ES2955539T3 - Composiciones de omisión exónica múltiple para DMD - Google Patents
Composiciones de omisión exónica múltiple para DMD Download PDFInfo
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- ES2955539T3 ES2955539T3 ES21155461T ES21155461T ES2955539T3 ES 2955539 T3 ES2955539 T3 ES 2955539T3 ES 21155461 T ES21155461 T ES 21155461T ES 21155461 T ES21155461 T ES 21155461T ES 2955539 T3 ES2955539 T3 ES 2955539T3
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- Prior art keywords
- exon
- antisense
- dystrophin
- seq
- oligomer
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Classifications
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- 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
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
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- A—HUMAN NECESSITIES
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- 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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- 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
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
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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
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/111—General methods applicable to biologically active non-coding nucleic acids
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Families Citing this family (142)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004083432A1 (en) * | 2003-03-21 | 2004-09-30 | Academisch Ziekenhuis Leiden | Modulation of exon recognition in pre-mrna by interfering with the secondary rna structure |
| CA2523672C (en) | 2003-04-29 | 2012-07-17 | Avi Biopharma, Inc. | Compositions for enhancing transport of molecules into cells |
| CA2553104A1 (en) | 2004-01-23 | 2005-08-11 | Avi Biopharma, Inc. | Antisense oligomers and methods for inducing immune tolerance and immunosuppression |
| US20050288246A1 (en) | 2004-05-24 | 2005-12-29 | Iversen Patrick L | Peptide conjugated, inosine-substituted antisense oligomer compound and method |
| HUE028632T2 (en) | 2004-06-28 | 2016-12-28 | Univ Western Australia | Antisense oligonucleotides for inducing exon skipping and methods of use thereof |
| USRE48960E1 (en) | 2004-06-28 | 2022-03-08 | 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 |
| US8067571B2 (en) | 2005-07-13 | 2011-11-29 | Avi Biopharma, Inc. | Antibacterial antisense oligonucleotide and method |
| EP3443976A1 (en) * | 2007-06-29 | 2019-02-20 | 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 |
| NZ584793A (en) * | 2007-10-26 | 2012-05-25 | Academisch Ziekenhuis Leiden | Means and methods for counteracting muscle disorders |
| AU2008345033B2 (en) * | 2007-12-28 | 2014-04-03 | Sarepta Therapeutics, Inc. | Immunomodulatory agents and methods of use |
| 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 |
| IL313162A (en) | 2008-10-24 | 2024-07-01 | Sarepta Therapeutics Inc | Antisense compounds for inducing axon termination and preparations containing them for the treatment of muscular dystrophy |
| SI2607484T1 (sl) * | 2008-10-27 | 2016-11-30 | Biomarin Technologies B.V. | Metode in sredstva za učinkovito preskakovanje eksona 45 v pre-mRNA Duchennove mišične distrofije |
| EP2421971B1 (en) | 2009-04-24 | 2016-07-06 | BioMarin Technologies B.V. | Oligonucleotide comprising an inosine for treating dmd |
| US20110269665A1 (en) | 2009-06-26 | 2011-11-03 | Avi Biopharma, Inc. | Compound and method for treating myotonic dystrophy |
| NZ626359A (en) | 2009-11-12 | 2016-02-26 | Univ Western Australia | Antisense molecules and methods for treating pathologies |
| KR101981705B1 (ko) | 2010-05-28 | 2019-05-24 | 사렙타 쎄러퓨틱스, 인코퍼레이티드 | 변형된 서브유니트간 결합 및/또는 말단 그룹을 갖는 올리고뉴클레오타이드 유사체 |
| TWI541024B (zh) * | 2010-09-01 | 2016-07-11 | 日本新藥股份有限公司 | 反義核酸 |
| US10017763B2 (en) | 2010-09-03 | 2018-07-10 | Sarepta Therapeutics, Inc. | dsRNA molecules comprising oligonucleotide analogs having modified intersubunit linkages and/or terminal groups |
| BR112013020273A2 (pt) * | 2011-02-08 | 2016-10-18 | Charlotte Mecklenburg Hospital | oligonucleotídeos antissenso |
| US9161948B2 (en) | 2011-05-05 | 2015-10-20 | Sarepta Therapeutics, Inc. | Peptide oligonucleotide conjugates |
| KR102229650B1 (ko) * | 2011-05-05 | 2021-03-19 | 사렙타 쎄러퓨틱스, 인코퍼레이티드 | 펩타이드 올리고뉴클레오타이드 접합체 |
| US20140080896A1 (en) * | 2011-08-30 | 2014-03-20 | The Regents Of The University Of California | Identification of small molecules that facilitate therapeutic exon skipping |
| US20130085139A1 (en) | 2011-10-04 | 2013-04-04 | Royal Holloway And Bedford New College | Oligomers |
| US9278987B2 (en) | 2011-11-18 | 2016-03-08 | Sarepta Therapeutics, Inc. | Functionally-modified oligonucleotides and subunits thereof |
| PT2788487T (pt) | 2011-12-08 | 2018-07-03 | Sarepta Therapeutics Inc | Análogos de oligonucleótido visando lmna humano |
| CA3132111A1 (en) * | 2011-12-28 | 2013-07-04 | Nippon Shinyaku Co., Ltd. | Antisense nucleic acids for skipping of exon 55 of human dystrophin gene |
| EP4043039A1 (en) * | 2012-01-27 | 2022-08-17 | BioMarin Technologies B.V. | Rna modulating oligonucleotides with improved characteristics for the treatment of duchenne and becker muscular dystrophy |
| JP6928025B2 (ja) * | 2012-01-27 | 2021-09-01 | バイオマリン テクノロジーズ ベー．フェー． | デュシェンヌ型及びベッカー型筋ジストロフィーの治療のための改善された特徴を有するｒｎａ調節オリゴヌクレオチド |
| AU2013216828B2 (en) | 2012-02-09 | 2017-01-12 | Novus International Inc. | Functionalized polymer compositions |
| CN104411831B (zh) | 2012-03-20 | 2020-08-11 | 萨勒普塔医疗公司 | 寡核苷酸类似物的硼酸缀合物 |
| DE102012103041A1 (de) | 2012-04-10 | 2013-10-10 | Eberhard-Karls-Universität Tübingen Universitätsklinikum | Behandlung der dilativen Kardiomyopathie mittels Antisense-Oligonucleotiden |
| WO2013163628A2 (en) | 2012-04-27 | 2013-10-31 | Duke University | Genetic correction of mutated genes |
| EP3608407A1 (en) * | 2012-07-03 | 2020-02-12 | BioMarin Technologies B.V. | Oligonucleotide for the treatment of muscular dystrophy patients |
| MX2015000395A (es) | 2012-07-12 | 2015-04-10 | Novus Int Inc | Composiciones de matriz y capa para proteccion de bioactivos. |
| HK1216902A1 (zh) * | 2012-12-20 | 2016-12-09 | Sarepta Therapeutics, Inc. | 用作治疗肌肉萎缩的改进外显子跳跃组合物 |
| AU2014236140B2 (en) | 2013-03-14 | 2019-10-03 | Sarepta Therapeutics, Inc. | Exon skipping compositions for treating muscular dystrophy |
| BR112015023038A2 (pt) * | 2013-03-14 | 2017-11-14 | Sarepta Therapeutics Inc | composições para salto de exon para o tratamento da distrofia muscular |
| EP3662912B1 (en) | 2013-03-15 | 2025-12-03 | Sarepta Therapeutics, Inc. | Improved dosages of eteplirsen for treating duchenne muscular dystrophy |
| US9828582B2 (en) | 2013-03-19 | 2017-11-28 | Duke University | Compositions and methods for the induction and tuning of gene expression |
| WO2015097600A2 (en) | 2013-12-24 | 2015-07-02 | Sentiss Pharma Private Limited | Topical brimonidine tartrate ophthalmic solution |
| RS58573B1 (sr) * | 2014-03-12 | 2019-05-31 | Nippon Shinyaku Co Ltd | Antisensna nukleinska kiselina |
| BR112016027236A2 (pt) | 2014-05-23 | 2017-10-17 | Genzyme Corp | porções de múltiplos oligonucleotídeos em veículo de peptídeo |
| PT3159409T (pt) * | 2014-06-17 | 2020-01-21 | Nippon Shinyaku Co Ltd | Ácido nucleico anti-sentido para utilização no tratamento da distrofia muscular de duchenne |
| EP3180034B1 (en) * | 2014-08-11 | 2022-04-20 | The Board of Regents of The University of Texas System | Prevention of muscular dystrophy by crispr/cas9-mediated gene editing |
| KR20240123409A (ko) | 2014-09-07 | 2024-08-13 | 셀렉타 바이오사이언시즈, 인크. | 유전자 편집 항-바이러스 전달 벡터 면역 반응을 약화시키기 위한 방법 및 조성물 |
| US10676726B2 (en) | 2015-02-09 | 2020-06-09 | Duke University | Compositions and methods for epigenome editing |
| 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 |
| MA42134A (fr) | 2015-05-19 | 2018-03-28 | Sarepta Therapeutics Inc | Conjugués peptides/oligonucléotides |
| EP3302489A4 (en) | 2015-06-04 | 2019-02-06 | Sarepta Therapeutics, Inc. | METHOD AND COMPOUNDS FOR THE TREATMENT OF DISEASES AND SUFFERING IN CONNECTION WITH LYMPHOCYTES |
| 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 |
| RS60493B1 (sr) | 2015-09-15 | 2020-08-31 | Nippon Shinyaku Co Ltd | Antismisaona nukleinska kiselina |
| BR112018006445A2 (pt) * | 2015-09-30 | 2018-12-11 | Sarepta Therapeutics Inc | métodos para tratar distrofia muscular |
| US20190127733A1 (en) | 2015-10-09 | 2019-05-02 | Wave Life Sciences Ltd. | Oligonucleotide compositions and methods 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 |
| EP3362571A4 (en) | 2015-10-13 | 2019-07-10 | Duke University | GENOM ENGINEERING WITH TYPE I CRISPR SYSTEMS IN EUKARYOTIC CELLS |
| KR20250044471A (ko) | 2015-11-30 | 2025-03-31 | 듀크 유니버시티 | 유전자 편집에 의한 인간 디스트로핀 유전자의 교정을 위한 치료용 표적 및 사용 방법 |
| GB2545898B (en) * | 2015-12-21 | 2019-10-09 | Sutura Therapeutics Ltd | Improved drug delivery by conjugating oligonucleotides to stitched/stapled peptides |
| MA45328A (fr) | 2016-04-01 | 2019-02-06 | Avidity Biosciences Llc | Compositions acide nucléique-polypeptide et utilisations de celles-ci |
| US20190127713A1 (en) | 2016-04-13 | 2019-05-02 | Duke University | Crispr/cas9-based repressors for silencing gene targets in vivo and methods of use |
| MA45183A (fr) | 2016-05-24 | 2019-04-10 | Sarepta Therapeutics Inc | Procédés de préparation d'oligomères morpholino de phosphorodiamidate |
| US11472824B2 (en) | 2016-05-24 | 2022-10-18 | Sarepta Therapeutics, Inc. | Processes for preparing phosphorodiamidate morpholino oligomers |
| MD3464305T2 (ro) | 2016-05-24 | 2025-01-31 | Sarepta Therapeutics Inc | Procedee de preparare de oligomeri |
| CA3025575A1 (en) | 2016-06-30 | 2018-01-04 | Sarepta Therapeutics, Inc. | Exon skipping oligomers for muscular dystrophy |
| US12214056B2 (en) | 2016-07-19 | 2025-02-04 | Duke University | Therapeutic applications of CPF1-based genome editing |
| WO2018098480A1 (en) * | 2016-11-28 | 2018-05-31 | The Board Of Regents Of The University Of Texas System | Prevention of muscular dystrophy by crispr/cpf1-mediated gene editing |
| KR102646318B1 (ko) | 2016-12-19 | 2024-03-12 | 사렙타 쎄러퓨틱스 인코퍼레이티드 | 근육 이상증에 대한 엑손 스킵핑 올리고머 결합체 |
| AU2017382723B2 (en) | 2016-12-19 | 2025-01-30 | Sarepta Therapeutics, Inc. | Exon skipping oligomer conjugates for muscular dystrophy |
| AU2017382741B2 (en) * | 2016-12-19 | 2025-01-30 | Sarepta Therapeutics, Inc. | Exon skipping oligomer conjugates for muscular dystrophy |
| SG11201906200WA (en) * | 2017-01-06 | 2019-08-27 | Avidity Biosciences Llc | Nucleic acid-polypeptide compositions and methods of inducing exon skipping |
| AU2017407272B2 (en) * | 2017-03-30 | 2024-06-13 | Kyoto University | Method for inducing exon skipping by genome editing |
| EP3641741B1 (en) | 2017-06-19 | 2024-03-20 | University of Maryland, Baltimore | Microtubule polymerization inhibitor prodrugs and methods of using the same |
| CN111164211B (zh) | 2017-07-18 | 2024-08-02 | 杰特贝林基因治疗股份有限公司 | 用于治疗β-血红蛋白病的组合物和方法 |
| GB201711809D0 (en) | 2017-07-21 | 2017-09-06 | Governors Of The Univ Of Alberta | Antisense oligonucleotide |
| CN109295053B (zh) * | 2017-07-25 | 2023-12-22 | 中国科学院上海营养与健康研究所 | 通过诱导剪接位点碱基突变或多聚嘧啶区碱基置换调控rna剪接的方法 |
| US10584306B2 (en) | 2017-08-11 | 2020-03-10 | Board Of Regents Of The University Of Oklahoma | Surfactant microemulsions |
| EA201991450A1 (ru) | 2017-09-22 | 2019-12-30 | Сарепта Терапьютикс, Инк. | Конъюгаты олигомеров для пропуска экзона при мышечной дистрофии |
| US20200282074A1 (en) * | 2017-09-22 | 2020-09-10 | Avidity Biosciences, Inc. | Nucleic acid-polypeptide compositions and methods of inducing exon skipping |
| MX2020003838A (es) | 2017-10-13 | 2020-08-06 | Selecta Biosciences Inc | Metodos y composiciones para atenuar las respuestas de inmunoglobulina m del vector de transferencia antiviral. |
| EP3697910A4 (en) * | 2017-10-18 | 2021-07-14 | Sarepta Therapeutics, Inc. | ANTISENSE OLIGOMER COMPOUNDS |
| SG11202005022YA (en) | 2017-12-06 | 2020-06-29 | Avidity Biosciences Inc | Compositions and methods of treating muscle atrophy and myotonic dystrophy |
| EP3740580A4 (en) | 2018-01-19 | 2021-10-20 | Duke University | GENOMIC ENGINEERING WITH CRISPR-CAS SYSTEMS IN EUKARYOTES |
| BR112020015617A2 (pt) * | 2018-01-31 | 2021-01-05 | The Board Of Regents Of The University Of Texas System | Composições e métodos para correção de mutações da distrofina em cardiomiócitos humanos |
| JP7575273B2 (ja) | 2018-04-16 | 2024-10-29 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | デュシェンヌ型筋ジストロフィーを治療するための組成物及び方法 |
| US20210102205A1 (en) * | 2018-04-26 | 2021-04-08 | Sarepta Therapeutics, Inc. | Exon skipping oligomers and oligomer conjugates for muscular dystrophy |
| US10758629B2 (en) * | 2018-05-29 | 2020-09-01 | Sarepta Therapeutics, Inc. | Exon skipping oligomer conjugates for muscular dystrophy |
| WO2019241385A2 (en) * | 2018-06-13 | 2019-12-19 | Sarepta Therapeutics, Inc. | Exon skipping oligomers for muscular dystropy |
| MY209148A (en) | 2018-06-26 | 2025-06-24 | Nippon Shinyaku Co Ltd | Composition comprising antisense oligonucleotide and use thereof for treatment of duchenne muscular dystrophy |
| US12370264B1 (en) | 2018-08-02 | 2025-07-29 | Dyne Therapeutics, Inc. | Complexes comprising an anti-transferrin receptor antibody linked to an oligonucleotide and method of delivering oligonucleotide to a subject |
| SG11202100934PA (en) | 2018-08-02 | 2021-02-25 | Dyne Therapeutics Inc | Muscle targeting complexes and uses thereof for treating dystrophinopathies |
| US11911484B2 (en) | 2018-08-02 | 2024-02-27 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating myotonic dystrophy |
| US11168141B2 (en) | 2018-08-02 | 2021-11-09 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating dystrophinopathies |
| US12097263B2 (en) | 2018-08-02 | 2024-09-24 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating myotonic dystrophy |
| WO2020028864A1 (en) | 2018-08-02 | 2020-02-06 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating facioscapulohumeral muscular dystrophy |
| 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 |
| GB201812972D0 (en) | 2018-08-09 | 2018-09-26 | Univ Oxford Innovation Ltd | Cell-penetrating peptides |
| GB201812980D0 (en) | 2018-08-09 | 2018-09-26 | Univ Oxford Innovation Ltd | Cell-penetrating peptides |
| US12331293B2 (en) | 2018-11-02 | 2025-06-17 | Biomarin Technologies B.V. | Bispecific antisense oligonucleotides for dystrophin exon skipping |
| CA3122200A1 (en) | 2018-12-07 | 2020-06-11 | Oxford University Innovation Limited | Linkers |
| IL283646B2 (en) * | 2018-12-13 | 2025-11-01 | Sarepta Therapeutics Inc | Exon skipping oligomer conjugates for muscular dystrophy |
| CA3123045A1 (en) | 2018-12-23 | 2020-07-02 | Csl Behring L.L.C. | Donor t-cells with kill switch |
| BR112021012240A2 (pt) | 2018-12-23 | 2022-01-18 | Csl Behring Llc | Terapia de gene-célula-tronco hematopoiética para síndrome wiskott-aldrich |
| EP3954395A4 (en) * | 2019-04-08 | 2023-06-28 | National University Corporation Tokyo Medical and Dental University | Pharmaceutical composition for muscle disease treatment |
| EP3959319A4 (en) * | 2019-04-25 | 2023-06-07 | Avidity Biosciences, Inc. | NUCLEIC ACID COMPOSITIONS AND METHODS FOR MULTI-EXON SKIPPING |
| KR20220015425A (ko) | 2019-05-28 | 2022-02-08 | 셀렉타 바이오사이언시즈, 인크. | 약화된 항바이러스 전달 벡터 면역 반응을 위한 방법 및 조성물 |
| EP3997228A4 (en) * | 2019-07-09 | 2024-05-15 | The Governors of the University of Alberta | SKIP OF EXONS 45 TO 55 USING MUTATION-ADAPTED COCKTAILS, OF ANTISENS MORPHOLINOS, IN THE DMD GENE |
| CA3149488A1 (en) * | 2019-08-02 | 2021-02-11 | Research Institute At Nationwide Children's Hospital | Exon 44-targeted nucleic acids and recombinant adeno-associated virus comprising said nucleic acids for treatment of dystrophin-based myopathies |
| AU2020408773A1 (en) * | 2019-12-19 | 2022-07-14 | National Center Of Neurology And Psychiatry | Antisense nucleic acid enabling exon skipping |
| CA3165961A1 (en) | 2019-12-26 | 2021-07-01 | Nippon Shinyaku Co., Ltd. | Antisense nucleic acid that induces skipping of exon 50 |
| MX2022010545A (es) | 2020-02-28 | 2022-09-21 | Nippon Shinyaku Co Ltd | Acidos nucleicos antisentido que inducen la omision del exon 51. |
| JP7788060B2 (ja) | 2020-03-19 | 2025-12-18 | アビディティー バイオサイエンシーズ，インク． | 顔面肩甲上腕型筋ジストロフィーを処置するための組成物および方法 |
| EP4172335A1 (en) | 2020-06-26 | 2023-05-03 | CSL Behring LLC | Donor t-cells with kill switch |
| EP3978608A1 (en) * | 2020-10-05 | 2022-04-06 | SQY Therapeutics | Oligomeric compound for dystrophin rescue in dmd patients throughout skipping of exon-51 |
| AU2021427595A1 (en) * | 2021-02-12 | 2023-09-28 | Oxford University Innovation Limited | Cell-penetrating peptide conjugates and methods of their use |
| IL307298A (en) | 2021-03-31 | 2023-11-01 | Entrada Therapeutics Inc | Cell-penetrating circular peptides |
| US20240358845A1 (en) | 2021-05-10 | 2024-10-31 | Entrada Therapeutics, Inc. | Compositions and methods for intracellular therapeutics |
| US20240287511A1 (en) | 2021-05-13 | 2024-08-29 | National University Corporation Chiba University | Antisense Oligomer |
| KR20240013202A (ko) * | 2021-05-28 | 2024-01-30 | 스미토모 파마 가부시키가이샤 | 안티센스 핵산 |
| JP7522079B2 (ja) | 2021-06-16 | 2024-07-24 | 株式会社神戸製鋼所 | 積層計画作成方法 |
| US12378267B2 (en) | 2021-06-17 | 2025-08-05 | Entrada Therapeutics, Inc. | Synthesis of FMOC-protected morpholino monomers and oligomers |
| MX2023014417A (es) | 2021-06-23 | 2023-12-15 | Nippon Shinyaku Co Ltd | Combinacion de oligomeros antisentido. |
| US11648318B2 (en) | 2021-07-09 | 2023-05-16 | Dyne Therapeutics, Inc. | Anti-transferrin receptor (TFR) antibody and uses thereof |
| US11771776B2 (en) | 2021-07-09 | 2023-10-03 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating dystrophinopathies |
| US11633498B2 (en) | 2021-07-09 | 2023-04-25 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating myotonic dystrophy |
| US11638761B2 (en) | 2021-07-09 | 2023-05-02 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating Facioscapulohumeral muscular dystrophy |
| US11969475B2 (en) | 2021-07-09 | 2024-04-30 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating facioscapulohumeral muscular dystrophy |
| CA3226366A1 (en) | 2021-07-09 | 2023-01-12 | Dyne Therapeutics, Inc. | Muscle targeting complexes and formulations for treating dystrophinopathies |
| US11912779B2 (en) | 2021-09-16 | 2024-02-27 | Avidity Biosciences, Inc. | Compositions and methods of treating facioscapulohumeral muscular dystrophy |
| US20230141563A1 (en) | 2021-10-12 | 2023-05-11 | Selecta Biosciences, Inc. | Methods and compositions for attenuating anti-viral transfer vector igm responses |
| JPWO2023127918A1 (enExample) | 2021-12-27 | 2023-07-06 | ||
| EP4215614A1 (en) | 2022-01-24 | 2023-07-26 | Dynacure | Combination therapy for dystrophin-related diseases |
| US20230357437A1 (en) | 2022-03-09 | 2023-11-09 | Selecta Biosciences, Inc. | Immunosuppressants in combination with anti-igm agents and related dosing |
| US12071621B2 (en) | 2022-04-05 | 2024-08-27 | Avidity Biosciences, Inc. | Anti-transferrin receptor antibody-PMO conjugates for inducing DMD exon 44 skipping |
| JP2025512464A (ja) | 2022-04-15 | 2025-04-17 | ダイン セラピューティクス，インコーポレーテッド | 筋緊張性ジストロフィーを処置するための筋標的化複合体および製剤 |
| JP2025513521A (ja) | 2022-04-22 | 2025-04-24 | エントラーダ セラピューティクス，インコーポレイティド | 治療薬を送達するための環状ペプチド |
| IL317874A (en) | 2022-06-24 | 2025-02-01 | Tune Therapeutics Inc | Compounds, systems and methods for reducing low density lipoproteins through targeted gene suppression |
| WO2024112809A2 (en) * | 2022-11-21 | 2024-05-30 | Pepgen Inc. | Cell-penetrating peptides, conjugates thereof, and methods of their use |
| WO2025072246A1 (en) * | 2023-09-26 | 2025-04-03 | Entrada Therapeutics, Inc. | Compounds and methods for skipping exon 50 in duchenne muscular dystrophy |
| WO2025072886A1 (en) * | 2023-09-28 | 2025-04-03 | Wave Life Sciences Ltd. | Oligonucleotide compositions and methods thereof |
Family Cites Families (134)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH445129A (fr) | 1964-04-29 | 1967-10-15 | Nestle Sa | Procédé pour la préparation de composés d'inclusion à poids moléculaire élevé |
| US3459731A (en) | 1966-12-16 | 1969-08-05 | Corn Products Co | Cyclodextrin polyethers and their production |
| US3453257A (en) | 1967-02-13 | 1969-07-01 | Corn Products Co | Cyclodextrin with cationic properties |
| US3426011A (en) | 1967-02-13 | 1969-02-04 | Corn Products Co | Cyclodextrins with anionic properties |
| US3453259A (en) | 1967-03-22 | 1969-07-01 | Corn Products Co | Cyclodextrin polyol ethers and their oxidation products |
| US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
| US4458066A (en) * | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing polynucleotides |
| DE3100514A1 (de) | 1981-01-10 | 1982-08-05 | Robert Bosch Gmbh, 7000 Stuttgart | Vorrichtung zur steuerung eines durchflussquerschnittes in einer steuerleitung |
| US5190931A (en) | 1983-10-20 | 1993-03-02 | The Research Foundation Of State University Of New York | Regulation of gene expression by employing translational inhibition of MRNA utilizing interfering complementary MRNA |
| US5521063A (en) | 1985-03-15 | 1996-05-28 | Antivirals Inc. | Polynucleotide reagent containing chiral subunits and methods of use |
| US5506337A (en) | 1985-03-15 | 1996-04-09 | Antivirals Inc. | Morpholino-subunit combinatorial library and method |
| US5166315A (en) | 1989-12-20 | 1992-11-24 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
| US5217866A (en) | 1985-03-15 | 1993-06-08 | Anti-Gene Development Group | Polynucleotide assay reagent and method |
| ATE171185T1 (de) | 1985-03-15 | 1998-10-15 | Antivirals Inc | Immunotestmittel für polynukleotid und verfahren |
| US5185444A (en) | 1985-03-15 | 1993-02-09 | Anti-Gene Deveopment Group | Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages |
| US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
| US4737323A (en) | 1986-02-13 | 1988-04-12 | Liposome Technology, Inc. | Liposome extrusion method |
| KR0166088B1 (ko) | 1990-01-23 | 1999-01-15 | . | 수용해도가 증가된 시클로덱스트린 유도체 및 이의 용도 |
| US5149797A (en) * | 1990-02-15 | 1992-09-22 | The Worcester Foundation For Experimental Biology | Method of site-specific alteration of rna and production of encoded polypeptides |
| US5138045A (en) | 1990-07-27 | 1992-08-11 | Isis Pharmaceuticals | Polyamine conjugated oligonucleotides |
| US20020123476A1 (en) * | 1991-03-19 | 2002-09-05 | Emanuele R. Martin | Therapeutic delivery compositions and methods of use thereof |
| US5869252A (en) * | 1992-03-31 | 1999-02-09 | Abbott Laboratories | Method of multiplex ligase chain reaction |
| AU3942993A (en) | 1992-03-31 | 1993-11-08 | Abbott Laboratories | Method of multiplex ligase chain reaction |
| US6806084B1 (en) * | 1992-06-04 | 2004-10-19 | The Regents Of The University Of California | Methods for compositions for in vivo gene delivery |
| EP0786522A2 (en) | 1992-07-17 | 1997-07-30 | Ribozyme Pharmaceuticals, Inc. | Enzymatic RNA molecules for treatment of stenotic conditions |
| US5985558A (en) | 1997-04-14 | 1999-11-16 | Isis Pharmaceuticals Inc. | Antisense oligonucleotide compositions and methods for the inibition of c-Jun and c-Fos |
| FI955428A7 (fi) | 1993-05-11 | 1996-01-04 | The Univ Of North Carolina At | Antisene-oligonukleotideja, jotka vastustavat poikkeavaa kietoutumista , ja menetelmiä niiden käyttämiseksi |
| US5801154A (en) * | 1993-10-18 | 1998-09-01 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of multidrug resistance-associated protein |
| US6391636B1 (en) | 1994-05-31 | 2002-05-21 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of raf gene expression |
| 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 |
| IL115849A0 (en) | 1994-11-03 | 1996-01-31 | Merz & Co Gmbh & Co | Tangential filtration preparation of liposomal drugs and liposome product thereof |
| GB9510718D0 (en) * | 1995-05-26 | 1995-07-19 | Sod Conseils Rech Applic | Antisense oligonucleotides |
| ATE267207T1 (de) | 1996-02-14 | 2004-06-15 | Isis Pharmaceuticals Inc | Kohlenhydratmodifizierte luckenhafte oligonukleotide |
| WO1997034638A1 (en) | 1996-03-20 | 1997-09-25 | The Regents Of The University Of California | Antisense approach to gene inhibition |
| US6153436A (en) * | 1997-01-10 | 2000-11-28 | The Board Of Trustees Of The University Of Arkansas | Method of gene delivery using wildtype adeno associated viral (AAV) vectors with insertions |
| WO1999042091A2 (en) | 1998-02-19 | 1999-08-26 | Massachusetts Institute Of Technology | Use of polycations as endosomolytic agents |
| US20030114401A1 (en) | 2001-12-06 | 2003-06-19 | Isis Pharmaceuticals Inc. | Antisense modulation of Ship-1 expression |
| GB9819999D0 (en) | 1998-09-14 | 1998-11-04 | Univ London | Treatment of cancer |
| US6210892B1 (en) | 1998-10-07 | 2001-04-03 | Isis Pharmaceuticals, Inc. | Alteration of cellular behavior by antisense modulation of mRNA processing |
| EP1135121B1 (en) | 1998-11-13 | 2003-03-12 | Eli Lilly And Company | Combination of duloxetine with non-steroidal antiinflammatory drug for treating pain |
| CA2360997A1 (en) | 1999-01-29 | 2000-08-03 | Avi Biopharma, Inc. | Non-invasive method for detecting target rna |
| US20020049173A1 (en) | 1999-03-26 | 2002-04-25 | Bennett C. Frank | Alteration of cellular behavior by antisense modulation of mRNA processing |
| 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 |
| CA2374499A1 (en) * | 1999-05-24 | 2000-11-30 | Avi Biopharma, Inc. | Antisense to c-myc for treatment of polycystic kidney disease |
| CA2376284A1 (en) | 1999-06-21 | 2000-12-28 | Murdoch Childrens Research Institute | A method for the prophylaxis and/or treatment of medical disorders |
| US7070807B2 (en) | 1999-12-29 | 2006-07-04 | Mixson A James | Branched histidine copolymers and methods for using same |
| EP1242052A4 (en) | 1999-12-29 | 2003-07-02 | A James Mixson | HISTIDIN COPOLYMER AND METHODS OF USE THEREOF |
| WO2001049775A2 (en) | 2000-01-04 | 2001-07-12 | Avi Biopharma, Inc. | Antisense antibacterial cell division composition and method |
| CA2400573A1 (en) | 2000-03-28 | 2001-10-04 | Isis Pharmaceuticals Inc. | Alteration of cellular behavior by antisense modulation of mrna processing |
| US6653467B1 (en) * | 2000-04-26 | 2003-11-25 | Jcr Pharmaceutical Co., Ltd. | Medicament for treatment of Duchenne muscular dystrophy |
| ES2330615T3 (es) | 2000-04-28 | 2009-12-14 | Asklepios Biopharmaceutical, Inc. | Secuencias de adn que codifican para minigenes de distrofina y metodos de uso de las mismas. |
| EP1278761B1 (en) | 2000-05-01 | 2005-04-06 | Hybridon, Inc. | MODULATION OF OLIGONUCLEOTIDE CpG-MEDIATED IMMUNE STIMULATION BY POSITIONAL MODIFICATION OF NUCLEOSIDES |
| WO2001083740A2 (en) * | 2000-05-04 | 2001-11-08 | Avi Biopharma, Inc. | Splice-region antisense composition and method |
| 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 |
| ES2263651T3 (es) | 2000-08-30 | 2006-12-16 | Avi Biopharma, Inc. | Metodo para analidis de analogos de oligonucleotidos. |
| US6559279B1 (en) * | 2000-09-08 | 2003-05-06 | Isis Pharmaceuticals, Inc. | Process for preparing peptide derivatized oligomeric compounds |
| US20070037165A1 (en) * | 2000-09-08 | 2007-02-15 | Applera Corporation | Polymorphisms in known genes associated with human disease, methods of detection and uses thereof |
| EP1319014A1 (en) * | 2000-09-20 | 2003-06-18 | Isis Pharmaceuticals, Inc. | Antisense modulation of flip-c expression |
| EP1191097A1 (en) * | 2000-09-21 | 2002-03-27 | Leids Universitair Medisch Centrum | Induction of exon skipping in eukaryotic cells |
| US6689615B1 (en) | 2000-10-04 | 2004-02-10 | James Murto | Methods and devices for processing blood samples |
| JP3781687B2 (ja) | 2001-02-23 | 2006-05-31 | 松下電器産業株式会社 | 遺伝子診断装置及び遺伝子診断方法 |
| US6656732B1 (en) * | 2001-05-18 | 2003-12-02 | Isis Pharmaceuticals, Inc. | Antisense inhibition of src-c expression |
| US20030224353A1 (en) * | 2001-10-16 | 2003-12-04 | Stein David A. | Antisense antiviral agent and method for treating ssRNA viral infection |
| EP2314691A3 (en) | 2002-11-14 | 2012-01-18 | Dharmacon, Inc. | Fuctional and hyperfunctional siRNA |
| US7655785B1 (en) * | 2002-11-14 | 2010-02-02 | Rosetta Genomics Ltd. | Bioinformatically detectable group of novel regulatory oligonucleotides and uses thereof |
| US7314750B2 (en) * | 2002-11-20 | 2008-01-01 | Affymetrix, Inc. | Addressable oligonucleotide array of the rat genome |
| US7250289B2 (en) * | 2002-11-20 | 2007-07-31 | Affymetrix, Inc. | Methods of genetic analysis of mouse |
| ES2509140T3 (es) | 2002-11-25 | 2014-10-17 | Masafumi Matsuo | Fármacos de ácido nucleico ENA que modifican el corte y empalme en precursores de ARNm |
| WO2004083432A1 (en) | 2003-03-21 | 2004-09-30 | Academisch Ziekenhuis Leiden | Modulation of exon recognition in pre-mrna by interfering with the secondary rna structure |
| CA2523672C (en) * | 2003-04-29 | 2012-07-17 | Avi Biopharma, Inc. | Compositions for enhancing transport of molecules into cells |
| EP1495769B1 (en) | 2003-07-11 | 2008-02-27 | LBR Medbiotech B.V. | Mannose-6-phosphate receptor mediated gene transfer into muscle cells |
| CN1829794B (zh) | 2003-08-05 | 2011-06-08 | Avi生物制药公司 | 寡核苷酸类似物和用于治疗黄病毒感染的方法 |
| US20050048495A1 (en) | 2003-08-29 | 2005-03-03 | Baker Brenda F. | Isoform-specific targeting of splice variants |
| US20050153935A1 (en) * | 2003-09-12 | 2005-07-14 | Iversen Patrick L. | Compound and method for treating androgen-independent prostate cancer |
| US20050171044A1 (en) | 2003-12-24 | 2005-08-04 | Stein David A. | Oligonucleotide compound and method for treating nidovirus infections |
| US20050288246A1 (en) | 2004-05-24 | 2005-12-29 | Iversen Patrick L | Peptide conjugated, inosine-substituted antisense oligomer compound and method |
| HUE028632T2 (en) | 2004-06-28 | 2016-12-28 | Univ Western Australia | Antisense oligonucleotides for inducing exon skipping and methods of use thereof |
| 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 |
| US8129352B2 (en) | 2004-09-16 | 2012-03-06 | Avi Biopharma, Inc. | Antisense antiviral compound and method for treating ssRNA viral infection |
| US20060148740A1 (en) | 2005-01-05 | 2006-07-06 | Prosensa B.V. | Mannose-6-phosphate receptor mediated gene transfer into muscle cells |
| US20120122801A1 (en) * | 2005-01-05 | 2012-05-17 | Prosensa B.V. | Mannose-6-phosphate receptor mediated gene transfer into muscle cells |
| CA2596506C (en) | 2005-02-09 | 2021-04-06 | Avi Biopharma, Inc. | Antisense composition and method for treating muscle atrophy |
| JP2008538500A (ja) * | 2005-04-22 | 2008-10-30 | アカデミス ツィーケンホイス ライデン | ＳＲタンパク質の結合に対する干渉とＲＮＡ二次構造に対する干渉による、ｍＲＮＡ前駆体におけるエクソン認識の調節 |
| US8067571B2 (en) * | 2005-07-13 | 2011-11-29 | Avi Biopharma, Inc. | Antibacterial antisense oligonucleotide and method |
| WO2007028065A2 (en) | 2005-08-30 | 2007-03-08 | Isis Pharmaceuticals, Inc. | Chimeric oligomeric compounds for modulation of splicing |
| US8524676B2 (en) | 2005-09-08 | 2013-09-03 | Sarepta Therapeutics, Inc. | Method for treating enterovirus or rhinovirus infection using antisense antiviral compounds |
| US8501704B2 (en) | 2005-11-08 | 2013-08-06 | Sarepta Therapeutics, Inc. | Immunosuppression compound and treatment method |
| WO2007058894A2 (en) | 2005-11-10 | 2007-05-24 | The University Of North Carolina At Chapel Hill | Splice switching oligomers for tnf superfamily receptors and their use in treatment of disease |
| WO2007133812A2 (en) * | 2005-12-30 | 2007-11-22 | Philadelphia Health & Education Corporation, D/B/A Drexel University College Of Medicine | Improved carriers for delivery of nucleic acid agents to cells and tissues |
| US8785407B2 (en) | 2006-05-10 | 2014-07-22 | Sarepta Therapeutics, Inc. | Antisense antiviral agent and method for treating ssRNA viral infection |
| EP2024499B1 (en) * | 2006-05-10 | 2017-10-25 | Sarepta Therapeutics, Inc. | Oligonucleotide analogs having cationic intersubunit linkages |
| US20070265215A1 (en) | 2006-05-11 | 2007-11-15 | Iversen Patrick L | Antisense restenosis composition and method |
| EP1857548A1 (en) | 2006-05-19 | 2007-11-21 | Academisch Ziekenhuis Leiden | Means and method for inducing exon-skipping |
| US20100016215A1 (en) * | 2007-06-29 | 2010-01-21 | Avi Biopharma, Inc. | Compound and method for treating myotonic dystrophy |
| EP3443976A1 (en) * | 2007-06-29 | 2019-02-20 | Sarepta Therapeutics, Inc. | Tissue specific peptide conjugates and methods |
| NZ584793A (en) | 2007-10-26 | 2012-05-25 | Academisch Ziekenhuis Leiden | Means and methods for counteracting muscle disorders |
| WO2009101399A1 (en) | 2008-02-12 | 2009-08-20 | Isis Innovation Limited | Treatment of muscular dystrophy using peptide nucleic acid ( pna) |
| 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 |
| IL313162A (en) | 2008-10-24 | 2024-07-01 | Sarepta Therapeutics Inc | Antisense compounds for inducing axon termination and preparations containing them for the treatment of muscular dystrophy |
| SI2607484T1 (sl) | 2008-10-27 | 2016-11-30 | Biomarin Technologies B.V. | Metode in sredstva za učinkovito preskakovanje eksona 45 v pre-mRNA Duchennove mišične distrofije |
| AU2009335740B2 (en) | 2008-12-17 | 2016-04-21 | Sarepta Therapeutics, Inc. | Antisense compositions and methods for modulating contact hypersensitivity or contact dermatitis |
| PT2417257E (pt) | 2009-04-10 | 2016-06-03 | Universität Bern | Oligonucleótidos triciclo-dna anti-sentido, composições, e métodos para o tratamento de doença |
| EP2421971B1 (en) | 2009-04-24 | 2016-07-06 | BioMarin Technologies B.V. | Oligonucleotide comprising an inosine for treating dmd |
| EP2258863A1 (en) * | 2009-05-25 | 2010-12-08 | Universita'Degli Studi di Roma "La Sapienza" | miRNA biomarkers for the diagnosis of duchenne muscular dystrophy progression, for monitoring therapeutic interventions, and as therapeutics |
| US9034838B2 (en) | 2009-05-25 | 2015-05-19 | Universita Degli Studi Di Roma “La Sapienza” | miR-31 in duchenne muscular dystrophy therapy |
| US20110269665A1 (en) | 2009-06-26 | 2011-11-03 | Avi Biopharma, Inc. | Compound and method for treating myotonic dystrophy |
| ITTO20090487A1 (it) | 2009-06-26 | 2010-12-27 | Univ Ferrara | Oligonucleotidi antisenso atti ad indurre lo skipping esonico e loro impiego come medicamento per il trattamento della distrofia muscolare di duchenne (dmd) |
| US20120172415A1 (en) * | 2009-08-31 | 2012-07-05 | Thomas Voit | Exon Skipping Therapy for Functional Amelioration of Semifunctional Dystrophin in Becker and Duchenne Muscular Dystrophy |
| IT1397011B1 (it) | 2009-10-14 | 2012-12-20 | Univ Ferrara | Nanoparticella del tipo core-shell idonea per la veicolazione di oligonucleotidi terapeutici in tessuti bersaglio e suo impiego per la preparazione di un medicamento per il trattamento della distrofia muscolare di duchenne. |
| NZ626359A (en) | 2009-11-12 | 2016-02-26 | Univ Western Australia | Antisense molecules and methods for treating pathologies |
| TWI495473B (zh) | 2009-11-13 | 2015-08-11 | Sarepta Therapeutics Inc | 反義抗病毒化合物及治療流感病毒感染的方法 |
| US9050373B2 (en) | 2010-05-13 | 2015-06-09 | The Charlotte-Mecklenburg Hospital Authority | Pharmaceutical compositions comprising antisense oligonucleotides and methods of using same |
| KR101981705B1 (ko) | 2010-05-28 | 2019-05-24 | 사렙타 쎄러퓨틱스, 인코퍼레이티드 | 변형된 서브유니트간 결합 및/또는 말단 그룹을 갖는 올리고뉴클레오타이드 유사체 |
| US9241929B2 (en) | 2010-06-28 | 2016-01-26 | Masatoshi Hagiwara | Prophylactic or ameliorating agent for genetic diseases |
| TWI541024B (zh) | 2010-09-01 | 2016-07-11 | 日本新藥股份有限公司 | 反義核酸 |
| PL2623507T3 (pl) | 2010-09-30 | 2017-03-31 | Nippon Shinyaku Co., Ltd. | Pochodna kwasu morfolinonukleinowego |
| BR112013020273A2 (pt) * | 2011-02-08 | 2016-10-18 | Charlotte Mecklenburg Hospital | oligonucleotídeos antissenso |
| US9161948B2 (en) | 2011-05-05 | 2015-10-20 | Sarepta Therapeutics, Inc. | Peptide oligonucleotide conjugates |
| KR102229650B1 (ko) | 2011-05-05 | 2021-03-19 | 사렙타 쎄러퓨틱스, 인코퍼레이티드 | 펩타이드 올리고뉴클레오타이드 접합체 |
| US20140080896A1 (en) | 2011-08-30 | 2014-03-20 | The Regents Of The University Of California | Identification of small molecules that facilitate therapeutic exon skipping |
| WO2013033407A2 (en) | 2011-08-30 | 2013-03-07 | The Regents Of The University Of California | Identification of small molecules that enhance therapeutic exon skipping |
| EP2581448B1 (en) | 2011-10-13 | 2015-01-28 | Association Institut de Myologie | Tricyclo-phosphorothioate DNA |
| CA3132111A1 (en) | 2011-12-28 | 2013-07-04 | Nippon Shinyaku Co., Ltd. | Antisense nucleic acids for skipping of exon 55 of human dystrophin gene |
| EP4043039A1 (en) | 2012-01-27 | 2022-08-17 | BioMarin Technologies B.V. | Rna modulating oligonucleotides with improved characteristics for the treatment of duchenne and becker muscular dystrophy |
| EP3608407A1 (en) | 2012-07-03 | 2020-02-12 | BioMarin Technologies B.V. | Oligonucleotide for the treatment of muscular dystrophy patients |
| US10071013B2 (en) | 2012-07-20 | 2018-09-11 | Thomas R. Allen | Massager and method of making the same |
| HK1216902A1 (zh) | 2012-12-20 | 2016-12-09 | Sarepta Therapeutics, Inc. | 用作治疗肌肉萎缩的改进外显子跳跃组合物 |
| AU2014236140B2 (en) | 2013-03-14 | 2019-10-03 | Sarepta Therapeutics, Inc. | Exon skipping compositions for treating muscular dystrophy |
| BR112015023038A2 (pt) | 2013-03-14 | 2017-11-14 | Sarepta Therapeutics Inc | composições para salto de exon para o tratamento da distrofia muscular |
| EP3662912B1 (en) | 2013-03-15 | 2025-12-03 | Sarepta Therapeutics, Inc. | Improved dosages of eteplirsen for treating duchenne muscular dystrophy |
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