ES2567411T3 - Ácido nucleico antisentido - Google Patents
Ácido nucleico antisentido Download PDFInfo
- Publication number
- ES2567411T3 ES2567411T3 ES11821996.3T ES11821996T ES2567411T3 ES 2567411 T3 ES2567411 T3 ES 2567411T3 ES 11821996 T ES11821996 T ES 11821996T ES 2567411 T3 ES2567411 T3 ES 2567411T3
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- seq
- nucleic acid
- synthetic nucleic
- solution
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Classifications
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- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7125—Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4707—Muscular dystrophy
- C07K14/4708—Duchenne dystrophy
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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
- 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
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Families Citing this family (73)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| USRE48960E1 (en) | 2004-06-28 | 2022-03-08 | The University Of Western Australia | Antisense oligonucleotides for inducing exon skipping and methods of use thereof |
| USRE47769E1 (en) | 2004-06-28 | 2019-12-17 | The University Of Western Australia | Antisense oligonucleotides for inducing exon skipping and methods of use thereof |
| CA2596506C (en) | 2005-02-09 | 2021-04-06 | Avi Biopharma, Inc. | Antisense composition and method for treating muscle atrophy |
| HUE028662T2 (en) | 2007-10-26 | 2016-12-28 | Academisch Ziekenhuis Leiden | Preparations and methods for controlling muscle disorders |
| 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 |
| US8084601B2 (en) | 2008-09-11 | 2011-12-27 | Royal Holloway And Bedford New College Royal Holloway, University Of London | Oligomers |
| TR201902952T4 (tr) | 2008-10-24 | 2019-03-21 | Sarepta Therapeutics Inc | Dmd için ekson atlama bileşimleri. |
| WO2011057350A1 (en) | 2009-11-12 | 2011-05-19 | The University Of Western Australia | Antisense molecules and methods for treating pathologies |
| TWI541024B (zh) * | 2010-09-01 | 2016-07-11 | 日本新藥股份有限公司 | 反義核酸 |
| US20130085139A1 (en) | 2011-10-04 | 2013-04-04 | Royal Holloway And Bedford New College | Oligomers |
| CN111893117B (zh) * | 2012-01-27 | 2024-06-04 | 比奥马林技术公司 | 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 |
| BR112015014987A2 (pt) * | 2012-12-20 | 2017-08-15 | Sarepta Therapeutics Inc | Aprimoradas composições que pulam éxon para o tratamento da distrofia muscular |
| US9217148B2 (en) | 2013-03-14 | 2015-12-22 | Sarepta Therapeutics, Inc. | Exon skipping compositions for treating muscular dystrophy |
| SMT201900139T1 (it) | 2013-03-14 | 2019-05-10 | Sarepta Therapeutics Inc | Composizioni di salto dell'esone per il trattamento della distrofia muscolare |
| MX373959B (es) | 2013-03-15 | 2020-07-13 | Sarepta Therapeutics Inc | Composición para usarse en el tratamiento de la distrofia muscular de duchenne (dmd). |
| EP3514234A1 (en) * | 2014-03-12 | 2019-07-24 | Nippon Shinyaku Co., Ltd. | Antisense nucleic acid |
| ES2930274T3 (es) * | 2014-05-19 | 2022-12-09 | Knc Laboratories Co Ltd | Fármaco de ácido nucleico para inducir la omisión de variantes exónicas del gen de CD44 y aumentar la expresión de ARNm de CD44 de tipo normal |
| UA121117C2 (uk) | 2014-06-17 | 2020-04-10 | Ніппон Шин'Яку Ко., Лтд. | Антисенсова нуклеїнова кислота |
| MA41795A (fr) | 2015-03-18 | 2018-01-23 | Sarepta Therapeutics Inc | Exclusion d'un exon induite par des composés antisens dans la myostatine |
| RU2724554C2 (ru) | 2015-09-15 | 2020-06-23 | Ниппон Синяку Ко., Лтд. | Антисмысловая нуклеиновая кислота |
| WO2017047741A1 (ja) * | 2015-09-16 | 2017-03-23 | 日本新薬株式会社 | 筋萎縮症治療用アンチセンス核酸 |
| JP7511326B2 (ja) | 2015-10-09 | 2024-07-05 | ウェイブ ライフ サイエンシズ リミテッド | オリゴヌクレオチド組成物およびその方法 |
| BR112018007066A2 (pt) | 2015-10-09 | 2018-10-23 | Sarepta Therapeutics Inc | composições e métodos para tratamento da distrofia muscular de duchene e distúrbios relacionados |
| FR3044926B1 (fr) | 2015-12-09 | 2020-01-31 | Genethon | Outils de therapie genique efficaces pour le saut de l'exon 53 de la dystrophine |
| KR101686379B1 (ko) | 2016-02-05 | 2016-12-13 | 박정열 | 휴대용 구이기 |
| US11472824B2 (en) | 2016-05-24 | 2022-10-18 | Sarepta Therapeutics, Inc. | Processes for preparing phosphorodiamidate morpholino oligomers |
| CN109311920B (zh) | 2016-05-24 | 2021-11-09 | 萨勒普塔医疗公司 | 制备磷酸二酰胺吗啉代寡聚物的方法 |
| MA45183A (fr) | 2016-05-24 | 2019-04-10 | Sarepta Therapeutics Inc | Procédés de préparation d'oligomères morpholino de phosphorodiamidate |
| MA45362A (fr) | 2016-05-24 | 2019-04-10 | Sarepta Therapeutics Inc | Procédés de préparation d'oligomères morpholino de phosphorodiamidate |
| EP3464305B1 (en) * | 2016-05-24 | 2024-08-21 | Sarepta Therapeutics, Inc. | Processes for preparing oligomers |
| AU2017270598B2 (en) * | 2016-05-24 | 2022-12-01 | Sarepta Therapeutics, Inc. | Processes for preparing phosphorodiamidate morpholino oligomers |
| JP2019525742A (ja) | 2016-06-30 | 2019-09-12 | サレプタ セラピューティクス， インコーポレイテッド | 筋ジストロフィーに対するエクソンスキッピングオリゴマー |
| US20180028554A1 (en) * | 2016-07-05 | 2018-02-01 | Biomarin Technologies B.V. | Oligomers Having Bicyclic Scaffold Moeities |
| KR101715572B1 (ko) | 2016-10-11 | 2017-03-22 | 박종찬 | 구이대 승강구조를 갖는 양방향 구이기 |
| CA3047010A1 (en) | 2016-12-19 | 2018-06-28 | Sarepta Therapeutics, Inc. | Exon skipping oligomer conjugates for muscular dystrophy |
| EP3554553B1 (en) | 2016-12-19 | 2022-07-20 | Sarepta Therapeutics, Inc. | Exon skipping oligomer conjugates for muscular dystrophy |
| KR20240006023A (ko) | 2016-12-19 | 2024-01-12 | 사렙타 쎄러퓨틱스 인코퍼레이티드 | 근육 이상증에 대한 엑손 스킵핑 올리고머 결합체 |
| US11603532B2 (en) | 2017-06-02 | 2023-03-14 | Wave Life Sciences Ltd. | Oligonucleotide compositions and methods of use thereof |
| WO2019046755A1 (en) * | 2017-08-31 | 2019-03-07 | Sarepta Therapeutics, Inc. | METHODS FOR TREATING MUSCLE DYSTROPHY |
| EA201991450A1 (ru) | 2017-09-22 | 2019-12-30 | Сарепта Терапьютикс, Инк. | Конъюгаты олигомеров для пропуска экзона при мышечной дистрофии |
| JP2020536057A (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 |
| WO2019209764A2 (en) * | 2018-04-26 | 2019-10-31 | Sarepta Therapeutics, Inc. | Exon skipping oligomers and oligomer conjugates for muscular dystrophy |
| AU2019265904A1 (en) * | 2018-05-11 | 2020-11-12 | Wave Life Sciences Ltd. | Oligonucleotide compositions and methods of use thereof |
| US10765760B2 (en) | 2018-05-29 | 2020-09-08 | Sarepta Therapeutics, Inc. | Exon skipping oligomer conjugates for muscular dystrophy |
| JP7345466B2 (ja) * | 2018-06-26 | 2023-09-15 | 日本新薬株式会社 | アンチセンスオリゴヌクレオチドを含有する組成物およびデュシェンヌ型筋ジストロフィーの治療へのその使用 |
| SG11202100934PA (en) | 2018-08-02 | 2021-02-25 | Dyne Therapeutics Inc | Muscle targeting complexes and uses thereof for treating dystrophinopathies |
| US12018087B2 (en) | 2018-08-02 | 2024-06-25 | Dyne Therapeutics, Inc. | Muscle-targeting complexes comprising an anti-transferrin receptor antibody linked to an oligonucleotide and methods of delivering oligonucleotide to a subject |
| US11168141B2 (en) | 2018-08-02 | 2021-11-09 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating dystrophinopathies |
| SG11202100928QA (en) | 2018-08-02 | 2021-02-25 | Dyne Therapeutics Inc | Muscle targeting complexes and uses thereof for treating facioscapulohumeral muscular dystrophy |
| GB201812980D0 (en) | 2018-08-09 | 2018-09-26 | Univ Oxford Innovation Ltd | Cell-penetrating peptides |
| GB201812972D0 (en) | 2018-08-09 | 2018-09-26 | Univ Oxford Innovation Ltd | Cell-penetrating peptides |
| EP3890783A1 (en) | 2018-12-07 | 2021-10-13 | Oxford University Innovation Limited | Linkers |
| AU2018454784A1 (en) * | 2018-12-25 | 2021-08-05 | National Center Of Neurology And Psychiatry | Method for inducing muscular cells using cells in spot urine |
| GB201821269D0 (en) * | 2018-12-28 | 2019-02-13 | Nippon Shinyaku Co Ltd | Myostatin signal inhibitor |
| CN118109469A (zh) | 2019-12-26 | 2024-05-31 | 日本新药株式会社 | 诱导外显子50的跳读的反义核酸 |
| BR112022017066A2 (pt) | 2020-02-28 | 2022-11-16 | Nippon Shinyaku Co Ltd | Ácido nucleico antissentido indutor de salto do éxon 51 |
| EP4119167A4 (en) | 2020-03-11 | 2025-08-06 | Biocomber Co Ltd | SINGLE-STRANDED NUCLEIC ACID MOLECULE FOR INDUCING FRAME SHIFT-1 AND COMPOSITION |
| JPWO2022059754A1 (OSRAM) * | 2020-09-18 | 2022-03-24 | ||
| CA3211038A1 (en) | 2021-02-12 | 2022-08-18 | Oxford University Innovation Limited | Cell-penetrating peptide conjugates and methods of their use |
| IL307937A (en) | 2021-04-30 | 2023-12-01 | Sarepta Therapeutics Inc | Treatment methods for muscular dystrophy |
| US11969475B2 (en) | 2021-07-09 | 2024-04-30 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating facioscapulohumeral muscular dystrophy |
| US11771776B2 (en) | 2021-07-09 | 2023-10-03 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating dystrophinopathies |
| US11638761B2 (en) | 2021-07-09 | 2023-05-02 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating Facioscapulohumeral muscular dystrophy |
| MX2024000489A (es) | 2021-07-09 | 2024-04-09 | Dyne Therapeutics Inc | Complejos dirigidos al musculo y formulaciones para el tratamiento de las distrofinopatías. |
| WO2023026994A1 (ja) | 2021-08-21 | 2023-03-02 | 武田薬品工業株式会社 | ヒトトランスフェリンレセプター結合ペプチド－薬物コンジュゲート |
| CA3229962A1 (en) | 2021-08-24 | 2023-03-02 | Peptidream Inc. | Human transferrin receptor-binding antibody-peptide conjugate |
| US20250066396A1 (en) | 2021-12-27 | 2025-02-27 | Nippon Shinyaku Co., Ltd. | Method for producing oligonucleic acid compound |
| EP4215614A1 (en) | 2022-01-24 | 2023-07-26 | Dynacure | Combination therapy for dystrophin-related diseases |
| WO2023168427A1 (en) | 2022-03-03 | 2023-09-07 | Yale University | Compositions and methods for delivering therapeutic polynucleotides for exon skipping |
| JP2025079347A (ja) * | 2022-03-11 | 2025-05-22 | 日本新薬株式会社 | キャリアペプチドが連結された核酸 |
| US20250195667A1 (en) | 2022-03-17 | 2025-06-19 | Sarepta Therapeutics, Inc. | Phosphorodiamidate morpholino oligomer conjugates |
| WO2023214512A1 (ja) | 2022-05-06 | 2023-11-09 | 学校法人常翔学園 | 人工ｒｎａ分子 |
| WO2025153061A1 (zh) * | 2024-01-19 | 2025-07-24 | 云合智药（苏州）生物科技有限公司 | 用于抑制激活素iib型受体基因表达的核酸及其用途 |
Family Cites Families (62)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991009033A1 (en) | 1989-12-20 | 1991-06-27 | Anti-Gene Development Group | Uncharged morpholino-based polymers having phosphorous-containing chiral intersubunit linkages |
| JP2924179B2 (ja) | 1993-02-19 | 1999-07-26 | 日本新薬株式会社 | グリセロール誘導体，デバイス及び医薬組成物 |
| US7321828B2 (en) | 1998-04-13 | 2008-01-22 | Isis Pharmaceuticals, Inc. | System of components for preparing oligonucleotides |
| JP2000325085A (ja) | 1999-05-21 | 2000-11-28 | Masafumi Matsuo | デュシェンヌ型筋ジストロフィー治療剤 |
| US6653467B1 (en) | 2000-04-26 | 2003-11-25 | Jcr Pharmaceutical Co., Ltd. | Medicament for treatment of Duchenne muscular dystrophy |
| KR20020097241A (ko) | 2000-05-04 | 2002-12-31 | 에이브이아이 바이오파마 인코포레이티드 | 스플라이스-영역 안티센스 조성물 및 방법 |
| US6727355B2 (en) | 2000-08-25 | 2004-04-27 | Jcr Pharmaceuticals Co., Ltd. | Pharmaceutical composition 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 |
| EP1191097A1 (en) | 2000-09-21 | 2002-03-27 | Leids Universitair Medisch Centrum | Induction of exon skipping in eukaryotic cells |
| ITRM20020253A1 (it) | 2002-05-08 | 2003-11-10 | Univ Roma | Molecole chimeriche di snrna con sequenze antisenso per le giunzioni di splicing del gene della distrofina e applicazioni terapeutiche. |
| CA2942791C (en) | 2002-11-25 | 2019-08-20 | Masafumi Matsuo | Ena nucleic acid pharmaceuticals capable of modifying splicing of mrna precursors |
| CA2524255C (en) | 2003-03-21 | 2014-02-11 | Academisch Ziekenhuis Leiden | Modulation of exon recognition in pre-mrna by interfering with the secondary rna structure |
| USRE47769E1 (en) | 2004-06-28 | 2019-12-17 | The University Of Western Australia | Antisense oligonucleotides for inducing exon skipping and methods of use thereof |
| JP2006038608A (ja) | 2004-07-27 | 2006-02-09 | Tokyo Electric Power Co Inc:The | 超音波検査装置及び方法 |
| WO2006017522A2 (en) | 2004-08-03 | 2006-02-16 | University Of Utah Research Foundation | Use of antisense oligonucleotides to effect translation modulation |
| FR2874384B1 (fr) | 2004-08-17 | 2010-07-30 | Genethon | Vecteur viral adeno-associe pour realiser du saut d'exons dans un gene codant une proteine a domaines dispensables |
| EP1811024A1 (en) | 2004-10-05 | 2007-07-25 | Nippon Shinyaku Co., Ltd. | Oligo double-stranded rna and medicinal composition |
| JP2006129594A (ja) | 2004-10-28 | 2006-05-18 | Hitachi Ltd | 船舶用電気推進装置の制御方法及びその装置 |
| KR20080031164A (ko) | 2005-04-22 | 2008-04-08 | 아카데미슈 지켄후이스 라이덴 | ＳＲ 단백질의 결합의 방해에 의해 그리고 이차 ＲＮＡ구조의 방해에 의한 ｐｒｅ－ｍＲＮＡ에서 엑손 인식의조절 |
| WO2006129594A1 (ja) | 2005-05-30 | 2006-12-07 | Nippon Shinyaku Co., Ltd. | 核酸含有複合体製剤の製造方法 |
| DK1910395T3 (da) * | 2005-06-23 | 2013-02-04 | Isis Pharmaceuticals Inc | Sammensætninger og fremgangsmåder til modulation af SMN2-splejsning |
| US7943762B2 (en) | 2006-05-10 | 2011-05-17 | Avi Biopharma, Inc. | Oligonucleotide analogs having cationic intersubunit linkages |
| EP1857548A1 (en) | 2006-05-19 | 2007-11-21 | Academisch Ziekenhuis Leiden | Means and method for inducing exon-skipping |
| JP4816396B2 (ja) | 2006-10-12 | 2011-11-16 | 富士ゼロックス株式会社 | 画像形成装置 |
| US8466255B2 (en) | 2007-02-05 | 2013-06-18 | Nippon Shinyaku Co., Ltd. | Polyethylene glycol derivative |
| HUE028662T2 (en) | 2007-10-26 | 2016-12-28 | Academisch Ziekenhuis Leiden | Preparations and methods for controlling muscle disorders |
| HRP20140646T1 (hr) | 2007-11-15 | 2014-09-26 | Sarepta Therapeutics, Inc. | Postupak sinteze morfolino oligomera |
| 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 |
| US8084601B2 (en) * | 2008-09-11 | 2011-12-27 | Royal Holloway And Bedford New College Royal Holloway, University Of London | Oligomers |
| TR201902952T4 (tr) * | 2008-10-24 | 2019-03-21 | Sarepta Therapeutics Inc | Dmd için ekson atlama bileşimleri. |
| PT2344637E (pt) | 2008-10-27 | 2015-03-23 | Academisch Ziekenhuis Leiden | Métodos e meios para o salto eficiente do exão 45 no pré-mrna de distrofia muscular de duchenne |
| JP2010196032A (ja) | 2009-01-29 | 2010-09-09 | Fujifilm Corp | 水不溶性色材の分散体及びこの製造方法、これを用いた記録液、インクセット、印画物、画像形成方法、及び画像形成装置 |
| JP2012524540A (ja) | 2009-04-24 | 2012-10-18 | プロセンサ テクノロジーズ ビー．ブイ． | Ｄｍｄを処置するためのイノシンを含むオリゴヌクレオチド |
| SI3305302T1 (sl) * | 2009-06-17 | 2018-12-31 | Biogen Ma Inc. | Sestave in metode za modulacijo združevanja smn2 pri subjektu |
| WO2011057350A1 (en) | 2009-11-12 | 2011-05-19 | The University Of Western Australia | Antisense molecules and methods for treating pathologies |
| TWI541024B (zh) | 2010-09-01 | 2016-07-11 | 日本新藥股份有限公司 | 反義核酸 |
| JP2014507143A (ja) | 2011-02-08 | 2014-03-27 | ザ シャーロット−メクレンバーグ ホスピタル オーソリティ ドゥーイング／ビジネス／アズ キャロライナズ ヘルスケア システム | アンチセンスオリゴヌクレオチド |
| KR102229650B1 (ko) | 2011-05-05 | 2021-03-19 | 사렙타 쎄러퓨틱스, 인코퍼레이티드 | 펩타이드 올리고뉴클레오타이드 접합체 |
| CN111893117B (zh) | 2012-01-27 | 2024-06-04 | 比奥马林技术公司 | 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 |
| RU2674600C2 (ru) | 2012-07-03 | 2018-12-11 | Просенса Текнолоджиз Б.В. | Олигонуклеотид для лечения пациентов с мышечной дистрофией |
| BR112015014987A2 (pt) | 2012-12-20 | 2017-08-15 | Sarepta Therapeutics Inc | Aprimoradas composições que pulam éxon para o tratamento da distrofia muscular |
| US9217148B2 (en) | 2013-03-14 | 2015-12-22 | Sarepta Therapeutics, Inc. | Exon skipping compositions for treating muscular dystrophy |
| SMT201900139T1 (it) | 2013-03-14 | 2019-05-10 | Sarepta Therapeutics Inc | Composizioni di salto dell'esone per il trattamento della distrofia muscolare |
| MX373959B (es) | 2013-03-15 | 2020-07-13 | Sarepta Therapeutics Inc | Composición para usarse en el tratamiento de la distrofia muscular de duchenne (dmd). |
| US10112977B2 (en) | 2014-06-23 | 2018-10-30 | Toagosei Co., Ltd. | Peptide for inducing multinucleation in cells, and use therefor |
| EP3180435A4 (en) | 2014-08-09 | 2018-01-17 | The Research Institute at Nationwide Children's Hospital | Methods and materials for activating an internal ribosomal entry site in exon 5 of the dmd gene |
| WO2017059131A1 (en) | 2015-09-30 | 2017-04-06 | Sarepta Therapeutics, Inc. | Methods for treating muscular dystrophy |
| BR112018007066A2 (pt) | 2015-10-09 | 2018-10-23 | Sarepta Therapeutics Inc | composições e métodos para tratamento da distrofia muscular de duchene e distúrbios relacionados |
| AU2017270598B2 (en) | 2016-05-24 | 2022-12-01 | Sarepta Therapeutics, Inc. | Processes for preparing phosphorodiamidate morpholino oligomers |
| KR20190009343A (ko) | 2016-05-24 | 2019-01-28 | 사렙타 쎄러퓨틱스 인코퍼레이티드 | 에테플리센을 포함하는 약제학적 조성물 |
| EP3464305B1 (en) | 2016-05-24 | 2024-08-21 | Sarepta Therapeutics, Inc. | Processes for preparing oligomers |
| MA45183A (fr) | 2016-05-24 | 2019-04-10 | Sarepta Therapeutics Inc | Procédés de préparation d'oligomères morpholino de phosphorodiamidate |
| CN109311920B (zh) | 2016-05-24 | 2021-11-09 | 萨勒普塔医疗公司 | 制备磷酸二酰胺吗啉代寡聚物的方法 |
| JP2019525742A (ja) | 2016-06-30 | 2019-09-12 | サレプタ セラピューティクス， インコーポレイテッド | 筋ジストロフィーに対するエクソンスキッピングオリゴマー |
| CA3043864A1 (en) | 2016-11-16 | 2018-05-24 | Biomarin Technologies B.V. | Substances for targeting various selected organs or tissues |
| CA3047010A1 (en) | 2016-12-19 | 2018-06-28 | Sarepta Therapeutics, Inc. | Exon skipping oligomer conjugates for muscular dystrophy |
| EP3554553B1 (en) | 2016-12-19 | 2022-07-20 | Sarepta Therapeutics, Inc. | Exon skipping oligomer conjugates for muscular dystrophy |
| KR20240006023A (ko) | 2016-12-19 | 2024-01-12 | 사렙타 쎄러퓨틱스 인코퍼레이티드 | 근육 이상증에 대한 엑손 스킵핑 올리고머 결합체 |
| WO2019046755A1 (en) | 2017-08-31 | 2019-03-07 | Sarepta Therapeutics, Inc. | METHODS FOR TREATING MUSCLE DYSTROPHY |
| US20210145852A1 (en) | 2017-09-28 | 2021-05-20 | Sarepta Therapeutics, Inc. | Combination Therapies for Treating Muscular Dystrophy |
| JP2020536057A (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 |
| US20200248178A1 (en) | 2017-09-28 | 2020-08-06 | Sarepta Therapeutics, Inc. | Combination therapies for treating muscular dystrophy |
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