CN109517820A - 一种靶向HPK1的gRNA以及HPK1基因编辑方法 - Google Patents
一种靶向HPK1的gRNA以及HPK1基因编辑方法 Download PDFInfo
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Abstract
Description
Claims (20)
Priority Applications (12)
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CN201710853090.2A CN109517820B (zh) | 2017-09-20 | 2017-09-20 | 一种靶向HPK1的gRNA以及HPK1基因编辑方法 |
BR112020008517-0A BR112020008517A2 (pt) | 2017-09-20 | 2018-09-20 | um grna alvejador de hpk1 e um método para edição do gene hpk1 |
US16/648,907 US11786550B2 (en) | 2017-09-20 | 2018-09-20 | gRNA targeting HPK1 and a method for editing HPK1 gene |
CA3076095A CA3076095A1 (en) | 2017-09-20 | 2018-09-20 | A grna targeting hpk1 and a method for editing hpk1 gene |
PL18859478.2T PL3682000T3 (pl) | 2017-09-20 | 2018-09-20 | gRNA ukierunkowany na HPK1 i sposób edycji genu HPK1 |
AU2018336522A AU2018336522A1 (en) | 2017-09-20 | 2018-09-20 | A gRNA targeting HPK1 and a method for editing HPK1 gene |
PCT/CN2018/106636 WO2019057102A1 (en) | 2017-09-20 | 2018-09-20 | HPK1 TARGETING ARNG AND HPK1 GENE EDITING METHOD |
JP2020517124A JP7412666B2 (ja) | 2017-09-20 | 2018-09-20 | HPK1を標的とするgRNA及びHPK1遺伝子の編集方法 |
CN201880060379.1A CN111263808B (zh) | 2017-09-20 | 2018-09-20 | 一种靶向HPK1的gRNA和一种编辑HPK1基因的方法 |
EP18859478.2A EP3682000B8 (en) | 2017-09-20 | 2018-09-20 | A grna targeting hpk1 and a method for editing hpk1 gene |
KR1020207011114A KR102547477B1 (ko) | 2017-09-20 | 2018-09-20 | HPK-1을 표적화하는 gRNA 및 HPK-1 유전자의 편집 방법 |
ES18859478T ES2946332T3 (es) | 2017-09-20 | 2018-09-20 | Un ARNg dirigido a HPK1 y un método para editar el gen HPK1 |
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CN201710853090.2A CN109517820B (zh) | 2017-09-20 | 2017-09-20 | 一种靶向HPK1的gRNA以及HPK1基因编辑方法 |
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CN109517820A true CN109517820A (zh) | 2019-03-26 |
CN109517820B CN109517820B (zh) | 2021-09-24 |
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CN201880060379.1A Active CN111263808B (zh) | 2017-09-20 | 2018-09-20 | 一种靶向HPK1的gRNA和一种编辑HPK1基因的方法 |
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---|---|---|---|---|
BR112020018658A2 (pt) | 2018-03-15 | 2020-12-29 | KSQ Therapeutics, Inc. | Composições de regulação gênica e métodos para imu-noterapia aprimorada |
CN113227089A (zh) | 2018-10-31 | 2021-08-06 | 吉利德科学公司 | 作为hpk1抑制剂的取代的6-氮杂苯并咪唑化合物 |
CA3116347A1 (en) | 2018-10-31 | 2020-05-07 | Gilead Sciences, Inc. | Substituted 6-azabenzimidazole compounds having hpk1 inhibitory activity |
EP3972695A1 (en) | 2019-05-23 | 2022-03-30 | Gilead Sciences, Inc. | Substituted exo-methylene-oxindoles which are hpk1/map4k1 inhibitors |
WO2021064655A1 (en) * | 2019-10-02 | 2021-04-08 | Massachusetts Institute Of Technology | High-throughput genetic screening |
CN114107292B (zh) * | 2020-08-27 | 2024-03-12 | 阿思科力(苏州)生物科技有限公司 | 用于外源基因定点***的基因编辑***和方法 |
CN116893265A (zh) * | 2023-09-08 | 2023-10-17 | 军科正源(北京)药物研究有限责任公司 | 检测pbmc中蛋白磷酸化的方法和试剂盒以及相关应用 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007041511A2 (en) * | 2005-09-30 | 2007-04-12 | New York University | Hematopoietic progenitor kinase 1 for modulation of an immune response |
WO2016090300A1 (en) * | 2014-12-05 | 2016-06-09 | Genentech, Inc. | Methods and compositions for treating cancer using pd-1 axis antagonists and hpk1 antagonists |
WO2017120546A1 (en) * | 2016-01-08 | 2017-07-13 | The Regents Of The University Of California | Conditionally active heterodimeric polypeptides and methods of use thereof |
Family Cites Families (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US825259A (en) | 1903-11-07 | 1906-07-03 | Gen Electric | Snap-switch. |
IN165717B (zh) | 1986-08-07 | 1989-12-23 | Battelle Memorial Institute | |
US6451995B1 (en) | 1996-03-20 | 2002-09-17 | Sloan-Kettering Institute For Cancer Research | Single chain FV polynucleotide or peptide constructs of anti-ganglioside GD2 antibodies, cells expressing same and related methods |
CA2343156A1 (en) | 1998-09-04 | 2000-03-16 | Sloan-Kettering Institute For Cancer Research | Fusion receptors specific for prostate-specific membrane antigen and uses thereof |
WO2000023573A2 (en) | 1998-10-20 | 2000-04-27 | City Of Hope | Cd20-specific redirected t cells and their use in cellular immunotherapy of cd20+ malignancies |
CA2410510A1 (en) | 2000-06-02 | 2001-12-13 | Memorial Sloan-Kettering Cancer Center | Artificial antigen presenting cells and methods of use thereof |
EP1334188B1 (en) | 2000-11-07 | 2006-08-30 | City of Hope | Cd19-specific redirected immune cells |
US7070995B2 (en) | 2001-04-11 | 2006-07-04 | City Of Hope | CE7-specific redirected immune cells |
US20090257994A1 (en) | 2001-04-30 | 2009-10-15 | City Of Hope | Chimeric immunoreceptor useful in treating human cancers |
US7446190B2 (en) | 2002-05-28 | 2008-11-04 | Sloan-Kettering Institute For Cancer Research | Nucleic acids encoding chimeric T cell receptors |
US20050129671A1 (en) | 2003-03-11 | 2005-06-16 | City Of Hope | Mammalian antigen-presenting T cells and bi-specific T cells |
EP2141997B1 (en) | 2007-03-30 | 2012-10-31 | Memorial Sloan-Kettering Cancer Center | Constitutive expression of costimulatory ligands on adoptively transferred t lymphocytes |
US8479118B2 (en) | 2007-12-10 | 2013-07-02 | Microsoft Corporation | Switching search providers within a browser search box |
JP5173594B2 (ja) | 2008-05-27 | 2013-04-03 | キヤノン株式会社 | 管理装置、画像形成装置及びそれらの処理方法 |
CA2779526C (en) | 2009-11-03 | 2022-12-06 | City Of Hope | Truncated epiderimal growth factor receptor (egfrt) for transduced t cell selection |
DK2649086T3 (en) | 2010-12-09 | 2017-09-18 | Univ Pennsylvania | USING CHEMICAL ANTIGEN RECEPTOR-MODIFIED T-CELLS TO TREAT CANCER |
BR112013024395B1 (pt) | 2011-03-23 | 2021-10-26 | Fred Hutchinson Cancer Research Center | Composições adotivas de imunoterapia celular e método para fabricação da dita composição |
US8398282B2 (en) | 2011-05-12 | 2013-03-19 | Delphi Technologies, Inc. | Vehicle front lighting assembly and systems having a variable tint electrowetting element |
EP2776451B1 (en) | 2011-11-11 | 2018-07-18 | Fred Hutchinson Cancer Research Center | Cyclin a1-targeted t-cell immunotherapy for cancer |
EP2814846B1 (en) | 2012-02-13 | 2020-01-08 | Seattle Children's Hospital d/b/a Seattle Children's Research Institute | Bispecific chimeric antigen receptors and therapeutic uses thereof |
WO2013126726A1 (en) | 2012-02-22 | 2013-08-29 | The Trustees Of The University Of Pennsylvania | Double transgenic t cells comprising a car and a tcr and their methods of use |
EP2844743B1 (en) | 2012-05-03 | 2021-01-13 | Fred Hutchinson Cancer Research Center | Enhanced affinity t cell receptors and methods for making the same |
LT2884999T (lt) | 2012-08-20 | 2021-04-12 | Fred Hutchinson Cancer Research Center | Ląstelinės imunoterapijos būdas ir kompozicijos |
AU2013327136A1 (en) | 2012-10-02 | 2015-04-16 | Memorial Sloan-Kettering Cancer Center | Compositions and methods for immunotherapy |
US20140189896A1 (en) | 2012-12-12 | 2014-07-03 | Feng Zhang | Crispr-cas component systems, methods and compositions for sequence manipulation |
JP6879910B2 (ja) * | 2014-10-31 | 2021-06-02 | ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア | Cart細胞における遺伝子発現の改変およびその使用 |
JP6949728B2 (ja) * | 2015-05-29 | 2021-10-13 | ジュノー セラピューティクス インコーポレイテッド | 遺伝子操作された細胞における阻害相互作用を調節するための組成物および方法 |
MY201101A (en) | 2015-09-17 | 2024-02-05 | Novartis Ag | Car t cell therapies with enhanced efficacy |
JP2019517788A (ja) | 2016-05-06 | 2019-06-27 | ジュノー セラピューティクス インコーポレイテッド | 遺伝子操作された細胞および同細胞を作製する方法 |
WO2018081531A2 (en) * | 2016-10-28 | 2018-05-03 | Ariad Pharmaceuticals, Inc. | Methods for human t-cell activation |
WO2018085275A1 (en) | 2016-11-02 | 2018-05-11 | The Regents Of The University Of California | Targeting lats1/2 and the hippo intracellular signaling pathway for cancer immunotherapy |
KR20200130826A (ko) | 2018-03-15 | 2020-11-20 | 케이에스큐 세러퓨틱스 인코포레이티드 | 개선된 면역요법을 위한 유전자-조절 조성물 및 방법 |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007041511A2 (en) * | 2005-09-30 | 2007-04-12 | New York University | Hematopoietic progenitor kinase 1 for modulation of an immune response |
WO2016090300A1 (en) * | 2014-12-05 | 2016-06-09 | Genentech, Inc. | Methods and compositions for treating cancer using pd-1 axis antagonists and hpk1 antagonists |
WO2017120546A1 (en) * | 2016-01-08 | 2017-07-13 | The Regents Of The University Of California | Conditionally active heterodimeric polypeptides and methods of use thereof |
Non-Patent Citations (1)
Title |
---|
SAWASDIKOSOL S等: "HPK1 as a novel target for cancer immunotherapy", 《IMMUNOL RES.》 * |
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CN111263808B (zh) | 2023-10-20 |
CN111263808A (zh) | 2020-06-09 |
CA3076095A1 (en) | 2019-03-28 |
US20220023340A1 (en) | 2022-01-27 |
JP7412666B2 (ja) | 2024-01-15 |
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KR20200051805A (ko) | 2020-05-13 |
PL3682000T3 (pl) | 2023-08-07 |
BR112020008517A2 (pt) | 2021-01-26 |
KR102547477B1 (ko) | 2023-06-27 |
EP3682000A1 (en) | 2020-07-22 |
WO2019057102A1 (en) | 2019-03-28 |
US11786550B2 (en) | 2023-10-17 |
EP3682000A4 (en) | 2021-01-20 |
AU2018336522A1 (en) | 2020-04-30 |
EP3682000B8 (en) | 2023-05-24 |
CN109517820B (zh) | 2021-09-24 |
JP2020536514A (ja) | 2020-12-17 |
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