JP7413256B2 - 神経変性疾患の遺伝子治療 - Google Patents
神経変性疾患の遺伝子治療 Download PDFInfo
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- JP7413256B2 JP7413256B2 JP2020523011A JP2020523011A JP7413256B2 JP 7413256 B2 JP7413256 B2 JP 7413256B2 JP 2020523011 A JP2020523011 A JP 2020523011A JP 2020523011 A JP2020523011 A JP 2020523011A JP 7413256 B2 JP7413256 B2 JP 7413256B2
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- nucleic acid
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- raav
- c9orf72
- protein
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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
- C12N15/113—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
- C12N15/1138—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 against receptors or cell surface proteins
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- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
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- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0085—Brain, e.g. brain implants; Spinal cord
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/50—Physical structure
- C12N2310/53—Physical structure partially self-complementary or closed
- C12N2310/531—Stem-loop; Hairpin
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
- C12N2320/32—Special delivery means, e.g. tissue-specific
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2330/00—Production
- C12N2330/50—Biochemical production, i.e. in a transformed host cell
- C12N2330/51—Specially adapted vectors
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/14011—Baculoviridae
- C12N2710/14041—Use of virus, viral particle or viral elements as a vector
- C12N2710/14043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vectore
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14121—Viruses as such, e.g. new isolates, mutants or their genomic sequences
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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
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14141—Use of virus, viral particle or viral elements as a vector
- C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- 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
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14151—Methods of production or purification of viral material
- C12N2750/14152—Methods of production or purification of viral material relating to complementing cells and packaging systems for producing virus or viral particles
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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
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/48—Vector systems having a special element relevant for transcription regulating transport or export of RNA, e.g. RRE, PRE, WPRE, CTE
-
- 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
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/50—Vector systems having a special element relevant for transcription regulating RNA stability, not being an intron, e.g. poly A signal
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Virology (AREA)
- Neurology (AREA)
- Medicinal Chemistry (AREA)
- Neurosurgery (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychology (AREA)
- Epidemiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Immunology (AREA)
- Psychiatry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2023220260A JP2024045131A (ja) | 2017-10-23 | 2023-12-27 | 神経変性疾患の遺伝子治療 |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762575795P | 2017-10-23 | 2017-10-23 | |
| US62/575,795 | 2017-10-23 | ||
| US201862742723P | 2018-10-08 | 2018-10-08 | |
| US62/742,723 | 2018-10-08 | ||
| PCT/US2018/057187 WO2019084068A1 (en) | 2017-10-23 | 2018-10-23 | GENE THERAPIES FOR NEURODEGENERATIVE DISEASE |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2023220260A Division JP2024045131A (ja) | 2017-10-23 | 2023-12-27 | 神経変性疾患の遺伝子治療 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2021500049A JP2021500049A (ja) | 2021-01-07 |
| JP2021500049A5 JP2021500049A5 (enExample) | 2021-11-25 |
| JP7413256B2 true JP7413256B2 (ja) | 2024-01-15 |
Family
ID=66247008
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020523011A Active JP7413256B2 (ja) | 2017-10-23 | 2018-10-23 | 神経変性疾患の遺伝子治療 |
| JP2023220260A Pending JP2024045131A (ja) | 2017-10-23 | 2023-12-27 | 神経変性疾患の遺伝子治療 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2023220260A Pending JP2024045131A (ja) | 2017-10-23 | 2023-12-27 | 神経変性疾患の遺伝子治療 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20210261981A1 (enExample) |
| EP (1) | EP3701030A4 (enExample) |
| JP (2) | JP7413256B2 (enExample) |
| KR (1) | KR20200075865A (enExample) |
| CN (2) | CN111819281B (enExample) |
| AU (1) | AU2018354195A1 (enExample) |
| BR (1) | BR112020008033A2 (enExample) |
| CA (2) | CA3083582A1 (enExample) |
| IL (2) | IL274129A (enExample) |
| MX (1) | MX2020004207A (enExample) |
| WO (1) | WO2019084068A1 (enExample) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP7361037B2 (ja) | 2017-10-03 | 2023-10-13 | プリベイル セラピューティクス,インコーポレーテッド | ライソゾーム病の遺伝子治療 |
| US11802294B2 (en) * | 2017-10-03 | 2023-10-31 | Prevail Therapeutics, Inc. | Gene therapies for lysosomal disorders |
| KR20200078513A (ko) | 2017-10-03 | 2020-07-01 | 프리베일 테라퓨틱스, 인크. | 리소좀 장애를 위한 유전자 요법 |
| US20210000929A1 (en) * | 2018-03-09 | 2021-01-07 | Avrobio, Inc. | Compositions and methods for treating parkinson's disease |
| CN114174324A (zh) | 2019-04-10 | 2022-03-11 | 普利维尔治疗公司 | 用于溶酶体病症的基因疗法 |
| BR112021019880A2 (pt) | 2019-04-10 | 2022-02-15 | Prevail Therapeutics Inc | Terapias gênicas para distúrbios lisossomais |
| WO2021081236A1 (en) * | 2019-10-22 | 2021-04-29 | Applied Genetic Technologies Corporation | Triple function adeno-associated virus (aav) vectors for the treatment of c9orf72 associated diseases |
| US20240294906A1 (en) * | 2020-07-29 | 2024-09-05 | Alnylam Pharmaceuticals, Inc. | Atxn2 irna compositions and methods of use thereof for treating or preventing atxn2-associated neurodegenerative diseases |
| CN116710567A (zh) | 2020-10-15 | 2023-09-05 | 普利维尔治疗公司 | 重组腺相关病毒组合物及其产生方法 |
| WO2022081985A1 (en) | 2020-10-15 | 2022-04-21 | Prevail Therapeutics, Inc. | Assay for measuring potency of gene therapy drug product |
| JPWO2022097727A1 (enExample) | 2020-11-06 | 2022-05-12 | ||
| KR20220109347A (ko) | 2021-01-28 | 2022-08-04 | 주식회사 에이브레인 | 신경 퇴행성 질환의 치료를 위한 유전자 요법 |
| KR102711715B1 (ko) | 2021-01-28 | 2024-09-30 | 주식회사 에이브레인 | 신경 퇴행성 질환의 치료를 위한 유전자 요법 |
| KR102707250B1 (ko) | 2021-10-28 | 2024-09-13 | 한국해양과학기술원 | 신규 화합물 및 이를 유효성분으로 포함하는 신경염증성 뇌질환 예방 또는 치료용 조성물 |
| WO2023133574A1 (en) * | 2022-01-10 | 2023-07-13 | The Trustees Of The University Of Pennsylvania | Compositions and methods useful for treatment of c9orf72-mediated disorders |
| WO2024257847A1 (ja) | 2023-06-16 | 2024-12-19 | 住友ファーマ株式会社 | Rps25遺伝子の発現及び/又はその機能を調節するアンチセンスオリゴヌクレオチド |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007525415A (ja) | 2003-01-31 | 2007-09-06 | ザ・トラスティーズ・オブ・ザ・ユニバーシティ・オブ・ペンシルベニア | 炎症反応を調節するための方法 |
| JP2012508220A (ja) | 2008-11-11 | 2012-04-05 | オックスフォード バイオメディカ(ユーケー)リミテッド | 方法 |
| JP2015514418A (ja) | 2012-04-23 | 2015-05-21 | プロセンサ テクノロジーズ ビー.ブイ.Prosensa Technologies B.V. | 神経筋障害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 |
| JP2016503405A (ja) | 2012-11-05 | 2016-02-04 | ジェンザイム・コーポレーション | タンパク質症を処置するための組成物および方法 |
| JP2017510298A (ja) | 2014-03-18 | 2017-04-13 | ユニバーシティ オブ マサチューセッツ | 筋萎縮性側索硬化症を処置するためのrAAVベースの組成物および方法 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6204059B1 (en) * | 1994-06-30 | 2001-03-20 | University Of Pittsburgh | AAV capsid vehicles for molecular transfer |
| US20040053876A1 (en) * | 2002-03-26 | 2004-03-18 | The Regents Of The University Of Michigan | siRNAs and uses therof |
| US7829694B2 (en) * | 2002-11-26 | 2010-11-09 | Medtronic, Inc. | Treatment of neurodegenerative disease through intracranial delivery of siRNA |
| AU2006210973A1 (en) * | 2005-01-31 | 2006-08-10 | University Of Iowa Research Foundation | Nucleic acid silencing of Huntington's Disease gene |
| US20110142789A1 (en) * | 2009-12-10 | 2011-06-16 | The Trustees Of The University Of Pennsylvania | Compositions and Methods for the Diagnosis and Treatment of Amyotrophic Lateral Sclerosis |
| EP2678433B1 (en) * | 2011-02-22 | 2017-05-03 | California Institute of Technology | Delivery of proteins using adeno-associated virus (aav) vectors |
| US20140271550A1 (en) * | 2013-03-14 | 2014-09-18 | The Trustees Of The University Of Pennsylvania | Constructs and Methods for Delivering Molecules via Viral Vectors with Blunted Innate Immune Responses |
| RU2748426C2 (ru) * | 2013-10-11 | 2021-05-25 | Ионис Фармасьютикалз, Инк. | Композиции для модуляции экспрессии c90rf72 |
| PL3119888T3 (pl) * | 2014-03-19 | 2021-12-20 | Ionis Pharmaceuticals, Inc. | Kompozycje do modulacji ekspresji ataksyny 2 |
| WO2015153760A2 (en) * | 2014-04-01 | 2015-10-08 | Sangamo Biosciences, Inc. | Methods and compositions for prevention or treatment of a nervous system disorder |
| WO2016024205A1 (en) * | 2014-08-15 | 2016-02-18 | Pfizer Inc. | Oligomers targeting hexanucleotide repeat expansion in human c9orf72 gene |
| US10597660B2 (en) * | 2014-11-14 | 2020-03-24 | Voyager Therapeutics, Inc. | Compositions and methods of treating amyotrophic lateral sclerosis (ALS) |
| WO2016172155A1 (en) * | 2015-04-23 | 2016-10-27 | University Of Massachusetts | Modulation of aav vector transgene expression |
| EP3292206B8 (en) * | 2015-05-07 | 2022-02-09 | Takeda Pharmaceutical Company Limited | Glucocerebrosidase gene therapy for parkinson's disease |
| CA3016314A1 (en) * | 2016-03-02 | 2017-09-08 | Julianne REIDERS | Therapy for frontotemporal dementia |
| EP3518667B1 (en) * | 2016-09-30 | 2024-10-30 | Regeneron Pharmaceuticals, Inc. | Rodents having a hexanucleotide repeat expansion in a c9orf72 locus |
| EP3850098A1 (en) * | 2018-09-12 | 2021-07-21 | uniQure IP B.V. | Rnai induced c9orf72 suppression for the treatment of als/ftd |
-
2018
- 2018-10-23 US US16/758,077 patent/US20210261981A1/en not_active Abandoned
- 2018-10-23 EP EP18870021.5A patent/EP3701030A4/en not_active Withdrawn
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| JP2024045131A (ja) | 2024-04-02 |
| WO2019084068A1 (en) | 2019-05-02 |
| EP3701030A1 (en) | 2020-09-02 |
| JP2021500049A (ja) | 2021-01-07 |
| US20210261981A1 (en) | 2021-08-26 |
| CA3177979A1 (en) | 2019-05-02 |
| AU2018354195A1 (en) | 2020-06-04 |
| IL274129A (en) | 2020-06-30 |
| CN111819281A (zh) | 2020-10-23 |
| CN111819281B (zh) | 2024-12-31 |
| BR112020008033A2 (pt) | 2020-10-27 |
| CA3083582A1 (en) | 2019-05-02 |
| MX2020004207A (es) | 2020-11-11 |
| IL281057A (en) | 2021-04-29 |
| CN113005123A (zh) | 2021-06-22 |
| KR20200075865A (ko) | 2020-06-26 |
| EP3701030A4 (en) | 2022-04-20 |
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