JP7242573B2 - Ｒｏｒ１抗体 - Google Patents
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- JP7242573B2 JP7242573B2 JP2019572456A JP2019572456A JP7242573B2 JP 7242573 B2 JP7242573 B2 JP 7242573B2 JP 2019572456 A JP2019572456 A JP 2019572456A JP 2019572456 A JP2019572456 A JP 2019572456A JP 7242573 B2 JP7242573 B2 JP 7242573B2
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| PL2884999T3 (pl) | 2012-08-20 | 2021-07-05 | Fred Hutchinson Cancer Research Center | Sposób i kompozycje do immunoterapii komórkowej |
| PL3489261T3 (pl) * | 2012-08-24 | 2021-08-16 | The Regents Of The University Of California | Przeciwciała i szczepionki do stosowania w leczeniu nowotworów z ekspresją ROR1 i w hamowaniu przerzutu |
| NZ726520A (en) | 2014-05-29 | 2018-12-21 | Macrogenics Inc | Tri-specific binding molecules that specifically bind to multiple cancer antigens and methods of use thereof |
| BR112017001821A2 (pt) * | 2014-07-29 | 2017-11-21 | Cellectis | receptores de antígenos quiméricos específicos de ror1 (ntrkr1) para imunoterapia de câncer |
| WO2016016343A1 (en) | 2014-07-31 | 2016-02-04 | Cellectis | Ror1 specific multi-chain chimeric antigen receptor |
| IL250848B (en) | 2014-09-08 | 2022-07-01 | Rin Inst Inc | Cancer-cell-specific antibody, anticancer agent, and cancer testing method |
| EP3204415B1 (en) | 2014-10-09 | 2020-06-17 | EngMab Sàrl | Bispecific antibodies against cd3epsilon and ror1 |
| JP2017536341A (ja) | 2014-10-09 | 2017-12-07 | エンクマフ アーゲー | 卵巣がんの処置における使用のためのＣＤ３εおよびＲＯＲ１に対する二特異性抗体 |
| WO2016094873A2 (en) | 2014-12-12 | 2016-06-16 | Emergent Product Development Seattle, Llc | Receptor tyrosine kinase-like orphan receptor 1 binding proteins and related compositions and methods |
| NZ733841A (en) | 2015-01-16 | 2024-01-26 | Juno Therapeutics Inc | Antibodies and chimeric antigen receptors specific for ror1 |
| CA2973773C (en) | 2015-02-02 | 2023-10-17 | Kancera Ab | 2-phenyl-3h-imidazo[4,5-b]pyridine derivatives useful as inhibitors of mammalian tyrosine kinase ror1 activity |
| EP3842072A1 (en) * | 2015-05-18 | 2021-06-30 | Eureka Therapeutics, Inc. | Anti-ror1 antibodies |
| EP3298032A1 (en) | 2015-05-18 | 2018-03-28 | Bluebird Bio, Inc. | Anti-ror1 chimeric antigen receptors |
| EP3368574A1 (en) | 2015-10-30 | 2018-09-05 | NBE-Therapeutics AG | Anti-ror1 antibodies |
| 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 |
| JP2019506158A (ja) | 2016-01-22 | 2019-03-07 | ヤンセン バイオテツク，インコーポレーテツド | 抗ｒｏｒ１抗体、ｒｏｒ１×ｃｄ３二重特異性抗体、及びそれらの使用法 |
| WO2017142928A1 (en) | 2016-02-17 | 2017-08-24 | Macrogenics, Inc. | Ror1-binding molecules, and methods of use thereof |
| WO2017156479A1 (en) | 2016-03-11 | 2017-09-14 | Bluebird Bio, Inc. | Ror1 chimeric antigen receptors |
| KR102466810B1 (ko) | 2016-07-11 | 2022-11-11 | 칸세라 아베 | 포유류 티로신 키나제 ror1 활성의 저해제로서 유용한 2-페닐이미다조[4,5-b]피리딘-7-아민 유도체 |
| WO2018119314A1 (en) | 2016-12-22 | 2018-06-28 | Ardeagen Corporation | Anti-ror1 antibody and conjugates thereof |
| CA3064743A1 (en) | 2017-05-23 | 2018-11-29 | Dragonfly Therapeutics, Inc. | A protein binding nkg2d, cd16 and ror1 or ror2 |
| AU2018289581C1 (en) | 2017-06-23 | 2025-01-30 | VelosBio Inc. | ROR1 antibody immunoconjugates |
| CN116925227A (zh) | 2017-06-25 | 2023-10-24 | 西雅图免疫公司 | 抗ror1抗体及其制备和使用方法 |
| 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 |
| EP3703711A4 (en) | 2017-11-03 | 2021-01-13 | Lentigen Technology, Inc. | COMPOSITIONS AND METHODS FOR THE TREATMENT OF CANCER WITH ANTI-MMR1 IMMUNOTHERAPY |
| GB201721802D0 (en) | 2017-12-22 | 2018-02-07 | Almac Discovery Ltd | Ror1-specific antigen binding molecules |
| WO2019225777A1 (ko) | 2018-05-23 | 2019-11-28 | 에이비엘바이오 주식회사 | 항-ror1 항체 및 그 용도 |
-
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014167022A1 (en) | 2013-04-09 | 2014-10-16 | Engmab Ag | BISPECIFIC ANTIBODIES AGAINST CD3EPSILON and ROR1 |
Non-Patent Citations (3)
| Title |
|---|
| Almagro, J. C. et al.，Humanization of antibodies，Front. Biosci.，2008年，Vol. 13，pp. 1619-1633 |
| Gohil S H. et al.，An ROR1 bi-specific T-cell engager provides effective targeting and cytotoxicity against a range of solid tumors，Oncoimmunology，2017年05月17日，Vol. 6(7):e1326437，pp. 1-11 |
| Paredes-Moscosso S R. et al.，Novel ROR1 Antibody Is Able to Trigger Specific and Superior Complement-Dependent Cytotoxicity (CDC) on Primary CLL Cells，Blood，2016年，Vol. 128(22)，p. 2052 |
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| AU2018297630A1 (en) | 2020-01-16 |
| US20230220073A1 (en) | 2023-07-13 |
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| CN110891973A (zh) | 2020-03-17 |
| JP2020530272A (ja) | 2020-10-22 |
| US20200354448A1 (en) | 2020-11-12 |
| CN110891973B (zh) | 2023-06-27 |
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| US20250066472A1 (en) | 2025-02-27 |
| EP3649152A1 (en) | 2020-05-13 |
| US11466083B2 (en) | 2022-10-11 |
| DK3649152T3 (da) | 2025-11-10 |
| AU2018297630B2 (en) | 2025-03-06 |
| MX2019015348A (es) | 2020-07-20 |
| WO2019008377A1 (en) | 2019-01-10 |
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