JP2020511481A5 - - Google Patents
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- JP2020511481A5 JP2020511481A5 JP2019551449A JP2019551449A JP2020511481A5 JP 2020511481 A5 JP2020511481 A5 JP 2020511481A5 JP 2019551449 A JP2019551449 A JP 2019551449A JP 2019551449 A JP2019551449 A JP 2019551449A JP 2020511481 A5 JP2020511481 A5 JP 2020511481A5
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- Prior art keywords
- seq
- amino acid
- acid sequence
- variable domain
- heavy chain
- Prior art date
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- 125000003275 alpha amino acid group Chemical group 0.000 claims 92
- 150000001413 amino acids Chemical class 0.000 claims 48
- 239000000203 mixture Substances 0.000 claims 33
- 230000002195 synergetic Effects 0.000 claims 29
- 201000011510 cancer Diseases 0.000 claims 15
- 239000000427 antigen Substances 0.000 claims 11
- 102000038129 antigens Human genes 0.000 claims 11
- 108091007172 antigens Proteins 0.000 claims 11
- 206010029592 Non-Hodgkin's lymphomas Diseases 0.000 claims 10
- 102000005614 monoclonal antibodies Human genes 0.000 claims 10
- 108010045030 monoclonal antibodies Proteins 0.000 claims 10
- 230000001225 therapeutic Effects 0.000 claims 8
- 206010025323 Lymphomas Diseases 0.000 claims 5
- 206010028980 Neoplasm Diseases 0.000 claims 4
- 206010025310 Other lymphomas Diseases 0.000 claims 4
- 239000002246 antineoplastic agent Substances 0.000 claims 4
- 238000002560 therapeutic procedure Methods 0.000 claims 4
- 210000004881 tumor cells Anatomy 0.000 claims 4
- 102100013078 CD47 Human genes 0.000 claims 3
- 101700033237 CD47 Proteins 0.000 claims 3
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims 3
- 206010039491 Sarcoma Diseases 0.000 claims 3
- 201000005510 acute lymphocytic leukemia Diseases 0.000 claims 3
- 210000004027 cells Anatomy 0.000 claims 3
- 206010000880 Acute myeloid leukaemia Diseases 0.000 claims 2
- 206010008958 Chronic lymphocytic leukaemia Diseases 0.000 claims 2
- STQGQHZAVUOBTE-VGBVRHCVSA-N DAUNOMYCIN Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims 2
- 206010020243 Hodgkin's disease Diseases 0.000 claims 2
- RCINICONZNJXQF-MZXODVADSA-N Intaxel Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims 2
- 206010024324 Leukaemias Diseases 0.000 claims 2
- 208000000429 Leukemia, Lymphocytic, Chronic, B-Cell Diseases 0.000 claims 2
- 208000008456 Leukemia, Myelogenous, Chronic, BCR-ABL Positive Diseases 0.000 claims 2
- 208000007046 Leukemia, Myeloid, Acute Diseases 0.000 claims 2
- 208000009285 Lymphoma, Large B-Cell, Diffuse Diseases 0.000 claims 2
- 229960001592 Paclitaxel Drugs 0.000 claims 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 2
- 102000004965 antibodies Human genes 0.000 claims 2
- 108090001123 antibodies Proteins 0.000 claims 2
- 201000006934 chronic myeloid leukemia Diseases 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 230000000527 lymphocytic Effects 0.000 claims 2
- 239000012528 membrane Substances 0.000 claims 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims 2
- 229930003347 taxol Natural products 0.000 claims 2
- ZROHGHOFXNOHSO-BNTLRKBRSA-L (1R,2R)-cyclohexane-1,2-diamine;oxalate;platinum(2+) Chemical compound [H][N]([C@@H]1CCCC[C@H]1[N]1([H])[H])([H])[Pt]11OC(=O)C(=O)O1 ZROHGHOFXNOHSO-BNTLRKBRSA-L 0.000 claims 1
- AOJJSUZBOXZQNB-TZSSRYMLSA-N ADRIAMYCIN Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims 1
- 229940100198 ALKYLATING AGENTS Drugs 0.000 claims 1
- 208000009956 Adenocarcinoma Diseases 0.000 claims 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 claims 1
- 210000001130 Astrocytes Anatomy 0.000 claims 1
- 208000003950 B-Cell Lymphoma Diseases 0.000 claims 1
- 206010004593 Bile duct cancer Diseases 0.000 claims 1
- 206010005003 Bladder cancer Diseases 0.000 claims 1
- 206010005949 Bone cancer Diseases 0.000 claims 1
- GXJABQQUPOEUTA-RDJZCZTQSA-N Bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 claims 1
- 208000003174 Brain Neoplasms Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims 1
- 229960004562 Carboplatin Drugs 0.000 claims 1
- OLESAACUTLOWQZ-UHFFFAOYSA-L Carboplatin Chemical compound O=C1O[Pt]([N]([H])([H])[H])([N]([H])([H])[H])OC(=O)C11CCC1 OLESAACUTLOWQZ-UHFFFAOYSA-L 0.000 claims 1
- BLMPQMFVWMYDKT-NZTKNTHTSA-N Carfilzomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)[C@]1(C)OC1)NC(=O)CN1CCOCC1)CC1=CC=CC=C1 BLMPQMFVWMYDKT-NZTKNTHTSA-N 0.000 claims 1
- 206010008342 Cervix carcinoma Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 229960000975 Daunorubicin Drugs 0.000 claims 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N Docetaxel Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims 1
- 229960004679 Doxorubicin Drugs 0.000 claims 1
- 229960001904 EPIRUBICIN Drugs 0.000 claims 1
- AOJJSUZBOXZQNB-VTZDEGQISA-N EPIRUBICIN Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 claims 1
- 206010014733 Endometrial cancer Diseases 0.000 claims 1
- 210000003743 Erythrocytes Anatomy 0.000 claims 1
- 229960005420 Etoposide Drugs 0.000 claims 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N Etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims 1
- 208000006168 Ewing Sarcoma Diseases 0.000 claims 1
- 206010017758 Gastric cancer Diseases 0.000 claims 1
- SDUQYLNIPVEERB-QPPQHZFASA-N Gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims 1
- 208000005017 Glioblastoma Diseases 0.000 claims 1
- 206010018338 Glioma Diseases 0.000 claims 1
- 208000001258 Hemangiosarcoma Diseases 0.000 claims 1
- 201000006743 Hodgkin's lymphoma Diseases 0.000 claims 1
- 206010021042 Hypopharyngeal cancer Diseases 0.000 claims 1
- 229960000908 Idarubicin Drugs 0.000 claims 1
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin hydrochloride Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 claims 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N Irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims 1
- 206010024305 Leukaemia monocytic Diseases 0.000 claims 1
- 210000004072 Lung Anatomy 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 206010025650 Malignant melanoma Diseases 0.000 claims 1
- 210000002418 Meninges Anatomy 0.000 claims 1
- 229960001156 Mitoxantrone Drugs 0.000 claims 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N Mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims 1
- 210000002464 Muscle, Smooth, Vascular Anatomy 0.000 claims 1
- 206010028549 Myeloid leukaemia Diseases 0.000 claims 1
- 206010029260 Neuroblastoma Diseases 0.000 claims 1
- 208000002154 Non-Small-Cell Lung Carcinoma Diseases 0.000 claims 1
- 108009000071 Non-small cell lung cancer Proteins 0.000 claims 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 208000008443 Pancreatic Carcinoma Diseases 0.000 claims 1
- 206010057249 Phagocytosis Diseases 0.000 claims 1
- 208000003359 Plasma Cell Leukemia Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 210000003324 RBC Anatomy 0.000 claims 1
- 206010038038 Rectal cancer Diseases 0.000 claims 1
- 208000006265 Renal Cell Carcinoma Diseases 0.000 claims 1
- 102100004476 SIRPA Human genes 0.000 claims 1
- 101710024246 SIRPA Proteins 0.000 claims 1
- 206010073145 Soft tissue cancer Diseases 0.000 claims 1
- 210000000278 Spinal Cord Anatomy 0.000 claims 1
- 206010042863 Synovial sarcoma Diseases 0.000 claims 1
- 206010042971 T-cell lymphoma Diseases 0.000 claims 1
- 206010057644 Testis cancer Diseases 0.000 claims 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N Topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims 1
- 210000001635 Urinary Tract Anatomy 0.000 claims 1
- 206010046766 Uterine cancer Diseases 0.000 claims 1
- 229960003048 Vinblastine Drugs 0.000 claims 1
- HOFQVRTUGATRFI-XQKSVPLYSA-N Vinblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 HOFQVRTUGATRFI-XQKSVPLYSA-N 0.000 claims 1
- 229960004528 Vincristine Drugs 0.000 claims 1
- 206010047802 Waldenstrom's macroglobulinaemias Diseases 0.000 claims 1
- 230000002378 acidificating Effects 0.000 claims 1
- 201000005188 adrenal gland cancer Diseases 0.000 claims 1
- 230000002776 aggregation Effects 0.000 claims 1
- 238000004220 aggregation Methods 0.000 claims 1
- 239000002168 alkylating agent Substances 0.000 claims 1
- 201000003076 angiosarcoma Diseases 0.000 claims 1
- 230000000340 anti-metabolite Effects 0.000 claims 1
- 239000002256 antimetabolite Substances 0.000 claims 1
- 239000003972 antineoplastic antibiotic Substances 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 229960001467 bortezomib Drugs 0.000 claims 1
- 229960002438 carfilzomib Drugs 0.000 claims 1
- 108010021331 carfilzomib Proteins 0.000 claims 1
- 230000030833 cell death Effects 0.000 claims 1
- 230000001413 cellular Effects 0.000 claims 1
- 201000010881 cervical cancer Diseases 0.000 claims 1
- 108091006028 chimera Proteins 0.000 claims 1
- 229960004316 cisplatin Drugs 0.000 claims 1
- -1 citarabin Chemical compound 0.000 claims 1
- 230000034994 death Effects 0.000 claims 1
- 230000001809 detectable Effects 0.000 claims 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 claims 1
- 229960003668 docetaxel Drugs 0.000 claims 1
- 230000002124 endocrine Effects 0.000 claims 1
- 201000004101 esophageal cancer Diseases 0.000 claims 1
- 201000008808 fibrosarcoma Diseases 0.000 claims 1
- 230000003325 follicular Effects 0.000 claims 1
- 238000005755 formation reaction Methods 0.000 claims 1
- 201000000052 gastrinoma Diseases 0.000 claims 1
- 229960005277 gemcitabine Drugs 0.000 claims 1
- 201000010536 head and neck cancer Diseases 0.000 claims 1
- 201000006866 hypopharynx cancer Diseases 0.000 claims 1
- 230000002163 immunogen Effects 0.000 claims 1
- 230000001939 inductive effect Effects 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 229960004768 irinotecan Drugs 0.000 claims 1
- 201000005249 lung adenocarcinoma Diseases 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 230000000394 mitotic Effects 0.000 claims 1
- 201000006894 monocytic leukemia Diseases 0.000 claims 1
- 201000009251 multiple myeloma Diseases 0.000 claims 1
- 230000003387 muscular Effects 0.000 claims 1
- 201000003793 myelodysplastic syndrome Diseases 0.000 claims 1
- 201000000050 myeloid neoplasm Diseases 0.000 claims 1
- 201000004458 myoma Diseases 0.000 claims 1
- 201000008968 osteosarcoma Diseases 0.000 claims 1
- 229960001756 oxaliplatin Drugs 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 230000008782 phagocytosis Effects 0.000 claims 1
- 201000002511 pituitary cancer Diseases 0.000 claims 1
- 229910052697 platinum Inorganic materials 0.000 claims 1
- 230000002062 proliferating Effects 0.000 claims 1
- 201000001275 rectum cancer Diseases 0.000 claims 1
- 201000000849 skin cancer Diseases 0.000 claims 1
- 201000011549 stomach cancer Diseases 0.000 claims 1
- 201000010874 syndrome Diseases 0.000 claims 1
- 201000003120 testicular cancer Diseases 0.000 claims 1
- 201000002510 thyroid cancer Diseases 0.000 claims 1
- 210000001519 tissues Anatomy 0.000 claims 1
- 229960000303 topotecan Drugs 0.000 claims 1
- LXZZYRPGZAFOLE-UHFFFAOYSA-L transplatin Chemical compound [H][N]([H])([H])[Pt](Cl)(Cl)[N]([H])([H])[H] LXZZYRPGZAFOLE-UHFFFAOYSA-L 0.000 claims 1
- 201000005112 urinary bladder cancer Diseases 0.000 claims 1
- 201000011531 vascular cancer Diseases 0.000 claims 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims 1
Claims (16)
(i)配列番号1を含むHCDR1、配列番号4を含むHCDR2、配列番号7を含むHCDR3、配列番号11を含むLCDR1、配列番号15を含むLCDR2、配列番号18を含むLCDR3;
(ii)配列番号1を含むHCDR1、配列番号4を含むHCDR2、配列番号8を含むHCDR3、配列番号11を含むLCDR1、配列番号15を含むLCDR2、配列番号18を含むLCDR3;
(iii)配列番号2を含むHCDR1、配列番号5を含むHCDR2、配列番号9を含むHCDR3、配列番号12を含むLCDR1、配列番号16を含むLCDR2、配列番号19を含むLCDR3;
(iv)配列番号3を含むHCDR1、配列番号6を含むHCDR2、配列番号10を含むHCDR3、配列番号14を含むLCDR1、配列番号17を含むLCDR2、配列番号19を含むLCDR3;
(v)配列番号3を含むHCDR1、配列番号6を含むHCDR2、配列番号10を含むHCDR3、配列番号14を含むLCDR1、配列番号17を含むLCDR2、配列番号18を含むLCDR3
からなる群から選択されることを特徴とする相乗的治療の組合わせ。 In the combination of synergistic treatments according to any one of claims 1 to 6, the antibody or antigen-binding fragment thereof is a variable heavy chain CDR1 (HCDR1), a variable heavy chain CDR2 (HCDR2), and a variable heavy chain. Includes combinations of CDR3 (HCDR3), variable light chain CDR1 (LCDR1), variable light chain CDR2 (LCDR2), and variable light chain CDR3 (LCDR3), wherein the combination is:
(I) HCDR1 containing SEQ ID NO: 1, HCDR2 containing SEQ ID NO: 4, HCDR3 containing SEQ ID NO: 7, LCDR1 containing SEQ ID NO: 11, LCDR2 containing SEQ ID NO: 15, LCDR3 containing SEQ ID NO: 18;
(Ii) HCDR1 containing SEQ ID NO: 1, HCDR2 containing SEQ ID NO: 4, HCDR3 containing SEQ ID NO: 8, LCDR1 containing SEQ ID NO: 11, LCDR2 containing SEQ ID NO: 15, LCDR3 containing SEQ ID NO: 18;
(Iii) HCDR1 including SEQ ID NO: 2, HCDR2 including SEQ ID NO: 5, HCDR3 including SEQ ID NO: 9, LCDR1 including SEQ ID NO: 12, LCDR2 including SEQ ID NO: 16, LCDR3 including SEQ ID NO: 19;
(Iv) SEQ ID NO: 3 including HCDR1, HCDR2 comprising SEQ ID NO: 6, HCDR3 comprising SEQ ID NO: 10, LCDR1 comprising SEQ ID NO: 14, LCDR2 comprising SEQ ID NO: 17, LCDR3 comprising SEQ ID NO: 19;
(V) HCDR1 containing SEQ ID NO: 3, HCDR2 containing SEQ ID NO: 6, HCDR3 containing SEQ ID NO: 10, LCDR1 containing SEQ ID NO: 14, LCDR2 containing SEQ ID NO: 17, LCDR3 containing SEQ ID NO: 18.
Synergistic therapeutic combination which is characterized and selected Turkey from the group consisting of.
(i)配列番号21のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号41を含む軽鎖可変ドメイン;
(ii)配列番号23のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号43を含む軽鎖可変ドメイン;
(iii)配列番号34のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号49を含む軽鎖可変ドメイン;
(iv)配列番号36のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号52を含む軽鎖可変ドメイン;
(v)配列番号38のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号52を含む軽鎖可変ドメイン;
(vi)配列番号39のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号52を含む軽鎖可変ドメイン;
(vii)配列番号24のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号43を含む軽鎖可変ドメイン;
(viii)配列番号37のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号52を含む軽鎖可変ドメイン;
(ix)配列番号33のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号48を含む軽鎖可変ドメイン;
(x)配列番号26のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号44を含む軽鎖可変ドメイン;
(xi)配列番号27のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号44を含む軽鎖可変ドメイン;
(xii)配列番号38のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号51を含む軽鎖可変ドメイン;
(xiii)配列番号39のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号51を含む軽鎖可変ドメイン;
(xiv)配列番号40のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号52を含む軽鎖可変ドメイン;
(xv)配列番号36のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号51を含む軽鎖可変ドメイン;
(xvi)配列番号29のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号47を含む軽鎖可変ドメイン;
(xvii)配列番号30のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号47を含む軽鎖可変ドメイン;
(xviii)配列番号31のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号47を含む軽鎖可変ドメイン;
(xix)配列番号32のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号47を含む軽鎖可変ドメイン;
(xx)配列番号33のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号47を含む軽鎖可変ドメイン;
(xxi)配列番号29のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号48を含む軽鎖可変ドメイン;
(xxii)配列番号30のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号48を含む軽鎖可変ドメイン;
(xxiii)配列番号31のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号48を含む軽鎖可変ドメイン;
(xxiv)配列番号32のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号48を含む軽鎖可変ドメイン;
(xxv)配列番号26のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号43を含む軽鎖可変ドメイン;
(xxvi)配列番号27のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号43を含む軽鎖可変ドメイン;
(xxvii)配列番号28のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号46を含む軽鎖可変ドメイン;
(xxviii)配列番号35のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号50を含む軽鎖可変ドメイン;
(xxix)配列番号29のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号48を含む軽鎖可変ドメイン;
(xxx)配列番号30のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号48を含む軽鎖可変ドメイン;
(xxxi)配列番号31のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号48を含む軽鎖可変ドメイン;
(xxxii)配列番号32のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号48を含む軽鎖可変ドメイン;
(xxxiii)配列番号37のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号51を含む軽鎖可変ドメイン;及び
(xxxiv)配列番号40のアミノ酸配列を含む重鎖可変ドメインと、アミノ酸配列配列番号51を含む軽鎖可変ドメイン
からなる群から選択される重鎖可変ドメイン(VH)と軽鎖可変ドメイン(VL)の組合せを含むことを特徴とする相乗的治療の組合わせ。 In the combination of synergistic treatments according to any one of claims 1 to 7, the monoclonal antibody or the antigen-binding fragment thereof is described below.
(I) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 21 and a light chain variable domain containing the amino acid SEQ ID NO: 41;
(Ii) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 23 and a light chain variable domain containing the amino acid SEQ ID NO: 43;
(Iii) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 34 and a light chain variable domain containing the amino acid SEQ ID NO: 49;
(Iv) A heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 36 and a light chain variable domain comprising the amino acid SEQ ID NO: 52;
(V) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 38 and a light chain variable domain containing the amino acid SEQ ID NO: 52;
(Vi) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 39 and a light chain variable domain containing the amino acid SEQ ID NO: 52;
(Vii) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 24 and a light chain variable domain containing the amino acid SEQ ID NO: 43;
(Viii) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 37 and a light chain variable domain containing the amino acid sequence No. 52;
(Ix) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 33 and a light chain variable domain containing the amino acid SEQ ID NO: 48;
(X) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 26 and a light chain variable domain containing the amino acid SEQ ID NO: 44;
(Xi) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 27 and a light chain variable domain containing the amino acid SEQ ID NO: 44;
(Xii) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 38 and a light chain variable domain containing the amino acid SEQ ID NO: 51;
(Xiii) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 39 and a light chain variable domain containing the amino acid sequence No. 51;
(Xiv) A heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 40 and a light chain variable domain comprising the amino acid SEQ ID NO: 52;
(Xv) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 36 and a light chain variable domain containing the amino acid SEQ ID NO: 51;
(Xvi) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 29 and a light chain variable domain containing the amino acid SEQ ID NO: 47;
(Xvii) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 30 and a light chain variable domain containing the amino acid sequence No. 47;
(Xviii) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 31 and a light chain variable domain containing the amino acid sequence No. 47;
(Xix) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 32 and a light chain variable domain containing the amino acid SEQ ID NO: 47;
(Xx) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 33 and a light chain variable domain containing the amino acid SEQ ID NO: 47;
(Xxi) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 29 and a light chain variable domain containing the amino acid SEQ ID NO: 48;
(Xxii) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 30 and a light chain variable domain containing the amino acid SEQ ID NO: 48;
(Xxiii) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 31 and a light chain variable domain containing the amino acid sequence No. 48;
(Xxiv) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 32 and a light chain variable domain containing the amino acid SEQ ID NO: 48;
(Xxv) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 26 and a light chain variable domain containing the amino acid SEQ ID NO: 43;
(Xxvi) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 27 and a light chain variable domain containing the amino acid sequence No. 43;
(Xxvii) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 28 and a light chain variable domain containing the amino acid sequence No. 46;
(Xxxviii) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 35 and a light chain variable domain containing the amino acid sequence No. 50;
(Xxix) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 29 and a light chain variable domain containing the amino acid SEQ ID NO: 48;
(Xxxx) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 30 and a light chain variable domain containing the amino acid SEQ ID NO: 48;
(Xxxxi) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 31 and a light chain variable domain containing the amino acid SEQ ID NO: 48;
(Xxxxi) A heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 32 and a light chain variable domain containing the amino acid sequence No. 48;
(Xxxxiii) Heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 37, light chain variable domain containing amino acid SEQ ID NO: 51; and (xxxx) Heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 40, and amino acid sequence sequence. synergistic therapeutic combination, characterized in combinations including that the heavy chain variable domain selected from the group consisting of a light chain variable domain (VH) and light chain variable domain (VL) including the number 51.
(i)配列番号78のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号67を含む軽鎖;
(ii)配列番号79のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号69を含む軽鎖;
(iii)配列番号80のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号70を含む軽鎖;
(iv)配列番号81のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号71を含む軽鎖;
(v)配列番号82のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号71を含む軽鎖;
(vi)配列番号83のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号71を含む軽鎖;
(vii)配列番号84のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号69を含む軽鎖;
(viii)配列番号85のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号71を含む軽鎖;
(ix)配列番号86のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号72を含む軽鎖;
(x)配列番号87のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号73を含む軽鎖;
(xi)配列番号88のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号73を含む軽鎖;
(xii)配列番号82のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号74を含む軽鎖;
(xiii)配列番号83のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号74を含む軽鎖;
(xiv)配列番号89のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号71を含む軽鎖;
(xv)配列番号81のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号74を含む軽鎖;
(xvi)配列番号90のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号75を含む軽鎖;
(xvii)配列番号91のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号75を含む軽鎖;
(xviii)配列番号92のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号75を含む軽鎖;
(xix)配列番号93のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号75を含む軽鎖;
(xx)配列番号86のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号75を含む軽鎖;
(xxi)配列番号94のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号72を含む軽鎖;
(xxii)配列番号91のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号72を含む軽鎖;
(xxiii)配列番号92のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号72を含む軽鎖;
(xxiv)配列番号93のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号72を含む軽鎖;
(xxv)配列番号87のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号69を含む軽鎖;
(xxvi)配列番号88のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号69を含む軽鎖;
(xxvii)配列番号95のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号76を含む軽鎖;
(xxviii)配列番号96のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号77を含む軽鎖;
(xxix)配列番号97のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号72を含む軽鎖;
(xxx)配列番号98のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号72を含む軽鎖;
(xxxi)配列番号99のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号72を含む軽鎖;
(xxxii)配列番号100のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号72を含む軽鎖;
(xxxiii)配列番号85のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号74を含む軽鎖;
(xxxiv)配列番号89のアミノ酸配列を含む重鎖と、アミノ酸配列配列番号74を含む軽鎖
からなる群から選択される少なくとも1つの重鎖及び少なくとも1つの軽鎖を含むことを特徴とする、モノクローナル抗体又はその抗原結合断片。 The monoclonal antibody according to any one of claims 1 to 7 and 9 or an antigen-binding fragment thereof.
(I) A heavy chain containing the amino acid sequence of SEQ ID NO: 78 and a light chain containing the amino acid SEQ ID NO: 67;
(Ii) A heavy chain containing the amino acid sequence of SEQ ID NO: 79 and a light chain containing the amino acid SEQ ID NO: 69;
(Iii) A heavy chain containing the amino acid sequence of SEQ ID NO: 80 and a light chain containing the amino acid SEQ ID NO: 70;
(Iv) A heavy chain containing the amino acid sequence of SEQ ID NO: 81 and a light chain containing the amino acid SEQ ID NO: 71;
(V) A heavy chain containing the amino acid sequence of SEQ ID NO: 82 and a light chain containing the amino acid SEQ ID NO: 71;
(Vi) A heavy chain containing the amino acid sequence of SEQ ID NO: 83 and a light chain containing the amino acid SEQ ID NO: 71;
(Vii) A heavy chain containing the amino acid sequence of SEQ ID NO: 84 and a light chain containing the amino acid SEQ ID NO: 69;
(Viii) A heavy chain containing the amino acid sequence of SEQ ID NO: 85 and a light chain containing the amino acid SEQ ID NO: 71;
(Ix) A heavy chain containing the amino acid sequence of SEQ ID NO: 86 and a light chain containing the amino acid SEQ ID NO: 72;
(X) A heavy chain containing the amino acid sequence of SEQ ID NO: 87 and a light chain containing the amino acid SEQ ID NO: 73;
(Xi) A heavy chain containing the amino acid sequence of SEQ ID NO: 88 and a light chain containing the amino acid SEQ ID NO: 73;
(Xii) A heavy chain containing the amino acid sequence of SEQ ID NO: 82 and a light chain containing the amino acid SEQ ID NO: 74;
(Xiii) A heavy chain containing the amino acid sequence of SEQ ID NO: 83 and a light chain containing the amino acid SEQ ID NO: 74;
(Xiv) A heavy chain containing the amino acid sequence of SEQ ID NO: 89 and a light chain containing the amino acid SEQ ID NO: 71;
(Xv) A heavy chain containing the amino acid sequence of SEQ ID NO: 81 and a light chain containing the amino acid SEQ ID NO: 74;
(Xvi) A heavy chain containing the amino acid sequence of SEQ ID NO: 90 and a light chain containing the amino acid SEQ ID NO: 75;
(Xvii) A heavy chain containing the amino acid sequence of SEQ ID NO: 91 and a light chain containing the amino acid SEQ ID NO: 75;
(Xviii) A heavy chain containing the amino acid sequence of SEQ ID NO: 92 and a light chain containing the amino acid sequence No. 75;
(Xix) A heavy chain containing the amino acid sequence of SEQ ID NO: 93 and a light chain containing the amino acid SEQ ID NO: 75;
(Xx) A heavy chain containing the amino acid sequence of SEQ ID NO: 86 and a light chain containing the amino acid SEQ ID NO: 75;
(Xxi) A heavy chain containing the amino acid sequence of SEQ ID NO: 94 and a light chain containing the amino acid SEQ ID NO: 72;
(Xxii) A heavy chain containing the amino acid sequence of SEQ ID NO: 91 and a light chain containing the amino acid sequence No. 72;
(Xxiii) A heavy chain containing the amino acid sequence of SEQ ID NO: 92 and a light chain containing the amino acid sequence No. 72;
(Xxiv) A heavy chain containing the amino acid sequence of SEQ ID NO: 93 and a light chain containing the amino acid SEQ ID NO: 72;
(Xxv) A heavy chain containing the amino acid sequence of SEQ ID NO: 87 and a light chain containing the amino acid SEQ ID NO: 69;
(Xxvi) A heavy chain containing the amino acid sequence of SEQ ID NO: 88 and a light chain containing the amino acid SEQ ID NO: 69;
(Xxvii) A heavy chain containing the amino acid sequence of SEQ ID NO: 95 and a light chain containing the amino acid sequence No. 76;
(Xxxviii) A heavy chain containing the amino acid sequence of SEQ ID NO: 96 and a light chain containing the amino acid sequence No. 77;
(Xxix) A heavy chain containing the amino acid sequence of SEQ ID NO: 97 and a light chain containing the amino acid sequence No. 72;
(Xxxx) A heavy chain containing the amino acid sequence of SEQ ID NO: 98 and a light chain containing the amino acid SEQ ID NO: 72;
(Xxxxi) A heavy chain containing the amino acid sequence of SEQ ID NO: 99 and a light chain containing the amino acid sequence No. 72;
(Xxxxi) A heavy chain containing the amino acid sequence of SEQ ID NO: 100 and a light chain containing the amino acid sequence No. 72;
(Xxxxiii) A heavy chain containing the amino acid sequence of SEQ ID NO: 85 and a light chain containing the amino acid sequence No. 74;
To a heavy chain comprising the amino acid sequence of (xxxiv) SEQ ID NO: 89, and at least one heavy chain and wherein including that at least one light chain are selected from the group consisting of a light chain comprising the amino acid sequence SEQ ID NO: 74 , Monoclonal antibody or antigen-binding fragment thereof.
In the combination of synergistic treatments according to any one of claims 1 to 15, the cancer is leukemia, lymphoma, ovarian cancer, breast cancer, endometrial cancer, colon cancer ( colon-rectal cancer), rectal cancer, and the like. Bladgkin cancer, urinary tract epithelial cancer, lung cancer (non-small cell lung cancer, lung adenocarcinoma, squamous epithelial cancer of the lung), bronchial cancer, bone cancer, prostate cancer, pancreatic cancer, gastric cancer, hepatocellular cancer, bladder cancer, bile duct cancer , Esophageal cancer, renal cell cancer, thyroid cancer, flat epithelial cancer of the head and neck (head and neck cancer), testicular cancer, endocrine adenocarcinoma, adrenal adenocarcinoma, pituitary gland cancer, skin cancer, soft tissue cancer, Vascular cancer, brain tumor, nerve cancer, eye cancer, mening membrane cancer, mesopharyngeal cancer, hypopharyngeal cancer, cervical cancer, and uterine cancer, glioblastoma, myelblastoma, astrocyte tumor, glioma, spinal cord Selected from the group consisting of membrane tumor, gastrinoma, neuroblastoma, melanoma, myelodysplastic syndrome, and sarcoma , the leukemia is systemic obeskinosis, acute lymphocytic leukemia (ALL). , T cell ALL, acute myeloid leukemia (AML), myeloid leukemia, chronic lymphocytic leukemia (CLL), multiple myeloma (MM), chronic myeloid leukemia (CML), myelloid proliferative disease / tumor, myelodyskinosis Selected from the group consisting of formation syndrome, monocytic leukemia, and plasma cell leukemia; the lymphomas are Hodgkin's lymphoma and, for example, low-grade / non-Hodgkin's non-Hodgkin's lymphoma (NHL), cell lymphoma (FCC), mantle. Cellular lymphoma (MCL), diffuse large cell lymphoma (DLCL), small lymphocytic (SL) NHL, medium-grade / follicular NHL, medium-grade diffuse NHL, high-grade immunoblastic NHL, high-grade Tissues containing non-Hodgkin's lymphoma such as degree lymphocytic NHL, high-grade small non-notgkinous nuclear cell NHL, bulky disease NHL, and Waldenstrom's Macroglobulinemia Selected from the group consisting of globular lymphoma, T-cell lymphoma, and B-cell lymphoma; the sarcoma is osteosarcoma, Ewing sarcoma, smooth muscle muscular tumor, synovial sarcoma, fodgkin soft sarcoma, angiosarcoma, liposkinoma, fibrosarcoma , A combination of synergistic treatments characterized by being selected from the group consisting of rhombic myoma, and chondroskinoma .
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US62/475,036 | 2017-03-22 | ||
US15/871,802 | 2018-01-15 | ||
US15/871,802 US20180142019A1 (en) | 2016-10-21 | 2018-01-15 | Therapeutic cd47 antibodies |
PCT/US2018/023860 WO2018175790A1 (en) | 2017-03-22 | 2018-03-22 | Combination therapy for the treatment of solid and hematological cancers |
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US9221908B2 (en) | 2012-12-12 | 2015-12-29 | Vasculox, Inc. | Therapeutic CD47 antibodies |
BR112015013431A2 (en) | 2012-12-12 | 2017-11-14 | Vasculox Inc | monoclonal antibodies or antigen-binding fragments thereof, pharmaceutical composition, and uses of monoclonal antibody or antigen-binding fragment thereof |
NZ740686A (en) | 2015-09-18 | 2021-12-24 | Arch Oncology Inc | Therapeutic cd47 antibodies |
WO2018075960A1 (en) | 2016-10-21 | 2018-04-26 | Tioma Therapeutics, Inc. | Therapeutic cd47 antibodies |
CN113166257B (en) * | 2018-12-03 | 2023-05-30 | 上海开拓者生物医药有限公司 | CD47 antibody and preparation method and application thereof |
CN114555190A (en) * | 2019-05-16 | 2022-05-27 | 安驰肿瘤公司 | Therapeutic compositions and methods for treating cancer in combination with analogs of interleukin proteins |
US20200400662A1 (en) | 2019-06-07 | 2020-12-24 | ALX Oncology Inc. | Methods and reagents for reducing the interference of drugs that bind cd47 in serological assays |
EP4048406A4 (en) * | 2019-10-23 | 2023-11-22 | Arch Oncology, Inc. | Combination therapy for the treatment of solid and hematological cancers |
MX2022006578A (en) | 2019-12-17 | 2022-07-04 | Pfizer | Antibodies specific for cd47, pd-l1, and uses thereof. |
US20220196651A1 (en) | 2020-12-06 | 2022-06-23 | ALX Oncology Inc. | Multimers for reducing the interference of drugs that bind cd47 in serological assays |
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US7696325B2 (en) * | 1999-03-10 | 2010-04-13 | Chugai Seiyaku Kabushiki Kaisha | Polypeptide inducing apoptosis |
WO2005044857A1 (en) * | 2003-11-11 | 2005-05-19 | Chugai Seiyaku Kabushiki Kaisha | Humanized anti-cd47 antibody |
CN104548091A (en) * | 2008-02-11 | 2015-04-29 | 治疗科技公司 | Monoclonal antibodies for tumor treatment |
EP2526118A4 (en) * | 2010-01-21 | 2013-11-13 | Immunogen Inc | Compositions and methods for treatment of ovarian cancer |
PL2812443T3 (en) | 2012-02-06 | 2020-01-31 | Inhibrx, Inc. | Cd47 antibodies and methods of use thereof |
EP2744830A4 (en) * | 2012-06-21 | 2015-06-17 | Compugen Ltd | Lsr antibodies, and uses thereof for treatment of cancer |
US9221908B2 (en) * | 2012-12-12 | 2015-12-29 | Vasculox, Inc. | Therapeutic CD47 antibodies |
ES2944477T3 (en) | 2013-02-06 | 2023-06-21 | Inhibrx Inc | Non-Platelet Reducing and Non-Red Cell Reducing CD47 Antibodies and Methods of Using Them |
NZ740686A (en) * | 2015-09-18 | 2021-12-24 | Arch Oncology Inc | Therapeutic cd47 antibodies |
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