CA3044339A1 - Anti-cd137 antibodies and uses thereof - Google Patents
Anti-cd137 antibodies and uses thereof Download PDFInfo
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- CA3044339A1 CA3044339A1 CA3044339A CA3044339A CA3044339A1 CA 3044339 A1 CA3044339 A1 CA 3044339A1 CA 3044339 A CA3044339 A CA 3044339A CA 3044339 A CA3044339 A CA 3044339A CA 3044339 A1 CA3044339 A1 CA 3044339A1
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Classifications
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- 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
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
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- 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
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
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- 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
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- 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
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- 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
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- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/70596—Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
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- Urology & Nephrology (AREA)
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- Pathology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1619648.7A GB201619648D0 (en) | 2016-11-21 | 2016-11-21 | Novel antibodies and uses thereof |
| GB1619648.7 | 2016-11-21 | ||
| PCT/EP2017/079930 WO2018091740A2 (en) | 2016-11-21 | 2017-11-21 | Novel antibodies and uses thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3044339A1 true CA3044339A1 (en) | 2018-05-24 |
Family
ID=57993708
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3044339A Pending CA3044339A1 (en) | 2016-11-21 | 2017-11-21 | Anti-cd137 antibodies and uses thereof |
Country Status (14)
| Country | Link |
|---|---|
| US (3) | US11535678B2 (enExample) |
| EP (1) | EP3541844A2 (enExample) |
| JP (1) | JP7068303B2 (enExample) |
| KR (1) | KR102679632B1 (enExample) |
| CN (1) | CN109963873B (enExample) |
| AU (1) | AU2017360094B2 (enExample) |
| BR (1) | BR112019010265A2 (enExample) |
| CA (1) | CA3044339A1 (enExample) |
| GB (1) | GB201619648D0 (enExample) |
| IL (1) | IL266738B2 (enExample) |
| MX (1) | MX2019005911A (enExample) |
| NZ (1) | NZ754051A (enExample) |
| RU (1) | RU2019116624A (enExample) |
| WO (1) | WO2018091740A2 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP7085708B2 (ja) | 2016-06-20 | 2022-06-17 | エフ－スター セラピューティクス リミテッド | Ｌａｇ－３結合要素 |
| BR112019007714B1 (pt) * | 2017-01-06 | 2022-01-18 | Eutilex Co., Ltd | Anticorpos anti-4-1bb, uso do mesmo, composição farmacêutica, métodos para determinar uma dose, para aumentar a secreção de ifn-gama por uma célula in vitro e para proliferação ex vivo ou isolamento de células t ativadas e uso das mesmas |
| WO2018191502A2 (en) | 2017-04-13 | 2018-10-18 | Agenus Inc. | Anti-cd137 antibodies and methods of use thereof |
| US11512134B2 (en) | 2017-08-01 | 2022-11-29 | Eli Lilly And Company | Anti-CD137 antibodies |
| AU2018311804B2 (en) | 2017-08-01 | 2021-09-02 | Eli Lilly And Company | Anti-CD137 antibodies |
| CN111511762B (zh) | 2017-08-21 | 2025-05-06 | 天演药业公司 | 抗cd137分子及其用途 |
| WO2019148445A1 (en) | 2018-02-02 | 2019-08-08 | Adagene Inc. | Precision/context-dependent activatable antibodies, and methods of making and using the same |
| WO2019148444A1 (en) | 2018-02-02 | 2019-08-08 | Adagene Inc. | Anti-ctla4 antibodies and methods of making and using the same |
| JP7059388B2 (ja) | 2018-03-23 | 2022-04-25 | イーライ リリー アンド カンパニー | 抗ｐｄ－ｌ１抗体との組み合わせのための抗ｃｄ１３７抗体 |
| GB201811403D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | Antibody molecules |
| US12344672B2 (en) | 2018-07-12 | 2025-07-01 | Invox Pharma Limited | Antibody molecules that bind PD-L1 and CD137 |
| GB201811404D0 (en) * | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | Anti-CD137 Antibodies |
| EP3820898B1 (en) | 2018-07-12 | 2025-09-03 | invoX Pharma Limited | Antibody molecules that bind cd137 and ox40 |
| GB201811450D0 (en) | 2018-07-12 | 2018-08-29 | F Star Delta Ltd | Mesothelin and CD137 binding molecules |
| GB201811408D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | CD137 Binding Molecules |
| GB201811410D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | OX40 Binding molecules |
| GB201811415D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | Anti-Mesothelin Anti bodies |
| WO2020023556A1 (en) | 2018-07-23 | 2020-01-30 | Magenta Therapeutics, Inc. | Use of anti-cd137 antibody drug conjugate (adc) in allogeneic cell therapy |
| CN118754986A (zh) | 2018-08-10 | 2024-10-11 | 中外制药株式会社 | 抗cd137抗原结合分子及其应用 |
| BR112021004698A2 (pt) * | 2018-09-12 | 2021-06-01 | Eucure (Beijing) Biopharma Co., Ltd | anticorpos anti-tnfrsf9 e usos dos mesmos |
| JP7558534B2 (ja) * | 2019-01-02 | 2024-10-01 | キューエルエスエフ バイオセラピューティック インコーポレイテッド | Ｃｄ１３７アゴニスト性抗体とその使用 |
| CA3137373A1 (en) | 2019-04-24 | 2020-10-29 | Heidelberg Pharma Research Gmbh | Amatoxin antibody-drug conjugates and uses thereof |
| TW202108629A (zh) | 2019-06-26 | 2021-03-01 | 圓祥生命科技股份有限公司 | 用於t細胞活化之抗體 |
| US20220411523A1 (en) * | 2019-11-13 | 2022-12-29 | Hefei Hankemab Biotechnology Co., Ltd | Molecule capable of binding to human 4-1bb and its application thereof |
| KR20220124718A (ko) | 2020-01-07 | 2022-09-14 | 더 보드 오브 리젠츠 오브 더 유니버시티 오브 텍사스 시스템 | 암 치료를 위한 개선된 인간 메틸 티오아데노신/아데노신 고갈 효소 변이체 |
| CA3166295A1 (en) | 2020-01-29 | 2021-08-05 | John Heymach | Use of poziotinib for the treatment of cancers with nrg1 fusions |
| CA3166133A1 (en) | 2020-01-29 | 2021-08-05 | John Heymach | Use of egfr/her2 tyrosine kinase inhibitors and/or her2/her3 antibodies for the treatment of cancers with nrg1 fusions |
| CA3169939A1 (en) * | 2020-02-28 | 2021-09-02 | Jie Xue | Anti-cd137 construct and use thereof |
| US12146000B2 (en) | 2020-05-19 | 2024-11-19 | Boehringer Ingelheim International Gmbh | Bispecific and tetravalent CD137 and FAP molecules for the treatment of cancer |
| CN113842456B (zh) * | 2020-06-28 | 2022-07-26 | 上海齐鲁制药研究中心有限公司 | 一种抗人4-1bb的单克隆抗体制剂及其用途 |
| JP2023531042A (ja) * | 2020-06-30 | 2023-07-20 | 諾納生物（蘇州）有限公司 | ４－１ｂｂ結合タンパク質及びその用途 |
| KR20230129484A (ko) * | 2021-01-08 | 2023-09-08 | 베이징 한미 파마슈티컬 컴퍼니 리미티드 | 4-1bb와 특이적으로 결합하는 항체 및 그 항원 결합단편 |
| JP2024522234A (ja) | 2021-06-18 | 2024-06-11 | アリゲーター・バイオサイエンス・アーベー | 新規な併用療法及びその使用 |
| GB202210965D0 (en) | 2022-07-27 | 2022-09-07 | Alligator Bioscience Ab | Novel dosages |
| GB202210957D0 (en) | 2022-07-27 | 2022-09-07 | Alligator Bioscience Ab | Novel dosages |
| EP4572772A1 (en) | 2022-08-17 | 2025-06-25 | Capstan Therapeutics, Inc. | Conditioning for in vivo immune cell engineering |
| 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 |
| CN116041517B (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抗体及其应用 |
| CN116162162B (zh) * | 2022-12-19 | 2025-05-27 | 首都医科大学附属北京胸科医院 | 一种大鼠抗小鼠cd137抗体或其功能性片段、工具抗体及其应用 |
| CN116271009A (zh) * | 2023-01-13 | 2023-06-23 | 深圳市乐土生物医药有限公司 | 含有CpG佐剂和4-1BB抗体的药物组合物及其用途 |
| WO2024249954A1 (en) | 2023-05-31 | 2024-12-05 | Capstan Therapeutics, Inc. | Lipid nanoparticle formulations and compositions |
| WO2025076127A1 (en) | 2023-10-05 | 2025-04-10 | Capstan Therapeutics, Inc. | Constrained ionizable cationic lipids and lipid nanoparticles |
| WO2025076113A1 (en) | 2023-10-05 | 2025-04-10 | Capstan Therapeutics, Inc. | Ionizable cationic lipids with conserved spacing and lipid nanoparticles |
| WO2025179294A2 (en) | 2024-02-22 | 2025-08-28 | Capstan Therapeutics, Inc. | Immune engineering amplification |
| WO2025217452A1 (en) | 2024-04-11 | 2025-10-16 | Capstan Therapeutics, Inc. | Constrained ionizable cationic lipids and lipid nanoparticles |
| WO2025217454A2 (en) | 2024-04-11 | 2025-10-16 | Capstan Therapeutics, Inc. | Ionizable cationic lipids and lipid nanoparticles |
Family Cites Families (9)
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| US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| SE459005B (sv) | 1985-07-12 | 1989-05-29 | Aake Rikard Lindahl | Saett att framstaella sfaeriska polymerpartiklar |
| CA2192782C (en) | 1995-12-15 | 2008-10-14 | Nobuyuki Takechi | Production of microspheres |
| AR046094A1 (es) * | 2003-10-10 | 2005-11-23 | Bristol Myers Squibb Co | Anticuerpos completamente humanos contra 4-1bb humano |
| JP5496669B2 (ja) | 2006-09-01 | 2014-05-21 | ジェンティセル | リンパ除去化合物、および抗原配列を含みかつプロフェッショナル抗原提示細胞をターゲットとする分子を含んでなる、特異的ｃｔｌ応答を誘発する組成物 |
| EP3183269A2 (en) * | 2014-08-22 | 2017-06-28 | Bristol-Myers Squibb Company | Treatment of cancer using a combination of an anti-pd-1 antibody and an anti-cd137 antibody |
| US10233251B2 (en) * | 2015-02-22 | 2019-03-19 | Sorrento Therapeutics, Inc. | Antibody therapeutics that bind CD137 |
| EP3988577A1 (en) * | 2015-05-21 | 2022-04-27 | Alligator Bioscience AB | Anti-cd137 antibodies |
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