ES2933961T3 - Células T transgénicas y composiciones de células T de receptor de antígeno quimérico y métodos relacionados - Google Patents
Células T transgénicas y composiciones de células T de receptor de antígeno quimérico y métodos relacionados Download PDFInfo
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| JP2018518181A (ja) * | 2015-06-17 | 2018-07-12 | ザ ユーエービー リサーチ ファンデーション | 血液細胞系列の細胞に機能的ポリペプチドを導入するためのＣＲＩＳＰＲ／Ｃａｓ９複合体 |
| CA2989831A1 (en) | 2015-06-17 | 2016-12-22 | The Uab Research Foundation | Crispr/cas9 complex for genomic editing |
| AU2016333898B2 (en) * | 2015-10-05 | 2020-11-12 | Precision Biosciences, Inc. | Genetically-modified cells comprising a modified human T cell receptor alpha constant region gene |
| ES2768984T3 (es) | 2015-10-05 | 2020-06-24 | Prec Biosciences Inc | Meganucleasas diseñadas con secuencias de reconocimiento encontradas en el gen de la región constante alfa del receptor de células T humanas |
| EP4249074A3 (en) | 2015-11-04 | 2024-01-10 | Fate Therapeutics, Inc. | Genomic engineering of pluripotent cells |
| CN115927199A (zh) | 2015-11-04 | 2023-04-07 | 菲特治疗公司 | 用于诱导造血细胞分化的方法和组合物 |
| US20190161530A1 (en) * | 2016-04-07 | 2019-05-30 | Bluebird Bio, Inc. | Chimeric antigen receptor t cell compositions |
| EP3443075B1 (en) | 2016-04-15 | 2022-09-28 | Memorial Sloan Kettering Cancer Center | Transgenic t cell and chimeric antigen receptor t cell compositions and related methods |
| KR102709329B1 (ko) * | 2016-10-19 | 2024-09-23 | 셀렉티스 에스.에이. | 개선된 면역 세포들 치료를 위한 타겟인 유전자 삽입 |
| GB2573663B (en) * | 2016-10-27 | 2023-04-26 | Intima Bioscience Inc | Viral methods of making genetically modified cells |
| CN118370809A (zh) | 2017-04-03 | 2024-07-23 | 百欧恩泰美国公司 | 蛋白质抗原及其用途 |
| US11220538B2 (en) | 2017-05-01 | 2022-01-11 | The Trustees Of The University Of Pennsylvania | Monoclonal antibodies against alpha-synuclein fibrils |
| AU2018283405B2 (en) | 2017-06-15 | 2025-06-26 | The Regents Of The University Of California | Targeted non-viral DNA insertions |
| CA3068465A1 (en) | 2017-06-30 | 2019-01-03 | Precision Biosciences, Inc. | Genetically-modified t cells comprising a modified intron in the t cell receptor alpha gene |
| AU2018308923A1 (en) * | 2017-07-26 | 2020-03-12 | Cellectis | Methods of antigen-dependent chimeric antigen receptor (CAR) immune cell selection |
| EP3700924A4 (en) | 2017-10-27 | 2021-11-03 | The Regents of the University of California | TARGETED REPLACEMENT OF ENDOGENOUS T-CELL RECEPTORS |
| TW201930340A (zh) | 2017-12-18 | 2019-08-01 | 美商尼恩醫療公司 | 新抗原及其用途 |
| SG11202007622SA (en) * | 2018-02-11 | 2020-09-29 | Memorial Sloan Kettering Cancer Center | Non-hla restricted t cell receptors and uses thereof |
| CN112534044A (zh) * | 2018-02-16 | 2021-03-19 | 凯德药业股份有限公司 | 经修饰的多能干细胞及制备和使用方法 |
| US20200224160A1 (en) * | 2018-02-27 | 2020-07-16 | Sorrento Therapeutics, Inc. | Process for dna integration using rna-guided endonucleases |
| WO2019199689A1 (en) * | 2018-04-09 | 2019-10-17 | The Trustees Of The University Of Pennsylvania | Methods and compositions comprising a viral vector for expression of a transgene and an effector |
| KR102617818B1 (ko) | 2018-04-12 | 2023-12-27 | 프리시젼 바이오사이언시스 인코포레이티드 | 인간 t 세포 수용체 알파 불변 영역 유전자에 대한 특이성을 갖는 최적화된 조작된 뉴클레아제 |
| WO2019204397A1 (en) * | 2018-04-17 | 2019-10-24 | Wake Forest University Health Sciences | Methods and compositions for th9 cell mediated cancer treatment |
| WO2019226998A1 (en) * | 2018-05-25 | 2019-11-28 | The Regents Of The University Of California | Genetic engineering of endogenous proteins |
| WO2019232425A1 (en) * | 2018-06-01 | 2019-12-05 | Washington University | Suppression of cytokine release syndrome in chimeric antigen receptor cell therapy |
| BR112020025764A2 (pt) | 2018-06-19 | 2021-05-11 | Biontech Us Inc. | neoantígenos e usos dos mesmos |
| CN110616188B (zh) * | 2018-06-20 | 2023-05-09 | 上海隆耀生物科技有限公司 | 一种通用型car-t细胞及其制备方法和应用 |
| US12359169B2 (en) | 2018-06-20 | 2025-07-15 | Shanghai Longyao Biotechnology Inc., Ltd. | Universal CAR-T cell and preparation method and use thereof |
| CA3104862A1 (en) * | 2018-07-03 | 2020-01-09 | Sotio, LLC | Chimeric receptors in combination with trans metabolism molecules enhancing glucose import and therapeutic uses thereof |
| AU2019312008A1 (en) * | 2018-07-26 | 2021-03-18 | Kyoto University | Method for generating cells into which an exogenous antigen receptor is introduced |
| SG11202101284UA (en) | 2018-08-14 | 2021-03-30 | Sotio Llc | Chimeric antigen receptor polypeptides in combination with trans metabolism molecules modulating krebs cycle and therapeutic uses thereof |
| EP4578507A3 (en) | 2018-11-01 | 2025-11-12 | Gracell Biotechnologies (Shanghai) Co., Ltd. | Compositions and methods for t cell engineering |
| BR112021012172A2 (pt) | 2018-12-12 | 2021-08-31 | Kite Pharma, Inc. | Receptores de antígenos quiméricos e de célula t e métodos de uso |
| WO2020127513A1 (en) * | 2018-12-19 | 2020-06-25 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Mucosal-associated invariant t (mait) cells expressing chimeric antigen receptors |
| JP7642548B2 (ja) * | 2019-02-01 | 2025-03-10 | ケーエスキュー セラピューティクス， インコーポレイテッド | 免疫療法の改善のための遺伝子調節組成物及び遺伝子調節方法 |
| US12419913B2 (en) | 2019-02-08 | 2025-09-23 | Dna Twopointo, Inc. | Modification of CAR-T cells |
| EP3927735A4 (en) * | 2019-02-18 | 2023-09-06 | Memorial Sloan Kettering Cancer Center | COMBINATIONS OF MULTIPLE CHIMERIC ANTIGEN RECEPTORS FOR IMMUNOTHERAPY |
| JP7650809B2 (ja) | 2019-03-06 | 2025-03-25 | レンティジェン・テクノロジー・インコーポレイテッド | 自己駆動型キメラ抗原受容体を用いてがんを処置するための組成物および方法 |
| MX2021011837A (es) | 2019-03-29 | 2021-10-22 | Hoffmann La Roche | Método para la generación de una célula que expresa el receptor neonatal de región de fragmento cristalizable (fcrn) mediante la integración dirigida de múltiples casetes de expresión en una organización definida. |
| AU2020271523A1 (en) * | 2019-04-11 | 2021-10-14 | Fate Therapeutics, Inc. | CD3 reconstitution in engineered iPSC and immune effector cells |
| BR112021021200A2 (pt) | 2019-05-01 | 2021-12-21 | Juno Therapeutics Inc | Células expressando um receptor quimérico de um locus cd247 modificado, polinucleotídeos relacionados e métodos |
| EP3969482A1 (en) * | 2019-05-16 | 2022-03-23 | University of Washington | Lockr-mediated recruitment of car t cells |
| MX2021015540A (es) * | 2019-06-19 | 2022-02-10 | Hoffmann La Roche | Metodo para la generacion de una celula que expresa un anticuerpo trivalente mediante la integracion dirigida de multiples casetes de expresion en una organizacion definida. |
| CA3148072A1 (en) | 2019-07-19 | 2021-01-28 | Memorial Sloan-Kettering Cancer Center | Fusion polypeptide for immunotherapy |
| JP7735249B2 (ja) | 2019-07-23 | 2025-09-08 | ムネモ・セラピューティクス | Ｓｕｖ３９ｈ１欠損免疫細胞 |
| CN117925528A (zh) * | 2019-07-24 | 2024-04-26 | 浙江煦顼技术有限公司 | 具有增强记忆t细胞表型的修饰t细胞 |
| WO2021061832A1 (en) * | 2019-09-23 | 2021-04-01 | Regents Of The University Of Minnesota | Genetically-edited immune cells and methods of therapy |
| US20220362407A1 (en) * | 2019-09-25 | 2022-11-17 | The Board Of Trustees Of The Leland Stanford Junior University | A promoter specific for non-pigmented ciliary epithelial cells |
| SG10201909544YA (en) * | 2019-10-11 | 2021-05-28 | Nat Univ Singapore | Genetically Modified T Cells And Uses Thereof |
| IL292351A (en) * | 2019-11-13 | 2022-06-01 | Crispr Therapeutics Ag | Methods of manufacturing car-t cells |
| CN114929862A (zh) * | 2019-11-13 | 2022-08-19 | 克里斯珀医疗股份公司 | 用于制备表达嵌合抗原受体的t细胞的生产方法 |
| CN113122576A (zh) * | 2019-12-31 | 2021-07-16 | 博雅辑因（北京）生物科技有限公司 | 一种通用型truck-t细胞、其制备方法以及用途 |
| CN115209909A (zh) * | 2020-01-02 | 2022-10-18 | 伊迪生物治疗公司 | 递送组合物和方法 |
| EP4110356A4 (en) * | 2020-02-28 | 2024-03-27 | Wisconsin Alumni Research Foundation | NON-VIRAL GENERATION OF CHIMERIC ANTIGEN RECEPTOR T CELLS OBTAINED BY GENE EDITING |
| AU2021237738A1 (en) * | 2020-03-20 | 2022-11-10 | Orna Therapeutics, Inc. | Circular RNA compositions and methods |
| GB202006903D0 (en) * | 2020-05-11 | 2020-06-24 | Adaptimmune Ltd | Modified iPSCs |
| US20230242666A1 (en) * | 2020-06-29 | 2023-08-03 | Cell Medica, Inc. | Methods and Compositions for the Reduction of Chimeric Antigen Receptor Tonic Signaling |
| WO2022011065A1 (en) * | 2020-07-07 | 2022-01-13 | The Nemours Foundation | Tumor-activated alloreactive and xenoreactive t cells and their use in immunotherapy against cancer |
| CN116096864A (zh) | 2020-07-30 | 2023-05-09 | 居里研究所 | Socs1缺陷的免疫细胞 |
| JP2023537048A (ja) * | 2020-08-07 | 2023-08-30 | ネオジン セラピューティクス ビー．ブイ． | 遺伝子改変したｔ細胞の濃縮方法 |
| JP2023544337A (ja) * | 2020-09-30 | 2023-10-23 | ブイオーアール バイオファーマ インコーポレーテッド | キメラ抗原受容体発現系 |
| AU2021392094A1 (en) * | 2020-12-01 | 2023-07-06 | Lepton Pharmaceuticals Ltd. | Methods for enhancing therapeutic efficacy of isolated cells for cell therapy |
| US11661459B2 (en) | 2020-12-03 | 2023-05-30 | Century Therapeutics, Inc. | Artificial cell death polypeptide for chimeric antigen receptor and uses thereof |
| JP2023553419A (ja) | 2020-12-03 | 2023-12-21 | センチュリー セラピューティクス，インコーポレイテッド | 遺伝子操作細胞およびその使用 |
| EP4019538A1 (en) * | 2020-12-22 | 2022-06-29 | Charité - Universitätsmedizin Berlin | Reprogramming immune cells by targeted integration of zeta-deficient chimeric antigen receptor transgenes |
| KR20240006721A (ko) | 2021-03-11 | 2024-01-15 | 엥스띠뛰 퀴리 | 막 형질 전환 네오 안티젠 펩타이드 |
| MX2023010641A (es) | 2021-03-11 | 2024-02-07 | Mnemo Therapeutics | Peptidos neoantigénicos tumorales y usos de los mismos. |
| CA3212964A1 (en) | 2021-03-11 | 2022-09-15 | Mnemo Therapeutics | Tumor neoantigenic peptides |
| AU2022272317A1 (en) * | 2021-05-14 | 2023-11-30 | Appia Bio, Inc. | Production of engineered t cells from stem cells |
| US20250235477A1 (en) | 2021-10-06 | 2025-07-24 | Miltenyi Biotec B.V. & Co. KG | Method for targeted gene insertion into immune cells |
| WO2023064455A1 (en) * | 2021-10-14 | 2023-04-20 | Appia Bio, Inc. | Engineering stem cell t cells with multiple t cell receptors |
| CR20240195A (es) | 2021-10-14 | 2024-06-20 | Arsenal Biosciences Inc | Células inmunitarias que tienen arnhc coexpresados y sistemas de compuerta lógica |
| US20250000907A1 (en) * | 2021-11-22 | 2025-01-02 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Engineered immune cells with reduced sirt6 expression |
| EP4456910A1 (en) | 2021-12-28 | 2024-11-06 | Mnemo Therapeutics | Immune cells with inactivated suv39h1 and modified tcr |
| AU2023209589A1 (en) | 2022-01-21 | 2024-08-08 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Modulation of suv39h1 expression by rnas |
| CN115304679B (zh) * | 2022-01-21 | 2024-07-16 | 郑州大学第一附属医院 | 一种促进t细胞分化的限制型car及其应用 |
| WO2023178227A2 (en) * | 2022-03-17 | 2023-09-21 | University Of Florida Research Foundation, Incorporated | Chimeric lactate receptor engineered t cells |
| EP4279085A1 (en) | 2022-05-20 | 2023-11-22 | Mnemo Therapeutics | Compositions and methods for treating a refractory or relapsed cancer or a chronic infectious disease |
| WO2023225670A2 (en) * | 2022-05-20 | 2023-11-23 | Tome Biosciences, Inc. | Ex vivo programmable gene insertion |
| EP4573114A2 (en) | 2022-08-19 | 2025-06-25 | Memorial Sloan-Kettering Cancer Center | T cell receptors targeting ras mutations and uses thereof |
| EP4580604A2 (en) * | 2022-09-02 | 2025-07-09 | OncoSenX, Inc. | Compositions and methods for in vivo expression of chimeric antigen receptors |
| BE1031219B1 (fr) | 2022-12-28 | 2024-07-29 | Quidditas Sa | Composition, cellules immunitaires la comprenant et utilisation de ces dernières |
| WO2025096560A1 (en) * | 2023-10-30 | 2025-05-08 | Allogene Therapeutics, Inc. | Engineered cells |
| WO2025096594A2 (en) * | 2023-10-30 | 2025-05-08 | Allogene Therapeutics, Inc. | Cells expressing anti-cd19 chimeric antigen receptors and methods of use thereof |
| WO2025163107A1 (en) | 2024-02-01 | 2025-08-07 | Institut Gustave Roussy | Immune cells defective for znf217 and uses thereof |
| WO2025213167A1 (en) * | 2024-04-05 | 2025-10-09 | Roswell Park Cancer Institute Corporation | Complement signaling as a t-cell checkpoint in the tumor microenvironment (tme) |
Family Cites Families (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5132405A (en) | 1987-05-21 | 1992-07-21 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
| US5091513A (en) | 1987-05-21 | 1992-02-25 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
| JPS6412935A (en) | 1987-07-02 | 1989-01-17 | Mitsubishi Electric Corp | Constant-speed travel device for vehicle |
| US5399346A (en) | 1989-06-14 | 1995-03-21 | The United States Of America As Represented By The Department Of Health And Human Services | Gene therapy |
| US6436703B1 (en) | 2000-03-31 | 2002-08-20 | Hyseq, Inc. | Nucleic acids and polypeptides |
| DK1409646T3 (da) | 2000-12-19 | 2012-08-06 | Altor Bioscience Corp | Transgene dyr omfattende et humaniseret immunsystem |
| JP4238138B2 (ja) | 2001-12-22 | 2009-03-11 | ４−アンチボディ アーゲー | 遺伝的に修飾された脊椎動物前駆体リンパ球の生成方法及び異種結合タンパク質の産生を目的としたその使用。 |
| DK1321477T3 (da) | 2001-12-22 | 2005-02-14 | 4Antibody Ag | Fremgangsmåde til frembringelsen af genetisk modificerede vertebrate precursor-lymfocytter og anvendelse deraf til fremstillingen af heterologe bindende proteiner |
| US7446190B2 (en) | 2002-05-28 | 2008-11-04 | Sloan-Kettering Institute For Cancer Research | Nucleic acids encoding chimeric T cell receptors |
| WO2005026718A1 (en) | 2003-08-28 | 2005-03-24 | Five Prime Therapeutics, Inc. | Stem cell libraries |
| US20110213288A1 (en) | 2007-04-23 | 2011-09-01 | The Board Of Regents, The University Of Texas System | Device And Method For Transfecting Cells For Therapeutic Uses |
| JP5271901B2 (ja) | 2007-06-11 | 2013-08-21 | タカラバイオ株式会社 | 特異的遺伝子発現方法 |
| AU2009322964B2 (en) | 2008-12-04 | 2014-10-09 | Sangamo Therapeutics, Inc. | Genome editing in rats using zinc-finger nucleases |
| JP2013500018A (ja) * | 2009-07-24 | 2013-01-07 | シグマ−アルドリッチ・カンパニー・リミテッド・ライアビリティ・カンパニー | ゲノム編集のための方法 |
| WO2011059836A2 (en) | 2009-10-29 | 2011-05-19 | Trustees Of Dartmouth College | T cell receptor-deficient t cell compositions |
| US9273283B2 (en) | 2009-10-29 | 2016-03-01 | The Trustees Of Dartmouth College | Method of producing T cell receptor-deficient T cells expressing a chimeric receptor |
| ES2717629T3 (es) | 2009-11-03 | 2019-06-24 | Hope City | Receptor del factor de crecimiento epidérmico truncado (EGFRt) para selección de células T transducidas |
| US8956828B2 (en) * | 2009-11-10 | 2015-02-17 | Sangamo Biosciences, Inc. | Targeted disruption of T cell receptor genes using engineered zinc finger protein nucleases |
| EP2596011B1 (en) | 2010-07-21 | 2018-10-03 | Sangamo Therapeutics, Inc. | Methods and compositions for modification of a hla locus |
| JP6339015B2 (ja) | 2011-08-23 | 2018-06-06 | ロシュ グリクアート アーゲー | 二重特異性ｔ細胞活性化抗原結合分子 |
| EP3839050A3 (en) | 2012-04-18 | 2021-09-29 | The Board of Trustees of the Leland Stanford Junior University | Non-disruptive gene targeting |
| WO2013176772A1 (en) | 2012-05-25 | 2013-11-28 | The Regents Of The University Of California | Methods and compositions for rna-directed target dna modification and for rna-directed modulation of transcription |
| WO2013176915A1 (en) | 2012-05-25 | 2013-11-28 | Roman Galetto | Methods for engineering allogeneic and immunosuppressive resistant t cell for immunotherapy |
| WO2014059173A2 (en) | 2012-10-10 | 2014-04-17 | Sangamo Biosciences, Inc. | T cell modifying compounds and uses thereof |
| US8697359B1 (en) | 2012-12-12 | 2014-04-15 | The Broad Institute, Inc. | CRISPR-Cas systems and methods for altering expression of gene products |
| KR102064230B1 (ko) | 2013-02-15 | 2020-01-13 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | 키메라 항원 수용체 및 이의 이용 방법 |
| US9499855B2 (en) | 2013-03-14 | 2016-11-22 | Elwha Llc | Compositions, methods, and computer systems related to making and administering modified T cells |
| US9937207B2 (en) | 2013-03-21 | 2018-04-10 | Sangamo Therapeutics, Inc. | Targeted disruption of T cell receptor genes using talens |
| WO2014165707A2 (en) | 2013-04-03 | 2014-10-09 | Memorial Sloan-Kettering Cancer Center | Effective generation of tumor-targeted t-cells derived from pluripotent stem cells |
| CN105452287A (zh) | 2013-04-17 | 2016-03-30 | 贝勒医学院 | 免疫抑制性TGF-β信号转换器 |
| CN105408473B9 (zh) | 2013-05-14 | 2021-09-17 | 得克萨斯州大学系统董事会 | 工程化嵌合抗原受体(car)t细胞的人应用 |
| ES2883131T3 (es) | 2013-05-29 | 2021-12-07 | Cellectis | Métodos para la modificación de células T para inmunoterapia utilizando el sistema de nucleasa CAS guiado por ARN |
| WO2014191128A1 (en) | 2013-05-29 | 2014-12-04 | Cellectis | Methods for engineering t cells for immunotherapy by using rna-guided cas nuclease system |
| AU2015233347A1 (en) | 2014-03-21 | 2016-09-08 | Cellectis | Engineering mammalian genome using DNA-guided Argonaute interference systems (DAIS) |
| AU2015249371B2 (en) * | 2014-04-24 | 2020-04-30 | Board Of Regents, The University Of Texas System | Application of induced pluripotent stem cells to generate adoptive cell therapy products |
| CA2948614A1 (en) | 2014-05-09 | 2015-11-12 | Research Foundation Of The City University Of New York | Tcr(alpha)-lcr-derived gene regulatory cassettes |
| EP3151846A4 (en) * | 2014-06-05 | 2017-12-27 | Sangamo BioSciences, Inc. | Methods and compositions for nuclease design |
| CN106795521B (zh) | 2014-06-06 | 2021-06-04 | 瑞泽恩制药公司 | 用于修饰所靶向基因座的方法和组合物 |
| WO2016044745A1 (en) | 2014-09-19 | 2016-03-24 | Regeneron Pharmaceuticals, Inc. | Chimeric antigen receptors |
| WO2016081924A1 (en) * | 2014-11-20 | 2016-05-26 | Duke University | Compositions, systems and methods for cell therapy |
| CN107847524A (zh) | 2015-03-27 | 2018-03-27 | 哈佛学院校长同事会 | 经过修饰的t细胞及其制备和使用方法 |
| WO2016166268A1 (en) | 2015-04-17 | 2016-10-20 | Cellectis | Engineering animal or plant genome using dna-guided argonaute interference systems (dais) from mesophilic prokaryotes |
| WO2016187104A1 (en) * | 2015-05-15 | 2016-11-24 | Oru Kayak, Inc. | Collapsible kayak with large cockpit |
| EP3322297B1 (en) * | 2015-07-13 | 2024-12-04 | Sangamo Therapeutics, Inc. | Delivery methods and compositions for nuclease-mediated genome engineering |
| WO2017023801A1 (en) | 2015-07-31 | 2017-02-09 | Regents Of The University Of Minnesota | Intracellular genomic transplant and methods of therapy |
| AU2016333898B2 (en) | 2015-10-05 | 2020-11-12 | Precision Biosciences, Inc. | Genetically-modified cells comprising a modified human T cell receptor alpha constant region gene |
| ES2768984T3 (es) * | 2015-10-05 | 2020-06-24 | Prec Biosciences Inc | Meganucleasas diseñadas con secuencias de reconocimiento encontradas en el gen de la región constante alfa del receptor de células T humanas |
| CN115927199A (zh) | 2015-11-04 | 2023-04-07 | 菲特治疗公司 | 用于诱导造血细胞分化的方法和组合物 |
| EP4249074A3 (en) | 2015-11-04 | 2024-01-10 | Fate Therapeutics, Inc. | Genomic engineering of pluripotent cells |
| WO2017087723A1 (en) | 2015-11-19 | 2017-05-26 | The Regents Of The University Of California | Conditionally repressible immune cell receptors and methods of use thereof |
| BR112018068354A2 (pt) | 2016-03-11 | 2019-01-15 | Bluebird Bio Inc | células efetoras imunológicas do genoma editado |
| SG10202104509PA (en) | 2016-03-19 | 2021-06-29 | Exuma Biotech Corp | Methods and compositions for transducing lymphocytes and regulated expansion thereof |
| US20190161530A1 (en) | 2016-04-07 | 2019-05-30 | Bluebird Bio, Inc. | Chimeric antigen receptor t cell compositions |
| EP3443075B1 (en) | 2016-04-15 | 2022-09-28 | Memorial Sloan Kettering Cancer Center | Transgenic t cell and chimeric antigen receptor t cell compositions and related methods |
-
2017
- 2017-04-14 EP EP17735670.6A patent/EP3443075B1/en active Active
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- 2017-04-14 ES ES22197444T patent/ES3039670T3/es active Active
- 2017-04-14 CN CN201780037351.1A patent/CN109790517B/zh active Active
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- 2017-04-14 US US16/091,494 patent/US11377637B2/en active Active
- 2017-04-14 CA CA3020923A patent/CA3020923A1/en active Pending
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- 2017-04-14 WO PCT/US2017/027601 patent/WO2017180989A2/en not_active Ceased
- 2017-04-14 KR KR1020227029151A patent/KR102614675B1/ko active Active
- 2017-04-14 EP EP22197444.7A patent/EP4180519B1/en active Active
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2022
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|---|---|
| KR20220123325A (ko) | 2022-09-06 |
| JP2019511236A (ja) | 2019-04-25 |
| KR102437015B1 (ko) | 2022-08-29 |
| PT3443075T (pt) | 2022-12-16 |
| US20190119638A1 (en) | 2019-04-25 |
| EP4628587A2 (en) | 2025-10-08 |
| KR102614675B1 (ko) | 2023-12-19 |
| KR20180133496A (ko) | 2018-12-14 |
| US12404316B2 (en) | 2025-09-02 |
| ES3039670T3 (en) | 2025-10-23 |
| EP3443075B1 (en) | 2022-09-28 |
| US11377637B2 (en) | 2022-07-05 |
| EP3443075A2 (en) | 2019-02-20 |
| EP4180519B1 (en) | 2025-06-11 |
| AU2017250769A1 (en) | 2018-11-01 |
| BR112018071199A2 (pt) | 2019-02-12 |
| AU2017250769B2 (en) | 2022-07-14 |
| PT4180519T (pt) | 2025-09-04 |
| WO2017180989A2 (en) | 2017-10-19 |
| SG11201808831TA (en) | 2018-11-29 |
| WO2017180989A3 (en) | 2017-12-14 |
| CN109790517A (zh) | 2019-05-21 |
| CA3020923A1 (en) | 2017-10-19 |
| KR20240000616A (ko) | 2024-01-02 |
| US20220411753A1 (en) | 2022-12-29 |
| JP7058223B2 (ja) | 2022-04-21 |
| CN109790517B (zh) | 2023-05-02 |
| EP4180519A1 (en) | 2023-05-17 |
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