CN101843641B - 腺病毒和编码其的核酸的新应用 - Google Patents
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| DE10223534.1 | 2002-05-27 | ||
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| DE10225400.1 | 2002-06-07 | ||
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| DE10248039 | 2002-10-15 | ||
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| JP5213298B2 (ja) | 2002-05-27 | 2013-06-19 | ホルム，ペル・ゾンネ | アデノウイルスおよびそれをコードしている核酸の新たな使用 |
| EP1689446B1 (de) * | 2003-11-14 | 2015-01-07 | Per Sonne Holm | Neue adenoviren, dafür codierende nukleinsäuren und deren verwendung |
| CA2546178A1 (en) * | 2003-11-14 | 2005-06-09 | Per Sonne Holm | New use of adenovirus and nucleic acids coding therefor |
| US8361976B2 (en) | 2004-07-09 | 2013-01-29 | University Of Massachusetts | Therapeutic alteration of transplantable tissues through in situ or ex vivo exposure to RNA interference molecules |
| US20090232800A1 (en) * | 2004-12-31 | 2009-09-17 | Per Sonne Holm | E1-minus adenoviruses and use thereof |
| SG158133A1 (en) | 2004-12-31 | 2010-01-29 | Sonne Holm | Method for reversing multiple resistance in animal cells |
| WO2012022496A2 (en) | 2010-08-19 | 2012-02-23 | Per Sonne Holm | Method for killing tumor stem cells |
| SG11201507393TA (en) | 2013-03-14 | 2015-10-29 | Salk Inst For Biological Studi | Oncolytic adenovirus compositions |
| KR102608590B1 (ko) | 2014-09-24 | 2023-12-01 | 솔크 인스티튜트 포 바이올로지칼 스터디즈 | 종양 살상 바이러스 및 이의 사용방법 |
| WO2017147265A1 (en) | 2016-02-23 | 2017-08-31 | Salk Institute For Biological Studies | High throughput assay for measuring adenovirus replication kinetics |
| WO2017147269A1 (en) | 2016-02-23 | 2017-08-31 | Salk Institute For Biological Studies | Exogenous gene expression in therapeutic adenovirus for minimal impact on viral kinetics |
| EP3532082A4 (en) | 2016-12-12 | 2020-08-26 | Salk Institute for Biological Studies | SYNTHETIC ADENOVIRUS TUMOR TARGETING AND THEIR USES |
| KR20210031852A (ko) | 2018-03-05 | 2021-03-23 | 클리니쿰 레히츠 데어 이자르 데어 테크니쉔 우니베르지테트 뮌헨 | 종양 세포 붕괴성 아데노바이러스와 cdk4/6 억제제의 조합물에 의한 종양의 치료 |
| CN112292449A (zh) | 2018-04-09 | 2021-01-29 | 萨克生物研究学院 | 具有增强的复制特性的溶瘤腺病毒组合物 |
| AU2019294294A1 (en) | 2018-06-25 | 2021-02-11 | Fondazione Telethon Ets | Gene therapy |
| KR20220079551A (ko) | 2019-09-05 | 2022-06-13 | 클리니쿰 레히츠 데어 이자르 데어 테크니쉔 우니베르지테트 뮌헨 | 종양 세포 붕괴성 아데노바이러스, cdk4/6 억제제 및 추가의 치료 활성제의 조합물에 의한 종양의 치료 |
| CN120060368A (zh) * | 2020-03-23 | 2025-05-30 | 株式会社库利金 | 包含双特异性核酸分子的溶瘤病毒的结构 |
| CN114540349B (zh) * | 2020-11-27 | 2024-11-22 | 中国科学院分子细胞科学卓越创新中心 | 结合yb-1蛋白的核酸分子 |
| CA3233100A1 (en) | 2021-09-23 | 2023-03-30 | Sagittarius Bio, Inc. | Adenoviruses and methods for using adenoviruses |
Family Cites Families (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US931830A (en) * | 1907-09-17 | 1909-08-24 | Harry Zimmerman | Material-cutter. |
| US4947842A (en) | 1988-09-22 | 1990-08-14 | Medical Engineering And Development Institute, Inc. | Method and apparatus for treating tissue with first and second modalities |
| ES2259800T3 (es) | 1990-06-11 | 2006-10-16 | Gilead Sciences, Inc. | Procedimientos de uso de ligandos de acido nucleico. |
| US5801029A (en) | 1993-02-16 | 1998-09-01 | Onyx Pharmaceuticals, Inc. | Cytopathic viruses for therapy and prophylaxis of neoplasia |
| ATE178490T1 (de) * | 1993-02-16 | 1999-04-15 | Onyx Pharmaceuticals | Cytopathische viren zur therapie und prophylaxe der neoplasie |
| US5698443A (en) | 1995-06-27 | 1997-12-16 | Calydon, Inc. | Tissue specific viral vectors |
| ATE336587T1 (de) | 1994-06-10 | 2006-09-15 | Genvec Inc | Adenoviren-vektor systeme und zelllinien |
| US5998205A (en) | 1994-11-28 | 1999-12-07 | Genetic Therapy, Inc. | Vectors for tissue-specific replication |
| US6326356B1 (en) * | 1996-10-18 | 2001-12-04 | Board Of Regents, The University Of Texas System | Suppression of neu overexpression using a mini-E1A gene |
| US5707618A (en) | 1995-03-24 | 1998-01-13 | Genzyme Corporation | Adenovirus vectors for gene therapy |
| JP3827163B2 (ja) | 1995-03-24 | 2006-09-27 | ジェンザイム・コーポレーション | 遺伝子治療用のアデノウイルスベクター |
| US6676935B2 (en) | 1995-06-27 | 2004-01-13 | Cell Genesys, Inc. | Tissue specific adenoviral vectors |
| AU7674896A (en) | 1995-10-31 | 1997-05-22 | Board Of Regents, The University Of Texas System | Adenovirus-antisense k-ras expression vectors and their application in cancer therapy |
| US6022863A (en) | 1996-05-21 | 2000-02-08 | Yale University | Regulation of gene expression |
| US6730662B1 (en) * | 1996-07-05 | 2004-05-04 | Mcgill University | Adenovirus E4 proteins for inducing cell death |
| DE69725882T2 (de) | 1996-07-05 | 2004-07-29 | Branton, Philip E., St. Lambert | Adenovirus e4 proteine für induktion von zelltod |
| DE59708838D1 (de) | 1996-08-30 | 2003-01-09 | Jens Peter Fuerste | Spiegelselektion und spiegelevolution von nucleinsäuren |
| US5994132A (en) | 1996-10-23 | 1999-11-30 | University Of Michigan | Adenovirus vectors |
| US6110744A (en) | 1996-11-13 | 2000-08-29 | Board Of Regents, The University Of Texas System | Diminishing viral gene expression by promoter replacement |
| US6080578A (en) | 1996-12-31 | 2000-06-27 | Onyx Pharmaceuticals, Inc. | Cytopathic adenoviral E1B mutated viruses for therapy and prophylaxis of neoplasia |
| US6100086A (en) | 1997-04-14 | 2000-08-08 | Genzyme Corporation | Transgene expression systems |
| DE69838584T2 (de) | 1997-08-04 | 2008-06-26 | Cell Genesys, Inc., Foster City | Enhancer des menschlichen glandulären kallikreingens, vektoren die ihn enthalten und methoden für seine verwendung |
| DE19742706B4 (de) | 1997-09-26 | 2013-07-25 | Pieris Proteolab Ag | Lipocalinmuteine |
| CN101618049A (zh) | 1997-10-09 | 2010-01-06 | 威尔斯塔特生物公司 | 使用病毒来治疗赘生物 |
| CN1110553C (zh) * | 1998-07-15 | 2003-06-04 | 杭州赛狮生物技术开发有限公司 | 基因工程腺病毒及其用途 |
| AU1092500A (en) | 1998-10-15 | 2000-05-01 | Canji, Inc. | Recombinant e1a deleted adenoviral vectors |
| US6649158B1 (en) | 1998-10-15 | 2003-11-18 | Canji, Inc. | Methods and compositions to induce antitumor response |
| DE19860602A1 (de) | 1998-12-29 | 2000-07-06 | Max Delbrueck Centrum | Gentransfervektor für die Diagnostik und die Therapie von malignen Tumoren |
| US6428968B1 (en) | 1999-03-15 | 2002-08-06 | The Trustees Of The University Of Pennsylvania | Combined therapy with a chemotherapeutic agent and an oncolytic virus for killing tumor cells in a subject |
| GB9906815D0 (en) | 1999-03-24 | 1999-05-19 | Isrec | Anti-neoplastic viral agents |
| DE19929569A1 (de) | 1999-06-21 | 2000-12-28 | Holm Per Sonne | Mittel zur Behandlung maligner Erkrankungen unter Verwendung des Proteins YB-1 |
| AU6425800A (en) | 1999-06-30 | 2001-01-22 | Max-Delbruck-Centrum Fur Molekulare Medizin | Agents for the diagnosis, prognosis and treatment of malignant diseases |
| US6955808B2 (en) | 1999-09-24 | 2005-10-18 | Uab Research Foundation | Capsid-modified recombinant adenovirus and methods of use |
| AU1087701A (en) | 1999-10-15 | 2001-04-30 | Canji, Inc. | Targeted vectors |
| US6140126A (en) | 1999-10-26 | 2000-10-31 | Isis Pharmaceuticals Inc. | Antisense modulation of Y-box binding protein 1 expression |
| CN1382218A (zh) * | 1999-11-15 | 2002-11-27 | 昂尼克斯药物公司 | 溶瘤腺病毒 |
| DE10015413A1 (de) | 2000-03-23 | 2001-09-27 | Max Delbrueck Centrum | Mittel zur Diagnose und Therapie viraler Erkrankungen |
| WO2001092549A2 (en) | 2000-05-31 | 2001-12-06 | Genvec, Inc. | Method and composition for targeting an adenoviral vector |
| AU784975B2 (en) | 2000-10-11 | 2006-08-10 | Sumitomo Chemical Company, Limited | DNA-binding protein YB-1-containing collagen accumulation inhibitors |
| AU2002235141A1 (en) | 2000-11-27 | 2002-06-03 | Geron Corporation | Glycosyltransferase vectors for treating cancer |
| US20030095989A1 (en) | 2000-12-18 | 2003-05-22 | Irving John M. | Chimeric cytolytic viruses for cancer treatment |
| DE10150945A1 (de) | 2001-10-16 | 2003-04-17 | Holm Per Sonne | Adenovirale Systeme und deren Anwendungen |
| EP1346058B1 (de) | 2000-12-28 | 2007-05-02 | Per Sonne Holm | Adenovirale systeme und deren anwendungen |
| US20030138405A1 (en) | 2001-04-17 | 2003-07-24 | Juan Fueyo | Conditionally replicative adenovirus to target the Rb and Rb-related pathways |
| WO2003025190A1 (en) | 2001-09-14 | 2003-03-27 | The New Industry Research Organization | Tumor-specific promoter and use thereof |
| DE10150984A1 (de) | 2001-10-16 | 2003-04-17 | Holm Per Sonne | Verwendung des adenoviralen E2-late-Promotors |
| EP1497440B1 (en) | 2002-04-25 | 2008-08-20 | Crucell Holland B.V. | Stable adenoviral vectors and methods for propagation thereof |
| JP5213298B2 (ja) * | 2002-05-27 | 2013-06-19 | ホルム，ペル・ゾンネ | アデノウイルスおよびそれをコードしている核酸の新たな使用 |
| MXPA05004074A (es) | 2002-10-15 | 2005-09-20 | Sonne Holm Per | Nuevos adenovirus, acidos nucleicos que los codifican y su uso. |
| US20050042217A1 (en) | 2003-03-19 | 2005-02-24 | Yan Qi | Specific inhibition of allorejection |
| EP1689446B1 (de) | 2003-11-14 | 2015-01-07 | Per Sonne Holm | Neue adenoviren, dafür codierende nukleinsäuren und deren verwendung |
| CA2546178A1 (en) | 2003-11-14 | 2005-06-09 | Per Sonne Holm | New use of adenovirus and nucleic acids coding therefor |
| US7851218B2 (en) | 2004-12-13 | 2010-12-14 | Schering Corporation | Cell lines for production of replication-defective adenovirus |
| US20090232800A1 (en) | 2004-12-31 | 2009-09-17 | Per Sonne Holm | E1-minus adenoviruses and use thereof |
| SG158133A1 (en) | 2004-12-31 | 2010-01-29 | Sonne Holm | Method for reversing multiple resistance in animal cells |
| WO2007103825A2 (en) | 2006-03-02 | 2007-09-13 | The Board Of Regents Of The University Of Texas System | Combination therapy with oncolytic adenovirus |
-
2003
- 2003-05-27 JP JP2004508113A patent/JP5213298B2/ja not_active Expired - Lifetime
- 2003-05-27 AU AU2003242585A patent/AU2003242585A1/en not_active Abandoned
- 2003-05-27 CN CN201010161559.4A patent/CN101843641B/zh not_active Expired - Fee Related
- 2003-05-27 US US10/515,238 patent/US20060099178A1/en not_active Abandoned
- 2003-05-27 KR KR1020047019231A patent/KR101083450B1/ko not_active Expired - Fee Related
- 2003-05-27 CA CA002487811A patent/CA2487811A1/en not_active Abandoned
- 2003-05-27 WO PCT/EP2003/005583 patent/WO2003099859A2/de not_active Ceased
- 2003-05-27 EP EP03755145.4A patent/EP1506021B1/de not_active Expired - Lifetime
- 2003-05-27 CN CN03812310XA patent/CN1655827B/zh not_active Expired - Fee Related
-
2004
- 2004-11-22 ZA ZA2004/09361A patent/ZA200409361B/en unknown
-
2010
- 2010-04-28 US US12/769,435 patent/US10155930B2/en not_active Expired - Lifetime
- 2010-09-09 AU AU2010219364A patent/AU2010219364B2/en not_active Ceased
-
2012
- 2012-05-22 JP JP2012116438A patent/JP5719800B2/ja not_active Expired - Lifetime
-
2014
- 2014-08-04 JP JP2014158673A patent/JP2014224141A/ja not_active Withdrawn
-
2017
- 2017-03-07 US US15/452,470 patent/US10538744B2/en not_active Expired - Fee Related
-
2018
- 2018-10-31 US US16/176,461 patent/US10731136B2/en not_active Expired - Fee Related
-
2019
- 2019-12-05 US US16/704,669 patent/US11268073B2/en not_active Expired - Fee Related
Non-Patent Citations (2)
| Title |
|---|
| Per S. Holm等.YB-1 Relocates to the Nucleus in Adenovirus-infected Cells and Facilitates Viral Replication by Inducing E2 Gene Expression through the E2 Late Promoter.《The Journal of Biological Chemistry》.2002,第277卷(第12期),10427-10434. |
| YB-1 Relocates to the Nucleus in Adenovirus-infected Cells and Facilitates Viral Replication by Inducing E2 Gene Expression through the E2 Late Promoter;Per S. Holm等;《The Journal of Biological Chemistry》;20020322;第277卷(第12期);10427-10434 * |
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| CA2487811A1 (en) | 2003-12-04 |
| CN101843641A (zh) | 2010-09-29 |
| US10731136B2 (en) | 2020-08-04 |
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| US10155930B2 (en) | 2018-12-18 |
| US20190055522A1 (en) | 2019-02-21 |
| WO2003099859A2 (de) | 2003-12-04 |
| JP2012179058A (ja) | 2012-09-20 |
| AU2010219364A1 (en) | 2010-09-30 |
| US10538744B2 (en) | 2020-01-21 |
| AU2003242585A2 (en) | 2003-12-12 |
| JP5213298B2 (ja) | 2013-06-19 |
| JP2014224141A (ja) | 2014-12-04 |
| US20110033424A1 (en) | 2011-02-10 |
| US20060099178A1 (en) | 2006-05-11 |
| JP5719800B2 (ja) | 2015-05-20 |
| CN1655827A (zh) | 2005-08-17 |
| US11268073B2 (en) | 2022-03-08 |
| US20180002674A1 (en) | 2018-01-04 |
| EP1506021B1 (de) | 2019-05-01 |
| KR101083450B1 (ko) | 2011-11-16 |
| ZA200409361B (en) | 2005-08-31 |
| EP1506021A2 (de) | 2005-02-16 |
| WO2003099859A3 (de) | 2004-04-15 |
| JP2006512284A (ja) | 2006-04-13 |
| AU2003242585A1 (en) | 2003-12-12 |
| KR20050008744A (ko) | 2005-01-21 |
| US20200095560A1 (en) | 2020-03-26 |
| AU2010219364B2 (en) | 2011-06-09 |
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