ES2801823T3 - Oligonucleótidos para tratar una enfermedad ocular - Google Patents
Oligonucleótidos para tratar una enfermedad ocular Download PDFInfo
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- ES2801823T3 ES2801823T3 ES17721984T ES17721984T ES2801823T3 ES 2801823 T3 ES2801823 T3 ES 2801823T3 ES 17721984 T ES17721984 T ES 17721984T ES 17721984 T ES17721984 T ES 17721984T ES 2801823 T3 ES2801823 T3 ES 2801823T3
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| GB201607141 | 2016-04-25 | ||
| PCT/EP2017/059830 WO2017186739A1 (en) | 2016-04-25 | 2017-04-25 | Oligonucleotides to treat eye disease |
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| ES2801823T3 true ES2801823T3 (es) | 2021-01-14 |
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| JP7043082B2 (ja) | 2016-04-25 | 2022-03-29 | プロキューアール セラピューティクス ツー ベスローテン フェンノートシャップ | 眼疾患を処置するオリゴヌクレオチド |
| WO2017220751A1 (en) | 2016-06-22 | 2017-12-28 | Proqr Therapeutics Ii B.V. | Single-stranded rna-editing oligonucleotides |
| CN110352244B (zh) | 2016-09-01 | 2023-03-21 | ProQR治疗上市公司Ⅱ | 化学修饰的编辑rna的单链寡核苷酸 |
| GB201706009D0 (en) | 2017-04-13 | 2017-05-31 | Proqr Therapeutics Ii Bv | Antisense oligonucleotides for the treatment of stargardt disease |
| AU2018393050A1 (en) | 2017-12-21 | 2020-06-18 | Bayer Healthcare Llc | Materials and methods for treatment of Usher Syndrome Type 2A |
| WO2019123430A1 (en) | 2017-12-21 | 2019-06-27 | Casebia Therapeutics Llp | Materials and methods for treatment of usher syndrome type 2a and/or non-syndromic autosomal recessive retinitis pigmentosa (arrp) |
| GB201808146D0 (en) | 2018-05-18 | 2018-07-11 | Proqr Therapeutics Ii Bv | Stereospecific Linkages in RNA Editing Oligonucleotides |
| US12398393B2 (en) | 2019-01-28 | 2025-08-26 | Proqr Therapeutics Ii B.V. | RNA-editing oligonucleotides for the treatment of usher syndrome |
| MX2021009750A (es) * | 2019-02-12 | 2021-09-08 | Univ Degli Studi Di Trento | Moleculas del acido ribonucleico guia de cas12a y usos de las mismas. |
| US20220177894A1 (en) | 2019-04-02 | 2022-06-09 | Proqr Therapeutics Ii B.V. | Antisense oligonucleotides for immunotherapy |
| EP3956449B1 (en) | 2019-04-15 | 2026-02-25 | EdiGene Therapeutics (Beijing) Inc. | Methods and compositions for editing rnas |
| CA3136172A1 (en) | 2019-04-18 | 2020-10-22 | Proqr Therapeutics Ii B.V. | Antisense oligonucleotides for the treatment of usher syndrome |
| WO2020254249A1 (en) | 2019-06-21 | 2020-12-24 | Proqr Therapeutics Ii B.V. | Delivery of nucleic acids for the treatment of auditory disorders |
| EP3997229A4 (en) | 2019-07-12 | 2024-07-03 | Peking University | TARGETED RNA EDITING BY HARNESSING ENDOGENOUS ADAR USING MODIFIED RNA |
| WO2021018750A1 (en) | 2019-07-26 | 2021-02-04 | Proqr Therapeutics Ii B.V. | Ophthalmic compositions comprising viscosifying polymers and nucleic acids |
| US20220290154A1 (en) * | 2019-08-08 | 2022-09-15 | Stichting Radboud Universitair Medisch Centrum | Antisense oligonucleotides rescue aberrant splicing of ABCA4 |
| CA3158528A1 (en) | 2019-12-23 | 2021-07-01 | Jim SWILDENS | Antisense oligonucleotides for nucleotide deamination in the treatment of stargardt disease |
| CN113122577A (zh) * | 2019-12-30 | 2021-07-16 | 博雅辑因(北京)生物科技有限公司 | 一种治疗Usher综合征的方法和其组合物 |
| BR112022012921A2 (pt) * | 2019-12-30 | 2022-09-06 | Edigene Therapeutics Beijing Inc | Métodos para editar de forma alvejada ácido ribonucleico e para tratar a síndrome de usher tipo ii, ácido ribonucleico de recrutamento da adenosina desaminase, construto ou vetor de entrega, célula, e, uso do ácido ribonucleico de recrutamento da adenosina desaminase ou do construto ou vetor de entrega |
| CA3166720A1 (en) | 2020-03-04 | 2021-09-10 | Jim SWILDENS | Antisense oligonucleotides for use in the treatment of usher syndrome |
| EP4301856A2 (en) | 2021-03-05 | 2024-01-10 | ProQR Therapeutics II B.V. | Antisense oligonucleotides for use in the treatment of corneal dystrophies |
| TR2022001648A2 (tr) * | 2022-02-09 | 2022-02-21 | T C Ueskuedar Ueniversitesi | Ush2a kaynaklı retinitis pigmentosa hastalığının genetik tedavisi için ekzon 13 atlama işlevi gören kseno nükleik asit antisens-oligonükleotit (xna-aso) dizileri. |
| EP4479535A1 (en) | 2022-02-14 | 2024-12-25 | ProQR Therapeutics II B.V. | Guide oligonucleotides for nucleic acid editing in the treatment of hypercholesterolemia |
| EP4599060A1 (en) * | 2022-10-06 | 2025-08-13 | Stichting Radboud universitair medisch centrum | Antisense oligonucleotides for treatment of usher 2a. exons 30-31 |
| EP4599061A1 (en) * | 2022-10-06 | 2025-08-13 | Stichting Radboud universitair medisch centrum | Antisense oligonucleotides for treatment of usher 2a. exon 68 |
| EP4603585A1 (en) * | 2022-10-11 | 2025-08-20 | Guangzhou Reforgene Medicine Co., Ltd. | Snrna nucleic acid molecule and application thereof |
| EP4619522A1 (en) * | 2022-11-15 | 2025-09-24 | Stichting Radboud universitair medisch centrum | Antisense oligonucleotides for treatment of usher 2a. exons 39-40 |
| WO2025007937A1 (zh) * | 2023-07-04 | 2025-01-09 | 广州瑞风生物科技有限公司 | 靶向USH2A pre-mRNA假外显子PE40的snRNA及其应用 |
Family Cites Families (10)
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|---|---|---|---|---|
| DE60042338D1 (de) | 1999-10-04 | 2009-07-16 | Univ New Jersey Med | TAR RNA bindende Peptide |
| EP1191097A1 (en) | 2000-09-21 | 2002-03-27 | Leids Universitair Medisch Centrum | Induction of exon skipping in eukaryotic cells |
| US20100196889A1 (en) | 2006-11-13 | 2010-08-05 | Bankaitis-Davis Danute M | Gene Expression Profiling for Identification, Monitoring and Treatment of Colorectal Cancer |
| US8093000B2 (en) | 2008-05-09 | 2012-01-10 | The Regents Of The University Of California | Methods for predicting and treating tumors resistant to drug, immunotherapy, and radiation |
| US20110070582A1 (en) | 2008-11-03 | 2011-03-24 | Source Precision Medicine, Inc. d/b/d Source MDX | Gene Expression Profiling for Predicting the Response to Immunotherapy and/or the Survivability of Melanoma Subjects |
| PT2425814E (pt) | 2010-09-03 | 2013-09-02 | Novagali Pharma Sa | Emulsão de tipo água em óleo para tratamento de uma doença ocular |
| US10131910B2 (en) * | 2014-07-10 | 2018-11-20 | Stichting Katholieke Universiteit | Antisense oligonucleotides for the treatment of Usher syndrome type 2 |
| US9927034B2 (en) | 2015-08-25 | 2018-03-27 | Mueller International, Llc | Valve seat stiffener |
| EP3359667A1 (en) | 2015-10-05 | 2018-08-15 | ProQR Therapeutics II B.V. | Use of single-stranded antisense oligonucleotide in prevention or treatment of genetic diseases involving a trinucleotide repeat expansion |
| JP7043082B2 (ja) | 2016-04-25 | 2022-03-29 | プロキューアール セラピューティクス ツー ベスローテン フェンノートシャップ | 眼疾患を処置するオリゴヌクレオチド |
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| EP3448999A1 (en) | 2019-03-06 |
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| US20200237802A1 (en) | 2020-07-30 |
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