CA2723968C - Method for efficient exon (44) skipping in duchenne muscular dystrophy and associated means - Google Patents
Method for efficient exon (44) skipping in duchenne muscular dystrophy and associated means Download PDFInfo
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- CA2723968C CA2723968C CA2723968A CA2723968A CA2723968C CA 2723968 C CA2723968 C CA 2723968C CA 2723968 A CA2723968 A CA 2723968A CA 2723968 A CA2723968 A CA 2723968A CA 2723968 C CA2723968 C CA 2723968C
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Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA3048624A CA3048624C (en) | 2008-05-14 | 2009-05-14 | EFFECTIVE METHOD FOR EXON OMISSION (44) IN DUCHENNE MUSCULAR DYSTROPHY AND ASSOCIATED MEANS |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
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| EP08156193.8 | 2008-05-14 | ||
| EP08156193A EP2119783A1 (en) | 2008-05-14 | 2008-05-14 | Method for efficient exon (44) skipping in Duchenne Muscular Dystrophy and associated means |
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| CA3253824A Pending CA3253824A1 (en) | 2008-05-14 | 2009-05-14 | Method for efficient exon (44) skipping in duchenne muscular dystrophy and associated means |
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Families Citing this family (74)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| ATE498685T1 (de) | 2004-06-28 | 2011-03-15 | Univ Western Australia | Antisense-oligonukleotide zur induktion von exon- skipping sowie verfahren zur verwendung davon |
| USRE48960E1 (en) | 2004-06-28 | 2022-03-08 | The University Of Western Australia | Antisense oligonucleotides for inducing exon skipping and methods of use thereof |
| AU2006213686A1 (en) | 2005-02-09 | 2006-08-17 | Avi Bio Pharma, Inc. | Antisense composition and method for treating muscle atrophy |
| AU2007282224B2 (en) | 2006-08-11 | 2013-08-29 | Vico Therapeutics B.V. | Methods and means for treating DNA repeat instability associated genetic disorders |
| AU2008317566B2 (en) | 2007-10-26 | 2014-05-01 | Academisch Ziekenhuis Leiden | Means and methods for counteracting 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 |
| CN112574988A (zh) | 2008-10-24 | 2021-03-30 | 萨雷普塔治疗公司 | 用于dmd的多外显子跳跃组合物 |
| PT3305302T (pt) | 2009-06-17 | 2018-12-14 | Biogen Ma Inc | Composições e métodos de modulação de excisões de smn2 em um sujeito |
| LT2499249T (lt) | 2009-11-12 | 2018-12-27 | The University Of Western Australia | Priešprasmės molekulės ir patologijų gydymo būdai |
| WO2011078672A1 (en) | 2009-12-24 | 2011-06-30 | Prosensa Technologies B.V. | Molecule for treating an inflammatory disorder |
| EP2582397A4 (en) * | 2010-06-15 | 2014-10-29 | Isis Pharmaceuticals Inc | COMPOUNDS AND METHOD FOR MODULATING INTERACTION BETWEEN PROTEINS AND TARGET NUCLEIC ACIDS |
| TWI541024B (zh) | 2010-09-01 | 2016-07-11 | 日本新藥股份有限公司 | 反義核酸 |
| WO2012138223A2 (en) | 2011-04-05 | 2012-10-11 | Academisch Ziekenhuis Leiden H.O.D.N. Lumc | Compounds and methods for altering activin receptor-like kinase signalling |
| US20140128449A1 (en) * | 2011-04-07 | 2014-05-08 | The Board Of Regents Of The University Of Texas System | Oligonucleotide modulation of splicing |
| US20130085139A1 (en) | 2011-10-04 | 2013-04-04 | Royal Holloway And Bedford New College | Oligomers |
| CN117721110A (zh) * | 2011-12-28 | 2024-03-19 | 日本新药株式会社 | 反义核酸 |
| CN112251436A (zh) | 2012-01-27 | 2021-01-22 | 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 |
| EP2870246B1 (en) * | 2012-07-03 | 2019-09-11 | BioMarin Technologies B.V. | Oligonucleotide for the treatment of muscular dystrophy patients |
| EP2943225A4 (en) * | 2013-01-09 | 2016-07-13 | Ionis Pharmaceuticals Inc | COMPOSITIONS AND METHODS FOR MODULATING SMN2 DISTRIBUTION IN THE BODY OF A PATIENT |
| NZ731587A (en) | 2013-03-14 | 2021-07-30 | Sarepta Therapeutics Inc | Exon skipping compositions for treating muscular dystrophy |
| CA2906812A1 (en) | 2013-03-15 | 2014-09-18 | Sarepta Therapeutics, Inc. | Improved compositions for treating muscular dystrophy |
| WO2015161170A2 (en) | 2014-04-17 | 2015-10-22 | Isis Pharmaceuticals, Inc. | Compositions and methods for modulation of smn2 splicing in a subject |
| GB201410693D0 (en) * | 2014-06-16 | 2014-07-30 | Univ Southampton | Splicing modulation |
| RU2695430C2 (ru) | 2014-06-17 | 2019-07-23 | Ниппон Синяку Ко., Лтд. | Антисмысловые нуклеиновые кислоты |
| BR112017004056A2 (pt) | 2014-09-12 | 2017-12-05 | Biogen Ma Inc | composições e métodos para detecção da proteína smn em um indivíduo e tratamento de um indivíduo |
| MA41795A (fr) | 2015-03-18 | 2018-01-23 | Sarepta Therapeutics Inc | Exclusion d'un exon induite par des composés antisens dans la myostatine |
| EP3085785A1 (en) * | 2015-04-22 | 2016-10-26 | Université de Strasbourg | Dynamin 2 inhibitor for the treatment of duchenne's muscular dystrophy |
| JP7007199B2 (ja) * | 2015-06-10 | 2022-02-10 | アソシアシオン・アンスティテュ・ドゥ・ミオロジー | デュシェンヌ型筋ジストロフィーのための併用療法 |
| SI3351633T1 (sl) | 2015-09-15 | 2020-09-30 | Nippon Shinyaku Co., Ltd. | Protismiselna nukleinska kislina |
| EP3858993A1 (en) | 2015-10-09 | 2021-08-04 | Sarepta Therapeutics, Inc. | Compositions and methods for treating duchenne muscular dystrophy and related disorders |
| 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 |
| JP2019513371A (ja) | 2016-04-01 | 2019-05-30 | アビディティー バイオサイエンシーズ エルエルシー | 核酸ポリペプチド組成物とその使用 |
| WO2017218884A1 (en) | 2016-06-16 | 2017-12-21 | Ionis Pharmaceuticals, Inc. | Combinations for the modulation of smn expression |
| TW201811807A (zh) | 2016-06-30 | 2018-04-01 | 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 |
| BR112019000195A2 (pt) | 2016-07-07 | 2019-04-24 | Rubius Therapeutics, Inc. | composições e métodos relacionados a sistemas celulares terapêuticos que expressam rna exógeno |
| JP7416406B2 (ja) * | 2016-12-08 | 2024-01-17 | ケース ウェスタン リザーブ ユニバーシティ | 機能的ミエリン産生を増進させるための方法および組成物 |
| SMT202200366T1 (it) | 2016-12-19 | 2022-11-18 | Sarepta Therapeutics Inc | Coniugati di oligomeri per salto di esone per distrofia muscolare |
| SI3554554T1 (sl) | 2016-12-19 | 2023-02-28 | Sarepta Therapeutics, Inc. | Oligomerni konjugati, ki preskakujejo ekson za mišično distrofijo |
| IL297528A (en) | 2016-12-19 | 2022-12-01 | Sarepta Therapeutics Inc | Exon-skipping oligomer conjugates for muscular dystrophy |
| MX2019008199A (es) | 2017-01-06 | 2019-11-25 | Avidity Biosciences Llc | Composiciones de acido nucleico polipeptido y metodos de induccion de la omision de exon. |
| GB201711809D0 (en) | 2017-07-21 | 2017-09-06 | Governors Of The Univ Of Alberta | Antisense oligonucleotide |
| US20200282074A1 (en) * | 2017-09-22 | 2020-09-10 | Avidity Biosciences, Inc. | Nucleic acid-polypeptide compositions and methods of inducing exon skipping |
| EA201991450A1 (ru) | 2017-09-22 | 2019-12-30 | Сарепта Терапьютикс, Инк. | Конъюгаты олигомеров для пропуска экзона при мышечной дистрофии |
| JP7506601B2 (ja) | 2017-12-06 | 2024-06-26 | アビディティー バイオサイエンシーズ，インク． | 筋萎縮症と筋緊張性ジストロフィーを処置するための組成物および方法 |
| US10758629B2 (en) | 2018-05-29 | 2020-09-01 | Sarepta Therapeutics, Inc. | Exon skipping oligomer conjugates for muscular dystrophy |
| CN110760511B (zh) * | 2018-07-27 | 2021-09-07 | 广东赤萌医疗科技有限公司 | 一种用于治疗杜氏肌营养不良症的gRNA、表达载体、CRISPR-Cas9系统 |
| 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 |
| EP3829595A4 (en) * | 2018-08-02 | 2022-08-24 | Dyne Therapeutics, Inc. | MUSCLE-DIRECTED COMPLEXES AND USES THEREOF IN THE TREATMENT OF DYSTROPHINOPATHIES |
| US20220193250A1 (en) | 2018-08-02 | 2022-06-23 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating facioscapulohumeral muscular dystrophy |
| IL282818B1 (en) | 2018-11-02 | 2026-04-01 | Biomarin Tech Bv | Bispecific antisense oligonucleotides for dystrophin exon skipping |
| KR20210134003A (ko) | 2019-02-27 | 2021-11-08 | 스톡 테라퓨틱스, 인크. | 병태 및 질환의 치료를 위한 안티센스 올리고머 |
| US12497615B2 (en) | 2019-04-25 | 2025-12-16 | Avidity Biosciences, Inc. | Nucleic acid compositions and methods of multi-exon skipping |
| EP4007633A4 (en) * | 2019-08-02 | 2024-05-08 | Research Institute at Nationwide Children's Hospital | NUCLEIC ACIDS TARGETING EXON 44 AND RECOMBINANT ADENO-ASSOCIATED VIRUS COMPRISING SAID NUCLEIC ACIDS FOR THE TREATMENT OF DYSTROPHIN-BASED MYOPATHIES |
| JP7842395B2 (ja) | 2019-12-19 | 2026-04-08 | 日本新薬株式会社 | エクソンスキッピングを可能にするアンチセンス核酸 |
| US20230020092A1 (en) | 2019-12-19 | 2023-01-19 | Entrada Therapeutics, Inc. | Compositions for delivery of antisense compounds |
| CR20220485A (es) | 2020-02-28 | 2022-11-10 | Ionis Pharmaceuticals Inc | Compuestos y métodos para modular smn2 |
| US11555190B2 (en) | 2020-03-19 | 2023-01-17 | Avidity Biosciences, Inc. | Compositions and methods of treating Facioscapulohumeral muscular dystrophy |
| BR112022022889A2 (pt) | 2020-05-11 | 2023-04-04 | Stoke Therapeutics Inc | Oligômeros antissentido de opa1 para tratamento de condições e doenças |
| WO2021242674A1 (en) * | 2020-05-26 | 2021-12-02 | Ptc Therapeutics, Inc. | Quantification of dystrophin |
| CN115011598A (zh) * | 2020-09-02 | 2022-09-06 | 西湖大学 | 杜氏肌营养不良症相关的外显子剪接增强子、sgRNA、基因编辑工具及应用 |
| JPWO2022181807A1 (https=) * | 2021-02-25 | 2022-09-01 | ||
| US20240358845A1 (en) | 2021-05-10 | 2024-10-31 | Entrada Therapeutics, Inc. | Compositions and methods for intracellular therapeutics |
| WO2022270585A1 (ja) | 2021-06-23 | 2022-12-29 | 日本新薬株式会社 | アンチセンスオリゴマーの組み合わせ |
| PE20242357A1 (es) | 2021-06-23 | 2024-12-16 | Entrada Therapeutics Inc | Compuestos antisentido y metodos para dirigirse a repeticiones cug |
| US11969475B2 (en) | 2021-07-09 | 2024-04-30 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating facioscapulohumeral muscular dystrophy |
| IL309936A (en) | 2021-07-09 | 2024-03-01 | Dyne Therapeutics Inc | Muscle targeting complexes and formulations for the treatment of dystrophinopathy |
| US11771776B2 (en) * | 2021-07-09 | 2023-10-03 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating dystrophinopathies |
| MX2024003266A (es) | 2021-09-16 | 2024-04-03 | Avidity Biosciences Inc | Composiciones y metodos de tratamiento de la distrofia muscular facioescapulohumeral. |
| EP4215614A1 (en) | 2022-01-24 | 2023-07-26 | Dynacure | Combination therapy for dystrophin-related diseases |
| US12071621B2 (en) | 2022-04-05 | 2024-08-27 | Avidity Biosciences, Inc. | Anti-transferrin receptor antibody-PMO conjugates for inducing DMD exon 44 skipping |
| WO2025194138A1 (en) | 2024-03-14 | 2025-09-18 | Tessera Therapeutics, Inc. | St1cas9 compositions and methods for modulating a genome |
Family Cites Families (201)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
| US5541308A (en) | 1986-11-24 | 1996-07-30 | Gen-Probe Incorporated | Nucleic acid probes for detection and/or quantitation of non-viral organisms |
| DE3834636A1 (de) | 1988-10-11 | 1990-04-19 | Max Planck Gesellschaft | Verfahren zur analyse von laengenpolymorphismen in dna-bereichen |
| US5766847A (en) | 1988-10-11 | 1998-06-16 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Process for analyzing length polymorphisms in DNA regions |
| US6867195B1 (en) | 1989-03-21 | 2005-03-15 | Vical Incorporated | Lipid-mediated polynucleotide administration to reduce likelihood of subject's becoming infected |
| US5681941A (en) | 1990-01-11 | 1997-10-28 | Isis Pharmaceuticals, Inc. | Substituted purines and oligonucleotide cross-linking |
| US5608046A (en) | 1990-07-27 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Conjugated 4'-desmethyl nucleoside analog compounds |
| FR2675803B1 (fr) | 1991-04-25 | 1996-09-06 | Genset Sa | Oligonucleotides fermes, antisens et sens et leurs applications. |
| CA2082411A1 (en) | 1991-06-28 | 1992-12-29 | Robert D. Rosenberg | Localized oligonucleotide therapy |
| WO1993001286A2 (en) | 1991-06-28 | 1993-01-21 | Massachusetts Institute Of Technology | Localized oligonucleotide therapy |
| US6200747B1 (en) | 1992-01-28 | 2001-03-13 | North Shore University Hospital Research Corp. | Method and kits for detection of fragile X specific, GC-rich DNA sequences |
| US5869252A (en) | 1992-03-31 | 1999-02-09 | Abbott Laboratories | Method of multiplex ligase chain reaction |
| US6172208B1 (en) | 1992-07-06 | 2001-01-09 | Genzyme Corporation | Oligonucleotides modified with conjugate groups |
| US5418139A (en) | 1993-02-10 | 1995-05-23 | University Of Iowa Research Foundation | Method for screening for cardiomyopathy |
| CA2116280A1 (en) | 1993-03-05 | 1994-09-06 | Marcy E. Macdonald | Huntingtin dna, protein and uses thereof |
| CN1123038A (zh) | 1993-05-11 | 1996-05-22 | 北卡罗来纳大学查珀尔希尔分校 | 阻止异常剪接的反义寡核苷酸及其使用方法 |
| US5741645A (en) | 1993-06-29 | 1998-04-21 | Regents Of The University Of Minnesota | Gene sequence for spinocerebellar ataxia type 1 and method for diagnosis |
| US5624803A (en) | 1993-10-14 | 1997-04-29 | The Regents Of The University Of California | In vivo oligonucleotide generator, and methods of testing the binding affinity of triplex forming oligonucleotides derived therefrom |
| US5627263A (en) | 1993-11-24 | 1997-05-06 | La Jolla Cancer Research Foundation | Integrin-binding peptides |
| DE4342605A1 (de) | 1993-12-14 | 1995-06-22 | Buna Gmbh | Funktionalisierte Olefinhomo- und -copolymere |
| US5962332A (en) | 1994-03-17 | 1999-10-05 | University Of Massachusetts | Detection of trinucleotide repeats by in situ hybridization |
| WO1995030774A1 (en) | 1994-05-05 | 1995-11-16 | Beckman Instruments, Inc. | Oligonucleotide repeat arrays |
| US5968909A (en) | 1995-08-04 | 1999-10-19 | Hybridon, Inc. | Method of modulating gene expression with reduced immunostimulatory response |
| US5854223A (en) | 1995-10-06 | 1998-12-29 | The Trustees Of Columbia University In The City Of New York | S-DC28 as an antirestenosis agent after balloon injury |
| US7034009B2 (en) * | 1995-10-26 | 2006-04-25 | Sirna Therapeutics, Inc. | Enzymatic nucleic acid-mediated treatment of ocular diseases or conditions related to levels of vascular endothelial growth factor receptor (VEGF-R) |
| US6300060B1 (en) | 1995-11-09 | 2001-10-09 | Dana-Farber Cancer Institute, Inc. | Method for predicting the risk of prostate cancer morbidity and mortality |
| ATE267207T1 (de) | 1996-02-14 | 2004-06-15 | Isis Pharmaceuticals Inc | Kohlenhydratmodifizierte luckenhafte oligonukleotide |
| JP3950480B2 (ja) | 1996-07-18 | 2007-08-01 | 株式会社エスアールエル | 脊髄小脳変性症２型の原因遺伝子の検出方法及びそのためのプライマー |
| JP3976346B2 (ja) | 1996-10-30 | 2007-09-19 | 株式会社エスアールエル | 脊髄小脳変性症２型の原因遺伝子のｃＤＮＡ断片 |
| US5853995A (en) | 1997-01-07 | 1998-12-29 | Research Development Foundation | Large scale genotyping of diseases and a diagnostic test for spinocerebellar ataxia type 6 |
| US20020137890A1 (en) | 1997-03-31 | 2002-09-26 | Genentech, Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
| AU6591798A (en) | 1997-03-31 | 1998-10-22 | Yale University | Nucleic acid catalysts |
| AU7265298A (en) | 1997-04-29 | 1998-11-24 | Trustees Of Boston University | Methods and compositions for targeted dna differential display |
| US6329501B1 (en) | 1997-05-29 | 2001-12-11 | Auburn University | Methods and compositions for targeting compounds to muscle |
| US6280938B1 (en) | 1997-08-19 | 2001-08-28 | Regents Of The University Of Minnesota | SCA7 gene and method of use |
| US6514755B1 (en) | 1998-08-18 | 2003-02-04 | Regents Of The University Of Minnesota | SCA7 gene and methods of use |
| US6794499B2 (en) | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
| CA2304813A1 (en) | 1997-09-22 | 1999-04-08 | Fritz Eckstein | Nucleic acid catalysts with endonuclease activity |
| US6130207A (en) | 1997-11-05 | 2000-10-10 | South Alabama Medical Science Foundation | Cell-specific molecule and method for importing DNA into a nucleus |
| JP3012923B2 (ja) | 1998-01-26 | 2000-02-28 | 新潟大学長 | Ｃａｇリピート病の治療薬 |
| KR100280219B1 (ko) | 1998-02-26 | 2001-04-02 | 이수빈 | 삼핵산 반복 서열을 이용한 신경정신 질환의 진단 방법 및 진단 시약 |
| US6322978B1 (en) | 1998-04-20 | 2001-11-27 | Joslin Diabetes Center, Inc. | Repeat polymorphism in the frataxin gene and uses therefore |
| EP1073732A2 (en) | 1998-04-29 | 2001-02-07 | Ribozyme Pharmaceuticals, Inc. | Nucleoside triphosphates and their incorporation into ribozymes |
| DE69919869T2 (de) | 1998-06-10 | 2005-09-29 | Biognostik Gesellschaft für Biomolekulare Diagnostik mbH | Stimulierung des immunsystems |
| US20030096955A1 (en) | 1998-09-01 | 2003-05-22 | Genentech, Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
| CA2343934A1 (en) | 1998-09-25 | 2000-04-06 | The Children's Medical Center Corporation | Short peptides which selectively modulate the activity of protein kinases |
| US6210892B1 (en) | 1998-10-07 | 2001-04-03 | Isis Pharmaceuticals, Inc. | Alteration of cellular behavior by antisense modulation of mRNA processing |
| US6172216B1 (en) | 1998-10-07 | 2001-01-09 | Isis Pharmaceuticals Inc. | Antisense modulation of BCL-X expression |
| AU771579B2 (en) | 1998-10-26 | 2004-03-25 | Avi Biopharma, Inc. | p53 antisense agent and method |
| US6399575B1 (en) | 1998-11-10 | 2002-06-04 | Auburn University | Methods and compositions for targeting compounds to the central nervous system |
| US6133031A (en) | 1999-08-19 | 2000-10-17 | Isis Pharmaceuticals Inc. | Antisense inhibition of focal adhesion kinase expression |
| US20040226056A1 (en) | 1998-12-22 | 2004-11-11 | Myriad Genetics, Incorporated | Compositions and methods for treating neurological disorders and diseases |
| US20020049173A1 (en) | 1999-03-26 | 2002-04-25 | Bennett C. Frank | Alteration of cellular behavior by antisense modulation of mRNA processing |
| US6379698B1 (en) | 1999-04-06 | 2002-04-30 | Isis Pharmaceuticals, Inc. | Fusogenic lipids and vesicles |
| CA2365984A1 (en) | 1999-04-08 | 2000-10-19 | Oasis Biosciences, Inc. | Antisense oligonucleotides comprising universal and/or degenerate bases |
| 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 |
| US20030236214A1 (en) | 1999-06-09 | 2003-12-25 | Wolff Jon A. | Charge reversal of polyion complexes and treatment of peripheral occlusive disease |
| US6656730B1 (en) | 1999-06-15 | 2003-12-02 | Isis Pharmaceuticals, Inc. | Oligonucleotides conjugated to protein-binding drugs |
| US6355481B1 (en) | 1999-06-18 | 2002-03-12 | Emory University | Hybridoma cell line and monoclonal antibody for huntingtin protein |
| CA2403243A1 (en) | 1999-08-31 | 2001-03-08 | Ribozyme Pharmaceuticals, Inc. | Nucleic acid based modulators of gene expression |
| AU7855900A (en) | 1999-10-04 | 2001-05-10 | University Of Medicine And Dentistry Of New Jersey | Methods for identifying rna binding compounds |
| US6165786A (en) | 1999-11-03 | 2000-12-26 | Isis Pharmaceuticals, Inc. | Antisense modulation of nucleolin expression |
| EP1257639A2 (en) | 2000-02-08 | 2002-11-20 | Ribozyme Pharmaceuticals, Inc. | Nucleozymes with endonuclease activity |
| WO2005019453A2 (en) | 2001-05-18 | 2005-03-03 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING CHEMICALLY MODIFIED SHORT INTERFERING NUCLEIC ACID (siNA) |
| EP1133993A1 (en) | 2000-03-10 | 2001-09-19 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Substances for the treatment of spinal muscular atrophy |
| AU4819101A (en) | 2000-04-13 | 2001-10-30 | University Of British Columbia, The | Modulating cell survival by modulating huntingtin function |
| US6653467B1 (en) | 2000-04-26 | 2003-11-25 | Jcr Pharmaceutical Co., Ltd. | Medicament for treatment of Duchenne muscular dystrophy |
| ATE437944T1 (de) | 2000-04-28 | 2009-08-15 | Asklepios Biopharmaceutical In | Für das dystrophin-minigen kodierende dna- sequenzen und verfahren zu deren verwendung |
| AU5736601A (en) | 2000-05-01 | 2001-11-12 | Hybridon Inc | Modulation of oligonucleotide cpg-mediated immune stimulation by positional modification of nucleosides |
| AU2001259706A1 (en) | 2000-05-09 | 2001-11-20 | Reliable Biopharmaceutical, Inc. | Polymeric compounds useful as prodrugs |
| WO2001092330A2 (en) | 2000-05-31 | 2001-12-06 | Genset S.A. | Use of acrp30 globular head to promote increases in muscle mass and muscle differentiation |
| CN1326990A (zh) | 2000-06-07 | 2001-12-19 | 上海博德基因开发有限公司 | 一种新的多肽——人类dna cgg重复结合蛋白16.17和编码这种多肽的多核苷酸 |
| US20030124523A1 (en) | 2000-06-22 | 2003-07-03 | Asselbergs Fredericus Alphonsus Maria | Organic compounds |
| US6794192B2 (en) | 2000-06-29 | 2004-09-21 | Pfizer Inc. | Target |
| RU2165149C1 (ru) | 2000-07-03 | 2001-04-20 | Шапошников Валерий Геннадьевич | Система формования и упаковки изделий из сахарной ваты |
| 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 |
| US6727355B2 (en) | 2000-08-25 | 2004-04-27 | Jcr Pharmaceuticals Co., Ltd. | Pharmaceutical composition for treatment of Duchenne muscular dystrophy |
| EP1191097A1 (en) | 2000-09-21 | 2002-03-27 | Leids Universitair Medisch Centrum | Induction of exon skipping in eukaryotic cells |
| AU3922802A (en) | 2000-10-02 | 2002-05-27 | Keck Graduate Inst | Methods for identifying nucleotides at defined positions in target nucleic acidsusing fluorescence polarization |
| ATE400656T1 (de) | 2000-10-06 | 2008-07-15 | Univ Michigan | Mini-dystrophin nukleinsäure- und peptidsequenzen |
| US6623927B1 (en) | 2000-11-08 | 2003-09-23 | Council Of Scientific And Industrial Research | Method of detection of allelic variants of SCA2 gene |
| US6743893B2 (en) | 2000-11-30 | 2004-06-01 | The Uab Research Foundation | Receptor-mediated uptake of peptides that bind the human transferrin receptor |
| US7001994B2 (en) | 2001-01-18 | 2006-02-21 | Genzyme Corporation | Methods for introducing mannose 6-phosphate and other oligosaccharides onto glycoproteins |
| TWI329129B (en) | 2001-02-08 | 2010-08-21 | Wyeth Corp | Modified and stabilized gdf propeptides and uses thereof |
| US20070021360A1 (en) | 2001-04-24 | 2007-01-25 | Nyce Jonathan W | Compositions, formulations and kit with anti-sense oligonucleotide and anti-inflammatory steroid and/or obiquinone for treatment of respiratory and lung disesase |
| JP4162494B2 (ja) | 2001-05-11 | 2008-10-08 | リージェンツ オブ ザ ユニバーシティ オブ ミネソタ | 筋緊張性ジストロフィー２型に関連するイントロン、および使用方法 |
| US20050014172A1 (en) | 2002-02-20 | 2005-01-20 | Ivan Richards | RNA interference mediated inhibition of muscarinic cholinergic receptor gene expression using short interfering nucleic acid (siNA) |
| US20050277133A1 (en) | 2001-05-18 | 2005-12-15 | Sirna Therapeutics, Inc. | RNA interference mediated treatment of polyglutamine (polyQ) repeat expansion diseases using short interfering nucleic acid (siNA) |
| US20050282188A1 (en) | 2001-05-18 | 2005-12-22 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA) |
| IL143379A (en) | 2001-05-24 | 2013-11-28 | Yissum Res Dev Co | Oligonucleotide against human ache isoform r and its uses |
| US20030139435A1 (en) | 2001-06-26 | 2003-07-24 | Gulzar Ahmed | N-heterocyclic inhibitors of TNF-alpha expression |
| US7745420B2 (en) | 2001-07-06 | 2010-06-29 | Topigen Pharmaceutique, Inc. | Methods for increasing in vivo efficacy of oligonucleotides and inhibiting inflammation in mammals |
| AU2002326589B2 (en) | 2001-08-07 | 2008-06-05 | University Of Delaware | Compositions and methods for the prevention and treatment of Huntington's disease |
| WO2003014145A2 (en) | 2001-08-10 | 2003-02-20 | Novartis Ag | Peptides that bind to atherosclerotic lesions |
| US20060074034A1 (en) | 2001-09-17 | 2006-04-06 | Collins Douglas A | Cobalamin mediated delivery of nucleic acids, analogs and derivatives thereof |
| KR20030035047A (ko) | 2001-10-29 | 2003-05-09 | (주)바이오코돈 | Bmp-4 유전자 발현을 이용한 편평태선 질환의 치료 및진단방법 |
| WO2003037172A2 (en) | 2001-11-01 | 2003-05-08 | Gpc Biotech Inc. | Endothelial-cell binding peptides for diagnosis and therapy |
| US20030134790A1 (en) | 2002-01-11 | 2003-07-17 | University Of Medicine And Dentistry Of New Jersey | Bone Morphogenetic Protein-2 And Bone Morphogenetic Protein-4 In The Treatment And Diagnosis Of Cancer |
| WO2003062258A1 (en) | 2002-01-22 | 2003-07-31 | The Cleveland Clinic Foundation | Rnase l activator-antisense complexes |
| WO2003069330A1 (en) | 2002-02-11 | 2003-08-21 | The Trustees Of Columbia University In The City Of New York | System and method for identifying proteins involved in force-initiated signal transduction |
| US20050096284A1 (en) | 2002-02-20 | 2005-05-05 | Sirna Therapeutics, Inc. | RNA interference mediated treatment of polyglutamine (polyQ) repeat expansion diseases using short interfering nucleic acid (siNA) |
| EP1487493B1 (en) | 2002-03-01 | 2010-01-20 | The Administrators of The Tulane Educational Fund | Conjugates of cytotoxic agents and biologically active peptides |
| US20040101852A1 (en) | 2002-11-21 | 2004-05-27 | Isis Pharmaceuticals Inc. | Modulation of CGG triplet repeat binding protein 1 expression |
| 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. |
| US20040102395A1 (en) | 2002-11-22 | 2004-05-27 | Isis Pharmaceuticals Inc. | Modulation of IAP-like expression |
| EP1380644A1 (en) | 2002-07-08 | 2004-01-14 | Kylix B.V. | The use of specified TCF target genes to identify drugs for the treatment of cancer, in particular colorectal cancer, in which TCF/beta-catenin/WNT signalling plays a central role |
| WO2004011060A2 (en) | 2002-07-26 | 2004-02-05 | Mirus Corporation | Delivery of molecules and complexes to mammalian cells in vivo |
| US20050255086A1 (en) | 2002-08-05 | 2005-11-17 | Davidson Beverly L | Nucleic acid silencing of Huntington's Disease gene |
| EP1529105B1 (en) | 2002-08-12 | 2012-10-03 | Société de commercialisation des produits de la recherche appliquée SOCPRA Sciences Santé et Humaines s.e.c. | Methods to reprogram splice site selection in pre-messenger rnas |
| GB0219143D0 (en) | 2002-08-16 | 2002-09-25 | Univ Leicester | Modified tailed oligonucleotides |
| AU2002342850A1 (en) | 2002-10-23 | 2004-05-13 | Centre For Research And Technology Hellas/Institute Of Agrobiotechnology In.A | Prion protein-binding peptide sequences |
| US7892793B2 (en) | 2002-11-04 | 2011-02-22 | University Of Massachusetts | Allele-specific RNA interference |
| US7655785B1 (en) * | 2002-11-14 | 2010-02-02 | Rosetta Genomics Ltd. | Bioinformatically detectable group of novel regulatory oligonucleotides and uses thereof |
| US7250496B2 (en) | 2002-11-14 | 2007-07-31 | Rosetta Genomics Ltd. | Bioinformatically detectable group of novel regulatory genes and uses thereof |
| EP2305812A3 (en) * | 2002-11-14 | 2012-06-06 | Dharmacon, Inc. | Fuctional and hyperfunctional sirna |
| JP4777777B2 (ja) | 2002-11-25 | 2011-09-21 | 雅文 松尾 | ｍＲＮＡ前駆体のスプライシングを修飾するＥＮＡ核酸医薬 |
| GB0228079D0 (en) | 2002-12-02 | 2003-01-08 | Laxdale Ltd | Huntington's Disease |
| WO2004080406A2 (en) | 2003-03-07 | 2004-09-23 | Alnylam Pharmaceuticals | Therapeutic compositions |
| 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 |
| US20040198640A1 (en) * | 2003-04-02 | 2004-10-07 | Dharmacon, Inc. | Stabilized polynucleotides for use in RNA interference |
| US7514551B2 (en) | 2003-04-03 | 2009-04-07 | Enzo Life Sciences, Inc. | Multisignal labeling reagents, and processes and uses therefor |
| CA2523672C (en) * | 2003-04-29 | 2012-07-17 | Avi Biopharma, Inc. | Compositions for enhancing transport of molecules into cells |
| WO2004101787A1 (ja) | 2003-05-14 | 2004-11-25 | Japan Science And Technology Agency | ハンチンチン遺伝子の発現抑制 |
| BRPI0410927A (pt) | 2003-06-02 | 2006-06-27 | Wyeth Corp | métodos terapêuticos e profiláticos para distúrbios neuromusculares |
| DE60319354T2 (de) | 2003-07-11 | 2009-03-26 | Lbr Medbiotech B.V. | Mannose-6-Phosphat Rezeptor vermittelter Gentransfer zu Muskelzellen |
| US20050048495A1 (en) | 2003-08-29 | 2005-03-03 | Baker Brenda F. | Isoform-specific targeting of splice variants |
| US20050054752A1 (en) | 2003-09-08 | 2005-03-10 | O'brien John P. | Peptide-based diblock and triblock dispersants and diblock polymers |
| US7355018B2 (en) | 2003-09-30 | 2008-04-08 | Regeneron Pharmaceuticals, Inc. | Modified IGF1 polypeptides with increased stability and potency |
| JP2007508030A (ja) | 2003-10-14 | 2007-04-05 | カーネル・バイオファーマ・インコーポレイテッド | 血液脳関門を介してｐｎａを送達するための２相ｐｎａ結合体 |
| US20050244851A1 (en) * | 2004-01-13 | 2005-11-03 | Affymetrix, Inc. | Methods of analysis of alternative splicing in human |
| US20050191636A1 (en) | 2004-03-01 | 2005-09-01 | Biocept, Inc. | Detection of STRP, such as fragile X syndrome |
| WO2005086768A2 (en) | 2004-03-11 | 2005-09-22 | Albert Einstein College Of Medicine Of Yeshiva University | Enhanced production of functional proteins from defective genes |
| WO2005105995A2 (en) | 2004-04-14 | 2005-11-10 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED TREATMENT OF POLYGLUTAMINE (POLYQ) REPEAT EXPANSION DISEASES USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| EP1752536A4 (en) | 2004-05-11 | 2008-04-16 | Alphagen Co Ltd | POLYNUCLEOTIDE CAUSING RNA INTERFERENCE AND METHOD OF REGULATING GENE EXPRESSION WITH THE USE OF THE SAME |
| US20050288246A1 (en) | 2004-05-24 | 2005-12-29 | Iversen Patrick L | Peptide conjugated, inosine-substituted antisense oligomer compound and method |
| AU2005247508A1 (en) | 2004-05-27 | 2005-12-08 | Acceleron Pharma Inc. | Cerberus/coco derivatives and uses thereof |
| ATE498685T1 (de) | 2004-06-28 | 2011-03-15 | Univ Western Australia | Antisense-oligonukleotide zur induktion von exon- skipping sowie verfahren zur verwendung davon |
| US7361468B2 (en) | 2004-07-02 | 2008-04-22 | Affymetrix, Inc. | Methods for genotyping polymorphisms in humans |
| EP1618881A1 (en) | 2004-07-20 | 2006-01-25 | Santhera Pharmaceuticals (Schweiz) GmbH | Use of non-glucocorticoid steroids for the treatment of muscular dystrophy |
| US20110046200A1 (en) | 2004-08-03 | 2011-02-24 | Michael T Howard | Use of antisense oligonucleotides to effect translation modulation |
| US20060099612A1 (en) | 2004-09-02 | 2006-05-11 | Suntory Limited | Method for analyzing genes of industrial yeasts |
| AU2005335216A1 (en) | 2004-10-05 | 2007-02-15 | Wyeth | Probe arrays for detecting multiple strains of different species |
| ITRM20040568A1 (it) | 2004-11-18 | 2005-02-18 | Uni Degli Studi Di Roma Tor Vergata | Uso della tecnica "phage display" per l'identificazione di peptidi con capacita' di legame a cellule staminali/progenitore, peptidi cosi' ottenuti e loro usi. |
| US7838657B2 (en) | 2004-12-03 | 2010-11-23 | University Of Massachusetts | Spinal muscular atrophy (SMA) treatment via targeting of SMN2 splice site inhibitory sequences |
| US20120122801A1 (en) | 2005-01-05 | 2012-05-17 | Prosensa B.V. | Mannose-6-phosphate receptor mediated gene transfer into muscle cells |
| US20060148740A1 (en) | 2005-01-05 | 2006-07-06 | Prosensa B.V. | Mannose-6-phosphate receptor mediated gene transfer into muscle cells |
| EP1844148A2 (en) | 2005-01-31 | 2007-10-17 | University of Iowa Research Foundation | Nucleic acid silencing of huntington's disease gene |
| EP1877099B1 (en) | 2005-04-06 | 2012-09-19 | Genzyme Corporation | Therapeutic conjugates comprising a lysosomal enzyme, polysialic acid and a targeting moiety |
| NZ563206A (en) | 2005-04-22 | 2009-09-25 | Academisch Ziekenhuis Leiden | Modulation of exon recognition in pre-mRNA by interfering with the binding or SR proteins and by interfering with secondary RNA structure |
| US7902352B2 (en) | 2005-05-06 | 2011-03-08 | Medtronic, Inc. | Isolated nucleic acid duplex for reducing huntington gene expression |
| EP1885854B1 (en) | 2005-05-06 | 2012-10-17 | Medtronic, Inc. | Methods and sequences to suppress primate huntington gene expression |
| WO2007002904A2 (en) | 2005-06-28 | 2007-01-04 | Medtronic, Inc. | Methods and sequences to preferentially suppress expression of mutated huntingtin |
| PL2179737T3 (pl) | 2005-07-01 | 2014-01-31 | Index Pharmaceuticals Ab | Sposób do modulowania wrażliwości na steroidy |
| KR101789603B1 (ko) * | 2005-11-10 | 2017-11-21 | 더 유니버시티 오브 노쓰 캐롤라이나 엣 채플 힐 | Ｔｎｆ 수퍼패밀리 수용체에 대한 스플라이스 스위칭올리고머 및 염증성 질환 치료용 약제학적 조성물 |
| US7906617B2 (en) | 2005-12-15 | 2011-03-15 | E. I. Du Pont De Nemours And Company | Polyethylene binding peptides and methods of use |
| PT2161038E (pt) | 2006-01-26 | 2014-03-10 | Isis Pharmaceuticals Inc | Composições e suas utilizações dirigidas à huntingtina |
| US7901882B2 (en) * | 2006-03-31 | 2011-03-08 | Affymetrix, Inc. | Analysis of methylation using nucleic acid arrays |
| WO2007123391A1 (en) | 2006-04-20 | 2007-11-01 | Academisch Ziekenhuis Leiden | Therapeutic intervention in a genetic disease in an individual by modifying expression of an aberrantly expressed gene. |
| EP1857548A1 (en) | 2006-05-19 | 2007-11-21 | Academisch Ziekenhuis Leiden | Means and method for inducing exon-skipping |
| US7855053B2 (en) | 2006-07-19 | 2010-12-21 | The Regents Of The University Of California | Methods for detecting the presence of expanded CGG repeats in the FMR1 gene 5′ untranslated region |
| AU2007282224B2 (en) | 2006-08-11 | 2013-08-29 | Vico Therapeutics B.V. | Methods and means for treating DNA repeat instability associated genetic disorders |
| US20090253744A1 (en) | 2006-09-27 | 2009-10-08 | Bakshi Raman K | Acylated piperidine derivatives as melanocortin-4 receptor modulators |
| JP2010505897A (ja) | 2006-10-11 | 2010-02-25 | マックス−プランク−ゲゼルシャフト・ツア・フェルデルング・デア・ヴィッセンシャフテン・エー・ファオ | インフルエンザターゲット |
| PL381824A1 (pl) | 2007-02-22 | 2008-09-01 | Instytut Chemii Bioorganicznej Pan W Poznaniu | Sekwencja siRNA, wektor, cel molekularny dla reagentów siRNA i wektorów wprowadzanych do komórek i tkanek, sposób oceny specyficzności wyciszania zmutowanego transkryptu, sposób badania oddziaływań enzymów szlaku interferencji RNA z transkryptami oraz zastosowanie sekwencji siRNA i wektora |
| EP3443976A1 (en) * | 2007-06-29 | 2019-02-20 | Sarepta Therapeutics, Inc. | Tissue specific peptide conjugates and methods |
| WO2009008727A2 (en) | 2007-07-12 | 2009-01-15 | Prosensa Technologies B.V. | Molecules for targeting compounds to various selected organs or tissues |
| CA2693742A1 (en) | 2007-07-12 | 2009-01-15 | Prosensa Technologies B.V. | Molecules for targeting compounds to various selected organs, tissues or tumor cells |
| US9212205B2 (en) | 2007-07-26 | 2015-12-15 | University Of Rochester | Nucleic acid binding compounds and methods of use |
| WO2009023855A2 (en) | 2007-08-15 | 2009-02-19 | Isis Pharmaceuticals, Inc. | Tetrahydropyran nucleic acid analogs |
| AU2008317566B2 (en) | 2007-10-26 | 2014-05-01 | Academisch Ziekenhuis Leiden | Means and methods for counteracting muscle disorders |
| NZ587178A (en) | 2008-02-08 | 2011-11-25 | Prosensa Holding Bv | Methods and means for treating dna repeat instability associated genetic disorders |
| WO2009101399A1 (en) | 2008-02-12 | 2009-08-20 | Isis Innovation Limited | Treatment of muscular dystrophy using peptide nucleic acid ( pna) |
| EP2105145A1 (en) | 2008-03-27 | 2009-09-30 | ETH Zürich | Method for muscle-specific delivery lipid-conjugated oligonucleotides |
| CA2726866A1 (en) | 2008-05-09 | 2009-11-12 | The University Of British Columbia | Methods and compositions for the treatment of huntington's disease |
| 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 |
| US20110130346A1 (en) | 2008-05-30 | 2011-06-02 | Isis Innovation Limited | Peptide conjugates for delvery of biologically active compounds |
| US20110152352A1 (en) | 2008-06-10 | 2011-06-23 | Tufts University | Smad proteins control drosha-mediated mirna maturation |
| US8084601B2 (en) | 2008-09-11 | 2011-12-27 | Royal Holloway And Bedford New College Royal Holloway, University Of London | Oligomers |
| US8609615B2 (en) | 2008-10-15 | 2013-12-17 | Valerion Therapeutics, Llc | Methods and compositions for treatment of myotonic dystrophy |
| CN112574988A (zh) | 2008-10-24 | 2021-03-30 | 萨雷普塔治疗公司 | 用于dmd的多外显子跳跃组合物 |
| JP5786109B2 (ja) | 2008-10-27 | 2015-09-30 | プロセンサ テクノロジーズ ベー．フェー． | Ｄｕｃｈｅｎｎｅ型筋ジストロフィーｍＲＮＡ前駆体のエクソン４５の効率的なスキッピングのための方法及び手段 |
| BRPI1013410B1 (pt) | 2009-03-24 | 2020-10-06 | Asuragen, Inc. | Método de analisar se uma sequência de interrupção está presente em pelo menos uma região rica em cgg compreendida por pelo menos um molde em uma amostra |
| US20100248239A1 (en) | 2009-03-24 | 2010-09-30 | Mayo Foundation For Medical Education And Research | Methods and materials for detecting fragile x mutations |
| US20120149756A1 (en) | 2009-04-10 | 2012-06-14 | Associatin Institut de Myologie | Tricyclo-dna antisense oligonucleotides, compositions, and methods for the treatment of disease |
| CA2759899A1 (en) | 2009-04-24 | 2010-10-28 | Prosensa Technologies B.V. | Oligonucleotide comprising an inosine for treating dmd |
| EP3626823A1 (en) | 2009-09-11 | 2020-03-25 | Ionis Pharmaceuticals, Inc. | Modulation of huntingtin expression |
| LT2499249T (lt) | 2009-11-12 | 2018-12-27 | The University Of Western Australia | Priešprasmės molekulės ir patologijų gydymo būdai |
| US20110166081A1 (en) | 2009-12-03 | 2011-07-07 | University Of Iowa Research Foundation | Alpha-dystroglycan as a Protein Therapeutic |
| WO2011078797A2 (en) | 2009-12-22 | 2011-06-30 | Singapore Health Services Pte. Ltd | Antisense oligonucleotides and uses threreof |
| WO2011078672A1 (en) | 2009-12-24 | 2011-06-30 | Prosensa Technologies B.V. | Molecule for treating an inflammatory disorder |
| EP2536738A4 (en) | 2010-02-08 | 2014-09-17 | Isis Pharmaceuticals Inc | METHODS AND COMPOSITIONS FOR THE TREATMENT OF DISEASES OR SUFFERING IN CONNECTION WITH REPEAT EXTENSIONS |
| BR112013003875B1 (pt) | 2010-08-20 | 2021-10-05 | Replicor Inc | Composições farmacêuticas compreendendo complexo de quelato de oligonucleotídeo, formulação de oligonucleotídeo, e usos |
| TWI541024B (zh) | 2010-09-01 | 2016-07-11 | 日本新藥股份有限公司 | 反義核酸 |
| EP2672977A1 (en) | 2011-02-08 | 2013-12-18 | The Charlotte-Mecklenburg Hospital Authority d/b/a Carolina Healthcare System | Antisense oligonucleotides |
| JP2014513946A (ja) | 2011-04-22 | 2014-06-19 | プロセンサ テクノロジーズ ビー．ブイ． | 筋強直性ジストロフィー１型（ｄｍ１）などのヒト遺伝性疾患の治療、遅延及び／又は予防のための新規の化合物 |
| WO2012150960A1 (en) | 2011-05-05 | 2012-11-08 | Avi Biopharma, Inc. | Peptide oligonucleotide conjugates |
| CN117721110A (zh) | 2011-12-28 | 2024-03-19 | 日本新药株式会社 | 反义核酸 |
| CN112251436A (zh) | 2012-01-27 | 2021-01-22 | 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 |
| SMT201700339T1 (it) | 2012-04-23 | 2017-09-07 | Biomarin Tech Bv | Oligonucleotidi di modulazione dell'rna con caratteristiche migliorate per il trattamento dei disturbi neuromuscolari |
| 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 |
| EP2870246B1 (en) | 2012-07-03 | 2019-09-11 | BioMarin Technologies B.V. | Oligonucleotide for the treatment of muscular dystrophy patients |
-
2008
- 2008-05-14 EP EP08156193A patent/EP2119783A1/en not_active Ceased
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- 2009-05-14 NZ NZ589230A patent/NZ589230A/xx not_active IP Right Cessation
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