Claudin18 antibodies and methods of treating cancer

{
  "publication_number": "US2026104418A1",
  "country": "US",
  "kind": "A1",
  "title": "Claudin18 antibodies and methods of treating cancer",
  "abstract": "The present disclosure provides antigen-binding proteins which bind to Claudin-18.2 (CLDN18.2); bispecific antigen-binding proteins which bind to CLDN18.2 and a second antigen; and conjugates thereof. In various aspects, the antigen-binding proteins bind to Extracellular Loop 1 (EL1) of the extracellular domain of CLDN18.2. Related polypeptides, nucleic acids, vectors, host cells, and conjugates are further provided herein. Kits and pharmaceutical compositions comprising such entities are moreover provided. Also provided are methods of making an antigen-binding protein and methods of treating a subject having cancer.",
  "claims": [
    "1. An antigen-binding protein that binds to a human Claudin18.2 (CLDN18.2) protein (SEQ ID NO: 1), wherein: a. the antigen-binding protein binds to Extracellular Loop 1 (EL1) of an extracellular domain (ECD) of CLDN18.2 and does not bind to Extracellular Loop 2 (EL2) of the ECD of CLDN18.2; or b. does not bind to Claudin18.1 (CLDN18.1), and binds to CLDN18.2 endogenously expressed by HUPT4 cells with an affinity greater than 1.5 times that of a reference antibody; or c. a combination thereof. 2. The antigen-binding protein of claim 1, which binds to an epitope within the amino acid sequence of residues 28 to 74 of CLDN18.2 (SEQ ID NO: 1). 3. The antigen-binding protein of claim 2, which binds to the amino acid sequence of GLWRSCVRESSGFTECRFYFTL (SEQ ID NO: 4), QGLWRSCVRESSGFTECRGYFTLK (SEQ ID NO: 5), DQWSTQDLYNNPVTAVFNYQG LWRSC (SEQ ID NO: 6) or CRGYFTLLFLPAMLQAVR (SEQ ID NO: 7) of CLDN 18.2. 4. (canceled) 5. The antigen-binding protein of claim 1 comprising: a. a heavy chain (CDR) 1 amino acid sequence set forth in Table A or a sequence selected from the group consisting of: SEQ ID NOs: 64, 88, 69, 89, 72, 75, 91, 94, 95, 97, 99, 101, 103, 106, 109; or a variant sequence thereof which differs by only one or two amino acids or which has at least or about 70% (e.g., at least about 80%, at least about 85%, at least about 90%, at least about 95%) sequence identity; b. an HC CDR2 amino acid sequence set forth in Table A or a sequence selected from the group consisting of: SEQ ID NOs: 65, 67, 70, 90, 73, 76, 92, 73, 96, 98, 100, 102, 104, 107, 110; or a variant sequence thereof which differs by only one or two amino acids or which has at least or about 70% (e.g., at least about 80%, at least about 85%, at least about 90%, at least about 95%) sequence identity; c. an HC CDR3 amino acid sequence set forth in Table A or a sequence selected from the group consisting of: SEQ ID NOs: 66, 68, 71, 77, 74, 77, 93, 74, 105, 108, 111; or a variant sequence thereof which differs by only one or two amino acids or which has at least or about 70% (e.g., at least about 80%, at least about 85%, at least about 90%, at least about 95%) sequence identity; d. a light chain (LC) CDR1 amino acid sequence set forth in Table A or a sequence selected from the group consisting of: SEQ ID NOs: 78, 81, 82, 86, 114, 120, 123, 126; or a variant sequence thereof which differs by only one or two amino acids or which has at least or about 70% (e.g., at least about 80%, at least about 85%, at least about 90%, at least about 95%) sequence identity; e. an LC CDR2 amino acid sequence set forth in Table A or a sequence selected from the group consisting of: SEQ ID NOs: 79, 112, 79, 84, 116, 118, 119, 129, 121, 124, 127; or a variant sequence thereof which differs by only one or two amino acids or which has at least or about 70% (e.g., at least about 80%, at least about 85%, at least about 90%, at least about 95%) sequence identity; f. an LC CDR3 amino acid sequence set forth in Table A or a sequence selected from the group consisting of: SEQ ID NOs: 80, 83, 113, 85, 87, 115, 117, 122, 125, 128; and g. a combination of any two or more of (a)-(f). 6 - 31. (canceled) 32. A bispecific antigen-binding protein that binds CLDN18.2 and a second antigen, wherein the antigen-binding protein that binds CLDN18.2 is an antigen-binding protein of claim 1. 33 - 50. (canceled) 51. A conjugate comprising an antigen-binding protein or a bispecific antigen-binding protein of claim 1. 52 - 67. (canceled) 68. A fusion protein comprising an antigen-binding protein or a bispecific antigen-binding protein of claim 1. 69 - 74. (canceled) 75. A pharmaceutical composition comprising an antigen-binding protein of claim 1, and a pharmaceutically acceptable carrier, diluent or excipient. 76. A method of treating a subject with a CLDN18.2-expressing cancer comprising administering to the subject a. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO 42) EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVAT IIIGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLV KGNAMDYWGQGTLVTVSS or a variant sequence thereof which differs by 1-5 amino acids; and b. CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO 45) DIVMTQSPDSLAVSLGERVTMNCKSSQSLLNSGNQKNYLSWYQQKPGQPP KLLFYWASTRESGVPDRESGSGSGTDFTLTISSVQAEDVAVYYCQNDYSY PFTFGQGTKLEIK or a variant sequence thereof which differs by 1-5 amino acids in an amount effective to treat the cancer. 77. A method of inhibiting tumor growth in a subject, comprising administering to the subject a pharmaceutical composition of claim 75 in an amount effective to inhibit tumor growth. 78. A method of reducing tumor size in a subject, comprising administering to the subject a pharmaceutical composition of claim 75 in an amount effective to reduce tumor size. 79. A method of preventing the recurrence of cancer in a subject, comprising administering to the subject a pharmaceutical composition of claim 75 in an amount effective to prevent the recurrence of cancer. 80. A method of treating cancer in a subject with a CLDN18.2-expressing cancer, comprising administering to the subject an antigen-binding protein comprising any one of: a. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 42) EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATII IGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLVKGN AMDYWGQGTLVTVSS; and- CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 45) DIVMTQSPDSLAVSLGERVTMNCKSSQSLLNSGNQKNYLSWYQQ KPGQPPKLLFYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQN DYSYPFTFGQGTKLEIK; b. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 42) EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATII IGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLVKGN AMDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 43) DIVMTQSPDSLAVSLGERATINCKSSQSLLNSGNQKNYLSWYQQKPGQPPKL LIYWASTRESGVPDRESGSGSGTDFTLTISSLQAEDVAVYYCQNDYSYPFTFG QGTKLEIK; c. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 42) EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATII IGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLVKGN AMDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 44) DIVMTQSPDSLAVSLGERATINCKSSQSLLNSGNQKNYLSWYQQKPGQPPKL LFYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQNDYSYPFTF GQGTKLEIK; d. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 42) EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATII IGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLVKGN AMDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 140) DIVMTQSPDSLAVSLGERVTMNCKSSQSLLQSGNQKNYLSWYQQKPGQPPK LLFYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNDYSYPFT FGQGTKLEIK; e. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 42) EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATII IGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLVKGN AMDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 130) DIVMTQSPDSLAVSLGERVTMNCKSSQSLLSSGNQKNYLSWYQQKPGQPPK LLFYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNDYSYPFT FGQGTKLEIK; f. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 138) EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATII IGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLVKGQ AMDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 142) DIVMTQSPDSLAVSLGERVTMNCKSSQSLLNSGNQKNYLSWYQQKPGQPPK LLFYWASTRESGVPDRESGSGSGTDFTLTISSVQAEDVAVYYCQNDYSYPFT FGQGTKLEIK; g. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 138) EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATII IGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLVKGQ AMDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 140) DIVMTQSPDSLAVSLGERVTMNCKSSQSLLQSGNQKNYLSWYQQKPGQPPK LLFYWASTRESGVPDRESGSGSGTDFTLTISSVQAEDVAVYYCQNDYSYPFT FGQGTKLEIK; h. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 138) EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATII IGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLVKGQ AMDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 141) DIVMTQSPDSLAVSLGERVTMNCKSSQSLLSSGNQKNYLSWYQQKPGQPPK LLFYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNDYSYPFT FGQGTKLEIK; i. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 139) EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATII IGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLVKGS AMDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 142) DIVMTQSPDSLAVSLGERVTMNCKSSQSLLNSGNQKNYLSWYQQKPGQPPK LLFYWASTRESGVPDRESGSGSGTDFTLTISSVQAEDVAVYYCQNDYSYPFT FGQGTKLEIK; j. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 139) EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATII IGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLVKGS AMDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 140) DIVMTQSPDSLAVSLGERVTMNCKSSQSLLQSGNQKNYLSWYQQKPGQPPK LLFYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNDYSYPFT FGQGTKLEIK; k. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 139) EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATII IGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLVKGS AMDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 141) DIVMTQSPDSLAVSLGERVTMNCKSSQSLLSSGNQKNYLSWYQQKPGQPPK LLFYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNDYSYPFT FGQGTKLEIK; l. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 40) EVQLQQSGPELVKPGASVKISCKASGYSFTVYYMNWVKQSPEKSLEWIGEIN PSTGGTTYNPKFKAKATLTVDKSSSTAYMQLKSLTSEDSAIYFCVRWADYW GQGTTLTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 41) DIVITQDELSNPVTSGESVSISCRSSKSLLYKDGKTYLNWFLQRPGQSPQLLV YWMSTRASGVSDRFSGSGSGTDFTLEISRVKAEDVGVYYCQQVVYYPYTFG SGTKLEIK; m. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 46) EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATI SSGVSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLTKG NAMDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 47) DIVMTQSPDSLAVSLGERATINCKSSQSLLNSGNQKNYLTWYQQKPGQPPKL LIYWASTRESGVPDRESGSGSGTDFTLTISSLQAEDVAVYYCQNDYSYPFTFG QGTKLEIK; n. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 46) EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATI SSGVSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLTKG NAMDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 48) DIVMTQSPDSLAVSLGERVTMNCKSSQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNDYSYPFTF GQGTKLEIK; o. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 131) EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSFGMHWVRQAPGKGLEWVAYI SSGTTNIYYADSVKGRFTVSRDNAKNSLYLQMNSLRAEDTAVYYCVRSGYY GNSLDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 149) DIVMTQSPDSLAVSLGERATINCKSSQSLFNSGNQRNYLTWYQQKPGQPPKL LIYWASTRESGVPDRESGSGSGTDFTLTISSLQAEDVAVYYCQNVYIYPLTFG QGTKLEIK; p. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 131) EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSFGMHWVRQAPGKGLEWVAYI SSGTTNIYYADSVKGRFTVSRDNAKNSLYLQMNSLRAEDTAVYYCVRSGYY GNSLDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 150) DIVMTQSPDSLAVSLGERVTMNCKSSQSLFNSGNQRNYLTWYQQKPGQPPK LLIYWASTRESGVPDRESGSGSGTDFTLTISSVQAEDVAVYYCQNVYIYPLTF GQGTKLEIK; q. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 131) EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSFGMHWVRQAPGKGLEWVAYI SSGTTNIYYADSVKGRFTVSRDNAKNSLYLQMNSLRAEDTAVYYCVRSGYY GNSLDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 147) DIVMTQSPDSLAVSLGERVTMNCKSSQSLENSGNQRNYLTWYQQKPGQPPK LLIYWASTRESGVPDRESGSGSGTDFTLTISSVQAEDVAVYYCQNVYIYPLTF GQGTKLEIK; r. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 131) EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSFGMHWVRQAPGKGLEWVAYI SSGTTNIYYADSVKGRFTVSRDNAKNSLYLQMNSLRAEDTAVYYCVRSGYY GNSLDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 135) DIVMTQSPDSLAVSLGERVTMNCKSSQSLFQSGNQRNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNVYIYPLTF GQGTKLEIK; s. CDR1-derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 131) EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSFGMHWVRQAPGKGLEWVAYI SSGTTNIYYADSVKGRFTVSRDNAKNSLYLQMNSLRAEDTAVYYCVRSGYY GNSLDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 136) DIVMTQSPDSLAVSLGERVTMNCKSSQSLFSSGNQRNYLTWYQQKPGQPPK LLIYWASTRESGVPDRESGSGSGTDFTLTISSVQAEDVAVYYCQNVYIYPLTF GQGTKLEIK; t. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 133) EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSFGMHWVRQAPGKGLEWVAYI SSGTTNIYYADSVKGRFTVSRDNAKNSLYLQMNSLRAEDTAVYYCVRSGYY GQSLDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 137) DIVMTQSPDSLAVSLGERVTMNCKSSQSLENSGNQRNYLTWYQQKPGQPPK LLIYWASTRESGVPDRESGSGSGTDFTLTISSVQAEDVAVYYCQNVYIYPLTF GQGTKLEIK; u. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 134) EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSFGMHWVRQAPGKGLEWVAYI SSGTTNIYYADSVKGRFTVSRDNAKNSLYLQMNSLRAEDTAVYYCVRSGYY GSSLDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 137) DIVMTQSPDSLAVSLGERVTMNCKSSQSLENSGNQRNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNVYIYPLTF GQGTKLEIK; v. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 133) EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSFGMHWVRQAPGKGLEWVAYI SSGTTNIYYADSVKGRFTVSRDNAKNSLYLQMNSLRAEDTAVYYCVRSGYY GQSLDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 135) DIVMTQSPDSLAVSLGERVTMNCKSSQSLFQSGNQRNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNVYIYPLTF GQGTKLEIK; w. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 133) EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSFGMHWVRQAPGKGLEWVAYI SSGTTNIYYADSVKGRFTVSRDNAKNSLYLQMNSLRAEDTAVYYCVRSGYY GQSLDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 136) DIVMTQSPDSLAVSLGERVTMNCKSSQSLFSSGNQRNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNVYIYPLTF GQGTKLEIK; x. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 134) EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSFGMHWVRQAPGKGLEWVAYI SSGTTNIYYADSVKGRFTVSRDNAKNSLYLQMNSLRAEDTAVYYCVRSGYY GSSLDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 135) DIVMTQSPDSLAVSLGERVTMNCKSSQSLFQSGNQRNYLTWYQQKPGQPPK LLIYWASTRESGVPDRESGSGSGTDFTLTISSVQAEDVAVYYCQNVYIYPLTF GQGTKLEIK; y. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 134) EVQLVESGGGLVQPGGSLRLSCAVSGFTESSFGMHWVRQAPGKGLEWVAYI SSGTTNIYYADSVKGRFTVSRDNAKNSLYLQMNSLRAEDTAVYYCVRSGYY GSSLDYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 136) DIVMTQSPDSLAVSLGERVTMNCKSSQSLESSGNQRNYLTWYQQKPGQPPK LLIYWASTRESGVPDRESGSGSGTDFTLTISSVQAEDVAVYYCQNVYIYPLTF GQGTKLEIK; z. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 52) QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYLMHWVRQAPGQGLEWIGY INPYNDGTNYAQKFQGRVTMTSDTSTSTVYMELSSLRSEDTAVYYCTRGDY WGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 53) DIVMTQSPDSLAVSLGERATINCKSSQSLLNSGNQKNYLTWYQQKPGQPPKL LIYWASIRQSGVPDRESGSGSGTDFTLTISSLQAEDVAVYYCLNDYGFPLTFG QGTKLEIK; aa. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 52) QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYLMHWVRQAPGQGLEWIGY INPYNDGTNYAQKFQGRVTMTSDTSTSTVYMELSSLRSEDTAVYYCTRGDY WGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 54) DIVMTQSPDSLAVSLGERVTMNCKSSQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASIRQSGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCLNDYGFPLTF GQGTKLEIK; ab. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 55) QVQLVQSGAEVKKPGASVKMSCKASGYTFTSYLMHWVRQAPGQGLEWIG YINPYNDGTNYAQKFQGRATLTSDTSTSTAYMELSSLRSEDTAVYYCTRGD YWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 53) DIVMTQSPDSLAVSLGERATINCKSSQSLLNSGNQKNYLTWYQQKPGQPPKL LIYWASIRQSGVPDRESGSGSGTDFTLTISSLQAEDVAVYYCLNDYGFPLTFG QGTKLEIK; ac. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 55) QVQLVQSGAEVKKPGASVKMSCKASGYTFTSYLMHWVRQAPGQGLEWIG YINPYNDGTNYAQKFQGRATLTSDTSTSTAYMELSSLRSEDTAVYYCTRGD YWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 54) DIVMTQSPDSLAVSLGERVTMNCKSSQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASIRQSGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCLNDYGFPLTF GQGTKLEIK; ad. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 56) QVQLVQSGAEVKKPGASVKMSCKASGYTFTSYLMHWVRQAPGQGLEWIG YINPYNDGTNYAQKFQGRATLTSDKSTSTAYMELSSLRSEDTAVYYCTRGD YWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 53) DIVMTQSPDSLAVSLGERATINCKSSQSLLNSGNQKNYLTWYQQKPGQPPKL LIYWASIRQSGVPDRESGSGSGTDFTLTISSLQAEDVAVYYCLNDYGFPLTFG QGTKLEIK; ae CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 56) QVQLVQSGAEVKKPGASVKMSCKASGYTFTSYLMHWVRQAPGQGLEWIG YINPYNDGTNYAQKFQGRATLTSDKSTSTAYMELSSLRSEDTAVYYCTRGD YWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 54) DIVMTQSPDSLAVSLGERVTMNCKSSQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASIRQSGVPDRESGSGSGTDFTLTISSVQAEDVAVYYCLNDYGFPLTF GQGTKLEIK; af. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 57) QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSDVISWVRQAPGQGLEWMGE SYLRNGNTYYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCARSYY GNSFAYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 50) DIVMTQSPDSLAVSLGERATINCKSTQSLLNSGNQKNYLTWYQQKPGQPPKL LIYWASTRESGVPDRESGSGSGTDFTLTISSLQAEDVAVYYCQNAYYYPFTF GQGTKLEIK; ag. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 57) QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSDVISWVRQAPGQGLEWMGE SYLRNGNTYYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCARSYY GNSFAYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 51) DIVMTQSPDSLAVSLGERVTMNCKSTQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNAYYYPFT FGQGTKLEIK; ah. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 49) QVQLVQSGAEVKKPGSSVKLSCKASGYTFTSDVISWVRQAPGQGLEWIGES YLRNGNTYYAQKFQGRATLTADKSTSTAYMELSSLRSEDTAVYYCARSYYG NSFAYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 50) DIVMTQSPDSLAVSLGERATINCKSTQSLLNSGNQKNYLTWYQQKPGQPPKL LIYWASTRESGVPDRESGSGSGTDFTLTISSLQAEDVAVYYCQNAYYYPFTF GQGTKLEIK; or ai. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 49) QVQLVQSGAEVKKPGSSVKLSCKASGYTFTSDVISWVRQAPGQGLEWIGES YLRNGNTYYAQKFQGRATLTADKSTSTAYMELSSLRSEDTAVYYCARSYYG NSFAYWGQGTLVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 51) DIVMTQSPDSLAVSLGERVTMNCKSTQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNAYYYPFT FGQGTKLEIK; aj. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 10) DVKLVESGGGLVKPGGSLKLSCAASGFTFSSYTMSWVRQTPEKRLEWVATII IGGSYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCTRLVKGN AMDYWGQGTSVAVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 11) DIVMTQSPSSLTVTTGEKVTMSCKSSQSLLNSGNQKNYLSWYQQIPGQPPKL LFYWASTRESGVPDRFTGSGSGTDFTLTISNVQAEDLAVYYCQNDYSYPFTF GAGTKLELR; ak. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 12) DVKLVESGGGLVKPGGSLKLSCAASGFTFTSYTMSWVRQTPEKRLEWVATII IGGSYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCTRLVKGN AMDYWGQGTSVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 13) DILMTQSPSSLTVTAGEKVTMTCKSSQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASSRESGVPDRFTGSGSGTDFTLTISSVQAEDLAVYYCQNDYSYPFTF GAGTKLELK; al. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 14) DVKLVESGGGLVKPGGSLKLSCAASGFTFSSYTMSWVRQTPEKRLYWVATI SSGVSYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCTRLTKG NAMDYWGQGTSVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 15) DIVMTQSPSSLTVTAGEKVTMSCKSSQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFTGSGSGTGFTLTISSVQAEDLAVYYCQNDYSYPFTF GAGTKLELK; am. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 16) VVQLVESGGDFVQPGGSRKLSCAVSGFTFSSFGMHWVRQAPEKGLEWVAYI SSGTTNIYYADTVKGRFTVSRDNPKNSLFLHMTSLRSEDTAMYYCVRSGYY GNSLDYWGQGTPLTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 17) DIVMTQSPSSLTVTAGEKVTMSCKSSQSLFNSGNQRNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFTGSGSGTGFTLTISSVQAEDLAFYYCQNVYIYPLTF GLGTKLELR; an. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 18) QVQLQQSGAELARPGASVKLSCKASDYTFTSYVISWVKQRTGQGLEWIGEIY PRNGNTYYNEKFKGKATLTADKSSSTAYMELRSLTSEDSAVYFCARSYYGN SFAYWGQGTLVTVSA, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 19) DIVMTQSPSSLTVTAGEKVTMSCKSSQSLLNSGNQKNYLTWYQQRPGQPPK LLIYWASTRESGVPDRFTGSGSGTDFTLTISSVQAEDLAVYCCQNNYYYPFTF GGGTKLGIK; ao. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 20) VVQLQQSGPELVKPGASVKMSCKASGYTFTSYLMHWVRQKPGLGLDWIGY INPYNDGTNYNAKFIDKATLTSDKTSSTAYMELSSLTSEDSAIYYCTRGDYW GQGTSVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 21) DIVMTQSPSSLAVTAGEQVTMSCKSSQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASIRQSGVPDRFTGSGSGTDFTLTISSVQAEDLAVYYCLNDYGFPLTF GAGTKLELK; ap. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 22) QIQLQQSGAELARPRASVKLSCKASGYTFTSDVISWVKQRPGQGLEWIGESY LRNGNTYYNENEKGKATLTADKSSSTAYMELRSLTSEDSAVYFCARSYYGN SFAYWGQGTLVTVSA, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 23) DIVMTQSPSSLTVTAREKVTMNCKSTQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFTGSGSGTDFTLTISSVQAEDLAVYYCQNAYYYPFTF GGGTKLEIK; aq. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 24) QVQLKESGPGLVAPSQSLSITCTVSGFSLNSYGVSWVRQPPGKGLEWLGVIW GDGSTNYHSALKSRLNINKDKSKSQVFLKLNSLQTDDTATYYCARPTRGNA MDYWGQGTSVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 25) DVVMTQSPSSLTVTAGEKVTMNCKSSQSLLNSGNQRSYLTWYQQKPGQPPK LLIYWASTRESGAPDRFTGSGSGADFTLTISSVQAEDLAIYYCQNNYNYPFTF GSGTKLEIK; ar. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 26) EVQLQQSGPELVKPGASVRMSCKASGYTFTSYIMHWVKQKPGQGPEWMGY INPYNDGTNYNEKFKDKATLTSDKSSSTAYMDLSSLTSEDSAVYYCTRGDY WGQGTSVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 27) DIVMTQSPSSLTVTAGEKVTMSCKSSQSLLNSGNQKNYLTWYQQKPGQPPK LLFYWASTKKSGVPDRFTGSGSRTDFTLTISSVQAEDLAVYYCLNDYSFPLTF GAGTKLELK; as. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 28) EVQLQQSGPELVKPGASVKMSCKASGYTFTSYLIHWVKQKPGQGLEWIGYI NPYNDATYYNEKFKAKATLTSDKSSSTAYMELSSLTSEDTAIYYCTRGDYW SQGTSVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 29) DIVMTQSPSSLTVTAGEKVTMSCKSSQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASTRQSGVPDRFTGSGSGTDFTLTISSVQAEDLTVYYCLNDYSFPLTF GAGTKLELK; at. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 30) EVQLQQSGPELVKPGASVKMSCKASGYTFTSYVMHWVKQKPGQGLEWIGY FNPYNDDTKYNEKFKGKATLTSDKSSSTAYMDLSSLTSEDSAVYXCTRGDY WGQGTSVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 31) DIVMTQSPSSLTVTAGEKVTMTCKSSQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASTGASGVPDRFTGSGSGTDFTLTISSAQAADLAVYYCLNDYSFPLTF GAGTKLELK; au. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 32) VVQLQQSGPELVKPGASVKMSCKASGYTFTSFLIHWVRQKPGLGLEWIGYIN PYDYGINYNVKFMDKVTLTSDKTSSTAYMELSSLTSADSAIYYCTRGDYWG QGTSVIVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 33) DIVMTQSPSSLAVTTGEQVTMNCKSSQSLLNSGNQKNYLTWYQQKTGQSPK LLIYWASTRQSGVPDRFTGSGSGTDFTLTISSVQAEDLAVYYCLNDYGFPLTF GAGTKLELK; av. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 34) EVQLQQSGPELVKPGASVKMSCKASGFTFTSYVMHWVKQKSGQGLEWIGYI NPYNDDIKYNAKFEDKATLTSDRSSSTAYMELSSLTSDDSAVYFCTRGDYW GQGTTLTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 35) DIVMTQSPSSLTVTTGEKVTMDCKSSQSLLNSGNQKNYLTWYQQKSGQPPK LLIYWASIRKSGVPDRFTGSGSGTDFTLTISSVQAEDLAVYYCLNDYSFPLTF GAGTKLELK; aw. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 36) EFQLQQSGPELVKPGASVKISCKASVYSFTGYNMNWVKQSNGKSLEWIGVI NPNYGNTNYNQRFKGKATLTVDQSSSTAYMQLNSLTSEDSAVYYCARSEDY YNIRGASWGQGTLVTVSA, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 37) QIVLTQSPAIMSASPGQKVTITCSASSTINYMHWYQQKLGSSPKLWIYDTSKL APGVPARFSGSGSGTSYSLTISSMEAEDAASYFCHQWSSYPPTFGSGTKLELK; and ax. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence: (SEQ ID NO: 38) QVQLQQSGAELARPGASVKLSCKASGYTFTSYGISWVKQRTGQGLEWIGEIS PRSGNTYYNEKFKGKATLTADKSSSTAYMELRSLTSEDSAVYFCATGVITTV IPTDWYFDVWGTGTTVTVSS, and CDR1-3 derived from a light chain variable region comprising the amino acid sequence: (SEQ ID NO: 39) DIQMTQTTSSLSASLGDRVTISCRASQDISNYLNWYQQKPDGTVKLLIYYTSR LHSGVPSRFSGSGSGTDYSLTISNLEPEDIATYYCQHYSKLPPTFGSGTKLEIK in an amount effective to prevent the recurrence of cancer. 81. The method of claim 76, wherein the administering induces apoptosis in tumor cells. 82. The method of claim 76, wherein the administering induces apoptosis in cells expressing CLDN18.2. 83. The method of claim 80, wherein the antigen-binding protein is selected from the group consisting of: a. an antigen-binding protein which comprises i. a heavy chain (HC) variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 64) GFTESSYTMS, HC CDR2 comprising amino acid sequence (SEQ ID NO: 65) TIIIGGSYTY, and HC CDR3 comprising amino acid sequence (SEQ ID NO: 66) LVKGNAMDY; and ii. a light chain (LC) variable region comprising LC CDR1 comprising (SEQ ID NO: 78) KSSQSLLNSGNQKNYLS, LC CDR2 comprising amino acid sequence (SEQ ID NO: 79) WASTRES, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 80) QNDYSYPFT; b. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 88) GFTFTSYTMS, HC CDR2 comprising amino acid sequence (SEQ ID NO: 65) TIIIGGSYTY and HC CDR3 comprising amino acid sequence (SEQ ID NO: 66) LVKGNAMDY; and ii. a LC variable region comprising LC CDR1 comprising amino acid sequence (SEQ ID NO: 81) KSSQSLLNSGNQKNYLT, LC CDR2 comprising amino acid sequence (SEQ ID NO: 112) WASSRES, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 80) QNDYSYPFT; c. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 64) GFTESSYTMS, HC CDR2 comprising amino acid sequence (SEQ ID NO: 67) TISSGVSYTY, and HC CDR3 comprising amino acid sequence (SEQ ID NO: 68) LTKGNAMDY; and ii. a LC variable region comprising LC CDR1 comprising amino acid sequence (SEQ ID NO: 81) KSSQSLLNSGNQKNYLT, LC CDR2 comprising amino acid sequence (SEQ ID NO: 79) WASTRES, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 80) QNDYSYPFT; d. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 69) GFTFSSFGMH, HC CDR2 comprising amino acid sequence (SEQ ID NO: 70) YISSGTTNIY, and HC CDR3 comprising amino acid sequence (SEQ ID NO: 71) SGYYGNSLDY; and ii. a LC variable region comprising a LC CDR1 comprising amino acid sequence (SEQ ID NO: 82) KSSQSLFNSGNQRNYLT, LC CDR2 comprising amino acid sequence (SEQ ID NO: 79) WASTRES, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 83) QNVYIYPLT; e. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 89) DYTFTSYVIS, HC CDR2 comprising amino acid sequence (SEQ ID NO: 90) EIYPRNGNTY, and HC CDR3 comprising amino acid sequence (SEQ ID NO: 77) SYYGNSFAY; and ii. a LC variable region comprising LC CDR1 comprising amino acid sequence (SEQ ID NO: 81) KSSQSLLNSGNQKNYLT, LC CDR2 comprising amino acid sequence (SEQ ID NO: 79) WASTRES, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 113) QNNYYYPFT; f. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 72) GYTFTSYLMH, HC CDR2 comprising amino acid sequence (SEQ ID NO: 73) YINPYNDGTN, and HC CDR3 comprising amino acid sequence (SEQ ID NO: 74) GDY; and ii. a LC variable region comprising LC CDR1 comprising amino acid sequence (SEQ ID NO: 81) KSSQSLLNSGNQKNYLT, LC CDR2 comprising amino acid sequence (SEQ ID NO: 84) WASIRQS, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 85) LNDYGFPLT; g. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 75) GYTFTSDVIS, HC CDR2 comprising amino acid sequence (SEQ ID NO: 76) ESYLRNGNTY, and HC CDR3 comprising amino acid sequence (SEQ ID NO: 77) SYYGNSFAY; and ii. a LC variable region comprising LC CDR1 comprising amino acid sequence (SEQ ID NO: 86) KSTQSLLNSGNQKNYLT, LC CDR2 comprising amino acid sequence (SEQ ID NO: 79) WASTRES, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 87) QNAYYYPFT; h. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 91) GFSLNSYGVS, HC CDR2 comprising amino acid sequence (SEQ ID NO: 92) VIWGDGSTN, and HC CDR3 comprising amino acid sequence (SEQ ID NO: 93) PTRGNAMDY; and ii. a LC variable region comprising LC CDR1 comprising amino acid sequence (SEQ ID NO: 114) KSSQSLLNSGNQRSYLT, LC CDR2 comprising amino acid sequence (SEQ ID NO: 79) WASTRES, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 115) QNNYNYPFT; i. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 94) GYTFTSYIMH, HC CDR2 comprising amino acid sequence (SEQ ID NO: 73) YINPYNDGTN, and HC CDR3 comprising amino acid sequence (SEQ ID NO: 74) GDY; and ii. a LC variable region comprising LC CDR1 comprising amino acid sequence (SEQ ID NO: 81) KSSQSLLNSGNQKNYLT, LC CDR2 comprising amino acid sequence (SEQ ID NO: 116) WASTKKS, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 117) LNDYSFPLT; j. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 95) GYTFTSYLIH, HC CDR2 comprising amino acid sequence (SEQ ID NO: 96) YINPYNDATY, and HC CDR3 comprising amino acid sequence (SEQ ID NO: 74) GDY; and ii. a LC variable region comprising LC CDR1 comprising amino acid sequence (SEQ ID NO: 81) KSSQSLLNSGNQKNYLT, LC CDR2 comprising amino acid sequence (SEQ ID NO: 118) WASTRQS, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 117) LNDYSFPLT; k. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 97) GYTFTSYVMH, HC CDR2 comprising amino acid sequence (SEQ ID NO: 98) YFNPYNDDTK, and HC CDR3 comprising amino acid sequence (SEQ ID NO: 74) GDY; and ii. a LC variable region comprising LC CDR1 comprising amino acid sequence (SEQ ID NO: 81) KSSQSLLNSGNQKNYLT, LC CDR2 comprising amino acid sequence (SEQ ID NO: 119) WASTGAS, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 117) LNDYSFPLT; l. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 99) GYTFTSFLIH, HC CDR2 comprising amino acid sequence (SEQ ID NO: 100) YINPYDYGIN, and HC CDR3 comprising amino acid sequence (SEQ ID NO: 74) GDY; and ii. a LC variable region comprising LC CDR1 comprising amino acid sequence (SEQ ID NO: 81) KSSQSLLNSGNQKNYLT, LC CDR2 comprising amino acid sequence (SEQ ID NO: 118) WASTRQS, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 85) LNDYGFPLT; m. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 101) GFTFTSYVMH, HC CDR2 comprising amino acid sequence (SEQ ID NO: 102) YINPYNDDIK, and HC CDR3 comprising amino acid sequence (SEQ ID NO: 74) GDY; and ii. a LC variable region comprising LC CDR1 comprising amino acid sequence (SEQ ID NO: 81) KSSQSLLNSGNQKNYLT, LC CDR2 comprising amino acid sequence (SEQ ID NO: 129) WASIRKS, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 117) LNDYSFPLT; n. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 103) VYSFTGYNMN, HC CDR2 comprising amino acid sequence (SEQ ID NO: 104) VINPNYGNTN, and HC CDR3 comprising amino acid sequence (SEQ ID NO: 105) SEDYYNIRGAS; and ii. a LC variable region comprising LC CDR1 comprising amino acid sequence (SEQ ID NO: 120) SASSTINYMH, LC CDR2 comprising amino acid sequence (SEQ ID NO: 121) DTSKLAP, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 122) HQWSSYPPT; o. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 106) GYTFTSYGIS, HC CDR2 comprising amino acid sequence (SEQ ID NO: 107) EISPRSGNTY, and HC CDR3 comprising amino acid sequence (SEQ ID NO: 108) GVITTVIPTDWYFDV; and ii. a LC variable region comprising LC CDR 1 comprising amino acid sequence (SEQ ID NO: 123) RASQDISNYLN, LC CDR2 comprising amino acid sequence (SEQ ID NO: 124) YTSRLHS, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 125) QHYSKLPPT; and p. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 109) GYSFTVYYMN, HC CDR2 comprising amino acid sequence (SEQ ID NO: 110) EINPSTGGTT, and HC CDR3 comprising amino acid sequence (SEQ ID NO: 111) WADY; and ii. a LC variable region comprising LC CDR1 comprising amino acid sequence (SEQ ID NO: 126) RSSKSLLYKDGKTYLN, LC CDR2 comprising amino acid sequence (SEQ ID NO: 127) WMSTRAS, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 128) QQVVYYPYT; q. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 64) GFTESSYTMS, HC CDR2 comprising amino acid sequence (SEQ ID NO: 65) TIIIGGSYTY, and HC CDR3 comprising amino acid sequence (SEQ ID NO: 66) LVKGNAMDY; and ii. a LC variable region comprising LC CDR1 comprising an amino acid sequence (SEQ ID NO: 140 starting at position 24 and ending at position 40) KSSQSLLQSGNQKNYLS, LC CDR2 comprising amino acid sequence (SEQ ID NO: 79) WASTRES, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 80) QNDYSYPFT; r. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 64) GFTESSYTMS, HC CDR2 comprising amino acid sequence (SEQ ID NO: 65) TIIIGGSYTY, and HC CDR3 comprising amino acid sequence (SEQ ID NO: 66) LVKGNAMDY; and ii. a LC variable region comprising LC CDR1 comprising an amino acid sequence (SEQ ID NO: 130 starting at position 24 and ending at position 40) KSSQSLLSSGNQKNYLS, LC CDR2 comprising amino acid sequence (SEQ ID NO: 79) WASTRES, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 80) QNDYSYPFT; s. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 64) GFTESSYTMS, HC CDR2 comprising amino acid sequence (SEQ ID NO: 65) TIHIGGSYTY, and HC CDR3 comprising an amino acid sequence (SEQ ID NO: 138 starting at position 99 and ending at position 107) LVKGQAMDY; and ii. a LC variable region comprising LC CDR1 comprising amino acid sequence (SEQ ID NO: 78) KSSQSLLNSGNQKNYLS, LC CDR2 comprising amino acid sequence (SEQ ID NO: 79) WASTRES, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 80) QNDYSYPFT; t. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 64) GFTFSSYTMS, HC CDR2 comprising amino acid sequence (SEQ ID NO: 65) TIHIGGSYTY, and HC CDR3 comprising an amino acid sequence (SEQ ID NO: 138 starting at position 99 and ending at position 107) LVKGQAMDY; and ii. a LC variable region comprising LC CDR1 comprising an amino acid sequence SEQ ID NO: 140 starting at position 24 and ending at position 40) KSSQSLLQSGNQKNYLS or SEQ ID NO: 130 starting at position 24 and ending at position 40) KSSQSLLSSGNQKNYLS, LC CDR2 comprising amino acid sequence (SEQ ID NO: 79) WASTRES, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 80) QNDYSYPFT, u. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 64) GFTFSSYTMS, HC CDR2 comprising amino acid sequence (SEQ ID NO: 65) TIHIGGSYTY, and HC CDR3 comprising an amino acid sequence (SEQ ID NO: 139 starting at position 99 and ending at position 107 LVKGSAMDY; and ii. a LC variable region comprising LC CDR1 comprising amino acid sequence (SEQ ID NO: 78) KSSQSLLNSGNQKNYLS, LC CDR2 comprising amino acid sequence (SEQ ID NO: 79) WASTRES, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 80) QNDYSYPFT; v. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 64) GFTESSYTMS, HC CDR2 comprising amino acid sequence (SEQ ID NO: 65) TIIIGGSYTY, and HC CDR3 comprising an amino acid sequence (SEQ ID NO: 139 starting at position 99 and ending at position 107) LVKGSAMDY; and ii. a LC variable region comprising LC CDR1 comprising a an amino acid sequence SEQ ID NO: 140 starting at position 24 and ending at position 40) KSSQSLLQSGNQKNYLS or SEQ ID NO: 130 starting at position 24 and ending at position 40) KSSQSLLSSGNQKNYLS, LC CDR2 comprising amino acid sequence (SEQ ID NO: 79) WASTRES, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 80) QNDYSYPFT; w. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 69) GFTFSSFGMH, HC CDR2 comprising amino acid sequence (SEQ ID NO: 70) YISSGTTNIY, and HC CDR3 comprising amino acid sequence (SEQ ID NO: 71) SGYYGNSLDY; and ii. a LC variable region comprising a LC CDR1 comprising an amino acid sequence (SEQ ID NO: 135 starting at position 24 and ending at position 40) KSSQSLFQSGNQRNYLT or (SEQ ID NO: 136 starting at position 24 and ending at position 40) KSSQSLFSSGNQRNYLT, LC CDR2 comprising amino acid sequence (SEQ ID NO: 79) WASTRES, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 83) QNVYIYPLT; x. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 69) GFTFSSFGMH, HC CDR2 comprising amino acid sequence (SEQ ID NO: 70) YISSGTTNIY, and HC CDR3 comprising an amino acid sequence (SEQ ID NO: 133 starting at position 99 and ending at position 108) SGYYGQSLDY or (SEQ ID NO: 134 starting at position 99 and ending at position 108) SGYYGSSLDY; and ii. a LC variable region comprising a LC CDR1 comprising amino acid sequence (SEQ ID NO: 82) KSSQSLENSGNQRNYLT, LC CDR2 comprising amino acid sequence (SEQ ID NO: 79) WASTRES, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 83) QNVYIYPLT; and y. an antigen-binding protein which comprises i. a HC variable region comprising HC CDR1 comprising amino acid sequence (SEQ ID NO: 69) GFTFSSFGMH, HC CDR2 comprising amino acid sequence (SEQ ID NO: 70) YISSGTTNIY, and HC CDR3 comprising an amino acid sequence (SEQ ID NO: 133 starting at position 99 and ending at position 108) SGYYGQSLDY or (SEQ ID NO: 134 starting at position 99 and ending at position 108) SGYYGSSLDY; and ii. a LC variable region comprising a LC CDR1 comprising an amino acid sequence (SEQ ID NO: 135 starting at position 24 and ending at position 40) KSSQSLFQSGNQRNYLT or (SEQ ID NO: 132 starting at position 24 and ending at position 40) KSSQSLFSSGNQRNYLT, LC CDR2 comprising amino acid sequence (SEQ ID NO: 79) WASTRES, and LC CDR3 comprising amino acid sequence (SEQ ID NO: 83) QNVYIYPLT. 84. (canceled)"
  ],
  "cpc": [
    "G01N 33/57557",
    "A61K 2039/505",
    "A61K 47/68031",
    "A61K 47/6849",
    "A61P 1/18",
    "A61P 35/00",
    "C07K 16/28",
    "C07K 16/2809",
    "C07K 2317/24",
    "C07K 2317/31",
    "C07K 2317/56",
    "C07K 2317/77",
    "C07K 2317/92",
    "G01N 33/57525",
    "G01N 33/5759",
    "G01N 33/68"
  ],
  "filing_date": "2025-05-27",
  "publication_date": "2026-04-16",
  "application_number": "US-202519219107-A"
}