CA2287508A1 - Materials and methods for ribozyme treatment of retinal diseases - Google Patents
Materials and methods for ribozyme treatment of retinal diseases Download PDFInfo
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- CA2287508A1 CA2287508A1 CA002287508A CA2287508A CA2287508A1 CA 2287508 A1 CA2287508 A1 CA 2287508A1 CA 002287508 A CA002287508 A CA 002287508A CA 2287508 A CA2287508 A CA 2287508A CA 2287508 A1 CA2287508 A1 CA 2287508A1
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- ribozyme
- ribozymes
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- retina
- retinal
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
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| US4449297P | 1997-04-21 | 1997-04-21 | |
| US60/044,492 | 1997-04-21 | ||
| US4614797P | 1997-05-09 | 1997-05-09 | |
| US60/046,147 | 1997-05-09 | ||
| PCT/US1998/007968 WO1998048009A2 (en) | 1997-04-21 | 1998-04-21 | Materials and methods for ribozyme treatment of retinal diseases |
Publications (1)
| Publication Number | Publication Date |
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| CA2287508A1 true CA2287508A1 (en) | 1998-10-29 |
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| CA002287508A Abandoned CA2287508A1 (en) | 1997-04-21 | 1998-04-21 | Materials and methods for ribozyme treatment of retinal diseases |
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| US (1) | US6225291B1 (enExample) |
| EP (1) | EP0977841A2 (enExample) |
| JP (1) | JP2001523959A (enExample) |
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| BR (1) | BR9808606A (enExample) |
| CA (1) | CA2287508A1 (enExample) |
| NZ (1) | NZ500427A (enExample) |
| WO (1) | WO1998048009A2 (enExample) |
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| NZ500427A (en) | 1997-04-21 | 2002-12-20 | Univ Florida | The use of ribozyme treatment for retinal diseases |
| DE19956568A1 (de) * | 1999-01-30 | 2000-08-17 | Roland Kreutzer | Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens |
| JP2002542805A (ja) * | 1999-04-30 | 2002-12-17 | ユニバーシティ オブ フロリダ | アデノ随伴ウイルス送達リボザイム組成物および使用方法 |
| WO2000066720A2 (en) * | 1999-04-30 | 2000-11-09 | City Of Hope | The use of adeno-associated virus (aav) deliver cytoprotective genes |
| US7829693B2 (en) * | 1999-11-24 | 2010-11-09 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of a target gene |
| US8546143B2 (en) | 2001-01-09 | 2013-10-01 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of a target gene |
| US20030003582A1 (en) * | 2001-05-08 | 2003-01-02 | Tranzyme, Inc. | Trans-viral vector mediated gene transfer to the retina |
| US20050222061A1 (en) | 2002-04-18 | 2005-10-06 | Schulte Ralf W | Means and methods for the specific inhibition of genes in cells and tissue of the cns and/or eye |
| US7148342B2 (en) | 2002-07-24 | 2006-12-12 | The Trustees Of The University Of Pennyslvania | Compositions and methods for sirna inhibition of angiogenesis |
| AU2003290586B2 (en) * | 2002-11-04 | 2009-07-02 | University Of Massachusetts | Allele-specific RNA interference |
| US8680063B2 (en) | 2003-09-12 | 2014-03-25 | University Of Massachusetts | RNA interference for the treatment of gain-of-function disorders |
| EP2239328A3 (en) | 2005-08-18 | 2011-01-05 | Alnylam Pharmaceuticals Inc. | Methods and compositions for treating neurological disease |
| US8257969B2 (en) * | 2007-04-12 | 2012-09-04 | The Provost Fellows And Scholars Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth | Genetic suppression and replacement |
| JP5832293B2 (ja) | 2008-12-04 | 2015-12-16 | オプコ ファーマシューティカルズ、エルエルシー | 血管新生促進ｖｅｇｆイソ型を選択的に抑制する組成物および方法 |
| US8450473B2 (en) | 2009-04-30 | 2013-05-28 | The Research Foundation Of State University Of New York | Compositions and methods for therapy of macular degeneration |
| HUE041571T2 (hu) | 2010-04-23 | 2019-05-28 | Univ Florida | RAAV-guanilát-cikláz-készítmények és ejárások 1-es típusú Leber-féle veleszületett vakság (LCA1) kezelésére |
| LT3137497T (lt) | 2014-05-02 | 2021-07-26 | Genzyme Corporation | Aav vektoriai, skirti tinklainės ir cns genų terapijai |
| PT4012035T (pt) | 2014-09-16 | 2025-02-11 | Genzyme Corp | Vetores virais adenoassociados para tratar o glaucoma de miocilina (mioc) |
| EP4012035B1 (en) | 2014-09-16 | 2024-11-06 | Genzyme Corporation | Adeno-associated viral vectors for treating myocilin (myoc) glaucoma |
| MX391217B (es) | 2015-02-26 | 2025-03-21 | Ionis Pharmaceuticals Inc | Moduladores de rodopsina p23h con especificidad de alelo. |
| US11653636B2 (en) * | 2019-11-15 | 2023-05-23 | University Of Ulsan Foundation For Industry Cooperation | Method of making a rat model of retinal degeneration and rat model made thereby |
| WO2021155137A1 (en) | 2020-01-29 | 2021-08-05 | Genzyme Corporation | Modified adeno-associated viral capsid proteins for ocular gene therapy and methods of use thereof |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5037746A (en) | 1986-12-03 | 1991-08-06 | University Patents, Inc. | RNA ribozyme polymerases, and methods |
| US5116742A (en) | 1986-12-03 | 1992-05-26 | University Patents, Inc. | RNA ribozyme restriction endoribonucleases and methods |
| US4987071A (en) | 1986-12-03 | 1991-01-22 | University Patents, Inc. | RNA ribozyme polymerases, dephosphorylases, restriction endoribonucleases and methods |
| US5646020A (en) | 1992-05-14 | 1997-07-08 | Ribozyme Pharmaceuticals, Inc. | Hammerhead ribozymes for preferred targets |
| US5498539A (en) * | 1992-07-02 | 1996-03-12 | Daiichi Pharmaceutical Co., Ltd. | Bovine endothelial nitric oxide synthase nucleic acids |
| US5639655A (en) | 1993-01-19 | 1997-06-17 | Ribozyme Pharmaceuticals, Inc. | PML-RARA targeted ribozymes |
| US6410322B1 (en) * | 1993-07-27 | 2002-06-25 | Hybridon Inc | Antisense oligonucleotide inhibition of vascular endothelial growth factor expression |
| US5646031A (en) | 1995-05-16 | 1997-07-08 | Northern Illinois University | SArMV and sCYMVI hairpin ribozymes |
| GB9519299D0 (en) * | 1995-09-21 | 1995-11-22 | Farrar Gwyneth J | Genetic strategy |
| GB9604449D0 (en) | 1996-03-01 | 1996-05-01 | Farrar Gwyneth J | Genetic strategy ii |
| EP0977880A2 (en) | 1997-04-21 | 2000-02-09 | University Of Florida | Materials and methods for treatment of retinal diseases |
| NZ500427A (en) | 1997-04-21 | 2002-12-20 | Univ Florida | The use of ribozyme treatment for retinal diseases |
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1998
- 1998-04-21 NZ NZ500427A patent/NZ500427A/xx unknown
- 1998-04-21 WO PCT/US1998/007968 patent/WO1998048009A2/en not_active Ceased
- 1998-04-21 AU AU71406/98A patent/AU735788B2/en not_active Ceased
- 1998-04-21 CA CA002287508A patent/CA2287508A1/en not_active Abandoned
- 1998-04-21 EP EP98918493A patent/EP0977841A2/en not_active Withdrawn
- 1998-04-21 BR BR9808606-5A patent/BR9808606A/pt not_active IP Right Cessation
- 1998-04-21 US US09/063,667 patent/US6225291B1/en not_active Expired - Lifetime
- 1998-04-21 JP JP54625498A patent/JP2001523959A/ja not_active Ceased
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| JP2001523959A (ja) | 2001-11-27 |
| BR9808606A (pt) | 2000-05-23 |
| AU735788B2 (en) | 2001-07-12 |
| WO1998048009A3 (en) | 1999-03-25 |
| US6225291B1 (en) | 2001-05-01 |
| EP0977841A2 (en) | 2000-02-09 |
| WO1998048009A2 (en) | 1998-10-29 |
| AU7140698A (en) | 1998-11-13 |
| NZ500427A (en) | 2002-12-20 |
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