JP7341217B2 - 抗ｃｄ１３７抗体 - Google Patents
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- JP7341217B2 JP7341217B2 JP2021500559A JP2021500559A JP7341217B2 JP 7341217 B2 JP7341217 B2 JP 7341217B2 JP 2021500559 A JP2021500559 A JP 2021500559A JP 2021500559 A JP2021500559 A JP 2021500559A JP 7341217 B2 JP7341217 B2 JP 7341217B2
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/64—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/75—Agonist effect on antigen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1811404.1A GB201811404D0 (en) | 2018-07-12 | 2018-07-12 | Anti-CD137 Antibodies |
| GB1811404.1 | 2018-07-12 | ||
| PCT/EP2019/068798 WO2020011968A1 (en) | 2018-07-12 | 2019-07-12 | Anti-cd137 antibodies |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2021525546A JP2021525546A (ja) | 2021-09-27 |
| JPWO2020011968A5 JPWO2020011968A5 (enExample) | 2022-07-20 |
| JP7341217B2 true JP7341217B2 (ja) | 2023-09-08 |
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|---|---|---|---|
| JP2021500559A Active JP7341217B2 (ja) | 2018-07-12 | 2019-07-12 | 抗ｃｄ１３７抗体 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20210238299A1 (enExample) |
| EP (1) | EP3820570A1 (enExample) |
| JP (1) | JP7341217B2 (enExample) |
| AU (1) | AU2019301208A1 (enExample) |
| CA (1) | CA3106050A1 (enExample) |
| GB (1) | GB201811404D0 (enExample) |
| TW (1) | TW202019964A (enExample) |
| WO (1) | WO2020011968A1 (enExample) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US11214620B2 (en) | 2016-06-20 | 2022-01-04 | F-Star Therapeutics Limited | Binding molecules binding PD-L1 and LAG-3 |
| US11214618B2 (en) | 2016-06-20 | 2022-01-04 | F-Star Therapeutics Limited | LAG-3 binding members |
| GB201612520D0 (en) | 2016-07-19 | 2016-08-31 | F-Star Beta Ltd | Binding molecules |
| CN111741976B (zh) | 2017-12-19 | 2024-09-17 | 英沃克斯制药有限公司 | 包括pd-l1抗原结合位点的fc结合片段 |
| MA52366A (fr) | 2018-04-25 | 2021-03-03 | Prometheus Biosciences Inc | Anticorps anti-tl1a optimisés |
| GB201811410D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | OX40 Binding molecules |
| CN112423845B (zh) | 2018-07-12 | 2024-07-30 | F-星治疗有限公司 | 结合pd-l1和cd137的抗体分子 |
| GB201811403D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | Antibody molecules |
| GB201811415D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | Anti-Mesothelin Anti bodies |
| GB201811408D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | CD137 Binding Molecules |
| GB201811450D0 (en) | 2018-07-12 | 2018-08-29 | F Star Delta Ltd | Mesothelin and CD137 binding molecules |
| CA3106048A1 (en) | 2018-07-12 | 2020-01-16 | F-Star Beta Limited | Antibody molecules that bind cd137 and ox40 |
| AU2020226754A1 (en) | 2019-02-20 | 2021-09-16 | Denali Therapeutics Inc. | Anti-TREM2 antibodies and methods of use thereof |
| JP7504992B2 (ja) | 2019-10-24 | 2024-06-24 | プロメテウス バイオサイエンシーズ，インク． | Ｔｎｆ様リガンド１ａ（ｔｌ１ａ）に対するヒト化抗体およびその使用 |
| CN115279790A (zh) | 2020-01-13 | 2022-11-01 | 戴纳立制药公司 | 抗trem2抗体和其使用方法 |
| WO2021167915A1 (en) * | 2020-02-17 | 2021-08-26 | Board Of Regents, The University Of Texas System | Human 4-1bb agonist antibodies and methods of use thereof |
| US20230242658A1 (en) * | 2020-06-30 | 2023-08-03 | Nona Biosciences (Suzhou) Co., Ltd. | 4-1bb-binding protein and use thereof |
| JP2025521865A (ja) * | 2022-06-28 | 2025-07-10 | ベイジン スターマブ バイオメド テクノロジ リミテッド | 単特異性抗体および多重特異性抗体 |
| WO2024051752A1 (en) * | 2022-09-06 | 2024-03-14 | I-Mab Biopharma Co., Ltd. | Multispecific constructs and uses thereof |
| WO2024061364A1 (zh) * | 2022-09-22 | 2024-03-28 | 成都盛世君联生物技术有限公司 | 一种抗4-1bb纳米抗体及其制备和应用 |
| CN115850487B (zh) * | 2022-12-19 | 2025-02-25 | 首都医科大学附属北京胸科医院 | 一种抗人cd137抗体、核酸分子及应用 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017055398A2 (en) | 2015-10-02 | 2017-04-06 | F. Hoffmann-La Roche Ag | Bispecific antibodies specific for a costimulatory tnf receptor |
| WO2017182672A1 (en) | 2016-04-22 | 2017-10-26 | Alligator Bioscience Ab | Novel bispecific polypeptides against cd137 |
| WO2018056821A1 (en) | 2016-09-23 | 2018-03-29 | Merus N.V. | Binding molecules that modulate a biological activity expressed by a cell |
| WO2018091740A2 (en) | 2016-11-21 | 2018-05-24 | Alligator Bioscience Ab | Novel antibodies and uses thereof |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61134325A (ja) | 1984-12-04 | 1986-06-21 | Teijin Ltd | ハイブリツド抗体遺伝子の発現方法 |
| GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
| US5530101A (en) * | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US6235525B1 (en) | 1991-05-23 | 2001-05-22 | Ludwig Institute For Cancer Research | Isolated nucleic acid molecules coding for tumor rejection antigen precursor MAGE-3 and uses thereof |
| US5541104A (en) | 1991-05-23 | 1996-07-30 | Ludwig Institute For Cancer Research | Monoclonal antibodies which bind to tumor rejection antigen precursor mage-1 |
| US5342774A (en) | 1991-05-23 | 1994-08-30 | Ludwig Institute For Cancer Research | Nucleotide sequence encoding the tumor rejection antigen precursor, MAGE-1 |
| CA2143335C (en) | 1992-08-31 | 2000-03-14 | Thierry Boon-Falleur | Isolated nonapeptide derived from mage-3 gene and presented by hla-a1, and uses thereof |
| US6222012B1 (en) | 1992-08-31 | 2001-04-24 | Ludwig Institute For Cancer Research | Isolated nonapeptides presented by HLA molecules, and uses thereof |
| DE69524264T2 (de) | 1994-03-01 | 2002-07-18 | Ludwig Institute For Cancer Research, New York | Bestimmung krebsartiger beschaffenheiten durch die genexpression eines mitgliedes der melanomartigengruppe, mage |
| US6291430B1 (en) | 1997-09-12 | 2001-09-18 | Ludwig Institute For Cancer Research | Mage-3 peptides presented by HLA class II molecules |
| US7288638B2 (en) * | 2003-10-10 | 2007-10-30 | Bristol-Myers Squibb Company | Fully human antibodies against human 4-1BB |
| AU2006204459B2 (en) | 2005-01-05 | 2012-11-01 | F-Star Therapeutics Limited | Synthetic immunoglobulin domains with binding properties engineered in regions of the molecule different from the complementarity determining regions |
| SG186656A1 (en) | 2007-12-14 | 2013-01-30 | Bristol Myers Squibb Co | Binding molecules to the human ox40 receptor |
| EP2113255A1 (en) | 2008-05-02 | 2009-11-04 | f-star Biotechnologische Forschungs- und Entwicklungsges.m.b.H. | Cytotoxic immunoglobulin |
| MX337040B (es) | 2010-09-09 | 2016-02-09 | Pfizer | Moleculas de union a 4-1bb. |
| US20150307620A1 (en) * | 2014-04-16 | 2015-10-29 | University Of Connecticut | Linked immunotherapeutic agonists that costimulate multiple pathways |
| HRP20191824T1 (hr) * | 2015-01-08 | 2020-01-24 | BioNTech SE | Agonistička sredstva za vezivanje tnf receptora |
| EP3258959A4 (en) * | 2015-02-22 | 2018-10-17 | Sorrento Therapeutics, Inc. | Antibody therapeutics that bind cd137 |
| CN107636014B (zh) | 2015-05-04 | 2021-12-07 | 皮里斯制药有限公司 | 抗癌融合多肽 |
| WO2018115859A1 (en) * | 2016-12-20 | 2018-06-28 | Kymab Limited | Multispecific antibody with combination therapy for immuno-oncology |
-
2018
- 2018-07-12 GB GBGB1811404.1A patent/GB201811404D0/en not_active Ceased
-
2019
- 2019-07-12 WO PCT/EP2019/068798 patent/WO2020011968A1/en not_active Ceased
- 2019-07-12 EP EP19742153.0A patent/EP3820570A1/en not_active Withdrawn
- 2019-07-12 JP JP2021500559A patent/JP7341217B2/ja active Active
- 2019-07-12 TW TW108124778A patent/TW202019964A/zh unknown
- 2019-07-12 CA CA3106050A patent/CA3106050A1/en active Pending
- 2019-07-12 AU AU2019301208A patent/AU2019301208A1/en active Pending
- 2019-07-12 US US17/259,680 patent/US20210238299A1/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017055398A2 (en) | 2015-10-02 | 2017-04-06 | F. Hoffmann-La Roche Ag | Bispecific antibodies specific for a costimulatory tnf receptor |
| WO2017182672A1 (en) | 2016-04-22 | 2017-10-26 | Alligator Bioscience Ab | Novel bispecific polypeptides against cd137 |
| WO2018056821A1 (en) | 2016-09-23 | 2018-03-29 | Merus N.V. | Binding molecules that modulate a biological activity expressed by a cell |
| WO2018091740A2 (en) | 2016-11-21 | 2018-05-24 | Alligator Bioscience Ab | Novel antibodies and uses thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2021525546A (ja) | 2021-09-27 |
| WO2020011968A1 (en) | 2020-01-16 |
| AU2019301208A1 (en) | 2021-03-04 |
| GB201811404D0 (en) | 2018-08-29 |
| TW202019964A (zh) | 2020-06-01 |
| EP3820570A1 (en) | 2021-05-19 |
| US20210238299A1 (en) | 2021-08-05 |
| CA3106050A1 (en) | 2020-01-16 |
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