CN114375337A - 具有改进包装效率的重组修饰的腺相关病毒(rAAV) - Google Patents
具有改进包装效率的重组修饰的腺相关病毒(rAAV) Download PDFInfo
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- CN114375337A CN114375337A CN202080064371.XA CN202080064371A CN114375337A CN 114375337 A CN114375337 A CN 114375337A CN 202080064371 A CN202080064371 A CN 202080064371A CN 114375337 A CN114375337 A CN 114375337A
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| US20060205079A1 (en) * | 1997-10-21 | 2006-09-14 | Lynch Carmel M | Amplifiable adeno-associated virus (AAV) packaging cassettes for the production of recombinant AAV vectors |
| CN108727486A (zh) * | 2017-04-24 | 2018-11-02 | 舒泰神（北京）生物制药股份有限公司 | 长效神经生长因子、制备方法及其组合物 |
| CN108884446A (zh) * | 2016-01-29 | 2018-11-23 | 西里昂生物技术有限责任公司 | 基于aav的条件表达系统 |
| EP3461893A1 (en) * | 2014-05-02 | 2019-04-03 | Iontas Limited | Preparation of libraries of protein variants expressed in eukaryotic cells and use for selecting binding molecules |
| CN109844124A (zh) * | 2016-05-20 | 2019-06-04 | 哈佛学院董事及会员团体 | 年龄相关疾病和病症的基因治疗方法 |
| US20220257678A1 (en) * | 2019-07-15 | 2022-08-18 | Charles River Laboratories, Inc. | Recombinantly-modified adeno-associated virus (raav) having improved packaging efficiency |
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| US6093570A (en) | 1995-06-07 | 2000-07-25 | The University Of North Carolina At Chapel Hill | Helper virus-free AAV production |
| CA2265460A1 (en) | 1996-09-11 | 1998-03-19 | The Government Of The United States Of America, Represented By The Secre Tary, Department Of Health And Human Services | Aav4 vector and uses thereof |
| US6995006B2 (en) | 1997-09-05 | 2006-02-07 | Targeted Genetics Corporation | Methods for generating high titer helper-free preparations of released recombinant AAV vectors |
| US6566118B1 (en) | 1997-09-05 | 2003-05-20 | Targeted Genetics Corporation | Methods for generating high titer helper-free preparations of released recombinant AAV vectors |
| IT1297074B1 (it) | 1997-11-21 | 1999-08-03 | Angeletti P Ist Richerche Bio | Forme ormone-dipendenti delle proteine rep del virus adeno-associato (aav-2), sequenze di dna codificanti per esse, vettori che le |
| EP1082413B1 (en) | 1998-05-28 | 2008-07-23 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES | Aav5 vector and uses thereof |
| US6984517B1 (en) | 1998-05-28 | 2006-01-10 | The United States Of America As Represented By The Department Of Health And Human Services | AAV5 vector and uses thereof |
| US6759237B1 (en) | 1998-11-05 | 2004-07-06 | The Trustees Of The University Of Pennsylvania | Adeno-associated virus serotype 1 nucleic acid sequences, vectors and host cells containing same |
| US6759050B1 (en) | 1998-12-03 | 2004-07-06 | Avigen, Inc. | Excipients for use in adeno-associated virus pharmaceutical formulations, and pharmaceutical formulations made therewith |
| DE19905501B4 (de) | 1999-02-10 | 2005-05-19 | MediGene AG, Gesellschaft für molekularbiologische Kardiologie und Onkologie | Verfahren zur Herstellung eines rekombinanten Adeno-assoziierten Virus, geeignete Mittel hierzu sowie Verwendung zur Herstellung eines Arzneimittels |
| US6498244B1 (en) | 1999-05-28 | 2002-12-24 | Cell Genesys, Inc. | Adeno-associated virus capsid immunologic determinants |
| US7115391B1 (en) | 1999-10-01 | 2006-10-03 | Genovo, Inc. | Production of recombinant AAV using adenovirus comprising AAV rep/cap genes |
| US7208315B2 (en) | 2000-01-05 | 2007-04-24 | Fred Hutchinson Cancer Research Center | Compositions and methods for efficient AAV vector production |
| AU2002248297A1 (en) | 2001-01-05 | 2002-07-16 | Children's Hospital, Inc. | Aav2 vectors and methods |
| US6841357B1 (en) | 2001-03-30 | 2005-01-11 | Stratagene California | Method and kits for titering adeno-associated virus vectors |
| US6723551B2 (en) | 2001-11-09 | 2004-04-20 | The United States Of America As Represented By The Department Of Health And Human Services | Production of adeno-associated virus in insect cells |
| WO2003042361A2 (en) | 2001-11-09 | 2003-05-22 | Government Of The United States Of America, Department Of Health And Human Services | Production of adeno-associated virus in insect cells |
| NZ532635A (en) * | 2001-11-13 | 2007-05-31 | Univ Pennsylvania | A method of identifying unknown adeno-associated virus (AAV) sequences and a kit for the method |
| DK2359869T3 (en) | 2001-12-17 | 2019-04-15 | Univ Pennsylvania | Sequences of adeno-associated virus (AAV) serotype 8, vectors containing these, and uses thereof |
| US7419817B2 (en) | 2002-05-17 | 2008-09-02 | The United States Of America As Represented By The Secretary Department Of Health And Human Services, Nih. | Scalable purification of AAV2, AAV4 or AAV5 using ion-exchange chromatography |
| US7122348B2 (en) | 2002-12-11 | 2006-10-17 | City Of Hope | AAV2 Rep protein fusions |
| US9441244B2 (en) | 2003-06-30 | 2016-09-13 | The Regents Of The University Of California | Mutant adeno-associated virus virions and methods of use thereof |
| US9233131B2 (en) | 2003-06-30 | 2016-01-12 | The Regents Of The University Of California | Mutant adeno-associated virus virions and methods of use thereof |
| CN1856576B (zh) | 2003-09-30 | 2011-05-04 | 宾夕法尼亚州立大学托管会 | 腺伴随病毒(aav)进化支、序列、含有这些序列的载体及它们的应用 |
| US7625570B1 (en) | 2005-03-10 | 2009-12-01 | The Regents Of The University Of California | Methods for purifying adeno-associated virus |
| EP2311967B1 (en) | 2005-10-20 | 2017-09-20 | UniQure IP B.V. | Improved AAV vectors produced in insect cells |
| ES2385679T3 (es) | 2006-08-24 | 2012-07-30 | Virovek, Inc. | Expresión de células de insecto de genes con marcos de lectura abiertos superpuestos, métodos y composiciones de éstos |
| WO2010022195A2 (en) | 2008-08-20 | 2010-02-25 | Virxsys Corporation | Non-integrating lenti/adeno-associated virus hybrid vector system |
| HUE028341T2 (en) | 2009-06-16 | 2016-12-28 | Genzyme Corp | Improved methods for purification of recombinant aav vectors |
| JP2014503173A (ja) * | 2009-11-05 | 2014-02-13 | プロイェクト、デ、ビオメディシナ、シーマ、ソシエダッド、リミターダ | 制御された発現系 |
| US8663624B2 (en) | 2010-10-06 | 2014-03-04 | The Regents Of The University Of California | Adeno-associated virus virions with variant capsid and methods of use thereof |
| DK2675902T3 (da) | 2011-02-17 | 2019-06-03 | Univ Pennsylvania | Sammensætninger og fremgangsmåder til at ændre vævsspecificitet og forbedre aav9-medieret genoverførsel |
| EP2500434A1 (en) | 2011-03-12 | 2012-09-19 | Association Institut de Myologie | Capsid-free AAV vectors, compositions, and methods for vector production and gene delivery |
| WO2012145509A2 (en) | 2011-04-19 | 2012-10-26 | The Research Foundation Of State University Of New York | Adeno-associated-virus rep sequences, vectors, and viruses |
| HRP20171334T1 (hr) | 2011-04-22 | 2017-11-17 | The Regents Of The University Of California | Virioni adeno-povezanog virusa s kapsid varijantom i postupci njihove upotrebe |
| US9441206B2 (en) | 2011-10-28 | 2016-09-13 | The University Of North Carolina At Chapel Hill | Cell line for production of adeno-associated virus |
| EP3241902B1 (en) | 2012-05-25 | 2018-02-28 | The Regents of The University of California | Methods and compositions for rna-directed target dna modification and for rna-directed modulation of transcription |
| US8697359B1 (en) | 2012-12-12 | 2014-04-15 | The Broad Institute, Inc. | CRISPR-Cas systems and methods for altering expression of gene products |
| US10106816B2 (en) * | 2012-12-14 | 2018-10-23 | Case Western Reserve University | Genomic RNA packaging enhancer element |
| US9447433B2 (en) | 2013-03-15 | 2016-09-20 | The University Of North Carolina At Chapel Hill | Synthetic adeno-associated virus inverted terminal repeats |
| CN105765066B (zh) | 2013-11-29 | 2018-12-14 | 宝生物工程株式会社 | 用于定量腺伴随病毒的方法 |
| JP7023842B2 (ja) * | 2015-10-29 | 2022-02-22 | テンプル ユニヴァーシティ － オブ ザ コモンウェルス システム オブ ハイアー エデュケーション | Ｄｎａポリメラーゼシータによる核酸の３’末端の修飾 |
| US11208630B2 (en) | 2015-12-24 | 2021-12-28 | University Of Florida Research Foundation, Incorporated | AAV production using suspension adapted cells |
| US10294452B2 (en) | 2016-11-22 | 2019-05-21 | Dao-Yao He | Lysis, extraction and purification of adeno-associated virus and adenovirus from host cells |
-
2019
- 2019-07-15 US US16/512,051 patent/US10653731B1/en active Active
-
2020
- 2020-03-12 US US17/627,165 patent/US12156894B2/en active Active
- 2020-03-12 WO PCT/US2020/022326 patent/WO2021011034A1/en not_active Ceased
- 2020-03-12 KR KR1020227004899A patent/KR20220034214A/ko not_active Ceased
- 2020-03-12 CN CN202080064371.XA patent/CN114375337A/zh active Pending
- 2020-03-12 AU AU2020315513A patent/AU2020315513A1/en active Pending
- 2020-03-12 EP EP20839897.4A patent/EP3999648A4/en active Pending
- 2020-03-12 JP JP2022502942A patent/JP2022542829A/ja active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060205079A1 (en) * | 1997-10-21 | 2006-09-14 | Lynch Carmel M | Amplifiable adeno-associated virus (AAV) packaging cassettes for the production of recombinant AAV vectors |
| EP3461893A1 (en) * | 2014-05-02 | 2019-04-03 | Iontas Limited | Preparation of libraries of protein variants expressed in eukaryotic cells and use for selecting binding molecules |
| CN108884446A (zh) * | 2016-01-29 | 2018-11-23 | 西里昂生物技术有限责任公司 | 基于aav的条件表达系统 |
| CN109844124A (zh) * | 2016-05-20 | 2019-06-04 | 哈佛学院董事及会员团体 | 年龄相关疾病和病症的基因治疗方法 |
| CN108727486A (zh) * | 2017-04-24 | 2018-11-02 | 舒泰神（北京）生物制药股份有限公司 | 长效神经生长因子、制备方法及其组合物 |
| US20220257678A1 (en) * | 2019-07-15 | 2022-08-18 | Charles River Laboratories, Inc. | Recombinantly-modified adeno-associated virus (raav) having improved packaging efficiency |
Non-Patent Citations (2)
| Title |
|---|
| STIFANI SATKUNANTHAN等: "The function of DNA binding proteion nucleophosmin in AAV replication", VIROLOGY, 10 July 2017 (2017-07-10) * |
| 吴园: "基于核酸适体的多功能上转换纳米探针的研究", 中国优秀博士学位论文全文数据库 工程科技I辑, 15 January 2019 (2019-01-15) * |
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| KR20220034214A (ko) | 2022-03-17 |
| US12156894B2 (en) | 2024-12-03 |
| US10653731B1 (en) | 2020-05-19 |
| US20220257678A1 (en) | 2022-08-18 |
| AU2020315513A1 (en) | 2022-02-17 |
| WO2021011034A1 (en) | 2021-01-21 |
| EP3999648A1 (en) | 2022-05-25 |
| EP3999648A4 (en) | 2023-08-16 |
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