DK2279253T3 - Construction and application of therapeutic compositions of freshly isolated cells - Google Patents
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| US10155038B2 (en) | 2007-02-02 | 2018-12-18 | Yale University | Cells prepared by transient transfection and methods of use thereof |
| US9249423B2 (en) | 2007-02-02 | 2016-02-02 | Yale University | Method of de-differentiating and re-differentiating somatic cells using RNA |
| US8859229B2 (en) * | 2007-02-02 | 2014-10-14 | Yale University | Transient transfection with RNA |
| JP5779090B2 (ja) * | 2008-04-09 | 2015-09-16 | マックスサイト インコーポレーティッド | 新規に単離された細胞の治療組成物の操作および送達 |
| PH12013501201A1 (en) * | 2010-12-09 | 2013-07-29 | Univ Pennsylvania | Use of chimeric antigen receptor-modified t cells to treat cancer |
| JP5572863B2 (ja) * | 2011-06-24 | 2014-08-20 | 国立大学法人九州大学 | Ｎｋ細胞の増幅方法 |
| JP5989016B2 (ja) * | 2011-06-24 | 2016-09-07 | 国立大学法人九州大学 | Ｎｋ細胞の増幅方法 |
| CA2848410A1 (en) | 2011-09-16 | 2013-03-21 | The Trustees Of The University Of Pennsylvania | Rna engineered t cells for the treatment of cancer |
| US9272002B2 (en) | 2011-10-28 | 2016-03-01 | The Trustees Of The University Of Pennsylvania | Fully human, anti-mesothelin specific chimeric immune receptor for redirected mesothelin-expressing cell targeting |
| EP3421489B1 (en) | 2012-03-23 | 2021-05-05 | The United States of America, as represented by The Secretary, Department of Health and Human Services | Anti-mesothelin chimeric antigen receptors |
| EP4282419A1 (en) | 2012-12-20 | 2023-11-29 | Purdue Research Foundation | Chimeric antigen receptor-expressing t cells as anti-cancer therapeutics |
| US10144770B2 (en) | 2013-10-17 | 2018-12-04 | National University Of Singapore | Chimeric receptors and uses thereof in immune therapy |
| KR102508166B1 (ko) | 2014-04-10 | 2023-03-13 | 시애틀 칠드런즈 호스피탈 디/비/에이 시애틀 칠드런즈 리서치 인스티튜트 | 세포 면역요법을 위한 방법 및 조성물 |
| WO2016095934A2 (en) * | 2014-12-14 | 2016-06-23 | El Abd Hisham Mohamed Magdy | A novel genetic device to engineer cell behavior |
| KR102605464B1 (ko) | 2015-01-30 | 2023-11-22 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | 일차 조혈 세포에서의 단백질 전달 |
| US11059880B2 (en) | 2015-06-30 | 2021-07-13 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Redirected cells with MHC chimeric receptors and methods of use in immunotherapy |
| KR20240132100A (ko) | 2015-07-28 | 2024-09-02 | 더 트러스티스 오브 더 유니버시티 오브 펜실베니아 | 키메릭 항원 수용체를 발현하는 변형된 단핵세포/대식세포 및 그의 용도 |
| MX2018001568A (es) | 2015-08-07 | 2019-04-25 | Seattle Children´S Hospital Dba Seattle Children´S Res Institute | Celulas t biespecificas de receptor quimerico de antigeno (car) para focalizacion a tumores solidos. |
| EP3380117B1 (en) | 2015-11-27 | 2021-01-06 | Cartherics Pty. Ltd. | Genetically modified cells and uses thereof |
| JP7282521B2 (ja) | 2016-04-08 | 2023-05-29 | パーデュー・リサーチ・ファウンデイション | Ｃａｒ ｔ細胞療法のための方法および組成物 |
| US11293021B1 (en) | 2016-06-23 | 2022-04-05 | Inscripta, Inc. | Automated cell processing methods, modules, instruments, and systems |
| US11408005B2 (en) | 2016-12-12 | 2022-08-09 | Seattle Children's Hospital | Chimeric transcription factor variants with augmented sensitivity to drug ligand induction of transgene expression in mammalian cells |
| CN110612119B (zh) | 2017-02-07 | 2024-10-29 | 西雅图儿童医院（Dba西雅图儿童研究所） | 磷脂醚(ple)car t细胞肿瘤靶向(ctct)剂 |
| WO2018160622A1 (en) | 2017-02-28 | 2018-09-07 | Endocyte, Inc. | Compositions and methods for car t cell therapy |
| CA3060443A1 (en) | 2017-04-19 | 2018-10-25 | Board Of Regents, The University Of Texas System | Immune cells expressing engineered antigen receptors |
| CA3067382A1 (en) | 2017-06-15 | 2018-12-20 | The Regents Of The University Of California | Targeted non-viral dna insertions |
| US10011849B1 (en) | 2017-06-23 | 2018-07-03 | Inscripta, Inc. | Nucleic acid-guided nucleases |
| US9982279B1 (en) | 2017-06-23 | 2018-05-29 | Inscripta, Inc. | Nucleic acid-guided nucleases |
| RS63202B1 (sr) | 2017-06-30 | 2022-06-30 | Inscripta Inc | Automatizovani postupci, moduli, instrumenti i sistemi za obradu ćelija |
| US11471490B2 (en) | 2017-07-03 | 2022-10-18 | Torque Therapeutics, Inc. | T cells surface-loaded with immunostimulatory fusion molecules and uses thereof |
| US10738327B2 (en) | 2017-08-28 | 2020-08-11 | Inscripta, Inc. | Electroporation cuvettes for automation |
| CA3074495A1 (en) * | 2017-09-01 | 2019-03-07 | Gpb Scientific, Llc | Methods for preparing therapeutically active cells using microfluidics |
| CN111372650A (zh) | 2017-09-30 | 2020-07-03 | 因思科瑞普特公司 | 流通式电穿孔仪器 |
| IL305485B2 (en) | 2017-10-27 | 2025-10-01 | Univ California | Targeted replacement of endogenous T cell receptors |
| WO2019090355A1 (en) * | 2017-11-06 | 2019-05-09 | Children's National Medical Center | Cells expressing antibodies and methods of treatment using the same |
| AU2019205315A1 (en) * | 2018-01-05 | 2020-07-16 | Maxcyte, Inc. | Chronic car treatment for cancer |
| CN120154716A (zh) | 2018-01-22 | 2025-06-17 | 恩多塞特公司 | Car t细胞的使用方法 |
| CN111936518A (zh) | 2018-02-06 | 2020-11-13 | 西雅图儿童医院（Dba西雅图儿童研究所） | 对fl-ple标记的肿瘤表现出最佳的t细胞功能的荧光素特异性car |
| BR112020016176A2 (pt) * | 2018-02-09 | 2022-02-22 | Immatics Us Inc | Métodos de transdução de uma célula t, célula t transduzida geneticamente, composição farmacêutica, métodos de preparação de uma população de células t e uso da célula t |
| JP7273421B2 (ja) | 2018-02-21 | 2023-05-15 | ボード オブ リージェンツ，ザ ユニバーシティ オブ テキサス システム | ナチュラルキラー細胞の活性化および拡大のための方法ならびにその使用 |
| TW202000229A (zh) | 2018-02-23 | 2020-01-01 | 美商安德賽特公司 | Car t細胞療法之順序方法 |
| WO2019190874A1 (en) | 2018-03-29 | 2019-10-03 | Inscripta, Inc. | Automated control of cell growth rates for induction and transformation |
| WO2019200004A1 (en) | 2018-04-13 | 2019-10-17 | Inscripta, Inc. | Automated cell processing instruments comprising reagent cartridges |
| WO2019209926A1 (en) | 2018-04-24 | 2019-10-31 | Inscripta, Inc. | Automated instrumentation for production of peptide libraries |
| US10858761B2 (en) | 2018-04-24 | 2020-12-08 | Inscripta, Inc. | Nucleic acid-guided editing of exogenous polynucleotides in heterologous cells |
| US10526598B2 (en) | 2018-04-24 | 2020-01-07 | Inscripta, Inc. | Methods for identifying T-cell receptor antigens |
| WO2020014235A1 (en) | 2018-07-09 | 2020-01-16 | The Regents Of The University Of California | Gene targets for t-cell-based immunotherapy |
| IL280322B2 (en) | 2018-08-14 | 2025-06-01 | Sotio Llc | Chimeric antigen receptor polypeptides in combination with trans metabolism molecules modulating krebs cycle and therapeutic uses thereof |
| US11142740B2 (en) | 2018-08-14 | 2021-10-12 | Inscripta, Inc. | Detection of nuclease edited sequences in automated modules and instruments |
| IL292273B2 (en) | 2018-08-14 | 2023-10-01 | Inscripta Inc | Devices, modules and methods for improved detection of edited sequences in living cells |
| US10532324B1 (en) | 2018-08-14 | 2020-01-14 | Inscripta, Inc. | Instruments, modules, and methods for improved detection of edited sequences in live cells |
| US11965154B2 (en) | 2018-08-30 | 2024-04-23 | Inscripta, Inc. | Detection of nuclease edited sequences in automated modules and instruments |
| CA3111706A1 (en) * | 2018-09-07 | 2020-03-12 | Sotio, LLC | Chimeric receptor polypeptides in combination with trans metabolism molecules modulating intracellular lactate concentrations and therapeutic uses thereof |
| WO2020080908A1 (ko) * | 2018-10-19 | 2020-04-23 | 주식회사 헬릭스미스 | 항-l1cam 항체 또는 그의 항원결합 단편, 및 이를 포함하는 키메라 항원 수용체 |
| US11214781B2 (en) | 2018-10-22 | 2022-01-04 | Inscripta, Inc. | Engineered enzyme |
| EP3870697A4 (en) | 2018-10-22 | 2022-11-09 | Inscripta, Inc. | GMO ENZYMES |
| CN111349615B (zh) * | 2018-12-24 | 2024-08-13 | 上海细胞治疗集团股份有限公司 | 制备过表达外源基因的细胞的方法 |
| CN118546959A (zh) | 2019-03-05 | 2024-08-27 | 恩卡尔塔公司 | Cd19定向性嵌合抗原受体及其在免疫疗法中的用途 |
| US10815467B2 (en) | 2019-03-25 | 2020-10-27 | Inscripta, Inc. | Simultaneous multiplex genome editing in yeast |
| US11001831B2 (en) | 2019-03-25 | 2021-05-11 | Inscripta, Inc. | Simultaneous multiplex genome editing in yeast |
| CN113939593A (zh) | 2019-06-06 | 2022-01-14 | 因思科瑞普特公司 | 用于递归的核酸指导的细胞编辑的处治 |
| US10920189B2 (en) | 2019-06-21 | 2021-02-16 | Inscripta, Inc. | Genome-wide rationally-designed mutations leading to enhanced lysine production in E. coli |
| US10927385B2 (en) | 2019-06-25 | 2021-02-23 | Inscripta, Inc. | Increased nucleic-acid guided cell editing in yeast |
| WO2021102059A1 (en) | 2019-11-19 | 2021-05-27 | Inscripta, Inc. | Methods for increasing observed editing in bacteria |
| US10883095B1 (en) | 2019-12-10 | 2021-01-05 | Inscripta, Inc. | Mad nucleases |
| US10704033B1 (en) | 2019-12-13 | 2020-07-07 | Inscripta, Inc. | Nucleic acid-guided nucleases |
| JP2023507566A (ja) | 2019-12-18 | 2023-02-24 | インスクリプタ， インコーポレイテッド | 核酸誘導ヌクレアーゼ編集済み細胞のｉｎ ｖｉｖｏ検出のためのカスケード／ｄＣａｓ３相補性アッセイ |
| US10689669B1 (en) | 2020-01-11 | 2020-06-23 | Inscripta, Inc. | Automated multi-module cell processing methods, instruments, and systems |
| KR20220133257A (ko) | 2020-01-27 | 2022-10-04 | 인스크립타 인코포레이티드 | 전기천공 모듈 및 기구 |
| US20210332388A1 (en) | 2020-04-24 | 2021-10-28 | Inscripta, Inc. | Compositions, methods, modules and instruments for automated nucleic acid-guided nuclease editing in mammalian cells |
| US11787841B2 (en) | 2020-05-19 | 2023-10-17 | Inscripta, Inc. | Rationally-designed mutations to the thrA gene for enhanced lysine production in E. coli |
| CA3184807A1 (en) | 2020-06-04 | 2021-12-09 | Carisma Therapeutics Inc. | Novel constructs for chimeric antigen receptors |
| WO2022060749A1 (en) | 2020-09-15 | 2022-03-24 | Inscripta, Inc. | Crispr editing to embed nucleic acid landing pads into genomes of live cells |
| US11512297B2 (en) | 2020-11-09 | 2022-11-29 | Inscripta, Inc. | Affinity tag for recombination protein recruitment |
| AU2021415461A1 (en) | 2021-01-04 | 2023-08-17 | Inscripta, Inc. | Mad nucleases |
| US20240376451A1 (en) | 2021-01-07 | 2024-11-14 | Inscripta, Inc. | Mad nucleases |
| US11884924B2 (en) | 2021-02-16 | 2024-01-30 | Inscripta, Inc. | Dual strand nucleic acid-guided nickase editing |
| AU2022366987A1 (en) | 2021-10-14 | 2024-05-16 | Arsenal Biosciences, Inc. | Immune cells having co-expressed shrnas and logic gate systems |
| 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 |
| WO2024059618A2 (en) | 2022-09-13 | 2024-03-21 | Arsenal Biosciences, Inc. | Immune cells having co-expressed tgfbr shrnas |
| CA3265690A1 (en) | 2022-09-16 | 2024-03-21 | Arsenal Biosciences, Inc. | COMBINED GENE DISTURBANCES IMMUNE CELLS |
| WO2024186656A1 (en) | 2023-03-03 | 2024-09-12 | Arsenal Biosciences, Inc. | Systems targeting psma and ca9 |
| PE20252678A1 (es) | 2023-03-13 | 2025-11-24 | Arsenal Biosciences Inc | Activadores de vias sinteticas |
| WO2024226827A2 (en) | 2023-04-25 | 2024-10-31 | Arsenal Biosciences, Inc. | Novel receptors for transcription regulation |
| WO2024233494A2 (en) * | 2023-05-05 | 2024-11-14 | Cellfe, Inc. | Methods and systems for rapid engineering of resting cells |
| WO2024259299A1 (en) | 2023-06-14 | 2024-12-19 | The Broad Institute, Inc. | Compositions and methods for identification of vhh antibodies that bind a target antigen |
| WO2024259305A1 (en) | 2023-06-14 | 2024-12-19 | The Broad Institute, Inc. | Vhh polypeptides that bind to mesothelin, compositions and methods of use thereof |
| WO2025199346A1 (en) | 2024-03-20 | 2025-09-25 | Arsenal Biosciences, Inc. | Antigen binding proteins that bind tmprss4 and methods of use thereof |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| DE4228457A1 (de) | 1992-08-27 | 1994-04-28 | Beiersdorf Ag | Herstellung von heterodimerem PDGF-AB mit Hilfe eines bicistronischen Vektorsystems in Säugerzellen |
| ATE272311T1 (de) * | 1993-03-23 | 2004-08-15 | Cbr Lab Inc | Verfahren und vorrichtung zur einkapselung biologisch aktiver substanzen in zellen |
| FR2722208B1 (fr) | 1994-07-05 | 1996-10-04 | Inst Nat Sante Rech Med | Nouveau site interne d'entree des ribosomes, vecteur le contenant et utilisation therapeutique |
| US6103521A (en) * | 1995-02-06 | 2000-08-15 | Cell Genesys, Inc. | Multispecific chimeric receptors |
| US5720921A (en) * | 1995-03-10 | 1998-02-24 | Entremed, Inc. | Flow electroporation chamber and method |
| US6074605A (en) * | 1995-03-10 | 2000-06-13 | Entremed, Inc. | Flow electroporation chamber and method |
| US6773669B1 (en) | 1995-03-10 | 2004-08-10 | Maxcyte, Inc. | Flow electroporation chamber and method |
| US5928906A (en) | 1996-05-09 | 1999-07-27 | Sequenom, Inc. | Process for direct sequencing during template amplification |
| US6090617A (en) | 1996-12-05 | 2000-07-18 | Entremed, Inc. | Flow electroporation chamber with electrodes having a crystalline metal nitride coating |
| GB0025307D0 (en) | 2000-10-16 | 2000-11-29 | Celltech Chiroscience Ltd | Biological products |
| ATE338124T1 (de) | 2000-11-07 | 2006-09-15 | Hope City | Cd19-spezifische umgezielte immunzellen |
| US7029916B2 (en) * | 2001-02-21 | 2006-04-18 | Maxcyte, Inc. | Apparatus and method for flow electroporation of biological samples |
| US7723111B2 (en) * | 2001-03-09 | 2010-05-25 | The United States Of America As Represented By The Department Of Health And Human Services | Activated dual specificity lymphocytes and their methods of use |
| EP1456345B1 (en) * | 2001-08-22 | 2016-07-20 | Maxcyte, Inc. | Apparatus and method for electroporation of biological samples |
| WO2004031353A2 (en) | 2002-09-30 | 2004-04-15 | Maxcyte, Inc. | Apparatus and method for streaming electroporation |
| JP2006518219A (ja) * | 2003-02-18 | 2006-08-10 | マックスサイト インコーポレーティッド | 電気穿孔法による細胞への抗原の負荷方法 |
| US20060165668A1 (en) * | 2004-12-10 | 2006-07-27 | Liu Linda N | Genetically modified tumor cells as cancer vaccines |
| EP1795599A1 (en) | 2005-12-09 | 2007-06-13 | Schuler, Gerold, Prof. Dr. | Methods for generating antigen-specific effector T cells |
| US8859229B2 (en) * | 2007-02-02 | 2014-10-14 | Yale University | Transient transfection with RNA |
| EP2141997B1 (en) * | 2007-03-30 | 2012-10-31 | Memorial Sloan-Kettering Cancer Center | Constitutive expression of costimulatory ligands on adoptively transferred t lymphocytes |
| JP5779090B2 (ja) | 2008-04-09 | 2015-09-16 | マックスサイト インコーポレーティッド | 新規に単離された細胞の治療組成物の操作および送達 |
| KR101076879B1 (ko) | 2008-04-11 | 2011-10-25 | 주식회사 하이닉스반도체 | 셀프 부스팅을 이용한 플래시 메모리소자의 프로그램 방법 |
| WO2012050374A2 (en) | 2010-10-13 | 2012-04-19 | Innocell, Inc. | Immunotherapy for solid tumors |
| PH12013501201A1 (en) | 2010-12-09 | 2013-07-29 | Univ Pennsylvania | Use of chimeric antigen receptor-modified t cells to treat cancer |
| CN112795594B (zh) | 2013-05-14 | 2025-09-19 | 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 |
| ES2928000T3 (es) | 2014-06-06 | 2022-11-14 | Memorial Sloan Kettering Cancer Center | Receptores de antígeno quimérico dirigidos a mesotelina y usos de los mismos |
| CU24649B1 (es) | 2016-03-19 | 2023-02-13 | Exuma Biotech Corp | Retrovirus recombinantes incompetentes de replicación para la transducción de linfocitos y expansión regulada de los mismos |
| AU2019205315A1 (en) | 2018-01-05 | 2020-07-16 | Maxcyte, Inc. | Chronic car treatment for cancer |
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