JPWO2019147863A5 - - Google Patents
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- JPWO2019147863A5 JPWO2019147863A5 JP2020561600A JP2020561600A JPWO2019147863A5 JP WO2019147863 A5 JPWO2019147863 A5 JP WO2019147863A5 JP 2020561600 A JP2020561600 A JP 2020561600A JP 2020561600 A JP2020561600 A JP 2020561600A JP WO2019147863 A5 JPWO2019147863 A5 JP WO2019147863A5
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- monoclonal antibody
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- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 283
- 239000012634 fragment Substances 0.000 claims description 212
- 239000000427 antigen Substances 0.000 claims description 200
- 102000036639 antigens Human genes 0.000 claims description 200
- 108091007433 antigens Proteins 0.000 claims description 200
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 190
- 101000991061 Homo sapiens MHC class I polypeptide-related sequence B Proteins 0.000 claims description 108
- 108020003285 Isocitrate lyase Proteins 0.000 claims description 108
- 102100030301 MHC class I polypeptide-related sequence A Human genes 0.000 claims description 108
- 102100030300 MHC class I polypeptide-related sequence B Human genes 0.000 claims description 108
- 238000000034 method Methods 0.000 claims description 95
- 206010028980 Neoplasm Diseases 0.000 claims description 26
- 201000011510 cancer Diseases 0.000 claims description 24
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 22
- 239000012528 membrane Substances 0.000 claims description 20
- 108060003951 Immunoglobulin Proteins 0.000 claims description 12
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 12
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 12
- 102000018358 immunoglobulin Human genes 0.000 claims description 12
- 150000001413 amino acids Chemical class 0.000 claims description 10
- 239000010445 mica Substances 0.000 claims description 6
- 229910052618 mica group Inorganic materials 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- RBORURQQJIQWBS-QVRNUERCSA-N (4ar,6r,7r,7as)-6-(6-amino-8-bromopurin-9-yl)-2-hydroxy-2-sulfanylidene-4a,6,7,7a-tetrahydro-4h-furo[3,2-d][1,3,2]dioxaphosphinin-7-ol Chemical compound C([C@H]1O2)OP(O)(=S)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1Br RBORURQQJIQWBS-QVRNUERCSA-N 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
Description
ある特定の態様において、がんの処置を必要とする個体においてがんの処置で用いるための本明細書における開示のいずれかによるモノクローナル抗体またはその抗原結合断片が本明細書において開示される。ある特定の態様において、がんの処置を必要とする個体においてがんを処置するための医薬の調製で用いるための本明細書における開示のいずれかによるモノクローナル抗体またはその抗原結合断片も本明細書において開示される。いくつかの態様において、がんは肝細胞癌である。
[本発明1001]
SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、モノクローナル抗体またはその抗原結合断片であって、SEQ ID NO: 9として記載されるアミノ酸配列を有しない軽鎖を含むか、またはSEQ ID NO: 10として記載されるアミノ酸配列を有しない重鎖を含む、該モノクローナル抗体またはその抗原結合断片。
[本発明1002]
SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも90%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、モノクローナル抗体またはその抗原結合断片であって、SEQ ID NO: 9として記載されるアミノ酸配列を有しない軽鎖を含むか、またはSEQ ID NO: 10として記載されるアミノ酸配列を有しない重鎖を含む、該モノクローナル抗体またはその抗原結合断片。
[本発明1003]
SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも95%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、モノクローナル抗体またはその抗原結合断片であって、SEQ ID NO: 9として記載されるアミノ酸配列を有しない軽鎖を含むか、またはSEQ ID NO: 10として記載されるアミノ酸配列を有しない重鎖を含む、該モノクローナル抗体またはその抗原結合断片。
[本発明1004]
SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも99%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、モノクローナル抗体またはその抗原結合断片であって、SEQ ID NO: 9として記載されるアミノ酸配列を有しない軽鎖を含むか、またはSEQ ID NO: 10として記載されるアミノ酸配列を有しない重鎖を含む、該モノクローナル抗体またはその抗原結合断片。
[本発明1005]
SEQ ID NO: 7として記載されるアミノ酸配列と100%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、モノクローナル抗体またはその抗原結合断片であって、SEQ ID NO: 9として記載されるアミノ酸配列を有しない軽鎖を含むか、またはSEQ ID NO: 10として記載されるアミノ酸配列を有しない重鎖を含む、該モノクローナル抗体またはその抗原結合断片。
[本発明1006]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、本発明1001～1005のいずれかのモノクローナル抗体。
[本発明1007]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも90%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、本発明1001～1005のいずれかのモノクローナル抗体。
[本発明1008]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも95%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、本発明1001～1005のいずれかのモノクローナル抗体。
[本発明1009]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも99%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、本発明1001～1005のいずれかのモノクローナル抗体。
[本発明1010]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 8として記載されるアミノ酸配列と100%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、本発明1001～1005のいずれかのモノクローナル抗体。
[本発明1011]
前記軽鎖が、SEQ ID NO: 9として記載されるアミノ酸配列の少なくとも1～10個のアミノ酸が改変されているアミノ酸配列を含む、本発明1001～1010のいずれかのモノクローナル抗体。
[本発明1012]
前記重鎖が、SEQ ID NO: 10として記載されるアミノ酸配列の少なくとも1～10個のアミノ酸が改変されているアミノ酸配列を含む、本発明1001～1011のいずれかのモノクローナル抗体。
[本発明1013]
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方に特異的に結合する、本発明1001～1012のいずれかのモノクローナル抗体。
[本発明1014]
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方のα-3ドメインに結合する、本発明1001～1013のいずれかのモノクローナル抗体。
[本発明1015]
MICAタンパク質が、膜結合MICAタンパク質、可溶性MICAタンパク質、またはその両方である、本発明1013または本発明1014のモノクローナル抗体。
[本発明1016]
MICBタンパク質が、膜結合MICBタンパク質、可溶性MICBタンパク質、またはその両方である、本発明1013または本発明1014のモノクローナル抗体。
[本発明1017]
前記モノクローナル抗体またはその抗原結合断片が、免疫グロブリン全体、scFv、Fab、F(ab')
2
またはジスルフィド結合Fvから選択される、本発明1001～1016のいずれかのモノクローナル抗体。
[本発明1018]
前記モノクローナル抗体またはその抗原結合断片が、IgGまたはIgMである、本発明1001～1017のいずれかのモノクローナル抗体。
[本発明1019]
前記モノクローナル抗体またはその断片が、ヒト化されているか、またはキメラである、本発明1001～1018のいずれかのモノクローナル抗体。
[本発明1020]
SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、モノクローナル抗体またはその抗原結合断片であって、SEQ ID NO: 10として記載されるアミノ酸配列を有しない重鎖を含むか、またはSEQ ID NO: 9として記載されるアミノ酸配列を有しない軽鎖を含む、該モノクローナル抗体またはその抗原結合断片。
[本発明1021]
SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも90%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、モノクローナル抗体またはその抗原結合断片であって、SEQ ID NO: 10として記載されるアミノ酸配列を有しない重鎖を含むか、またはSEQ ID NO: 9として記載されるアミノ酸配列を有しない軽鎖を含む、該モノクローナル抗体またはその抗原結合断片。
[本発明1022]
SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも95%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、モノクローナル抗体またはその抗原結合断片であって、SEQ ID NO: 10として記載されるアミノ酸配列を有しない重鎖を含むか、またはSEQ ID NO: 9として記載されるアミノ酸配列を有しない軽鎖を含む、該モノクローナル抗体またはその抗原結合断片。
[本発明1023]
SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも99%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、モノクローナル抗体またはその抗原結合断片であって、SEQ ID NO: 10として記載されるアミノ酸配列を有しない重鎖を含むか、またはSEQ ID NO: 9として記載されるアミノ酸配列を有しない軽鎖を含む、該モノクローナル抗体またはその抗原結合断片。
[本発明1024]
SEQ ID NO: 8として記載されるアミノ酸配列と100%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、モノクローナル抗体またはその抗原結合断片であって、SEQ ID NO: 10として記載されるアミノ酸配列を有しない重鎖を含むか、またはSEQ ID NO: 9として記載されるアミノ酸配列を有しない軽鎖を含む、該モノクローナル抗体またはその抗原結合断片。
[本発明1025]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、本発明1020～1024のいずれかのモノクローナル抗体。
[本発明1026]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも90%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、本発明1020～1024のいずれかのモノクローナル抗体。
[本発明1027]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも95%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、本発明1020～1024のいずれかのモノクローナル抗体。
[本発明1028]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも99%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、本発明1020～1024のいずれかのモノクローナル抗体。
[本発明1029]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 7として記載されるアミノ酸配列と100%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、本発明1020～1024のいずれかのモノクローナル抗体。
[本発明1030]
前記重鎖が、SEQ ID NO: 10として記載されるアミノ酸配列の少なくとも1～10個のアミノ酸が改変されているアミノ酸配列を含む、本発明1020～1029のいずれかのモノクローナル抗体。
[本発明1031]
前記軽鎖が、SEQ ID NO: 9として記載されるアミノ酸配列の少なくとも1～10個のアミノ酸が改変されているアミノ酸配列を含む、本発明1020～1030のいずれかのモノクローナル抗体。
[本発明1032]
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方に特異的に結合する、本発明1020～1031のいずれかのモノクローナル抗体。
[本発明1033]
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方のα-3ドメインに結合する、本発明1020～1032のいずれかのモノクローナル抗体。
[本発明1034]
MICAタンパク質が、膜結合MICAタンパク質、可溶性MICAタンパク質、またはその両方である、本発明1036または本発明1033のモノクローナル抗体。
[本発明1035]
MICBタンパク質が、膜結合MICBタンパク質、可溶性MICBタンパク質、またはその両方である、本発明1036または本発明1033のモノクローナル抗体。
[本発明1036]
前記モノクローナル抗体またはその抗原結合断片が、免疫グロブリン全体、scFv、Fab、F(ab')
2
またはジスルフィド結合Fvから選択される、本発明1020～1035のいずれかのモノクローナル抗体。
[本発明1037]
前記モノクローナル抗体またはその抗原結合断片が、IgGまたはIgMである、本発明1020～1036のいずれかのモノクローナル抗体。
[本発明1038]
前記モノクローナル抗体またはその断片が、ヒト化されているか、またはキメラである、本発明1020～1037のいずれかのモノクローナル抗体。
[本発明1039]
SEQ ID NO: 1と少なくとも80%同一の軽鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 2と少なくとも80%同一の軽鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 3と少なくとも80%同一の軽鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、モノクローナル抗体またはその抗原結合断片であって、SEQ ID NO: 9として記載されるアミノ酸配列を有しない軽鎖を含むか、またはSEQ ID NO: 10として記載されるアミノ酸配列を有しない重鎖を含む、該モノクローナル抗体またはその抗原結合断片。
[本発明1040]
SEQ ID NO: 1と少なくとも90%同一の軽鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 2と少なくとも90%同一の軽鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 3と少なくとも90%同一の軽鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、モノクローナル抗体またはその抗原結合断片であって、SEQ ID NO: 9として記載されるアミノ酸配列を有しない軽鎖を含むか、またはSEQ ID NO: 10として記載されるアミノ酸配列を有しない重鎖を含む、該モノクローナル抗体またはその抗原結合断片。
[本発明1041]
SEQ ID NO: 1と少なくとも95%同一の軽鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 2と少なくとも95%同一の軽鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 3と少なくとも95%同一の軽鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、モノクローナル抗体またはその抗原結合断片であって、SEQ ID NO: 9として記載されるアミノ酸配列を有しない軽鎖を含むか、またはSEQ ID NO: 10として記載されるアミノ酸配列を有しない重鎖を含む、該モノクローナル抗体またはその抗原結合断片。
[本発明1042]
SEQ ID NO: 1と少なくとも99%同一の軽鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 2と少なくとも99%同一の軽鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 3と少なくとも99%同一の軽鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、モノクローナル抗体またはその抗原結合断片であって、SEQ ID NO: 9として記載されるアミノ酸配列を有しない軽鎖を含むか、またはSEQ ID NO: 10として記載されるアミノ酸配列を有しない重鎖を含む、該モノクローナル抗体またはその抗原結合断片。
[本発明1043]
SEQ ID NO: 1と少なくとも100%同一の軽鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 2と少なくとも100%同一の軽鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 3と少なくとも100%同一の軽鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、モノクローナル抗体またはその抗原結合断片であって、SEQ ID NO: 9として記載されるアミノ酸配列を有しない軽鎖を含むか、またはSEQ ID NO: 10として記載されるアミノ酸配列を有しない重鎖を含む、該モノクローナル抗体またはその抗原結合断片。
[本発明1044]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 4と少なくとも80%同一の重鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 5と少なくとも80%同一の重鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 6と少なくとも80%同一の重鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、本発明1039～1043のいずれかのモノクローナル抗体。
[本発明1045]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 4と少なくとも90%同一の重鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 5と少なくとも90%同一の重鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 6と少なくとも90%同一の重鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、本発明1039～1043のいずれかのモノクローナル抗体。
[本発明1046]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 4と少なくとも95%同一の重鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 5と少なくとも95%同一の重鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 6と少なくとも95%同一の重鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、本発明1039～1043のいずれかのモノクローナル抗体。
[本発明1047]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 4と少なくとも99%同一の重鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 5と少なくとも99%同一の重鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 6と少なくとも99%同一の重鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、本発明1039～1043のいずれかのモノクローナル抗体。
[本発明1048]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 4と100%同一の重鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 5と100%同一の重鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 6と100%同一の重鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、本発明1039～1043のいずれかのモノクローナル抗体。
[本発明1049]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、本発明1039～1048のいずれかのモノクローナル抗体。
[本発明1050]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、本発明1049のモノクローナル抗体。
[本発明1051]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、本発明1039～1048のいずれかのモノクローナル抗体。
[本発明1052]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、本発明1051のモノクローナル抗体。
[本発明1053]
前記軽鎖が、SEQ ID NO: 9として記載されるアミノ酸配列の少なくとも1～10個のアミノ酸が改変されているアミノ酸配列を含む、本発明1039～1052のいずれかのモノクローナル抗体。
[本発明1054]
前記重鎖が、SEQ ID NO: 10として記載されるアミノ酸配列の少なくとも1～10個のアミノ酸が改変されているアミノ酸配列を含む、本発明1039～1053のいずれかのモノクローナル抗体。
[本発明1055]
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方に特異的に結合する、本発明1039～1054のいずれかのモノクローナル抗体。
[本発明1056]
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方のα-3ドメインに結合する、本発明1039～1055のいずれかのモノクローナル抗体。
[本発明1057]
MICAタンパク質が、膜結合MICAタンパク質、可溶性MICAタンパク質、またはその両方である、本発明1055または本発明1056のモノクローナル抗体。
[本発明1058]
MICBタンパク質が、膜結合MICBタンパク質、可溶性MICBタンパク質、またはその両方である、本発明1055または本発明1056のモノクローナル抗体。
[本発明1059]
前記モノクローナル抗体またはその抗原結合断片が、免疫グロブリン全体、scFv、Fab、F(ab')
2
またはジスルフィド結合Fvから選択される、本発明1039～1058のいずれかのモノクローナル抗体。
[本発明1060]
前記モノクローナル抗体またはその抗原結合断片が、IgGまたはIgMである、本発明1039～1059のいずれかのモノクローナル抗体。
[本発明1061]
前記モノクローナル抗体またはその断片が、ヒト化されているか、またはキメラである、本発明1039～1060のいずれかのモノクローナル抗体。
[本発明1062]
SEQ ID NO: 4と少なくとも80%同一の重鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 5と少なくとも80%同一の重鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 6と少なくとも80%同一の重鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、モノクローナル抗体またはその抗原結合断片であって、SEQ ID NO: 10として記載されるアミノ酸配列を有しない重鎖を含むか、またはSEQ ID NO: 9として記載されるアミノ酸配列を有しない軽鎖を含む、該モノクローナル抗体またはその抗原結合断片。
[本発明1063]
SEQ ID NO: 4と少なくとも90%同一の重鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 5と少なくとも90%同一の重鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 6と少なくとも90%同一の重鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、モノクローナル抗体またはその抗原結合断片であって、SEQ ID NO: 10として記載されるアミノ酸配列を有しない重鎖を含むか、またはSEQ ID NO: 9として記載されるアミノ酸配列を有しない軽鎖を含む、該モノクローナル抗体またはその抗原結合断片。
[本発明1064]
SEQ ID NO: 4と少なくとも95%同一の重鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 5と少なくとも95%同一の重鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 6と少なくとも95%同一の重鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、モノクローナル抗体またはその抗原結合断片であって、SEQ ID NO: 10として記載されるアミノ酸配列を有しない重鎖を含むか、またはSEQ ID NO: 9として記載されるアミノ酸配列を有しない軽鎖を含む、該モノクローナル抗体またはその抗原結合断片。
[本発明1065]
SEQ ID NO: 4と少なくとも99%同一の重鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 5と少なくとも99%同一の重鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 6と少なくとも99%同一の重鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、モノクローナル抗体またはその抗原結合断片であって、SEQ ID NO: 10として記載されるアミノ酸配列を有しない重鎖を含むか、またはSEQ ID NO: 9として記載されるアミノ酸配列を有しない軽鎖を含む、該モノクローナル抗体またはその抗原結合断片。
[本発明1066]
SEQ ID NO: 4と100%同一の重鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 5と100%同一の重鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 6と100%同一の重鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、モノクローナル抗体またはその抗原結合断片であって、SEQ ID NO: 10として記載されるアミノ酸配列を有しない重鎖を含むか、またはSEQ ID NO: 9として記載されるアミノ酸配列を有しない軽鎖を含む、該モノクローナル抗体またはその抗原結合断片。
[本発明1067]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 1と少なくとも80%同一の軽鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 2と少なくとも80%同一の軽鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 3と少なくとも80%同一の軽鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、本発明1062～1066のいずれかのモノクローナル抗体。
[本発明1068]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 1と少なくとも90%同一の軽鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 2と少なくとも90%同一の軽鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 3と少なくとも90%同一の軽鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、本発明1062～1066のいずれかのモノクローナル抗体。
[本発明1069]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 1と少なくとも95%同一の軽鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 2と少なくとも95%同一の軽鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 3と少なくとも95%同一の軽鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、本発明1062～1066のいずれかのモノクローナル抗体。
[本発明1070]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 1と少なくとも99%同一の軽鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 2と少なくとも99%同一の軽鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 3と少なくとも99%同一の軽鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、本発明1062～1066のいずれかのモノクローナル抗体。
[本発明1071]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 1と100%同一の軽鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 2と100%同一の軽鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 3と100%同一の軽鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、本発明1062～1066のいずれかのモノクローナル抗体。
[本発明1072]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、本発明1062～1071のいずれかのモノクローナル抗体。
[本発明1073]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、本発明1072のモノクローナル抗体。
[本発明1074]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、本発明1062～1071のいずれかのモノクローナル抗体。
[本発明1075]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、本発明1074のモノクローナル抗体。
[本発明1076]
前記重鎖が、SEQ ID NO: 10として記載されるアミノ酸配列の少なくとも1～10個のアミノ酸が改変されているアミノ酸配列を含む、本発明1062～1075のいずれかのモノクローナル抗体。
[本発明1077]
前記軽鎖が、SEQ ID NO: 9として記載されるアミノ酸配列の少なくとも1～10個のアミノ酸が改変されているアミノ酸配列を含む、本発明1062～1076のいずれかのモノクローナル抗体。
[本発明1078]
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方に特異的に結合する、本発明1062～1077のいずれかのモノクローナル抗体。
[本発明1079]
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方のα-3ドメインに結合する、本発明1062～1078のいずれかのモノクローナル抗体。
[本発明1080]
MICAタンパク質が、膜結合MICAタンパク質、可溶性MICAタンパク質、またはその両方である、本発明1078または本発明1079のモノクローナル抗体。
[本発明1081]
MICBタンパク質が、膜結合MICBタンパク質、可溶性MICBタンパク質、またはその両方である、本発明1078または本発明1079のモノクローナル抗体。
[本発明1082]
前記モノクローナル抗体またはその抗原結合断片が、免疫グロブリン全体、scFv、Fab、F(ab')
2
またはジスルフィド結合Fvから選択される、本発明1062～1081のいずれかのモノクローナル抗体。
[本発明1083]
前記モノクローナル抗体またはその抗原結合断片が、IgGまたはIgMである、本発明1062～1082のいずれかのモノクローナル抗体。
[本発明1084]
前記モノクローナル抗体またはその断片が、ヒト化されているか、またはキメラである、本発明1062～1083のいずれかのモノクローナル抗体。
[本発明1085]
本発明1001～1084のいずれかのモノクローナル抗体またはその抗原結合断片と、薬学的に許容される担体または賦形剤とを含む、薬学的組成物。
[本発明1086]
SEQ ID NO: 1と少なくとも80%同一の軽鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 2と少なくとも80%同一の軽鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 3と少なくとも80%同一の軽鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、モノクローナル抗体またはその抗原結合断片の有効量を個体に投与する段階を含む、がんの処置を必要とする個体においてがんを処置する方法。
[本発明1087]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 4と少なくとも80%同一の重鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 5と少なくとも80%同一の重鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 6と少なくとも80%同一の重鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、本発明1086の方法。
[本発明1088]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、本発明1086または1087のいずれかの方法。
[本発明1089]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、本発明1088の方法。
[本発明1090]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、本発明1086または1087のいずれかの方法。
[本発明1091]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、本発明1090の方法。
[本発明1092]
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方に特異的に結合する、本発明1086～1091のいずれかの方法。
[本発明1093]
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方のα-3ドメインに結合する、本発明1086～1092のいずれかの方法。
[本発明1094]
MICAタンパク質が、膜結合MICAタンパク質、可溶性MICAタンパク質、またはその両方である、本発明1092または本発明1093の方法。
[本発明1095]
MICBタンパク質が、膜結合MICBタンパク質、可溶性MICBタンパク質、またはその両方である、本発明1092または本発明1093の方法。
[本発明1096]
前記モノクローナル抗体またはその抗原結合断片が、免疫グロブリン全体、scFv、Fab、F(ab')
2
またはジスルフィド結合Fvから選択される、本発明1086～1095のいずれかの方法。
[本発明1097]
前記モノクローナル抗体またはその抗原結合断片が、IgGまたはIgMである、本発明1086～1096のいずれかの方法。
[本発明1098]
前記モノクローナル抗体またはその断片が、ヒト化されているか、またはキメラである、本発明1086～1097のいずれかの方法。
[本発明1099]
前記モノクローナル抗体またはその抗原結合断片が、可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のレベルを低減する、本発明1086～1098のいずれかの方法。
[本発明1100]
前記モノクローナル抗体またはその抗原結合断片が、可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のシェディングを低減する、本発明1086～1098のいずれかの方法。
[本発明1101]
前記モノクローナル抗体またはその抗原結合断片が、可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のシェディングを阻害する、本発明1086～1098のいずれかの方法。
[本発明1102]
がんが肝細胞癌である、本発明1086～1101のいずれかの方法。
[本発明1103]
SEQ ID NO: 4と少なくとも80%同一の重鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 5と少なくとも80%同一の重鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 6と少なくとも80%同一の重鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、モノクローナル抗体またはその抗原結合断片の有効量を個体に投与する段階を含む、がんの処置を必要とする個体においてがんを処置する方法。
[本発明1104]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 1と少なくとも80%同一の軽鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 2と少なくとも80%同一の軽鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 3と少なくとも80%同一の軽鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、本発明1103の方法。
[本発明1105]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、本発明1103または1104のいずれかの方法。
[本発明1106]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、本発明1105の方法。
[本発明1107]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、本発明1103または1104のいずれかの方法。
[本発明1108]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、本発明1107の方法。
[本発明1109]
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方に特異的に結合する、本発明1103～1108のいずれかの方法。
[本発明1110]
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方のα-3ドメインに結合する、本発明1103～1109のいずれかの方法。
[本発明1111]
MICAタンパク質が、膜結合MICAタンパク質、可溶性MICAタンパク質、またはその両方である、本発明1109または本発明1110の方法。
[本発明1112]
MICBタンパク質が、膜結合MICBタンパク質、可溶性MICBタンパク質、またはその両方である、本発明1109または本発明1110の方法。
[本発明1113]
前記モノクローナル抗体またはその抗原結合断片が、免疫グロブリン全体、scFv、Fab、F(ab')
2
またはジスルフィド結合Fvから選択される、本発明1103～1112のいずれかの方法。
[本発明1114]
前記モノクローナル抗体またはその抗原結合断片が、IgGまたはIgMである、本発明1103～1113のいずれかの方法。
[本発明1115]
前記モノクローナル抗体またはその断片が、ヒト化されているか、またはキメラである、本発明1103～1114のいずれかの方法。
[本発明1116]
前記モノクローナル抗体またはその抗原結合断片が、可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のレベルを低減する、本発明1103～1115のいずれかの方法。
[本発明1117]
前記モノクローナル抗体またはその抗原結合断片が、可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のシェディングを低減する、本発明1103～1115のいずれかの方法。
[本発明1118]
前記モノクローナル抗体またはその抗原結合断片が、可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のシェディングを阻害する、本発明1103～1115のいずれかの方法。
[本発明1119]
がんが肝細胞癌である、本発明1103～1118のいずれかの方法。
[本発明1120]
SEQ ID NO: 1と少なくとも80%同一の軽鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 2と少なくとも80%同一の軽鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 3と少なくとも80%同一の軽鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、モノクローナル抗体またはその抗原結合断片の有効量を個体に投与する段階を含む、肝細胞癌の処置を必要とする個体において肝細胞癌を処置する方法。
[本発明1121]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 4と少なくとも80%同一の重鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 5と少なくとも80%同一の重鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 6と少なくとも80%同一の重鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、本発明1120の方法。
[本発明1122]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、本発明1120または1121のいずれかの方法。
[本発明1123]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、本発明1122の方法。
[本発明1124]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、本発明1120または1121のいずれかの方法。
[本発明1125]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、本発明1124の方法。
[本発明1126]
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方に特異的に結合する、本発明1120～1125のいずれかの方法。
[本発明1127]
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方のα-3ドメインに結合する、本発明1120～1126のいずれかの方法。
[本発明1128]
MICAタンパク質が、膜結合MICAタンパク質、可溶性MICAタンパク質、またはその両方である、本発明1126または本発明1127の方法。
[本発明1129]
MICBタンパク質が、膜結合MICBタンパク質、可溶性MICBタンパク質、またはその両方である、本発明1126または本発明1127の方法。
[本発明1130]
前記モノクローナル抗体またはその抗原結合断片が、免疫グロブリン全体、scFv、Fab、F(ab')
2
またはジスルフィド結合Fvから選択される、本発明1120～1129のいずれかの方法。
[本発明1131]
前記モノクローナル抗体またはその抗原結合断片が、IgGまたはIgMである、本発明1120～1130のいずれかの方法。
[本発明1132]
前記モノクローナル抗体またはその断片が、ヒト化されているか、またはキメラである、本発明1120～1131のいずれかの方法。
[本発明1133]
前記モノクローナル抗体またはその抗原結合断片が、可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のレベルを低減する、本発明1120～1132のいずれかの方法。
[本発明1134]
前記モノクローナル抗体またはその抗原結合断片が、可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のシェディングを低減する、本発明1120～1132のいずれかの方法。
[本発明1135]
前記モノクローナル抗体またはその抗原結合断片が、可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のシェディングを阻害する、本発明1120～1132のいずれかの方法。
[本発明1136]
SEQ ID NO: 4と少なくとも80%同一の重鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 5と少なくとも80%同一の重鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 6と少なくとも80%同一の重鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、モノクローナル抗体またはその抗原結合断片の有効量を個体に投与する段階を含む、肝細胞癌の処置を必要とする個体において肝細胞癌を処置する方法。
[本発明1137]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 1と少なくとも80%同一の軽鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 2と少なくとも80%同一の軽鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 3と少なくとも80%同一の軽鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、本発明1136の方法。
[本発明1138]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、本発明1136または1137のいずれかの方法。
[本発明1139]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、本発明1138の方法。
[本発明1140]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、本発明1136または1137のいずれかの方法。
[本発明1141]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、本発明1140の方法。
[本発明1142]
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方に特異的に結合する、本発明1136～1141のいずれかの方法。
[本発明1143]
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方のα-3ドメインに結合する、本発明1136～1142のいずれかの方法。
[本発明1144]
MICAタンパク質が、膜結合MICAタンパク質、可溶性MICAタンパク質、またはその両方である、本発明1142または本発明1143の方法。
[本発明1145]
MICBタンパク質が、膜結合MICBタンパク質、可溶性MICBタンパク質、またはその両方である、本発明1142または本発明1143の方法。
[本発明1146]
前記モノクローナル抗体またはその抗原結合断片が、免疫グロブリン全体、scFv、Fab、F(ab')
2
またはジスルフィド結合Fvから選択される、本発明1136～1145のいずれかの方法。
[本発明1147]
前記モノクローナル抗体またはその抗原結合断片が、IgGまたはIgMである、本発明1136～1146のいずれかの方法。
[本発明1148]
前記モノクローナル抗体またはその断片が、ヒト化されているか、またはキメラである、本発明1136～1147のいずれかの方法。
[本発明1149]
前記モノクローナル抗体またはその抗原結合断片が、可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のレベルを低減する、本発明1136～1148のいずれかの方法。
[本発明1150]
前記モノクローナル抗体またはその抗原結合断片が、可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のシェディングを低減する、本発明1136～1148のいずれかの方法。
[本発明1151]
前記モノクローナル抗体またはその抗原結合断片が、可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のシェディングを阻害する、本発明1136～1148のいずれかの方法。
[本発明1152]
SEQ ID NO: 1と少なくとも80%同一の軽鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 2と少なくとも80%同一の軽鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 3と少なくとも80%同一の軽鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、モノクローナル抗体またはその抗原結合断片の有効量を個体に投与する段階を含む、可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のレベルの低減を必要とする個体において可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のレベルを低減する方法。
[本発明1153]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 4と少なくとも80%同一の重鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 5と少なくとも80%同一の重鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 6と少なくとも80%同一の重鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、本発明1152の方法。
[本発明1154]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、本発明1152または1153のいずれかの方法。
[本発明1155]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、本発明1154の方法。
[本発明1156]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、本発明1152または1153のいずれかの方法。
[本発明1157]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、本発明1156の方法。
[本発明1158]
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方に特異的に結合する、本発明1152～1157のいずれかの方法。
[本発明1159]
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方のα-3ドメインに結合する、本発明1152～1158のいずれかの方法。
[本発明1160]
MICAタンパク質が、可溶性MICAタンパク質である、本発明1158または本発明1159の方法。
[本発明1161]
MICBタンパク質が、可溶性MICBタンパク質である、本発明1158または本発明1159の方法。
[本発明1162]
前記モノクローナル抗体またはその抗原結合断片が、免疫グロブリン全体、scFv、Fab、F(ab')
2
またはジスルフィド結合Fvから選択される、本発明1152～1161のいずれかの方法。
[本発明1163]
前記モノクローナル抗体またはその抗原結合断片が、IgGまたはIgMである、本発明1152～1162のいずれかの方法。
[本発明1164]
前記モノクローナル抗体またはその断片が、ヒト化されているか、またはキメラである、本発明1152～1163のいずれかの方法。
[本発明1165]
前記モノクローナル抗体またはその抗原結合断片が、可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のシェディングを低減または阻害し、それにより、個体における可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のレベルを低減する、本発明1152～1164のいずれかの方法。
[本発明1166]
前記個体が、可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のレベルの上昇によって特徴付けられるがんを有する、本発明1152～1165のいずれかの方法。
[本発明1167]
前記がんが肝細胞癌である、本発明1166の方法。
[本発明1168]
SEQ ID NO: 4と少なくとも80%同一の重鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 5と少なくとも80%同一の重鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 6と少なくとも80%同一の重鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、モノクローナル抗体またはその抗原結合断片の有効量を個体に投与する段階を含む、可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のレベルの低減を必要とする個体において可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のレベルを低減する方法。
[本発明1169]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 1と少なくとも80%同一の軽鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 2と少なくとも80%同一の軽鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 3と少なくとも80%同一の軽鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、本発明1168の方法。
[本発明1170]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、本発明1168または1169のいずれかの方法。
[本発明1171]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、本発明1170の方法。
[本発明1172]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、本発明1168または1169のいずれかの方法。
[本発明1173]
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、本発明1172の方法。
[本発明1174]
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方に特異的に結合する、本発明1168～1173のいずれかの方法。
[本発明1175]
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方のα-3ドメインに結合する、本発明1168～1174のいずれかの方法。
[本発明1176]
MICAタンパク質が、可溶性MICAタンパク質である、本発明1174または本発明1175の方法。
[本発明1177]
MICBタンパク質が、可溶性MICBタンパク質である、本発明1174または本発明1175の方法。
[本発明1178]
前記モノクローナル抗体またはその抗原結合断片が、免疫グロブリン全体、scFv、Fab、F(ab')
2
またはジスルフィド結合Fvから選択される、本発明1168～1177のいずれかの方法。
[本発明1179]
前記モノクローナル抗体またはその抗原結合断片が、IgGまたはIgMである、本発明1168～1178のいずれかの方法。
[本発明1180]
前記モノクローナル抗体またはその断片が、ヒト化されているか、またはキメラである、本発明1168～1179のいずれかの方法。
[本発明1181]
前記モノクローナル抗体またはその抗原結合断片が、可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のシェディングを低減または阻害し、それにより、個体における可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のレベルを低減する、本発明1168～1180のいずれかの方法。
[本発明1182]
前記個体が、可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のレベルの上昇によって特徴付けられるがんを有する、本発明1168～1181のいずれかの方法。
[本発明1183]
前記がんが肝細胞癌である、本発明1182の方法。
[本発明1184]
がんの処置を必要とする個体においてがんの処置で用いるための、本発明1001～1084のいずれかのモノクローナル抗体またはその抗原結合断片。
[本発明1185]
がんの処置を必要とする個体においてがんを処置するための医薬の調製で用いるための、本発明1001～1084のいずれかのモノクローナル抗体。
[本発明1186]
がんが肝細胞癌である、本発明1184または本発明1185の使用のための、モノクローナル抗体。
In certain embodiments, monoclonal antibodies or antigen-binding fragments thereof according to any of the disclosures herein for use in the treatment of cancer in individuals in need of treatment for cancer are disclosed herein. Also herein is a monoclonal antibody or antigen-binding fragment thereof according to any of the disclosures herein for use in the preparation of a pharmaceutical for treating cancer in an individual in need of treatment of the cancer in certain embodiments. Will be disclosed in. In some embodiments, the cancer is hepatocellular carcinoma.
[Invention 1001]
A monoclonal antibody or antigen-binding fragment thereof comprising a light chain variable domain (VL) containing an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 7 and is described as SEQ ID NO: 9. A monoclonal antibody or antigen-binding fragment thereof comprising a light chain having no amino acid sequence or a heavy chain having no amino acid sequence described as SEQ ID NO: 10.
[Invention 1002]
A monoclonal antibody or antigen-binding fragment thereof comprising a light chain variable domain (VL) containing an amino acid sequence that is at least 90% identical to the amino acid sequence described as SEQ ID NO: 7 and is described as SEQ ID NO: 9. A monoclonal antibody or antigen-binding fragment thereof comprising a light chain having no amino acid sequence or a heavy chain having no amino acid sequence described as SEQ ID NO: 10.
[Invention 1003]
A monoclonal antibody or antigen-binding fragment thereof comprising a light chain variable domain (VL) containing an amino acid sequence that is at least 95% identical to the amino acid sequence described as SEQ ID NO: 7 and is described as SEQ ID NO: 9. A monoclonal antibody or antigen-binding fragment thereof comprising a light chain having no amino acid sequence or a heavy chain having no amino acid sequence described as SEQ ID NO: 10.
[Invention 1004]
A monoclonal antibody or antigen-binding fragment thereof comprising a light chain variable domain (VL) containing an amino acid sequence that is at least 99% identical to the amino acid sequence described as SEQ ID NO: 7 and is described as SEQ ID NO: 9. A monoclonal antibody or antigen-binding fragment thereof comprising a light chain having no amino acid sequence or a heavy chain having no amino acid sequence described as SEQ ID NO: 10.
[Invention 1005]
A monoclonal antibody or antigen-binding fragment thereof comprising a light chain variable domain (VL) containing an amino acid sequence that is 100% identical to the amino acid sequence described as SEQ ID NO: 7 and is described as SEQ ID NO: 9. The monoclonal antibody or antigen-binding fragment thereof comprising a light chain having no amino acid sequence or a heavy chain having no amino acid sequence described as SEQ ID NO: 10.
[Invention 1006]
Any of 1001-1005 of the present invention, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain variable domain (VH) containing an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 8. Monoclonal antibody.
[Invention 1007]
Any of 1001-1005 of the present invention, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain variable domain (VH) containing an amino acid sequence that is at least 90% identical to the amino acid sequence described as SEQ ID NO: 8. Monoclonal antibody.
[Invention 1008]
Any of 1001-1005 of the invention, wherein the monoclonal antibody or antigen binding fragment thereof comprises a heavy chain variable domain (VH) comprising an amino acid sequence that is at least 95% identical to the amino acid sequence described as SEQ ID NO: 8. Monoclonal antibody.
[Invention 1009]
Any of 1001-1005 of the invention, wherein the monoclonal antibody or antigen binding fragment thereof comprises a heavy chain variable domain (VH) comprising an amino acid sequence that is at least 99% identical to the amino acid sequence described as SEQ ID NO: 8. Monoclonal antibody.
[Invention 1010]
The monoclonal of any of the present inventions 1001 to 1005, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain variable domain (VH) containing an amino acid sequence that is 100% identical to the amino acid sequence described as SEQ ID NO: 8. antibody.
[Invention 1011]
The monoclonal antibody of any of 1001-1010 of the present invention, wherein the light chain comprises an amino acid sequence in which at least 1-10 amino acids of the amino acid sequence described as SEQ ID NO: 9 are modified.
[Invention 1012]
The monoclonal antibody according to any one of the present inventions 1001 to 1011, wherein the heavy chain comprises an amino acid sequence in which at least 1 to 10 amino acids of the amino acid sequence described as SEQ ID NO: 10 are modified.
[Invention 1013]
The monoclonal antibody of any of the present inventions 1001 to 1012, wherein the monoclonal antibody or an antigen-binding fragment thereof specifically binds to a MICA protein, a MICB protein, or both MICA and the MICB protein.
[Invention 1014]
The monoclonal antibody of any of 1001 to 1013 of the present invention, wherein the monoclonal antibody or an antigen-binding fragment thereof binds to the α-3 domain of MICA protein, MICB protein, or both MICA and MICB protein.
[Invention 1015]
A monoclonal antibody of the present invention 1013 or the present invention 1014, wherein the MICA protein is a membrane-bound MICA protein, a soluble MICA protein, or both.
[Invention 1016]
The monoclonal antibody of the present invention 1013 or the present invention 1014, wherein the MICB protein is a membrane-bound MICB protein, a soluble MICB protein, or both.
[Invention 1017]
The monoclonal antibody according to any one of the present inventions 1001 to 1016, wherein the monoclonal antibody or an antigen-binding fragment thereof is selected from whole immunoglobulin, scFv, Fab, F (ab') 2 or disulfide bond Fv.
[Invention 1018]
The monoclonal antibody according to any one of the present inventions 1001 to 1017, wherein the monoclonal antibody or an antigen-binding fragment thereof is IgG or IgM.
[Invention 1019]
The monoclonal antibody according to any one of the present inventions 1001 to 1018, wherein the monoclonal antibody or a fragment thereof is humanized or chimeric.
[Invention 1020]
A monoclonal antibody or antigen-binding fragment thereof comprising a heavy chain variable domain (VH) containing at least 80% identical amino acid sequence to the amino acid sequence described as SEQ ID NO: 8 and described as SEQ ID NO: 10. A monoclonal antibody or antigen-binding fragment thereof comprising a heavy chain having no amino acid sequence or a light chain having no amino acid sequence described as SEQ ID NO: 9.
[Invention 1021]
A monoclonal antibody or antigen-binding fragment thereof comprising a heavy chain variable domain (VH) containing at least 90% identical amino acid sequence to the amino acid sequence described as SEQ ID NO: 8 and described as SEQ ID NO: 10. A monoclonal antibody or antigen-binding fragment thereof comprising a heavy chain having no amino acid sequence or a light chain having no amino acid sequence described as SEQ ID NO: 9.
[Invention 1022]
A monoclonal antibody or antigen-binding fragment thereof comprising a heavy chain variable domain (VH) containing at least 95% identical amino acid sequence to the amino acid sequence described as SEQ ID NO: 8 and described as SEQ ID NO: 10. A monoclonal antibody or antigen-binding fragment thereof comprising a heavy chain having no amino acid sequence or a light chain having no amino acid sequence described as SEQ ID NO: 9.
[Invention 1023]
A monoclonal antibody or antigen-binding fragment thereof comprising a heavy chain variable domain (VH) containing at least 99% identical amino acid sequence to the amino acid sequence described as SEQ ID NO: 8 and described as SEQ ID NO: 10. A monoclonal antibody or antigen-binding fragment thereof comprising a heavy chain having no amino acid sequence or a light chain having no amino acid sequence described as SEQ ID NO: 9.
[Invention 1024]
A monoclonal antibody or antigen-binding fragment thereof comprising a heavy chain variable domain (VH) containing an amino acid sequence that is 100% identical to the amino acid sequence described as SEQ ID NO: 8 and is described as SEQ ID NO: 10. The monoclonal antibody or antigen-binding fragment thereof comprising a heavy chain having no amino acid sequence or a light chain having no amino acid sequence described as SEQ ID NO: 9.
[Invention 1025]
Any of the inventions 1020-1024, wherein the monoclonal antibody or antigen binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 7. Monoclonal antibody.
[Invention 1026]
Any of the inventions 1020-1024, wherein the monoclonal antibody or antigen binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence that is at least 90% identical to the amino acid sequence described as SEQ ID NO: 7. Monoclonal antibody.
[Invention 1027]
Any of the inventions 1020-1024, wherein the monoclonal antibody or antigen binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence that is at least 95% identical to the amino acid sequence described as SEQ ID NO: 7. Monoclonal antibody.
[Invention 1028]
Any of the inventions 1020-1024, wherein the monoclonal antibody or antigen binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence that is at least 99% identical to the amino acid sequence described as SEQ ID NO: 7. Monoclonal antibody.
[Invention 1029]
The monoclonal of any of the present inventions 1020 to 1024, wherein the monoclonal antibody or antigen binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence that is 100% identical to the amino acid sequence described as SEQ ID NO: 7. antibody.
[Invention 1030]
The monoclonal antibody of any of the present invention 1020-1029, wherein the heavy chain comprises an amino acid sequence in which at least 1-10 amino acids of the amino acid sequence described as SEQ ID NO: 10 have been modified.
[Invention 1031]
The monoclonal antibody of any of the present invention 1020-1030, wherein the light chain comprises an amino acid sequence in which at least 1-10 amino acids of the amino acid sequence described as SEQ ID NO: 9 have been modified.
[Invention 1032]
The monoclonal antibody of any of the present inventions 1020 to 1031, wherein the monoclonal antibody or an antigen-binding fragment thereof specifically binds to MICA protein, MICB protein, or both MICA and MICB protein.
[Invention 1033]
The monoclonal antibody of any of the present inventions 1020 to 1032, wherein the monoclonal antibody or an antigen-binding fragment thereof binds to the α-3 domain of MICA protein, MICB protein, or both MICA and MICB protein.
[Invention 1034]
The monoclonal antibody of the present invention 1036 or the present invention 1033, wherein the MICA protein is a membrane-bound MICA protein, a soluble MICA protein, or both.
[Invention 1035]
The monoclonal antibody of the invention 1036 or the invention 1033, wherein the MICB protein is a membrane-bound MICB protein, a soluble MICB protein, or both.
[Invention 1036]
The monoclonal antibody of any of the present inventions 1020-1035 , wherein the monoclonal antibody or antigen-binding fragment thereof is selected from whole immunoglobulin, scFv, Fab, F (ab') 2 or disulfide-bonded Fv.
[Invention 1037]
The monoclonal antibody according to any one of the present inventions 1020 to 1036, wherein the monoclonal antibody or an antigen-binding fragment thereof is IgG or IgM.
[Invention 1038]
The monoclonal antibody of any of the present inventions 1020-1037, wherein the monoclonal antibody or fragment thereof is humanized or chimeric.
[Invention 1039]
Light chain complementarity determining region 1 (CDR1) sequences that are at least 80% identical to SEQ ID NO: 1, light chain complementarity determining region 2 (CDR2) sequences that are at least 80% identical to SEQ ID NO: 2, and SEQ ID NO. A monoclonal antibody or antigen-binding fragment thereof comprising: at least one of the light chain complementarity determining region 3 (CDR3) sequences identical to: 3 and having an amino acid sequence described as SEQ ID NO: 9. The monoclonal antibody or antigen-binding fragment thereof, comprising a light chain that does not contain, or a heavy chain that does not have the amino acid sequence described as SEQ ID NO: 10.
[Invention 1040]
Light chain complementarity determining region 1 (CDR1) sequences that are at least 90% identical to SEQ ID NO: 1, light chain complementarity determining region 2 (CDR2) sequences that are at least 90% identical to SEQ ID NO: 2, and SEQ ID NO. A monoclonal antibody or antigen-binding fragment thereof comprising: at least one of the light chain complementarity determining region 3 (CDR3) sequences identical to: 3 and having an amino acid sequence described as SEQ ID NO: 9. The monoclonal antibody or antigen-binding fragment thereof, comprising a light chain that does not contain, or a heavy chain that does not have the amino acid sequence described as SEQ ID NO: 10.
[Invention 1041]
Light chain complementarity determining region 1 (CDR1) sequences that are at least 95% identical to SEQ ID NO: 1, light chain complementarity determining region 2 (CDR2) sequences that are at least 95% identical to SEQ ID NO: 2, and SEQ ID NO. A monoclonal antibody or antigen-binding fragment thereof comprising: at least one of the light chain complementarity determining region 3 (CDR3) sequences identical to: 3 and having an amino acid sequence described as SEQ ID NO: 9. The monoclonal antibody or antigen-binding fragment thereof, comprising a light chain that does not contain, or a heavy chain that does not have the amino acid sequence described as SEQ ID NO: 10.
[Invention 1042]
Light chain complementarity determining region 1 (CDR1) sequences that are at least 99% identical to SEQ ID NO: 1, light chain complementarity determining region 2 (CDR2) sequences that are at least 99% identical to SEQ ID NO: 2, and SEQ ID NO. A monoclonal antibody or antigen-binding fragment thereof comprising: at least one of the light chain complementarity determining region 3 (CDR3) sequences identical to: 3 and having an amino acid sequence described as SEQ ID NO: 9. The monoclonal antibody or antigen-binding fragment thereof, comprising a light chain that does not contain, or a heavy chain that does not have the amino acid sequence described as SEQ ID NO: 10.
[Invention 1043]
Light chain complementarity determining region 1 (CDR1) sequences that are at least 100% identical to SEQ ID NO: 1, light chain complementarity determining region 2 (CDR2) sequences that are at least 100% identical to SEQ ID NO: 2, and SEQ ID NO. A monoclonal antibody or antigen-binding fragment thereof comprising: at least one of the light chain complementarity determining region 3 (CDR3) sequences identical to: 3 and having an amino acid sequence described as SEQ ID NO: 9. The monoclonal antibody or antigen-binding fragment thereof, comprising a light chain that does not contain, or a heavy chain that does not have the amino acid sequence described as SEQ ID NO: 10.
[Invention 1044]
A heavy chain complementarity determining region 1 (CDR1) sequence in which the monoclonal antibody or its antigen-binding fragment is at least 80% identical to SEQ ID NO: 4, and a heavy chain complementarity determining region 1 (CDR1) that is at least 80% identical to SEQ ID NO: 5. A monoclonal antibody according to any of the inventions 1039 to 1043, comprising 2 (CDR2) sequences and at least one of the heavy chain complementarity determining region 3 (CDR3) sequences that are at least 80% identical to SEQ ID NO: 6.
[Invention 1045]
A heavy chain complementarity determining region 1 (CDR1) sequence in which the monoclonal antibody or its antigen-binding fragment is at least 90% identical to SEQ ID NO: 4, and a heavy chain complementarity determining region 1 (CDR1) that is at least 90% identical to SEQ ID NO: 5. A monoclonal antibody according to any of the inventions 1039 to 1043, comprising 2 (CDR2) sequences and at least one of the heavy chain complementarity determining region 3 (CDR3) sequences that are at least 90% identical to SEQ ID NO: 6.
[Invention 1046]
A heavy chain complementarity determining region 1 (CDR1) sequence in which the monoclonal antibody or its antigen-binding fragment is at least 95% identical to SEQ ID NO: 4, and a heavy chain complementarity determining region 1 (CDR1) that is at least 95% identical to SEQ ID NO: 5. A monoclonal antibody according to any of the inventions 1039 to 1043, comprising 2 (CDR2) sequences and at least one of the heavy chain complementarity determining region 3 (CDR3) sequences that are at least 95% identical to SEQ ID NO: 6.
[Invention 1047]
The monoclonal antibody or its antigen-binding fragment has at least 99% identical heavy chain complementarity determining regions 1 (CDR1) sequences with SEQ ID NO: 4, and at least 99% identical heavy chain complementarity determining regions with SEQ ID NO: 5. A monoclonal antibody according to any of the inventions 1039 to 1043, comprising 2 (CDR2) sequences and at least one of the heavy chain complementarity determining region 3 (CDR3) sequences that are at least 99% identical to SEQ ID NO: 6.
[Invention 1048]
The monoclonal antibody or its antigen-binding fragment has a heavy chain complementarity determining region 1 (CDR1) sequence that is 100% identical to SEQ ID NO: 4, and a heavy chain complementarity determining region 2 that is 100% identical to SEQ ID NO: 5. Any monoclonal antibody of the invention 1039-1043 comprising a CDR2) sequence and at least one of the heavy chain complementarity determining region 3 (CDR3) sequences that are 100% identical to SEQ ID NO: 6.
[Invention 1049]
Any of 1039-1048 of the invention, wherein the monoclonal antibody or antigen binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 7. Monoclonal antibody.
[Invention 1050]
The monoclonal antibody of the present invention 1049, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain (VH) containing an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 8.
[Invention 1051]
Any of 1039-1048 of the invention, wherein the monoclonal antibody or antigen binding fragment thereof comprises a heavy chain variable domain (VH) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 8. Monoclonal antibody.
[Invention 1052]
The monoclonal antibody of the present invention 1051 wherein the monoclonal antibody or an antigen-binding fragment thereof comprises a light chain variable domain (VL) containing an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 7.
[Invention 1053]
The monoclonal antibody according to any one of the present inventions 1039 to 1052, wherein the light chain comprises an amino acid sequence in which at least 1 to 10 amino acids of the amino acid sequence described as SEQ ID NO: 9 are modified.
[Invention 1054]
The monoclonal antibody of any of the present invention 1039-1053, wherein the heavy chain comprises an amino acid sequence in which at least 1-10 amino acids of the amino acid sequence described as SEQ ID NO: 10 have been modified.
[Invention 1055]
The monoclonal antibody according to any one of 1039 to 1054 of the present invention, wherein the monoclonal antibody or an antigen-binding fragment thereof specifically binds to MICA protein, MICB protein, or both MICA and MICB protein.
[Invention 1056]
The monoclonal antibody of any of 1039-1055 of the present invention, wherein the monoclonal antibody or an antigen-binding fragment thereof binds to the α-3 domain of MICA protein, MICB protein, or both MICA and MICB protein.
[Invention 1057]
Monoclonal antibodies of the invention 1055 or invention 1056, wherein the MICA protein is a membrane-bound MICA protein, a soluble MICA protein, or both.
[Invention 1058]
A monoclonal antibody of the invention 1055 or the invention 1056, wherein the MICB protein is a membrane-bound MICB protein, a soluble MICB protein, or both.
[Invention 1059]
The monoclonal antibody of any of the present inventions 1039-1058, wherein the monoclonal antibody or antigen-binding fragment thereof is selected from whole immunoglobulin, scFv, Fab, F (ab') 2 or disulfide-bonded Fv.
[Invention 1060]
The monoclonal antibody according to any one of 1039 to 1059 of the present invention, wherein the monoclonal antibody or an antigen-binding fragment thereof is IgG or IgM.
[Invention 1061]
The monoclonal antibody of any of the present inventions 1039-1060, wherein the monoclonal antibody or fragment thereof is humanized or chimeric.
[Invention 1062]
Heavy chain complementarity determining region 1 (CDR1) sequences that are at least 80% identical to SEQ ID NO: 4, heavy chain complementarity determining region 2 (CDR2) sequences that are at least 80% identical to SEQ ID NO: 5. A monoclonal antibody or antigen-binding fragment thereof comprising: at least one of the heavy chain complementarity determining region 3 (CDR3) sequences identical to: 6 and having an amino acid sequence described as SEQ ID NO: 10. The monoclonal antibody or antigen-binding fragment thereof comprising a light chain that does not contain a heavy chain or that does not have the amino acid sequence described as SEQ ID NO: 9.
[Invention 1063]
Heavy chain complementarity determining region 1 (CDR1) sequences that are at least 90% identical to SEQ ID NO: 4, heavy chain complementarity determining region 2 (CDR2) sequences that are at least 90% identical to SEQ ID NO: 5. A monoclonal antibody or antigen-binding fragment thereof comprising: at least one of the heavy chain complementarity determining region 3 (CDR3) sequences identical to: 6 and having an amino acid sequence described as SEQ ID NO: 10. The monoclonal antibody or antigen-binding fragment thereof comprising a light chain that does not contain a heavy chain or that does not have the amino acid sequence described as SEQ ID NO: 9.
[Invention 1064]
Heavy chain complementarity determining region 1 (CDR1) sequences that are at least 95% identical to SEQ ID NO: 4, heavy chain complementarity determining region 2 (CDR2) sequences that are at least 95% identical to SEQ ID NO: 5. A monoclonal antibody or antigen-binding fragment thereof comprising: at least one of the heavy chain complementarity determining region 3 (CDR3) sequences identical to: 6 and having an amino acid sequence described as SEQ ID NO: 10. The monoclonal antibody or antigen-binding fragment thereof comprising a light chain that does not contain a heavy chain or that does not have the amino acid sequence described as SEQ ID NO: 9.
[Invention 1065]
Heavy chain complementarity determining region 1 (CDR1) sequences that are at least 99% identical to SEQ ID NO: 4, heavy chain complementarity determining region 2 (CDR2) sequences that are at least 99% identical to SEQ ID NO: 5. A monoclonal antibody or antigen-binding fragment thereof comprising: at least one of the heavy chain complementarity determining region 3 (CDR3) sequences identical to: 6 and having an amino acid sequence described as SEQ ID NO: 10. The monoclonal antibody or antigen-binding fragment thereof comprising a light chain that does not contain a heavy chain or that does not have the amino acid sequence described as SEQ ID NO: 9.
[Invention 1066]
SEQ ID NO: 4 and 100% identical heavy chain complementarity determining region 1 (CDR1) sequences, SEQ ID NO: 5 and 100% identical heavy chain complementarity determining region 2 (CDR2) sequences, and SEQ ID NO: 6 A heavy chain that contains at least one heavy chain complementarity determining region 3 (CDR3) sequence that is 100% identical to a monoclonal antibody or antigen-binding fragment thereof and that does not have the amino acid sequence described as SEQ ID NO: 10. The monoclonal antibody or antigen binding fragment thereof, comprising a light chain comprising, or not having the amino acid sequence described as SEQ ID NO: 9.
[Invention 1067]
A light chain complementarity determining region 1 (CDR1) sequence in which the monoclonal antibody or an antigen-binding fragment thereof is at least 80% identical to SEQ ID NO: 1 and a light chain complementarity determining region 1 (CDR1) which is at least 80% identical to SEQ ID NO: 2. A monoclonal antibody of any of the present invention 1062-1066 comprising 2 (CDR2) sequences and at least one of the light chain complementarity determining region 3 (CDR3) sequences that are at least 80% identical to SEQ ID NO: 3.
[Invention 1068]
A light chain complementarity determining region 1 (CDR1) sequence in which the monoclonal antibody or an antigen-binding fragment thereof is at least 90% identical to SEQ ID NO: 1 and a light chain complementarity determining region 1 (CDR1) which is at least 90% identical to SEQ ID NO: 2. A monoclonal antibody of any of 1062-1066 of the invention comprising 2 (CDR2) sequences and at least one of the light chain complementarity determining region 3 (CDR3) sequences that are at least 90% identical to SEQ ID NO: 3.
[Invention 1069]
A light chain complementarity determining region 1 (CDR1) sequence in which the monoclonal antibody or an antigen-binding fragment thereof is at least 95% identical to SEQ ID NO: 1 and a light chain complementarity determining region 1 (CDR1) which is at least 95% identical to SEQ ID NO: 2. A monoclonal antibody of any of the present invention 1062-1066 comprising 2 (CDR2) sequences and at least one of the light chain complementarity determining region 3 (CDR3) sequences that are at least 95% identical to SEQ ID NO: 3.
[Invention 1070]
A light chain complementarity determining region 1 (CDR1) sequence in which the monoclonal antibody or an antigen-binding fragment thereof is at least 99% identical to SEQ ID NO: 1 and a light chain complementarity determining region 1 (CDR1) which is at least 99% identical to SEQ ID NO: 2. A monoclonal antibody of any of 1062-1066 of the invention comprising 2 (CDR2) sequences and at least one of the light chain complementarity determining region 3 (CDR3) sequences that are at least 99% identical to SEQ ID NO: 3.
[Invention 1071]
The monoclonal antibody or its antigen-binding fragment has 100% identical light chain complementarity determining regions 1 (CDR1) sequences with SEQ ID NO: 1 and 100% identical light chain complementarity determining regions 2 with SEQ ID NO: 2. Any monoclonal antibody of the invention 1062-1066 comprising a CDR2) sequence and at least one of the light chain complementarity determining region 3 (CDR3) sequences that are 100% identical to SEQ ID NO: 3.
[Invention 1072]
Any of 1062 to 1071 of the invention, wherein the monoclonal antibody or antigen binding fragment thereof comprises a heavy chain variable domain (VH) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 8. Monoclonal antibody.
[Invention 1073]
The monoclonal antibody of the present invention 1072, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises a light chain variable domain (VL) containing an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 7.
[Invention 1074]
Any of 1062 to 1071 of the present invention, wherein the monoclonal antibody or antigen binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 7. Monoclonal antibody.
[Invention 1075]
The monoclonal antibody of the present invention 1074, wherein the monoclonal antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain (VH) containing an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 8.
[Invention 1076]
The monoclonal antibody of any of the present invention 1062-1075, wherein the heavy chain comprises an amino acid sequence in which at least 1-10 amino acids of the amino acid sequence described as SEQ ID NO: 10 have been modified.
[Invention 1077]
The monoclonal antibody of any of the present invention 1062-1076, wherein the light chain comprises an amino acid sequence in which at least 1-10 amino acids of the amino acid sequence described as SEQ ID NO: 9 have been modified.
[Invention 1078]
The monoclonal antibody of any of the present inventions 1062 to 1077, wherein the monoclonal antibody or an antigen-binding fragment thereof specifically binds to a MICA protein, a MICB protein, or both MICA and the MICB protein.
[Invention 1079]
The monoclonal antibody of any of the present invention 1062 to 1078, wherein the monoclonal antibody or an antigen-binding fragment thereof binds to the α-3 domain of MICA protein, MICB protein, or both MICA and MICB protein.
[Invention 1080]
A monoclonal antibody of the present invention 1078 or the present invention 1079, wherein the MICA protein is a membrane-bound MICA protein, a soluble MICA protein, or both.
[Invention 1081]
The monoclonal antibody of the present invention 1078 or the present invention 1079, wherein the MICB protein is a membrane-bound MICB protein, a soluble MICB protein, or both.
[Invention 1082]
The monoclonal antibody of any of the present invention 1062 to 1081, wherein the monoclonal antibody or an antigen-binding fragment thereof is selected from whole immunoglobulin, scFv, Fab, F (ab') 2 or disulfide bond Fv.
[Invention 1083]
The monoclonal antibody according to any one of 1062 to 1082 of the present invention, wherein the monoclonal antibody or an antigen-binding fragment thereof is IgG or IgM.
[Invention 1084]
The monoclonal antibody of any of the present invention 1062 to 1083, wherein the monoclonal antibody or a fragment thereof is humanized or chimeric.
[Invention 1085]
A pharmaceutical composition comprising the monoclonal antibody of any of 1001 to 1084 of the present invention or an antigen-binding fragment thereof, and a pharmaceutically acceptable carrier or excipient.
[Invention 1086]
Light chain complementarity determining region 1 (CDR1) sequences that are at least 80% identical to SEQ ID NO: 1, light chain complementarity determining region 2 (CDR2) sequences that are at least 80% identical to SEQ ID NO: 2, and SEQ ID NO. Treatment of cancer, including the step of administering to an individual an effective amount of a monoclonal antibody or antigen-binding fragment thereof, comprising at least one of the light chain complementarity determining region 3 (CDR3) sequences identical to: 3 by at least 80%. How to treat cancers in individuals in need.
[Invention 1087]
A heavy chain complementarity determining region 1 (CDR1) sequence in which the monoclonal antibody or its antigen-binding fragment is at least 80% identical to SEQ ID NO: 4, and a heavy chain complementarity determining region 1 (CDR1) that is at least 80% identical to SEQ ID NO: 5. The method of the invention 1086 comprising a 2 (CDR2) sequence and at least one of the heavy chain complementarity determining region 3 (CDR3) sequences that are at least 80% identical to SEQ ID NO: 6.
[Invention 1088]
Any of 1086 or 1087 of the invention, wherein the monoclonal antibody or antigen binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 7. Method.
[Invention 1089]
The method of the invention 1088, wherein the monoclonal antibody or antigen binding fragment thereof comprises a heavy chain variable domain (VH) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 8.
[Invention 1090]
Any of 1086 or 1087 of the invention, wherein the monoclonal antibody or antigen binding fragment thereof comprises a heavy chain variable domain (VH) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 8. Method.
[Invention 1091]
The method of the invention 1090, wherein the monoclonal antibody or antigen binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 7.
[Invention 1092]
The method of any of the present inventions 1086 to 1091, wherein the monoclonal antibody or antigen-binding fragment thereof specifically binds to a MICA protein, a MICB protein, or both a MICA and a MICB protein.
[Invention 1093]
The method of any of 1086-1092 of the present invention, wherein the monoclonal antibody or antigen-binding fragment thereof binds to the α-3 domain of MICA protein, MICB protein, or both MICA and MICB protein.
[Invention 1094]
The method of the invention 1092 or the invention 1093, wherein the MICA protein is a membrane-bound MICA protein, a soluble MICA protein, or both.
[Invention 1095]
The method of the invention 1092 or the invention 1093, wherein the MICB protein is a membrane-bound MICB protein, a soluble MICB protein, or both.
[Invention 1096]
The method of any of 1086-1095 of the present invention, wherein the monoclonal antibody or antigen-binding fragment thereof is selected from whole immunoglobulin, scFv, Fab, F (ab') 2 or disulfide-bonded Fv.
[Invention 1097]
The method of any of 1086-1096 of the present invention, wherein the monoclonal antibody or antigen-binding fragment thereof is IgG or IgM.
[Invention 1098]
The method of any of the present invention 1086-1097, wherein the monoclonal antibody or fragment thereof is humanized or chimeric.
[Invention 1099]
The method of any of the present inventions 1086-1098, wherein the monoclonal antibody or antigen-binding fragment thereof reduces levels of soluble MICA protein, soluble MICB protein, or both.
[Invention 1100]
The method of any of 1086-1098 of the present invention, wherein the monoclonal antibody or antigen-binding fragment thereof reduces shedding of soluble MICA protein, soluble MICB protein, or both.
[Invention 1101]
The method of any of 1086-1098 of the present invention, wherein the monoclonal antibody or antigen-binding fragment thereof inhibits shedding of soluble MICA protein, soluble MICB protein, or both.
[Invention 1102]
The method of any of the present inventions 1086-1101, wherein the cancer is hepatocellular carcinoma.
[Invention 1103]
Heavy chain complementarity determining region 1 (CDR1) sequences that are at least 80% identical to SEQ ID NO: 4, heavy chain complementarity determining region 2 (CDR2) sequences that are at least 80% identical to SEQ ID NO: 5. Treatment of cancer, including the step of administering to an individual an effective amount of a monoclonal antibody or antigen-binding fragment thereof, comprising at least one of the heavy chain complementarity determining region 3 (CDR3) sequences identical to: 6 by at least 80%. How to treat cancers in individuals in need.
[Invention 1104]
A light chain complementarity determining region 1 (CDR1) sequence in which the monoclonal antibody or its antigen-binding fragment is at least 80% identical to SEQ ID NO: 1 and a light chain complementarity determining region 1 (CDR1) which is at least 80% identical to SEQ ID NO: 2. The method of the invention 1103, comprising 2 (CDR2) sequences and at least one of the light chain complementarity determining region 3 (CDR3) sequences that are at least 80% identical to SEQ ID NO: 3.
[Invention 1105]
Any of 1103 or 1104 of the invention, wherein the monoclonal antibody or antigen binding fragment thereof comprises a heavy chain variable domain (VH) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 8. Method.
[Invention 1106]
The method of the invention 1105, wherein said monoclonal antibody or antigen binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 7.
[Invention 1107]
Any of 1103 or 1104 of the invention, wherein the monoclonal antibody or antigen binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 7. Method.
[Invention 1108]
The method of 1107 of the invention, wherein the monoclonal antibody or antigen binding fragment thereof comprises a heavy chain variable domain (VH) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 8.
[Invention 1109]
The method of any of 1103 to 1108 of the present invention, wherein the monoclonal antibody or antigen-binding fragment thereof specifically binds to MICA protein, MICB protein, or both MICA and MICB protein.
[Invention 1110]
The method of any of 1103-1109 of the present invention, wherein the monoclonal antibody or antigen-binding fragment thereof binds to the α-3 domain of MICA protein, MICB protein, or both MICA and MICB protein.
[Invention 1111]
The method of the invention 1109 or the invention 1110, wherein the MICA protein is a membrane-bound MICA protein, a soluble MICA protein, or both.
[Invention 1112]
The method of the invention 1109 or the invention 1110, wherein the MICB protein is a membrane-bound MICB protein, a soluble MICB protein, or both.
[Invention 1113]
The method of any of 1103-1112 of the present invention, wherein the monoclonal antibody or antigen-binding fragment thereof is selected from whole immunoglobulin, scFv, Fab, F (ab') 2 or disulfide-bonded Fv.
[Invention 1114]
The method of any of 1103 to 1113 of the present invention, wherein the monoclonal antibody or an antigen-binding fragment thereof is IgG or IgM.
[Invention 1115]
The method of any of the present invention 1103-1114, wherein the monoclonal antibody or fragment thereof is humanized or chimeric.
[Invention 1116]
The method of any of 1103-1115 of the present invention, wherein the monoclonal antibody or antigen-binding fragment thereof reduces the level of soluble MICA protein, soluble MICB protein, or both.
[Invention 1117]
The method of any of 1103-1115 of the present invention, wherein the monoclonal antibody or antigen-binding fragment thereof reduces shedding of soluble MICA protein, soluble MICB protein, or both.
[Invention 1118]
The method of any of 1103-1115 of the present invention, wherein the monoclonal antibody or antigen-binding fragment thereof inhibits shedding of soluble MICA protein, soluble MICB protein, or both.
[Invention 1119]
The method of any of the present invention 1103-1118, wherein the cancer is hepatocellular carcinoma.
[Invention 1120]
Light chain complementarity determining region 1 (CDR1) sequences that are at least 80% identical to SEQ ID NO: 1, light chain complementarity determining region 2 (CDR2) sequences that are at least 80% identical to SEQ ID NO: 2, and SEQ ID NO. Treatment of hepatocellular carcinoma, including the step of administering to an individual an effective amount of a monoclonal antibody or antigen-binding fragment thereof, comprising at least one of the light chain complementarity determining region 3 (CDR3) sequences identical to: 3 by at least 80%. How to treat hepatocellular carcinoma in individuals in need.
[Invention 1121]
A heavy chain complementarity determining region 1 (CDR1) sequence in which the monoclonal antibody or its antigen-binding fragment is at least 80% identical to SEQ ID NO: 4, and a heavy chain complementarity determining region 1 (CDR1) that is at least 80% identical to SEQ ID NO: 5. The method of 1120 of the present invention comprising a 2 (CDR2) sequence and at least one of the heavy chain complementarity determining region 3 (CDR3) sequences that are at least 80% identical to SEQ ID NO: 6.
[Invention 1122]
Any of 1120 or 1121 of the invention, wherein the monoclonal antibody or antigen binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 7. Method.
[Invention 1123]
The method of the invention 1122, wherein the monoclonal antibody or antigen binding fragment thereof comprises a heavy chain variable domain (VH) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 8.
[Invention 1124]
Either 1120 or 1121 of the invention, wherein the monoclonal antibody or antigen binding fragment thereof comprises a heavy chain variable domain (VH) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 8. Method.
[Invention 1125]
The method of 1124 of the invention, wherein the monoclonal antibody or antigen binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 7.
[Invention 1126]
The method of any of the present inventions 1120-1125, wherein the monoclonal antibody or antigen-binding fragment thereof specifically binds to MICA protein, MICB protein, or both MICA and MICB protein.
[Invention 1127]
The method of any of the present inventions 1120-1126, wherein the monoclonal antibody or antigen-binding fragment thereof binds to the α-3 domain of MICA protein, MICB protein, or both MICA and MICB protein.
[Invention 1128]
The method of the invention 1126 or the invention 1127, wherein the MICA protein is a membrane-bound MICA protein, a soluble MICA protein, or both.
[Invention 1129]
The method of the invention 1126 or the invention 1127, wherein the MICB protein is a membrane-bound MICB protein, a soluble MICB protein, or both.
[Invention 1130]
The method of any of the present inventions 1120-1129, wherein the monoclonal antibody or antigen-binding fragment thereof is selected from whole immunoglobulin, scFv, Fab, F (ab') 2 or disulfide-bonded Fv.
[Invention 1131]
The method of any of the present inventions 1120-1130, wherein the monoclonal antibody or antigen-binding fragment thereof is IgG or IgM.
[Invention 1132]
The method of any of the present inventions 1120-1131, wherein the monoclonal antibody or fragment thereof is humanized or chimeric.
[Invention 1133]
The method of any of the present inventions 1120-1132, wherein the monoclonal antibody or antigen-binding fragment thereof reduces levels of soluble MICA protein, soluble MICB protein, or both.
[Invention 1134]
The method of any of the present inventions 1120-1132, wherein the monoclonal antibody or antigen-binding fragment thereof reduces shedding of soluble MICA protein, soluble MICB protein, or both.
[Invention 1135]
The method of any of the present inventions 1120-1132, wherein the monoclonal antibody or antigen-binding fragment thereof inhibits shedding of soluble MICA protein, soluble MICB protein, or both.
[Invention 1136]
Heavy chain complementarity determining region 1 (CDR1) sequences that are at least 80% identical to SEQ ID NO: 4, heavy chain complementarity determining region 2 (CDR2) sequences that are at least 80% identical to SEQ ID NO: 5. Treatment of hepatocellular carcinoma, including the step of administering to an individual an effective amount of a monoclonal antibody or antigen-binding fragment thereof, comprising at least one of the heavy chain complementarity determining region 3 (CDR3) sequences identical to: 6 by at least 80%. How to treat hepatocellular carcinoma in individuals in need.
[Invention 1137]
A light chain complementarity determining region 1 (CDR1) sequence in which the monoclonal antibody or its antigen-binding fragment is at least 80% identical to SEQ ID NO: 1 and a light chain complementarity determining region 1 (CDR1) which is at least 80% identical to SEQ ID NO: 2. The method of 1136 of the invention comprising a 2 (CDR2) sequence and at least one of the light chain complementarity determining region 3 (CDR3) sequences that are at least 80% identical to SEQ ID NO: 3.
[Invention 1138]
Either 1136 or 1137 of the invention, wherein the monoclonal antibody or antigen binding fragment thereof comprises a heavy chain variable domain (VH) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 8. Method.
[Invention 1139]
The method of the invention 1138, wherein the monoclonal antibody or antigen binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 7.
[Invention 1140]
Any of 1136 or 1137 of the invention, wherein the monoclonal antibody or antigen binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 7. Method.
[Invention 1141]
The method of the invention 1140, wherein the monoclonal antibody or antigen binding fragment thereof comprises a heavy chain variable domain (VH) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 8.
[Invention 1142]
The method of any of 1136 to 1141 of the present invention, wherein the monoclonal antibody or antigen-binding fragment thereof specifically binds to MICA protein, MICB protein, or both MICA and MICB protein.
[Invention 1143]
The method of any of 1136 to 1142 of the present invention, wherein the monoclonal antibody or antigen-binding fragment thereof binds to the α-3 domain of MICA protein, MICB protein, or both MICA and MICB protein.
[Invention 1144]
The method of the invention 1142 or the invention 1143, wherein the MICA protein is a membrane-bound MICA protein, a soluble MICA protein, or both.
[Invention 1145]
The method of the invention 1142 or the invention 1143, wherein the MICB protein is a membrane-bound MICB protein, a soluble MICB protein, or both.
[Invention 1146]
The method of any of the present inventions 1136 to 1145, wherein the monoclonal antibody or antigen-binding fragment thereof is selected from whole immunoglobulin, scFv, Fab, F (ab') 2 or disulfide-bonded Fv.
[Invention 1147]
The method according to any one of 1136 to 1146 of the present invention, wherein the monoclonal antibody or an antigen-binding fragment thereof is IgG or IgM.
[Invention 1148]
The method of any of the present invention 1136 to 1147, wherein the monoclonal antibody or fragment thereof is humanized or chimeric.
[Invention 1149]
The method of any of 1136 to 1148 of the present invention, wherein the monoclonal antibody or antigen-binding fragment thereof reduces levels of soluble MICA protein, soluble MICB protein, or both.
[Invention 1150]
The method of any of 1136 to 1148 of the present invention, wherein the monoclonal antibody or antigen-binding fragment thereof reduces shedding of soluble MICA protein, soluble MICB protein, or both.
[Invention 1151]
The method of any of 1136 to 1148 of the present invention, wherein the monoclonal antibody or antigen-binding fragment thereof inhibits shedding of soluble MICA protein, soluble MICB protein, or both.
[Invention 1152]
Light chain complementarity determining region 1 (CDR1) sequences that are at least 80% identical to SEQ ID NO: 1, light chain complementarity determining region 2 (CDR2) sequences that are at least 80% identical to SEQ ID NO: 2, and SEQ ID NO. Soluble MICA protein, soluble, comprising administering to an individual an effective amount of a monoclonal antibody or antigen-binding fragment thereof, comprising at least one of the light chain complementarity determining regions 3 (CDR3) sequences identical to: 3 by at least 80%. Methods of reducing the levels of soluble MICA proteins, soluble MICB proteins, or both in individuals who require reductions in levels of MICB proteins, or both.
[Invention 1153]
A heavy chain complementarity determining region 1 (CDR1) sequence in which the monoclonal antibody or its antigen-binding fragment is at least 80% identical to SEQ ID NO: 4, and a heavy chain complementarity determining region 1 (CDR1) that is at least 80% identical to SEQ ID NO: 5. The method of the present invention 1152 comprising a 2 (CDR2) sequence and at least one of the heavy chain complementarity determining region 3 (CDR3) sequences that are at least 80% identical to SEQ ID NO: 6.
[Invention 1154]
Any of 1152 or 1153 of the invention, wherein the monoclonal antibody or antigen binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 7. Method.
[Invention 1155]
The method of the invention 1154, wherein the monoclonal antibody or antigen binding fragment thereof comprises a heavy chain variable domain (VH) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 8.
[Invention 1156]
Any of 1152 or 1153 of the invention, wherein the monoclonal antibody or antigen binding fragment thereof comprises a heavy chain variable domain (VH) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 8. Method.
[Invention 1157]
The method of the invention 1156, wherein said monoclonal antibody or antigen binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 7.
[Invention 1158]
The method of any of 1152-1157 of the present invention, wherein the monoclonal antibody or antigen-binding fragment thereof specifically binds to MICA protein, MICB protein, or both MICA and MICB protein.
[Invention 1159]
The method of any of 1152-1158 of the present invention, wherein the monoclonal antibody or antigen-binding fragment thereof binds to the α-3 domain of MICA protein, MICB protein, or both MICA and MICB protein.
[Invention 1160]
The method of the invention 1158 or the invention 1159, wherein the MICA protein is a soluble MICA protein.
[Invention 1161]
The method of the invention 1158 or the invention 1159, wherein the MICB protein is a soluble MICB protein.
[Invention 1162]
The method of any of 1152-1161 of the present invention, wherein the monoclonal antibody or antigen-binding fragment thereof is selected from whole immunoglobulin, scFv, Fab, F (ab') 2 or disulfide-bonded Fv.
[Invention 1163]
The method of any of 1152 to 1162 of the present invention, wherein the monoclonal antibody or antigen-binding fragment thereof is IgG or IgM.
[Invention 1164]
The method of any of 1152 to 1163 of the present invention, wherein the monoclonal antibody or fragment thereof is humanized or chimeric.
[Invention 1165]
The monoclonal antibody or antigen-binding fragment thereof reduces or inhibits shedding of soluble MICA protein, soluble MICB protein, or both, thereby reducing the level of soluble MICA protein, soluble MICB protein, or both in an individual. Any method of the present invention 1152-1164.
[Invention 1166]
The method of any of 1152-1165 of the present invention, wherein said individual has cancer characterized by elevated levels of soluble MICA protein, soluble MICB protein, or both.
[Invention 1167]
The method of the present invention 1166, wherein the cancer is hepatocellular carcinoma.
[Invention 1168]
Heavy chain complementarity determining region 1 (CDR1) sequences that are at least 80% identical to SEQ ID NO: 4, heavy chain complementarity determining region 2 (CDR2) sequences that are at least 80% identical to SEQ ID NO: 5. A soluble MICA protein, soluble, comprising administering to an individual an effective amount of a monoclonal antibody or antigen-binding fragment thereof, comprising at least one of the heavy chain complementarity determining region 3 (CDR3) sequences identical to: 6 by at least 80%. Methods of reducing the levels of soluble MICA proteins, soluble MICB proteins, or both in individuals who require reductions in levels of MICB proteins, or both.
[Invention 1169]
A light chain complementarity determining region 1 (CDR1) sequence in which the monoclonal antibody or its antigen-binding fragment is at least 80% identical to SEQ ID NO: 1 and a light chain complementarity determining region 1 (CDR1) which is at least 80% identical to SEQ ID NO: 2. The method of 1168 of the invention comprising a 2 (CDR2) sequence and at least one of the light chain complementarity determining region 3 (CDR3) sequences that are at least 80% identical to SEQ ID NO: 3.
[Invention 1170]
Either 1168 or 1169 of the invention, wherein the monoclonal antibody or antigen binding fragment thereof comprises a heavy chain variable domain (VH) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 8. Method.
[Invention 1171]
The method of the invention 1170, wherein the monoclonal antibody or antigen binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 7.
[Invention 1172]
Any of 1168 or 1169 of the invention, wherein the monoclonal antibody or antigen binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 7. Method.
[Invention 1173]
The method of 1172 of the invention, wherein the monoclonal antibody or antigen binding fragment thereof comprises a heavy chain variable domain (VH) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 8.
[Invention 1174]
The method of any of the present inventions 1168 to 1173, wherein the monoclonal antibody or antigen-binding fragment thereof specifically binds to a MICA protein, a MICB protein, or both a MICA and a MICB protein.
[Invention 1175]
The method of any of the present inventions 1168 to 1174, wherein the monoclonal antibody or antigen-binding fragment thereof binds to the α-3 domain of MICA protein, MICB protein, or both MICA and MICB protein.
[Invention 1176]
The method of the invention 1174 or the invention 1175, wherein the MICA protein is a soluble MICA protein.
[Invention 1177]
The method of the invention 1174 or the invention 1175, wherein the MICB protein is a soluble MICB protein.
[Invention 1178]
The method of any of the present inventions 1168 to 1177, wherein the monoclonal antibody or antigen-binding fragment thereof is selected from whole immunoglobulin, scFv, Fab, F (ab') 2 or disulfide-bonded Fv.
[Invention 1179]
The method of any of the present inventions 1168 to 1178, wherein the monoclonal antibody or antigen-binding fragment thereof is IgG or IgM.
[Invention 1180]
The method of any of the present inventions 1168 to 1179, wherein the monoclonal antibody or fragment thereof is humanized or chimeric.
[Invention 1181]
The monoclonal antibody or antigen-binding fragment thereof reduces or inhibits shedding of soluble MICA protein, soluble MICB protein, or both, thereby reducing the level of soluble MICA protein, soluble MICB protein, or both in an individual. The method according to any one of the present inventions 1168 to 1180.
[Invention 1182]
The method of any of 1168 to 1181 of the present invention, wherein said individual has cancer characterized by elevated levels of soluble MICA protein, soluble MICB protein, or both.
[Invention 1183]
The method of 1182 of the present invention, wherein the cancer is hepatocellular carcinoma.
[Invention 1184]
A monoclonal antibody according to any one of 1001 to 1084 of the present invention or an antigen-binding fragment thereof for use in the treatment of cancer in an individual in need of treatment for cancer.
[Invention 1185]
The monoclonal antibody of any of 1001 to 1084 of the present invention for use in the preparation of a pharmaceutical for treating cancer in an individual in need of treatment for cancer.
[Invention 1186]
A monoclonal antibody for use of the invention 1184 or the invention 1185, wherein the cancer is hepatocellular carcinoma.
Claims (17)
前記CDR1配列がSEQ ID NO: 1と少なくとも95%同一であり、前記CDR2配列がSEQ ID NO: 2と少なくとも95%同一であり、かつ前記CDR3配列がSEQ ID NO: 3と少なくとも95%同一である、
前記CDR1配列がSEQ ID NO: 1と少なくとも99%同一であり、前記CDR2配列がSEQ ID NO: 2と少なくとも99%同一であり、かつ前記CDR3配列がSEQ ID NO: 3と少なくとも99%同一である、または
前記CDR1配列がSEQ ID NO: 1と100%同一であり、前記CDR2配列がSEQ ID NO: 2と100%同一であり、かつ前記CDR3配列がSEQ ID NO: 3と100%同一である、
請求項6記載のモノクローナル抗体またはその抗原結合断片。 The CDR1 sequence is at least 90% identical to SEQ ID NO: 1, the CDR2 sequence is at least 90% identical to SEQ ID NO: 2 , and the CDR3 sequence is at least 90% identical to SEQ ID NO: 3. be,
The CDR1 sequence is at least 95% identical to SEQ ID NO: 1, the CDR2 sequence is at least 95% identical to SEQ ID NO: 2, and the CDR3 sequence is at least 95% identical to SEQ ID NO: 3. be,
The CDR1 sequence is at least 99% identical to SEQ ID NO: 1, the CDR2 sequence is at least 99% identical to SEQ ID NO: 2, and the CDR3 sequence is at least 99% identical to SEQ ID NO: 3. Yes or
The CDR1 sequence is 100% identical to SEQ ID NO: 1, the CDR2 sequence is 100% identical to SEQ ID NO: 2, and the CDR3 sequence is 100% identical to SEQ ID NO: 3.
The monoclonal antibody according to claim 6 or an antigen-binding fragment thereof.
SEQ ID NO: 4と少なくとも80%同一の重鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 5と少なくとも80%同一の重鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 6と少なくとも80%同一の重鎖相補性決定領域3 (CDR3)配列の少なくとも1つ、
SEQ ID NO: 4と少なくとも90%同一の重鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 5と少なくとも90%同一の重鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 6と少なくとも90%同一の重鎖相補性決定領域3 (CDR3)配列の少なくとも1つ、
SEQ ID NO: 4と少なくとも95%同一の重鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 5と少なくとも95%同一の重鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 6と少なくとも95%同一の重鎖相補性決定領域3 (CDR3)配列の少なくとも1つ、
SEQ ID NO: 4と少なくとも99%同一の重鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 5と少なくとも99%同一の重鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 6と少なくとも99%同一の重鎖相補性決定領域3 (CDR3)配列の少なくとも1つ、または
SEQ ID NO: 4と100%同一の重鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 5と100%同一の重鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 6と100%同一の重鎖相補性決定領域3 (CDR3)配列の少なくとも1つ。 The monoclonal antibody or antigen-binding fragment thereof according to claim 6 or 7, wherein the monoclonal antibody or antigen-binding fragment thereof comprises:
Heavy chain complementarity determining region 1 (CDR1) sequences that are at least 80% identical to SEQ ID NO: 4, heavy chain complementarity determining region 2 (CDR2) sequences that are at least 80% identical to SEQ ID NO: 5. : At least one of the heavy chain complementarity determining region 3 (CDR3) sequences that are at least 80% identical to 6
Heavy chain complementarity determining region 1 (CDR1) sequences that are at least 90% identical to SEQ ID NO: 4, heavy chain complementarity determining region 2 (CDR2) sequences that are at least 90% identical to SEQ ID NO: 5. : At least one of the heavy chain complementarity determining region 3 (CDR3) sequences that are at least 90% identical to 6.
Heavy chain complementarity determining region 1 (CDR1) sequences that are at least 95% identical to SEQ ID NO: 4, heavy chain complementarity determining region 2 (CDR2) sequences that are at least 95% identical to SEQ ID NO: 5. : At least one of the heavy chain complementarity determining region 3 (CDR3) sequences that are at least 95% identical to 6.
Heavy chain complementarity determining region 1 (CDR1) sequences that are at least 99% identical to SEQ ID NO: 4, heavy chain complementarity determining region 2 (CDR2) sequences that are at least 99% identical to SEQ ID NO: 5. : At least one of the heavy chain complementarity determining region 3 (CDR3) sequences that are at least 99% identical to 6 or
SEQ ID NO: 4 and 100% identical heavy chain complementarity determining region 1 (CDR1) sequences, SEQ ID NO: 5 and 100% identical heavy chain complementarity determining region 2 (CDR2) sequences, and SEQ ID NO: 6 At least one of the heavy chain complementarity determining regions 3 (CDR3) sequences that are 100% identical .
前記CDR1配列がSEQ ID NO: 4と少なくとも95%同一であり、前記CDR2配列がSEQ ID NO: 5と少なくとも95%同一であり、かつ前記CDR3配列がSEQ ID NO: 6と少なくとも95%同一である、
前記CDR1配列がSEQ ID NO: 4と少なくとも99%同一であり、前記CDR2配列がSEQ ID NO: 5と少なくとも99%同一であり、かつ前記CDR3配列がSEQ ID NO: 6と少なくとも99%同一である、または
前記CDR1配列がSEQ ID NO: 4と100%同一であり、前記CDR2配列がSEQ ID NO: 5と100%同一であり、かつ前記CDR3配列がSEQ ID NO: 6と100%同一である、
請求項9記載のモノクローナル抗体またはその抗原結合断片。 The CDR1 sequence is at least 90% identical to SEQ ID NO: 4, the CDR2 sequence is at least 90% identical to SEQ ID NO: 5, and the CDR3 sequence is at least 90% identical to SEQ ID NO: 6 . Yes ,
The CDR1 sequence is at least 95% identical to SEQ ID NO: 4, the CDR2 sequence is at least 95% identical to SEQ ID NO: 5, and the CDR3 sequence is at least 95% identical to SEQ ID NO: 6. be,
The CDR1 sequence is at least 99% identical to SEQ ID NO: 4, the CDR2 sequence is at least 99% identical to SEQ ID NO: 5, and the CDR3 sequence is at least 99% identical to SEQ ID NO: 6. Yes or
The CDR1 sequence is 100% identical to SEQ ID NO: 4, the CDR2 sequence is 100% identical to SEQ ID NO: 5, and the CDR3 sequence is 100% identical to SEQ ID NO: 6.
The monoclonal antibody according to claim 9 or an antigen-binding fragment thereof.
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 7として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む軽鎖可変ドメイン(VL)を含む、請求項6～10のいずれか一項記載のモノクローナル抗体またはその抗原結合断片。 The monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain variable domain (VH) containing an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 8 and / or .
Any one of claims 6-10, wherein the monoclonal antibody or antigen binding fragment thereof comprises a light chain variable domain (VL) comprising an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 7. The monoclonal antibody or antigen-binding fragment thereof according to the section .
前記軽鎖が、SEQ ID NO: 9として記載されるアミノ酸配列の少なくとも1～10個のアミノ酸が改変されているアミノ酸配列を含む、
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方に特異的に結合する、
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方のα-3ドメインに結合する、
前記モノクローナル抗体またはその抗原結合断片が、免疫グロブリン全体、scFv、Fab、F(ab')2またはジスルフィド結合Fvから選択される、
前記モノクローナル抗体またはその抗原結合断片が、IgGまたはIgMである、および／または
前記モノクローナル抗体またはその断片が、ヒト化されているか、またはキメラであり、任意で、
前記MICAタンパク質が、膜結合MICAタンパク質、可溶性MICAタンパク質、またはその両方である、または
前記MICBタンパク質が、膜結合MICBタンパク質、可溶性MICBタンパク質、またはその両方である、
請求項1～11のいずれか一項記載のモノクローナル抗体またはその抗原結合断片。 The heavy chain comprises an amino acid sequence in which at least 1-10 amino acids of the amino acid sequence described as SEQ ID NO: 10 have been modified .
The light chain comprises an amino acid sequence in which at least 1-10 amino acids of the amino acid sequence described as SEQ ID NO: 9 have been modified .
The monoclonal antibody or its antigen-binding fragment specifically binds to a MICA protein, a MICB protein, or both a MICA and a MICB protein.
The monoclonal antibody or antigen-binding fragment thereof binds to the α-3 domain of MICA protein, MICB protein, or both MICA and MICB protein.
The monoclonal antibody or antigen-binding fragment thereof is selected from whole immunoglobulin, scFv, Fab, F (ab') 2 or disulfide-bonded Fv.
The monoclonal antibody or antigen-binding fragment thereof is IgG or IgM, and / or
The monoclonal antibody or fragment thereof is humanized or chimeric and optionally.
The MICA protein is, or is, a membrane-bound MICA protein, a soluble MICA protein, or both.
The MICB protein is a membrane-bound MICB protein, a soluble MICB protein, or both.
The monoclonal antibody according to any one of claims 1 to 11 or an antigen-binding fragment thereof.
SEQ ID NO: 4と少なくとも80%同一の重鎖相補性決定領域1 (CDR1)配列、SEQ ID NO: 5と少なくとも80%同一の重鎖相補性決定領域2 (CDR2)配列、およびSEQ ID NO: 6と少なくとも80%同一の重鎖相補性決定領域3 (CDR3)配列の少なくとも1つを含む、
それを必要とする個体においてがんを処置する方法および／または可溶性MICAタンパク質、可溶性MICBタンパク質またはその両方のレベルを低減する方法における使用のための、モノクローナル抗体またはその抗原結合断片。 Light chain complementarity determining region 1 (CDR1) sequences that are at least 80% identical to SEQ ID NO: 1, light chain complementarity determining region 2 (CDR2) sequences that are at least 80% identical to SEQ ID NO: 2, and SEQ ID NO. : At least one of the light chain complementarity determining regions 3 (CDR3) sequences that are at least 80% identical to 3 and / or
Heavy chain complementarity determining region 1 (CDR1) sequences that are at least 80% identical to SEQ ID NO: 4, heavy chain complementarity determining region 2 (CDR2) sequences that are at least 80% identical to SEQ ID NO: 5. : Contains at least one of the heavy chain complementarity determining region 3 (CDR3) sequences that are at least 80% identical to 6.
Monoclonal antibodies or antigen-binding fragments thereof for use in methods of treating cancer in individuals in need thereof and / or reducing levels of soluble MICA protein, soluble MICB protein or both .
前記モノクローナル抗体またはその抗原結合断片が、SEQ ID NO: 8として記載されるアミノ酸配列と少なくとも80%同一のアミノ酸配列を含む重鎖可変ドメイン(VH)を含む、
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方に特異的に結合する、
前記モノクローナル抗体またはその抗原結合断片が、MICAタンパク質、MICBタンパク質、またはMICAおよびMICBタンパク質の両方のα-3ドメインに結合する、
前記モノクローナル抗体またはその抗原結合断片が、免疫グロブリン全体、scFv、Fab、F(ab')2またはジスルフィド結合Fvから選択される、
前記モノクローナル抗体またはその抗原結合断片が、IgGまたはIgMである、および／または
前記モノクローナル抗体またはその断片が、ヒト化されているか、またはキメラであり、任意で、
前記MICAタンパク質が、膜結合MICAタンパク質、可溶性MICAタンパク質、またはその両方である、または
前記MICBタンパク質が、膜結合MICBタンパク質、可溶性MICBタンパク質、またはその両方である、
請求項14記載の使用のためのモノクローナル抗体またはその抗原結合断片。 The monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain (VL) containing an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 7.
The monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain variable domain (VH) containing an amino acid sequence that is at least 80% identical to the amino acid sequence described as SEQ ID NO: 8.
The monoclonal antibody or its antigen-binding fragment specifically binds to a MICA protein, a MICB protein, or both a MICA and a MICB protein.
The monoclonal antibody or antigen-binding fragment thereof binds to the α-3 domain of MICA protein, MICB protein, or both MICA and MICB protein.
The monoclonal antibody or antigen-binding fragment thereof is selected from whole immunoglobulin, scFv, Fab, F (ab') 2 or disulfide-bonded Fv .
The monoclonal antibody or antigen-binding fragment thereof is IgG or IgM, and / or
The monoclonal antibody or fragment thereof is humanized or chimeric and optionally.
The MICA protein is, or is, a membrane-bound MICA protein, a soluble MICA protein, or both.
The MICB protein is a membrane-bound MICB protein, a soluble MICB protein, or both.
A monoclonal antibody or antigen-binding fragment thereof for use according to claim 14 .
(ii) 前記モノクローナル抗体またはその抗原結合断片が、可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のシェディングを低減する、または
(iii)前記モノクローナル抗体またはその抗原結合断片が、可溶性MICAタンパク質、可溶性MICBタンパク質、またはその両方のシェディングを阻害する、および／または
(b) がんが肝細胞癌である、
請求項14または15記載の使用のためのモノクローナル抗体またはその抗原結合断片。 (a) (i) The individual has a cancer characterized by elevated levels of soluble MICA protein, soluble MICB protein, or both.
(ii) The monoclonal antibody or antigen-binding fragment thereof reduces shedding of soluble MICA protein, soluble MICB protein, or both.
(iii) The monoclonal antibody or antigen-binding fragment thereof inhibits shedding of soluble MICA protein, soluble MICB protein, or both, and / or
(b) The cancer is hepatocellular carcinoma,
A monoclonal antibody or antigen-binding fragment thereof for use according to claim 14 or 15 .
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| WO2020035345A1 (en) | 2018-08-14 | 2020-02-20 | Innate Pharma | Treatment of colorectal cancer by a combination of an anti-mica antibody and an anti-nkg2a antibody |
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