JPWO2020176497A5 - - Google Patents
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- JPWO2020176497A5 JPWO2020176497A5 JP2021550091A JP2021550091A JPWO2020176497A5 JP WO2020176497 A5 JPWO2020176497 A5 JP WO2020176497A5 JP 2021550091 A JP2021550091 A JP 2021550091A JP 2021550091 A JP2021550091 A JP 2021550091A JP WO2020176497 A5 JPWO2020176497 A5 JP WO2020176497A5
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- antigen
- drug conjugate
- linker
- binding fragment
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- 239000000611 antibody drug conjugate Substances 0.000 claims description 76
- 229940049595 antibody-drug conjugate Drugs 0.000 claims description 76
- 239000000427 antigen Substances 0.000 claims description 68
- 102000036639 antigens Human genes 0.000 claims description 68
- 108091007433 antigens Proteins 0.000 claims description 68
- 239000012634 fragment Substances 0.000 claims description 57
- 238000000034 method Methods 0.000 claims description 39
- 206010028980 Neoplasm Diseases 0.000 claims description 34
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 34
- 239000003814 drug Substances 0.000 claims description 30
- 239000008194 pharmaceutical composition Substances 0.000 claims description 29
- 201000011510 cancer Diseases 0.000 claims description 28
- 229940127089 cytotoxic agent Drugs 0.000 claims description 28
- 239000002254 cytotoxic agent Substances 0.000 claims description 28
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 24
- 229940124597 therapeutic agent Drugs 0.000 claims description 18
- 210000004027 cell Anatomy 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 12
- 108091033319 polynucleotide Proteins 0.000 claims description 12
- 102000040430 polynucleotide Human genes 0.000 claims description 12
- 239000002157 polynucleotide Substances 0.000 claims description 12
- 108060003951 Immunoglobulin Proteins 0.000 claims description 11
- 102000018358 immunoglobulin Human genes 0.000 claims description 11
- 230000001268 conjugating effect Effects 0.000 claims description 10
- -1 LPR8 Proteins 0.000 claims description 9
- 101000973901 Homo sapiens Tyrosine-protein kinase Mer Proteins 0.000 claims description 8
- IEDXPSOJFSVCKU-HOKPPMCLSA-N [4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[6-(2,5-dioxopyrrolidin-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl N-[(2S)-1-[[(2S)-1-[[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylcarbamate Chemical group CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C)[C@@H](O)c1ccccc1)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C(=O)OCc1ccc(NC(=O)[C@H](CCCNC(N)=O)NC(=O)[C@@H](NC(=O)CCCCCN2C(=O)CCC2=O)C(C)C)cc1)C(C)C IEDXPSOJFSVCKU-HOKPPMCLSA-N 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 102000045684 human MERTK Human genes 0.000 claims description 8
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- 108010093470 monomethyl auristatin E Proteins 0.000 claims description 8
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- MFRNYXJJRJQHNW-DEMKXPNLSA-N (2s)-2-[[(2r,3r)-3-methoxy-3-[(2s)-1-[(3r,4s,5s)-3-methoxy-5-methyl-4-[methyl-[(2s)-3-methyl-2-[[(2s)-3-methyl-2-(methylamino)butanoyl]amino]butanoyl]amino]heptanoyl]pyrrolidin-2-yl]-2-methylpropanoyl]amino]-3-phenylpropanoic acid Chemical compound CN[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 MFRNYXJJRJQHNW-DEMKXPNLSA-N 0.000 claims description 4
- DLKUYSQUHXBYPB-NSSHGSRYSA-N (2s,4r)-4-[[2-[(1r,3r)-1-acetyloxy-4-methyl-3-[3-methylbutanoyloxymethyl-[(2s,3s)-3-methyl-2-[[(2r)-1-methylpiperidine-2-carbonyl]amino]pentanoyl]amino]pentyl]-1,3-thiazole-4-carbonyl]amino]-2-methyl-5-(4-methylphenyl)pentanoic acid Chemical compound N([C@@H]([C@@H](C)CC)C(=O)N(COC(=O)CC(C)C)[C@H](C[C@@H](OC(C)=O)C=1SC=C(N=1)C(=O)N[C@H](C[C@H](C)C(O)=O)CC=1C=CC(C)=CC=1)C(C)C)C(=O)[C@H]1CCCCN1C DLKUYSQUHXBYPB-NSSHGSRYSA-N 0.000 claims description 4
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 claims description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin 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 description 4
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- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 claims description 4
- 230000001270 agonistic effect Effects 0.000 claims description 4
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- 108010059074 monomethylauristatin F Proteins 0.000 claims description 4
- 150000003384 small molecules Chemical group 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 claims description 2
- ZLJZDYOBXVOTSA-XMMPIXPASA-N 2-[3-[(3r)-3-[[2-chloro-3-(trifluoromethyl)phenyl]methyl-(2,2-diphenylethyl)amino]butoxy]phenyl]acetic acid Chemical compound C([C@@H](C)N(CC(C=1C=CC=CC=1)C=1C=CC=CC=1)CC=1C(=C(C=CC=1)C(F)(F)F)Cl)COC1=CC=CC(CC(O)=O)=C1 ZLJZDYOBXVOTSA-XMMPIXPASA-N 0.000 claims description 2
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- 108010074708 B7-H1 Antigen Proteins 0.000 claims description 2
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 claims description 2
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- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 claims description 2
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- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 2
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 claims description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 2
- 208000032612 Glial tumor Diseases 0.000 claims description 2
- 206010018338 Glioma Diseases 0.000 claims description 2
- 101000896414 Homo sapiens Nuclear nucleic acid-binding protein C1D Proteins 0.000 claims description 2
- 101001043564 Homo sapiens Prolow-density lipoprotein receptor-related protein 1 Proteins 0.000 claims description 2
- 101000984753 Homo sapiens Serine/threonine-protein kinase B-raf Proteins 0.000 claims description 2
- 101000831007 Homo sapiens T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 claims description 2
- 101000801234 Homo sapiens Tumor necrosis factor receptor superfamily member 18 Proteins 0.000 claims description 2
- 108091008036 Immune checkpoint proteins Proteins 0.000 claims description 2
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- 208000007766 Kaposi sarcoma Diseases 0.000 claims description 2
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- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 2
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol 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 description 2
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- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
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- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- 102100024834 T-cell immunoreceptor with Ig and ITIM domains Human genes 0.000 claims description 2
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- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 claims description 2
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- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 2
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- HXCHCVDVKSCDHU-LULTVBGHSA-N calicheamicin Chemical compound C1[C@H](OC)[C@@H](NCC)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@](C/3=C/CSSSC)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HXCHCVDVKSCDHU-LULTVBGHSA-N 0.000 claims description 2
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- VQNATVDKACXKTF-XELLLNAOSA-N duocarmycin Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3C4=CC(=O)C5=C([C@@]64C[C@@H]6C3)C=C(N5)C(=O)OC)=CC2=C1 VQNATVDKACXKTF-XELLLNAOSA-N 0.000 claims description 2
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- YUOCYTRGANSSRY-UHFFFAOYSA-N pyrrolo[2,3-i][1,2]benzodiazepine Chemical compound C1=CN=NC2=C3C=CN=C3C=CC2=C1 YUOCYTRGANSSRY-UHFFFAOYSA-N 0.000 claims description 2
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 claims description 2
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- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine 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=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 2
- 229940125644 antibody drug Drugs 0.000 claims 1
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2023028368A JP2023054356A (ja) | 2019-02-26 | 2023-02-27 | 高親和性抗ｍｅｒｔｋ抗体およびその使用 |
| JP2025013855A JP2025061973A (ja) | 2019-02-26 | 2025-01-30 | 高親和性抗ｍｅｒｔｋ抗体およびその使用 |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962810841P | 2019-02-26 | 2019-02-26 | |
| US62/810,841 | 2019-02-26 | ||
| PCT/US2020/019690 WO2020176497A1 (en) | 2019-02-26 | 2020-02-25 | High-affinity anti-mertk antibodies and uses thereof |
Related Child Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2023028368A Division JP2023054356A (ja) | 2019-02-26 | 2023-02-27 | 高親和性抗ｍｅｒｔｋ抗体およびその使用 |
| JP2025013855A Division JP2025061973A (ja) | 2019-02-26 | 2025-01-30 | 高親和性抗ｍｅｒｔｋ抗体およびその使用 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2022522344A JP2022522344A (ja) | 2022-04-18 |
| JPWO2020176497A5 true JPWO2020176497A5 (enExample) | 2023-03-07 |
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| EP3645041A4 (en) * | 2017-06-28 | 2021-03-17 | The Rockefeller University | AGONISTIC ANTIBODY-ANTIBODY-ACTIVE INGREDIENT CONJUGATES AGAINST MERTK AND THEIR USES |
| CN113874081A (zh) | 2019-02-26 | 2021-12-31 | 茵思博纳公司 | 高-亲和力抗-mertk抗体及其用途 |
| AU2020401319A1 (en) | 2019-12-13 | 2022-06-30 | Alector Llc | Anti-MerTK antibodies and methods of use thereof |
| US20240294650A1 (en) * | 2020-03-31 | 2024-09-05 | Alector Llc | Anti-mertk antibodies and methods of use thereof |
| US11564989B2 (en) * | 2021-01-15 | 2023-01-31 | R.P. Scherer Technologies, Llc | Camptothecine antibody-drug conjugates and methods of use thereof |
| KR102549520B1 (ko) | 2021-01-29 | 2023-07-03 | 일리미스테라퓨틱스 주식회사 | 비염증성 식세포작용 유도 활성을 갖는 융합분자 |
| CN117651712A (zh) * | 2021-05-14 | 2024-03-05 | 茵思博纳公司 | Mertk肽及其用途 |
| WO2022266221A1 (en) | 2021-06-16 | 2022-12-22 | Alector Llc | Monovalent anti-mertk antibodies and methods of use thereof |
| WO2022266223A1 (en) * | 2021-06-16 | 2022-12-22 | Alector Llc | Bispecific anti-mertk and anti-pdl1 antibodies and methods of use thereof |
| WO2024022495A1 (en) * | 2022-07-28 | 2024-02-01 | Concept To Medicine Biotech Co., Ltd. | Anti-MerTK ANTIBODIES AND USES THEREOF |
| EP4646212A1 (en) * | 2023-01-05 | 2025-11-12 | Opus Genetics, Inc. | Gene therapy for ocular disease |
| WO2025070337A1 (ja) * | 2023-09-25 | 2025-04-03 | アステラス製薬株式会社 | 抗ＭｅｒＴＫアゴニスト抗体、抗ＭｅｒＴＫ二重特異性抗体、及びその使用 |
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-
2020
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- 2020-02-25 CN CN202510052041.3A patent/CN119735688A/zh active Pending
- 2020-02-25 US US16/801,078 patent/US11242407B2/en active Active
- 2020-02-25 DK DK20714383.5T patent/DK3930847T5/da active
- 2020-02-25 AU AU2020228033A patent/AU2020228033A1/en not_active Abandoned
- 2020-02-25 MA MA055080A patent/MA55080A/fr unknown
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- 2020-02-25 JP JP2021550091A patent/JP7668534B2/ja active Active
- 2020-02-25 PL PL20714383.5T patent/PL3930847T3/pl unknown
- 2020-02-25 WO PCT/US2020/019690 patent/WO2020176497A1/en not_active Ceased
- 2020-02-25 EP EP24156716.3A patent/EP4378958A3/en active Pending
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