CA2956014C - Bispecific her2 and cd3 binding molecules - Google Patents
Bispecific her2 and cd3 binding molecules Download PDFInfo
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- CA2956014C CA2956014C CA2956014A CA2956014A CA2956014C CA 2956014 C CA2956014 C CA 2956014C CA 2956014 A CA2956014 A CA 2956014A CA 2956014 A CA2956014 A CA 2956014A CA 2956014 C CA2956014 C CA 2956014C
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- her2
- bispecific binding
- binding molecule
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Classifications
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- C07K16/2809—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 immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
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- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
- A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the cancer treated
- A61K2239/59—Reproductive system, e.g. uterus, ovaries, cervix or testes
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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
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
- C07K2317/41—Glycosylation, sialylation, or fucosylation
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- 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
- C07K2317/60—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
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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
- C07K2317/71—Decreased effector function due to an Fc-modification
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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
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
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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
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
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- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Oncology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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- Engineering & Computer Science (AREA)
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- Bioinformatics & Cheminformatics (AREA)
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- Hematology (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462029342P | 2014-07-25 | 2014-07-25 | |
| US62/029,342 | 2014-07-25 | ||
| PCT/US2015/041989 WO2016014942A1 (en) | 2014-07-25 | 2015-07-24 | Bispecific her2 and cd3 binding molecules |
Publications (2)
| Publication Number | Publication Date |
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| CA2956014A1 CA2956014A1 (en) | 2016-01-28 |
| CA2956014C true CA2956014C (en) | 2023-10-31 |
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| Application Number | Title | Priority Date | Filing Date |
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| CA2956014A Active CA2956014C (en) | 2014-07-25 | 2015-07-24 | Bispecific her2 and cd3 binding molecules |
Country Status (15)
| Country | Link |
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| US (2) | US10519248B2 (enExample) |
| EP (1) | EP3172236B1 (enExample) |
| JP (1) | JP6871155B2 (enExample) |
| KR (1) | KR102638104B1 (enExample) |
| CN (1) | CN107124884B (enExample) |
| AU (1) | AU2015292374B2 (enExample) |
| BR (1) | BR112017001513A2 (enExample) |
| CA (1) | CA2956014C (enExample) |
| ES (1) | ES2832704T3 (enExample) |
| IL (1) | IL250249B (enExample) |
| MX (1) | MX386342B (enExample) |
| RU (1) | RU2017105849A (enExample) |
| SG (1) | SG11201700506TA (enExample) |
| WO (1) | WO2016014942A1 (enExample) |
| ZA (1) | ZA201701341B (enExample) |
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| CA3131724A1 (en) | 2013-12-17 | 2015-06-25 | Genentech, Inc. | Anti-cd3 antibodies and methods of use |
| US11820832B2 (en) | 2014-07-25 | 2023-11-21 | Memorial Sloan Kettering Cancer Center | Bispecific HER2 and CD3 binding molecules |
| SG11201700506TA (en) | 2014-07-25 | 2017-02-27 | Sloan Kettering Inst Cancer | Bispecific her2 and cd3 binding molecules |
| CN107849145B (zh) | 2015-06-16 | 2021-10-26 | 基因泰克公司 | 抗cd3抗体及其使用方法 |
| KR20190074300A (ko) | 2016-11-15 | 2019-06-27 | 제넨테크, 인크. | 항-cd20/항-cd3 이중특이적 항체에 의한 치료를 위한 투약 |
| US11046768B2 (en) * | 2017-01-27 | 2021-06-29 | Memorial Sloan Kettering Cancer Center | Bispecific HER2 and CD3 binding molecules |
| EP3574012A1 (en) * | 2017-01-27 | 2019-12-04 | Memorial Sloan Kettering Cancer Center | Bispecific her2 and cd3 binding molecules |
| KR20190140943A (ko) * | 2017-04-24 | 2019-12-20 | 메모리얼 슬로안 케터링 캔서 센터 | 항-cd33 항체 제제 |
| CN107854490A (zh) * | 2017-09-26 | 2018-03-30 | 首都医科大学附属北京世纪坛医院 | 一种经修饰的t细胞及其应用 |
| KR20200118065A (ko) | 2018-02-08 | 2020-10-14 | 제넨테크, 인크. | 이중특이적 항원-결합 분자 및 이의 사용 방법 |
| EP3765523A1 (en) * | 2018-03-12 | 2021-01-20 | Memorial Sloan Kettering Cancer Center | Bispecific binding agents and uses thereof |
| IL271348B2 (en) * | 2018-03-27 | 2024-09-01 | Systimmune Inc | Methods of making and using guidance and navigation control proteins |
| CN110357960A (zh) * | 2018-04-10 | 2019-10-22 | 广州爱思迈生物医药科技有限公司 | 抗体及抗体改造方法 |
| AR114284A1 (es) * | 2018-04-13 | 2020-08-12 | Hoffmann La Roche | Moléculas de unión a antígeno dirigidas a her2 que comprenden 4-1bbl |
| JP7539701B2 (ja) | 2018-06-14 | 2024-08-26 | バイオアトラ インコーポレイテッド | 多重特異性抗体構造体 |
| CN111138542B (zh) * | 2018-11-01 | 2022-09-23 | 山东新时代药业有限公司 | 双特异性抗体及其用途 |
| CN111196856A (zh) * | 2018-11-19 | 2020-05-26 | 三生国健药业（上海）股份有限公司 | 抗her2/pd1双特异性抗体 |
| JP2022510218A (ja) * | 2018-11-30 | 2022-01-26 | メモリアル スローン ケタリング キャンサー センター | ヘテロ二量体四価特異性抗体およびこれらの使用 |
| EP3894601A4 (en) * | 2018-12-11 | 2023-01-11 | The Translational Genomics Research Institute | IDENTIFICATION OF HER2 MUTATIONS IN LUNG CANCER AND METHODS OF TREATMENT |
| AU2020225631A1 (en) * | 2019-02-22 | 2021-09-16 | Memorial Sloan Kettering Cancer Center | CD33 antibodies and methods of using the same to treat cancer |
| WO2020210232A1 (en) * | 2019-04-08 | 2020-10-15 | Memorial Sloan Kettering Cancer Center | Cd19 antibodies and methods of using the same |
| BR112021022682A2 (pt) | 2019-05-14 | 2022-02-22 | Provention Bio Inc | Métodos e composições para prevenir diabetes do tipo 1 |
| AU2020277489A1 (en) * | 2019-05-23 | 2021-11-25 | VelosBio Inc. | Anti-ROR1/anti-CD3 bispecific binding molecules |
| CA3149683A1 (en) * | 2019-06-26 | 2020-12-30 | Memorial Sloan Kettering Cancer Center | Anti-cd33 antibodies for treating cancer |
| CR20220330A (es) | 2019-12-13 | 2022-08-04 | Genentech Inc | Anticuerpos anti-ly6g6d y métodos de uso. |
| JP2023530109A (ja) | 2020-06-11 | 2023-07-13 | プロヴェンション・バイオ・インコーポレイテッド | １型糖尿病を予防するための方法および組成物 |
| AU2021315882A1 (en) * | 2020-07-28 | 2023-03-02 | Memorial Sloan Kettering Cancer Center | Compositions including ex vivo armed T cells with multi-specific antibodies and uses thereof |
| US20230374150A1 (en) * | 2020-10-12 | 2023-11-23 | Memorial Sloan Kettering Cancer Center | Anti-psma antibodies and uses thereof |
| TWI874719B (zh) | 2020-11-04 | 2025-03-01 | 美商建南德克公司 | 用抗cd20/抗cd3雙特異性抗體進行治療之給藥 |
| TW202237827A (zh) | 2020-12-03 | 2022-10-01 | 美商世紀治療股份有限公司 | 經基因工程改造之細胞及其用途 |
| US11661459B2 (en) | 2020-12-03 | 2023-05-30 | Century Therapeutics, Inc. | Artificial cell death polypeptide for chimeric antigen receptor and uses thereof |
| EP4263600A1 (en) | 2020-12-18 | 2023-10-25 | Century Therapeutics, Inc. | Chimeric antigen receptor systems with adaptable receptor specificity |
| US12291575B2 (en) | 2021-05-14 | 2025-05-06 | Genentech, Inc. | Methods for treatment of CD20-positive proliferative disorder with mosunetuzumab and polatuzumab vedotin |
| JP2024531913A (ja) * | 2021-08-04 | 2024-09-03 | アブプロ コーポレーション | 抗ｈｅｒ２抗体及びそれらの使用 |
| AU2022373303A1 (en) * | 2021-10-20 | 2024-05-09 | Memorial Hospital For Cancer And Allied Diseases | Anti-tshr multi-specific antibodies and uses thereof |
| KR102803655B1 (ko) | 2021-12-29 | 2025-05-08 | 건국대학교 글로컬산학협력단 | 개과 동물의 her1 및 cd3에 특이적으로 결합하는 이중특이적 항체 및 이의 용도 |
| KR102857671B1 (ko) | 2021-12-29 | 2025-09-10 | 건국대학교 글로컬산학협력단 | 개과 동물의 her2 및 cd3에 특이적으로 결합하는 이중특이적 항체 및 이의 용도 |
| WO2023201291A1 (en) | 2022-04-13 | 2023-10-19 | Genentech, Inc. | Pharmaceutical compositions of mosunetuzumab and methods of use |
| KR20250141218A (ko) * | 2023-02-04 | 2025-09-26 | 이미지온 바이오시스템즈, 인크. | 자기 공명 영상에서 산화철 나노입자를 사용하여 결절성 질환을 평가하는 방법 |
| WO2025076473A1 (en) * | 2023-10-06 | 2025-04-10 | Fred Hutchinson Cancer Center | Proteins bispecific to cd3 and nkg2dl and associated uses thereof |
| WO2025085781A1 (en) | 2023-10-19 | 2025-04-24 | Genentech, Inc. | Combinations of il15/il15r alpha heterodimeric fc-fusion proteins and her2xcd3 bispecific antibodies for the treatment of her2-positive cancers |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5885573A (en) * | 1993-06-01 | 1999-03-23 | Arch Development Corporation | Methods and materials for modulation of the immunosuppressive activity and toxicity of monoclonal antibodies |
| SG155883A1 (en) | 2004-06-03 | 2009-10-29 | Novimmune Sa | Anti-cd3 antibodies and methods of use thereof |
| EP2155783B2 (en) | 2007-04-03 | 2022-10-19 | Amgen Research (Munich) GmbH | Cross-species-specific cd3-epsilon binding domain |
| WO2010099536A2 (en) | 2009-02-27 | 2010-09-02 | Massachusetts Institute Of Technology | Engineered proteins with high affinity for dota chelates |
| JP6320753B2 (ja) * | 2010-05-27 | 2018-05-09 | ゲンマブ エー／エス | Ｈｅｒ２に対するモノクローナル抗体 |
| EP2582722A4 (en) * | 2010-06-19 | 2013-12-18 | Sloan Kettering Inst Cancer | ANTIBODIES AGAINST GD2 |
| AU2012245116A1 (en) | 2011-04-20 | 2013-11-07 | Genmab A/S | Bispecific antibodies against HER2 and CD3 |
| CA2835576C (en) * | 2011-05-08 | 2021-01-05 | Legochem Biosciences, Inc. | Protein-active agent conjugates and method for preparing the same |
| WO2012178137A1 (en) * | 2011-06-24 | 2012-12-27 | Gillies Stephen D | Light chain immunoglobulin fusion proteins and methods of use thereof |
| EP2748340B1 (en) * | 2011-11-02 | 2016-06-01 | Ajinomoto Co., Inc. | Method for secretory production of proteins |
| WO2013188693A1 (en) * | 2012-06-15 | 2013-12-19 | Imaginab, Inc. | Antigen binding constructs to cd3 |
| EP2922874A4 (en) | 2012-11-21 | 2016-10-19 | Wuhan Yzy Biopharma Co Ltd | BISPECIFIC ANTIBODIES |
| EP3406633B1 (en) * | 2013-07-25 | 2022-03-02 | Cytomx Therapeutics Inc. | Multispecific antibodies, multispecific activatable antibodies and methods of using the same |
| EP3647324A1 (en) | 2013-12-17 | 2020-05-06 | F. Hoffmann-La Roche AG | Methods of treating cancers using pd-1 axis binding antagonists and taxanes |
| SG11201700506TA (en) | 2014-07-25 | 2017-02-27 | Sloan Kettering Inst Cancer | Bispecific her2 and cd3 binding molecules |
| JP6970017B2 (ja) | 2015-02-09 | 2021-11-24 | メモリアル スローン ケタリング キャンサー センター | ヒトａ３３抗原とｄｏｔａ金属複合体に親和性を有する多重特異性抗体及びその使用 |
| EP3574012A1 (en) | 2017-01-27 | 2019-12-04 | Memorial Sloan Kettering Cancer Center | Bispecific her2 and cd3 binding molecules |
| US11046768B2 (en) | 2017-01-27 | 2021-06-29 | Memorial Sloan Kettering Cancer Center | Bispecific HER2 and CD3 binding molecules |
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