AU2016206518B2 - Novel micro-dystrophins and related methods of use - Google Patents
Novel micro-dystrophins and related methods of use Download PDFInfo
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- AU2016206518B2 AU2016206518B2 AU2016206518A AU2016206518A AU2016206518B2 AU 2016206518 B2 AU2016206518 B2 AU 2016206518B2 AU 2016206518 A AU2016206518 A AU 2016206518A AU 2016206518 A AU2016206518 A AU 2016206518A AU 2016206518 B2 AU2016206518 B2 AU 2016206518B2
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- 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
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- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
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- 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
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
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| GB201507842D0 (en) * | 2015-05-07 | 2015-06-17 | New Royal Holloway & Bedford | Production of large-sized microdystrophins in an AAV-based vector configuration |
| ES3040945T3 (en) | 2015-10-28 | 2025-11-06 | Vertex Pharma | Materials and methods for treatment of duchenne muscular dystrophy |
| KR102877920B1 (ko) | 2015-11-16 | 2025-10-30 | 더 리서치 인스티튜트 앳 네이션와이드 칠드런스 하스피탈 | 티틴-기반 근증 및 다른 티틴성병증의 치료를 위한 물질 및 방법 |
| MA45477A (fr) | 2016-04-15 | 2019-02-20 | Res Inst Nationwide Childrens Hospital | Administration à vecteurs de virus adéno-associé de microarn-29 et micro-dystrophine pour traiter la dystrophie musculaire |
| US20170362635A1 (en) * | 2016-06-20 | 2017-12-21 | University Of Washington | Muscle-specific crispr/cas9 editing of genes |
| CA2971303A1 (en) | 2016-06-21 | 2017-12-21 | Bamboo Therapeutics, Inc. | Optimized mini-dystrophin genes and expression cassettes and their use |
| JOP20190166A1 (ar) * | 2017-01-05 | 2019-07-02 | Univ Texas | استراتيجية مثلى من أجل تعديلات تخطي إكسون باستخدام crispr/cas9 مع متواليات توجيه ثلاثي |
| BR112019015081A2 (pt) | 2017-01-23 | 2020-03-10 | Rutgers, The State University Of New Jersey | Composições para reduzir a expressão da sarcolipina e prevenir e tratar a distrofia muscular e a cardiomiopatia e os métodos de utilização |
| US10687520B2 (en) | 2017-03-07 | 2020-06-23 | The Board Of Regents Of The University Of Texas System | Generation and correction of a humanized mouse model with a deletion of dystrophin exon 44 |
| JP7162021B2 (ja) * | 2017-03-17 | 2022-10-27 | ニューカッスル ユニバーシティ | 筋ジストロフィーを治療するためのマイクロジストロフィン断片のアデノ随伴ウイルスベクター送達 |
| US11534501B2 (en) | 2017-10-18 | 2022-12-27 | Research Institute At Nationwide Children's Hospital | Adeno-associated virus vector delivery of muscle specific micro-dystrophin to treat muscular dystrophy |
| TW201936201A (zh) | 2017-12-14 | 2019-09-16 | 美商堅固生物科技公司 | 基因之非病毒生產及遞送 |
| SG11202006722RA (en) | 2018-01-31 | 2020-08-28 | Res Inst Nationwide Childrens Hospital | Gene therapy for limb-girdle muscular dystrophy type 2c |
| EP3780952A4 (en) | 2018-04-16 | 2022-03-09 | The Trustees of the University of Pennsylvania | COMPOSITIONS AND METHODS OF TREATMENT OF DUCHENNE MUSCULAR DYSTROPHY |
| MY208145A (en) | 2018-06-18 | 2025-04-18 | Res Inst Nationwide Childrens Hospital | Adeno-associated virus vector delivery of muscle specific micro-dystrophin to treat muscular dystrophy |
| KR20210028162A (ko) | 2018-06-29 | 2021-03-11 | 더 리서치 인스티튜트 앳 네이션와이드 칠드런스 하스피탈 | 지대근 이영양증 2a형을 치료하기 위한 재조합 아데노 연관 바이러스 생성물 및 방법 |
| AU2019333315B2 (en) | 2018-08-30 | 2022-09-29 | Tenaya Therapeutics, Inc. | Cardiac cell reprogramming with myocardin and ASCL1 |
| BR112021007480A2 (pt) * | 2018-10-24 | 2021-08-10 | Bristol-Myers Squibb Company | distrofinas miniaturizadas e seus usos |
| US20220031865A1 (en) * | 2018-12-12 | 2022-02-03 | Solid Biosciences Inc. | Combination therapy for treating muscular dystrophy |
| CA3131390A1 (en) | 2019-02-26 | 2020-09-03 | Research Institute Of Nationwide Children's Hospital | Adeno-associated virus vector delivery of b-sarcoglycan and the treatment of muscular dystrophy |
| CA3130196A1 (en) * | 2019-03-25 | 2020-10-01 | Isabelle Richard | Production of large-sized quasidystrophins using overlapping aav vectors |
| CN114207120A (zh) | 2019-05-30 | 2022-03-18 | 坚固生物科技公司 | 重组疱疹病毒载体 |
| US20200405824A1 (en) * | 2019-06-26 | 2020-12-31 | University Of Washington | Use of ribonucleotide reductase alone or in combination with micro-dystrophin to treat duchenne muscular dystrophy striated muscle disease |
| HRP20240505T1 (hr) | 2019-08-21 | 2024-07-05 | Research Institute At Nationwide Children's Hospital | Dostava alfa-sarkoglikana vektorom povezanim s adenovirusom i liječenje mišićne distrofije |
| CA3153902A1 (en) | 2019-10-16 | 2021-04-22 | Pardis SABETI | Engineered muscle targeting compositions |
| KR20220107222A (ko) * | 2019-11-28 | 2022-08-02 | 리젠엑스바이오 인크. | 마이크로디스트로핀 유전자 치료 작제물 및 이의 용도 |
| WO2021163357A2 (en) * | 2020-02-13 | 2021-08-19 | Tenaya Therapeutics, Inc. | Gene therapy vectors for treating heart disease |
| MY209860A (en) * | 2020-02-13 | 2025-08-07 | Tenaya Therapeutics Inc | Gene therapy vectors for treating heart disease |
| MX2022013477A (es) | 2020-04-29 | 2022-11-30 | Bristol Myers Squibb Co | Distrofinas miniaturizadas con dominios de fusion de espectrina y usos de las mismas. |
| WO2021257595A1 (en) | 2020-06-15 | 2021-12-23 | Research Institute At Nationwide Children's Hospital | Adeno-associated virus vector delivery for muscular dystrophies |
| WO2022004788A1 (ja) * | 2020-06-30 | 2022-01-06 | 東レ株式会社 | 代謝異常を伴う疾患又は症候群における筋力低下症状の改善剤又は予防剤 |
| WO2022076750A2 (en) | 2020-10-07 | 2022-04-14 | Regenxbio Inc. | Recombinant adeno-associated viruses for cns or muscle delivery |
| US20240003898A1 (en) | 2020-10-30 | 2024-01-04 | Pfizer Inc. | Methods for measuring dystrophin in tissue samples |
| RU2767335C1 (ru) * | 2021-03-02 | 2022-03-17 | Общество с ограниченной ответственностью «Марлин Биотех» | Химерные белки на основе утрофина и дистрофина человека и их применение для лечения миодистрофии Дюшенна |
| WO2022216749A1 (en) | 2021-04-05 | 2022-10-13 | Solid Biosciences Inc. | Recombinant herpesvirales vector |
| US20240200093A1 (en) * | 2021-04-09 | 2024-06-20 | University Of Washington | Artificial regulatory cassettes for muscle-specific gene expression |
| CA3216744A1 (en) * | 2021-04-26 | 2022-11-03 | Regenxbio Inc. | Microdystrophin gene therapy administration for treatment of dystrophinopathies |
| US20240358857A1 (en) * | 2021-05-11 | 2024-10-31 | Regenxbio Inc. | Treatment of duchenne muscular dystrophy and combinations thereof |
| EP4108263A3 (en) | 2021-06-02 | 2023-03-22 | Research Institute at Nationwide Children's Hospital | Recombinant adeno-associated virus products and methods for treating limb girdle muscular dystrophy 2a |
| US20240269329A1 (en) * | 2021-06-07 | 2024-08-15 | University Of Florida Research Foundation, Incorporated | Gene therapy for duchenne muscular dystrophy |
| US20250019721A1 (en) | 2021-08-11 | 2025-01-16 | Ultragenyx Pharmaceutical Inc. | Compositions and methods for treating a muscular dystrophy |
| KR20240095165A (ko) | 2021-08-11 | 2024-06-25 | 솔리드 바이오사이언시즈 인크. | 근이영양증의 치료 |
| WO2023060269A1 (en) | 2021-10-07 | 2023-04-13 | Regenxbio Inc. | Recombinant adeno-associated viruses for targeted delivery |
| EP4219726A1 (en) | 2021-10-15 | 2023-08-02 | Research Institute at Nationwide Children's Hospital | Self-complementary adeno-associated virus vector and its use in treatment of muscular dystrophy |
| WO2023081850A1 (en) | 2021-11-04 | 2023-05-11 | Regeneron Pharmaceuticals, Inc. | Viral particles retargeted to skeletal muscle |
| CN114316070B (zh) * | 2021-12-29 | 2022-11-15 | 上海勉亦生物科技有限公司 | 用于治疗肌营养不良症的转基因表达盒 |
| EP4215614A1 (en) | 2022-01-24 | 2023-07-26 | Dynacure | Combination therapy for dystrophin-related diseases |
| US20250288641A1 (en) * | 2022-04-27 | 2025-09-18 | The Curators Of The University Of Missouri | Micro-dystrophin for heart protection |
| WO2024138158A2 (en) * | 2022-12-23 | 2024-06-27 | Ultragenyx Pharmaceutical Inc. | Method of producing soluble microdystrophin protein and uses of the same |
| AU2024220647A1 (en) | 2023-02-13 | 2025-08-21 | Regeneron Pharmaceuticals, Inc. | Treatment of muscle related disorders with anti-human cacng1 antibodies |
| WO2024216244A2 (en) | 2023-04-13 | 2024-10-17 | Regenxbio Inc. | Targeting aav capsids, methods of manufacturing and using same |
Citations (1)
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|---|---|---|---|---|
| US20080249052A1 (en) * | 2007-01-18 | 2008-10-09 | Dongsheng Duan | Synthetic mini/micro-dystrophin genes to restore nNOS to the sarcolemma |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60134786D1 (de) * | 2000-10-06 | 2008-08-21 | Univ Michigan | Mini-dystrophin nukleinsäure- und peptidsequenzen |
| US20070202587A1 (en) | 2002-09-23 | 2007-08-30 | Applied Genetic Technologies Corporation | Recombinant AAV production in mammalian cells |
| EP2298926A1 (en) | 2003-09-30 | 2011-03-23 | The Trustees of The University of Pennsylvania | Adeno-associated virus (AAV) clades, sequences, vectors containing same, and uses thereof |
| US20080044393A1 (en) * | 2004-07-16 | 2008-02-21 | White Robert L | Retinal dystrophin transgene and methods of use thereof |
| US7436622B2 (en) * | 2006-07-31 | 2008-10-14 | Imation Corp. | Concurrent servo and data track writing |
| WO2009097129A1 (en) | 2008-01-29 | 2009-08-06 | Applied Genetic Technologies Corporation | Recombinant virus production using mammalian cells in suspension |
| KR101555083B1 (ko) * | 2008-11-11 | 2015-09-22 | 인터내셔널 비지네스 머신즈 코포레이션 | 제공 장치, 시스템, 서버 장치, 프로그램 및 방법 |
| KR20140035967A (ko) * | 2011-05-26 | 2014-03-24 | 유니버시티 오브 워싱톤 | 세포 및 유전자에 기반한 심장 기능을 개선하는 방법 |
| US20130136729A1 (en) * | 2011-11-11 | 2013-05-30 | University of Virginia Patent Foundation, d/b/a University of Virginia Licensing & Ventures Group | Compositions and methods for targeting and treating diseases and injuries using adeno-associated virus vectors |
| US9624282B2 (en) * | 2012-11-26 | 2017-04-18 | The Curators Of The University Of Missouri | Microdystrophin peptides and methods for treating muscular dystrophy using the same |
| US20150329609A1 (en) * | 2014-03-03 | 2015-11-19 | Sujata Acharjee | Chimeric dystrophin proteins to treat dystrophinopathies |
| EP2960336A1 (en) | 2014-06-27 | 2015-12-30 | Genethon | Efficient systemic treatment of dystrophic muscle pathologies |
| AU2016206518B2 (en) * | 2015-01-16 | 2020-03-05 | University Of Washington | Novel micro-dystrophins and related methods of use |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080249052A1 (en) * | 2007-01-18 | 2008-10-09 | Dongsheng Duan | Synthetic mini/micro-dystrophin genes to restore nNOS to the sarcolemma |
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