EA026660B1 - Введение олигонуклеотидов в виде хелатных комплексов - Google Patents
Введение олигонуклеотидов в виде хелатных комплексов Download PDFInfo
- Publication number
- EA026660B1 EA026660B1 EA201300259A EA201300259A EA026660B1 EA 026660 B1 EA026660 B1 EA 026660B1 EA 201300259 A EA201300259 A EA 201300259A EA 201300259 A EA201300259 A EA 201300259A EA 026660 B1 EA026660 B1 EA 026660B1
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- EA
- Eurasian Patent Office
- Prior art keywords
- kep
- oligonucleotide
- chelate
- calcium
- formation
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| US37525710P | 2010-08-20 | 2010-08-20 | |
| PCT/CA2011/000956 WO2012021985A1 (en) | 2010-08-20 | 2011-08-18 | Oligonucleotide chelate complexes |
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| EA201300259A1 EA201300259A1 (ru) | 2013-12-30 |
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| DK2049664T3 (da) | 2006-08-11 | 2012-01-02 | Prosensa Technologies Bv | Enkeltstrengede oligonukleotider, som er komplementære til repetitive elementer, til behandling af med DNA-repetitiv-ustabilitet associerede lidelser |
| HRP20150759T1 (hr) | 2007-05-11 | 2015-08-14 | Adynxx, Inc. | Ekspresija gena i bolovi |
| ES2564563T3 (es) | 2007-10-26 | 2016-03-23 | Academisch Ziekenhuis Leiden | Medios y métodos para contrarrestar trastornos del músculo |
| EP2119783A1 (en) | 2008-05-14 | 2009-11-18 | Prosensa Technologies B.V. | Method for efficient exon (44) skipping in Duchenne Muscular Dystrophy and associated means |
| CN118581086A (zh) | 2012-01-27 | 2024-09-03 | 比奥马林技术公司 | 用于治疗杜兴型肌营养不良症和贝克型肌营养不良症的具有改善特性的rna调节性寡核苷酸 |
| EP4400169A3 (en) | 2012-04-23 | 2024-12-25 | Vico Therapeutics B.V. | Rna modulating oligonucleotides with improved characteristics for the treatment of neuromuscular disorders |
| PT2846839T (pt) | 2012-05-10 | 2019-05-29 | Adynxx Inc | Formulações para a administração de ingredientes ativos |
| AR091065A1 (es) * | 2012-05-18 | 2014-12-30 | Replicor Inc | Una formulacion farmaceutica que comprende un quelato de oligonucleotidos antiviral para el tratamiento de una infeccion antiviral |
| TWI635864B (zh) * | 2012-05-18 | 2018-09-21 | 雷普利可公司 | 寡核苷酸螯合複合物－多肽組合物及方法 |
| CN110257379B (zh) | 2012-07-03 | 2023-08-11 | 马林生物科技有限公司 | 用于治疗肌肉萎缩症患者的寡核苷酸 |
| CN104837501B (zh) * | 2012-08-30 | 2018-11-02 | 里普利科股份有限公司 | 治疗乙型肝炎及丁型肝炎感染的方法 |
| HRP20231400T1 (hr) | 2014-07-10 | 2024-02-16 | Replicor Inc. | Kelirani fosforotioirani polimeri nukleinskih kiselina, namijenjeni upotrebi u kombinaciji s inhibitorom hbv polimeraze u liječenju infekcija virusima hepatitisa b i hepatitisa d |
| BR112017002629A2 (pt) | 2014-08-15 | 2018-02-20 | Adynxx, Inc. | decoys de oligonucleotídeo para o tratamento de dor |
| WO2016030863A1 (en) | 2014-08-29 | 2016-03-03 | Glaxosmithkline Intellectual Property Development Limited | Compounds and methods for treating viral infections |
| SMT202000389T1 (it) * | 2015-04-23 | 2020-09-10 | Geron Corp | Metodi di preparazione di polinucleotidi usando composizioni di sali cationici multivalenti |
| CN113286803A (zh) * | 2018-11-08 | 2021-08-20 | 阿里戈斯治疗公司 | S-抗原转运抑制寡核苷酸聚合物和方法 |
| US11166976B2 (en) | 2018-11-08 | 2021-11-09 | Aligos Therapeutics, Inc. | S-antigen transport inhibiting oligonucleotide polymers and methods |
| WO2021198958A1 (en) | 2020-04-01 | 2021-10-07 | Janssen Biopharma, Inc. | Nucleic acid polymers |
| AU2021383758A1 (en) * | 2020-11-20 | 2023-06-15 | Aligos Therapeutics, Inc. | Conjugates of s-antigen transport inhibiting oligonucleotide polymers having enhanced liver targeting |
| WO2022133230A1 (en) | 2020-12-18 | 2022-06-23 | Janssen Pharmaceuticals, Inc. | Combination therapy for treating hepatitis b virus infection |
| WO2022152869A1 (en) | 2021-01-15 | 2022-07-21 | Janssen Sciences Ireland Unlimited Company | Use of oligonucleotides for individuals with hepatic impairment |
| US20240336921A1 (en) | 2021-07-09 | 2024-10-10 | Glaxo Smith Kline Intellectual Property (No. 3) Limited | Use of oligonucleotides for individuals with renal impairment |
| WO2024255846A1 (en) * | 2023-06-16 | 2024-12-19 | Ractigen Therapeutics | Oligonucleotide formulation |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6011143A (en) * | 1997-09-12 | 2000-01-04 | Canon Kabushiki Kaisha | Artificial nucleic acids and a method of making |
| US20060293510A1 (en) * | 2003-09-08 | 2006-12-28 | Japan Science And Technology Agency | Metal complex type nucleic acid |
| US20070105116A1 (en) * | 2003-09-02 | 2007-05-10 | Japan Science And Technology Agency | Metal complex type nucleic acid |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1019429A4 (en) * | 1997-08-20 | 2001-08-08 | Somagenics Inc | ANTISENSE THERAPEUTIC PRODUCTS WITH IMPROVED BINDING PROPERTIES AND METHODS OF USE |
| US6653467B1 (en) * | 2000-04-26 | 2003-11-25 | Jcr Pharmaceutical Co., Ltd. | Medicament for treatment of Duchenne muscular dystrophy |
| JP4836366B2 (ja) * | 2000-08-25 | 2011-12-14 | 雅文 松尾 | デュシェンヌ型筋ジストロフィー治療剤 |
| JP2009500020A (ja) * | 2005-07-01 | 2009-01-08 | バイオヴェリス コーポレイション | 核酸を検出、増幅および／また単離するための組成物および方法 |
| WO2009065181A1 (en) * | 2007-11-21 | 2009-05-28 | Apollo Life Sciences Limited | Nanostructures suitable for delivery of agents |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6011143A (en) * | 1997-09-12 | 2000-01-04 | Canon Kabushiki Kaisha | Artificial nucleic acids and a method of making |
| US20070105116A1 (en) * | 2003-09-02 | 2007-05-10 | Japan Science And Technology Agency | Metal complex type nucleic acid |
| US20060293510A1 (en) * | 2003-09-08 | 2006-12-28 | Japan Science And Technology Agency | Metal complex type nucleic acid |
Non-Patent Citations (3)
| Title |
|---|
| Eur: Mass Spectrom., 1999, 5, pp. 489-500 (BECK ET AL.) *Abstract* * |
| J. Biol. Inorg. Chem., 13 February 2010, 15, pp. 601-620 (ZOBEL ET AL.) *Abstract* * |
| Nucleic Acids Research, 1978, 3(10), pp. 2757-2770 (ZIMMER ET AL.) *Abstract* * |
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