CA2776651C - Tricyclo-phosphorothioate dna - Google Patents
Tricyclo-phosphorothioate dna Download PDFInfo
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- CA2776651C CA2776651C CA2776651A CA2776651A CA2776651C CA 2776651 C CA2776651 C CA 2776651C CA 2776651 A CA2776651 A CA 2776651A CA 2776651 A CA2776651 A CA 2776651A CA 2776651 C CA2776651 C CA 2776651C
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| BR112014009066A BR112014009066B8 (pt) | 2011-10-13 | 2012-10-12 | molécula de ácido nucleico, método para a sintetização de uma molécula de dna de triciclo-fosforotioato e composição farmacêutica |
| JP2014535113A JP6181653B2 (ja) | 2011-10-13 | 2012-10-12 | トリシクロ−ホスホロチオエートｄｎａ |
| ES12770503.6T ES2651216T3 (es) | 2011-10-13 | 2012-10-12 | Triciclo-ADN fosforotioato |
| PCT/EP2012/070349 WO2013053928A1 (en) | 2011-10-13 | 2012-10-12 | Tricyclo-phosphorothioate dna |
| CA2851970A CA2851970A1 (en) | 2011-10-13 | 2012-10-12 | Tricyclo-phosphorothioate dna |
| AU2012322903A AU2012322903B2 (en) | 2011-10-13 | 2012-10-12 | Tricyclo-phosphorothioate dna |
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| IL231983A IL231983B (en) | 2011-10-13 | 2014-04-07 | Dna containing tricyclo-phosphorothioate |
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| EP11185129.1A EP2581448B1 (en) | 2011-10-13 | 2011-10-13 | Tricyclo-phosphorothioate DNA |
| EP11185129.1 | 2011-10-13 |
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Families Citing this family (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2206781B1 (en) | 2004-06-28 | 2015-12-02 | The University Of Western Australia | Antisense oligonucleotides for inducing exon skipping and methods of use thereof |
| EP1855694B1 (en) | 2005-02-09 | 2020-12-02 | Sarepta Therapeutics, Inc. | Antisense composition for treating muscle atrophy |
| EP2762567B1 (en) | 2008-10-24 | 2016-07-13 | Sarepta Therapeutics, Inc. | Multiple exon skipping compositions for DMD |
| PL2499249T3 (pl) | 2009-11-12 | 2019-03-29 | Univ Western Australia | Cząsteczki antysensowne i sposoby leczenia patologii |
| US20130085139A1 (en) | 2011-10-04 | 2013-04-04 | Royal Holloway And Bedford New College | Oligomers |
| BR122020016865B1 (pt) | 2013-03-14 | 2022-12-27 | Sarepta Therapeutics, Inc. | Oligonucleotídeo antisenso, composição farmacêutica compreendendo o mesmo e uso da dita composição para o tratamento de distrofia muscular de duchenne (dmd) |
| BR112015022998A2 (pt) | 2013-03-15 | 2017-11-14 | Sarepta Therapeutics Inc | composições melhoradas para o tratamento de distrofia muscular |
| WO2015035231A1 (en) | 2013-09-05 | 2015-03-12 | Sarepta Therapeutics, Inc. | Antisense-induced exon2 inclusion in acid alpha-glucosidase |
| EP3480312A1 (en) | 2013-09-11 | 2019-05-08 | Synthena AG | Nucleic acids and methods for the treatment of pompe disease |
| ES2806087T3 (es) | 2014-07-31 | 2021-02-16 | Association Inst De Myologie | Tratamiento de la esclerosis lateral amiotrófica |
| WO2016040748A1 (en) | 2014-09-12 | 2016-03-17 | Ionis Pharmaceuticals, Inc. | Compositions and methods for detection of smn protein in a subject and treatment of a subject |
| MA41795A (fr) | 2015-03-18 | 2018-01-23 | Sarepta Therapeutics Inc | Exclusion d'un exon induite par des composés antisens dans la myostatine |
| US10849917B2 (en) | 2015-06-01 | 2020-12-01 | Sarepta Therapeutics, Inc. | Antisense-induced exon exclusion in type VII collagen |
| WO2017050836A1 (en) | 2015-09-21 | 2017-03-30 | Association Institut De Myologie | Antisense oligonucleotides and uses thereof |
| BR112018007066A2 (pt) | 2015-10-09 | 2018-10-23 | Sarepta Therapeutics Inc | composições e métodos para tratamento da distrofia muscular de duchene e distúrbios relacionados |
| WO2017136435A1 (en) | 2016-02-01 | 2017-08-10 | The Usa, As Represented By The Secretary, Department Of Health And Human Services Office Of Technology Transfer National Institute Of Health | Compounds for modulating fc-epsilon-ri-beta expression and uses thereof |
| US11060089B2 (en) | 2016-04-18 | 2021-07-13 | Sarepta Therapeutics, Inc. | Antisense oligomers and methods of using the same for treating diseases associated with the acid alpha-glucosidase gene |
| KR102329187B1 (ko) | 2016-04-29 | 2021-11-22 | 사렙타 쎄러퓨틱스, 인코퍼레이티드 | 인간 lmna를 표적화하는 올리고뉴클레오타이드 유사체 |
| US11472824B2 (en) | 2016-05-24 | 2022-10-18 | Sarepta Therapeutics, Inc. | Processes for preparing phosphorodiamidate morpholino oligomers |
| DK3464305T3 (da) | 2016-05-24 | 2024-10-28 | Sarepta Therapeutics Inc | Fremgangsmåder til fremstilling af oligomerer |
| AU2017270975B2 (en) | 2016-05-24 | 2021-04-15 | Sarepta Therapeutics, Inc. | Processes for preparing phosphorodiamidate morpholino oligomers |
| PT3464306T (pt) | 2016-05-24 | 2024-05-17 | Sarepta Therapeutics Inc | Processos para preparar oligómeros morfolino de fosforodiamidato |
| MA45362A (fr) | 2016-05-24 | 2019-04-10 | Sarepta Therapeutics Inc | Procédés de préparation d'oligomères morpholino de phosphorodiamidate |
| SG11201810143PA (en) | 2016-06-30 | 2019-01-30 | Sarepta Therapeutics Inc | Exon skipping oligomers for muscular dystrophy |
| CA3037663A1 (en) | 2016-09-23 | 2018-03-29 | Synthena Ag | Mixed tricyclo-dna, 2'-modified-rna oligonucleotide compositions and uses thereof |
| WO2018055577A1 (en) * | 2016-09-23 | 2018-03-29 | Synthena Ag | Mixed tricyclo-dna, 2'-modified rna oligonucleotide compositions and uses thereof |
| PL3554552T3 (pl) | 2016-12-19 | 2022-11-21 | Sarepta Therapeutics, Inc. | Koniugaty oligomerów do pomijania egzonów dla dystrofii mięśniowej |
| SMT202200366T1 (it) | 2016-12-19 | 2022-11-18 | Sarepta Therapeutics Inc | Coniugati di oligomeri per salto di esone per distrofia muscolare |
| MY205600A (en) | 2016-12-19 | 2024-10-29 | Sarepta Therapeutics Inc | Exon skipping oligomer conjugates for muscular dystrophy |
| US11767520B2 (en) | 2017-04-20 | 2023-09-26 | Atyr Pharma, Inc. | Compositions and methods for treating lung inflammation |
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| WO2018193428A1 (en) | 2017-04-20 | 2018-10-25 | Synthena Ag | Modified oligomeric compounds comprising tricyclo-dna nucleosides and uses thereof |
| EA201991450A1 (ru) | 2017-09-22 | 2019-12-30 | Сарепта Терапьютикс, Инк. | Конъюгаты олигомеров для пропуска экзона при мышечной дистрофии |
| EP3687519A1 (en) | 2017-09-28 | 2020-08-05 | Sarepta Therapeutics, Inc. | Combination therapies for treating muscular dystrophy |
| EP3687547A1 (en) | 2017-09-28 | 2020-08-05 | Sarepta Therapeutics, Inc. | Combination therapies for treating muscular dystrophy |
| JP2020536058A (ja) | 2017-09-28 | 2020-12-10 | サレプタ セラピューティクス， インコーポレイテッド | 筋ジストロフィーを処置するための併用療法 |
| US11555189B2 (en) | 2017-10-18 | 2023-01-17 | Sarepta Therapeutics, Inc. | Antisense oligomer compounds |
| US10765760B2 (en) | 2018-05-29 | 2020-09-08 | Sarepta Therapeutics, Inc. | Exon skipping oligomer conjugates for muscular dystrophy |
| EP4219717A3 (en) | 2018-06-13 | 2023-12-20 | Sarepta Therapeutics, Inc. | Exon skipping oligomers for muscular dystrophy |
| TW202449155A (zh) | 2018-07-27 | 2024-12-16 | 美商薩羅塔治療公司 | 用於肌肉萎縮症之外顯子跳躍寡聚物 |
| IL318474A (en) | 2018-12-13 | 2025-03-01 | Sarepta Therapeutics Inc | Axon-skipping oligomer complexes for muscular dystrophy |
| EP3955966A1 (en) | 2019-04-18 | 2022-02-23 | Sarepta Therapeutics, Inc. | Compositions for treating muscular dystrophy |
| EP4054618A1 (en) | 2019-11-06 | 2022-09-14 | Association Institut de Myologie | Combined therapy for muscular diseases |
| AU2021225957A1 (en) | 2020-02-28 | 2022-09-08 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating SMN2 |
| EP4133073A2 (en) | 2020-04-09 | 2023-02-15 | Association Institut de Myologie | Antisense sequences for treating amyotrophic lateral sclerosis |
| EP3978608A1 (en) | 2020-10-05 | 2022-04-06 | SQY Therapeutics | Oligomeric compound for dystrophin rescue in dmd patients throughout skipping of exon-51 |
| IL311568A (en) | 2021-09-30 | 2024-05-01 | Sarepta Therapeutics Inc | Antisense oligonucleotides having one or more abasic units |
| JP2024539223A (ja) | 2021-10-22 | 2024-10-28 | サレプタ セラピューティクス， インコーポレイテッド | 末梢ミエリンタンパク質２２関連疾患の処置のためのモルフォリノオリゴマー |
| EP4590311A2 (en) | 2022-09-21 | 2025-07-30 | Sarepta Therapeutics, Inc. | Dmd antisense oligonucleotide-mediated exon skipping efficiency |
| TW202442246A (zh) | 2023-04-27 | 2024-11-01 | 美商薩羅塔治療公司 | 用於治療慢性腎病之反義寡聚物 |
| WO2025085810A2 (en) | 2023-10-18 | 2025-04-24 | Sarepta Therapeutics, Inc. | Antisense oligomers for treatment of centronuclear myopathies |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5753613A (en) | 1994-09-30 | 1998-05-19 | Inex Pharmaceuticals Corporation | Compositions for the introduction of polyanionic materials into cells |
| US5820873A (en) | 1994-09-30 | 1998-10-13 | The University Of British Columbia | Polyethylene glycol modified ceramide lipids and liposome uses thereof |
| US5885613A (en) | 1994-09-30 | 1999-03-23 | The University Of British Columbia | Bilayer stabilizing components and their use in forming programmable fusogenic liposomes |
| JP2003528024A (ja) | 1997-12-16 | 2003-09-24 | バレンティス・インコーポレーテッド | 製剤化された核酸分子の無針注入 |
| WO2000053722A2 (en) | 1999-03-10 | 2000-09-14 | Phogen Limited | Delivery of nucleic acids and proteins to cells |
| KR20060015505A (ko) * | 2003-04-13 | 2006-02-17 | 엔존 파마슈티컬즈, 인코포레이티드 | 올리고뉴클레오타이드 전구약물 |
| WO2007073149A1 (en) * | 2005-12-22 | 2007-06-28 | Keygene N.V. | Alternative nucleotides for improved targeted nucleotide exchange |
| CA2662978A1 (en) * | 2006-09-15 | 2008-03-20 | Enzon Pharmaceuticals, Inc. | Hindered ester-based biodegradable linkers for oligonucleotide delivery |
| AU2008271050B2 (en) * | 2007-06-29 | 2014-11-06 | Sarepta Therapeutics, Inc. | Tissue specific peptide conjugates and methods |
| US20100016215A1 (en) * | 2007-06-29 | 2010-01-21 | Avi Biopharma, Inc. | Compound and method for treating myotonic dystrophy |
| CA2742838A1 (en) * | 2008-11-17 | 2010-05-20 | Enzon Pharmaceuticals, Inc. | Releasable polymeric lipids for nucleic acids delivery systems |
| CA2758189C (en) * | 2009-04-10 | 2020-12-29 | Association Institut De Myologie | Tricyclo-dna antisense oligonucleotides, compositions, and methods for the treatment of disease |
| JP2014511547A (ja) | 2011-02-25 | 2014-05-15 | ルミテックス， インコーポレイテッド | ディスプレイ前方照明装置 |
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| JP2015501144A (ja) | 2015-01-15 |
| AU2012322903B2 (en) | 2017-09-14 |
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| WO2013053928A1 (en) | 2013-04-18 |
| EP2581448B1 (en) | 2015-01-28 |
| CN104245935A (zh) | 2014-12-24 |
| DK2581448T3 (en) | 2015-04-27 |
| EP2766479B1 (en) | 2017-09-13 |
| HK1186205A1 (en) | 2014-03-07 |
| ES2535654T3 (es) | 2015-05-13 |
| CA2776651A1 (en) | 2013-04-13 |
| CA2851970A1 (en) | 2013-04-18 |
| BR112014009066B8 (pt) | 2021-02-23 |
| US20140296323A1 (en) | 2014-10-02 |
| PT2581448E (pt) | 2015-05-21 |
| US9738891B2 (en) | 2017-08-22 |
| IN2014DN03463A (cg-RX-API-DMAC7.html) | 2015-06-05 |
| BR112014009066A2 (pt) | 2017-04-18 |
| JP6181653B2 (ja) | 2017-08-16 |
| BR112014009066A8 (pt) | 2018-01-09 |
| ES2651216T3 (es) | 2018-01-25 |
| EP2581448A1 (en) | 2013-04-17 |
| IL231983B (en) | 2018-04-30 |
| PL2581448T3 (pl) | 2015-08-31 |
| AU2012322903A1 (en) | 2014-05-29 |
| IL231983A0 (en) | 2014-05-28 |
| EP2766479A1 (en) | 2014-08-20 |
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