrichment of variants across the tested VH sites for adagrasiv-p7 in complex with HLA-A*03. C shows the enrichment of variants across the tested VH sites for adagrasiv-p7 in complex with HLA-A*11. [Figure 7] The results of drug cross-reactivity scans to evaluate the binding response of peptide conjugate / MHC complexes to adagrasib (ada-p7 / A11), sotrasib (soto-p7 / A11), or diavalasib (GDC6036-p7 / A11) with the binding partner RM_010 are shown. RM_010 showed binding to all complexes with different affinities. [Figure 8] The results of the sotracib scan are shown. The position of the targeted covalent inhibitor (e.g., sotracib) covalently bound to the peptide was altered by introducing a unique cysteine ​​residue to replace the residues at positions 7, 9, 10, 11, 12, 13, 14, or 15 of the peptide VVVGAGGVGK. The binding partner RM_010 showed the strongest binding response to the peptide conjugate / MHC complex and to the haptenized p7 peptide at position 12 (e.g., the cysteine ​​residue at position 12 conjugated to the targeted covalent inhibitor). [Figure 9] This shows the binding of the antibody clone to the peptide conjugate / MHC complex and adagrasiv (adagrasiv-p7 / A11). Multiple binders showed a higher MFI signal 60 minutes after dissociation in the presence of non-biotinylating competitors compared to the MFI signal of the parent clone RM010. [Figure 10]This shows the binding of antibody clones to peptide conjugate / MHC complexes and adagrasiv (ada-p7 / A11 or ada-p7 / A03). Several binders showed a higher MFI signal and stronger binding with ada-p7 / A11 compared to the parent clone RM010. Binder RM119 showed a higher MFI signal with ada-p7 / 03 compared to the parent clone RM010 and exhibited stronger binding with respect to this peptide conjugate / MHC complex. [Modes for carrying out the invention]

[0224] Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art to which this invention pertains.

[0225] All numerical ranges given throughout this specification include their upper and lower limits, as well as all narrower numerical ranges contained therein, all of which are expressly described herein.

[0226] As used herein and in the appended claims, the singular forms “a,” “and,” and “the” include plural referents unless the context should otherwise interpret them. Ranges may be expressed herein as “about” one particular value to and / or “about” another particular value. Where such ranges are expressed, another embodiment includes the one particular value to and / or the other particular value. Similarly, the use of the antecedent “about” will be understood to mean that when a value is expressed as an approximation, the particular value forms another embodiment. The term “about” in relation to numbers encompasses variations of + / -10%, + / -5%, or + / -1%.

[0227] This disclosure includes all amino acid sequences and all nucleotide sequences encoding said amino acid sequences. It also includes all antibody sequences and their antigen-binding fragments. Polynucleotide sequences and amino acid sequences having 80–99% similarity (including upper and lower limits, and all numerical values ​​and ranges between them) to the sequences provided herein are included in the present invention. All amino acid sequences described herein may include amino acid substitutions, such as conservative substitutions, that do not adversely affect the function of the protein containing said amino acid sequence. In this regard, this disclosure provides alternative residues at specific positions of the described binding partners, as described below. In certain examples, the alternative residues were identified by deep mutation scanning. This demonstrates the binding function for each binding partner, including the described amino acid changes(s). This disclosure includes each binding partner substituted with each alternative residue, both alone with the original residue and in any combination with the described alternative residues. Thus, any binding partner described herein may have any single described residue change or combination of described changes. Representative changes for a particular antibody are shown in the table. These changes may be present in CDR1, CDR2, CDR3, and combinations thereof. The changes may also include the insertion of amino acids. This disclosure includes each amino acid sequence encompassed by the description of alternative amino acids, by reference to specific sequence identifiers and those listed in the table above.

[0228] As stated above, this disclosure provides antibodies and antigen-binding domains or fragments thereof (collectively, “binding partners,” and each individually, “binding partners”). The term “antibody” includes the format of each binding partner as used herein. The antibody may comprise a polypeptide having an antigen-binding domain or fragment thereof. The binding partner specifically binds to a protein or fragment thereof, or to a peptide provided in peptide form, which includes a covalently bound molecule. The covalently bound molecule forms a peptide conjugate. As used herein, “peptide conjugate” means any protein or peptide modified to covalently conjugate to another molecule. The peptide conjugate is considered to be a novel antigen, i.e., a neoantigen. The other molecule covalently conjugating to the protein or peptide to form the peptide conjugate is not particularly limited, however, that the other molecule is not further amino acids added to the described peptide conjugate. In embodiments, the molecule that covalently conjugates to the protein or peptide may have or had biological activity before conjugation, or may be biologically inactive before conjugation. In embodiments, the molecule may be a small molecule drug, but is not limited to such drugs. As used herein, molecules that covalently conjugate to a peptide to form a peptide conjugate are referred to as “targeted covalent inhibitors (TCIs)” or “covalent drugs.” Representative and non-limiting examples of drugs that covalently conjugate to a peptide or protein to form a peptide conjugate are described below. Peptide conjugates may be covalently modified full-length proteins and their fragments, but are not limited to these. Peptide conjugates include covalent modifications and, for example, fragments of full-length proteins produced by intracellular processing. In certain embodiments, a full-length protein may be covalently modified in a cell and then processed to produce a peptide conjugate, which is a fragment of the full-length protein.In one embodiment, the peptide conjugate comprises a fragment of a full-length protein. As further described below, the produced peptide conjugate can be presented on the cell surface. Cell surface presentation of the peptide conjugate may be by any form of cell surface presentation, including but not limited to any receptor having an extracellular segment, or by any type of major histocompatibility complex (MHC) or human leukocyte antigen (HLA). Non-limited examples of HLA types that present the peptide conjugate and to which the described binding partners specifically bind are further described below.

[0229] As used herein, the term “peptide conjugate / MHC complex” refers to a peptide conjugate comprising a peptide and a chemical fragment of a targeted covalent inhibitor presented by a major histocompatibility complex (MHC). For example, such a peptide conjugate may be formed by a covalent reaction between a targeted covalent inhibitor and a residue of the peptide (e.g., a cysteine ​​residue). In some embodiments, the peptide conjugate is AMG-510 and KRAS G12C It is formed by a covalent bonding reaction with a peptide. In some embodiments, the peptide is introduced externally as a vaccine. In some embodiments, the peptide contains a nucleophilic or electrophilic residue. In some embodiments, the residue contains cysteine, aspartic acid, or arginine. In some embodiments, the MHC is a human leukocyte antigen (HLA). In some embodiments, the HLA is HLA-A*02:01, HLA-A*03:01, or HLA-A*11:01.

[0230] As used herein, the terms “CDR” or “complementarity-determining region” refer to discontinuous antigen-binding sites found within the variable regions of heavy and light chain polypeptides. These specific regions are described, for example, by Kabat et al., J. Biol. Chem. 252, 6609-6616 (1977) and Kabat et al., Sequences of protein of immunological interest (1991), Chothia et al., J. Mol. Biol. 196:901-917 (1987), and MacCallum et al., J. Mol. Biol. 262:732-745 (1996), all of which are incorporated herein by reference as a whole. These definitions include duplication or subsets of amino acid residues when compared to one another. In certain embodiments, the term "CDR" refers to the CDR as defined by MacCallum et al., J.Mol.Biol.262:732-745 (1996) and Martin A. "Protein Sequence and Structure Analysis of Antibody Variable Domains," in Antibody Engineering, Kontermann and Dubel, eds., Chapter 31, pp.422-439, Springer-Verlag, Berlin (2001). In certain embodiments, the term "CDR" refers to the CDR as defined by Kabat et al., J.Biol.Chem.252, 6609-6616 (1977) and Kabat et al., Sequences of protein of immunological interest (1991). In certain embodiments, the heavy chain CDR and light chain CDR of an antibody are defined using different rules. In certain embodiments, heavy chain CDRs and / or light chain CDRs are defined by performing a structural analysis of the antibody and identifying residues within a variable region(s) that are predicted to contact the epitope region of the target molecule (e.g., a peptide conjugate).HC CDR1, HC CDR2, and HC CDR3 represent heavy chain CDRs, and LC CDR1, LC CDR2, and LC CDR3 represent light chain CDRs. Any binder CDRs described herein (e.g., binding partners or antigen-binding domains) may be designated by Kabat's numbering scheme. In some cases, light chain (LC) CDRs may be designated by Kabat's numbering scheme. In some cases, LC CDRs may be designated by modifications to Kabat's numbering scheme. In some cases, heavy chain (HC) CDRs may be designated by Kabat's numbering scheme. In some cases, HC CDRs may be designated by modifications to Kabat's numbering scheme. For example, such CDRs may contain one or more additional amino acids compared to a CDR designated by Kabat's numbering scheme.

[0231] The determination of the "percentage of identity" between two sequences (e.g., amino acid sequences or nucleic acid sequences) can be achieved using mathematical algorithms. A specific non-restrictive example of a mathematical algorithm used to compare two sequences is the algorithm of Karlin S & Altschul SF (1990) PNAS 87:2264-2268, modified as shown in Karlin S & Altschul SF (1993) PNAS 90:5873-5877. Each of these is incorporated herein by reference as a whole. Such algorithms are incorporated into the NBLAST and XBLAST programs of Altschul SF et al., (1990) J Mol Biol 215:403, which are incorporated herein by reference as a whole. A BLAST nucleotide search may be performed by setting the NBLAST nucleotide program parameters to, for example, score = 100 and word length = 12 to obtain nucleotide sequences homologous to the nucleic acid molecules described herein. BLAST protein searches can be performed by setting the XBLAST program parameters to, for example, score=50 and word length=3 to obtain amino acid sequences homologous to the protein molecules described herein. To obtain gap alignment for comparison purposes, Gapped BLAST can be used as described in Altschul SF et al., (1997) Nuc Acids Res 25:3389-3402, which is incorporated herein by reference in its entirety. Alternatively, PSI BLAST can be used to perform iterative searches to detect intermolecular distance relationships (ibid.). When using the BLAST, Gapped BLAST, and PSI Blast programs, the default parameters for each program (e.g., XBLAST and NBLAST) can be used (see, for example, the National Center for Biotechnology Information (NCBI) on the World Wide Web, ncbi.nlm.nih.gov).Another specific, non-restrictive example of a mathematical algorithm used for sequence comparison is the algorithm of Myers and Miller, 1988, CABIOS 4:11–17, which is incorporated herein by reference in its entirety. Such an algorithm is incorporated into the ALIGN program (version 2.0), which is part of the GCG sequence alignment software package. When using the ALIGN program to compare amino acid sequences, the PAM120 weighted residue table, gap length penalty 12, and gap penalty 4 may be used. The percentage of identity between two sequences can be determined with or without gaps using techniques similar to those described above. When calculating the percentage of identity, typically only perfect matches are counted.

[0232] As used herein, the terms “free targeted covalent inhibitor” or “free drug” refer to a targeted covalent inhibitor that is not covalently bound to a protein or peptide. When such targeted covalent inhibitor is covalently bound to a protein or peptide, the targeted covalent inhibitor may be referred to as part or fragment of the free targeted covalent inhibitor or drug. For example, the protein or fragment may be a chemical fragment that binds to a cysteine ​​residue of the peptide during the covalent bonding reaction between the free drug and the cysteine ​​residue of the peptide. G12C The term "KRAS" refers to the G12C mutation, i.e., the KRAS protein (UniProt accession number P01116) having a cysteine ​​at amino acid position 12. G12D The term "KRAS" refers to the G12D mutation, i.e., the KRAS protein (UniProt accession number P01116) having aspartic acid at amino acid position 12. G12R The term "KRAS" refers to the G12R mutation, i.e., the KRAS protein having arginine at amino acid position 12 (UniProt accession number P01116). As used herein, "KRAS" G12SThe term "G12S mutation" refers to the KRAS protein (UniProt accession number P01116) that has serine at amino acid position 12.

[0233] In embodiments, when the binding partner is covalently bound to the peptide conjugate, it selectively binds (e.g., specifically binds) to the protein or peptide, or to the complex containing the protein or peptide, compared to the same protein or peptide that is not bound to the drug. Therefore, the binding partners described herein either do not bind detectably to the same protein or fragment in the absence of the covalently bound molecule, or bind with a lower affinity. In embodiments, the binding partner binds to the protein or peptide containing the covalently bound drug with an affinity 10 to 10,000 times greater (including all numerical values ​​and ranges of 10 to 10,000) than to the protein or peptide that does not contain the covalently bound molecule. In this regard, while not intended to be bound to any particular theory, it is assumed that the presence of the covalently bound molecule contributes to the epitope to which the binding partner specifically binds. The term "specifically binds" refers to a molecule (e.g., an antibody or its antigen-binding portion) binding to that epitope or target or peptide-MHC complex in a sample with greater affinity, greater affinity, and / or for a longer duration than it would to bind to another epitope or non-target compound or non-target or peptide-MHC complex (e.g., a peptide-MHC complex having a structurally different antigen, different MHC and different peptide, a peptide-MHC complex having different MHC and the same peptide, or a peptide-MHC complex having the same MHC and different peptide). For example, a molecule that specifically binds to an epitope or target or peptide-MHC complex (e.g., an antibody or its antigen-binding portion) may be a molecule (e.g., an antibody or its antigen-binding portion) that binds to this epitope or target or peptide-MHC complex with greater affinity, greater affinity, and / or for a longer duration than it would to bind to other epitopes or target or peptide-MHC complexes.In some embodiments, a molecule that specifically binds to an epitope or target or peptide-MHC complex (e.g., an antibody or its antigen-binding moiety) is a molecule that binds to the epitope or target or peptide-MHC complex with an affinity at least 5 times greater than that of other epitopes or non-target compounds or non-target peptide-MHC complexes, for example, at least 5 times, 10 times, 100 times, 1,000 times, 10,000 times, or greater. A molecule that specifically binds to a particular epitope or target or peptide-MHC complex (e.g., an antibody or its antigen-binding moiety) is, for example, 10⁻⁴M or less, for example, 10, with respect to the epitope or target or peptide-MHC complex to which it binds. -5 M, 10 -6 M, 10 -7 M, 10 -8 M, 10 -9 M, 10 -10 M, 10 -11 M, or 10 -12 Equilibrium dissociation constant K for M DThis can be indicated by molecules having this property, and can be identified, for example, by immunoassays, surface plasma resonance (e.g., Biacore® assay), biolayer interferometry, or other assays known in the art. Those skilled in the art will recognize that an antibody that specifically binds to a target derived from one species may also specifically bind to the orthologue of that target. In some embodiments, the degree of binding of a molecule (e.g., an antibody or its antigen-binding moiety) to an unrelated epitope or unrelated target or unrelated peptide-MHC complex is less than about 0.0001%, 0.001%, 0.01%, 0.1%, 1%, 10%, or 20% of the antibody's binding to the epitope or target or peptide-MHC complex, as measured, for example, by immunoassays, surface plasma resonance (e.g., Biacore® assay), biolayer interferometry, or other assays known in the art. Similarly, the binding partners of this disclosure selectively bind to the peptide conjugate compared to binding to the free drug. In embodiments, the binding partner binds to the peptide containing the covalently bound drug (e.g., the peptide conjugate / MHC complex) with an affinity 10 to 10,000 times greater (including all numerical values ​​and ranges from 10 to 10,000) than to the free drug. In some embodiments, the interaction between the binding partner and the peptide conjugate / MHC complex is not inhibited by the free drug. For example, the interaction between the binding partner and the peptide conjugate / MHC complex is not inhibited by 100 times, 1,000 times, 10,000 times, 100,000 times, or more of the free drug.

[0234] In some embodiments, the polypeptide containing the antigen-binding domain (i) has a dissociation constant of up to about 100 nM (K) in the first peptide conjugate / MHC complex. D (ii) The second peptide conjugate / MHC complex contains up to approximately 100 nM of K D(iii) a third peptide conjugate / MHC complex with up to approximately 100 nM of K D The first peptide conjugate / MHC complex may include a first peptide conjugate, wherein the first peptide conjugate of the first peptide conjugate / MHC complex is a first peptide covalently bound to a first targeted covalent inhibitor or a fragment thereof, and a first MHC. The second peptide conjugate / MHC complex may include a second peptide conjugate, wherein the second peptide conjugate of the second peptide conjugate / MHC complex is a second peptide covalently bound to a second targeted covalent inhibitor or a fragment thereof, and a second MHC. The third peptide conjugate / MHC complex may include a third peptide conjugate, wherein the third peptide conjugate of the third peptide conjugate / MHC complex is a third peptide covalently bound to a third targeted covalent inhibitor or a fragment thereof, and a third MHC. In some embodiments, the first targeted covalent inhibitor, the second targeted covalent inhibitor, and the third targeted covalent inhibitor may differ. The first targeted covalent inhibitor may be an adagrasib, and the second and third covalent inhibitors may be selected from the group consisting of sotrasib and divalasib. In some embodiments, the antigen-binding domain (i) has a dissociation constant (K) of up to about 50 nM to the first peptide conjugate / MHC complex. D (ii) the second peptide conjugate / MHC complex contains up to approximately 50 nM of K D (iii) the third peptide conjugate / MHC complex with up to approximately 50 nM of K D It can bind to the antigen-binding domain (i) the first peptide conjugate / MHC complex with a dissociation constant (K) up to about 10 nM. D (ii) the second peptide conjugate / MHC complex contains up to approximately 10 nM of K D(iii) the third peptide conjugate / MHC complex with up to approximately 10 nM of K D They can be joined together.

[0235] In some embodiments, the polypeptides described herein may bind to peptide conjugate / MHC complexes containing adagrucib-covalently bound peptides with greater affinity than the affinity to peptide conjugate / MHC complexes containing divalacib-covalently bound peptides.

[0236] In some embodiments, the binding partners described herein have a dissociation constant (K) due to the binding partner bound to the first peptide conjugate / MHC complex (e.g., the peptide conjugate to which adaglacib is covalently bound) or the second conjugate / MHC complex (e.g., the peptide conjugate to which sotracib is covalently bound) or the third conjugate / MHC complex (e.g., the peptide conjugate to which divalacib is covalently bound) of the first peptide conjugate / MHC complex (e.g., the peptide conjugate to which adaglacib is covalently bound). D The dissociation constant (K) is at least approximately 2 times higher, at least approximately 5 times higher, at least approximately 10 times higher, at least approximately 15 times higher, at least approximately 20 times higher, at least approximately 50 times higher, at least approximately 100 times higher, at least approximately 150 times higher, at least approximately 250 times higher, at least approximately 500 times higher, at least approximately 1,000 times higher, at least approximately 2,500 times higher, at least approximately 5,000 times higher, at least approximately 10,000 times higher, at least approximately 50,000 times higher, at least approximately 100,000 times higher, or may be approximately 100,000 times higher or more. D) can be bound. In some embodiments, the binding partners described herein can be bound to a first peptide conjugate / MHC complex (e.g., the peptide conjugate to which adaglacib is covalently bound) by a binding partner bound to a second conjugate / MHC complex (e.g., the peptide conjugate to which sotracib is covalently bound) or a third conjugate / MHC complex (e.g., the peptide conjugate to which divalacib is covalently bound) by a dissociation constant (K D The dissociation constant (K) can be up to approximately 100,000 times higher, up to approximately 50,000 times higher, up to approximately 10,000 times higher, up to approximately 5,000 times higher, up to approximately 2,500 times higher, up to approximately 1,000 times higher, up to approximately 500 times higher, up to approximately 250 times higher, up to approximately 150 times higher, up to approximately 100 times higher, up to approximately 50 times higher, up to approximately 10 times higher, up to approximately 5 times higher, up to approximately 2 times higher, or less than approximately 2 times higher. D They can be joined together.

[0237] In embodiments, the molecule that covalently forms a peptide conjugate is a drug, which may be any targeted covalent inhibitor (TCI), but the covalent drug does not necessarily have to inhibit the target peptide. In embodiments, the molecule reacts with a specific residue in the target protein. In embodiments, the molecule reacts at least partially with a segment of a protein or peptide containing a nucleophilic or electrophilic residue. In embodiments, the segment of a protein or peptide with which the molecule reacts includes one of Cys, Lys, Tyr, His, Ser, Thr, or Arg, the latter of which is described in Ziyang Zhang, Johannes Morstein, Andrew K. Ecker, Keelan Z. Guiley, and Kevan M. Shokat, Journal of the American Chemical Society Article ASAP, DOI:10.1021 / jacs.2c05377. That disclosure is incorporated herein by reference. In embodiments, the protein or peptide includes selenocysteine. In embodiments, the targeted covalent inhibitor reacts with selenocysteine. In embodiments, the molecule may react at least partially with wild-type Cys, or with a protein or peptide segment containing a mutation to Cys at a residue, and thus covalently bond via a so-called sulfur tether. In embodiments, the drug is any drug described in Ghosh AK, Samanta I, Mondal A, Liu WR. Covalent Inhibition in Drug Discovery. ChemMedChem. 2019;14(9):889-906.doi:10.1002 / cmdc.201900107, or De Cesco, et al., European Journal of Medicinal Chemistry 138(2017)96e114, or Bauer, RA, Drug Discovery Today, Volume 20, Number 9, September 2015. The disclosure of compounds that covalently modify protein targets is incorporated herein by reference.

[0238] In non-limiting embodiments, the gene encoding the wild-type protein is mutated to encode a protein containing one or more of the described residues, so that any of the amino acids Asp, Cys, and Arg are present in the protein or peptide to which the molecule binds. In non-limiting embodiments, the molecule binds to a protein or peptide associated with a disease or condition treated with the targeted covalent inhibitor, such as cancer, autoimmune disease, or other disease or disorder. In embodiments, the target (e.g., the protein or peptide to which the molecule covalently binds) is a receptor, including but not limited to any receptor having a catalytically active segment. In embodiments, the drug binds to an enzyme, including but not limited to any kinase, which is not necessarily a receptor. In embodiments, the protein target includes a receptor having one or more activating mutations that promote ligand-independent enzyme activity.

[0239] In embodiments, the molecule targets and covalently binds to an amino acid sequence present in any of the following proteins and / or variants thereof, which may or may not include mutations associated with a particular condition, such as any cancer type. In embodiments, the protein is any protein described in Visscher M, et al., Covalent targeting of acquired cysteines in cancer. Curr Opin Chem Biol. 2016;30:61-67.doi:10.1016 / j.cbpa.2015.11.004, which is incorporated herein by reference. Visscher et al. also teach a method for identifying disease-associated mutant genes into which Cys residues suitable for covalent modification are introduced. In embodiments, the protein is KRAS, Bruton's tyrosine kinase (BTK), any member of the epidermal growth factor receptor (EGFR) family, also known as the ERBB family, including but not limited to EGFR(ERBB1), HER2 / NEU(ERBB2), HER3(ERBB3), and HER4(ERBB4), fibroblast growth factor receptor (FGFR), receptor kinases known in the art as MET, BRAF, and cyclin-dependent kinase (CDK), acetylcholinesterase (ACHE), TP53, IDH1, GNAS, FBXW7, CTNNB1, DNMT3A, any cathepsin including cathepsins B, C, F, H, K, L, O, S, V, W, and X, any caspase, any protein involved in obesity, such as pancreatic lipase and METAP2, or any cancer testicular antigen. In embodiments, the drug targets and covalently binds to any viral protein, including, but not limited to, any viral DNA polymerase, RNA polymerase, reverse transcriptase, or RNA-dependent RNA polymerase, or, for example, a viral protein necessary for viral entry into a cell, or a protein encoded by any transposable element.In embodiments, the drug targets EGFR and may be selected from PD168393, PF00299804 (dacomitinib), EKB569 (peritinib), afatinib, WZ4002, osimertinib (formerly AZD9291), PF-06459988, nazartinib, naquotinib, olmutinib, abitinib, and rosiletinib, neratinib, pirotinib, poziotinib, and their derivatives. In embodiments, the drug targets Bruton's tyrosine kinase (BTK) and may be selected from ibrutinib, acalabrutinib, zanubrutinib, CHMFL-BTK-11, ONO / GS-405, PRN1008, and CC-292. In some embodiments, the drug targets any p90 ribosomal S6 kinase (RSK) and may be selected from fluoromethyl ketone (FMK) and dimethyl fumarate. In some embodiments, the drug targets any FGFR and may be selected from FIIN-1, FIIN-2, FIIN-3, BGJ398, AZD4547, PRN1371, and FGF401. In some embodiments, the targeted covalent inhibitor targets E3 ligases, such as RNF4, HOIP, RSP5, SMURF1, E6AP, HUWE1, and NEDD4-1. In some embodiments, the targeted covalent inhibitor targets DDB1 and CUL4-related factors (DCAFs), such as DCAF1 or DCAF15. In some embodiments, the targeted covalent inhibitor targets any cancer-testis antigen, any endogenous retroviral protein, long-chain scattered repeat sequence 1 (LINE-1), or short-chain scattered repeat sequence (SINE). In some embodiments, the targeted covalent inhibitor targets a short-chain scattered repeat sequence that is optionally Alu. In some embodiments, the targeted covalent inhibitor is iniparib, abiraterone, carfilzomib, afatinib, or neratinib. In some embodiments, the targeted covalent inhibitor is a targeted covalent agent. The targeted covalent agent may not inhibit the cancer-testis antigen, endogenous retroviral protein, long-chain scattered repeat sequence 1 (LINE-1), or short-chain scattered repeat sequence (SINE).

[0240] In embodiments, the molecules that covalently bond to form the peptide conjugate target any RAS oncogene protein product, including but not limited to HRAS, NRAS, KRAS4A, and KRAS4B. The amino acid sequences of the RAS proteins are known in the art, and the residue numbering is identical for relevant portions of all RAS isotypes discussed herein. The amino acid sequences are available, for example, from UniProt P01116, and these amino acid sequences are incorporated herein as of the effective filing date of this application or patent. The G12 position is numbered according to known amino acid sequences, regardless of whether G12 is the 12th amino acid in the expressed RAS peptide sequence of this disclosure.

[0241] In one embodiment, the molecule is covalently bound to a KRAS protein or peptide containing a mutation. In this embodiment, the mutation is at least one of KRAS residues 12, 13, or 61. Any reference to a drug herein includes its name in both uppercase and lowercase letters.

[0242] In some embodiments, the drug targets the KRAS protein containing the KRAS G12C mutation. In some embodiments, the drug targets the KRAS protein containing the KRAS G12D mutation. In some embodiments, the drug targets the KRAS protein containing the KRAS G12R mutation. In some embodiments, the drug targets the KRAS protein containing the KRAS G12S mutation. In non-limiting embodiments, drugs targeting the KRAS protein are selected from 2E07, 6H05, SML-8-73-1, MRTX849 (e.g., adaglacib), JNJ74699157, LY3499446, ARS-853, ARS-1620, ARS-3284, GDC-6036 (e.g., divalacib), D-1553, JDQ443, RMC-6291, RMC-9805, BI 1823911, MRTX1257, AMG-510 (e.g., sotracib), or derivatives thereof. Further examples of compounds capable of covalently targeting KRAS peptides containing the G12C mutation can be found in Internal Application PCT / IB2019 / 050993, Internal Application PCT / EP2018 / 083853, and U.S. Application US16 / 917,128. Each of these is incorporated herein by reference as a whole. In some embodiments, the drug comprises a proteolytic chimeric (PROTAC) derivative of a covalent drug, a non-limiting description of which is available at doi:10.1021 / acscentsci.0c00411, and a description of the PROTAC therein is incorporated herein by reference. In embodiments, the PROTAC is LC-1 or LC-2. In embodiments, this disclosure relates to an autophagy-mediated degradation inducer called AUTAC, as described in doi.org / 10.1080 / 15548627.2020.1718362, the description of AUTAC is incorporated herein by reference.

[0243] The peptide conjugates described herein may be formed by a covalent reaction between a free targeted covalent inhibitor and a KRAS peptide. G12C Peptides, KRAS G12D Peptides, KRAS G12R Peptides, or KRAS G12S It may be formed by a covalent bonding reaction with a peptide. The free targeted covalent inhibitor may be any of the free targeted covalent inhibitors described herein. For example, the free targeted covalent inhibitor may be AMG-510 (e.g., sotrasib), MRTX849 (e.g., adaglasib), or GDC6036 (e.g., divalasib). In some cases, the peptide conjugate may be AMG-510 and KRAS G12C It may be formed by a covalent bond reaction with a peptide. The peptide may contain or consist of the amino acid sequence VVVGACGVGK, VVGACGVGK, or KLVVVGACGV. In some cases, the targeted covalent inhibitor may be beta-lactone G12Si-1, G12Si-2, G12Si-3, G12Si-4, or G12Si-5.

[0244] The antigen-binding domains of the polypeptides described herein or the binding partners described herein can bind to peptide conjugate / MHC complexes presented by different HLAs. For example, in certain embodiments, the antigen-binding domain may have specificity to (i) a peptide conjugate / MHC complex containing VVGACGVGK conjugated to a targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, (ii) a peptide conjugate / MHC complex containing VVVGACGVGK conjugated to a targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, or (iii) both. In certain other embodiments, the antigen-binding domain may be specific to (i) a peptide conjugate / MHC complex containing VVVGACGVGK conjugated to a targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, (ii) a peptide conjugate / MHC complex containing VVVGACGVGK conjugated to a targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01, or (iii) both.In other embodiments, the antigen-binding domain is (i) a peptide conjugate / MHC complex containing VVGACGVGK conjugated to a targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, (ii) a peptide conjugate / MHC complex containing VVVGACGVGK conjugated to a targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, or (iii) a targeted covalent inhibitor presented by HLA-A*11:01 (iv) A peptide conjugate / MHC complex containing VVVGACGVGK conjugated to a harmful agent or a fragment thereof, (iv) A peptide conjugate / MHC complex containing KLVVVGACGV conjugated to a targeted covalent inhibitor presented by HLA-A*02:01 or a fragment thereof, or (v) Any combination of (i) to (iv) (e.g., (i) and (ii), or (i), (ii), and (iv)), or (vi) Specificity may be found for all of (i) to (iv). In a particular embodiment, the polypeptide binds to (i) a peptide conjugate / HLA-A*03:01MHC complex containing a peptide with the amino acid sequence VVGACGVGK, (ii) a peptide conjugate / HLA-A*03:01MHC complex containing a peptide with the amino acid sequence VVVGACGVGK, (iii) a peptide conjugate / HLA-A*11:01MHC complex containing a peptide with the amino acid sequence VVVGACGVGK, and / or (iv) a peptide conjugate / HLA-A*02:01MHC complex containing a peptide with the amino acid sequence KLVVVGACGV.In further embodiments, the polypeptide binds to (i) a peptide conjugate / HLA-A*03:01MHC complex containing a peptide with the amino acid sequence VVGACGVGK and a peptide conjugate / HLA-A*03:01MHC complex containing a peptide with the amino acid sequence VVVGACGVGK, (ii) a peptide conjugate / HLA-A*03:01MHC complex containing a peptide with the amino acid sequence VVVGACGVGK and a peptide conjugate / HLA-A*11:01MHC complex containing a peptide with the amino acid sequence VVVGACGVGK, (iii) a peptide conjugate / HLA-A*02:01MHC complex containing a peptide with the amino acid sequence KLVVVGACGV, or any combination of (i) to (iii) (for example, (i) and (ii), or (i) and (iii)), or all of (i) to (iii). A covalent inhibitor targeting the peptide conjugate / MHC complex may have a chemical structure containing C-R1, where C is a chemical fragment linked to R1 of any of the following compounds. [ka]

[0245] The R1 in the chemical structure of C-R1 of the covalent inhibitor may be one of the following structures: Compound (1) is designated as AMG-510 (sotrasib), Compound (2) is designated as MRTX849 (adaglasib), and Compound (3) is designated as GDC6036 (divalasib). [ka]

[0246] A targeted covalent inhibitor having a structure containing C-R1 may form covalent bonds with several different amino acid residues of the peptide. For example, the targeted covalent inhibitor may form covalent bonds with a cysteine ​​residue of a peptide containing the amino acid sequence VVVGACGVGK, VVGACGVGK, or KLVVVGACGV. In other embodiments, the targeted covalent inhibitor may form covalent bonds with an aspartic acid residue, a serine residue, or an arginine residue of a peptide containing the amino acid sequence VVVGADGVGK, VVGADGVGK, or KLVVVGADGV. In some embodiments, the antigen-binding domain of the polypeptide recognizes the C portion of the targeted covalent inhibitor having a structure containing C-R1 of the peptide conjugate / MHC complex. In certain other embodiments, the antigen-binding domain of the polypeptide recognizes the C portion of the targeted covalent inhibitor of the peptide conjugate / MHC complex but does not recognize the R1 portion.

[0247] Small molecules possessing electrophilic warhead groups (e.g., targeted covalent inhibitors) can form peptide-small molecule conjugates via covalent bonding reactions with cysteine ​​residues of peptides. This type of reaction is illustrated in the following scheme for AMG-510 (sotrasib). [ka]

[0248] The following table describes the chemical structures of targeted covalent inhibitors and fragments ("chemical fragments") that bind to cysteine ​​residues of the peptide when the drug covalently reacts with cysteine. In some embodiments, the binding partners disclosed herein bind to peptide conjugate / MHC complexes containing the peptide and MHC conjugated to the chemical fragments in Table A below. [Table 1] JPEG2026522426000007.jpg213159JPEG2026522426000008.jpg64159

[0249] In non-limiting embodiments, the binding partner specifically binds to a site containing a neoantigen, which includes a covalently bound small molecule drug or other covalently bound molecules, as a component of the antigen in a particular MHC context. In some embodiments, the binding partner provided herein specifically binds to a peptide conjugate / MHC complex, the peptide conjugate being formed by a covalent reaction between a targeted covalent inhibitor and a peptide. In some embodiments, the binding partner binds to the peptide conjugate / MHC complex with greater affinity than to the peptide or the free targeted covalent inhibitor.

[0250] In some embodiments, the Disclosure provides a binding partner that specifically binds to a peptide conjugate / MHC complex, the peptide conjugate / MHC complex comprising (a) a peptide conjugate formed by a covalent reaction between a targeted covalent inhibitor or a fragment thereof and a peptide, and (b) an MHC.

[0251] In some embodiments, the binding partner binds to the peptide conjugate / MHC complex with greater affinity than it binds to the peptide or the free targeted covalent inhibitor. In some embodiments, the affinity of the binding partner to the peptide conjugate / MHC complex is 100 to 10,000 times greater than the affinity of the binding partner to the peptide or the free targeted covalent inhibitor.

[0252] In some embodiments, the MHC is a human leukocyte antigen (HLA), which is optionally HLA-A, HLA-B, or HLA-C. In some embodiments, the HLA is HLA-A*02:01, HLA-A*03:01, or HLA-A*11:01.

[0253] In some embodiments, the peptide comprises a nucleophilic or electrophilic residue, which is optionally one of cysteine, aspartic acid, or arginine.

[0254] In some embodiments, the peptide includes a cysteine ​​residue.

[0255] In some embodiments, the peptide conjugate is formed by a covalent bond reaction between the targeted covalent inhibitor and a cysteine ​​residue of the peptide.

[0256] In some embodiments, the peptide is a segment of a cancer-related protein, which is optionally encoded by a gene that has been mutated in cancer.

[0257] In some embodiments, the peptide is a segment of an enzyme, and the targeted covalent inhibitor is an inhibitor of the enzyme. In some embodiments, the enzyme is a kinase or a GTPase.

[0258] In some embodiments, the peptide is or is derived from KRAS.

[0259] In some embodiments, the peptide is KRAS G12C KRAS G12D KRAS G12S or KRAS G12R Includes the segment.

[0260] In some embodiments, the peptide comprises the amino acid sequence VVVGACGVGK, VVGACGVGK, or KLVVVGACGV.

[0261] In some embodiments, the targeted covalent inhibitor is (i) tricomplex KRAS G12C Inhibitors or KRAS G12C Degradation-inducing factor, (ii) Tricomplex KRAS G12D Inhibitors or KRASG12D Degradation-inducing factor, (iii) Tricomplex KRAS G12R Inhibitors or KRAS G12R Degradation-inducing factors, or (iv) tricomplex KRAS G12S Inhibitors or KRAS G12S It is a degradation-inducing factor.

[0262] In some embodiments, the peptide is used in the KRAS G12C The targeted covalent inhibitor includes the mutation of KRAS G12C It is an inhibitor. In some embodiments, the peptide is an inhibitor of the KRAS G12D The targeted covalent inhibitor includes the mutation of KRAS G12D It is an inhibitor. In some embodiments, the peptide is an inhibitor of the KRAS G12R The targeted covalent inhibitor includes the mutation of KRAS G12R It is an inhibitor. In some embodiments, the peptide is an inhibitor of the KRAS G12S The targeted covalent inhibitor includes the mutation of KRAS G12S It is an inhibitor.

[0263] In some embodiments, the targeted covalent inhibitor is sotrasib (e.g., AMG-510), adagrasib (e.g., MRTX849), diavalasib (e.g., GDC6036), or any combination thereof.

[0264] In some cases, the targeted covalent inhibitor is 2E07, 6H05, SML-8-73-1, MRTX849, JNJ74699157, LY3499446, ARS-853, ARS-1620, ARS-3284, GDC-6036, D-1553, JDQ443, BI 1823911, or a derivative thereof.

[0265] In some embodiments, the peptide is a full-length protein that is processed in cells to produce smaller peptide fragments after a covalent reaction with the targeted covalent inhibitor.

[0266] In some embodiments, the peptide conjugate comprises a compound selected from the group consisting of compounds (1) and (2), which is covalently bonded to a cysteine ​​residue of a peptide containing the amino acid sequence VVVGACGVGK, VVGACGVGK, or KLVVVGACGV. [ka]

[0267] In some embodiments, the MHC is HLA-A*02:01, HLA-A*03:01, and / or HLA-A*11:01.

[0268] In some embodiments, the peptide comprises the amino acid sequence VVVGACGVGK or VVGACGVGK, and the MHC is HLA-A*03:01 or HLA-A*11:01. In some embodiments, the peptide comprises the amino acid sequence KLVVVGACGV, and the MHC is HLA-A*02:01.

[0269] In some embodiments, the MHC is HLA-A*01:01.

[0270] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, and the peptide conjugate is AMG-510 or MRTX849 and KRAS G12CFormed by a covalent bond reaction with a peptide, the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH comprises (i) HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes; (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes; and / or (iii) HC CDR3 comprising the amino acid sequence LWASGLDY. In some embodiments, the VL includes (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T, where X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V.

[0271] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, and the peptide conjugate is AMG-510 or MRTX849 and KRAS G12CFormed by a covalent bond reaction with a peptide, the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH comprises (i) HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes; (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes; and / or (iii) HC CDR3 comprising the amino acid sequence SYYGFWQALWALDY. In some embodiments, the VL includes (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T, where X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V.

[0272] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, and the peptide conjugate is AMG-510 or MRTX849 and KRAS G12CFormed by a covalent bond reaction with a peptide, the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH comprises (i) HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes; (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes; and / or (iii) HC CDR3 comprising the amino acid sequence GYYYPYYAMDY. In some embodiments, the VL includes (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC CDR3 comprising the amino acid sequence QQX1X2X3X4YPX5T, where X1 is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5 is I, L, or V.

[0273] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, and the peptide conjugate is AMG-510 or MRTX849 and KRAS G12CFormed by a covalent bond reaction with a peptide, the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH comprises (i) HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes; (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes; and / or (iii) HC CDR3 comprising the amino acid sequence GYYYPYYAMDY. In some embodiments, the VL includes (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T, where X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V.

[0274] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, and the peptide conjugate is AMG-510 or MRTX849 and KRAS G12CFormed by a covalent bond reaction with a peptide, the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH includes (i) HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes; (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes; and / or (iii) HC CDR3 comprising the amino acid sequence X1X2X3X4X5MDY, where X1 is F or G, X2 is Q or Y, X3 is W or G, X4 is Y or W, and X5 is A or G. In some embodiments, the VL includes (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T, where X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V.

[0275] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, and the peptide conjugate is AMG-510 or MRTX849 and KRAS G12CFormed by a covalent bond reaction with a peptide, the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH comprises (i) HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes; (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes; and / or (iii) HC CDR3 comprising the amino acid sequence SGYYSSHWYLQSWYQAMDY. In some embodiments, the VL includes (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC CDR3 comprising the amino acid sequence QQX1X2X3X4YPX5T, where X1 is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5 is I, L, or V.

[0276] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, and the peptide conjugate is AMG-510 or MRTX849 and KRAS G12CFormed by a covalent bond reaction with a peptide, the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH comprises (i) HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes; (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes; and / or (iii) HC CDR3 comprising the amino acid sequence SGYYSSHWYLQSWYQAMDY. In some embodiments, the VL includes (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6T, where X1 is G or A, X2 is S or Y, X3 is S or Y, X4 is G, D, or S, X5 is P or L, and X6 is I or L.

[0277] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, and the peptide conjugate is AMG-510 or MRTX849 and KRAS G12CFormed by a covalent bond reaction with a peptide, the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH comprises (i) HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes; (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes; and / or (iii) HC CDR3 comprising the amino acid sequence HYSEKWWGWYTMYIDAMDY. In some embodiments, the VL includes (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T, where X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V.

[0278] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, and the peptide conjugate is AMG-510 or MRTX849 and KRAS G12CFormed by a covalent bond reaction with a peptide, the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH includes (i) HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes; (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes; and / or (iii) HC CDR3 comprising the amino acid sequence X1WYYX2GMDY, where X1 is G or Y, and X2 is M or L. In some embodiments, the VL includes (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC CDR3 comprising the amino acid sequence QQX1X2X3X4YPX5T, where X1 is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5 is I, L, or V.

[0279] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, and the peptide conjugate is AMG-510 or MRTX849 and KRAS G12CFormed by a covalent bond reaction with a peptide, the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH includes (i) HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes; (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes; and / or (iii) HC CDR3 comprising the amino acid sequence X1WYYX2GMDY, where X1 is G or Y, and X2 is M or L. In some embodiments, the VL includes (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6T, where X1 is G or A, X2 is S or Y, X3 is S or Y, X4 is G, D, or S, X5 is P or L, and X6 is I or L.

[0280] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, and the peptide conjugate is AMG-510 or MRTX849 and KRAS G12CFormed by a covalent bond reaction with a peptide, the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH includes (i) HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes; (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes; and / or (iii) HC CDR3 comprising the amino acid sequence X1WYYX2GMDY, where X1 is G or Y and X2 is M or L. In some embodiments, the VL includes (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC CDR3 comprising the amino acid sequence QQX1X2X3X4X5X6LX7T, where X1 is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4 is G, L, S, E, or Y, X5 is W, S, Y, E, or F, X6 is P, W, G, E, or Q, and X7 is I, F, or V.

[0281] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, and the peptide conjugate is AMG-510 or MRTX849 and KRAS G12CFormed by a covalent bond reaction with a peptide, the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH comprises (i) HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising 1 to 3 amino acid changes; (ii) HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes; and / or (iii) HC CDR3 comprising the amino acid sequence SSRQYYHSQVEPPMAMDY. In some embodiments, the VL includes (i) LC CDR1 comprising the amino acid sequence RASQSVSSAVA or a variant thereof comprising 1 to 5 amino acid changes, (ii) LC CDR2 comprising the amino acid sequence SASSLYS or a variant thereof comprising 1 to 5 amino acid changes, and / or (iii) LC CDR3 comprising the amino acid sequence QQX1X2X3X4YPX5T, where X1 is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5 is I, L, or V.

[0282] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, and the peptide conjugate is AMG-510 or MRTX849 and KRAS G12CFormed by a covalent bonding reaction with a peptide, the binding partner is selected from the group consisting of RM_001, RM_002, RM_003, RM_004, RM_005, RM_006, RM_007, RM_008, RM_009, RM_010, RM_011, RM_012, RM_013, RM_014, RM_015, RM_016, RM_017, RM_018, RM_019, RM_020, RM_021, RM_022, RM_023, RM_024, RM_025, RM_026, RM_027, RM_028, RM_029, RM_030, RM_031, and RM_032, and / or the LC amino acid sequences of the VH amino acid sequence of the binding partner. The amino acid sequences of CDR1, LC CDR2, and LC CDR3, or variants thereof that include one to five amino acid changes in one or more of the amino acid sequences of the CDRs.

[0283] In some embodiments, the coupling partner is selected from the group consisting of RM_001, RM_002, RM_003, RM_004, RM_005, RM_006, RM_007, RM_008, RM_009, RM_010, RM_011, RM_012, RM_013, RM_014, RM_015, RM_016, RM_017, RM_018, RM_019, RM_020, RM_021, RM_022, RM_023, RM_024, RM_025, RM_026, RM_027, RM_028, RM_029, RM_030, RM_031, and RM_032, and is one of the coupling partners HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC The amino acid sequence of CDR3 (Tables A, B, and C), or a variant thereof containing one to five amino acid changes in one or more of the amino acid sequences of said CDR.

[0284] In some embodiments, the binding partner includes a VH and / or VL amino acid sequence that is 90%, 95%, or 100% identical to the following VH and VL sequences: RM_001 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTISSSSIHWVRQAPGKGLEWVASISSYYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARLWASGLDYWGQGTLVTVSS RM_002 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVP SRFSGSRSGTDFTL TISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSYYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARLWASGLDYWGQGTLVTVSS RM_003 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWWYGSPLFTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQALWALDYWGQGTLVTVSS RM_004 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWWYGSPLFTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQALWALDYWGQGTLVTVSS RM_005 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS RM_006 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISPYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS RM_007 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQTSWYHSLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS RM_008 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS RM_009 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS RM_010 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSWLYWLVTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFQWYAMDYWGQGTLVTVSS RM_011 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTISSYSIHWVRQAPGKGLEWVAYISSYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYGWGMDYWGQGTLVTVSS RM_012 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTISYSSIHWVRQAPGKGLEWVAYISSSSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSHWYLQSWYQAMDYWGQGTLVTVSS RM_013 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQASYGPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSHWYLQSWYQAMDYWGQGTLVTVSS RM_014 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWWSSSQLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYSSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARHYSEKWWGWYTMYIDAMDYWGQGTLVTVSS RM_015 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS RM_016 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS RM_017 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS RM_018 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS RM_019 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS RM_020 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS RM_021 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS RM_022 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS RM_023 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSYYEELITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS RM_024 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQAYSDPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS RM_025 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGSSSLLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS RM_026 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSGSYLLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS RM_027 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQADYEFGLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS RM_028 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS RM_029 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS RM_030 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSSSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS RM_031 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYSSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS RM_032 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGSSSLLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVAYISPYSGYTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYLGMDYWGQGTLVTVSS

[0285] In some embodiments, the binding partner has a higher affinity for the peptide conjugate / MHC complex containing the first HLA than for the peptide conjugate / MHC complex containing the second HLA.

[0286] In some embodiments, the first and second HLAs are each selected from the group consisting of HLA-A*02:01, HLA-A*03:01, and / or HLA-A*11:01.

[0287] In some embodiments, the binding partner is an intact antibody, a bispecific antibody, a multispecific antibody, an antigen-binding (Fab) fragment, a Fab' fragment, a (Fab')2 fragment, Fd, Fv, dAb, a single-domain fragment or a single monomer variable antibody domain, a single-chain diabody (scDb), a diabody (Db), a biaffinity retargeting (DART) molecule, a single-chain variable fragment (scFv), a camelid antibody, a bispecific T-cell engager (BiTE), a bispecific killer cell engager (BiKE), a CrossMab, a triplicate binding partner, a chimeric antigen receptor (CAR), a monobody (e.g., adnectin), a DARPin, an antikalin, an affibody, or an affimer. In some embodiments, the binding partner is bispecific. In some embodiments, the binding partner specifically binds to the peptide conjugate / MHC complex and the T-cell antigen. In some embodiments, the binding partner specifically binds to the peptide conjugate / MHC complex and human CD3.

[0288] In some embodiments, the binding partner includes the following VH and / or VL amino acid sequences. UCHT1: V H:EVQLQQSGPELVKPGASMKISKASGYSFTGYTMNWVKQSHGKNLEWMGLINPYKGVSTYNQKFKDKATLTVDKSSSTAYMELLSLTSEDSAVYYCARSGYYGDSDWYFDVWGQGTTLTVSS V L :DIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIK.

[0289] In some embodiments, the binding partner is a single-stranded diabody (scDb) and includes a sequence that is at least 90% identical to one of the following sequences: RM_001_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTVGGGG SEVQLVESGGGLVQPGGSLRLSCAASGFTISSSSIHWVRQAPGKGLEWVASISSYYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARLWASGLDYWGQGTLVTVSSGGG GSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGG GGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_002_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSYYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARLWASGLDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_003_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWWYGSPLFTFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQALWALDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_004_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWWYGSPLFTFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQALWALDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_005_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_006_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISPYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_007_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQTSWYHSLITFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_008_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_009_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_010_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWLVTFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFQWYAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_011_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSYSIHWVRQAPGKGLEWVAYISSYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYGWGMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_012_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISYSSIHWVRQAPGKGLEWVAYISSSSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSHWYLQSWYQAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_013_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASYGPITFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSHWYLQSWYQAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_014_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWWSSSQLITFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTVSYSSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARHYSEKWWGWYTMYIDAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_015_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_016_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_017_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_018_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_019_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_020_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_021_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_022_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_023_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSYYEELITFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_024_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQAYSDPLTFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_025_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGSSSLLTFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_026_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSGSYLLITFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_027_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQADYEFGLITFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_028_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_029_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_030_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTVSSSSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_031_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTVGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTVSYSSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM_032_UCHT1_scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGSSSLLTFGQGTKVEIKRTVGGGGS EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVAYISPYSGYTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYLGMDYWGQGTLVTVSSGGG GSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGG GGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0290] In some embodiments, the binding partner includes a heavy chain constant region selected from the group consisting of human IgM, IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2.

[0291] In some embodiments, the heavy chain constant region includes one or more amino acid substitutions, deletions, or additions in the Fc region.

[0292] In some embodiments, the binding partner includes a human kappa light chain constant region or a human lambda light chain constant re...

Claims

1. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain has a dissociation constant (K) of up to about 100 nM to the first peptide conjugate / MHC complex. Ｄ (ii) binds to the second peptide conjugate / MHC complex with up to approximately 100 nM of K Ｄ Combined with, The first peptide conjugate / MHC complex described above, (a) A first peptide conjugate, wherein the first peptide conjugate of the first peptide conjugate / MHC complex is a first peptide covalently bound to a first targeted covalent inhibitor or a fragment thereof, and (b) including the first MHC, The second peptide conjugate / MHC complex described above, (a) A second peptide conjugate, wherein the second peptide conjugate of the second peptide conjugate / MHC complex is a second peptide covalently bound to a second targeted covalent inhibitor or a fragment thereof, and (b) including the second MHC, The composition wherein the first targeted covalent inhibitor is different from the second targeted covalent inhibitor.

2. The antigen-binding domain (i) has a dissociation constant (K) of up to approximately 50 nM to the first peptide conjugate / MHC complex Ｄ (ii) bound to the second peptide conjugate / MHC complex with up to approximately 50 nM of K Ｄ The composition according to claim 1, which is bonded by

3. The antigen-binding domain (i) has a dissociation constant (K) of up to approximately 10 nM to the first peptide conjugate / MHC complex Ｄ (ii) bound to the second peptide conjugate / MHC complex with up to approximately 10 nM of K Ｄ The composition according to claim 1, which is bonded by

4. The antigen-binding domain (i) has a maximum dissociation constant (K) of approximately 5 nM to the first peptide conjugate / MHC complex. Ｄ (ii) bound to the second peptide conjugate / MHC complex with up to approximately 5 nM of K Ｄ The composition according to claim 1, which is bonded by

5. The composition according to any one of claims 1 to 4, wherein the first targeted covalent inhibitor is a covalent inhibitor of the RAS protein, and the second targeted covalent inhibitor is a covalent inhibitor of the RAS protein.

6. where the first targeted covalent inhibitor is a covalent inhibitor of KRAS Ｇ１２Ｃ and the second targeted covalent inhibitor is a covalent inhibitor of KRAS Ｇ１２Ｃ The composition according to any one of claims 1 to 5, which is a covalent inhibitor of.

7. (i) the first targeted covalent inhibitor is adagrasib and the second targeted covalent inhibitor is sotrasib; (ii) the first targeted covalent inhibitor is adagrasib and the second targeted covalent inhibitor is divalasib; or (iii) the first targeted covalent inhibitor is divalasib and the second targeted covalent inhibitor is sotrasib, according to any one of claims 1 to 6.

8. The antigen-binding domain, (i) To a free first targeted covalent inhibitor not conjugated to a peptide, the dissociation constant (K Ｄ ) Does not bind at less than 200 nM, (ii) K in the first peptide Ｄ Does it not bind at less than 200 nM? (iii) K to the free first peptide conjugate that does not form a complex with MHC Ｄ It does not bind below 200 nM, or (iv) The composition according to any one of claims 1 to 7, which is any combination of the above.

9. The composition according to claim 8, wherein the antigen-binding domain binds to the first peptide conjugate / MHC complex with greater affinity than to the first peptide, the free first targeted covalent inhibitor, and / or the free first peptide conjugate.

10. The composition according to claim 8 or 9, wherein the affinity of the antigen-binding domain to the first peptide conjugate / MHC complex is 100 to 10,000 times greater than the affinity of the antigen-binding domain to the first peptide or the free first targeted covalent inhibitor.

11. The composition according to any one of claims 1 to 10, wherein the antigen-binding domain does not bind to the complex of the first peptide and the first MHC in a detectable manner, and in this case, the first peptide is not covalently bound to the first targeted covalent inhibitor or a fragment thereof.

12. The composition according to any one of claims 8 to 11, wherein the antigen-binding domain does not bind to the free first targeted covalent inhibitor in a detectable manner.

13. The antigen-binding domain has a dissociation constant (K) for the antibody or antigen-binding fragment relative to the first peptide conjugate / MHC complex. Ｄ ) at least 2.5 times K Ｄ A composition according to any one of claims 1 to 12, which is bonded by

14. The antigen-binding domain, (i) A second targeted covalent inhibitor that is not conjugated to a peptide, with a dissociation constant (K Ｄ ) Does not bind at less than 200 nM, (ii) K in the second peptide Ｄ Does it not bind at less than 200 nM? (iii) K to the free second peptide conjugate that does not form a complex with MHC Ｄ It does not bind below 200 nM, or (iv) The composition according to any one of claims 1 to 13, which is any combination of the above.

15. The composition according to claim 14, wherein the antigen-binding domain binds to the second peptide conjugate / MHC complex with greater affinity than to the second peptide, the free second targeted covalent inhibitor, and / or the free second peptide conjugate.

16. The composition according to claim 14 or 15, wherein the affinity of the antigen-binding domain to the second peptide conjugate / MHC complex is 100 to 10,000 times greater than the affinity of the antigen-binding domain to the second peptide or the free second targeted covalent inhibitor.

17. The composition according to any one of claims 1 to 16, wherein the antigen-binding domain does not bind to the complex of the second peptide and the second MHC in a detectable manner, and in this case, the second peptide is not covalently bound to the second targeted covalent inhibitor or a fragment thereof.

18. The composition according to any one of claims 14 to 17, wherein the antigen-binding domain does not bind to the free second targeted covalent inhibitor in a detectable manner.

19. The antigen-binding domain has a dissociation constant (K) for the second peptide conjugate / MHC complex of the antibody or the antigen-binding fragment to the free second peptide conjugate. Ｄ ) at least 2.5 times K Ｄ A composition according to any one of claims 1 to 18, which is bonded by

20. The composition according to any one of claims 1 to 19, wherein the first peptide and the second peptide contain the same amino acid sequence.

21. The composition according to any one of claims 1 to 20, wherein the first peptide and the second peptide have the same amino acid sequence.

22. The composition according to claim 20 or 21, wherein the first peptide or the second peptide comprises the amino acid sequence VVVGACGVGK.

23. The composition according to any one of claims 1 to 22, wherein the first peptide and the second peptide comprise different amino acid sequences.

24. The composition according to claim 23, wherein the first peptide and the second peptide contain a common continuous amino acid sequence having a length of at least 3, 4, 5, 6, 7, 8, or 9 amino acids.

25. The composition according to any one of claims 22 to 24, wherein the first peptide and / or the second peptide comprises the amino acid sequence VVVGACGVGK, VVGACGVGK, or KLVVVGGACGV.

26. The composition according to any one of claims 1 to 25, wherein the first MHC or the second MHC is coded by an HLA, and the HLA is HLA-A*02:01, HLA-A*03:01, or HLA-A*11:

01.

27. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain is bound to a peptide conjugate / MHC complex, the peptide conjugate of the peptide conjugate / MHC complex is a targeted covalent inhibitor or a fragment thereof and a peptide covalently bound to MHC, and the antigen-binding domain has a maximum dissociation constant (K) of approximately 50 nM to the peptide conjugate / MHC complex. Ｄ The composition wherein the target covalent inhibitor is adagrab, and the target covalent inhibitor is conjugated by )

28. The composition according to claim 27, wherein the peptide conjugate / MHC complex is a first peptide conjugate comprising a first peptide conjugate comprising a first peptide and a first targeted covalent inhibitor or a fragment thereof, the antigen-binding domain further bound to a second peptide conjugate / MHC complex, and the second peptide conjugate / MHC complex comprises (a) a second peptide conjugate, wherein the second peptide conjugate of the second peptide conjugate / MHC complex is a second peptide covalently bound to a second targeted covalent inhibitor or a fragment thereof, and (b) a second MHC.

29. The antigen-binding domain provides the second peptide conjugate / MHC complex with a maximum of approximately 50 nM of K Ｄ The composition according to claim 28, which is bonded by

30. The antigen-binding domain (i) has a dissociation constant (K) of up to approximately 10 nM to the first peptide conjugate / MHC complex Ｄ (ii) binds to the second peptide conjugate / MHC complex with up to approximately 10 nM of K Ｄ The composition according to claim 28, which is bonded by

31. The antigen-binding domain (i) has a maximum dissociation constant (K) of approximately 5 nM to the first peptide conjugate / MHC complex. Ｄ (ii) binds to the second peptide conjugate / MHC complex with up to approximately 5 nM of K Ｄ The composition according to claim 28, which is bonded by

32. The composition according to any one of claims 28 to 31, wherein the second targeted covalent inhibitor is sotrasib or diasib.

33. The antigen-binding domain is released to the first targeted covalent inhibitor with a dissociation constant (K Ｄ The composition according to any one of claims 28 to 32, wherein the bonding does not occur at a M of less than 200 nM.

34. The composition according to claim 33, wherein the antigen-binding domain binds to the first peptide conjugate / MHC complex with greater affinity than to the first peptide or the free first targeted covalent inhibitor.

35. The composition according to claim 33 or 34, wherein the affinity of the antigen-binding domain to the first peptide conjugate / MHC complex is 100 to 10,000 times greater than the affinity of the antigen-binding domain to the first peptide or the free first targeted covalent inhibitor.

36. The composition according to any one of claims 28 to 35, wherein the antigen-binding domain does not bind to the complex of the first peptide and the first MHC in a detectable manner, and in this case, the first peptide is not covalently bound to the first targeted covalent inhibitor or a fragment thereof.

37. The composition according to any one of claims 33 to 36, wherein the antigen-binding domain does not bind to the free first targeted covalent inhibitor in a detectable manner.

38. The antigen-binding domain has a dissociation constant (K) for the antibody or antigen-binding fragment relative to the first peptide conjugate / MHC complex. Ｄ ) at least 2.5 times K Ｄ A composition according to any one of claims 28 to 37, which is bonded by

39. The antigen-binding domain is released to a second targeted covalent inhibitor with a dissociation constant (K Ｄ The composition according to any one of claims 28 to 38, wherein no bonding occurs at a M of less than 200 nM.

40. The composition according to claim 39, wherein the antigen-binding domain binds to the second peptide conjugate / MHC complex with greater affinity than to the second peptide or the free second targeted covalent inhibitor.

41. The composition according to claim 39 or 40, wherein the affinity of the antigen-binding domain to the second peptide conjugate / MHC complex is 100 to 10,000 times greater than the affinity of the antigen-binding domain to the second peptide or the free second targeted covalent inhibitor.

42. The composition according to any one of claims 28 to 41, wherein the antigen-binding domain does not bind to the complex of the second peptide and the second MHC in a detectable manner, and in this case, the second peptide is not covalently bound to the second targeted covalent inhibitor or a fragment thereof.

43. The composition according to any one of claims 39 to 42, wherein the antigen-binding domain does not bind to the free second targeted covalent inhibitor in a detectable manner.

44. The antigen-binding domain has a dissociation constant (K) for the second peptide conjugate / MHC complex of the antibody or the antigen-binding fragment to the free second peptide conjugate. Ｄ ) at least 2.5 times K Ｄ A composition according to any one of claims 28 to 43, which is bonded by

45. The composition according to any one of claims 28 to 44, wherein the first peptide and the second peptide contain the same amino acid sequence.

46. The composition according to any one of claims 28 to 45, wherein the first peptide and the second peptide have the same amino acid sequence.

47. The composition according to claim 46, wherein the first peptide or the second peptide comprises the amino acid sequence VVVGACGVGK.

48. The composition according to any one of claims 28 to 44, wherein the first peptide and the second peptide comprise different amino acid sequences.

49. The composition according to claim 48, wherein the first peptide or the second peptide comprises the amino acid sequence VVVGACGVGK, VVGACGVGK, or KLVVVGGACGV.

50. The composition according to any one of claims 28 to 49, wherein the MHC or the second MHC is an HLA, and the HLA is HLA-A*02:01, HLA-A*03:01, or HLA-A*11:

01.

51. The composition according to any one of claims 1 to 26 and 28 to 50, wherein the first peptide or the second peptide comprises a nucleophilic or electrophilic residue, and the residue comprises cysteine, aspartic acid, or arginine.

52. The composition according to any one of claims 1 to 26 and 28 to 51, wherein the first peptide or the second peptide comprises a cysteine ​​residue.

53. The composition according to any one of claims 1 to 26 and 28 to 52, wherein the first peptide conjugate is formed by a covalent bonding reaction between the first targeted covalent inhibitor and a cysteine ​​residue of the first peptide.

54. The composition according to any one of claims 1 to 26 and 28 to 53, wherein the second peptide conjugate is formed by a covalent bonding reaction between the second targeted covalent inhibitor and a cysteine ​​residue of the second peptide.

55. The composition according to any one of claims 1 to 26 and 28 to 54, wherein the first peptide or the second peptide is a segment of a cancer-related protein, and optionally the protein is encoded by a gene that has been mutated in cancer.

56. The composition according to any one of claims 1 to 26 and 28 to 55, wherein the first peptide or the second peptide is a segment of an enzyme, and the first targeted covalent inhibitor or the second targeted covalent inhibitor is an inhibitor of the enzyme.

57. The composition according to claim 56, wherein the enzyme is a kinase or a GTPase.

58. The composition according to any one of claims 1 to 26 and 28 to 57, wherein the first peptide or the second peptide is KRAS or derived from KRAS.

59. The first peptide or the second peptide is KRAS Ｇ１２Ｃ , KRAS Ｇ１２Ｄ , KRAS Ｇ１２Ｒ , or KRAS Ｇ１２Ｓ A composition according to any one of claims 1 to 26 and 28 to 58, comprising the segment.

60. The first targeted covalent inhibitor or the second targeted covalent inhibitor is (i) tricomplex KRAS Ｇ１２Ｃ Inhibitors or KRAS Ｇ１２Ｃ Degradation-inducing factor, (ii) Tricomplex KRAS Ｇ１２Ｄ Inhibitors or KRAS Ｇ１２Ｄ Degradation-inducing factor, (iii) tricomplex KRAS Ｇ１２Ｒ Inhibitors or KRAS Ｇ１２Ｒ Degradation-inducing factor, (iv) tricomplex KRAS Ｇ１２Ｓ Inhibitors or KRAS Ｇ１２Ｓ A composition according to any one of claims 1 to 26 and 28 to 59, which is a degradation-inducing factor.

61. The first peptide conjugate or the second peptide conjugate comprises a compound selected from the group consisting of compounds 1, 2, and 3: 【Chemistry 1】 The aforementioned compound is covalently bonded to a cysteine ​​residue of the peptide. The composition according to any one of claims 1 to 26 and 28 to 60, wherein the peptide comprises the amino acid sequence VVVGACGVGK, VVGACGVGK, or KLVVVGGACGV.

62. The composition according to claim 61, wherein the peptide comprises the amino acid sequence VVVGACGGK or VVGACGVGK, and the MHC is HLA-A*03:01 or HLA-A*11:

01.

63. The composition according to claim 61, wherein the peptide comprises the amino acid sequence KLVVVGACGV, and the MHC is HLA-A*02:

01.

64. The first peptide conjugate is adagrasib and KRAS Ｇ１２Ｃ A composition according to any one of claims 1 to 26 and 28 to 63, formed by a covalent bonding reaction with a peptide.

65. The second peptide conjugate is sotrasib or diasib and KRAS Ｇ１２Ｃ A composition according to any one of claims 1 to 26 and 28 to 64, formed by a covalent bonding reaction with a peptide.

66. The antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), (a) The above VH is (i) Amino acid sequence X １ SX ３ X ４ HC CDR1 containing SIH, X １ However, it is I, F, or V. X ３ However, it is either S or Y. X ４ However, the HC CDR1 is S or Y. (ii) Amino acid sequence X １ ISX ４ X ５ X ６ X ７ X ８ TX １０ HC CDR2 containing YADSVKG, X １ However, it is either S or Y. X ４ However, it is either S or P. X ５ However, it is either S or Y. X ６ However, it is either S or Y. X ７ However, it is either S or G. X ８ However, it is either S or Y. X １０ However, the HC CDR2 is S or Y, Furthermore (iii) Amino acid sequence X Ｎ X １ X ２ HC CDR3 containing DY, X Ｎ However, the amino acid sequence is selected from LWAS, FQWY, GYGW, GWYYL, YWYYM, YWYYL, GYYYPYY, SYYGFWQALW, SSRQYYHSQVEPPPM, SGYYSSHWYLQSWYQ, and HYSEKWWGWYTMYID. X １ However, it is either G or A, X ２ However, it includes the HC CDR3, which is L or M, and / or (b) The VL is, (i) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (ii) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, (iii) Amino acid sequence QQX ３ X ４ X ５ X ６ X ７ X ８ X ９ X １０ LC CDR3 containing T, X ３ However, it is W, T, S, A or G, X ４ However, it is N, W, S, G, Y, D or K, X ５ However, it is W, Y, S, A or T, X ６ However, it is G, S, Y, L, W, E or D, X ７ However, it is either W, S, H, Y, E, F or does not exist. X ８ However, it is either P, Q, S, W, E, L, G or does not exist. X ９ However, it is either L or P. X １０ The composition according to any one of claims 1 to 26 and 28 to 66, comprising the LC CDR3 which is I, L, F, or V.

67. The antigen-binding domain includes a heavy chain variable region (VH) and a light chain variable region (VL), (a) The above VH is (i) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (ii) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) HC CDR3 containing the amino acid sequence LWASGLDY, and / or (b) The VL is, (i) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (ii) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) An amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LX ７ An LC CDR3 containing T, wherein X １ is W, S, or A, and X ２ is N, W, S, or D, and X ３ is W, S, or Y, and X ４ is G, L, S, E, or Y, and X ５ is W, S, Y, E, or F, and X ６ is P, W, G, E, or Q, and X ７ is I, F, or V, said LC CDR3, and the composition according to any one of claims 1 to 26 and 28 to 66.

68. The antigen-binding domain includes a heavy chain variable region (VH) and a light chain variable region (VL), (a) The above VH is (i) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (ii) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) HC CDR3 containing the amino acid sequence SYYGFWQALWALDY, and / or (b) The VL is, (i) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (ii) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LX ７ LC CDR3 containing T, X １ However, it is W, S, or A, and X ２ However, it is N, W, S, or D, and X ３ However, it is W, S, or Y, and X ４ However, it is G, L, S, E or Y, and X ５ However, it is W, S, Y, E, or F, and X ６ However, it is P, W, G, E, or Q, and X ７ The composition according to any one of claims 1 to 26 and 28 to 66, comprising the LC CDR3 which is I, F, or V.

69. The antigen-binding domain includes a heavy chain variable region (VH) and a light chain variable region (VL), (a) The above VH is (i) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (ii) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) HC CDR3 containing the amino acid sequence GYYYPYYAMDY, and / or (b) The VL is, (i) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (ii) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) Amino acid sequence QQX １ X ２ X ３ X ４ YPX ５ LC CDR3 containing T, X １ However, it is either W or S, and X ２ However, it is K, W, or S, and X ３ However, it is W, T, or A, and X ４ However, it is S, W, or Y, and X ５ The composition according to any one of claims 1 to 26 and 28 to 66, comprising the LC CDR3 which is I, L, or V.

70. The antigen-binding domain includes a heavy chain variable region (VH) and a light chain variable region (VL), (a) The above VH is (i) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (ii) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) HC CDR3 containing the amino acid sequence GYYYPYYAMDY, and / or (b) The VL is, (i) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (ii) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LX ７ LC CDR3 containing T, X １ However, it is W, S, or A, and X ２ However, it is N, W, S, or D, and X ３ However, it is W, S, or Y, and X ４ However, it is G, L, S, E or Y, and X ５ However, it is W, S, Y, E, or F, and X ６ However, it is P, W, G, E, or Q, and X ７ The composition according to any one of claims 1 to 26 and 28 to 66, comprising the LC CDR3 which is I, F, or V.

71. The antigen-binding domain includes a heavy chain variable region (VH) and a light chain variable region (VL), (a) The above VH is (i) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (ii) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) Amino acid sequence X １ X ２ X ３ X ４ X ５ HC CDR3 containing MDY, X １ However, it is either F or G, and X ２ However, it is either Q or Y, and X ３ However, it is either W or G, and X ４ However, it is either Y or W, and X ５ However, it includes the HC CDR3, which is A or G, and / or (b) The VL is, (i) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (ii) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LX ７ LC CDR3 containing T, X １ However, it is W, S, or A, and X ２ However, it is N, W, S, or D, and X ３ However, it is W, S, or Y, and X ４ However, it is G, L, S, E or Y, and X ５ However, it is W, S, Y, E, or F, and X ６ However, it is P, W, G, E, or Q, and X ７ The composition according to any one of claims 1 to 26 and 28 to 66, comprising the LC CDR3 which is I, F, or V.

72. The antigen-binding domain includes a heavy chain variable region (VH) and a light chain variable region (VL), (a) The above VH is (i) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (ii) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) HC CDR3 containing the amino acid sequence SGYYSSHWYLQSWYQAMDY, and / or (b) The VL is, (i) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (ii) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) Amino acid sequence QQX １ X ２ X ３ X ４ YPX ５ LC CDR3 containing T, X １ However, it is either W or S, and X ２ However, it is K, W, or S, and X ３ However, it is W, T, or A, and X ４ However, it is S, W, or Y, and X ５ The composition according to any one of claims 1 to 26 and 28 to 66, comprising the LC CDR3 which is I, L, or V.

73. The antigen-binding domain includes a heavy chain variable region (VH) and a light chain variable region (VL), (a) The above VH is (i) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (ii) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) HC CDR3 containing the amino acid sequence SGYYSSHWYLQSWYQAMDY, and / or (b) The VL is, (i) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (ii) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LC CDR3 containing T, X １ However, it is G or A, and X ２ However, it is either S or Y, and X ３ However, it is either S or Y, and X ４ However, it is G, D, or S, and X ５ However, it is either P or L, and X ６ The composition according to any one of claims 1 to 26 and 28 to 66, comprising the LC CDR3 which is I or L.

74. The antigen-binding domain includes a heavy chain variable region (VH) and a light chain variable region (VL), (a) The above VH is (i) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (ii) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) HC CDR3 containing the amino acid sequence HYSEKWWGWYTMYIDAMDY, and / or (b) The VL is, (i) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (ii) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LX ７ LC CDR3 containing T, X １ However, it is W, S, or A, and X ２ However, it is N, W, S, or D, and X ３ However, it is W, S, or Y, and X ４ However, it is G, L, S, E or Y, and X ５ However, it is W, S, Y, E, or F, and X ６ However, it is P, W, G, E, or Q, and X ７ The composition according to any one of claims 1 to 26 and 28 to 66, comprising the LC CDR3 which is I, F, or V.

75. The antigen-binding domain includes a heavy chain variable region (VH) and a light chain variable region (VL), (a) The above VH is (i) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (ii) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) Amino acid sequence X １ WYYX ２ HC CDR3 containing GMDY, X １ However, it is G or Y, and X ２ However, it includes the HC CDR3, which is M or L, and / or (b) The VL is, (i) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (ii) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) Amino acid sequence QQX １ X ２ X ３ X ４ YPX ５ LC CDR3 containing an amino acid including T, and X １ However, it is either W or S, and X ２ However, it is K, W, or S, and X ３ However, it is W, T, or A, and X ４ However, it is S, W, or Y, and X ５ The composition according to any one of claims 1 to 26 and 28 to 66, comprising the LC CDR3 which is I, L, or V.

76. The antigen-binding domain includes a heavy chain variable region (VH) and a light chain variable region (VL), (a) The above VH is (i) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (ii) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) Amino acid sequence X １ WYYX ２ HC CDR3 containing GMDY, X １ However, it is G or Y, and X ２ However, it includes the HC CDR3, which is M or L, and / or (b) The VL is, (i) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (ii) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LC CDR3 containing T, X １ However, it is G or A, and X ２ However, it is either S or Y, and X ３ However, it is either S or Y, and X ４ However, it is G, D, or S, and X ５ However, it is either P or L, and X ６ The composition according to any one of claims 1 to 26 and 28 to 66, comprising the LC CDR3 which is I or L.

77. The antigen-binding domain includes a heavy chain variable region (VH) and a light chain variable region (VL), (a) The above VH is (i) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (ii) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) Amino acid sequence X １ WYYX ２ HC CDR3 containing GMDY, X １ However, it is G or Y, and X ２ However, it includes the HC CDR3, which is M or L, and / or (b) The VL is, (i) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (ii) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LX ７ LC CDR3 containing T, X １ However, it is W, S, or A, and X ２ However, it is N, W, S, or D, and X ３ However, it is W, S, or Y, and X ４ However, it is G, L, S, E or Y, and X ５ However, it is W, S, Y, E, or F, and X ６ However, it is P, W, G, E, or Q, and X ７ The composition according to any one of claims 1 to 26 and 28 to 66, comprising the LC CDR3 which is I, F, or V.

78. The antigen-binding domain includes a heavy chain variable region (VH) and a light chain variable region (VL), (a) The above VH is (i) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (ii) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) HC CDR3 containing the amino acid sequence SSRQYYHSQVEPPMAMDY, and / or (b) The VL is, (i) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (ii) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (iii) Amino acid sequence QQX １ X ２ X ３ X ４ YPX ５ LC CDR3 containing an amino acid including T, and X １ However, it is either W or S, and X ２ However, it is K, W, or S, and X ３ However, it is W, T, or A, and X ４ However, it is S, W, or Y, and X ５ The composition according to any one of claims 1 to 26 and 28 to 66, comprising the LC CDR3 which is I, L, or V.

79. The antigen-binding domain is the HC of the VH amino acid sequence of a polypeptide selected from the group consisting of RM_001, RM_002, RM_003, RM_004, RM_005, RM_006, RM_007, RM_008, RM_009, RM_010, RM_011, RM_012, RM_013, RM_014, RM_015, RM_016, RM_017, RM_018, RM_019, RM_020, RM_021, RM_022, RM_023, RM_024, RM_025, RM_026, RM_027, RM_028, RM_029, RM_030, RM_031, and RM_032. The composition according to any one of claims 1 to 26 and 28 to 78, comprising the amino acid sequences of CDR1, HC CDR2, and HC CDR3 and / or the amino acid sequences of the VL amino acid sequences LC CDR1, LC CDR2, and LC CDR3, or a variant thereof containing one to five amino acid changes in one or more of the amino acid sequences of the CDRs.

80. The antigen-binding domain is HC CDR1 of a polypeptide selected from the group consisting of RM_001, RM_002, RM_003, RM_004, RM_005, RM_006, RM_007, RM_008, RM_009, RM_010, RM_011, RM_012, RM_013, RM_014, RM_015, RM_016, RM_017, RM_018, RM_019, RM_020, RM_021, RM_022, RM_023, RM_024, RM_025, RM_026, RM_027, RM_028, RM_029, RM_030, RM_031, and RM_032. The composition according to any one of claims 1 to 26 and 28 to 79, comprising the amino acid sequence of CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3, or a variant thereof comprising one to five amino acid changes in one or more of the amino acid sequences of the CDR.

81. The antigen-binding domain is the following VH and VL sequence: RM_001 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTISSSSIHWVRQAPGKGLEWVASISSYYGSTSYADSVKGRFTISAD TSKNTAYLQMNSLRAEDTAVYYCARLWASGLDYWGQGTLVTVSS RM_002 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVP SRFSGSRSGTDFTL TISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSYYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARLWASGLDYWGQGTLVTVSS RM_003 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWWYGSPLFTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQALWALDYWGQGTLVTVSS RM_004 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWWYGSPLFTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQALWALDYWGQGTLVTVSS RM_005 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS RM_006 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISPYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS RM_007 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQTSWYHSLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS RM_008 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS RM_009 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS RM_010 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSWLYWLVTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGRFTISAD TSKNTAYLQMNSLRAEDTAVYYCARFQWYAMDYWGQGTLVTVSS RM_011 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTISSYSIHWVRQAPGKGLEWVAYISSYSGYTSYADSVKGRFTISAD TSKNTAYLQMNSLRAEDTAVYYCARGYGWGMDYWGQGTLVTVSS RM_012 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTISYSSIHWVRQAPGKGLEWVAYISSSSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSHWYLQSWYQAMDYWGQGTLVTVSS RM_013 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQASYGPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSHWYLQSWYQAMDYWGQGTLVTVSS RM_014 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWWSSSQLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYSSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARHYSEKWWGWYTMYIDAMDYWGQGTLVTVSS RM_015 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS RM_016 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS RM_017 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS RM_018 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS RM_019 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS RM_020 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS RM_021 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS RM_022 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS RM_023 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSYYEELITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS RM_024 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQAYSDPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS RM_025 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGSSSLLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS RM_026 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSGSYLLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS RM_027 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQADYEFGLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS RM_028 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS RM_029 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVAYISSSYGYTSYAD SVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS RM_030 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSSSSIHWVRQAPGKGLEWVAYISSSYGYTSYAD SVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS RM_031 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYSSIHWVRQAPGKGLEWVAYISSSYGYTSYAD SVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS RM_032 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGSSSLLTFGQGTKVEIKRTV A composition according to any one of claims 1 to 26 and 28 to 80, comprising a VH and / or VL amino acid sequence that is 90%, 95%, or 100% identical to VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSSYSIHWVRQAPGKGLEWVAYISPYSGYTYYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARYWYYLGMDYWGQGTLVTVSS.

82. The composition according to any one of claims 1 to 26 and 28 to 81, wherein the polypeptide specifically binds to the first peptide conjugate / MHC complex and the T cell antigen.

83. The composition according to claim 82, wherein the polypeptide specifically binds to the first peptide conjugate / MHC complex and human CD3.

84. The composition according to any one of claims 1 to 26 and 28 to 83, wherein the polypeptide specifically binds to the second peptide conjugate / MHC complex and the T cell antigen.

85. The composition according to claim 84, wherein the polypeptide specifically binds to the second peptide conjugate / MHC complex and human CD3.

86. The polypeptide is human IgM, IgG １ , IgG ２ , IgG ３ , IgG ４ IgA １ The composition according to any one of claims 1 to 85, comprising a heavy chain constant region selected from the group consisting of and IgA.

87. The composition according to claim 86, wherein the heavy chain constant region comprises one or more amino acid substitutions, deletions, or additions to the Fc region.

88. The composition according to any one of claims 1 to 87, wherein the polypeptide is conjugated with a detectable label, a chemotherapeutic agent, a radioisotope, an enzyme, or a toxin.

89. The composition according to any one of claims 1 to 88, wherein the polypeptide is contained within a chimeric antigen receptor.

90. The composition according to claim 89, wherein the polypeptide is expressed by T cells, killer macrophages, neutrophils, or natural killer cells.

91. A polynucleotide encoding a polypeptide according to any one of claims 1 to 90.

92. A polynucleotide encoding a heavy chain variable region and / or a light chain variable region of a polypeptide according to any one of claims 1 to 91.

93. A vector comprising the polynucleotide described in claim 91 or 92.

94. The vector according to claim 93, which is a viral vector.

95. The vector according to claim 94, wherein the viral vector is an adenovirus vector, a lentivirus vector, a retrovirus vector, or an adeno-associated virus vector.

96. (a) The polynucleotide according to claim 91 or 92, (b) The vector according to any one of claims 93 to 95, (c) A first polynucleotide encoding the VH or heavy chain of the polypeptide according to any one of claims 1 to 90, and a second polynucleotide encoding the VL or light chain of the polypeptide according to any one of claims 1 to 90, or (d) Recombinant host cell comprising a first vector comprising a first polynucleotide encoding the VH or heavy chain of the polypeptide according to any one of claims 1 to 90, and a second vector comprising a second polynucleotide encoding the VL or light chain of the polypeptide according to any one of claims 1 to 90.

97. A pharmaceutical composition comprising a polypeptide according to any one of claims 1 to 90, a polynucleotide according to claim 91 or 92, a vector according to any one of claims 93 to 95, or a host cell according to claim 96, and a pharmaceutically acceptable carrier or excipient.

98. A method for producing polypeptides, comprising culturing the host cells described in claim 96 under suitable conditions such that the polynucleotide is expressed and the binding partner is produced.

99. A eukaryotic cell comprising the polynucleotide described in claim 91 or 92 or the vector described in any one of claims 93 to 95, wherein the cell is optionally a totipotent, pluripotent, or pluripotent stem cell, wherein the stem cell optionally has the phenotype of an induced pluripotent stem cell, or optionally a leukocyte, optionally a CD4+ T cell, optionally a CD8+ T cell, optionally a γδ T cell, optionally a natural killer cell, neutrophil, or macrophage.

100. A method comprising administering a polypeptide according to any one of claims 1 to 90, a polynucleotide according to claim 91 or 92, a vector according to any one of claims 93 to 95, a pharmaceutical composition according to claim 97, or a cell according to claim 96 to an individual in need thereof.

101. (a) an isolated peptide conjugate formed by a covalent reaction between a targeted covalent inhibitor and a peptide, and (b) A cell-free peptide conjugate / MHC complex comprising MHC, The targeted covalent inhibitor is sotrasib, adagrasib, or diavalasib. The aforementioned MHC is HLA, The cell-free peptide conjugate / MHC complex wherein the HLA is HLA-A*02:01, HLA-A*03:01, or HLA-A*11:

01.

102. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), (a) The above VH is (i) Amino acid sequence X Ｎ X １ X ２ HC CDR3 containing DY, X Ｎ However, the amino acid sequence is selected from LWAS, FQWY, GYGW, GWYYL, YWYYM, YWYYL, GYYYPYY, SYYGFWQALW, SSRQYYHSQVEPPPM, SGYYSSHWYLQSWYQ, and HYSEKWWGWYTMYID. X １ However, it is either G or A, X ２ However, it includes the HC CDR3, which is L or M, and / or (b) The VL is, (i) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (ii) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, (iii) Amino acid sequence QQX ３ X ４ X ５ X ６ X ７ X ８ X ９ X １０ LC CDR3 containing T, X ３ However, it is W, T, S, A or G, X ４ However, it is N, W, S, G, Y, D or K, X ５ However, it is W, Y, S, A or T, X ６ However, it is G, S, Y, L, W, E or D, X ７ However, it is either W, S, H, Y, E, F or does not exist. X ８ However, it is either P, Q, S, W, E, L, G or does not exist. X ９ However, it is either L or P. X １０ The composition comprises the LC CDR3, which is I, L, F, or V.

103. The aforementioned VH is an amino acid sequence X １ SX ３ X ４ HC CDR1 containing SIH, X １ However, it is I, F, or V, X ３ However, it is either S or Y, X ４ The composition according to claim 102, comprising the HC CDR1 which is S or Y.

104. The aforementioned VH is an amino acid sequence X １ ISX ４ X ５ X ６ X ７ X ８ TX １０ HC CDR2 containing YADSVKG, X １ However, it is either S or Y, X ４ However, it is S or P, X ５ However, it is either S or Y, X ６ However, it is either S or Y, X ７ However, it is S or G, X ８ However, it is either S or Y, X １０ The composition according to claim 102 or 103, comprising the HC CDR2, which is S or Y.

105. The composition according to any one of claims 102 to 104, wherein the VL comprises LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes.

106. The composition according to any one of claims 102 to 105, wherein the VL comprises LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes.

107. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), (a) The above VH is (i) Amino acid sequence X １ SX ３ X ４ HC CDR1 containing SIH, X １ However, it is I, F, or V. X ３ However, it is either S or Y. X ４ However, the HC CDR1 is S or Y. (ii) Amino acid sequence X １ ISX ４ X ５ X ６ X ７ X ８ TX １０ HC CDR2 containing YADSVKG, X １ However, it is either S or Y. X ４ However, it is either S or P. X ５ However, it is either S or Y. X ６ However, it is either S or Y. X ７ However, it is either S or G. X ８ However, it is either S or Y. X １０ However, the HC CDR2 is S or Y, Furthermore (iii) Amino acid sequence X Ｎ X １ X ２ HC CDR3 containing DY, X Ｎ However, the amino acid sequence is selected from LWAS, FQWY, GYGW, GWYYL, YWYYM, YWYYL, GYYYPYY, SYYGFWQALW, SSRQYYHSQVEPPPM, SGYYSSHWYLQSWYQ, and HYSEKWWGWYTMYID. X １ However, it is either G or A, X ２ However, it includes the HC CDR3, which is L or M, and / or (b) The VL is, (i) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (ii) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, (iii) Amino acid sequence QQX ３ X ４ X ５ X ６ X ７ X ８ X ９ X １０ LC CDR3 containing T, X ３ However, it is W, T, S, A or G, X ４ However, it is N, W, S, G, Y, D or K, X ５ However, it is W, Y, S, A or T, X ６ However, it is G, S, Y, L, W, E or D, X ７ However, it is either W, S, H, Y, E, F or does not exist. X ８ However, it is either P, Q, S, W, E, L, G or does not exist. X ９ However, it is either L or P. X １０ The composition comprises the LC CDR3, which is I, L, F, or V.

108. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence LWASGLDY (SEQ ID NO: 5).

109. The composition according to any one of claims 102 to 108, wherein the VH comprises the HC CDR2 sequence SISSYYGSTSYADSVKG (Sequence ID 4).

110. The composition according to any one of claims 102 to 109, wherein the VH comprises the HC CDR1 sequence ISSSSIH (SEQ ID NO: 3).

111. The composition according to any one of claims 102 to 110, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQWNWGWPLIT (SEQ ID NO: 8).

112. The composition according to any one of claims 102 to 111, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 7).

113. The composition according to any one of claims 102 to 112, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (Sequence ID 6).

114. The antigen-binding domain, HC CDR1 sequence ISSSSIH (Sequence ID 3), HC CDR2 sequence SISSYYGSTSYADSVKG (Sequence No. 4), HC CDR3 sequence LWASGLDY (Sequence ID 5), LC CDR1 sequence RASQSVSSAVA (Sequence ID 6), LC CDR2 sequence SASSLYS (SEQ ID NO: 7), and A composition according to any one of claims 102 to 113, comprising the LC CDR3 sequence QQWNWGWPLIT (SEQ ID NO: 8).

115. The composition according to any one of claims 102 to 114, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTISSSSSIHWVRQAPGKGLEWVASISSYYGSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARLWASGLDYWGQGTLVTVSS (Sequence ID 2).

116. The composition according to any one of claims 102 to 115, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV (Sequence ID 1).

117. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence LWASGLDY (SEQ ID NO: 13).

118. The composition according to claim 117, wherein the VH comprises the HC CDR2 sequence SISSYYGSTSYADSVKG (Sequence ID 12).

119. The composition according to claim 117 or 118, wherein the VH comprises the HC CDR1 sequence FSSSSSIH (Sequence ID 11).

120. The composition according to any one of claims 117 to 119, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQWNWGWPLIT (SEQ ID NO: 16).

121. The composition according to any one of claims 117 to 120, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 15).

122. The composition according to any one of claims 117 to 121, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (Sequence ID 14).

123. The antigen-binding domain, HC CDR1 sequence FSSSSSIH (Sequence ID 11), HC CDR2 sequence SISSYYGSTSYADSVKG (Sequence ID 12), HC CDR3 sequence LWASGLDY (Sequence ID 13), LC CDR1 sequence RASQSVSSAVA (Sequence ID 14), LC CDR2 sequence SASSLYS (SEQ ID NO: 15), and A composition according to any one of claims 117 to 122, comprising the LC CDR3 sequence QQWNWGWPLIT (SEQ ID NO: 16).

124. The composition according to any one of claims 117 to 123, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSYYGSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARLWASGLDYWGQGTLVTVSS (Sequence ID 10).

125. The composition according to any one of claims 117 to 124, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV (Sequence ID 9).

126. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence SYYGFWQALWALDY (SEQ ID NO: 21).

127. The composition according to claim 126, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 20).

128. The composition according to claim 126 or 127, wherein the VH comprises the HC CDR1 sequence FSSSSSIH (SEQ ID NO: 19).

129. The composition according to any one of claims 126 to 128, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQWWYGSPLFT (SEQ ID NO: 24).

130. The composition according to any one of claims 126 to 129, wherein the VL comprises the LC CDR2 sequence SASSLYS (SEQ ID NO: 23).

131. The composition according to any one of claims 126 to 130, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 22).

132. The antigen-binding domain, HC CDR1 sequence FSSSSSIH (Sequence ID 19), HC CDR2 sequence SISSSGSTSYADSVKG (Sequence ID 20), HC CDR3 sequence SYYGFWQALWALDY (Sequence ID 21), LC CDR1 sequence RASQSVSSAVA (Sequence ID 22), LC CDR2 sequence SASSLYS (SEQ ID NO: 23), and A composition according to any one of claims 126 to 131, comprising the LC CDR3 sequence QQWWYGSPLFT (SEQ ID NO: 24).

133. The composition according to any one of claims 126 to 132, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQALWALDYWGQGTLVTVSS (Sequence ID 18).

134. The composition according to any one of claims 126 to 133, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWWYGSPLFTFGQGTKVEIKRT (Sequence ID 17).

135. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence SYYGFWQALWALDY (SEQ ID NO: 29).

136. The composition according to claim 135, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (Sequence ID 28).

137. The composition according to claim 135 or 136, wherein the VH comprises the HC CDR1 sequence FSSYSH (SEQ ID NO: 27).

138. The composition according to any one of claims 135 to 137, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQWWYGSPLFT (SEQ ID NO: 32).

139. The composition according to any one of claims 135 to 138, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 31).

140. The composition according to any one of claims 135 to 139, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 30).

141. The antigen-binding domain, HC CDR1 sequence FSSYSIH (Sequence ID 27), HC CDR2 sequence SISSSGSTSYADSVKG (Sequence ID 28), HC CDR3 sequence SYYGFWQALWALDY (Sequence ID 29), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 30), LC CDR2 sequence SASSLYS (SEQ ID NO: 31), and A composition according to any one of claims 135 to 140, comprising the LC CDR3 sequence QQWWYGSPLFT (SEQ ID NO: 32).

142. The composition according to any one of claims 135 to 141, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSYSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQALWALDYWGQGTLVTVSS (Sequence ID 26).

143. The composition according to any one of claims 135 to 142, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWWYGSPLFTFGQGTKVEIKRT (Sequence ID 25).

144. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence GYYYPYYAMDY (SEQ ID NO: 37).

145. The composition according to claim 144, wherein the VH comprises the HC CDR2 sequence SISSYYGSTYYADSVKG (SEQ ID NO: 36).

146. The composition according to claim 144 or 145, wherein the VH comprises the HC CDR1 sequence FSYYSIH (SEQ ID NO: 35).

147. The composition according to any one of claims 144 to 146, wherein the antigen-binding domain comprises a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQGKTYYPIT (SEQ ID NO: 40).

148. The composition according to any one of claims 144 to 147, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 39).

149. The composition according to any one of claims 144 to 148, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 38).

150. The antigen-binding domain, HC CDR1 sequence FSYYSIH (Sequence ID 35), HC CDR2 sequence SISSYYGSTYYADSVKG (Sequence ID 36), HC CDR3 sequence GYYYPYYAMDY (sequence number 37), LC CDR1 sequence RASQSVSSAVA (Sequence ID 38), LC CDR2 sequence SASSLYS (SEQ ID NO: 39), and A composition according to any one of claims 144 to 149, comprising the LC CDR3 sequence QQGKTYYPIT (Sequence ID 40).

151. The composition according to any one of claims 144 to 150, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS (Sequence ID 34).

152. The composition according to any one of claims 144 to 151, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV (Sequence ID 33).

153. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence GYYYPYYAMDY (SEQ ID NO: 45).

154. The composition according to claim 153, wherein the VH comprises the HC CDR2 sequence SISPYYGSTYYADSVKG (SEQ ID NO: 44).

155. The composition according to claim 153 or 154, wherein the VH comprises the HC CDR1 sequence FSYYSIH (SEQ ID NO: 43).

156. The composition according to any one of claims 153 to 155, wherein the antigen-binding domain comprises a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQGKTYYPIT (SEQ ID NO: 48).

157. The composition according to any one of claims 153 to 156, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 47).

158. The composition according to any one of claims 153 to 157, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 46).

159. The antigen-binding domain, HC CDR1 sequence FSYYSIH (Sequence ID 43), HC CDR2 sequence SISPYYGSTYYADSVKG (Sequence No. 44), HC CDR3 sequence GYYYPYYAMDY (sequence number 45), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 46), LC CDR2 sequence SASSLYS (SEQ ID NO: 47), and A composition according to any one of claims 153 to 158, comprising the LC CDR3 sequence QQGKTYYPIT (Sequence ID 48).

160. The composition according to any one of claims 153 to 159, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISPYYGSTYYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS (Sequence ID 42).

161. The composition according to any one of claims 153 to 160, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV (Sequence ID 41).

162. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence GYYYPYYAMDY (SEQ ID NO: 53).

163. The composition according to claim 162, wherein the VH comprises the HC CDR2 sequence SISSYYGSTYYADSVKG (SEQ ID NO: 52).

164. The composition according to claim 162 or 163, wherein the VH comprises the HC CDR1 sequence FSYYSIH (SEQ ID NO: 51).

165. The composition according to any one of claims 162 to 164, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQTSWYHSLIT (SEQ ID NO: 56).

166. The composition according to any one of claims 162 to 165, wherein the VL comprises the LC CDR2 sequence SASSLYS (SEQ ID NO: 55).

167. The composition according to any one of claims 162 to 166, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 54).

168. The antigen-binding domain, HC CDR1 sequence FSYYSIH (Sequence ID 51), HC CDR2 sequence SISSYYGSTYYADSVKG (Sequence ID 52), HC CDR3 sequence GYYYPYYAMDY (Sequence ID 53), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 54), LC CDR2 sequence SASSLYS (SEQ ID NO: 55), and A composition according to any one of claims 162 to 167, comprising the LC CDR3 sequence QQTSWYHSLIT (SEQ ID NO: 56).

169. The composition according to any one of claims 162 to 168, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS (Sequence ID 50).

170. The composition according to any one of claims 162 to 169, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQTSWYHSLITFGQGTKVEIKRTV (Sequence ID 49).

171. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence GYYYPYYAMDY (SEQ ID NO: 61).

172. The composition according to claim 171, wherein the VH comprises the HC CDR2 sequence SISSYYGSTYYADSVKG (SEQ ID NO: 60).

173. The composition according to claim 171 or 172, wherein the VH comprises the HC CDR1 sequence VSYYSIH (SEQ ID NO: 59).

174. The composition according to any one of claims 171 to 173, wherein the antigen-binding domain comprises a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQGKTYYPIT (SEQ ID NO: 64).

175. The composition according to any one of claims 171 to 174, wherein the VL comprises the LC CDR2 sequence SASSLYS (SEQ ID NO: 63).

176. The composition according to any one of claims 171 to 175, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 62).

177. The antigen-binding domain, HC CDR1 sequence VSYYSIH (Sequence ID 59), HC CDR2 sequence SISSYYGSTYYADSVKG (Sequence ID 60), HC CDR3 sequence GYYYPYYAMDY (sequence number 61), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 62), LC CDR2 sequence SASSLYS (SEQ ID NO: 63), and A composition according to any one of claims 171 to 176, comprising the LC CDR3 sequence QQGKTYYPIT (Sequence ID 64).

178. The composition according to any one of claims 171 to 177, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS (Sequence ID 58).

179. The composition according to any one of claims 171 to 178, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV (Sequence ID 57).

180. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence GYYYPYYAMDY (SEQ ID NO: 69).

181. The composition according to claim 180, wherein the VH comprises the HC CDR2 sequence SISSYYGSTYYADSVKG (SEQ ID NO: 68).

182. The composition according to claim 180 or 181, wherein the VH comprises the HC CDR1 sequence FSYYSIH (SEQ ID NO: 67).

183. The composition according to any one of claims 180 to 182, wherein the antigen-binding domain comprises a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSWSYPLT (SEQ ID NO: 72).

184. The composition according to any one of claims 180 to 183, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 71).

185. The composition according to any one of claims 180 to 184, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 70).

186. The antigen-binding domain, HC CDR1 sequence FSYYSIH (Sequence ID 67), HC CDR2 sequence SISSYYGSTYYADSVKG (Sequence ID 68), HC CDR3 sequence GYYYPYYAMDY (sequence number 69), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 70), LC CDR2 sequence SASSLYS (SEQ ID NO: 71), and A composition according to any one of claims 180 to 185, comprising the LC CDR3 sequence QQSWWSYPLT (SEQ ID NO: 72).

187. The composition according to any one of claims 180 to 186, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSS (Sequence ID 66).

188. The composition according to any one of claims 180 to 187, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (Sequence ID 65).

189. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence FQWYAMDY (SEQ ID NO: 77).

190. The composition according to claim 189, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 76).

191. The composition according to claim 189 or 190, wherein the VH comprises the HC CDR1 sequence FSSSSSIH (SEQ ID NO: 75).

192. The composition according to any one of claims 189 to 191, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSWLYWLVT (SEQ ID NO: 80).

193. The composition according to any one of claims 189 to 192, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 79).

194. The composition according to any one of claims 189 to 193, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 78).

195. The antigen-binding domain, HC CDR1 sequence FSSSSSIH (SEQ ID NO: 75), HC CDR2 sequence SISSSGSSTSYADSVKG (Sequence ID 76), HC CDR3 sequence FQWYAMDY (sequence number 77), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 78), LC CDR2 sequence SASSLYS (SEQ ID NO: 79), and A composition according to any one of claims 189 to 194, comprising the LC CDR3 sequence QQSSWLYWLVT (SEQ ID NO: 80).

196. The composition according to any one of claims 189 to 195, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARFQWYAMDYWGQGTLVTVSS (Sequence ID 74).

197. The composition according to any one of claims 189 to 196, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWLVTFGQGTKVEIKRTV (Sequence ID 73).

198. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence GYGWGMDY (SEQ ID NO: 85).

199. The composition according to claim 198, wherein the VH comprises the HC CDR2 sequence YISSYSGYTSYADSVKG (Sequence ID 84).

200. The composition according to claim 198 or 199, wherein the VH comprises the HC CDR1 sequence ISSYSIH (SEQ ID NO: 83).

201. The composition according to any one of claims 198 to 200, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQWNWGWPLIT (SEQ ID NO: 88).

202. The composition according to any one of claims 198 to 201, wherein the VL comprises the LC CDR2 sequence SASSLLYS (Sequence ID 87).

203. The composition according to any one of claims 198 to 202, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 86).

204. The antigen-binding domain, HC CDR1 sequence ISSYSIH (Sequence ID 83), HC CDR2 sequence YISSYSGYTSYADSVKG (Sequence No. 84), HC CDR3 sequence GYGWGMDY (Sequence ID 85), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 86), LC CDR2 sequence SASSLYS (SEQ ID NO: 87), and A composition according to any one of claims 198 to 203, comprising the LC CDR3 sequence QQWNWGWPLIT (SEQ ID NO: 88).

205. The composition according to any one of claims 198 to 204, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTISISSYSIHWVRQAPGKGLEWVAYISSYSGYTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARGYGWGMDYWGQGTLVTVSS (Sequence ID 82).

206. The composition according to any one of claims 198 to 205, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV (Sequence ID 81).

207. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence SGYYSSHWYLQSWYQAMDY (SEQ ID NO: 93).

208. The composition according to claim 207, wherein the VH comprises the HC CDR2 sequence YISSSSGYTSYADSVKG (SEQ ID NO: 92).

209. The composition according to claim 207 or 208, wherein the VH comprises the HC CDR1 sequence ISYSSIH (SEQ ID NO: 91).

210. The composition according to any one of claims 207 to 209, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSAWYPVT (SEQ ID NO: 96).

211. The composition according to any one of claims 207 to 210, wherein the VL comprises the LC CDR2 sequence SASSLYS (SEQ ID NO: 95).

212. The composition according to any one of claims 207 to 211, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 94).

213. The antigen-binding domain, HC CDR1 sequence ISYSSIH (Sequence ID 91), HC CDR2 sequence YISSSSGYTSYADSVKG (Sequence ID 92), HC CDR3 sequence SGYYSSHWYLQSWYQAMDY (Sequence ID 93), LC CDR1 sequence RASQSVSSAVA (Sequence ID 94), LC CDR2 sequence SASSLYS (SEQ ID NO: 95), and A composition according to any one of claims 207 to 212, comprising the LC CDR3 sequence QQSSAWYPVT (SEQ ID NO: 96).

214. The composition according to any one of claims 207 to 213, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTISYSSIHWVRQAPGKGLEWVAYISSSSSGYTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSHWYLQSWYQAMDYWGQGTLVTVSS (Sequence ID 90).

215. The composition according to any one of claims 207 to 214, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV (Sequence ID 89).

216. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence SGYYSSHWYLQSWYQAMDY (SEQ ID NO: 101).

217. The composition according to claim 216, wherein the VH comprises the HC CDR2 sequence SISSYYGSTYYADSVKG (Sequence ID 100).

218. The composition according to claim 216 or 217, wherein the VH comprises the HC CDR1 sequence FSYYSIH (SEQ ID NO: 99).

219. The composition according to any one of claims 216 to 218, wherein the antigen-binding domain comprises a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQASYGPIT (SEQ ID NO: 104).

220. The composition according to any one of claims 216 to 219, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 103).

221. The composition according to any one of claims 216 to 220, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (Sequence ID 102).

222. The antigen-binding domain, HC CDR1 sequence FSYYSIH (sequence number 99), HC CDR2 sequence SISSYYGSTYYADSVKG (Sequence ID 100), HC CDR3 sequence SGYYSSHWYLQSWYQAMDY (Sequence ID 101), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 102), LC CDR2 sequence SASSLYS (SEQ ID NO: 103), and A composition according to any one of claims 216 to 221, comprising the LC CDR3 sequence QQASYGPIT (SEQ ID NO: 104).

223. The composition according to any one of claims 216 to 222, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSHWYLQSWYQAMDYWGQGTLVTVSS (Sequence ID 98).

224. The composition according to any one of claims 216 to 223, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASYGPITFGQGTKVEIKRTV (Sequence ID 97).

225. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence HYSEKWWGWYTMYIDAMDY (SEQ ID NO: 109).

226. The composition according to claim 225, wherein the VH comprises the HC CDR2 sequence SISSYYGSTYYADSVKG (Sequence ID 108).

227. The composition according to claim 225 or 226, wherein the VH comprises the HC CDR1 sequence VSYSSIH (Sequence ID 107).

228. The composition according to any one of claims 225 to 227, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQWWSSSQLIT (SEQ ID NO: 112).

229. The composition according to any one of claims 225 to 228, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 111).

230. The composition according to any one of claims 225 to 229, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 110).

231. The antigen-binding domain, HC CDR1 sequence VSYSSIH (sequence number 107), HC CDR2 sequence SISSYYGSTYYADSVKG (Sequence ID 108), HC CDR3 sequence HYSEKWWGWYTMYIDAMDY (Sequence ID 109), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 110), LC CDR2 sequence SASSLYS (SEQ ID NO: 111), and A composition according to any one of claims 225 to 230, comprising the LC CDR3 sequence QQWWSSSQLIT (SEQ ID NO: 112).

232. The composition according to any one of claims 225 to 231, wherein the VH comprises a sequence having at least 80% sequence identity with respect to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYSSSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARHYSEKWWGWYTMYIDAMDYWGQGTLVTVSS (Sequence ID 106).

233. The composition according to any one of claims 225 to 232, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWWSSSSQLITFGQGTKVEIKRTV (Sequence ID 105).

234. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence GWYYLGMDY (SEQ ID NO: 117).

235. The composition according to claim 234, wherein the VH comprises the HC CDR2 sequence YISPYSGYTSYADSVKG (Sequence ID 116).

236. The composition according to claim 234 or 235, wherein the VH comprises the HC CDR1 sequence VSYYSIH (Sequence ID 115).

237. The composition according to any one of claims 234 to 236, wherein the antigen-binding domain comprises a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQGKTYYPIT (SEQ ID NO: 120).

238. The composition according to any one of claims 234 to 237, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 119).

239. The composition according to any one of claims 234 to 238, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (Sequence ID 118).

240. The antigen-binding domain, HC CDR1 sequence VSYYSIH (sequence number 115), HC CDR2 sequence YISPYSGYTSYADSVKG (Sequence ID 116), HC CDR3 sequence GWYYLGMDY (Sequence ID 117), LC CDR1 sequence RASQSVSSAVA (Sequence ID 118), LC CDR2 sequence SASSLYS (Sequence ID 119), and A composition according to any one of claims 234 to 239, comprising the LC CDR3 sequence QQGKTYYPIT (SEQ ID NO: 120).

241. The composition according to any one of claims 234 to 240, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS (Sequence ID 114).

242. The composition according to any one of claims 234 to 241, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV (Sequence ID 113).

243. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence GWYYLGMDY (SEQ ID NO: 125).

244. The composition according to claim 243, wherein the VH comprises the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 124).

245. The composition according to claim 243 or 244, wherein the VH comprises the HC CDR1 sequence VSSYSIH (Sequence ID 123).

246. The composition according to any one of claims 243 to 245, wherein the antigen-binding domain comprises a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQGKTYYPIT (SEQ ID NO: 128).

247. The composition according to any one of claims 243 to 246, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 127).

248. The composition according to any one of claims 243 to 247, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (Sequence ID 126).

249. The antigen-binding domain, HC CDR1 sequence VSSYSIH (Sequence ID 123), HC CDR2 sequence SISPYSSYTSYADSVKG (Sequence ID 124), HC CDR3 sequence GWYYLGMDY (Sequence ID 125), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 126), LC CDR2 sequence SASSLYS (SEQ ID NO: 127), and A composition according to any one of claims 243 to 248, comprising the LC CDR3 sequence QQGKTYYPIT (Sequence ID 128).

250. The composition according to any one of claims 243 to 249, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS (Sequence ID 122).

251. The composition according to any one of claims 243 to 250, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV (Sequence ID 121).

252. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence GWYYLGMDY (SEQ ID NO: 133).

253. The composition according to claim 252, wherein the VH comprises the HC CDR2 sequence YISPYSGYTSYADSVKG (Sequence ID 132).

254. The composition according to claim 252 or 253, wherein the VH comprises the HC CDR1 sequence VSYYSIH (Sequence ID 131).

255. The composition according to any one of claims 252 to 254, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQSWWSYPLT (SEQ ID NO: 136).

256. The composition according to any one of claims 252 to 255, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 135).

257. The composition according to any one of claims 252 to 256, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 134).

258. The antigen-binding domain, HC CDR1 sequence VSYYSIH (sequence number 131), HC CDR2 sequence YISPYSGYTSYADSVKG (Sequence ID 132), HC CDR3 sequence GWYYLGMDY (Sequence ID 133), LC CDR1 sequence RASQSVSSAVA (Sequence ID 134), LC CDR2 sequence SASSLYS (SEQ ID NO: 135), and A composition according to any one of claims 252 to 257, comprising the LC CDR3 sequence QQSWWSYPLT (Sequence ID 136).

259. The composition according to any one of claims 252 to 258, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS (Sequence ID 130).

260. The composition according to any one of claims 252 to 259, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (Sequence ID 129).

261. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence GWYYLGMDY (SEQ ID NO: 141).

262. The composition according to claim 261, wherein the VH comprises the HC CDR2 sequence YISPYSGYTSYADSVKG (SEQ ID NO: 140).

263. The composition according to claim 261 or 262, wherein the VH comprises the HC CDR1 sequence VSSYSIH (SEQ ID NO: 139).

264. The composition according to any one of claims 261 to 263, wherein the antigen-binding domain comprises a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSWWSYPLT (SEQ ID NO: 144).

265. The composition according to any one of claims 261 to 264, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 143).

266. The composition according to any one of claims 261 to 265, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 142).

267. The antigen-binding domain, HC CDR1 sequence VSSYSIH (Sequence ID 139), HC CDR2 sequence YISPYSGYTSYADSVKG (Sequence ID 140), HC CDR3 sequence GWYYLGMDY (Sequence ID 141), LC CDR1 sequence RASQSVSSAVA (Sequence ID 142), LC CDR2 sequence SASSLYS (SEQ ID NO: 143), and A composition according to any one of claims 261 to 266, comprising the LC CDR3 sequence QQSWWSYPLT (Sequence ID 144).

268. The composition according to any one of claims 261 to 267, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS (Sequence ID 138).

269. The composition according to any one of claims 261 to 268, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (Sequence ID 137).

270. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence GWYYLGMDY (SEQ ID NO: 149).

271. The composition according to claim 270, wherein the VH comprises the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 148).

272. The composition according to claim 270 or 271, wherein the VH comprises the HC CDR1 sequence FSSYSH (SEQ ID NO: 147).

273. The composition according to any one of claims 270 to 272, wherein the antigen-binding domain comprises a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSWWSYPLT (SEQ ID NO: 152).

274. The composition according to any one of claims 270 to 273, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 151).

275. The composition according to any one of claims 270 to 274, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 150).

276. The antigen-binding domain, HC CDR1 sequence FSSYSIH (Sequence ID 147), HC CDR2 sequence SISPYSSYTSYADSVKG (Sequence ID 148), HC CDR3 sequence GWYYLGMDY (Sequence ID 149), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 150), LC CDR2 sequence SASSLYS (SEQ ID NO: 151), and A composition according to any one of claims 270 to 275, comprising the LC CDR3 sequence QQSWWSYPLT (SEQ ID NO: 152).

277. The composition according to any one of claims 270 to 276, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS (Sequence ID 146).

278. The composition according to any one of claims 270 to 277, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (Sequence ID 145).

279. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence GWYYLGMDY (SEQ ID NO: 157).

280. The composition according to claim 279, wherein the VH comprises the HC CDR2 sequence YISPYSGYTSYADSVKG (SEQ ID NO: 156).

281. The composition according to claim 279 or 280, wherein the VH comprises the HC CDR1 sequence VSYYSIH (Sequence ID 155).

282. The composition according to any one of claims 279 to 281, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSAWYPVT (SEQ ID NO: 160).

283. The composition according to any one of claims 279 to 282, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 159).

284. The composition according to any one of claims 279 to 283, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 158).

285. The antigen-binding domain, HC CDR1 sequence VSYYSIH (sequence number 155), HC CDR2 sequence YISPYSGYTSYADSVKG (Sequence ID 156), HC CDR3 sequence GWYYLGMDY (Sequence ID 157), LC CDR1 sequence RASQSVSSAVA (Sequence ID 158), LC CDR2 sequence SASSLYS (SEQ ID NO: 159), and A composition according to any one of claims 279 to 284, comprising the LC CDR3 sequence QQSSAWYPVT (SEQ ID NO: 160).

286. The composition according to any one of claims 279 to 285, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSS (Sequence ID 154).

287. The composition according to any one of claims 279 to 286, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV (Sequence ID 153).

288. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence YWYYMGMDY (SEQ ID NO: 165).

289. The composition according to claim 288, wherein the VH comprises the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 164).

290. The composition according to claim 288 or 289, wherein the VH comprises the HC CDR1 sequence VSSYSIH (Sequence ID 163).

291. The composition according to any one of claims 288 to 290, wherein the antigen-binding domain comprises a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSWWSYPLT (SEQ ID NO: 168).

292. The composition according to any one of claims 288 to 291, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 167).

293. The composition according to any one of claims 288 to 292, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 166).

294. The antigen-binding domain, HC CDR1 sequence VSSYSIH (Sequence ID 163), HC CDR2 sequence SISPYSSYTSYADSVKG (Sequence ID 164), HC CDR3 sequence YWYYMGMDY (Sequence ID 165), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 166), LC CDR2 sequence SASSLYS (SEQ ID NO: 167), and A composition according to any one of claims 288 to 293, comprising the LC CDR3 sequence QQSWWSYPLT (Sequence ID 168).

295. The composition according to any one of claims 288 to 294, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS (Sequence ID 162).

296. The composition according to any one of claims 288 to 295, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (Sequence ID 161).

297. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence YWYYMGMDY (SEQ ID NO: 173).

298. The composition according to claim 297, wherein the VH comprises the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 172).

299. The composition according to claim 297 or 298, wherein the VH comprises the HC CDR1 sequence VSSYSIH (SEQ ID NO: 171).

300. The composition according to any one of claims 297 to 299, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSAWYPVT (SEQ ID NO: 176).

301. The composition according to any one of claims 297 to 300, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 175).

302. The composition according to any one of claims 297 to 301, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 174).

303. The antigen-binding domain, HC CDR1 sequence VSSYSIH (Sequence ID 171), HC CDR2 sequence SISPYSSYTSYADSVKG (Sequence ID 172), HC CDR3 sequence YWYYMGMDY (Sequence ID 173), LC CDR1 sequence RASQSVSSAVA (Sequence ID 174), LC CDR2 sequence SASSLYS (SEQ ID NO: 175), and A composition according to any one of claims 297 to 302, comprising the LC CDR3 sequence QQSSAWYPVT (SEQ ID NO: 176).

304. The composition according to any one of claims 297 to 303, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS (Sequence ID 170).

305. The composition according to any one of claims 297 to 304, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV (Sequence ID 169).

306. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence YWYYMGMDY (SEQ ID NO: 181).

307. The composition according to claim 306, wherein the VH comprises the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 180).

308. The composition according to claim 306 or 307, wherein the VH comprises the HC CDR1 sequence VSSYSIH (SEQ ID NO: 179).

309. The composition according to any one of claims 306 to 308, wherein the antigen-binding domain comprises a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSYYEELIT (SEQ ID NO: 184).

310. The composition according to any one of claims 306 to 309, wherein the VL comprises the LC CDR2 sequence SASSLLYS (Sequence ID 183).

311. The composition according to any one of claims 306 to 310, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 182).

312. The antigen-binding domain, HC CDR1 sequence VSSYSIH (sequence number 179), HC CDR2 sequence SISPYSSYTSYADSVKG (Sequence ID 180), HC CDR3 sequence YWYYMGMDY (Sequence ID 181), LC CDR1 sequence RASQSVSSAVA (Sequence ID 182), LC CDR2 sequence SASSLYS (SEQ ID NO: 183), and A composition according to any one of claims 306 to 311, comprising the LC CDR3 sequence QQSSYYEELIT (Sequence ID 184).

313. The composition according to any one of claims 306 to 312, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS (Sequence ID 178).

314. The composition according to any one of claims 306 to 313, wherein the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSYYEELITFGQGTKVEIKRTV (Sequence ID 177).

315. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence YWYYMGMDY (SEQ ID NO: 189).

316. The composition according to claim 315, wherein the VH comprises the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 188).

317. The composition according to claim 315 or 316, wherein the VH comprises the HC CDR1 sequence VSSYSIH (Sequence ID 187).

318. The composition according to any one of claims 315 to 317, wherein the antigen-binding domain comprises a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQAYSDPLT (SEQ ID NO: 192).

319. The composition according to any one of claims 315 to 318, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 191).

320. The composition according to any one of claims 315 to 319, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 190).

321. The antigen-binding domain, HC CDR1 sequence VSSYSIH (Sequence ID 187), HC CDR2 sequence SISPYSSYTSYADSVKG (Sequence ID 188), HC CDR3 sequence YWYYMGMDY (Sequence ID 189), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 190), LC CDR2 sequence SASSLYS (Sequence ID 191), and A composition according to any one of claims 315 to 320, comprising the LC CDR3 sequence QQAYSDPLT (SEQ ID NO: 192).

322. The composition according to any one of claims 315 to 321, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS (Sequence ID 186).

323. The composition according to any one of claims 315 to 322, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQAYSDPLTFGQGTKVEIKRTV (Sequence ID 185).

324. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence YWYYMGMDY (SEQ ID NO: 197).

325. The composition according to claim 324, wherein the VH comprises the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 196).

326. The composition according to claim 324 or 325, wherein the VH comprises the HC CDR1 sequence VSSYSIH (SEQ ID NO: 195).

327. The composition according to any one of claims 324 to 326, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQGSSSLLT (SEQ ID NO: 200).

328. The composition according to any one of claims 324 to 327, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 199).

329. The composition according to any one of claims 324 to 328, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 198).

330. The antigen-binding domain, HC CDR1 sequence VSSYSIH (Sequence ID 195), HC CDR2 sequence SISPYSSYTSYADSVKG (Sequence ID 196), HC CDR3 sequence YWYYMGMDY (sequence number 197), LC CDR1 sequence RASQSVSSAVA (Sequence ID 198), LC CDR2 sequence SASSLYS (Sequence ID 199), and A composition according to any one of claims 324 to 329, comprising the LC CDR3 sequence QQGSSSLLLT (SEQ ID NO: 200).

331. The composition according to any one of claims 324 to 330, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS (Sequence ID 194).

332. The composition according to any one of claims 324 to 331, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGSSSLLLTFGQGTKVEIKRTV (Sequence ID 193).

333. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence YWYYMGMDY (SEQ ID NO: 205).

334. The composition according to claim 333, wherein the VH comprises the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 204).

335. The composition according to claim 333 or 334, wherein the VH comprises the HC CDR1 sequence VSSYSIH (Sequence ID 203).

336. The composition according to any one of claims 333 to 335, wherein the antigen-binding domain comprises a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSGSYLLIT (SEQ ID NO: 208).

337. The composition according to any one of claims 333 to 336, wherein the VL comprises the LC CDR2 sequence SASSLLYS (Sequence ID 207).

338. The composition according to any one of claims 333 to 337, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 206).

339. The antigen-binding domain, HC CDR1 sequence VSSYSIH (Sequence ID 203), HC CDR2 sequence SISPYSSYTSYADSVKG (Sequence ID 204), HC CDR3 sequence YWYYMGMDY (Sequence ID 205), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 206), LC CDR2 sequence SASSLYS (SEQ ID NO: 207), and A composition according to any one of claims 333 to 338, comprising the LC CDR3 sequence QQSGSYLLIT (SEQ ID NO: 208).

340. The composition according to any one of claims 333 to 339, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS (Sequence ID 202).

341. The composition according to any one of claims 333 to 340, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSGSYLLLITFGQGTKVEIKRTV (Sequence ID 201).

342. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence YWYYMGMDY (SEQ ID NO: 213).

343. The composition according to claim 342, wherein the VH comprises the HC CDR2 sequence SISPYSSYTSYADSVKG (SEQ ID NO: 212).

344. The composition according to claim 342 or 343, wherein the VH comprises the HC CDR1 sequence VSSYSIH (SEQ ID NO: 211).

345. The composition according to any one of claims 342 to 344, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQADYEFGLIT (SEQ ID NO: 216).

346. The composition according to any one of claims 342 to 345, wherein the VL comprises the LC CDR2 sequence SASSLYS (SEQ ID NO: 215).

347. The composition according to any one of claims 342 to 346, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 214).

348. The antigen-binding domain, HC CDR1 sequence VSSYSIH (Sequence ID 211), HC CDR2 sequence SISPYSSYTSYADSVKG (Sequence ID 212), HC CDR3 sequence YWYYMGMDY (Sequence ID 213), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 214), LC CDR2 sequence SASSLYS (SEQ ID NO: 215), and A composition according to any one of claims 342 to 347, comprising the LC CDR3 sequence QQADYEFGLIT (SEQ ID NO: 216).

349. The composition according to any one of claims 342 to 348, wherein the VH comprises a sequence having at least 80% sequence identity with respect to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSS (Sequence ID 210).

350. The composition according to any one of claims 342 to 349, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQADYEFGLITFGQGTKVEIKRTV (Sequence ID 209).

351. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence SSRQYYHSQVEPPMAMDY (SEQ ID NO: 221).

352. The composition according to claim 351, wherein the VH comprises the HC CDR2 sequence YISSSYGYTSYADSVKG (SEQ ID NO: 220).

353. The composition according to claim 351 or 352, wherein the VH comprises the HC CDR1 sequence FSSYSH (SEQ ID NO: 219).

354. The composition according to any one of claims 351 to 353, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQSWWSYPLT (SEQ ID NO: 224).

355. The composition according to any one of claims 351 to 354, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 223).

356. The composition according to any one of claims 351 to 355, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 222).

357. The antigen-binding domain, HC CDR1 sequence FSSYSIH (Sequence ID 219), HC CDR2 sequence YISSSYGYTSYADSVKG (Sequence ID 220), HC CDR3 sequence SSRQYYHSQVEPPMAMDY (Sequence ID 221), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 222), LC CDR2 sequence SASSLYS (SEQ ID NO: 223), and A composition according to any one of claims 351 to 356, comprising the LC CDR3 sequence QQSWWSYPLT (SEQ ID NO: 224).

358. The composition according to any one of claims 351 to 357, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSYSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS (Sequence ID 218).

359. The composition according to any one of claims 351 to 358, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (Sequence ID 217).

360. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence SSRQYYHSQVEPPMAMDY (SEQ ID NO: 229).

361. The composition according to claim 360, wherein the VH comprises the HC CDR2 sequence YISSSYGYTSYADSVKG (SEQ ID NO: 228).

362. The composition according to claim 360 or 361, wherein the VH comprises the HC CDR1 sequence FSYYSIH (SEQ ID NO: 227).

363. The composition according to any one of claims 360 to 362, wherein the antigen-binding domain comprises a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSWWSYPLT (SEQ ID NO: 232).

364. The composition according to any one of claims 360 to 363, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 231).

365. The composition according to any one of claims 360 to 364, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 230).

366. The antigen-binding domain, HC CDR1 sequence FSYYSIH (Sequence ID 227), HC CDR2 sequence YISSSYGYTSYADSVKG (Sequence ID 228), HC CDR3 sequence SSRQYYHSQVEPPMAMDY (Sequence ID 229), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 230), LC CDR2 sequence SASSLYS (SEQ ID NO: 231), and A composition according to any one of claims 360 to 365, comprising the LC CDR3 sequence QQSWWSYPLT (SEQ ID NO: 232).

367. The composition according to any one of claims 360 to 366, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS (Sequence ID 226).

368. The composition according to any one of claims 360 to 367, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (Sequence ID 225).

369. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence SSRQYYHSQVEPPMAMDY (SEQ ID NO: 237).

370. The composition according to claim 369, wherein the VH comprises the HC CDR2 sequence YISSSYGYTSYADSVKG (Sequence ID 236).

371. The composition according to claim 369 or 370, wherein the VH comprises the HC CDR1 sequence VSSSSIH (SEQ ID NO: 235).

372. The composition according to any one of claims 369 to 371, wherein the antigen-binding domain comprises a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSWWSYPLT (SEQ ID NO: 240).

373. The composition according to any one of claims 369 to 372, wherein the VL comprises the LC CDR2 sequence SASSLLYS (Sequence ID 239).

374. The composition according to any one of claims 369 to 373, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 238).

375. The antigen-binding domain, HC CDR1 sequence VSSSSIH (Sequence ID 235), HC CDR2 sequence YISSSYGYTSYADSVKG (Sequence ID 236), HC CDR3 sequence SSRQYYHSQVEPPMAMDY (Sequence ID 237), LC CDR1 sequence RASQSVSSAVA (Sequence ID 238), LC CDR2 sequence SASSLYS (Sequence ID 239), and A composition according to any one of claims 369 to 374, comprising the LC CDR3 sequence QQSWWSYPLT (SEQ ID NO: 240).

376. The composition according to any one of claims 369 to 375, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSSSSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS (Sequence ID 234).

377. The composition according to any one of claims 369 to 376, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (Sequence ID 233).

378. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence SSRQYYHSQVEPPMAMDY (SEQ ID NO: 245).

379. The composition according to claim 378, wherein the VH comprises the HC CDR2 sequence YISSSYGYTSYADSVKG (Sequence ID 244).

380. The composition according to claim 378 or 379, wherein the VH comprises the HC CDR1 sequence VSYSSIH (SEQ ID NO: 243).

381. The composition according to any one of claims 378 to 380, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQSWWSYPLT (SEQ ID NO: 248).

382. The composition according to any one of claims 378 to 381, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 247).

383. The composition according to any one of claims 378 to 382, ​​wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 246).

384. The antigen-binding domain, HC CDR1 sequence VSYSSIH (Sequence ID 243), HC CDR2 sequence YISSSYGYTSYADSVKG (Sequence ID 244), HC CDR3 sequence SSRQYYHSQVEPPMAMDY (Sequence ID 245), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 246), LC CDR2 sequence SASSLYS (SEQ ID NO: 247), and A composition according to any one of claims 378 to 383, comprising the LC CDR3 sequence QQSWWSYPLT (Sequence ID 248).

385. The composition according to any one of claims 378 to 384, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYSSSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS (Sequence ID 242).

386. The composition according to any one of claims 378 to 385, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (Sequence ID 241).

387. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3 (HC CDR3) sequence YWYYLGMDY (SEQ ID NO: 253).

388. The composition according to claim 387, wherein the VH comprises the HC CDR2 sequence YISPYSGYTYYADSVKG (Sequence ID 252).

389. The composition according to claim 387 or 388, wherein the VH comprises the HC CDR1 sequence VSSYSIH (SEQ ID NO: 251).

390. The composition according to any one of claims 387 to 389, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQGSSSLLT (SEQ ID NO: 256).

391. The composition according to any one of claims 387 to 390, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 255).

392. The composition according to any one of claims 387 to 391, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 254).

393. The antigen-binding domain, HC CDR1 sequence VSSYSIH (Sequence ID 251), HC CDR2 sequence YISPYSGYTYYADSVKG (Sequence ID 252), HC CDR3 sequence YWYYLGMDY (Sequence ID 253), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 254), LC CDR2 sequence SASSLYS (sequence number 255), and A composition according to any one of claims 387 to 392, comprising the LC CDR3 sequence QQGSSSLLLT (SEQ ID NO: 256).

394. The composition according to any one of claims 387 to 393, wherein the VH comprises a sequence having at least 80% sequence identity with respect to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSSYSIHWVRQAPGKGLEWVAYISPYSGYTYYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARYWYYLGMDYWGQGTLVTVSS (Sequence ID 250).

395. The composition according to any one of claims 387 to 394, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGSSSLLLTFGQGTKVEIKRTV (Sequence ID 249).

396. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), (a) The above VH is (i) HC CDR3 containing the amino acid sequence LWASGLDY, and / or (b) The VL is, (i) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LX ７ LC CDR3 containing T, X １ However, it is W, S, or A, and X ２ However, it is N, W, S, or D, and X ３ However, it is W, S, or Y, and X ４ However, it is G, L, S, E or Y, and X ５ However, it is W, S, Y, E, or F, and X ６ However, it is P, W, G, E, or Q, and X ７ The composition comprises the LC CDR3, which is I, F, or V.

397. The composition according to claim 396, wherein the VH comprises HC CDR1 comprising the amino acid sequence FSSSSSIH, or a variant thereof comprising one to three amino acid changes.

398. The composition according to claim 396 or 397, wherein the VH comprises HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes.

399. The composition according to any one of claims 396 to 398, wherein the VL comprises LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes.

400. The composition according to any one of claims 396 to 399, wherein the VL comprises LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes.

401. The aforementioned VH is, (a) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (b) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) The composition according to any one of claims 396 to 400, comprising HC CDR3 containing the amino acid sequence LWASGLDY.

402. The aforementioned VL is (a) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (b) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LX ７ LC CDR3 containing T, X １ However, it is W, S, or A, and X ２ However, it is N, W, S, or D, and X ３ However, it is W, S, or Y, and X ４ However, it is G, L, S, E or Y, and X ５ However, it is W, S, Y, E, or F, and X ６ However, it is P, W, G, E, or Q, and X ７ The composition according to any one of claims 396 to 401, comprising the LC CDR3 which is I, F, or V.

403. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), (a) The above VH is (i) HC CDR3 containing the amino acid sequence SYYGFWQALWALDY, and / or (b) The VL is, (i) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LX ７ LC CDR3 containing T, X １ However, it is W, S, or A, and X ２ However, it is N, W, S, or D, and X ３ However, it is W, S, or Y, and X ４ However, it is G, L, S, E or Y, and X ５ However, it is W, S, Y, E, or F, and X ６ However, it is P, W, G, E, or Q, and X ７ The composition comprises the LC CDR3, which is I, F, or V.

404. The composition according to claim 403, wherein the VH comprises HC CDR1 comprising the amino acid sequence FSSSSSIH, or a variant thereof comprising one to three amino acid changes.

405. The composition according to claim 403 or 404, wherein the VH comprises HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes.

406. The composition according to any one of claims 403 to 405, wherein the VL comprises LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes.

407. The composition according to any one of claims 403 to 406, wherein the VL comprises LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes.

408. The aforementioned VH is, (a) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (b) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) The composition according to any one of claims 403 to 407, comprising HC CDR3 having the amino acid sequence SYYGFWQALWALDY.

409. The aforementioned VL is (a) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (b) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LX ７ LC CDR3 containing T, X １ However, it is W, S, or A, and X ２ However, it is N, W, S, or D, and X ３ However, it is W, S, or Y, and X ４ However, it is G, L, S, E or Y, and X ５ However, it is W, S, Y, E, or F, and X ６ However, it is P, W, G, E, or Q, and X ７ The composition according to any one of claims 403 to 408, comprising the LC CDR3 which is I, F, or V.

410. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), (a) The above VH is (i) HC CDR3 containing the amino acid sequence GYYYPYYAMDY, and / or (b) The VL is, (i) Amino acid sequence QQX １ X ２ X ３ X ４ YPX ５ LC CDR3 containing T, X １ However, it is either W or S, and X ２ However, it is K, W, or S, and X ３ However, it is W, T, or A, and X ４ However, it is S, W, or Y, and X ５ The composition comprises the LC CDR3, which is I, L, or V.

411. The composition according to claim 410, wherein the VH comprises HC CDR1 comprising the amino acid sequence FSSSSSIH, or a variant thereof comprising one to three amino acid changes.

412. The composition according to claim 410 or 411, wherein the VH comprises HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes.

413. The composition according to any one of claims 410 to 412, wherein the VL comprises LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes.

414. The composition according to any one of claims 410 to 413, wherein the VL comprises LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes.

415. The aforementioned VH is, (a) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (b) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) The composition according to any one of claims 410 to 414, comprising HC CDR3 having the amino acid sequence GYYYPYYAMDY.

416. The aforementioned VL is (a) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (b) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) Amino acid sequence QQX １ X ２ X ３ X ４ YPX ５ LC CDR3 containing T, X １ However, it is either W or S, and X ２ However, it is K, W, or S, and X ３ However, it is W, T, or A, and X ４ However, it is S, W, or Y, and X ５ The composition according to any one of claims 410 to 415, comprising the LC CDR3 which is I, L, or V.

417. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), (a) The above VH is (i) HC CDR3 containing the amino acid sequence GYYYPYYAMDY, and / or (b) The VL is, (i) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LX ７ LC CDR3 containing T, X １ However, it is W, S, or A, and X ２ However, it is N, W, S, or D, and X ３ However, it is W, S, or Y, and X ４ However, it is G, L, S, E or Y, and X ５ However, it is W, S, Y, E, or F, and X ６ However, it is P, W, G, E, or Q, and X ７ The composition comprises the LC CDR3, which is I, F, or V.

418. The composition according to claim 417, wherein the VH comprises HC CDR1 comprising the amino acid sequence FSSSSSIH, or a variant thereof comprising one to three amino acid changes.

419. The composition according to claim 417 or 418, wherein the VH comprises HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes.

420. The composition according to any one of claims 417 to 419, wherein the VL comprises LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes.

421. The composition according to any one of claims 417 to 420, wherein the VL comprises LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes.

422. The aforementioned VH is, (a) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (b) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) The composition according to any one of claims 417 to 421, comprising HC CDR3 having the amino acid sequence GYYYPYYAMDY.

423. The aforementioned VL is (a) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (b) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LX ７ LC CDR3 containing T, X １ However, it is W, S, or A, and X ２ However, it is N, W, S, or D, and X ３ However, it is W, S, or Y, and X ４ However, it is G, L, S, E or Y, and X ５ However, it is W, S, Y, E, or F, and X ６ However, it is P, W, G, E, or Q, and X ７ The composition according to any one of claims 417 to 422, comprising the LC CDR3 which is I, F, or V.

424. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), (a) The above VH is (i) Amino acid sequence X １ X ２ X ３ X ４ X ５ HC CDR3 containing MDY, X １ However, it is either F or G, and X ２ However, it is either Q or Y, and X ３ However, it is either W or G, and X ４ However, it is either Y or W, and X ５ However, it includes and / or HC CDR3 which is A or G. (b) The VL is, (i) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LX ７ LC CDR3 containing T, X １ However, it is W, S, or A, and X ２ However, it is N, W, S, or D, and X ３ However, it is W, S, or Y, and X ４ However, it is G, L, S, E or Y, and X ５ However, it is W, S, Y, E, or F, and X ６ However, it is P, W, G, E, or Q, and X ７ The composition comprises the LC CDR3, which is I, F, or V.

425. The composition according to claim 424, wherein the VH comprises HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising one to three amino acid changes.

426. The composition according to claim 424 or 425, wherein the VH comprises HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes.

427. The composition according to any one of claims 424 to 426, wherein the VL comprises LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes.

428. The composition according to any one of claims 424 to 427, wherein the VL comprises LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes.

429. The aforementioned VH is, (a) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (b) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) Amino acid sequence X １ X ２ X ３ X ４ X ５ HC CDR3 containing MDY, X １ However, it is either F or G, and X ２ However, it is either Q or Y, and X ３ However, it is either W or G, and X ４ However, it is either Y or W, and X ５ The composition according to any one of claims 424 to 428, comprising the HC CDR3 which is A or G.

430. The aforementioned VL is (a) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (b) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LX ７ LC CDR3 containing T, X １ However, it is W, S, or A, and X ２ However, it is N, W, S, or D, and X ３ However, it is W, S, or Y, and X ４ However, it is G, L, S, E or Y, and X ５ However, it is W, S, Y, E, or F, and X ６ However, it is P, W, G, E, or Q, and X ７ The composition according to any one of claims 424 to 429, comprising the LC CDR3 which is I, F, or V.

431. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), (a) The above VH is (i) HC CDR3 containing the amino acid sequence SGYYSSHWYLQSWYQAMDY, and / or (b) The VL is, (i) Amino acid sequence QQX １ X ２ X ３ X ４ YPX ５ LC CDR3 containing T, X １ However, it is either W or S, and X ２ However, it is K, W, or S, and X ３ However, it is W, T, or A, and X ４ However, it is S, W, or Y, and X ５ The composition comprises the LC CDR3, which is I, L, or V.

432. The composition according to claim 431, wherein the VH comprises HC CDR1 comprising the amino acid sequence FSSSSSIH, or a variant thereof comprising one to three amino acid changes.

433. The composition according to claim 431 or 432, wherein the VH comprises HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes.

434. The composition according to any one of claims 431 to 433, wherein the VL comprises LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes.

435. The composition according to any one of claims 431 to 434, wherein the VL comprises LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes.

436. The aforementioned VH is, (a) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (b) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) The composition according to any one of claims 431 to 435, comprising HC CDR3 having the amino acid sequence SGYYSSHWYLQSWYQAMDY.

437. The aforementioned VL is (a) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (b) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) Amino acid sequence QQX １ X ２ X ３ X ４ YPX ５ LC CDR3 containing T, X １ However, it is either W or S, and X ２ However, it is K, W, or S, and X ３ However, it is W, T, or A, and X ４ However, it is S, W, or Y, and X ５ The composition according to any one of claims 431 to 436, comprising the LC CDR3 which is I, L, or V.

438. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), (a) The above VH is (i) HC CDR3 containing the amino acid sequence SGYYSSHWYLQSWYQAMDY, and / or (b) The VL is, (i) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LC CDR3 containing T, X １ However, it is G or A, and X ２ However, it is either S or Y, and X ３ However, it is either S or Y, and X ４ However, it is G, D, or S, and X ５ However, it is either P or L, and X ６ The composition comprises the LC CDR3, which is I or L.

439. The composition according to claim 438, wherein the VH comprises HC CDR1 comprising the amino acid sequence FSSSSSIH, or a variant thereof comprising one to three amino acid changes.

440. The composition according to claim 438 or 439, wherein the VH comprises HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes.

441. The composition according to any one of claims 438 to 440, wherein the VL comprises LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes.

442. The composition according to any one of claims 438 to 441, wherein the VL comprises LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes.

443. The aforementioned VH is, (a) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (b) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) The composition according to any one of claims 438 to 442, comprising HC CDR3 having the amino acid sequence SGYYSSHWYLQSWYQAMDY.

444. The aforementioned VL is (a) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (b) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LC CDR3 containing T, X １ However, it is G or A, and X ２ However, it is either S or Y, and X ３ However, it is either S or Y, and X ４ However, it is G, D, or S, and X ５ However, it is either P or L, and X ６ The composition according to any one of claims 438 to 443, comprising the LC CDR3 which is I or L.

445. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), (a) The above VH is (i) HC CDR3 comprising the amino acid sequence HYSEKWWGWYTMYIDAMDY, and / or (b) The VL is, (i) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LX ７ LC CDR3 containing T, X １ However, it is W, S, or A, and X ２ However, it is N, W, S, or D, and X ３ However, it is W, S, or Y, and X ４ However, it is G, L, S, E or Y, and X ５ However, it is W, S, Y, E, or F, and X ６ However, it is P, W, G, E, or Q, and X ７ The composition comprises the LC CDR3, which is I, F, or V.

446. The composition according to claim 445, wherein the VH comprises HC CDR1 comprising the amino acid sequence FSSSSSIH, or a variant thereof comprising one to three amino acid changes.

447. The composition according to claim 445 or 446, wherein the VH comprises HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes.

448. The composition according to any one of claims 445 to 447, wherein the VL comprises LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes.

449. The composition according to any one of claims 445 to 448, wherein the VL comprises LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes.

450. The aforementioned VH is, (a) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (b) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) The composition according to any one of claims 445 to 449, comprising HC CDR3 having the amino acid sequence HYSEKWWGWYTMYIDAMDY.

451. The aforementioned VL is (a) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (b) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LX ７ LC CDR3 containing T, X １ However, it is W, S, or A, and X ２ However, it is N, W, S, or D, and X ３ However, it is W, S, or Y, and X ４ However, it is G, L, S, E or Y, and X ５ However, it is W, S, Y, E, or F, and X ６ However, it is P, W, G, E, or Q, and X ７ The composition according to any one of claims 445 to 450, comprising the LC CDR3 which is I, F, or V.

452. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), (a) The above VH is (i) Amino acid sequence X １ WYYX ２ HC CDR3 containing GMDY, X １ However, it is G or Y, and X ２ However, it includes and / or HC CDR3, which is M or L. (b) The VL is, (i) Amino acid sequence QQX １ X ２ X ３ X ４ YPX ５ LC CDR3 containing T, X １ However, it is either W or S, and X ２ However, it is K, W, or S, and X ３ However, it is W, T, or A, and X ４ However, it is S, W, or Y, and X ５ The composition comprises the LC CDR3, which is I, L, or V.

453. The composition according to claim 452, wherein the VH comprises HC CDR1 comprising the amino acid sequence FSSSSSIH, or a variant thereof comprising one to three amino acid changes.

454. The composition according to claim 452 or 453, wherein the VH comprises HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes.

455. The composition according to any one of claims 452 to 454, wherein the VL comprises LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes.

456. The composition according to any one of claims 452 to 455, wherein the VL comprises LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes.

457. The aforementioned VH is, (a) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (b) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) Amino acid sequence X １ WYYX ２ HC CDR3 containing GMDY, X １ However, it is G or Y, and X ２ The composition according to any one of claims 452 to 456, comprising the HC CDR3 which is M or L.

458. The aforementioned VL is (a) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (b) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) Amino acid sequence QQX １ X ２ X ３ X ４ YPX ５ LC CDR3 containing T, X １ However, it is either W or S, and X ２ However, it is K, W, or S, and X ３ However, it is W, T, or A, and X ４ However, it is S, W, or Y, and X ５ The composition according to any one of claims 452 to 457, comprising the LC CDR3 which is I, L, or V.

459. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), (a) The above VH is (i) Amino acid sequence X １ WYYX ２ HC CDR3 containing GMDY, X １ However, it is G or Y, and X ２ However, it includes and / or HC CDR3, which is M or L. (b) The VL is, (i) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LC CDR3 containing T, X １ However, it is G or A, and X ２ However, it is either S or Y, and X ３ However, it is either S or Y, and X ４ However, it is G, D, or S, and X ５ However, it is either P or L, and X ６ The composition comprises the LC CDR3, which is I or L.

460. The composition according to claim 459, wherein the VH comprises HC CDR1 comprising the amino acid sequence FSSSSSIH, or a variant thereof comprising one to three amino acid changes.

461. The composition according to claim 459 or 460, wherein the VH comprises HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes.

462. The composition according to any one of claims 459 to 461, wherein the VL comprises LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes.

463. The composition according to any one of claims 459 to 462, wherein the VL comprises LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes.

464. The aforementioned VH is, (a) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (b) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) Amino acid sequence X １ WYYX ２ HC CDR3 containing GMDY, X １ However, it is G or Y, and X ２ The composition according to any one of claims 459 to 463, comprising the HC CDR3 which is M or L.

465. The aforementioned VL is (a) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (b) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LC CDR3 containing T, X １ However, it is G or A, and X ２ However, it is either S or Y, and X ３ However, it is either S or Y, and X ４ However, it is G, D, or S, and X ５ However, it is either P or L, and X ６ The composition according to any one of claims 459 to 464, comprising the LC CDR3 which is I or L.

466. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), (a) The above VH is (i) Amino acid sequence X １ WYYX ２ HC CDR3 containing GMDY, X １ However, it is G or Y, and X ２ However, it includes and / or HC CDR3, which is M or L. (b) The VL is, (i) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LX ７ LC CDR3 containing T, X １ However, it is W, S, or A, and X ２ However, it is N, W, S, or D, and X ３ However, it is W, S, or Y, and X ４ However, it is G, L, S, E or Y, and X ５ However, it is W, S, Y, E, or F, and X ６ However, it is P, W, G, E, or Q, and X ７ The composition comprises the LC CDR3, which is I, F, or V.

467. The composition according to claim 466, wherein the VH comprises HC CDR1 comprising the amino acid sequence FSSSSIH, or a variant thereof comprising one to three amino acid changes.

468. The composition according to claim 466 or 467, wherein the VH comprises HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes.

469. The composition according to any one of claims 466 to 468, wherein the VL comprises LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes.

470. The composition according to any one of claims 466 to 469, wherein the VL comprises LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes.

471. The aforementioned VH is, (a) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (b) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) Amino acid sequence X １ WYYX ２ HC CDR3 containing GMDY, X １ However, it is G or Y, and X ２ The composition according to any one of claims 466 to 470, comprising the HC CDR3, which is M or L.

472. The aforementioned VL is (a) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (b) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) Amino acid sequence QQX １ X ２ X ３ X ４ X ５ X ６ LX ７ LC CDR3 containing T, X １ However, it is W, S, or A, and X ２ However, it is N, W, S, or D, and X ３ However, it is W, S, or Y, and X ４ However, it is G, L, S, E or Y, and X ５ However, it is W, S, Y, E, or F, and X ６ However, it is P, W, G, E, or Q, and X ７ The composition according to any one of claims 466 to 471, comprising the LC CDR3 which is I, F, or V.

473. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), (a) The above VH is (i) HC CDR3 comprising the amino acid sequence SSRQYYHSQVEPPMAMDY, and / or (b) The VL is, (i) The composition comprising LC CDR3 having the amino acid sequence QQX1X2X3X4YPX5T, wherein X1 is W or S, X2 is K, W or S, X3 is W, T or A, X4 is S, W or Y, and X5 is I, L or V.

474. The composition according to claim 473, wherein the VH comprises HC CDR1 comprising the amino acid sequence FSSSSSIH, or a variant thereof comprising one to three amino acid changes.

475. The composition according to claim 473 or 474, wherein the VH comprises HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes.

476. The composition according to any one of claims 473 to 475, wherein the VL comprises LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes.

477. The composition according to any one of claims 473 to 476, wherein the VL comprises LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising 1 to 5 amino acid changes.

478. The aforementioned VH is, (a) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (b) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) The composition according to any one of claims 473 to 477, comprising HC CDR3 having the amino acid sequence SSRQYYHSQVEPPMAMDY.

479. The aforementioned VL is (a) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (b) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) The composition according to any one of claims 473 to 478, comprising LC CDR3 having the amino acid sequence QQX1X2X3X4YPX5T, wherein X1 is W or S, X2 is K, W or S, X3 is W, T or A, X4 is S, W or Y, and X5 is I, L or V.

480. The composition according to any one of claims 102 to 479, wherein the antigen-binding domain is bound to a peptide conjugate / MHC complex, and the peptide conjugate of the peptide conjugate / MHC complex is a targeted covalent inhibitor or a fragment thereof and a peptide covalently bound to MHC.

481. The composition according to claim 480, wherein the targeted covalent inhibitor is adaglacib, sotracib, or diasib.

482. The composition according to claim 480, wherein the peptide conjugate / MHC complex is a first peptide conjugate comprising a first peptide conjugate comprising a first peptide and a first targeted covalent inhibitor or a fragment thereof, the antigen-binding domain further bound to a second peptide conjugate / MHC complex, and the second peptide conjugate / MHC complex comprises (a) a second peptide conjugate, wherein the second peptide conjugate of the second peptide conjugate / MHC complex is a second peptide covalently bound to a second targeted covalent inhibitor or a fragment thereof, and (b) a second MHC.

483. The antigen-binding domain (i) has a dissociation constant (K) of up to approximately 50 nM to the first peptide conjugate / MHC complex Ｄ (ii) binds to the second peptide conjugate / MHC complex with up to approximately 50 nM of K Ｄ The composition according to claim 482, which is bonded by

484. The antigen-binding domain (i) has a dissociation constant (K) of up to approximately 10 nM to the first peptide conjugate / MHC complex Ｄ (ii) binds to the second peptide conjugate / MHC complex with up to approximately 10 nM of K Ｄ The composition according to claim 482, which is bonded by

485. The antigen-binding domain (i) has a maximum dissociation constant (K) of approximately 5 nM to the first peptide conjugate / MHC complex. Ｄ (ii) binds to the second peptide conjugate / MHC complex with up to approximately 5 nM of K Ｄ The composition according to claim 482, which is bonded by

486. The composition according to any one of claims 482 to 485, wherein (i) the first targeted covalent inhibitor is adagrasib and the second targeted covalent inhibitor is sotrasib, (ii) the first targeted covalent inhibitor is adagrasib and the second targeted covalent inhibitor is divalasib, or (iii) the first targeted covalent inhibitor is divalasib and the second targeted covalent inhibitor is sotrasib.

487. The antigen-binding domain is released to the first targeted covalent inhibitor with a dissociation constant (K Ｄ The composition according to any one of claims 480 to 486, wherein the molecules do not bond at a M of less than 200 nM.

488. The composition according to claim 487, wherein the antigen-binding domain binds to the first peptide conjugate / MHC complex with greater affinity than to the first peptide or the free first targeted covalent inhibitor.

489. The composition according to claim 487 or 488, wherein the affinity of the antigen-binding domain to the first peptide conjugate / MHC complex is 100 to 10,000 times greater than the affinity of the antigen-binding domain to the first peptide or the free first targeted covalent inhibitor.

490. The composition according to any one of claims 482 to 489, wherein the antigen-binding domain does not bind to the complex of the first peptide and MHC in a detectable manner, and in this case, the first peptide is not covalently bound to the first targeted covalent inhibitor or a fragment thereof.

491. The composition according to any one of claims 487 to 490, wherein the antigen-binding domain does not bind to the free first targeted covalent inhibitor in a detectable manner.

492. The antigen-binding domain has a dissociation constant (K) for the antibody or antigen-binding fragment relative to the first peptide conjugate / MHC complex. Ｄ ) at least 2.5 times K Ｄ A composition according to any one of claims 482 to 491, which is bonded by

493. The antigen-binding domain is released to a second targeted covalent inhibitor with a dissociation constant (K Ｄ The composition according to any one of claims 482 to 492, wherein the molecules do not bond at a M of less than 200 nM.

494. The composition according to claim 493, wherein the antigen-binding domain binds to the second peptide conjugate / MHC complex with greater affinity than to the second peptide or the free second targeted covalent inhibitor.

495. The composition according to claim 493 or 494, wherein the affinity of the antigen-binding domain to the second peptide conjugate / MHC complex is 100 to 10,000 times greater than the affinity of the antigen-binding domain to the second peptide or the free second targeted covalent inhibitor.

496. The composition according to any one of claims 482 to 495, wherein the antigen-binding domain does not bind to the complex of the second peptide and the second MHC in a detectable manner, and in this case, the second peptide is not covalently bound to the second targeted covalent inhibitor or a fragment thereof.

497. The composition according to any one of claims 493 to 496, wherein the antigen-binding domain does not bind to the free second targeted covalent inhibitor in a detectable manner.

498. The antigen-binding domain has a dissociation constant (K) for the second peptide conjugate / MHC complex of the antibody or the antigen-binding fragment to the free second peptide conjugate. Ｄ ) at least 2.5 times K Ｄ A composition according to any one of claims 482 to 497, which is bonded by

499. The composition according to any one of claims 482 to 498, wherein the first peptide and the second peptide contain the same amino acid sequence.

500. The composition according to any one of claims 482 to 499, wherein the first peptide and the second peptide have the same amino acid sequence.

501. The composition according to claim 499 or 500, wherein the first peptide or the second peptide comprises the amino acid sequence VVVGACGVGK.

502. The composition according to any one of claims 482 to 498, wherein the first peptide and the second peptide comprise different amino acid sequences.

503. The composition according to claim 502, wherein the first peptide or the second peptide comprises the amino acid sequence VVVGACGVGK, VVGACGVGK, or KLVVVGGACGV.

504. The composition according to any one of claims 482 to 503, wherein the MHC is an HLA, and the HLA is HLA-A*02:01, HLA-A*03:01, or HLA-A*11:

01.

505. The composition according to any one of claims 482 to 504, wherein the first peptide or the second peptide is KRAS or derived from KRAS.

506. The first peptide or the second peptide is KRAS Ｇ１２Ｃ , KRAS Ｇ１２Ｄ , KRAS Ｇ１２Ｒ , or KRAS Ｇ１２Ｓ A composition according to any one of claims 482 to 505, comprising the segment.

507. The first peptide conjugate is released as a first targeted covalent inhibitor and KRAS Ｇ１２Ｃ Peptides, KRAS Ｇ１２Ｄ Peptides, KRAS Ｇ１２Ｓ Peptides, or KRAS Ｇ１２Ｒ A composition according to any one of claims 482 to 506, formed by a covalent bonding reaction with a peptide.

508. The second peptide conjugate is released as a second targeted covalent inhibitor and KRAS Ｇ１２Ｃ Peptides, KRAS Ｇ１２Ｄ Peptides, KRAS Ｇ１２Ｓ Peptides, or KRAS Ｇ１２Ｒ A composition according to any one of claims 482 to 507, formed by a covalent bonding reaction with a peptide.

509. The composition according to claim 507 or 508, wherein the free first targeted covalent inhibitor or the free second targeted covalent inhibitor is sotrasib, adaglasib, or divalasib.

510. The composition according to any one of claims 482 to 509, wherein the first peptide or the second peptide comprises the amino acid sequence VVVGACGVGK, VVGACGVGK, or KLVVVGGACGV.

511. The antigen-binding domain, (a) A first peptide conjugate / MHC complex comprising VVVGACGGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex comprising VVVGACGGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:

01. (b) A first peptide conjugate / MHC complex comprising VVGACGGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex comprising VVGACGGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, or (c) The composition according to any one of claims 102 to 479, comprising a first peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01, and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:

01.

512. The antigen-binding domain, (a) A first peptide conjugate / MHC complex comprising VVVGACGGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex comprising VVVGACGGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, (b) A first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01, or (c) The composition according to any one of claims 102 to 479, comprising a first peptide conjugate / MHC complex comprising VVGACGGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex comprising KLVVVGGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:

01.

513. The antigen-binding domain, (a) A first peptide conjugate / MHC complex comprising VVVGACGGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex comprising VVVGACGGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01, (b) A first peptide conjugate / MHC complex comprising VVGACGGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex comprising VVGACGGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01, or (c) The composition according to any one of claims 102 to 479, comprising a first peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01, and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:

01.

514. The antigen-binding domain, (a) A first peptide conjugate / MHC complex comprising VVVGACGGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex comprising VVVGACGGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01, (b) A first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01, or (c) The composition according to any one of claims 102 to 479, comprising a first peptide conjugate / MHC complex comprising VVGACGGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex comprising KLVVVGGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:

01.

515. The antigen-binding domain, (a) A first peptide conjugate / MHC complex comprising VVVGACGGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex comprising VVVGACGGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01, (b) A first peptide conjugate / MHC complex comprising VVGACGGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex comprising VVGACGGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01, or (c) The composition according to any one of claims 102 to 479, comprising a first peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01, and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:

01.

516. The antigen-binding domain, (a) A first peptide conjugate / MHC complex comprising VVVGACGGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex comprising VVVGACGGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01, (b) A first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01, or (c) The composition according to any one of claims 102 to 479, comprising a first peptide conjugate / MHC complex comprising VVGACGGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, and a second peptide conjugate / MHC complex comprising KLVVVGGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:

01.

517. The antigen-binding domain, (a) A first peptide conjugate / MHC complex comprising VVVGACGGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01, and a second peptide conjugate / MHC complex comprising VVVGACGGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:

01. (b) A first peptide conjugate / MHC complex comprising VVGACGGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01, and a second peptide conjugate / MHC complex comprising VVGACGGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, or (c) The composition according to any one of claims 102 to 479, comprising a first peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01, and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:

01.

518. The antigen-binding domain, (a) A first peptide conjugate / MHC complex comprising VVVGACGGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01, and a second peptide conjugate / MHC complex comprising VVVGACGGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:

01. (b) A first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01, and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01, or (c) The composition according to any one of claims 102 to 479, comprising a first peptide conjugate / MHC complex comprising VVGACGGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*11:01, and a second peptide conjugate / MHC complex comprising KLVVVGGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:

01.

519. The composition according to any one of claims 511 to 518, wherein the first targeted covalent inhibitor or the second targeted covalent inhibitor is sotrasib, adaglasib, or diavalasib.

520. The composition according to any one of claims 102 to 519, wherein the VH is linked to the VL via a linker array.

521. The linker arrangement is (G ４ S) ｎ or (S ４ G) ｎ The composition according to claim 520, comprising, in this case, n being any integer from 1 to 10.

522. The linker is glycine-serine-alanine linker G ４ SA ３ or glycine-serine linker (G ４ S) ４ The composition according to claim 520 or 521, comprising:

523. The composition according to any one of claims 102 to 522, wherein the polypeptide is an intact antibody, a bispecific antibody, a multispecific antibody, an antigen-binding (Fab) fragment, a Fab' fragment, a (Fab')2 fragment, Fd, Fv, dAb, a single-domain fragment or a single monomer variable antibody domain, a single-chain diabody (scDb), a diabody (Db), a biaffinity retargeting (DART) molecule, a single-chain variable fragment (scFv), a bispecific T cell engager (BiTE), a bispecific killer cell engager (BiKE), a CrossMab, a triple-specific binding partner, a chimeric antigen receptor (CAR), a camelid antibody, a monobody, DARPin, antikalin, an affibody, or an affimer.

524. The composition according to any one of claims 102 to 522, wherein the polypeptide comprises a monobody, DARPin, anticharin, an affibody, or an affimer.

525. The composition according to any one of claims 102 to 524, wherein the polypeptide comprises a polypeptide chain containing the antigen-binding domain.

526. The composition according to claim 525, wherein the polypeptide chain further comprises a cytokine or a fragment thereof.

527. The composition according to claim 526, wherein the cytokine comprises IL-2, IL-7, IL-15, IL-12, IL-18, IL-21, or interferon (IFN).

528. A pharmaceutical composition comprising a polypeptide according to any one of claims 170 to 527, and a pharmaceutically acceptable carrier, excipient, adjuvant, or diluent.

529. A method for treating a subject in need of cancer treatment, wherein the subject has previously been treated with a free, targeted covalent inhibitor, and the method comprises administering to the subject a polypeptide according to any one of claims 170 to 527 or a pharmaceutical composition according to claim 528.

530. The method according to claim 529, wherein the free targeted covalent inhibitor is sotrasib, adaglasib, or diavalasib.

531. The method according to claim 529 or 530, wherein the subject is resistant to treatment with the free targeted covalent inhibitor.

532. A method for treating a subject in need of cancer treatment, comprising administering to the subject a polypeptide according to any one of claims 170 to 527 or a pharmaceutical composition according to claim 528.

533. Furthermore, the method according to claim 532, further comprising administering a small molecule drug simultaneously.

534. A polypeptide according to any one of claims 170 to 527 or a pharmaceutical composition according to claim 528, and a method for administering the free targeted covalent inhibitor to a subject requiring administration of the free targeted covalent inhibitor, wherein the free targeted covalent inhibitor is optionally sotrasib, adaglasib, or diasib.

535. The method according to claim 534, wherein the polypeptide according to any one of claims 170 to 527 or the pharmaceutical composition according to claim 528 is administered after or simultaneously with the administration of the free targeted covalent inhibitor.

536. A method for producing a T cell receptor (TCR) that recognizes a first peptide conjugate / MHC complex or a second peptide conjugate / MHC complex according to any one of claims 482 to 510, (a) Multiple candidate TCRs and the first peptide conjugate / MHC complex or the second peptide conjugate / MHC complex, (b) The method comprising identifying at least one TCR that binds to the first peptide conjugate / MHC complex or the second peptide conjugate / MHC complex.

537. The method according to claim 536, wherein the identification in (b) further comprises selecting or isolating the at least one TCR.

538. The method according to claim 536 or 537, wherein the plurality of candidate TCRs are a plurality of soluble TCRs or a plurality of TCRs expressed on the cell surface of a plurality of cells.

539. The method according to claim 538, wherein the plurality of candidate TCRs are a plurality of TCRs expressed on the cell surface of the plurality of cells, and the identification in (b) comprises isolating or selecting cells containing the at least one TCR based on an activation marker of the cell.

540. The method according to claim 539, wherein the activation marker is a T cell activation marker.

541. The method according to claim 540, wherein the T cell activation marker is CD26, CD27, CD28, CD30, CD154, CD40L, CD134, CD25, CD44, CD69, CD137, PD-1, or KLRG1.

542. A TCR comprising the at least one T cell receptor (TCR) according to (b) of any one of claims 536 to 541.

543. The TCR according to claim 542, wherein the TCR is a soluble TCR.

544. The TCR according to claim 542 or 543, wherein the TCR is a bispecific TCR.

545. The first peptide conjugate / MHC complex differs from the second peptide conjugate / MHC complex in that each of the first and second peptide conjugate / MHC complexes independently (a) Formula X ＃ X ＃＋１ X ＃＋２ X ＃＋３ X ＃＋４ (X ＃＋５ ) X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ and X ＃ X ＃＋１ X ＃＋２ X ＃＋３ (X ＃＋４ ) X ＃＋５ X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ and X ＃ X ＃＋１ X ＃＋２ (X ＃＋３ ) X ＃＋４ X ＃＋５ X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ and X ＃ X ＃＋１ (X ＃＋２ )X ＃＋３ X ＃＋４ X ＃＋５ X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ and X ＃－１ X ＃ X ＃＋１ X ＃＋２ X ＃＋３ X ＃＋４ (X ＃＋５ ) X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ and X ＃＋１ X ＃＋２ X ＃＋３ X ＃＋４ (X ＃＋５ ) X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ A different peptide selected from the group consisting of peptides including, The peptide conjugates of the first and second peptide conjugate / MHC complexes are formed by a covalent bonding reaction between the first targeted covalent inhibitor, the second targeted covalent inhibitor or a fragment thereof and the residue in parentheses, and (b) Including the same MHC, The polypeptide contains up to 100 nM of K in the first peptide conjugate / MHC complex. Ｄ It binds to the second peptide conjugate / MHC complex and contains up to 100 nM of K Ｄ Combine them with, or When the polypeptide is in contact with the first peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis with background subtraction, and when the polypeptide is in contact with the second peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis, or When the polypeptide is brought into contact with the first peptide conjugate / MHC complex, a maximum binding signal at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction, and when the polypeptide is brought into contact with the second peptide conjugate / MHC complex, a maximum binding signal at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction, and the reference binding signal is X ＃ X ＃＋１ X ＃＋２ X ＃＋３ X ＃＋４ (X ＃＋５ ) X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ The composition according to any one of claims 1 to 90 and 482 to 510, which is the maximum binding signal for the polypeptide that binds to it.

546. Formula X ＃ X ＃＋１ X ＃＋２ X ＃＋３ X ＃＋４ (X ＃＋５ ) X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ However, equation X ７ X ８ X ９ X １０ X １１ X １２ X １３ X １４ X １５ X １６ X １２ The composition according to claim 545, wherein the first targeted covalent inhibitor, the second targeted covalent inhibitor or a fragment thereof is covalently bound to the first targeted covalent inhibitor, the second targeted covalent inhibitor or a fragment thereof.

547. The polypeptide binds to the first peptide conjugate / MHC complex and the second peptide conjugate / MHC complex, and the first and second peptide conjugate / MHC complexes each (a) Formula X ７ X ８ X ９ X １０ X １１ X １２ X １３ X １４ X １５ X １６ Peptides containing, and (b) Including the same MHC, The first peptide conjugate of the first peptide conjugate / MHC complex is the first targeted covalent inhibitor or a fragment thereof and the peptide X １２ Formed by a covalent bonding reaction with, The second peptide conjugate of the second peptide conjugate / MHC complex is the second targeted covalent inhibitor or a fragment thereof and the peptide X １３ Formed by a covalent bond reaction with, the second targeted covalent inhibitor is the same as the first targeted covalent inhibitor, The polypeptide has a K in the second peptide conjugate / MHC complex relative to the first peptide conjugate / MHC complex. Ｄ K is up to 100,000 times higher Ｄ Combine them with, or The maximum wavelength shift of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum wavelength shift of the polypeptide bound to the first peptide conjugate / MHC complex, or The composition according to any one of claims 1 to 90 and 482 to 510, wherein the maximum binding signal of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum binding signal of the polypeptide bound to the first peptide conjugate / MHC complex.

548. The polypeptide binds to the first peptide conjugate / MHC complex and the second peptide conjugate / MHC complex, and the first and second peptide conjugate / MHC complexes each (a) Formula X ７ X ８ X ９ X １０ X １１ X １２ X １３ X １４ X １５ X １６ Peptides containing, and (b) Including the same MHC, The first peptide conjugate of the first peptide conjugate / MHC complex is the first targeted covalent inhibitor or a fragment thereof, and X ９ , X １０ , X １１ , and X １２ Formed by a covalent bond reaction with a residue selected from the group consisting of, The second peptide conjugate of the second peptide conjugate / MHC complex is the second targeted covalent inhibitor or a fragment thereof, and X １３ , X １４ , and X １５ It is formed by a covalent bonding reaction with a residue selected from the group consisting of the following, and the second targeted covalent inhibitor is the same as the first targeted covalent inhibitor. The polypeptide has a K in the second peptide conjugate / MHC complex relative to the first peptide conjugate / MHC complex. Ｄ K is up to 100,000 times higher Ｄ Combine them with, or The maximum wavelength shift of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum wavelength shift of the polypeptide bound to the first peptide conjugate / MHC complex, or The composition according to any one of claims 1 to 90 and 482 to 510, wherein the maximum binding signal of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum binding signal of the polypeptide bound to the first peptide conjugate / MHC complex.

549. The polypeptide binds to the first peptide conjugate / MHC complex and the second peptide conjugate / MHC complex, and the first and second peptide conjugate / MHC complexes each A peptide comprising formula A-B-C, wherein A contains three or fewer residues having an N-terminal anchor residue, B contains at least four but seven or fewer residues having a residue covalently bound to the first targeted covalent inhibitor or a fragment thereof or the second targeted covalent inhibitor or a fragment thereof, and C contains three or fewer residues having a C-terminal anchor residue, wherein the N-terminal anchor residue and the C-terminal anchor residue bind to MHC, and Including the same MHC, The residue covalently bound to the first targeted covalent inhibitor or fragment of the peptide in the first peptide conjugate / MHC complex is different from the residue covalently bound to the second targeted covalent inhibitor or fragment of the peptide in the second peptide conjugate / MHC complex, The polypeptide contains up to 100 nM of K in the first peptide conjugate / MHC complex. Ｄ It binds to the second peptide conjugate / MHC complex and contains up to 100 nM of K Ｄ Combine them with, or When the polypeptide is in contact with the first peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis with background subtraction, and when the polypeptide is in contact with the second peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis with background subtraction, or When the polypeptide is brought into contact with the first peptide conjugate / MHC complex, a maximum binding signal at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction, and when the polypeptide is brought into contact with the second peptide conjugate / MHC complex, a maximum binding signal at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction, and the reference binding signal is X ＃ X ＃＋１ X ＃＋２ X ＃＋３ X ＃＋４ (X ＃＋５ ) X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ The composition according to any one of claims 1 to 90 and 482 to 510, which is the maximum binding signal for the polypeptide that binds to it.

550. A has two residues X ７ X ８ The composition according to claim 549, comprising:

551. B has 7 residues X ９ X １０ X １１ X １２ X １３ X １４ X １５ The composition according to claim 549 or 550, comprising

552. C is one residue X １６ A composition according to any one of claims 549 to 551, comprising:

553. Equation A - B - C is Equation X ７ X ８ X ９ X １０ X １１ X １２ X １３ X １４ X １５ X １６ The composition according to any one of claims 549 to 552.

554. The first peptide conjugate of the first peptide conjugate / MHC complex is the first targeted covalent inhibitor or a fragment thereof and the peptide X １２ The composition according to claim 553, formed by a covalent bonding reaction with [another entity].

555. The second peptide conjugate of the second peptide conjugate / MHC complex is the second targeted covalent inhibitor or a fragment thereof and the peptide X １３ The composition according to claim 553 or 554, wherein the second targeted covalent inhibitor is formed by a covalent bonding reaction with the first targeted covalent inhibitor, and the second targeted covalent inhibitor is the same as the first targeted covalent inhibitor.

556. The polypeptide has a K in the second peptide conjugate / MHC complex relative to the first peptide conjugate / MHC complex. Ｄ K is up to 100,000 times higher Ｄ The composition according to claim 555, which is bonded by

557. The polypeptide has a K in the second peptide conjugate / MHC complex relative to the first peptide conjugate / MHC complex. Ｄ K is up to 100,000 times higher Ｄ The residue that is bound and covalently bound to the first targeted covalent inhibitor or fragment of the peptide of the first peptide conjugate / MHC complex is X ９ , X １０ , X １１ , and X １２ A residue selected from the group consisting of the following, the residue covalently bound to the second targeted covalent inhibitor or fragment of the peptide of the second peptide conjugate / MHC complex is X １３ , X １４ , and X １５ The composition according to any one of claims 551 to 556.

558. The composition according to any one of claims 544 to 557, wherein the peptide is a RAS peptide.

559. The composition according to claim 558, wherein the RAS peptide comprises a mutation.

560. The composition according to claim 559, wherein the mutation is G12C or G13C.

561. The composition according to any one of claims 558 to 560, wherein the RAS peptide comprises a sequence selected from the group consisting of VVVGACGVGK, VVGACGVGK, and KLVVVGGACGV.

562. The composition according to any one of claims 558 to 560, wherein the RAS peptide comprises a sequence selected from the group consisting of VVVGAGCVGK, VVGAGCVGK, or KLVVVGAGCV.

563. The composition according to any one of claims 544 to 562, wherein the same MHC is selected from the group consisting of HLA-A*03:01, HLA-A*11:01, HLA-A*02:01, HLA-A*68:01, HLA-A*31:01, HLA-A*30:01, HLA-A*33:03, HLA-A*33:01, HLA-A*74:01, HLA-A*34:02, HLA-A*66:01, HLA-A*68:02, HLA-A*02:05, HLA-A*02:02, and HLA-A*02:

06.

564. The composition according to any one of claims 544 to 563, wherein the targeted covalent inhibitor or fragment thereof comprises sotracib.

565. The peptide is RAS peptide, X １２ However, it is a G12C mutation, X １３ The composition according to any one of claims 546 to 548 and 553 to 564, wherein the G13C mutation is present.

566. The polypeptide is covalently bound to the first peptide conjugate / MHC complex having the G12C mutation Cys, which is covalently bound to the first targeted covalent inhibitor or fragment thereof, with up to 100 nM of K Ｄ The second peptide conjugate / MHC complex, which has the G13C mutation Cys covalently bound to the second targeted covalent inhibitor or fragment thereof, is subjected to up to 100 nM of K Ｄ Combine them with, or When the polypeptide is in contact with the first peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis with background subtraction, and when the polypeptide is in contact with the second peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis with background subtraction, or When the polypeptide is brought into contact with the first peptide conjugate / MHC complex, a maximum binding signal at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction, and when the polypeptide is brought into contact with the second peptide conjugate / MHC complex, a maximum binding signal at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction, and the reference binding signal is X ＃ X ＃＋１ X ＃＋２ X ＃＋３ X ＃＋４ X ＃＋５ X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ The composition according to claim 565, which is the maximum binding signal of a polypeptide that binds to a target.

567. The polypeptide is covalently bound to the second targeted covalent inhibitor or fragment, and to the second peptide conjugate / MHC complex having the G13C mutation Cys, and to the first peptide conjugate / MHC complex having the G12C mutation Cys, which is covalently bound to the first targeted covalent inhibitor or fragment. Ｄ K is up to 100,000 times higher Ｄ Combine them with, or The maximum wavelength shift of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum wavelength shift of the polypeptide bound to the first peptide conjugate / MHC complex, or The composition according to claim 565, wherein the maximum binding signal of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum binding signal of the polypeptide bound to the first peptide conjugate / MHC complex.

568. A composition comprising a polypeptide bound to a first peptide conjugate / MHC complex, and a second peptide conjugate / MHC complex different from the first peptide conjugate / MHC complex, wherein each of the first and second peptide conjugate / MHC complexes independently (a) Formula X ＃ X ＃＋１ X ＃＋２ X ＃＋３ X ＃＋４ (X ＃＋５ ) X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ and X ＃ X ＃＋１ X ＃＋２ X ＃＋３ (X ＃＋４ ) X ＃＋５ X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ and X ＃ X ＃＋１ X ＃＋２ (X ＃＋３ ) X ＃＋４ X ＃＋５ X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ and X ＃ X ＃＋１ (X ＃＋２ )X ＃＋３ X ＃＋４ X ＃＋５ X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ and X ＃－１ X ＃ X ＃＋１ X ＃＋２ X ＃＋３ X ＃＋４ (X ＃＋５ ) X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ and X ＃＋１ X ＃＋２ X ＃＋３ X ＃＋４ (X ＃＋５ ) X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ A different peptide selected from the group consisting of peptides including, The peptide conjugates of the first and second peptide conjugate / MHC complexes are formed by a covalent bond reaction between a targeted covalent inhibitor or a fragment thereof and the residue in parentheses, and (b) Including the same MHC, The polypeptide contains up to 100 nM of K in the first peptide conjugate / MHC complex. Ｄ It binds to the second peptide conjugate / MHC complex and contains up to 100 nM of K Ｄ Combine them with, or When the polypeptide is in contact with the first peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis with background subtraction, and when the polypeptide is in contact with the second peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis with background subtraction, or When the polypeptide is brought into contact with the first peptide conjugate / MHC complex, a maximum binding signal at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction, and when the polypeptide is brought into contact with the second peptide conjugate / MHC complex, a maximum binding signal at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction, and the reference binding signal is X ＃ X ＃＋１ X ＃＋２ X ＃＋３ X ＃＋４ (X ＃＋５ ) X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ The composition, which is the maximum binding signal for a polypeptide that binds to a target.

569. Each of the first and second peptide conjugate / MHC complexes is independently, X ＃ X ＃＋１ X ＃＋２ X ＃＋３ X ＃＋４ (X ＃＋５ ) X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ and X ＃ X ＃＋１ X ＃＋２ X ＃＋３ (X ＃＋４ )X ＃＋５ X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ and X ＃ X ＃＋１ X ＃＋２ (X ＃＋３ ) X ＃＋４ X ＃＋５ X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ 、 and X ＃ X ＃＋１ (X ＃＋２ )X ＃＋３ X ＃＋４ X ＃＋５ X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ The composition according to claim 568, comprising a different peptide selected from the group consisting of peptides containing the following.

570. The composition according to claim 568, wherein each of the first and second peptide conjugate / MHC complexes independently comprises a different peptide having an amino acid sequence selected from the group consisting of VVVGACGGVGK, VVVGCGGGVGK, VVVCAGGGVGK, and VVCGAGGVGK.

571. A composition comprising a polypeptide bound to a first peptide conjugate / MHC complex and a second peptide conjugate / MHC complex, wherein the first and second peptide conjugate / MHC complexes are each (a) Formula X ７ X ８ X ９ X １０ X １１ X １２ X １３ X １４ X １５ X １６ Peptides containing, and (b) Including the same MHC, The first peptide conjugate of the first peptide conjugate / MHC complex comprises a targeted covalent inhibitor or a fragment thereof and the peptide X １２ Formed by a covalent bonding reaction with, The second peptide conjugate of the second peptide conjugate / MHC complex is the same targeted covalent inhibitor or fragment thereof and the peptide X １３ Formed by a covalent bonding reaction with, The polypeptide has a K in the second peptide conjugate / MHC complex relative to the first peptide conjugate / MHC complex. Ｄ K is up to 100,000 times higher Ｄ Combine them with, or The maximum wavelength shift of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum wavelength shift of the polypeptide bound to the first peptide conjugate / MHC complex, or The composition wherein the maximum binding signal of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum binding signal of the polypeptide bound to the first peptide conjugate / MHC complex.

572. A composition comprising a polypeptide bound to a first peptide conjugate / MHC complex and a second peptide conjugate / MHC complex, wherein the first and second peptide conjugate / MHC complexes are each (a) Formula X ７ X ８ X ９ X １０ X １１ X １２ X １３ X １４ X １５ X １６ Peptides containing, and (b) Including the same MHC, The first peptide conjugate of the first peptide conjugate / MHC complex is a targeted covalent inhibitor or a fragment thereof, and X ９ , X １０ , X １１ , and X １２ Formed by a covalent bond reaction with a residue selected from the group consisting of, The second peptide conjugate of the second peptide conjugate / MHC complex is the same targeted covalent inhibitor or a fragment thereof, and X １３ , X １４ , and X １５ Formed by a covalent bond reaction with a residue selected from the group consisting of, The polypeptide has a K in the second peptide conjugate / MHC complex relative to the first peptide conjugate / MHC complex. Ｄ K is up to 100,000 times higher Ｄ Combine them with, or The maximum wavelength shift of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum wavelength shift of the polypeptide bound to the first peptide conjugate / MHC complex, or The composition wherein the maximum binding signal of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum binding signal of the polypeptide bound to the first peptide conjugate / MHC complex.

573. A composition comprising a polypeptide bound to a first peptide conjugate / MHC complex and a second peptide conjugate / MHC complex, wherein the first and second peptide conjugate / MHC complexes are each A peptide comprising formula A-B-C, wherein A contains three or fewer residues having an N-terminal anchor residue, B contains at least four but seven or fewer residues having a residue covalently bound to a targeted covalent inhibitor or a fragment thereof, and C contains three or fewer residues having a C-terminal anchor residue, wherein the N-terminal anchor residue and the C-terminal anchor residue bind to MHC, and Including the same MHC, The residue covalently bound to the targeted covalent inhibitor or fragment of the peptide in the first peptide conjugate / MHC complex is different from the residue covalently bound to the targeted covalent inhibitor or fragment of the peptide in the second peptide conjugate / MHC complex, The polypeptide contains up to 100 nM of K in the first peptide conjugate / MHC complex. Ｄ It binds to the second peptide conjugate / MHC complex and contains up to 100 nM of K Ｄ Combine them with, or When the polypeptide is in contact with the first peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis with background subtraction, and when the polypeptide is in contact with the second peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis with background subtraction, or When the polypeptide is brought into contact with the first peptide conjugate / MHC complex, a maximum binding signal at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction, and when the polypeptide is brought into contact with the second peptide conjugate / MHC complex, a maximum binding signal at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction, and the reference binding signal is X ＃ X ＃＋１ X ＃＋２ X ＃＋３ X ＃＋４ (X ＃＋５ ) X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ The composition, which is the maximum binding signal for a polypeptide that binds to a target.

574. A has two residues X ７ X ８ The composition according to claim 573, comprising:

575. B has 7 residues X ９ X １０ X １１ X １２ X １３ X １４ X １５ The composition according to claim 573 or 574, comprising:

576. The composition according to any one of claims 573 to 575, wherein C comprises one residue X16.

577. Equation A - B - C is Equation X ７ X ８ X ９ X １０ X １１ X １２ X １３ X １４ X １５ X １６ The composition according to any one of claims 573 to 576.

578. The first peptide conjugate of the first peptide conjugate / MHC complex is the targeted covalent inhibitor or a fragment thereof and the peptide X １２ The composition according to claim 577, formed by a covalent bonding reaction with [another entity].

579. The second peptide conjugate of the second peptide conjugate / MHC complex is the same targeted covalent inhibitor or fragment thereof and the peptide X １３ The composition according to claim 577 or 578, formed by a covalent bonding reaction with [another entity].

580. The polypeptide has a K in the second peptide conjugate / MHC complex relative to the first peptide conjugate / MHC complex. Ｄ K is up to 100,000 times higher Ｄ The composition according to claim 579, which is bonded by

581. The polypeptide has a K in the second peptide conjugate / MHC complex relative to the first peptide conjugate / MHC complex. Ｄ K is up to 100,000 times higher Ｄ The residue that is bound and covalently bound to the targeted covalent inhibitor or fragment of the peptide of the first peptide conjugate / MHC complex is X ９ , X １０ , X １１ , and X １２ A selection from the group consisting of, the residue covalently bound to the targeted covalent inhibitor or fragment of the peptide of the second peptide conjugate / MHC complex is X １３ , X １４ , and X １５ The composition according to any one of claims 575 to 580.

582. The composition according to any one of claims 568 to 581, wherein the peptide is a RAS peptide.

583. The composition according to claim 582, wherein the RAS peptide contains a mutation.

584. The composition according to claim 583, wherein the mutation is G12C or G13C.

585. The composition according to any one of claims 582 to 584, wherein the RAS peptide comprises a sequence selected from the group consisting of VVVGACGVGK, VVGACGVGK, and KLVVVGGACGV.

586. The composition according to any one of claims 582 to 584, wherein the RAS peptide comprises a sequence selected from the group consisting of VVVGAGCVGK, VVGAGCVGK, or KLVVVGAGCV.

587. The composition according to any one of claims 568 to 586, wherein the same MHC is selected from the group consisting of HLA-A*03:01, HLA-A*11:01, HLA-A*02:01, HLA-, HLA-A*68:01, HLA-A*31:01, HLA-A*30:01, HLA-A*33:03, HLA-A*33:01, HLA-A*74:01, HLA-A*34:02, HLA-A*66:01, HLA-A*68:02, HLA-A*02:05, HLA-A*02:02, and HLA-A*02:

06.

588. The composition according to any one of claims 568 to 587, wherein the targeted covalent inhibitor or fragment thereof comprises sotracib.

589. The peptide is RAS peptide, X １２ However, it is a G12C mutation, X １３ The composition according to any one of claims 570 to 573 and 577 to 588, wherein the G13C mutation is present.

590. The polypeptide is covalently bound to the first peptide conjugate / MHC complex having the G12C mutation Cys, which is covalently bound to the targeted covalent inhibitor or fragment thereof, with up to 100 nM of K Ｄ The second peptide conjugate / MHC complex, which has the G13C mutation Cys covalently bound to the targeted covalent inhibitor or fragment thereof, is subjected to up to 100 nM of K Ｄ Combine them with, or When the polypeptide is in contact with the first peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis with background subtraction, and when the polypeptide is in contact with the second peptide conjugate / MHC complex, a maximum wavelength shift of at least 0.1 nm is observed according to biolayer interferometry analysis with background subtraction, or When the polypeptide is brought into contact with the first peptide conjugate / MHC complex, a maximum binding signal at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction, and when the polypeptide is brought into contact with the second peptide conjugate / MHC complex, a maximum binding signal at least 0.1 times the reference binding signal is observed according to biolayer interferometry analysis with background subtraction, and the reference binding signal is X ＃ X ＃＋１ X ＃＋２ X ＃＋３ X ＃＋４ (X ＃＋５ ) X ＃＋６ X ＃＋７ X ＃＋８ X ＃＋９ The composition according to claim 589, which is the maximum binding signal of a polypeptide that binds to a target.

591. The polypeptide is covalently bound to the targeted covalent inhibitor or fragment, and to the second peptide conjugate / MHC complex having the G13C mutation Cys, and to the first peptide conjugate / MHC complex having the G12C mutation Cys, and to the targeted covalent inhibitor or fragment, and to the K of the polypeptide. Ｄ K is up to 100,000 times higher Ｄ Combine them with, or The maximum wavelength shift of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum wavelength shift of the polypeptide bound to the first peptide conjugate / MHC complex, or The composition according to claim 589, wherein the maximum binding signal of the polypeptide bound to the second peptide conjugate / MHC complex is at least 10 times lower than the maximum binding signal of the polypeptide bound to the first peptide conjugate / MHC complex.

592. The polynucleotide according to claim 91 or 92, which is a modified polynucleotide.

593. The composition according to claim 525, wherein the polypeptide chain further comprises an agonist molecule.

594. The composition according to claim 593, wherein the agonist molecule is a CD28 agonist or a 4-1BB agonist.

595. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), (a) The above VH is (i) Amino acid sequence FX ２ X ３ X ４ HC CDR3 containing AMDY, X ２ However, it is Y, L, T, H, E, A, or R, and X ３ However, it is D, V, L, E, H, T or R, and X ４ However, it includes HC CDR3 (SEQ ID NO: 267), which is L or Y, and / or (b) The VL is, (i) Amino acid sequence QQX ３ SWLX ７ WX ９ X １０ LC CDR3 containing T, X ３ However, it is A or S, and X ７ However, it is either Y or H, and X ９ However, it is L, K, V, Y or I, and X １０ The composition comprises LC CDR3 (SEQ ID NO: 268), which is L, V, or I.

596. The aforementioned VH is an amino acid sequence FX ２ X ３ X ４ HC CDR3 containing AMDY, X ２ However, it is Q, Y, L, T, H, E, A, or R, and X ３ However, it is W, D, V, L, E, H, T, or R, and X ４ The composition according to claim 595, comprising the HC CDR3, which is L or Y.

597. The composition according to claim 595 or 596, wherein the VH comprises HC CDR1 comprising the amino acid sequence FSSSSSIH, or a variant thereof comprising one to three amino acid changes.

598. The composition according to any one of claims 595 to 597, wherein the VH comprises HC CDR2 comprising the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof comprising 1 to 5 amino acid changes.

599. The composition according to any one of claims 595 to 598, wherein the VL comprises LC CDR1 comprising the amino acid sequence RASQSVSSAVA, or a variant thereof comprising 1 to 5 amino acid changes.

600. The composition according to any one of claims 595 to 599, wherein the VL comprises LC CDR2 comprising the amino acid sequence SASSLYS, or a variant thereof comprising one to three amino acid changes.

601. The aforementioned VH is, (a) HC CDR1 containing the amino acid sequence FSSSSIH, or a variant thereof containing one to three amino acid changes, (b) HC CDR2 containing the amino acid sequence SISSYYGSTYYADSVKG, or a variant thereof containing 1 to 5 amino acid changes, and / or (c) Amino acid sequence FX ２ X ３ X ４ HC CDR3 containing AMDY, X ２ However, Y, L, T, H, E, A and X ３ However, it is D, V, L, E, H, T or R, and X ４ The composition according to any one of claims 595 to 600, comprising the HC CDR3 which is L or Y.

602. The aforementioned VL is (a) LC CDR1 containing the amino acid sequence RASQSVSSAVA, or a variant thereof containing 1 to 5 amino acid changes, (b) LC CDR2 containing the amino acid sequence SASSLYS, or a variant thereof containing one to three amino acid changes, and / or (c) Amino acid sequence QQX ３ SWLX ７ WX ９ X １０ LC CDR3 containing T, X ３ However, it is A or S, and X ７ However, it is either Y or H, and X ８ However, it is L, K, V, Y or I, and X ９ The composition according to any one of claims 595 to 601, comprising the LC CDR3 which is L, V, or I.

603. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3FYDLAMDY (SEQ ID NO: 273).

604. The composition according to claim 603, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 272).

605. The composition according to claim 603 or 604, wherein the VH comprises the HC CDR1 sequence FSSSSSIH (Sequence ID 271).

606. The composition according to any one of claims 603 to 605, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLYWLIT (SEQ ID NO: 276).

607. The composition according to claim 606, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 275).

608. The composition according to claim 606 or 607, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 274).

609. The antigen-binding domain, HC CDR1 sequence FSSSSSIH (Sequence ID 271), HC CDR2 sequence SISSSGSSTSYADSVKG (Sequence ID 272), HC CDR3 sequence FYDLAMDY (SEQ ID NO: 273), LC CDR1 sequence RASQSVSSAVA (Sequence ID 274), LC CDR2 sequence SASSLYS (SEQ ID NO: 275), and A composition according to any one of claims 603 to 608, comprising the LC CDR3 sequence QQASWLYWLIT (SEQ ID NO: 276).

610. The composition according to any one of claims 603 to 609, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARFYDLAMDYWGQGTLVTVSS (Sequence ID 270).

611. The composition according to any one of claims 606 to 610, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWLITFGQGTKVEIK (Sequence ID 269).

612. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3FLDLAMDY (SEQ ID NO: 281).

613. The composition according to claim 612, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 280).

614. The composition according to claim 612 or 613, wherein the VH comprises the HC CDR1 sequence FSSSSSIH (Sequence ID 279).

615. The composition according to any one of claims 612 to 614, wherein the antigen-binding domain comprises a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLYWKIT (SEQ ID NO: 284).

616. The composition according to claim 615, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 283).

617. The composition according to claim 615 or 616, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 282).

618. The antigen-binding domain, HC CDR1 sequence FSSSSSIH (Sequence ID 279), HC CDR2 sequence SISSSGSSTSYADSVKG (Sequence ID 280), HC CDR3 sequence FLDLAMDY (SEQ ID NO: 281), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 282), LC CDR2 sequence SASSLYS (SEQ ID NO: 283), and A composition according to any one of claims 612 to 617, comprising the LC CDR3 sequence QQASWLYWKIT (SEQ ID NO: 284).

619. The composition according to any one of claims 612 to 618, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARFLDLAMDYWGQGTLVTVSS (Sequence ID 278).

620. The composition according to any one of claims 615 to 619, wherein the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWKITFGQGTKVEIK (Sequence ID 277).

621. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing a heavy chain complementarity-determining region 3FTVLAMDY (SEQ ID NO: 289).

622. The composition according to claim 621, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 288).

623. The composition according to claim 621 or 622, wherein the VH comprises the HC CDR1 sequence FSSSSIH (Sequence ID 287).

624. The composition according to any one of claims 621 to 623, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLYWLIT (SEQ ID NO: 292).

625. The composition according to claim 624, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 291).

626. The composition according to claim 624 or 625, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 290).

627. The antigen-binding domain, HC CDR1 sequence FSSSSSIH (Sequence ID 287), HC CDR2 sequence SISSSGSSTSYADSVKG (Sequence ID 288), HC CDR3 sequence FTVLAMDY (Sequence ID 289), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 290), LC CDR2 sequence SASSLYS (SEQ ID NO: 291), and A composition according to any one of claims 621 to 626, comprising the LC CDR3 sequence QQASWLYWLIT (SEQ ID NO: 292).

628. The composition according to any one of claims 621 to 627, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMDYWGQGTLVTVSS (Sequence ID 286).

629. The composition according to any one of claims 624 to 628, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWLITFGQGTKVEIK (Sequence ID 285).

630. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing a heavy chain complementarity-determining region 3FTVLAMDY (SEQ ID NO: 297).

631. The composition according to claim 630, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 296).

632. The composition according to claim 630 or 631, wherein the VH comprises the HC CDR1 sequence FSSSSSIH (SEQ ID NO: 295).

633. The composition according to any one of claims 630 to 632, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLYWKVT (SEQ ID NO: 300).

634. The composition according to claim 633, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 299).

635. The composition according to claim 633 or 634, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 298).

636. The antigen-binding domain, HC CDR1 sequence FSSSSSIH (Sequence ID 295), HC CDR2 sequence SISSSGSSTSYADSVKG (Sequence ID 296), HC CDR3 sequence FTVLAMDY (Sequence ID 297), LC CDR1 sequence RASQSVSSAVA (Sequence ID 297), LC CDR2 sequence SASSLYS (SEQ ID NO: 298), and A composition according to any one of claims 630 to 635, comprising the LC CDR3 sequence QQASWLYWKVT (SEQ ID NO: 300).

637. The composition according to any one of claims 630 to 636, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMDYWGQGTLVTVSS (Sequence ID 294).

638. The composition according to any one of claims 633 to 637, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWKVTFGQGTKVEIK (Sequence ID 293).

639. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing a heavy chain complementarity-determining region 3FTVLAMDY (SEQ ID NO: 305).

640. The composition according to claim 639, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 304).

641. The composition according to claim 639 or 640, wherein the VH comprises the HC CDR1 sequence FSSSSSIH (Sequence ID 303).

642. The composition according to any one of claims 639 to 641, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLYWVIT (SEQ ID NO: 308).

643. The composition according to claim 642, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 307).

644. The composition according to claim 642 or 643, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 306).

645. The antigen-binding domain, HC CDR1 sequence FSSSSSIH (SEQ ID NO: 303), HC CDR2 sequence SISSSGSTSYADSVKG (Sequence ID 304), HC CDR3 sequence FTVLAMDY (Sequence ID 305), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 306), LC CDR2 sequence SASSLYS (SEQ ID NO: 307), and A composition according to any one of claims 639 to 644, comprising the LC CDR3 sequence QQASWLYWVIT (SEQ ID NO: 308).

646. The composition according to any one of claims 639 to 645, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMDYWGQGTLVTVSS (Sequence ID 302).

647. The composition according to any one of claims 642 to 646, wherein the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWVITFGQGTKVEIK (Sequence ID 301).

648. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing a heavy chain complementarity-determining region 3FHDLAMDY (SEQ ID NO: 313).

649. The composition according to claim 648, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 312).

650. The composition according to claim 648 or 649, wherein the VH comprises the HC CDR1 sequence FSSSSSIH (Sequence ID 311).

651. The composition according to any one of claims 648 to 650, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLYWKIT (SEQ ID NO: 316).

652. The composition according to claim 651, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 315).

653. The composition according to claim 651 or 652, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 314).

654. The antigen-binding domain, HC CDR1 sequence FSSSSIH (Sequence ID 311), HC CDR2 sequence SISSSGSSTSYADSVKG (Sequence ID 312), HC CDR3 sequence FHDLAMDY (SEQ ID NO: 313), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 314), LC CDR2 sequence SASSLYS (SEQ ID NO: 315), and A composition according to any one of claims 648 to 653, comprising the LC CDR3 sequence QQASWLYWKIT (SEQ ID NO: 316).

655. The composition according to any one of claims 648 to 654, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARFHDLAMDYWGQGTLVTVSS (Sequence ID 310).

656. The composition according to any one of claims 651 to 655, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWKITFGQGTKVEIK (Sequence ID 309).

657. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing a heavy chain complementarity-determining region 3FHELAMDY (SEQ ID NO: 321).

658. The composition according to claim 657, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 320).

659. The composition according to claim 657 or 658, wherein the VH comprises the HC CDR1 sequence FSSSSSIH (SEQ ID NO: 319).

660. The composition according to any one of claims 657 to 659, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLYWLIT (SEQ ID NO: 324).

661. The composition according to claim 660, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 323).

662. The composition according to claim 660 or 661, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 322).

663. The antigen-binding domain, HC CDR1 sequence FSSSSSIH (Sequence ID 319), HC CDR2 sequence SISSSGSSTSYADSVKG (Sequence ID 320), HC CDR3 sequence FHELAMDY (SEQ ID NO: 321), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 322), LC CDR2 sequence SASSLYS (SEQ ID NO: 323), and A composition according to any one of claims 657 to 662, comprising the LC CDR3 sequence QQASWLYWLIT (SEQ ID NO: 324).

664. The composition according to any one of claims 657 to 663, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARFHELAMDYWGQGTLVTVSS (Sequence ID 318).

665. The composition according to any one of claims 660 to 664, wherein the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWLITFGQGTKVEIK (Sequence ID 317).

666. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing a heavy chain complementarity-determining region 3FTVLAMDY (SEQ ID NO: 329).

667. The composition according to claim 666, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 328).

668. The composition according to claim 666 or 667, wherein the VH comprises the HC CDR1 sequence FSSSSSIH (SEQ ID NO: 327).

669. The composition according to any one of claims 666 to 668, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSWLYWKIT (SEQ ID NO: 332).

670. The composition according to claim 669, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 331).

671. The composition according to claim 669 or 670, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 330).

672. The antigen-binding domain, HC CDR1 sequence FSSSSSIH (Sequence ID 327), HC CDR2 sequence SISSSGSSTSYADSVKG (Sequence ID 328), HC CDR3 sequence FTVLAMDY (Sequence ID 329), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 330), LC CDR2 sequence SASSLYS (SEQ ID NO: 331), and A composition according to any one of claims 666 to 671, comprising the LC CDR3 sequence QQSSWLYWKIT (SEQ ID NO: 332).

673. The composition according to any one of claims 666 to 672, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMDYWGQGTLVTVSS (Sequence ID 326).

674. The composition according to any one of claims 669 to 673, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWKITFGQGTKVEIK (Sequence ID 325).

675. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing a heavy chain complementarity-determining region 3FELLAMDY (SEQ ID NO: 337).

676. The composition according to claim 675, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 336).

677. The composition according to claim 675 or 676, wherein the VH comprises the HC CDR1 sequence FSSSSSIH (SEQ ID NO: 335).

678. The composition according to any one of claims 675 to 677, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSWLYWKIT (SEQ ID NO: 340).

679. The composition according to claim 678, wherein the VL comprises the LC CDR2 sequence SASSLYS (SEQ ID NO: 339).

680. The composition according to claim 678 or 679, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 338).

681. The antigen-binding domain, HC CDR1 sequence FSSSSSIH (Sequence ID 335), HC CDR2 sequence SISSSGSTSYADSVKG (Sequence ID 336), HC CDR3 sequence FELLAMDY (SEQ ID NO: 337), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 338), LC CDR2 sequence SASSLYS (SEQ ID NO: 339), and A composition according to any one of claims 675 to 680, comprising the LC CDR3 sequence QQSSWLYWKIT (SEQ ID NO: 340).

682. The composition according to any one of claims 675 to 681, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARFELLAMDYWGQGTLVTVSS (Sequence ID 334).

683. The composition according to any one of claims 678 to 682, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWKITFGQGTKVEIK (Sequence ID 333).

684. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing a heavy chain complementarity-determining region 3FTVLAMDY (SEQ ID NO: 345).

685. The composition according to claim 684, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 344).

686. The composition according to claim 684 or 685, wherein the VH comprises the HC CDR1 sequence FSSSSSIH (Sequence ID 343).

687. The composition according to any one of claims 684 to 686, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSWLYWKVT (SEQ ID NO: 348).

688. The composition according to claim 687, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 347).

689. The composition according to claim 687 or 688, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 346).

690. The antigen-binding domain, HC CDR1 sequence FSSSSSIH (Sequence ID 343), HC CDR2 sequence SISSSGSTSYADSVKG (Sequence ID 344), HC CDR3 sequence FTVLAMDY (sequence number 345), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 346), LC CDR2 sequence SASSLYS (SEQ ID NO: 347), and A composition according to any one of claims 684 to 689, comprising the LC CDR3 sequence QQSSWLYWKVT (SEQ ID NO: 348).

691. The composition according to any one of claims 684 to 690, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMDYWGQGTLVTVSS (Sequence ID 342).

692. The composition according to any one of claims 687 to 691, wherein the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWKVTFGQGTKVEIK (Sequence ID 341).

693. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3FYDLAMDY (SEQ ID NO: 353).

694. The composition according to claim 693, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 352).

695. The composition according to claim 693 or 694, wherein the VH comprises the HC CDR1 sequence FSSSSSIH (SEQ ID NO: 351).

696. The composition according to any one of claims 693 to 695, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSWLYWKVT (SEQ ID NO: 356).

697. The composition according to claim 696, wherein the VL comprises the LC CDR2 sequence SASSLYS (SEQ ID NO: 355).

698. The composition according to claim 696 or 697, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 354).

699. The antigen-binding domain, HC CDR1 sequence FSSSSIH (Sequence ID 351), HC CDR2 sequence SISSSGSSTSYADSVKG (Sequence ID 352), HC CDR3 sequence FYDLAMDY (SEQ ID NO: 353), LC CDR1 sequence RASQSVSSAVA (Sequence ID 354), LC CDR2 sequence SASSLYS (sequence number 355), and A composition according to any one of claims 693 to 698, comprising the LC CDR3 sequence QQSSWLYWKVT (SEQ ID NO: 356).

700. The composition according to any one of claims 693 to 699, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARFYDLAMDYWGQGTLVTVSS (Sequence ID 350).

701. The composition according to any one of claims 696 to 700, wherein the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWKVTFGQGTKVEIK (Sequence ID 349).

702. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing a heavy chain complementarity-determining region 3FHELAMDY (SEQ ID NO: 361).

703. The composition according to claim 702, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 360).

704. The composition according to claim 702 or 703, wherein the VH comprises the HC CDR1 sequence FSSSSSIH (SEQ ID NO: 359).

705. The composition according to any one of claims 702 to 704, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLYWLIT (SEQ ID NO: 364).

706. The composition according to claim 705, wherein the VL comprises the LC CDR2 sequence SASSLLYS (Sequence ID 363).

707. The composition according to claim 705 or 706, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 362).

708. The antigen-binding domain, HC CDR1 sequence FSSSSSIH (Sequence ID 359), HC CDR2 sequence SISSSGSTSYADSVKG (Sequence ID 360), HC CDR3 sequence FHELAMDY (SEQ ID NO: 361), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 362), LC CDR2 sequence SASSLYS (SEQ ID NO: 363), and A composition according to any one of claims 702 to 707, comprising the LC CDR3 sequence QQASWLYWLIT (SEQ ID NO: 364).

709. The composition according to any one of claims 702 to 708, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARFHELAMDYWGQGTLVTVSS (Sequence ID 358).

710. The composition according to any one of claims 705 to 709, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWLITFGQGTKVEIK (Sequence ID 357).

711. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing a heavy chain complementarity-determining region 3FTVLAMDY (SEQ ID NO: 369).

712. The composition according to claim 711, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 368).

713. The composition according to claim 711 or 712, wherein the VH comprises the HC CDR1 sequence FSSSSIH (Sequence ID 367).

714. The composition according to any one of claims 711 to 713, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLYWKVT (SEQ ID NO: 372).

715. The composition according to claim 714, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 371).

716. The composition according to claim 714 or 715, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 370).

717. The antigen-binding domain, HC CDR1 sequence FSSSSSIH (SEQ ID NO: 367), HC CDR2 sequence SISSSGSTSYADSVKG (Sequence ID 368), HC CDR3 sequence FTVLAMDY (Sequence ID 369), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 370), LC CDR2 sequence SASSLYS (SEQ ID NO: 371), and A composition according to any one of claims 711 to 716, comprising the LC CDR3 sequence QQASWLYWKVT (SEQ ID NO: 372).

718. The composition according to any one of claims 711 to 717, wherein the VH comprises a sequence having at least 80% sequence identity with respect to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMDYWGQGTLVTVSS (Sequence ID 366).

719. The composition according to any one of claims 714 to 718, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWKVTFGQGTKVEIK (Sequence ID 365).

720. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3FYDLAMDY (SEQ ID NO: 377).

721. The composition according to claim 720, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 376).

722. The composition according to claim 720 or 721, wherein the VH comprises the HC CDR1 sequence FSSSSSIH (SEQ ID NO: 375).

723. The composition according to any one of claims 720 to 722, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSWLYWVIT (SEQ ID NO: 380).

724. The composition according to claim 723, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 379).

725. The composition according to claim 723 or 724, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 378).

726. The antigen-binding domain, HC CDR1 sequence FSSSSSIH (SEQ ID NO: 375), HC CDR2 sequence SISSSGSTSYADSVKG (Sequence ID 376), HC CDR3 sequence FYDLAMDY (sequence number 377), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 378), LC CDR2 sequence SASSLYS (SEQ ID NO: 379), and A composition according to any one of claims 720 to 725, comprising the LC CDR3 sequence QQSSWLYWVIT (SEQ ID NO: 380).

727. The composition according to any one of claims 720 to 726, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARFYDLAMDYWGQGTLVTVSS (Sequence ID 374).

728. The composition according to any one of claims 723 to 727, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWVITFGQGTKVEIK (Sequence ID 373).

729. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing a heavy chain complementarity-determining region 3FHELAMDY (SEQ ID NO: 385).

730. The composition according to claim 729, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 384).

731. The composition according to claim 729 or 730, wherein the VH comprises the HC CDR1 sequence FSSSSSIH (SEQ ID NO: 383).

732. The composition according to any one of claims 729 to 731, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLYWLIT (SEQ ID NO: 388).

733. The composition according to claim 732, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 387).

734. The composition according to claim 732 or 733, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 386).

735. The antigen-binding domain, HC CDR1 sequence FSSSSSIH (Sequence ID 383), HC CDR2 sequence SISSSGSSTSYADSVKG (Sequence ID 384), HC CDR3 sequence FHELAMDY (SEQ ID NO: 385), LC CDR1 sequence RASQSVSSAVA (Sequence ID 386), LC CDR2 sequence SASSLYS (SEQ ID NO: 387), and A composition according to any one of claims 729 to 734, comprising the LC CDR3 sequence QQASWLYWLIT (SEQ ID NO: 388).

736. The composition according to any one of claims 729 to 735, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARFHELAMDYWGQGTLVTVSS (Sequence ID 382).

737. The composition according to any one of claims 732 to 736, wherein the VL includes a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWLITFGQGTKVEIK (Sequence ID 381).

738. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing a heavy chain complementarity-determining region 3FAHLAMDY (SEQ ID NO: 393).

739. The composition according to claim 738, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 392).

740. The composition according to claim 738 or 739, wherein the VH comprises the HC CDR1 sequence FSSSSSIH (Sequence ID 391).

741. The composition according to any one of claims 738 to 740, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSWLYWLIT (SEQ ID NO: 396).

742. The composition according to claim 741, wherein the VL comprises the LC CDR2 sequence SASSLYS (SEQ ID NO: 395).

743. The composition according to claim 741 or 742, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 394).

744. The antigen-binding domain, HC CDR1 sequence FSSSSSIH (Sequence ID 391), HC CDR2 sequence SISSSGSSTSYADSVKG (Sequence ID 392), HC CDR3 sequence FAHLAMDY (SEQ ID NO: 393), LC CDR1 sequence RASQSVSSAVA (Sequence ID 394), LC CDR2 sequence SASSLYS (SEQ ID NO: 395), and A composition according to any one of claims 738 to 743, comprising the LC CDR3 sequence QQSSWLYWLIT (SEQ ID NO: 396).

745. The composition according to any one of claims 738 to 744, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARFAHLAMDYWGQGTLVTVSS (Sequence ID 390).

746. The composition according to any one of claims 741 to 745, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWLITFGQGTKVEIK (Sequence ID 389).

747. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3FEDLAMDY (SEQ ID NO: 401).

748. The composition according to claim 747, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 400).

749. The composition according to claim 747 or 748, wherein the VH comprises the HC CDR1 sequence FSSSSSIH (SEQ ID NO: 399).

750. The composition according to any one of claims 747 to 749, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLYWYIT (SEQ ID NO: 404).

751. The composition according to claim 750, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 403).

752. The composition according to claim 750 or 751, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (Sequence ID 402).

753. The antigen-binding domain, HC CDR1 sequence FSSSSSIH (Sequence ID 399), HC CDR2 sequence SISSSGSTSYADSVKG (Sequence ID 400), HC CDR3 sequence FEDLAMDY (SEQ ID NO: 401), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 402), LC CDR2 sequence SASSLYS (SEQ ID NO: 403), and A composition according to any one of claims 747 to 752, comprising the LC CDR3 sequence QQASWLYWYIT (SEQ ID NO: 404).

754. The composition according to any one of claims 747 to 753, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARFEDLAMDYWGQGTLVTVSS (Sequence ID 398).

755. The composition according to any one of claims 750 to 754, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWYITFGQGTKVEIK (Sequence ID 397).

756. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3FRTLAMDY (SEQ ID NO: 409).

757. The composition according to claim 756, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 408).

758. The composition according to claim 756 or 757, wherein the VH comprises the HC CDR1 sequence FSSSSSIH (Sequence ID 407).

759. The composition according to any one of claims 756 to 758, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSWLYWIIT (SEQ ID NO: 412).

760. The composition according to claim 759, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 411).

761. The composition according to claim 759 or 760, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 410).

762. The antigen-binding domain, HC CDR1 sequence FSSSSSIH (Sequence ID 407), HC CDR2 sequence SISSSGSSTSYADSVKG (Sequence ID 408), HC CDR3 sequence FRTLAMDY (sequence number 409), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 410), LC CDR2 sequence SASSLYS (SEQ ID NO: 411), and A composition according to any one of claims 756 to 761, comprising the LC CDR3 sequence QQSSWLYWIIT (SEQ ID NO: 412).

763. The composition according to any one of claims 756 to 762, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARRFRTLAMDYWGQGTLVTVSS (Sequence ID 406).

764. The composition according to any one of claims 759 to 763, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWIITFGQGTKVEIK (Sequence ID 405).

765. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3FTHYAMDY (SEQ ID NO: 417).

766. The composition according to claim 765, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 416).

767. The composition according to claim 765 or 766, wherein the VH comprises the HC CDR1 sequence FSSSSSIH (SEQ ID NO: 415).

768. The composition according to any one of claims 765 to 767, wherein the antigen-binding domain comprises a light chain variable region (VL) containing the light chain complementarity-determining region 3 (LC CDR3) sequence QQSSWLYWKIT (SEQ ID NO: 420).

769. The composition according to claim 768, wherein the VL comprises the LC CDR2 sequence SASSLYS (Sequence ID 419).

770. The composition according to claim 768 or 769, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 418).

771. The antigen-binding domain, HC CDR1 sequence FSSSSSIH (Sequence ID 415), HC CDR2 sequence SISSSGSTSYADSVKG (Sequence ID 416), HC CDR3 sequence FTHYAMDY (sequence number 417), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 418), LC CDR2 sequence SASSLYS (SEQ ID NO: 419), and A composition according to any one of claims 765 to 770, comprising the LC CDR3 sequence QQSSWLYWKIT (SEQ ID NO: 420).

772. The composition according to any one of claims 765 to 771, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARFTHYAMDYWGQGTLVTVSS (Sequence ID 414).

773. The composition according to any one of claims 768 to 772, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWKITFGQGTKVEIK (Sequence ID 413).

774. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing the heavy chain complementarity-determining region 3FRLYAMDY (SEQ ID NO: 425).

775. The composition according to claim 774, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 424).

776. The composition according to claim 774 or 775, wherein the VH comprises the HC CDR1 sequence FSSSSSIH (SEQ ID NO: 423).

777. The composition according to any one of claims 774 to 776, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLHWKLT (SEQ ID NO: 428).

778. The composition according to claim 777, wherein the VL comprises the LC CDR2 sequence SASSLYS (SEQ ID NO: 427).

779. The composition according to claim 777 or 778, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 426).

780. The antigen-binding domain, HC CDR1 sequence FSSSSSIH (Sequence ID 423), HC CDR2 sequence SISSSGSSTSYADSVKG (Sequence ID 424), HC CDR3 sequence FRLYAMDY (sequence number 425), LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 426), LC CDR2 sequence SASSLYS (sequence number 427), and A composition according to any one of claims 774 to 779, comprising the LC CDR3 sequence QQASWLHWKLT (SEQ ID NO: 428).

781. The composition according to any one of claims 774 to 780, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARFRLYAMDYWGQGTLVTVSS (Sequence ID 422).

782. The composition according to any one of claims 777 to 781, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLHWKLTFGQGTKVEIK (Sequence ID 421).

783. A composition comprising a polypeptide containing an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) containing a heavy chain complementarity-determining region 3FHRLAMDY (SEQ ID NO: 433).

784. The composition according to claim 774, wherein the VH comprises the HC CDR2 sequence SISSSGSTSYADSVKG (SEQ ID NO: 432).

785. The composition according to claim 774 or 775, wherein the VH comprises the HC CDR1 sequence FSSSSIH (SEQ ID NO: 431).

786. The composition according to any one of claims 774 to 776, wherein the antigen-binding domain comprises a light chain variable region (VL) including the light chain complementarity-determining region 3 (LC CDR3) sequence QQASWLHWKLT (SEQ ID NO: 436).

787. The composition according to claim 777, wherein the VL comprises the LC CDR2 sequence SASSLYS (SEQ ID NO: 435).

788. The composition according to claim 777 or 778, wherein the VL comprises the LC CDR1 sequence RASQSVSSAVA (SEQ ID NO: 434).

789. The antigen-binding domain, HC CDR1 sequence FSSSSSIH (Sequence ID 431), HC CDR2 sequence SISSSGSTSYADSVKG (Sequence ID 432), HC CDR3 sequence FHRLAMDY (sequence number 433), LC CDR1 sequence RASQSVSSAVA (Sequence ID 434), LC CDR2 sequence SASSLYS (sequence number 435), and A composition according to any one of claims 774 to 779, comprising the LC CDR3 sequence QQASWLHWKLT (SEQ ID NO: 436).

790. The composition according to any one of claims 774 to 780, wherein the VH comprises a sequence having at least 80% sequence identity with the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSSIHWVRQAPGKGLEWVASISSSSSGSSTSYADSVKGRFTISAADTSKNTAYLQMNSLRAEDTAVYYCARFHRLAMDYWGQGTLVTVSS (Sequence ID 430).

791. The composition according to any one of claims 777 to 781, wherein the VL comprises a sequence having at least 80% sequence identity with the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLLIYSASSLYSGVPPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLHWKLTFGQGTKVEIK (Sequence ID 429).

792. A pharmaceutical composition comprising a polypeptide according to any one of claims 595 to 791, and a pharmaceutically acceptable carrier, excipient, adjuvant, or diluent.

793. A method for treating a subject in need of cancer treatment, wherein the subject has previously been treated with a free, targeted covalent inhibitor, and the method comprises administering to the subject a polypeptide according to any one of claims 595 to 791 or a pharmaceutical composition according to claim 792.

794. The method according to claim 793, wherein the free targeted covalent inhibitor is sotrasib, adaglasib, or diavalasib.

795. The method according to claim 793 or 794, wherein the subject is resistant to treatment with the free targeted covalent inhibitor.

796. A method for treating a subject in need of cancer treatment, comprising administering to the subject a polypeptide according to any one of claims 595 to 791 or a pharmaceutical composition according to claim 792.

797. Furthermore, the method according to claim 796, comprising administering a small molecule drug simultaneously.

798. A polypeptide according to any one of claims 595 to 791 or a pharmaceutical composition according to claim 792, and a method for administering the free targeted covalent inhibitor to a subject requiring administration of the free targeted covalent inhibitor, wherein the free targeted covalent inhibitor is optionally sotrasib, adaglasib, or diasib.

799. The method according to claim 798, wherein the polypeptide according to any one of claims 595 to 791 or the pharmaceutical composition according to claim 792 is administered after or simultaneously with the administration of the free targeted covalent inhibitor.

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