CA3101604A1 - Multi-specific binding proteins and improvements thereon - Google Patents
Multi-specific binding proteins and improvements thereon Download PDFInfo
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- CA3101604A1 CA3101604A1 CA3101604A CA3101604A CA3101604A1 CA 3101604 A1 CA3101604 A1 CA 3101604A1 CA 3101604 A CA3101604 A CA 3101604A CA 3101604 A CA3101604 A CA 3101604A CA 3101604 A1 CA3101604 A1 CA 3101604A1
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
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| PCT/US2019/034186 WO2019231920A1 (en) | 2018-05-28 | 2019-05-28 | Multi-specific binding proteins and improvements thereon |
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| JP (2) | JP2021525731A (enExample) |
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| AU (1) | AU2019277138B2 (enExample) |
| BR (1) | BR112020024235A2 (enExample) |
| CA (1) | CA3101604A1 (enExample) |
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| EA (2) | EA202091977A1 (enExample) |
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Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016142783A2 (en) * | 2015-03-10 | 2016-09-15 | Leiden University Medical Center | T-cell receptors directed against the preferentially expressed antigen of melanoma and uses thereof |
| KR20220038511A (ko) | 2016-12-08 | 2022-03-28 | 이매틱스 바이오테크놀로지스 게엠베하 | T 세포 수용체 및 이를 사용하는 면역 요법 |
| JP2020506971A (ja) | 2017-02-08 | 2020-03-05 | ドラゴンフライ セラピューティクス， インコーポレイテッド | ナチュラルキラー細胞の活性化のための多重特異性結合タンパク質およびがんを処置するためのその治療的使用 |
| SG11201907646YA (en) | 2017-02-20 | 2019-09-27 | Dragonfly Therapeutics Inc | Proteins binding her2, nkg2d and cd16 |
| ES2898210T3 (es) | 2017-07-14 | 2022-03-04 | Immatics Biotechnologies Gmbh | Molécula de polipéptido con especificidad dual mejorada |
| WO2019139987A1 (en) | 2018-01-09 | 2019-07-18 | Elstar Therapeutics, Inc. | Calreticulin binding constructs and engineered t cells for the treatment of diseases |
| PE20210375A1 (es) | 2018-02-08 | 2021-03-02 | Dragonfly Therapeutics Inc | Terapia de combinacion del cancer que incluye proteinas de union multiespecificas que activan a las celulas asesinas naturales |
| FI3749346T3 (fi) | 2018-02-08 | 2024-09-04 | Dragonfly Therapeutics Inc | Nkg2d-reseptoriin kohdistuvat vasta-aineen vaihtelevan domeenin yhdistelmät |
| MX2020008684A (es) * | 2018-02-20 | 2020-12-07 | Dragonfly Therapeutics Inc | Proteinas de union multiespecificas que se unen a cd33, nkg2d y cd16 y metodos de uso. |
| US12152073B2 (en) | 2018-03-14 | 2024-11-26 | Marengo Therapeutics, Inc. | Multifunctional molecules that bind to calreticulin and uses thereof |
| CN112955465A (zh) | 2018-07-03 | 2021-06-11 | 马伦戈治疗公司 | 抗tcr抗体分子及其用途 |
| JP7482363B2 (ja) | 2018-08-08 | 2024-05-14 | ドラゴンフライ セラピューティクス， インコーポレイテッド | Ｎｋｇ２ｄ、ｃｄ１６及び腫瘍関連抗原に結合するタンパク質 |
| MX2021001510A (es) * | 2018-08-08 | 2021-07-02 | Dragonfly Therapeutics Inc | Proteínas de union a nkg2d, cd16, y un antígeno asociado a tumores. |
| EA202091888A1 (ru) * | 2018-08-08 | 2020-10-23 | Драгонфлай Терапьютикс, Инк. | Вариабельные домены антител, нацеленные на рецептор nkg2d |
| US12384851B2 (en) | 2018-08-08 | 2025-08-12 | Dragonfly Therapeutics, Inc. | Multi-specific binding proteins that bind BCMA, NKG2D and CD16, and methods of use |
| AU2020209991B2 (en) * | 2019-01-17 | 2024-11-14 | Immunocore Limited | Formulations |
| WO2020172605A1 (en) | 2019-02-21 | 2020-08-27 | Elstar Therapeutics, Inc. | Antibody molecules that bind to nkp30 and uses thereof |
| JP7710373B2 (ja) | 2019-02-21 | 2025-07-18 | マレンゴ・セラピューティクス，インコーポレーテッド | Ｔ細胞関連のがん細胞に結合する多機能性分子およびその使用 |
| KR20220016083A (ko) | 2019-04-30 | 2022-02-08 | 센티 바이오사이언시스, 인코포레이티드 | 키메라 수용체 및 이의 사용 방법 |
| CA3166629A1 (en) | 2020-01-03 | 2021-07-08 | Marengo Therapeutics, Inc. | Anti-tcr antibody molecules and uses thereof |
| EP4143236A1 (en) * | 2020-05-01 | 2023-03-08 | Novartis AG | Engineered immunoglobulins |
| US20230312753A1 (en) * | 2020-05-04 | 2023-10-05 | Immunorizon Ltd. | Precursor tri-specific antibody constructs and methods of use thereof |
| TW202208428A (zh) | 2020-05-06 | 2022-03-01 | 美商蜻蜓醫療公司 | 結合ｎｋｇ２ｄ、ｃｄ１６及ｃｌｅｃ１２ａ之蛋白質 |
| JP2023545099A (ja) * | 2020-10-08 | 2023-10-26 | アフィメド ゲーエムベーハー | 三重特異性バインダー |
| TWI825544B (zh) * | 2020-12-31 | 2023-12-11 | 大陸商信達生物製藥（蘇州）有限公司 | 含異二聚體抗體Ｆｃ的蛋白以及其製備方法 |
| CN117440969A (zh) * | 2021-01-11 | 2024-01-23 | 阿迪马布有限责任公司 | 被工程化为优先进行ch3异源二聚化的变体ch3结构域、包括所述变体ch3结构域的多特异性抗体和其制备方法 |
| EP4301774A4 (en) | 2021-03-03 | 2025-08-13 | Dragonfly Therapeutics Inc | METHODS OF TREATING CANCER USING MULTI-SPECIFIC BINDING PROTEINS THAT BIND TO NKG2D, CD16, AND A TUMOR-ASSOCIATED ANTIGEN |
| WO2022212470A2 (en) * | 2021-03-31 | 2022-10-06 | Janssen Biotech, Inc. | Materials and methods for immune effector cells redirection |
| EP4334361A1 (en) | 2021-05-05 | 2024-03-13 | Immatics Biotechnologies GmbH | Antigen binding proteins specifically binding prame |
| EP4405398A4 (en) | 2021-09-21 | 2025-10-29 | Qilu Puget Sound Biotherapeutics Corp | FC HETERODIMERS ALLOWING THE MANUFACTURE OF FUSION PROTEINS AND BI-SPECIFIC ANTIBODIES |
| WO2023148494A1 (en) * | 2022-02-03 | 2023-08-10 | University College Cardiff Consultants Limited | Novel t-cell receptor |
| TW202502822A (zh) * | 2023-07-07 | 2025-01-16 | 大陸商四川科倫博泰生物醫藥股份有限公司 | Ｅｇｆｒ／ｃ－ｍｅｔ雙特異性結合蛋白及其用途 |
| WO2025050020A1 (en) * | 2023-08-30 | 2025-03-06 | Mink Therapeutics, Inc. | Novel t cell receptors that bind to preferentially expressed antigen in melanoma (prame) and methods of use thereof |
| WO2025233431A1 (en) * | 2024-05-07 | 2025-11-13 | Immatics Biotechnologies Gmbh | Heteromeric proteins comprising three heteromerization improving substitution, production, combinations and applications thereof |
Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10156482A1 (de) * | 2001-11-12 | 2003-05-28 | Gundram Jung | Bispezifisches Antikörper-Molekül |
| EP1809669A2 (en) * | 2004-10-01 | 2007-07-25 | Avidex Ltd | T-cell receptors containing a non-native disulfide interchain bond linked to therapeutic agents |
| GB0614780D0 (en) * | 2006-07-25 | 2006-09-06 | Ucb Sa | Biological products |
| PL2222706T5 (pl) | 2007-12-14 | 2017-09-29 | Novo Nordisk As | Przeciwciała przeciwko ludzkiemu NKG2D i ich zastosowania |
| WO2010017103A2 (en) | 2008-08-04 | 2010-02-11 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Servic | Fully human anti-human nkg2d monoclonal antibodies |
| TW201109438A (en) * | 2009-07-29 | 2011-03-16 | Abbott Lab | Dual variable domain immunoglobulins and uses thereof |
| BR112014015018A2 (pt) * | 2011-12-19 | 2020-10-27 | Synimmune Gmbh | moléculas de anticorpo biespecífico e seu método de produção, bem como composição farmacêutica e molécula de ácido nucleico |
| CN104271602B (zh) * | 2012-11-21 | 2020-08-21 | 武汉友芝友生物制药有限公司 | 双特异性抗体 |
| KR101522954B1 (ko) * | 2012-11-27 | 2015-05-27 | 아주대학교산학협력단 | 항체 중쇄불변부위의 이종이중체 고효율 형성을 유도하는 ch3 도메인 변이체 쌍, 이의 제조방법, 및 용도 |
| EP3587448B1 (en) * | 2013-03-15 | 2021-05-19 | Xencor, Inc. | Heterodimeric proteins |
| WO2015095412A1 (en) | 2013-12-19 | 2015-06-25 | Zhong Wang | Bispecific antibody with two single-domain antigen-binding fragments |
| JP6721590B2 (ja) * | 2014-12-03 | 2020-07-15 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | 多重特異性抗体 |
| WO2016100533A2 (en) * | 2014-12-17 | 2016-06-23 | Intrexon Corporation | Intercalated single-chain variable fragments |
| JP2018503399A (ja) * | 2015-01-14 | 2018-02-08 | コンパス セラピューティクス リミテッド ライアビリティ カンパニー | 多特異性免疫調節抗原結合構築物 |
| WO2016134371A2 (en) | 2015-02-20 | 2016-08-25 | Ohio State Innovation Foundation | Bivalent antibody directed against nkg2d and tumor associated antigens |
| EP3095792A1 (en) * | 2015-05-19 | 2016-11-23 | Klinikum rechts der Isar der Technischen Universität München | T cell receptor with specificity for myeloperoxidase peptide and uses thereof |
| AU2016284866B2 (en) * | 2015-06-23 | 2022-09-29 | Innate Pharma | Multispecific antigen binding proteins |
| US20180327499A1 (en) * | 2015-11-13 | 2018-11-15 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti- nkg2d single domain antibodies and uses thereof |
| US11291721B2 (en) * | 2016-03-21 | 2022-04-05 | Marengo Therapeutics, Inc. | Multispecific and multifunctional molecules and uses thereof |
| JP2020506971A (ja) * | 2017-02-08 | 2020-03-05 | ドラゴンフライ セラピューティクス， インコーポレイテッド | ナチュラルキラー細胞の活性化のための多重特異性結合タンパク質およびがんを処置するためのその治療的使用 |
| MY205850A (en) * | 2017-02-10 | 2024-11-15 | Dragonfly Therapeutics Inc | Proteins binding bcma, nkg2d and cd16 |
| US20210130471A1 (en) * | 2017-02-20 | 2021-05-06 | Dragonfly Therapeutics, Inc. | Proteins binding cd33, nkg2d and cd16 |
| SG11201907646YA (en) * | 2017-02-20 | 2019-09-27 | Dragonfly Therapeutics Inc | Proteins binding her2, nkg2d and cd16 |
| CA3176049A1 (en) * | 2017-08-16 | 2019-02-21 | Dragonfly Therapeutics, Inc. | Proteins binding nkg2d, cd16, and egfr, ccr4, or pd-l1 |
| KR20240167101A (ko) * | 2017-09-07 | 2024-11-26 | 드래곤플라이 쎄라퓨틱스, 인크. | Nkg2d, cd16 및 넥틴4에 결합하는 단백질 |
| MX2020008684A (es) * | 2018-02-20 | 2020-12-07 | Dragonfly Therapeutics Inc | Proteinas de union multiespecificas que se unen a cd33, nkg2d y cd16 y metodos de uso. |
| SG11202007943RA (en) * | 2018-02-20 | 2020-09-29 | Dragonfly Therapeutics Inc | Antibody variable domains targeting cd33, and use thereof |
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2019
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- 2019-05-28 CN CN202311768455.3A patent/CN117964773A/zh active Pending
- 2019-05-28 EA EA202092907A patent/EA202092907A1/ru unknown
- 2019-05-28 SG SG11202011763YA patent/SG11202011763YA/en unknown
- 2019-05-28 US US17/058,335 patent/US20210214436A1/en active Pending
- 2019-05-28 KR KR1020207036884A patent/KR20210013160A/ko not_active Ceased
- 2019-05-28 BR BR112020024235-7A patent/BR112020024235A2/pt unknown
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2023
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| KR20210013160A (ko) | 2021-02-03 |
| CN117964773A (zh) | 2024-05-03 |
| BR112020024235A2 (pt) | 2021-05-04 |
| EP3802581A4 (en) | 2022-04-13 |
| AU2019277138B2 (en) | 2024-06-13 |
| IL278943A (en) | 2021-01-31 |
| PE20210167A1 (es) | 2021-01-28 |
| JP7726967B2 (ja) | 2025-08-20 |
| CN112533944A (zh) | 2021-03-19 |
| EA202092907A1 (ru) | 2021-04-13 |
| SG11202011763YA (en) | 2020-12-30 |
| EP4537904A3 (en) | 2025-07-16 |
| EP3802581A1 (en) | 2021-04-14 |
| MX2020012905A (es) | 2021-05-27 |
| JP2024023438A (ja) | 2024-02-21 |
| AU2019277138A1 (en) | 2020-12-17 |
| CL2020003071A1 (es) | 2021-05-24 |
| WO2019231920A1 (en) | 2019-12-05 |
| EA202091977A1 (ru) | 2021-02-09 |
| EP4537904A2 (en) | 2025-04-16 |
| US20210214436A1 (en) | 2021-07-15 |
| JP2021525731A (ja) | 2021-09-27 |
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