CA2963696A1 - Bispecific antibodies against cd3epsilon and ror1 for use in the treatment of ovarian cancer - Google Patents
Bispecific antibodies against cd3epsilon and ror1 for use in the treatment of ovarian cancer Download PDFInfo
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- CA2963696A1 CA2963696A1 CA2963696A CA2963696A CA2963696A1 CA 2963696 A1 CA2963696 A1 CA 2963696A1 CA 2963696 A CA2963696 A CA 2963696A CA 2963696 A CA2963696 A CA 2963696A CA 2963696 A1 CA2963696 A1 CA 2963696A1
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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
- C07K16/2803—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
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- C07K16/46—Hybrid immunoglobulins
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
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- C—CHEMISTRY; METALLURGY
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- C07K2317/00—Immunoglobulins specific features
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- C07K—PEPTIDES
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- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
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- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
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- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
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- C—CHEMISTRY; METALLURGY
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- 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
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
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Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
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| EP14188378 | 2014-10-09 | ||
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| EP14188727 | 2014-10-14 | ||
| EP14188728.1 | 2014-10-14 | ||
| EP14188727.3 | 2014-10-14 | ||
| PCT/EP2015/073309 WO2016055593A1 (en) | 2014-10-09 | 2015-10-08 | Bispecific antibodies against cd3epsilon and ror1 for use in the treatment of ovarian cancer |
Publications (1)
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| CA2963696A1 true CA2963696A1 (en) | 2016-04-14 |
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| CA2963696A Abandoned CA2963696A1 (en) | 2014-10-09 | 2015-10-08 | Bispecific antibodies against cd3epsilon and ror1 for use in the treatment of ovarian cancer |
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| EP (1) | EP3204416A1 (OSRAM) |
| JP (1) | JP2017536341A (OSRAM) |
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| CA (1) | CA2963696A1 (OSRAM) |
| WO (1) | WO2016055593A1 (OSRAM) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107827984A (zh) * | 2017-09-13 | 2018-03-23 | 张慧林 | 嵌合抗ROR1抗体Fab分子及其制备方法和应用 |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2710042A2 (en) | 2011-05-16 | 2014-03-26 | Fabion Pharmaceuticals, Inc. | Multi-specific fab fusion proteins and methods of use |
| WO2013026839A1 (en) | 2011-08-23 | 2013-02-28 | Roche Glycart Ag | Bispecific antibodies specific for t-cell activating antigens and a tumor antigen and methods of use |
| RU2015117393A (ru) | 2012-10-08 | 2016-12-10 | Роше Гликарт Аг | Лишенные fc антитела, содержащие два Fab-фрагмента, и способы их применения |
| EA201891502A1 (ru) | 2013-02-26 | 2018-12-28 | Роше Гликарт Аг | Биспецифические антигенсвязывающие молекулы, активирующие т-клетки |
| EP2789630A1 (en) * | 2013-04-09 | 2014-10-15 | EngMab AG | Bispecific antibodies against CD3e and ROR1 |
| KR102411972B1 (ko) | 2014-08-04 | 2022-06-23 | 에프. 호프만-라 로슈 아게 | 이중특이적 t 세포 활성화 항원 결합 분자 |
| CN107074955B (zh) | 2014-11-20 | 2021-06-22 | 豪夫迈·罗氏有限公司 | 针对FolR1和CD3的T细胞活化性双特异性抗原结合分子 |
| LT3789402T (lt) | 2014-11-20 | 2022-09-26 | F. Hoffmann-La Roche Ag | Kompleksinė terapija, naudojant t ląsteles aktyvinančias bispecifines antigeną surišančias molekules ir pd-1 ašį surišančius antagonistus |
| RS60615B1 (sr) | 2014-11-20 | 2020-08-31 | Hoffmann La Roche | Zajednički laki lanci i postupci upotrebe |
| AR106188A1 (es) | 2015-10-01 | 2017-12-20 | Hoffmann La Roche | Anticuerpos anti-cd19 humano humanizados y métodos de utilización |
| CN107849137B (zh) | 2015-10-02 | 2021-11-26 | 豪夫迈·罗氏有限公司 | 双特异性抗ceaxcd3 t细胞活化性抗原结合分子 |
| EP3368574A1 (en) | 2015-10-30 | 2018-09-05 | NBE-Therapeutics AG | Anti-ror1 antibodies |
| IL257696B2 (en) | 2015-12-09 | 2024-11-01 | Hoffmann La Roche | Type ii anti-cd20 antibody for reducing formation of anti-drug antibodies |
| KR20180097615A (ko) | 2016-01-08 | 2018-08-31 | 에프. 호프만-라 로슈 아게 | Pd-1 축 결합 길항물질 및 항-cea/항-cd3 이중특이성 항체를 사용하는 cea-양성 암의 치료 방법 |
| CN108848669B (zh) | 2016-01-20 | 2022-06-07 | 斯克利普斯研究所 | Ror1抗体组合物和相关方法 |
| JP7034489B2 (ja) | 2016-03-15 | 2022-03-14 | アイタブメッド （エイチケイ） リミテッド | 多重特異性Ｆａｂ融合タンパクおよびその使用 |
| FI3433280T3 (fi) | 2016-03-22 | 2023-06-06 | Hoffmann La Roche | Proteaasin aktivoimia t-solubispesifisiä molekyylejä |
| WO2018060301A1 (en) * | 2016-09-30 | 2018-04-05 | F. Hoffmann-La Roche Ag | Bispecific antibodies against cd3 |
| MY200973A (en) | 2017-04-11 | 2024-01-26 | Inhibrx Inc | Multispecific Polypeptide Constructs Having Constrained Cd3 Binding And Methods Of Using The Same |
| AU2018289581C1 (en) | 2017-06-23 | 2025-01-30 | VelosBio Inc. | ROR1 antibody immunoconjugates |
| 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 |
| GB201710835D0 (en) | 2017-07-05 | 2017-08-16 | Ucl Business Plc | ROR1 Antibodies |
| US20210139579A1 (en) * | 2017-07-20 | 2021-05-13 | Nbe-Therapeutics Ag | Multispecific antibody product that binds to different ror1 epitopes |
| WO2019030240A1 (en) | 2017-08-07 | 2019-02-14 | Nbe-Therapeutics Ag | ANTIBODIES BINDING TO A LINEAR HUMAN CS1 EPITOPE |
| GB201721802D0 (en) * | 2017-12-22 | 2018-02-07 | Almac Discovery Ltd | Ror1-specific antigen binding molecules |
| MX2020008289A (es) | 2018-02-08 | 2020-09-25 | Genentech Inc | Moleculas biespecificas de union al antigeno y metodos de uso. |
| TWI829667B (zh) * | 2018-02-09 | 2024-01-21 | 瑞士商赫孚孟拉羅股份公司 | 結合gprc5d之抗體 |
| MX2020010267A (es) | 2018-03-30 | 2020-11-06 | Merus Nv | Anticuerpo multivalente. |
| IL323061A (en) | 2018-04-11 | 2025-10-01 | Inhibrx Biosciences Inc | Multispecific polypeptide constructs with forced CD3 binding and related methods and uses |
| WO2019204564A1 (en) * | 2018-04-18 | 2019-10-24 | Exelixis, Inc. | Anti-ror antibody constructs |
| CN112789294A (zh) | 2018-07-24 | 2021-05-11 | 印希比股份有限公司 | 含有受限cd3结合结构域和受体结合区的多特异性多肽构建体及其使用方法 |
| EP3847196A4 (en) * | 2018-09-07 | 2023-01-04 | ITabMed (HK) Limited | BISPECIFIC ANTIGEN BINDING PROTEINS AND USES THEREOF |
| TW202506736A (zh) * | 2018-10-11 | 2025-02-16 | 美商因荷布瑞克斯生物科學公司 | 5t4單域抗體及其治療性組合物 |
| CA3115089A1 (en) | 2018-10-11 | 2020-04-16 | Inhibrx, Inc. | Dll3 single domain antibodies and therapeutic compositions thereof |
| KR20220024637A (ko) * | 2019-06-19 | 2022-03-03 | 에프. 호프만-라 로슈 아게 | 정의된 조직의 다수 발현 카세트들의 표적화 통합에 의한 3가 항체 발현 세포의 생성 방법 |
| PE20220394A1 (es) * | 2019-07-31 | 2022-03-18 | Hoffmann La Roche | Anticuerpos que se fijan a gprc5d |
| TWI852680B (zh) | 2020-06-19 | 2024-08-11 | 瑞士商赫孚孟拉羅股份公司 | 與 cd3 及 cd19 結合之抗體 |
| CN114085288A (zh) * | 2020-08-24 | 2022-02-25 | 岸迈生物科技(苏州)有限公司 | 抗ror1抗体 |
| EP3988568A1 (en) * | 2020-10-21 | 2022-04-27 | Numab Therapeutics AG | Combination treatment |
| AU2021411896B2 (en) * | 2020-12-29 | 2025-12-11 | Samsung Biologics Co., Ltd. | Bi- or multi-specific antibody |
| PE20250740A1 (es) * | 2021-02-02 | 2025-03-13 | Numab Therapeutics AG | Anticuerpos multiespecificos con especificidad para ror1 y cd3 |
| MX2023012408A (es) | 2021-04-30 | 2023-10-31 | Hoffmann La Roche | Dosis para tratamiento conjunto con anticuerpo biespecifico anti-cd20/anti-cd3 y conjugado anticuerpo farmaco anti-cd79b. |
| IL322923A (en) * | 2023-02-23 | 2025-10-01 | Adanate Inc | Anti-CD3 antibodies and methods of using them |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| EP2496605A1 (en) * | 2009-11-02 | 2012-09-12 | Oxford Biotherapeutics Ltd. | Ror1 as therapeutic and diagnostic target |
| WO2012045085A1 (en) * | 2010-10-01 | 2012-04-05 | Oxford Biotherapeutics Ltd. | Anti-rori antibodies |
| 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 |
| WO2013026837A1 (en) * | 2011-08-23 | 2013-02-28 | Roche Glycart Ag | Bispecific t cell activating antigen binding molecules |
| US11851476B2 (en) * | 2011-10-31 | 2023-12-26 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule having regulated conjugation between heavy-chain and light-chain |
| TWI679212B (zh) * | 2011-11-15 | 2019-12-11 | 美商安進股份有限公司 | 針對ｂｃｍａ之e3以及ｃｄ３的結合分子 |
| JP2015520168A (ja) * | 2012-05-24 | 2015-07-16 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | 多重特異性抗体 |
| RU2015117393A (ru) * | 2012-10-08 | 2016-12-10 | Роше Гликарт Аг | Лишенные fc антитела, содержащие два Fab-фрагмента, и способы их применения |
| EA201891502A1 (ru) * | 2013-02-26 | 2018-12-28 | Роше Гликарт Аг | Биспецифические антигенсвязывающие молекулы, активирующие т-клетки |
| EP2968552B1 (en) * | 2013-03-14 | 2020-03-11 | The Scripps Research Institute | Targeting agent antibody conjugates and uses thereof |
| AU2014236769B2 (en) * | 2013-03-15 | 2018-09-27 | Amgen Inc. | Heterodimeric bispecific antibodies |
| EP2789630A1 (en) * | 2013-04-09 | 2014-10-15 | EngMab AG | Bispecific antibodies against CD3e and ROR1 |
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- 2015-10-08 WO PCT/EP2015/073309 patent/WO2016055593A1/en not_active Ceased
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- 2015-10-08 US US15/517,329 patent/US20170306044A1/en not_active Abandoned
- 2015-10-08 EP EP15778295.4A patent/EP3204416A1/en not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107827984A (zh) * | 2017-09-13 | 2018-03-23 | 张慧林 | 嵌合抗ROR1抗体Fab分子及其制备方法和应用 |
Also Published As
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| AU2015329966A1 (en) | 2017-04-27 |
| WO2016055593A1 (en) | 2016-04-14 |
| EP3204416A1 (en) | 2017-08-16 |
| JP2017536341A (ja) | 2017-12-07 |
| US20170306044A1 (en) | 2017-10-26 |
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| Date | Code | Title | Description |
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| FZDE | Discontinued |
Effective date: 20201008 |