BR112014009203B1 - Métodos para produção de camundongos geneticamente modificados com receptores de células t, para produção de receptores de células t e para identificação de células t - Google Patents
Métodos para produção de camundongos geneticamente modificados com receptores de células t, para produção de receptores de células t e para identificação de células t Download PDFInfo
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Applications Claiming Priority (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161552582P | 2011-10-28 | 2011-10-28 | |
| US61/552,582 | 2011-10-28 | ||
| US61,552,582 | 2011-10-28 | ||
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Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2771357B1 (en) * | 2011-10-28 | 2018-07-18 | Regeneron Pharmaceuticals, Inc. | Genetically modified t cell receptor mice |
| US20150073043A1 (en) * | 2012-01-19 | 2015-03-12 | Institut Pasteur Of Shanghai, Chinese Academy Of Sciences | Use of phosphorylation pathway-related factor in regulating function of regulatory t cell |
| CN104364380B (zh) | 2012-04-25 | 2018-10-09 | 瑞泽恩制药公司 | 核酸酶介导的使用大靶向载体的靶向 |
| GB2508414A (en) * | 2012-11-30 | 2014-06-04 | Max Delbrueck Centrum | Tumour specific T cell receptors (TCRs) |
| US20150342163A1 (en) | 2013-02-22 | 2015-12-03 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex mice |
| MX369747B (es) | 2013-04-16 | 2019-11-20 | Regeneron Pharma | Modificación dirigida del genoma de rata. |
| RU2685914C1 (ru) | 2013-12-11 | 2019-04-23 | Регенерон Фармасьютикалс, Инк. | Способы и композиции для направленной модификации генома |
| TWI681969B (zh) * | 2014-01-23 | 2020-01-11 | 美商再生元醫藥公司 | 針對ｐｄ-１的人類抗體 |
| HUE049776T2 (hu) | 2014-06-06 | 2020-10-28 | Regeneron Pharma | Módszerek és készítmények egy célzott lókusz módosítására |
| SMT202000184T1 (it) * | 2014-06-19 | 2020-05-08 | Regeneron Pharma | Animali non umani aventi un gene 1 della morte cellulare programmata umanizzato |
| WO2015200805A2 (en) | 2014-06-26 | 2015-12-30 | Regeneron Pharmaceuticals, Inc. | Methods and compositions for targeted genetic modifications and methods of use |
| AU2015317370A1 (en) * | 2014-09-19 | 2017-03-23 | Regeneron Pharmaceuticals, Inc. | Chimeric antigen receptors |
| RU2734770C2 (ru) | 2014-11-21 | 2020-10-23 | Регенерон Фармасьютикалз, Инк. | Способы и композиции для нацеленной генетической модификации с использованием парных гидовых рнк |
| EP3223605B9 (en) * | 2014-11-24 | 2021-08-18 | Regeneron Pharmaceuticals, Inc. | Non-human animals expressing humanized cd3 complex |
| RU2707137C2 (ru) | 2014-12-19 | 2019-11-22 | Регенерон Фармасьютикалз, Инк. | Способы и композиции для нацеленной генетической модификации посредством одноэтапного множественного нацеливания |
| WO2016164492A2 (en) * | 2015-04-06 | 2016-10-13 | Regeneron Pharmaceuticals, Inc. | Humanized t cell mediated immune responses in non-human animals |
| EP3461337A1 (en) | 2015-05-06 | 2019-04-03 | Snipr Technologies Limited | Altering microbial populations & modifying microbiota |
| EP3376857B1 (en) * | 2015-11-20 | 2021-02-24 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a humanized lymphocyte-activation gene 3 |
| CA3020330A1 (en) * | 2016-04-07 | 2017-10-12 | Bluebird Bio, Inc. | Chimeric antigen receptor t cell compositions |
| US11505590B2 (en) | 2016-04-08 | 2022-11-22 | Immunocore Limited | T cell receptors |
| KR102784608B1 (ko) * | 2016-06-03 | 2025-03-27 | 리제너론 파마슈티칼스 인코포레이티드 | 외인성 말단 데옥시뉴클레오타이드 전달효소를 발현하는 비인간 동물 |
| GB201609811D0 (en) | 2016-06-05 | 2016-07-20 | Snipr Technologies Ltd | Methods, cells, systems, arrays, RNA and kits |
| CN110996974A (zh) * | 2017-06-16 | 2020-04-10 | 梅约医学教育与研究基金会 | 增加免疫应答的材料和方法 |
| EP3692063A1 (en) | 2017-10-03 | 2020-08-12 | Juno Therapeutics, Inc. | Hpv-specific binding molecules |
| US10760075B2 (en) | 2018-04-30 | 2020-09-01 | Snipr Biome Aps | Treating and preventing microbial infections |
| JP7589047B2 (ja) * | 2018-04-05 | 2024-11-25 | ジュノー セラピューティクス インコーポレイテッド | 組換え受容体を発現する細胞の作製方法および関連組成物 |
| EP3845638A4 (en) * | 2018-07-26 | 2022-05-11 | Kyoto University | METHOD OF PRODUCTION OF A CELL DELIVERED BY A RECEPTOR GENE OF A FOREIGN ANTIGEN |
| US11851663B2 (en) | 2018-10-14 | 2023-12-26 | Snipr Biome Aps | Single-vector type I vectors |
| CA3154287A1 (en) * | 2019-09-12 | 2021-03-18 | TCR2 Therapeutics Inc. | Compositions and methods for tcr reprogramming using fusion proteins |
| CA3163549A1 (en) | 2019-12-02 | 2021-06-10 | Regeneron Pharmaceuticals, Inc. | Peptide-mhc ii protein constructs and uses thereof |
| KR20220160040A (ko) * | 2020-03-27 | 2022-12-05 | 2세븐티 바이오, 인코포레이티드 | T 세포 수용체 |
| CN113684258B (zh) * | 2020-05-18 | 2024-08-20 | 上海赛比曼生物科技有限公司 | 用于检测鼠源tcr转基因拷贝数的试剂盒及方法 |
| CN118511853A (zh) | 2021-03-31 | 2024-08-20 | 瑞泽恩制药公司 | 包含具有改善的tcrb组库多样性的人源化细胞免疫系统组分的基因修饰的小鼠 |
| GB202209518D0 (en) | 2022-06-29 | 2022-08-10 | Snipr Biome Aps | Treating & preventing E coli infections |
| CN120019068A (zh) * | 2022-08-12 | 2025-05-16 | 独创目标实验室 | 具有人源化γ和δTCR可变基因的经遗传修饰的非人类 |
| IL319060A (en) | 2022-08-18 | 2025-04-01 | Immunocore Ltd | MAGE A4-specific T-cell receptor fusion proteins |
| WO2024064860A1 (en) | 2022-09-22 | 2024-03-28 | Regeneron Pharmaceuticals, Inc. | Genetically modified mice expressing components of human cellular immune system |
| TW202520975A (zh) | 2023-08-09 | 2025-06-01 | 英商劍橋企業有限公司 | 基因改造之囓齒動物及囓齒動物細胞以及其等用途 |
| GB2640828A (en) | 2024-04-22 | 2025-11-12 | T Therapeutics Ltd | Methods and products for the generation and identification of T cells and TCRs |
| GB202405657D0 (en) | 2024-04-22 | 2024-06-05 | T Therapeutics Ltd | T cell receptor identification and provision |
Family Cites Families (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5175384A (en) | 1988-12-05 | 1992-12-29 | Genpharm International | Transgenic mice depleted in mature t-cells and methods for making transgenic mice |
| US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| EP0663952A4 (en) | 1992-09-11 | 1997-06-11 | Univ California | Transgenic non-human animals having targeted lymphocyte transduction genes. |
| US5523226A (en) | 1993-05-14 | 1996-06-04 | Biotechnology Research And Development Corp. | Transgenic swine compositions and methods |
| WO1997032603A1 (en) | 1996-03-05 | 1997-09-12 | The Scripps Research Institute | Recombinant constructs encoding t cell receptors specific for human hla-restricted tumor antigens |
| US6320306B1 (en) * | 1996-08-05 | 2001-11-20 | Samsung Display Devices Co., Ltd. | Shadow mask with porous insulating layer and heavy metal layer |
| ES2301183T3 (es) | 1996-12-03 | 2008-06-16 | Amgen Fremont Inc. | Anticuerpo completamente humano que se une al receptor del egfr. |
| AU1023401A (en) | 1999-10-12 | 2001-04-23 | Institut Pasteur | Design of a polyepitopic construct for the induction of hla-a2.1 restricted hiv 1 specific ctl responses using hhd mice |
| US7462486B2 (en) | 2000-05-12 | 2008-12-09 | Oregon Health & Science University | Methods of selecting T cell receptor V peptides for therapeutic use |
| US7105348B2 (en) | 2000-10-31 | 2006-09-12 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| US6586251B2 (en) | 2000-10-31 | 2003-07-01 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| US6596541B2 (en) * | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| US20050050580A1 (en) | 2000-12-13 | 2005-03-03 | Masashi Gotoh | Transgenic animal expressing hla-a24 and utilization thereof |
| DK1409646T3 (da) | 2000-12-19 | 2012-08-06 | Altor Bioscience Corp | Transgene dyr omfattende et humaniseret immunsystem |
| FR2827302B1 (fr) | 2001-07-13 | 2003-10-10 | Genoway | Cellule et animal transgenique modelisant la presentation antigenique humaine et leurs utilisations |
| WO2003020763A2 (en) | 2001-08-31 | 2003-03-13 | Avidex Limited | Soluble t cell receptor |
| EP1994824A1 (en) | 2001-11-15 | 2008-11-26 | Kirin Pharma Kabushiki Kaisha | Chimeric non-human animal |
| EP1321477B1 (en) * | 2001-12-22 | 2004-10-13 | 4-Antibody AG | Method for the generation of genetically modified vertebrate precursor lymphocytes and use thereof for the production of heterologous binding proteins |
| IL162111A0 (en) | 2001-12-22 | 2005-11-20 | 4Antibody Ag | Method for the generation of generically modified vertebrate precursor lymphocytes and use thereof for the production of heterologo |
| DE10244457A1 (de) | 2002-09-24 | 2004-04-01 | Johannes-Gutenberg-Universität Mainz | Verfahren zur rationalen Mutagenese von alpha/beta T-Zell Rezeptoren und entsprechend mutierte MDM2-Protein spezifische alpha/beta T-Zell Rezeptoren |
| NZ539225A (en) | 2002-10-09 | 2006-09-29 | Avidex Ltd | Single chain recombinant T cell receptors |
| US20060156419A1 (en) * | 2002-10-30 | 2006-07-13 | The Wistar Institute Of Anatomy And Biology | Mouse model for autoimmune disorders |
| US7663017B2 (en) | 2003-07-30 | 2010-02-16 | Institut Pasteur | Transgenic mice having a human major histocompatability complex (MHC) phenotype, experimental uses and applications |
| DK1802193T3 (da) | 2004-10-19 | 2014-06-10 | Regeneron Pharma | Fremgangsmåde til frembringelse af en homozygot mus til genetisk modifikation |
| EP2016102B1 (en) * | 2006-05-03 | 2012-03-21 | Government of the United States of America, Represented by the Secretary, Department of Health and Human Services | Chimeric t cell receptors and related materials and methods of use |
| EP1878342A1 (en) * | 2006-07-13 | 2008-01-16 | Institut Pasteur | Immunodeficient mice transgenic for HLA class I and HLA class II molecules and their uses |
| US9388425B2 (en) | 2006-10-20 | 2016-07-12 | Trustees Of Boston University | Tunable genetic switch for regulating gene expression |
| JP2008159109A (ja) | 2006-12-21 | 2008-07-10 | Matsushita Electric Ind Co Ltd | データ転送装置 |
| US20090271884A1 (en) | 2008-03-07 | 2009-10-29 | Regeneron Pharmaceuticals, Inc. | ES Cell-Derived Mice From Diploid Host Embryo Injection |
| US20090328240A1 (en) | 2008-06-24 | 2009-12-31 | Sing George L | Genetically modified mice as predictors of immune response |
| WO2010107400A1 (en) | 2009-03-20 | 2010-09-23 | Agency For Science, Technology And Research | Genetically modified animal and method of obtaining the same |
| EP2564695B1 (en) * | 2009-07-08 | 2015-04-15 | Kymab Limited | Animal models and therapeutic molecules |
| GB0917090D0 (en) | 2009-09-29 | 2009-11-11 | Ucl Biomedica Plc | T-cell receptor |
| WO2011044186A1 (en) | 2009-10-06 | 2011-04-14 | The Board Of Trustees Of The University Of Illinois | Human single-chain t cell receptors |
| US8956828B2 (en) | 2009-11-10 | 2015-02-17 | Sangamo Biosciences, Inc. | Targeted disruption of T cell receptor genes using engineered zinc finger protein nucleases |
| US9557323B2 (en) | 2010-09-24 | 2017-01-31 | The United States Of America As Represented By The Secretary Of The Navy | Humanized transgenic mouse model |
| US10765093B2 (en) | 2010-11-27 | 2020-09-08 | James Zhu | Humanized transgenic animal |
| EP2771357B1 (en) * | 2011-10-28 | 2018-07-18 | Regeneron Pharmaceuticals, Inc. | Genetically modified t cell receptor mice |
| WO2016164492A2 (en) | 2015-04-06 | 2016-10-13 | Regeneron Pharmaceuticals, Inc. | Humanized t cell mediated immune responses in non-human animals |
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