BR112020010928A2 - synpiii, um promotor para a expressão de gene específica em epitélio de pigmento retinal - Google Patents
synpiii, um promotor para a expressão de gene específica em epitélio de pigmento retinal Download PDFInfo
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/0075—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the delivery route, e.g. oral, subcutaneous
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
- A61K48/0058—Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14141—Use of virus, viral particle or viral elements as a vector
- C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/008—Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination
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- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
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- Biomedical Technology (AREA)
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- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
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| EP17204750.8 | 2017-11-30 | ||
| EP17204750 | 2017-11-30 | ||
| PCT/EP2018/082880 WO2019106035A1 (en) | 2017-11-30 | 2018-11-28 | Synpiii, a promoter for the specific expression of genes in retinal pigment epithelium |
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| BR112020010928A2 true BR112020010928A2 (pt) | 2020-11-24 |
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| BR112020010928-2A BR112020010928A2 (pt) | 2017-11-30 | 2018-11-28 | synpiii, um promotor para a expressão de gene específica em epitélio de pigmento retinal |
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| US (1) | US11591615B2 (https=) |
| EP (1) | EP3717651A1 (https=) |
| JP (1) | JP2021503934A (https=) |
| KR (1) | KR20200091432A (https=) |
| CN (1) | CN111542611A (https=) |
| AU (1) | AU2018376259A1 (https=) |
| BR (1) | BR112020010928A2 (https=) |
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| CR (1) | CR20200236A (https=) |
| IL (1) | IL274957A (https=) |
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| PH (1) | PH12020550748A1 (https=) |
| RU (1) | RU2020121408A (https=) |
| SG (1) | SG11202005024QA (https=) |
| WO (1) | WO2019106035A1 (https=) |
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| MX2010011467A (es) | 2008-04-18 | 2011-02-15 | Novartis Forschungsstiftung | Novedosas herramientas y metodos terapeuticos para tratar la ceguera. |
| US10941417B2 (en) | 2015-04-30 | 2021-03-09 | Friedrich Miescher Institute For Biomedical Research | Promoter for the specific expression of genes in Müller cells |
| US10857241B2 (en) | 2015-09-15 | 2020-12-08 | Friedrich Miescher Institute For Biomedical Research | Therapeutical tools and methods for treating blindness by targeting photoreceptors |
| WO2017064642A1 (en) | 2015-10-14 | 2017-04-20 | Fredrich Miescher Institute For Biomedical Research | Promoter for the specific expression of genes in retinal endothelial cells |
| EP3383440B1 (en) | 2015-12-03 | 2021-06-30 | Friedrich Miescher Institute for Biomedical Research | Synp162, a promoter for the specific expression of genes in rod photoreceptors |
| EP3383439B1 (en) | 2015-12-03 | 2019-09-25 | Friedrich Miescher Institute for Biomedical Research | Synp161, a promoter for the specific expression of genes in rod photoreceptors |
| WO2017093934A1 (en) | 2015-12-03 | 2017-06-08 | Friedrich Miescher Institute For Biomedical Research | Synp160, a promoter for the specific expression of genes in rod photoreceptors |
| ES2909444T3 (es) | 2015-12-03 | 2022-05-06 | Friedrich Miescher Institute For Biomedical Res | Synp159, un promotor para la expresión específica de genes en los fotorreceptores de los bastones |
| RU2766353C2 (ru) | 2016-11-02 | 2022-03-15 | Фридрих Мишер Инститьют Фор Байомедикал Рисерч | Synp198, промотор для специфической экспрессии генов в ганглионарных клетках сетчатки, избирательных в отношении направления |
| WO2018146588A1 (en) | 2017-02-08 | 2018-08-16 | Friedrich Miescher Institute For Biomedical Research | Synp88, a promoter for the specific expression of genes in retinal ganglion cells |
| MX2020005033A (es) | 2017-11-15 | 2020-10-28 | Friedrich Miescher Institute For Biomedical Res | Promotor especifico de las celulas del epitelio pigmentario retinal en primates. |
| SG11202005024QA (en) | 2017-11-30 | 2020-06-29 | Friedrich Miescher Institute For Biomedical Res | Synpiii, a promoter for the specific expression of genes in retinal pigment epithelium |
| WO2024110770A1 (en) * | 2022-11-22 | 2024-05-30 | INSERM (Institut National de la Santé et de la Recherche Médicale) | A new promoter for retinal pigment epithelium (rpe) targeted gene therapy |
| AU2024260900A1 (en) * | 2023-04-27 | 2025-11-13 | Korea Research Institute Of Bioscience And Biotechnology | Promoter for gene expression in retinal cells, and vector system comprising same |
Family Cites Families (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9206874D0 (en) | 1992-03-30 | 1992-05-13 | Connaught Lab | Generation of improved inducible mammalian expression vectors |
| CA2346262A1 (en) * | 1998-09-17 | 2000-03-23 | University Of Florida | Methods for treatment of degenerative retinal diseases |
| CN101484005A (zh) | 2006-05-04 | 2009-07-15 | 韦恩州立大学 | 通过向体内递送视紫红质核酸恢复视觉响应 |
| EP1891976A1 (en) | 2006-08-23 | 2008-02-27 | Novartis Forschungsstiftung, Zweigniederlassung Friedrich Miescher Institute for Biomedical Research | Use of light sensitive genes |
| WO2009112448A1 (en) | 2008-03-11 | 2009-09-17 | Novartis Forschungsstiftung, Zweigniederlassung | Novel tool for the analysis of neural circuits |
| MX2010011467A (es) | 2008-04-18 | 2011-02-15 | Novartis Forschungsstiftung | Novedosas herramientas y metodos terapeuticos para tratar la ceguera. |
| CN103608455B (zh) | 2011-01-07 | 2019-01-15 | 应用遗传科技公司 | 用于治疗色盲和其它疾病的启动子、表达盒、载体、药盒和方法 |
| WO2014033095A1 (en) * | 2012-08-27 | 2014-03-06 | Friedrich Miescher Institute For Biomedical Research | Retinal off circuit-specific promoter |
| EP3104895A1 (en) | 2014-02-10 | 2016-12-21 | Friedrich Miescher Institute for Biomedical Research | Aii retinal amacrine cell-specific promoter |
| EP3105334B1 (en) | 2014-02-11 | 2019-07-03 | Friedrich Miescher Institute for Biomedical Research | Müller cell-specific promoter |
| GB201502137D0 (en) * | 2015-02-09 | 2015-03-25 | Ucl Business Plc | Treatment |
| US10941417B2 (en) | 2015-04-30 | 2021-03-09 | Friedrich Miescher Institute For Biomedical Research | Promoter for the specific expression of genes in Müller cells |
| US10857241B2 (en) | 2015-09-15 | 2020-12-08 | Friedrich Miescher Institute For Biomedical Research | Therapeutical tools and methods for treating blindness by targeting photoreceptors |
| WO2017064642A1 (en) | 2015-10-14 | 2017-04-20 | Fredrich Miescher Institute For Biomedical Research | Promoter for the specific expression of genes in retinal endothelial cells |
| EP3383440B1 (en) | 2015-12-03 | 2021-06-30 | Friedrich Miescher Institute for Biomedical Research | Synp162, a promoter for the specific expression of genes in rod photoreceptors |
| ES2909444T3 (es) | 2015-12-03 | 2022-05-06 | Friedrich Miescher Institute For Biomedical Res | Synp159, un promotor para la expresión específica de genes en los fotorreceptores de los bastones |
| EP3383439B1 (en) | 2015-12-03 | 2019-09-25 | Friedrich Miescher Institute for Biomedical Research | Synp161, a promoter for the specific expression of genes in rod photoreceptors |
| WO2017093934A1 (en) | 2015-12-03 | 2017-06-08 | Friedrich Miescher Institute For Biomedical Research | Synp160, a promoter for the specific expression of genes in rod photoreceptors |
| WO2017093566A1 (en) * | 2015-12-04 | 2017-06-08 | Universite Pierre Et Marie Curie (Paris 6) | Promoters and uses thereof |
| US20190209708A1 (en) | 2016-05-17 | 2019-07-11 | Friedrich Miescher Institute For Biomedical Research | Novel therapeutic tools and methods for treating blindness |
| RU2766353C2 (ru) | 2016-11-02 | 2022-03-15 | Фридрих Мишер Инститьют Фор Байомедикал Рисерч | Synp198, промотор для специфической экспрессии генов в ганглионарных клетках сетчатки, избирательных в отношении направления |
| EP3548093A1 (en) | 2016-12-01 | 2019-10-09 | Friedrich Miescher Institute for Biomedical Research | Synp107, a promoter for the specific expression of genes in interneurons |
| US20190376083A1 (en) | 2016-12-01 | 2019-12-12 | Friedrich Miescher Institute For Biomedical Research | Synp1, a promoter for the specific expression of genes in interneurons |
| WO2018146588A1 (en) | 2017-02-08 | 2018-08-16 | Friedrich Miescher Institute For Biomedical Research | Synp88, a promoter for the specific expression of genes in retinal ganglion cells |
| MX2020005033A (es) | 2017-11-15 | 2020-10-28 | Friedrich Miescher Institute For Biomedical Res | Promotor especifico de las celulas del epitelio pigmentario retinal en primates. |
| SG11202005024QA (en) | 2017-11-30 | 2020-06-29 | Friedrich Miescher Institute For Biomedical Res | Synpiii, a promoter for the specific expression of genes in retinal pigment epithelium |
| CN111527102A (zh) | 2017-11-30 | 2020-08-11 | 弗里德里克·米谢尔生物医学研究所 | 灵长类动物视网膜色素上皮细胞特异性启动子SynP61 |
| EP3870240A1 (en) | 2018-10-25 | 2021-09-01 | Friedrich Miescher Institute for Biomedical Research | Synp78 (proa27), a promoter for the specific expression of genes in retinal ganglion cells |
| US20210353773A1 (en) | 2018-10-25 | 2021-11-18 | Friedrich Miescher Institute For Biomedical Research | Synp194 (prob15), a promoter for the specific expression of genes in retinal ganglion cells |
| EP3870239A1 (en) | 2018-10-25 | 2021-09-01 | Friedrich Miescher Institute for Biomedical Research | Synp57 (proa14), a promoter for the specific expression of genes in photoreceptors |
| EP3870709A1 (en) | 2018-10-25 | 2021-09-01 | Friedrich Miescher Institute for Biomedical Research | Synp27 (prob12), a promoter for the specific expression of genes in protoplasmic astrocytes |
| JP2022505517A (ja) | 2018-10-25 | 2022-01-14 | フリードリッヒ ミーシェー インスティトゥート フォー バイオメディカル リサーチ | 網膜神経節細胞中の遺伝子の特異的発現のためのプロモーターＳｙｎＰ１５１（ＰｒｏＣ２９） |
| WO2020084537A1 (en) | 2018-10-25 | 2020-04-30 | Friedrich Miescher Institute For Biomedical Research | Synp17 (prob1), a promoter for the specific expression of genes in retinal ganglion cells |
| US20220119807A1 (en) | 2019-01-24 | 2022-04-21 | Friedrich Miescher Institute For Biomedical Research | Synp35 (proc8), a promoter for the specific expression of genes in retinal ganglion cells |
| US20220119841A1 (en) | 2019-01-24 | 2022-04-21 | Friedrich Miescher Instit for Biomedical Research | Synp5 (proa9), a promoter for the specific expression of genes in retinal ganglion cells |
| WO2020152626A1 (en) | 2019-01-24 | 2020-07-30 | Friedrich Miescher Institute For Biomedical Research | Synp166 (proa36), a promoter for the specific expression of genes in photoreceptors |
| EP3914300A1 (en) | 2019-01-24 | 2021-12-01 | Friedrich Miescher Institute for Biomedical Research | Synp66 (proa21), a promoter for the specific expression of genes in retinal ganglion cells |
| SG11202108044YA (en) | 2019-02-25 | 2021-09-29 | Novartis Ag | Compositions and methods to treat bietti crystalline dystrophy |
| US20220154211A1 (en) | 2019-02-25 | 2022-05-19 | Novartis Ag | Compositions and methods to treat bietti crystalline dystrophy |
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- 2018-11-28 BR BR112020010928-2A patent/BR112020010928A2/pt not_active IP Right Cessation
- 2018-11-28 CA CA3083682A patent/CA3083682A1/en active Pending
- 2018-11-28 RU RU2020121408A patent/RU2020121408A/ru unknown
- 2018-11-28 US US16/768,057 patent/US11591615B2/en active Active
- 2018-11-28 CN CN201880084876.5A patent/CN111542611A/zh active Pending
- 2018-11-28 MX MX2020005649A patent/MX2020005649A/es unknown
- 2018-11-28 AU AU2018376259A patent/AU2018376259A1/en not_active Abandoned
- 2018-11-28 JP JP2020529489A patent/JP2021503934A/ja not_active Ceased
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- 2018-11-28 WO PCT/EP2018/082880 patent/WO2019106035A1/en not_active Ceased
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