JP7387585B2 - 混合系統白血病（ｍｌｌ）特異的ホスホペプチドに結合するｔ細胞受容体およびその使用方法 - Google Patents
混合系統白血病（ｍｌｌ）特異的ホスホペプチドに結合するｔ細胞受容体およびその使用方法 Download PDFInfo
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Family Cites Families (76)
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| US5580714A (en) | 1995-03-08 | 1996-12-03 | Celox Laboratories, Inc. | Cryopreservation solution |
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| EP1009429B1 (en) | 1997-08-29 | 2009-07-08 | Antigenics Inc. | Compositions comprising the adjuvant qs-21 and polysorbate or cyclodextrin as excipient |
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| IL127142A0 (en) | 1998-11-19 | 1999-09-22 | Yeda Res & Dev | Immune cells having predefined biological specificity |
| US6194137B1 (en) | 1999-04-13 | 2001-02-27 | Organ Recovery Systems, Inc. | Method of cryopreservation of blood vessels by vitrification |
| JP2002541845A (ja) | 1999-04-16 | 2002-12-10 | セルテック セラピューティックス リミテッド | 合成膜貫通成分 |
| EP1210428B1 (en) | 1999-08-23 | 2015-03-18 | Dana-Farber Cancer Institute, Inc. | Pd-1, a receptor for b7-4, and uses therefor |
| PT1234031T (pt) | 1999-11-30 | 2017-06-26 | Mayo Foundation | B7-h1, uma nova molécula imunoregulatória |
| JP4317940B2 (ja) | 2001-08-31 | 2009-08-19 | イミュノコア・リミテッド | 物質 |
| CA2466279A1 (en) | 2001-11-13 | 2003-05-22 | Dana-Farber Cancer Institute, Inc. | Agents that modulate immune cell activation and methods of use thereof |
| US20040014194A1 (en) | 2002-03-27 | 2004-01-22 | Schering Corporation | Beta-secretase crystals and methods for preparing and using the same |
| IL149820A0 (en) | 2002-05-23 | 2002-11-10 | Curetech Ltd | Humanized immunomodulatory monoclonal antibodies for the treatment of neoplastic disease or immunodeficiency |
| AU2003281200A1 (en) | 2002-07-03 | 2004-01-23 | Tasuku Honjo | Immunopotentiating compositions |
| US7569664B2 (en) | 2002-10-09 | 2009-08-04 | Immunocore Limited | Single chain recombinant T cell receptors |
| CN101899114A (zh) | 2002-12-23 | 2010-12-01 | 惠氏公司 | 抗pd-1抗体及其用途 |
| US9068234B2 (en) | 2003-01-21 | 2015-06-30 | Ptc Therapeutics, Inc. | Methods and agents for screening for compounds capable of modulating gene expression |
| CA2558366A1 (en) | 2004-02-23 | 2005-09-01 | Erasmus Universiteit Rotterdam | Classification, diagnosis and prognosis of acute myeloid leukemia by gene expression profiling |
| JP5563194B2 (ja) | 2004-06-29 | 2014-07-30 | イムノコア リミテッド | 改変ｔ細胞レセプターを発現する細胞 |
| CN109485727A (zh) | 2005-05-09 | 2019-03-19 | 小野药品工业株式会社 | 程序性死亡-1(pd-1)的人单克隆抗体及使用抗pd-1抗体来治疗癌症的方法 |
| KR101411165B1 (ko) | 2005-07-01 | 2014-06-25 | 메다렉스, 엘.엘.시. | 예정 사멸 리간드 1 (피디-엘1)에 대한 인간 모노클로날항체 |
| NZ600758A (en) | 2007-06-18 | 2013-09-27 | Merck Sharp & Dohme | Antibodies to human programmed death receptor pd-1 |
| GB0712670D0 (en) | 2007-06-29 | 2007-08-08 | King S College London | Isolated peptides and uses thereof |
| PL2242773T3 (pl) | 2008-02-11 | 2017-11-30 | Cure Tech Ltd. | Przeciwciała monoklonalne do leczenia nowotworu |
| EP2262837A4 (en) | 2008-03-12 | 2011-04-06 | Merck Sharp & Dohme | PD-1 BINDING PROTEINS |
| SG192485A1 (en) | 2008-07-08 | 2013-08-30 | Incyte Corp | 1,2,5-oxadiazoles as inhibitors of indoleamine 2,3-dioxygenase |
| EP2927240A1 (en) | 2008-08-25 | 2015-10-07 | Amplimmune, Inc. | Compositions of pd-1 antagonists and methods of use |
| EP2342229A1 (en) | 2008-09-12 | 2011-07-13 | ISIS Innovation Limited | Pd-1 specific antibodies and uses thereof |
| ES2592216T3 (es) | 2008-09-26 | 2016-11-28 | Dana-Farber Cancer Institute, Inc. | Anticuerpos anti-PD-1, PD-L1 y PD-L2 humanos y sus usos |
| WO2010077634A1 (en) | 2008-12-09 | 2010-07-08 | Genentech, Inc. | Anti-pd-l1 antibodies and their use to enhance t-cell function |
| US10464987B2 (en) | 2009-10-06 | 2019-11-05 | Abbvie Inc. | Human single-chain T cell receptors |
| NZ599405A (en) | 2009-11-24 | 2014-09-26 | Medimmune Ltd | Targeted binding agents against b7-h1 |
| WO2011100841A1 (en) | 2010-02-16 | 2011-08-25 | Valorisation-Recherche, Limited Partnership | Pd-1 modulation and uses thereof for modulating hiv replication |
| EP2545078A1 (en) | 2010-03-11 | 2013-01-16 | UCB Pharma, S.A. | Pd-1 antibody |
| US9089520B2 (en) | 2010-05-21 | 2015-07-28 | Baylor College Of Medicine | Methods for inducing selective apoptosis |
| PL2699264T3 (pl) | 2011-04-20 | 2018-08-31 | Medimmune, Llc | Przeciwciała i inne cząsteczki wiążące B7-H1 i PD-1 |
| LT2734551T (lt) | 2011-07-24 | 2018-04-10 | Cure Tech Ltd. | Humanizuotų imunomoduliuojančių monokloninių antikūnų variantai |
| US8920075B2 (en) | 2011-09-01 | 2014-12-30 | Halo Maritime Defense Systems, Inc. | Marine barrier and gate |
| EP2785375B1 (en) | 2011-11-28 | 2020-07-22 | Merck Patent GmbH | Anti-pd-l1 antibodies and uses thereof |
| CA2863799C (en) | 2012-02-22 | 2020-09-01 | Matthew J. FRIGAULT | Compositions and methods for generating a persisting population of t cells useful for the treatment of cancer |
| CN104736168B (zh) | 2012-05-31 | 2018-09-21 | 索伦托治疗有限公司 | 与pd-l1结合的抗原结合蛋白 |
| US9845356B2 (en) | 2012-08-03 | 2017-12-19 | Dana-Farber Cancer Institute, Inc. | Single agent anti-PD-L1 and PD-L2 dual binding antibodies and methods of use |
| JP6461800B2 (ja) | 2012-10-04 | 2019-01-30 | デイナ ファーバー キャンサー インスティチュート，インコーポレイテッド | ヒトモノクローナル抗ｐｄ−ｌ１抗体および使用方法 |
| AR093984A1 (es) | 2012-12-21 | 2015-07-01 | Merck Sharp & Dohme | Anticuerpos que se unen a ligando 1 de muerte programada (pd-l1) humano |
| HRP20210122T1 (hr) | 2013-05-02 | 2021-04-16 | Anaptysbio, Inc. | Protutijela usmjerena protiv programirane smrti-1 (pd-1) |
| CN111423511B (zh) | 2013-05-31 | 2024-02-23 | 索伦托药业有限公司 | 与pd-1结合的抗原结合蛋白 |
| WO2014209804A1 (en) | 2013-06-24 | 2014-12-31 | Biomed Valley Discoveries, Inc. | Bispecific antibodies |
| RU2645256C2 (ru) * | 2013-06-26 | 2018-02-19 | Гуандун Сянсюэ Лайф Сайенсис, Лтд. | Высокостабильный т-клеточный рецептор и способ его получения и применения |
| CN104250302B (zh) | 2013-06-26 | 2017-11-14 | 上海君实生物医药科技股份有限公司 | 抗pd‑1抗体及其应用 |
| WO2015036394A1 (en) | 2013-09-10 | 2015-03-19 | Medimmune Limited | Antibodies against pd-1 and uses thereof |
| ES2792183T3 (es) | 2013-09-13 | 2020-11-10 | Beigene Switzerland Gmbh | Anticuerpos anti-PD1 y su uso como productos terapéuticos y de diagnóstico |
| CN104558177B (zh) | 2013-10-25 | 2020-02-18 | 苏州思坦维生物技术股份有限公司 | 拮抗抑制程序性死亡受体pd-1与其配体结合的单克隆抗体及其编码序列与用途 |
| US10202454B2 (en) | 2013-10-25 | 2019-02-12 | Dana-Farber Cancer Institute, Inc. | Anti-PD-L1 monoclonal antibodies and fragments thereof |
| PE20160953A1 (es) | 2013-12-12 | 2016-09-26 | Shanghai hengrui pharmaceutical co ltd | Anticuerpo pd-1, fragmento de union al antigeno de este y uso medico de este |
| CN105263521B (zh) | 2014-01-15 | 2021-06-29 | 卡德门企业有限公司 | 免疫调节剂 |
| TWI680138B (zh) | 2014-01-23 | 2019-12-21 | 美商再生元醫藥公司 | 抗ｐｄ-ｌ１之人類抗體 |
| SG11201606577YA (en) | 2014-02-10 | 2016-09-29 | Merck Patent Gmbh | TARGETED TGFβ INHIBITION |
| CN106132423B (zh) | 2014-02-14 | 2020-07-31 | 贝里坤制药股份有限公司 | 用诱导型嵌合多肽活化t细胞的方法 |
| EP3137100B1 (en) * | 2014-04-15 | 2023-12-20 | University Of Virginia Patent Foundation | Isolated t cell receptors and methods of use therefor |
| US9885721B2 (en) | 2014-05-29 | 2018-02-06 | Spring Bioscience Corporation | PD-L1 antibodies and uses thereof |
| WO2015195163A1 (en) | 2014-06-20 | 2015-12-23 | R-Pharm Overseas, Inc. | Pd-l1 antagonist fully human antibody |
| TWI693232B (zh) | 2014-06-26 | 2020-05-11 | 美商宏觀基因股份有限公司 | 與pd-1和lag-3具有免疫反應性的共價結合的雙抗體和其使用方法 |
| CN106604742B (zh) | 2014-07-03 | 2019-01-11 | 百济神州有限公司 | 抗pd-l1抗体及其作为治疗剂及诊断剂的用途 |
| CN105330740B (zh) | 2014-07-30 | 2018-08-17 | 珠海市丽珠单抗生物技术有限公司 | 抗pd-1抗体及其应用 |
| CA2957258C (en) | 2014-08-05 | 2023-11-07 | MabQuest SA | Immunological reagents |
| AU2015308527C1 (en) | 2014-08-29 | 2021-07-15 | F. Hoffmann-La Roche Ag | Combination therapy of tumor-targeted IL-2 variant immunocytokines and antibodies against human PD-L1 |
| MA44907A (fr) * | 2015-09-11 | 2018-07-18 | Agenus Inc | Cellules hôtes génétiquement modifiées et leurs procédés d'utilisation |
| WO2019046856A1 (en) | 2017-09-04 | 2019-03-07 | Agenus Inc. | T-CELL RECEPTORS THAT BIND TO SPECIFIC PHOSPHOPEPTIDES OF MIXED LINEAR LEUKEMIA (MLL) AND METHODS OF USE THEREOF |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011149909A2 (en) | 2010-05-24 | 2011-12-01 | Hunt Donald F | Class i mhc phosphopeptides for cancer immunotherapy and diagnosis |
Non-Patent Citations (1)
| Title |
|---|
| PubMed Central, [online], PMCID: PMC4071620, Cobbold, M. et al.，"MHC class-I associated phosphopeptides are the targets of memory-like immunity in leukemia"，Sci. Transl. Med. Author manuscript; available in PMC 2014 Jun 26，Vol. 5, 203ra125，2013年，pp. 1-23, Supplementary Materials，Internet, [retrieved on 2020.07.20], <URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4071620/> |
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| MA50084A (fr) | 2020-07-15 |
| EP3679062B1 (en) | 2025-11-19 |
| US20200308246A1 (en) | 2020-10-01 |
| US12391741B2 (en) | 2025-08-19 |
| US11718658B2 (en) | 2023-08-08 |
| SG11202001319QA (en) | 2020-03-30 |
| EP3679062A1 (en) | 2020-07-15 |
| CN111278854A (zh) | 2020-06-12 |
| US20240301025A1 (en) | 2024-09-12 |
| JP2020532304A (ja) | 2020-11-12 |
| CA3073055A1 (en) | 2019-03-07 |
| WO2019046856A1 (en) | 2019-03-07 |
| KR20200052327A (ko) | 2020-05-14 |
| AU2018326875A1 (en) | 2020-03-19 |
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