AU2015329965A1 - Bispecific antibodies against CD3epsilon and ROR1 - Google Patents
Bispecific antibodies against CD3epsilon and ROR1 Download PDFInfo
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- AU2015329965A1 AU2015329965A1 AU2015329965A AU2015329965A AU2015329965A1 AU 2015329965 A1 AU2015329965 A1 AU 2015329965A1 AU 2015329965 A AU2015329965 A AU 2015329965A AU 2015329965 A AU2015329965 A AU 2015329965A AU 2015329965 A1 AU2015329965 A1 AU 2015329965A1
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- 230000004222 uncontrolled growth Effects 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
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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
- C07K16/2803—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
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
- C07K16/2803—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
-
- 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
-
- 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
-
- 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
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- 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
- C07K2317/77—Internalization into the cell
Landscapes
- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Hematology (AREA)
- Oncology (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)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14188378.5 | 2014-10-09 | ||
| EP14188378 | 2014-10-09 | ||
| EP14188727.3 | 2014-10-14 | ||
| EP14188727 | 2014-10-14 | ||
| PCT/EP2015/073308 WO2016055592A1 (en) | 2014-10-09 | 2015-10-08 | Bispecific antibodies against cd3epsilon and ror1 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2015329965A1 true AU2015329965A1 (en) | 2017-04-27 |
Family
ID=54291292
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2015329965A Abandoned AU2015329965A1 (en) | 2014-10-09 | 2015-10-08 | Bispecific antibodies against CD3epsilon and ROR1 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US11952421B2 (enExample) |
| EP (1) | EP3204415B1 (enExample) |
| JP (1) | JP6708635B2 (enExample) |
| AU (1) | AU2015329965A1 (enExample) |
| CA (1) | CA2963692A1 (enExample) |
| ES (1) | ES2850325T3 (enExample) |
| WO (1) | WO2016055592A1 (enExample) |
Families Citing this family (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090162359A1 (en) | 2007-12-21 | 2009-06-25 | Christian Klein | Bivalent, bispecific antibodies |
| SI2417156T1 (sl) | 2009-04-07 | 2015-06-30 | Roche Glycart Ag | Trivalentna, bispecifiäśna protitelesa |
| US9676845B2 (en) | 2009-06-16 | 2017-06-13 | Hoffmann-La Roche, Inc. | Bispecific antigen binding proteins |
| WO2012116926A1 (en) | 2011-02-28 | 2012-09-07 | F. Hoffmann-La Roche Ag | Antigen binding proteins |
| BR112013020338A2 (pt) | 2011-02-28 | 2016-10-18 | Hoffmann La Roche | proteína de ligação de antígeno monovalente, composição farmacêutica, uso da proteína de ligação de antígeno monovalente, método para o tratamento de um paciente com necessidade de terapia, método para a preparação de uma proteína de ligação de antígeno monovalente, ácido nucleico, vetor e célula hospedeira |
| KR101681818B1 (ko) | 2011-08-23 | 2016-12-01 | 로슈 글리카트 아게 | T 세포 활성화 항원 및 종양 항원에 대해 특이적인 이중특이적 항체 및 이의 사용 방법 |
| EP2904016B1 (en) | 2012-10-08 | 2018-11-14 | Roche Glycart AG | Fc-free antibodies comprising two fab-fragments and methods of use |
| KR20180023035A (ko) | 2013-02-26 | 2018-03-06 | 로슈 글리카트 아게 | 이중특이적 t 세포 활성화 항원 결합 분자 |
| EP2789630A1 (en) * | 2013-04-09 | 2014-10-15 | EngMab AG | Bispecific antibodies against CD3e and ROR1 |
| KR20160044060A (ko) | 2013-10-11 | 2016-04-22 | 에프. 호프만-라 로슈 아게 | 다중특이적 도메인 교환된 통상의 가변 경쇄 항체 |
| DK3177643T3 (da) | 2014-08-04 | 2019-07-15 | Hoffmann La Roche | Bispecifikke T-celle-aktiverende antigenbindende molekyler |
| JP6708635B2 (ja) * | 2014-10-09 | 2020-06-10 | エンクマフ エスアーエールエル | ＣＤ３εおよびＲＯＲ１に対する二特異性抗体 |
| DK3221357T3 (da) | 2014-11-20 | 2020-08-10 | Hoffmann La Roche | Fælles letkæder og fremgangsmåder til anvendelse |
| DK3221356T3 (da) | 2014-11-20 | 2020-11-02 | Hoffmann La Roche | T-celleaktiverende, bispecifikke, antigenbindende molekyler mod folr1 og cd3 |
| DK4141032T3 (da) | 2014-11-20 | 2024-08-05 | Hoffmann La Roche | Kombinationsbehandling med T-celleaktiverende bispecifikke antigenbindende molekyler og PD-1-aksebindende antagonister |
| WO2016087416A1 (en) | 2014-12-03 | 2016-06-09 | F. Hoffmann-La Roche Ag | Multispecific antibodies |
| AR106188A1 (es) | 2015-10-01 | 2017-12-20 | Hoffmann La Roche | Anticuerpos anti-cd19 humano humanizados y métodos de utilización |
| EP3150636A1 (en) * | 2015-10-02 | 2017-04-05 | F. Hoffmann-La Roche AG | Tetravalent multispecific antibodies |
| KR20180073561A (ko) | 2015-10-02 | 2018-07-02 | 에프. 호프만-라 로슈 아게 | 이중특이적 항-ceaxcd3 t 세포 활성화 항원 결합 분자 |
| HK1254836A1 (zh) | 2015-10-30 | 2019-07-26 | Nbe-Therapeutics Ag | 抗-ror1抗体 |
| KR102850929B1 (ko) | 2015-12-09 | 2025-08-27 | 에프. 호프만-라 로슈 아게 | 항-약물 항체의 형성을 감소시키기 위한 ii형 항-cd20 항체 |
| ES2837428T3 (es) | 2016-01-08 | 2021-06-30 | Hoffmann La Roche | Procedimientos de tratamiento de cánceres positivos para CEA usando antagonistas de unión al eje PD-1 y anticuerpos biespecíficos anti-CEA/anti-CD3 |
| RU2766190C2 (ru) | 2016-01-20 | 2022-02-09 | Дзе Скриппс Рисерч Инститьют | Композиции антител к ror1 и соответствующие способы |
| JP7015244B2 (ja) | 2016-03-22 | 2022-02-02 | エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト | プロテアーゼ活性化ｔ細胞二重特異性分子 |
| ES2897217T3 (es) | 2016-09-30 | 2022-02-28 | Hoffmann La Roche | Anticuerpos biespecíficos frente a p95HER2 |
| AU2018289581C1 (en) | 2017-06-23 | 2025-01-30 | VelosBio Inc. | ROR1 antibody immunoconjugates |
| CN111148761B (zh) * | 2017-06-25 | 2024-02-13 | 西雅图免疫公司 | 多特异性抗体及其制备和使用方法 |
| GB201710835D0 (en) | 2017-07-05 | 2017-08-16 | Ucl Business Plc | ROR1 Antibodies |
| GB201710838D0 (en) * | 2017-07-05 | 2017-08-16 | Ucl Business Plc | Bispecific antibodies |
| GB201710836D0 (en) | 2017-07-05 | 2017-08-16 | Ucl Business Plc | ROR1 Car T-Cells |
| US20210139579A1 (en) * | 2017-07-20 | 2021-05-13 | Nbe-Therapeutics Ag | Multispecific antibody product that binds to different ror1 epitopes |
| SG11202000846WA (en) | 2017-08-07 | 2020-02-27 | Nbe Therapeutics Ag | Anthracycline-based antibody drug conjugates having high in vivo tolerability |
| US11535667B2 (en) * | 2017-08-28 | 2022-12-27 | Systimmune, Inc. | Anti-CD3 antibodies and methods of making and using thereof |
| CA3074130A1 (en) * | 2017-09-21 | 2019-03-28 | WuXi Biologics Ireland Limited | Novel anti-cd3epsilon antibodies |
| US12486325B2 (en) | 2017-09-21 | 2025-12-02 | WuXi Biologics Ireland Limited | Anti-CD3epsilon antibodies |
| CN118772288A (zh) | 2018-02-08 | 2024-10-15 | 豪夫迈·罗氏有限公司 | 双特异性抗原结合分子和使用方法 |
| BR112020019795A2 (pt) | 2018-03-30 | 2021-01-05 | Merus N.V. | Anticorpo multivalente |
| MY207121A (en) | 2018-04-18 | 2025-01-31 | Exelixis Inc | Anti-ror antibody constructs |
| CN109580504B (zh) * | 2018-10-19 | 2021-10-26 | 东软威特曼生物科技(南京)有限公司 | 一种脂蛋白胆固醇测定试剂及试剂盒 |
| CN113874399B (zh) * | 2019-05-23 | 2025-07-11 | 维洛斯生物股份有限公司 | 抗ror1/抗cd3双特异性结合分子 |
| CA3160208A1 (en) * | 2019-11-07 | 2021-05-14 | Amgen Inc. | High salt washes during cation exchange chromatography to remove product-realated impurities |
| BR112022008649A2 (pt) * | 2019-11-07 | 2022-07-19 | Amgen Inc | Condicionamento de carga com alto teor de sal durante cromatografia de troca catiônica para remover impurezas relacionadas ao produto |
| MX2022009596A (es) | 2020-02-07 | 2022-09-02 | Velosbio Inc | Anticuerpos anti-ror1 y composiciones. |
| BR112022025856A2 (pt) | 2020-06-19 | 2023-01-10 | Hoffmann La Roche | Anticorpo que se liga a cd3 e cd19, polinucleotídeo isolado, célula hospedeira, método de produção de um anticorpo que se liga a cd3 e cd19, composição farmacêutica, uso do anticorpo, método para tratar uma doença em um indivíduo e invenção |
| WO2022042488A1 (en) * | 2020-08-24 | 2022-03-03 | Epimab Biotherapeutics (Hk) Limited | Anti-ror1 antibodies and related bispecific binding proteins |
| KR20230166075A (ko) | 2021-02-02 | 2023-12-06 | 누맙 세러퓨틱스 아게 | Ror1 및 cd3에 대한 특이성을 가지는 다중 특이적 항체 |
| AU2022227686A1 (en) | 2021-02-25 | 2023-07-27 | Lyell Immunopharma, Inc. | Ror1 targeting chimeric antigen receptor |
| EP4330282A1 (en) | 2021-04-30 | 2024-03-06 | F. Hoffmann-La Roche AG | Dosing for combination treatment with anti-cd20/anti-cd3 bispecific antibody and anti-cd79b antibody drug conjugate |
| JP2024540099A (ja) | 2021-10-28 | 2024-10-31 | ライエル・イミュノファーマ・インコーポレイテッド | Ｒｏｒ１結合タンパク質を発現する細胞を培養する方法 |
| WO2024064958A1 (en) | 2022-09-23 | 2024-03-28 | Lyell Immunopharma, Inc. | Methods for culturing nr4a-deficient cells |
| WO2024064952A1 (en) | 2022-09-23 | 2024-03-28 | Lyell Immunopharma, Inc. | Methods for culturing nr4a-deficient cells overexpressing c-jun |
| WO2024077174A1 (en) | 2022-10-05 | 2024-04-11 | Lyell Immunopharma, Inc. | Methods for culturing nr4a-deficient cells |
| CN116462768B (zh) * | 2023-06-13 | 2023-09-22 | 浙江时迈药业有限公司 | 针对folr1的双特异性抗体及其用途 |
| WO2025217398A1 (en) | 2024-04-10 | 2025-10-16 | Lyell Immunopharma, Inc. | Methods for culturing cells with improved culture medium |
Family Cites Families (111)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| EP0307434B2 (en) | 1987-03-18 | 1998-07-29 | Scotgen Biopharmaceuticals, Inc. | Altered antibodies |
| US5202238A (en) | 1987-10-27 | 1993-04-13 | Oncogen | Production of chimeric antibodies by homologous recombination |
| US5204244A (en) | 1987-10-27 | 1993-04-20 | Oncogen | Production of chimeric antibodies by homologous recombination |
| US5273743A (en) | 1990-03-09 | 1993-12-28 | Hybritech Incorporated | Trifunctional antibody-like compounds as a combined diagnostic and therapeutic agent |
| IL101661A (en) | 1991-04-23 | 1998-02-08 | Regeneron Pharma | Method for detecting, identifying or measuring agents having neurotrophin activity |
| US5837821A (en) | 1992-11-04 | 1998-11-17 | City Of Hope | Antibody construct |
| EP0672142B1 (en) | 1992-12-04 | 2001-02-28 | Medical Research Council | Multivalent and multispecific binding proteins, their manufacture and use |
| ES2162863T3 (es) | 1993-04-29 | 2002-01-16 | Unilever Nv | Produccion de anticuerpos o fragmentos (funcionalizados) de los mismos derivados de inmunoglobulinas de cadena pesada de camelidae. |
| DE69529674T3 (de) | 1994-04-04 | 2007-06-28 | Regeneron Pharmaceuticals, Inc. | Biologisch aktive liganden der eph-familie |
| DE69535557T2 (de) | 1994-12-30 | 2008-04-30 | Planet Biotechnology, Inc., San Diego | Verfahren zur herstellung von schutzproteine enthaltende immunoglobuline und ihre verwendung |
| GB9501079D0 (en) | 1995-01-19 | 1995-03-08 | Bioinvent Int Ab | Activation of T-cells |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| EP0739981A1 (en) | 1995-04-25 | 1996-10-30 | Vrije Universiteit Brussel | Variable fragments of immunoglobulins - use for therapeutic or veterinary purposes |
| DK0826696T3 (da) | 1996-09-03 | 2002-09-23 | Gsf Forschungszentrum Umwelt | Anvendelse af bi- og trispecifikke antistoffer til inducering af en tumorimmunitet |
| CA2288994C (en) | 1997-04-30 | 2011-07-05 | Enzon, Inc. | Polyalkylene oxide-modified single chain polypeptides |
| DK0979281T3 (da) | 1997-05-02 | 2005-11-21 | Genentech Inc | Fremgangsmåde til fremstilling af multispecifikke antistoffer med heteromultimere og fælles bestanddele |
| ES2234241T3 (es) | 1998-01-23 | 2005-06-16 | Vlaams Interuniversitair Instituut Voor Biotechnologie | Derivados de anticuerpo de multiples fines. |
| US20020142000A1 (en) | 1999-01-15 | 2002-10-03 | Digan Mary Ellen | Anti-CD3 immunotoxins and therapeutic uses therefor |
| GB0029407D0 (en) | 2000-12-01 | 2001-01-17 | Affitech As | Product |
| WO2002087618A1 (en) | 2001-04-27 | 2002-11-07 | Takeda Chemical Industries, Ltd. | Preventive/therapeutic method for cancer |
| EP2281837B1 (en) | 2001-08-10 | 2016-10-05 | Aberdeen University | Antigen binding domains from fish |
| ES2276735T3 (es) | 2001-09-14 | 2007-07-01 | Affimed Therapeutics Ag | Anticuerpos fv multimericos de cadena sencilla en tandem. |
| ES2283368T3 (es) | 2001-11-14 | 2007-11-01 | Affimed Therapeutics Ag | Anticuerpos biespecificos anti-cd19 y anti-cd16 y usos de los mismos. |
| US7317091B2 (en) | 2002-03-01 | 2008-01-08 | Xencor, Inc. | Optimized Fc variants |
| GB0230201D0 (en) | 2002-12-27 | 2003-02-05 | Domantis Ltd | Retargeting |
| WO2004076489A1 (en) | 2003-02-25 | 2004-09-10 | Medinnova As | Modified antibody |
| AU2003259718A1 (en) | 2003-08-07 | 2005-03-07 | Epitomics, Inc. | Methods for humanizing rabbit monoclonal antibodies |
| JP2007508801A (ja) | 2003-10-24 | 2007-04-12 | エスバテック・アーゲー | 受容体チロシンキナーゼ阻害剤の同定および／または確認のための方法 |
| US7235641B2 (en) | 2003-12-22 | 2007-06-26 | Micromet Ag | Bispecific antibodies |
| EP1735461A4 (en) | 2004-04-06 | 2008-10-29 | Univ California | RECEPTOR WITH TYROSINE KINASE ORPHAN ACTIVITY AS A TARGET IN BREAST CANCER |
| DK2330121T3 (en) | 2004-06-02 | 2014-12-15 | Adalta Pty Ltd | Binding moieties based on shark IgNar domains |
| ATE414718T1 (de) | 2005-01-05 | 2008-12-15 | F Star Biotech Forsch & Entw | Synthetische immunoglobulindomänen mit in regionen des moleküls, die sich von den die komplementarität bestimmenden bereichen unterscheiden, modifizierten bindeeigenschaften |
| WO2006093794A1 (en) | 2005-02-28 | 2006-09-08 | Centocor, Inc. | Heterodimeric protein binding compositions |
| CN101198698B (zh) | 2005-03-31 | 2014-03-19 | 中外制药株式会社 | 通过调节多肽缔合制备多肽的方法 |
| JP5838021B2 (ja) | 2005-04-15 | 2015-12-24 | マクロジェニクス，インコーポレーテッド | 共有結合型ダイアボディとその使用 |
| RU2008110060A (ru) | 2005-08-15 | 2009-09-27 | Арана Терапьютикс Лимитед (Au) | Сконструированные антитела с каркасными участками приматов нового света |
| EP3770174A1 (en) * | 2005-10-11 | 2021-01-27 | Amgen Research (Munich) GmbH | Compositions comprising cross-species-specific antibodies and uses thereof |
| WO2008103849A2 (en) | 2007-02-21 | 2008-08-28 | The Regents Of The University Of California | Methods and compounds for lymphoma cell detection and isolation |
| WO2007051077A2 (en) | 2005-10-28 | 2007-05-03 | The Regents Of The University Of California | Methods and compounds for lymphoma cell detection and isolation |
| ES2395969T3 (es) | 2006-03-24 | 2013-02-18 | Merck Patent Gmbh | Dominios de proteínas heterodiméricas genéticamente modificados |
| BRPI0710011A2 (pt) | 2006-04-14 | 2011-08-02 | Trubion Pharmaceuticals Inc | proteìnas de ligação compreendendo articulação de imunoglobulina e regiões fc dotadas de funções efetoras fc alteradas |
| MX380352B (es) | 2006-06-12 | 2025-03-12 | Aptevo Res & Development Llc | Proteinas de union multivalentes monocatenarias con funcion efectora. |
| WO2007146957A2 (en) | 2006-06-13 | 2007-12-21 | Irm Llc | Ror1 as a therapeutic target for lung cancer |
| WO2007147901A1 (en) | 2006-06-22 | 2007-12-27 | Novo Nordisk A/S | Production of bispecific antibodies |
| US20100021379A1 (en) | 2006-06-29 | 2010-01-28 | The Regents Of The University Of California | Chemical Antibodies for Immunotherapy and Imaging |
| WO2008076868A2 (en) | 2006-12-18 | 2008-06-26 | Abbott Laboratories | Methods and compositions related to modulation of receptor tyrosine kinase orphan receptor-1 (ror-1) |
| AU2008234248C1 (en) | 2007-03-29 | 2015-01-22 | Genmab A/S | Bispecific antibodies and methods for production thereof |
| RU2561457C2 (ru) | 2007-04-03 | 2015-08-27 | Эмджен Рисерч (Мьюник) Гмбх | Cd3-эпсилон-связывающий домен с межвидовой специфичностью |
| US20090162359A1 (en) | 2007-12-21 | 2009-06-25 | Christian Klein | Bivalent, bispecific antibodies |
| US9266967B2 (en) | 2007-12-21 | 2016-02-23 | Hoffmann-La Roche, Inc. | Bivalent, bispecific antibodies |
| US8242247B2 (en) | 2007-12-21 | 2012-08-14 | Hoffmann-La Roche Inc. | Bivalent, bispecific antibodies |
| US8227577B2 (en) | 2007-12-21 | 2012-07-24 | Hoffman-La Roche Inc. | Bivalent, bispecific antibodies |
| AU2009204501B2 (en) * | 2008-01-07 | 2015-02-12 | Amgen Inc. | Method for making antibody Fc-heterodimeric molecules using electrostatic steering effects |
| EP2842575B1 (en) | 2008-03-18 | 2017-09-27 | Seattle Genetics, Inc. | Auristatin drug linker conjugates |
| US20100260668A1 (en) | 2008-04-29 | 2010-10-14 | Abbott Laboratories | Dual Variable Domain Immunoglobulins and Uses Thereof |
| US8710022B2 (en) | 2008-07-18 | 2014-04-29 | National University Corporation Nagoya University | Cell proliferation inhibitor |
| BRPI0919840B1 (pt) | 2008-10-01 | 2023-02-28 | Amgen Research (Munich) Gmbh | Molécula de anticorpo de cadeia única biespecífica, seu uso, e composição farmacêutica que a compreende |
| AU2009324092A1 (en) | 2008-12-03 | 2011-06-23 | Genmab A/S | Antibody variants having modifications in the constant region |
| CA2759733C (en) | 2009-04-23 | 2019-09-03 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Anti-human ror1 antibodies |
| WO2010129304A2 (en) | 2009-04-27 | 2010-11-11 | Oncomed Pharmaceuticals, Inc. | Method for making heteromultimeric molecules |
| US9676845B2 (en) | 2009-06-16 | 2017-06-13 | Hoffmann-La Roche, Inc. | Bispecific antigen binding proteins |
| TW201109438A (en) | 2009-07-29 | 2011-03-16 | Abbott Lab | Dual variable domain immunoglobulins and uses thereof |
| WO2011054007A1 (en) | 2009-11-02 | 2011-05-05 | Oxford Biotherapeutics Ltd. | Ror1 as therapeutic and diagnostic target |
| CN102712695B (zh) | 2009-12-18 | 2015-01-21 | 堪瑟拉公司 | 能够诱导细胞死亡的ror1生物抑制剂 |
| PT2519543T (pt) | 2009-12-29 | 2016-10-07 | Emergent Product Dev Seattle | Proteínas de ligação de heterodímero e suas utilizações |
| WO2011143545A1 (en) | 2010-05-14 | 2011-11-17 | Rinat Neuroscience Corporation | Heterodimeric proteins and methods for producing and purifying them |
| US9242014B2 (en) | 2010-06-15 | 2016-01-26 | The Regents Of The University Of California | Receptor tyrosine kinase-like orphan receptor 1 (ROR1) single chain Fv antibody fragment conjugates and methods of use thereof |
| CN102330723A (zh) | 2010-07-13 | 2012-01-25 | 新秩序投资119股份有限公司 | 管配件 |
| EP3828205A1 (en) | 2010-10-01 | 2021-06-02 | Oxford BioTherapeutics Ltd | Anti-ror1 antibodies |
| AU2011325833C1 (en) | 2010-11-05 | 2017-07-13 | Zymeworks Bc Inc. | Stable heterodimeric antibody design with mutations in the Fc domain |
| EP4279513A3 (en) | 2010-11-30 | 2024-02-28 | Chugai Seiyaku Kabushiki Kaisha | Cytotoxicity-inducing therapeutic agent |
| US9758586B2 (en) | 2010-12-01 | 2017-09-12 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Chimeric rabbit/human ROR1 antibodies |
| GB201020995D0 (en) | 2010-12-10 | 2011-01-26 | Bioinvent Int Ab | Biological materials and uses thereof |
| DK2663579T3 (en) | 2011-01-14 | 2017-07-31 | Univ California | THERAPEUTIC ANTIBODIES AGAINST ROR-1 PROTEIN AND PROCEDURES FOR USE THEREOF |
| BR112013020338A2 (pt) | 2011-02-28 | 2016-10-18 | Hoffmann La Roche | proteína de ligação de antígeno monovalente, composição farmacêutica, uso da proteína de ligação de antígeno monovalente, método para o tratamento de um paciente com necessidade de terapia, método para a preparação de uma proteína de ligação de antígeno monovalente, ácido nucleico, vetor e célula hospedeira |
| US9683052B2 (en) | 2011-03-25 | 2017-06-20 | Glenmark Pharmaceuticals S.A. | Hetero-dimeric immunoglobulins |
| SI2691417T2 (sl) | 2011-03-29 | 2025-05-30 | Roche Glycart Ag | FC variante protitelesa |
| CN107903325B (zh) * | 2011-05-16 | 2021-10-29 | 埃泰美德(香港)有限公司 | 多特异性fab融合蛋白及其使用方法 |
| CN109517059B (zh) | 2011-06-30 | 2023-03-28 | 中外制药株式会社 | 异源二聚化多肽 |
| WO2013012733A1 (en) | 2011-07-15 | 2013-01-24 | Biogen Idec Ma Inc. | Heterodimeric fc regions, binding molecules comprising same, and methods relating thereto |
| KR101681818B1 (ko) * | 2011-08-23 | 2016-12-01 | 로슈 글리카트 아게 | T 세포 활성화 항원 및 종양 항원에 대해 특이적인 이중특이적 항체 및 이의 사용 방법 |
| US20130078250A1 (en) * | 2011-08-23 | 2013-03-28 | Oliver Ast | Bispecific t cell activating antigen binding molecules |
| NO2748201T3 (enExample) * | 2011-08-23 | 2018-05-12 | ||
| EP2787078B1 (en) | 2011-10-31 | 2019-05-22 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule having regulated conjugation between heavy-chain and light-chain |
| PT2794905T (pt) | 2011-12-20 | 2020-06-30 | Medimmune Llc | Polipéptidos modificados para estrutura de anticorpos bispecíficos |
| PT2838917T (pt) | 2012-04-20 | 2019-09-12 | Merus Nv | Métodos e meios para a produção de moléculas similares a ig heterodiméricas |
| EP2855531A1 (en) * | 2012-05-24 | 2015-04-08 | F. Hoffmann-La Roche AG | Multispecific antibodies |
| CN104662044B (zh) | 2012-08-24 | 2018-10-30 | 加利福尼亚大学董事会 | 用于治疗ror1癌症并抑制转移的抗体和疫苗 |
| EP2904016B1 (en) * | 2012-10-08 | 2018-11-14 | Roche Glycart AG | Fc-free antibodies comprising two fab-fragments and methods of use |
| UY35148A (es) * | 2012-11-21 | 2014-05-30 | Amgen Inc | Immunoglobulinas heterodiméricas |
| US10968276B2 (en) | 2013-03-12 | 2021-04-06 | Xencor, Inc. | Optimized anti-CD3 variable regions |
| CN105051069B (zh) | 2013-01-14 | 2019-12-10 | Xencor股份有限公司 | 新型异二聚体蛋白 |
| US10077315B2 (en) | 2013-02-05 | 2018-09-18 | Engmab Sàrl | Bispecific antibodies against CD3 and BCMA |
| KR20180023035A (ko) * | 2013-02-26 | 2018-03-06 | 로슈 글리카트 아게 | 이중특이적 t 세포 활성화 항원 결합 분자 |
| US20160017058A1 (en) * | 2013-03-14 | 2016-01-21 | The California Institute For Biomedical Research | Bispecific antibodies and uses thereof |
| EP2789630A1 (en) * | 2013-04-09 | 2014-10-15 | EngMab AG | Bispecific antibodies against CD3e and ROR1 |
| UA117289C2 (uk) * | 2014-04-02 | 2018-07-10 | Ф. Хоффманн-Ля Рош Аг | Мультиспецифічне антитіло |
| WO2015181805A1 (en) * | 2014-05-28 | 2015-12-03 | Zymeworks Inc. | Modified antigen binding polypeptide constructs and uses thereof |
| EP2982692A1 (en) * | 2014-08-04 | 2016-02-10 | EngMab AG | Bispecific antibodies against CD3epsilon and BCMA |
| DK3177643T3 (da) * | 2014-08-04 | 2019-07-15 | Hoffmann La Roche | Bispecifikke T-celle-aktiverende antigenbindende molekyler |
| AU2015318008B2 (en) * | 2014-09-15 | 2021-05-20 | Amgen Inc. | Bi-specific anti-CGRP receptor/PAC1 receptor antigen binding proteins and uses thereof |
| JP6708635B2 (ja) * | 2014-10-09 | 2020-06-10 | エンクマフ エスアーエールエル | ＣＤ３εおよびＲＯＲ１に対する二特異性抗体 |
| EP3029068A1 (en) | 2014-12-03 | 2016-06-08 | EngMab AG | Bispecific antibodies against CD3epsilon and BCMA for use in the treatment of diseases |
| CA2992797A1 (en) | 2015-08-03 | 2017-02-09 | Engmab Sarl | Monoclonal antibodies against bcma |
| CN110167964B (zh) | 2016-11-02 | 2023-12-01 | 百时美施贵宝公司 | 组合用于治疗多发性骨髓瘤的针对bcma和cd3的双特异性抗体和免疫药物 |
| WO2020219978A1 (en) | 2019-04-25 | 2020-10-29 | Celgene Corporation | Bcma/cd3 bispecific trivalent t-cell engaging (tce) antibodies and their use to treat hematological malignancies |
| IL292704A (en) | 2019-11-05 | 2022-07-01 | Bristol Myers Squibb Co | Methods of treatment with antibodies against bcma and cd3 |
| WO2021092060A1 (en) | 2019-11-05 | 2021-05-14 | Engmab Sarl | Methods of treatment |
| KR20220141306A (ko) | 2020-02-12 | 2022-10-19 | 브리스톨-마이어스 스큅 컴퍼니 | 자가면역 질환의 항-bcma 요법(anti-bcma therapy in autoimmune disorders) |
| US20230172923A1 (en) | 2020-04-30 | 2023-06-08 | Bristol-Myers Squibb Company | Methods of treating cytokine-related adverse events |
-
2015
- 2015-10-08 JP JP2017518525A patent/JP6708635B2/ja not_active Expired - Fee Related
- 2015-10-08 CA CA2963692A patent/CA2963692A1/en not_active Abandoned
- 2015-10-08 US US15/517,296 patent/US11952421B2/en active Active
- 2015-10-08 ES ES15778294T patent/ES2850325T3/es active Active
- 2015-10-08 WO PCT/EP2015/073308 patent/WO2016055592A1/en not_active Ceased
- 2015-10-08 EP EP15778294.7A patent/EP3204415B1/en active Active
- 2015-10-08 AU AU2015329965A patent/AU2015329965A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20170306018A1 (en) | 2017-10-26 |
| WO2016055592A1 (en) | 2016-04-14 |
| US11952421B2 (en) | 2024-04-09 |
| JP6708635B2 (ja) | 2020-06-10 |
| ES2850325T3 (es) | 2021-08-27 |
| JP2018502050A (ja) | 2018-01-25 |
| EP3204415B1 (en) | 2020-06-17 |
| EP3204415A1 (en) | 2017-08-16 |
| CA2963692A1 (en) | 2016-04-14 |
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