CN114502177A - 寡核苷酸组合物及其使用方法 - Google Patents

寡核苷酸组合物及其使用方法 Download PDF

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Publication number
CN114502177A
CN114502177A CN202080049469.8A CN202080049469A CN114502177A CN 114502177 A CN114502177 A CN 114502177A CN 202080049469 A CN202080049469 A CN 202080049469A CN 114502177 A CN114502177 A CN 114502177A
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oligonucleotide
oligonucleotides
c9orf72
composition
linkage
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Chinese (zh)
Inventor
刘元婧
岩本直树
钱德拉·瓦尔格赛
钟忠
埃米·亚达·安德烈乌奇
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Wave Life Sciences Pte Ltd
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Wave Life Sciences Pte Ltd
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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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/7125—Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
    • 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
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • 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
    • 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
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • C—CHEMISTRY; METALLURGY
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/314—Phosphoramidates
    • C—CHEMISTRY; METALLURGY
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
    • 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
    • C12N2310/30—Chemical structure
    • C12N2310/33—Chemical structure of the base
    • C12N2310/334—Modified C
    • C12N2310/3341—5-Methylcytosine
    • C—CHEMISTRY; METALLURGY
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/341—Gapmers, i.e. of the type ===---===
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
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    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C12N2320/34—Allele or polymorphism specific uses
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    • C12N2320/00—Applications; Uses
    • C12N2320/50—Methods for regulating/modulating their activity
    • C12N2320/53—Methods for regulating/modulating their activity reducing unwanted side-effects

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  • General Health & Medical Sciences (AREA)
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  • Epidemiology (AREA)
  • Biophysics (AREA)
  • Hospice & Palliative Care (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Physics & Mathematics (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
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  • General Chemical & Material Sciences (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
CN202080049469.8A 2019-05-09 2020-05-08 寡核苷酸组合物及其使用方法 Pending CN114502177A (zh)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
US201962845765P 2019-05-09 2019-05-09
US62/845,765 2019-05-09
US201962851558P 2019-05-22 2019-05-22
US62/851,558 2019-05-22
US201962911340P 2019-10-06 2019-10-06
US62/911,340 2019-10-06
US202062983736P 2020-03-01 2020-03-01
US62/983,736 2020-03-01
PCT/US2020/032244 WO2020227691A2 (en) 2019-05-09 2020-05-08 Oligonucleotide compositions and methods of use thereof

Publications (1)

Publication Number Publication Date
CN114502177A true CN114502177A (zh) 2022-05-13

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CN202080049469.8A Pending CN114502177A (zh) 2019-05-09 2020-05-08 寡核苷酸组合物及其使用方法

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US (1) US20220145300A1 (https=)
EP (1) EP3965780A4 (https=)
JP (2) JP2022532169A (https=)
CN (1) CN114502177A (https=)
AU (1) AU2020267775A1 (https=)
CA (1) CA3139513A1 (https=)
WO (1) WO2020227691A2 (https=)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114585370A (zh) * 2019-10-06 2022-06-03 波涛生命科学有限公司 寡核苷酸组合物及其使用方法

Families Citing this family (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102213609B1 (ko) 2012-07-13 2021-02-08 웨이브 라이프 사이언시스 리미티드 키랄 제어
PL2872485T3 (pl) 2012-07-13 2021-05-31 Wave Life Sciences Ltd. Asymetryczna grupa pomocnicza
BR112016016400A2 (pt) 2014-01-16 2017-10-03 Wave Life Sciences Ltd Composições de oligonucleotídeos quiralmente controlados, seu uso, sua composição farmacêutica, e métodos
IL320434A (en) 2015-07-22 2025-06-01 Wave Life Sciences Ltd Oligonucleotide preparations and methods
CN108779132B (zh) 2016-03-13 2022-04-15 波涛生命科学有限公司 用于亚磷酰胺和寡核苷酸合成的组合物和方法
JP2019520339A (ja) 2016-06-03 2019-07-18 ウェイブ ライフ サイエンシズ リミテッドＷａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｌｔｄ． オリゴヌクレオチド、その組成物および方法
WO2017220751A1 (en) 2016-06-22 2017-12-28 Proqr Therapeutics Ii B.V. Single-stranded rna-editing oligonucleotides
CN110352244B (zh) 2016-09-01 2023-03-21 ProQR治疗上市公司Ⅱ 化学修饰的编辑rna的单链寡核苷酸
US11873316B2 (en) 2016-11-23 2024-01-16 Wave Life Sciences Ltd. Compositions and methods for phosphoramidite and oligonucleotide synthesis
JP2020522510A (ja) 2017-06-02 2020-07-30 ウェイブ ライフ サイエンシズ リミテッドＷａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｌｔｄ． オリゴヌクレオチド組成物及びその使用方法
CA3065523A1 (en) 2017-06-02 2018-12-06 Wave Life Sciences Ltd. Oligonucleotide compositions and methods of use thereof
US11718638B2 (en) 2017-06-21 2023-08-08 Wave Life Sciences Ltd. Compounds, compositions and methods for synthesis
EP3664816A4 (en) 2017-08-08 2021-05-19 Wave Life Sciences Ltd. OLIGONUCLEOTIDE COMPOSITIONS AND RELATED PROCESSES
CA3072110A1 (en) 2017-09-18 2019-03-21 Wave Life Sciences Ltd. Technologies for oligonucleotide preparation
EP3694530A4 (en) 2017-10-12 2021-06-30 Wave Life Sciences Ltd. COMPOSITIONS OF OLIGONUCLEOTIDES AND RELATED PROCESSES
WO2019157531A1 (en) 2018-02-12 2019-08-15 Ionis Pharmaceuticals, Inc. Modified compounds and uses thereof
SG11202009877XA (en) 2018-04-12 2020-11-27 Wave Life Sciences Ltd Oligonucleotide compositions and methods of use thereof
US12391942B2 (en) 2018-05-11 2025-08-19 Wave Life Sciences Ltd. Oligonucleotide compositions and methods of use thereof
GB201808146D0 (en) 2018-05-18 2018-07-11 Proqr Therapeutics Ii Bv Stereospecific Linkages in RNA Editing Oligonucleotides
JP2022525541A (ja) 2019-03-20 2022-05-17 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調製に有用な技術
CA3236136A1 (en) * 2021-10-27 2023-05-04 Wave Life Sciences Ltd. Oligonucleotide compositions and methods of use thereof
EP4479535A1 (en) 2022-02-14 2024-12-25 ProQR Therapeutics II B.V. Guide oligonucleotides for nucleic acid editing in the treatment of hypercholesterolemia
JP2025524566A (ja) 2022-07-15 2025-07-30 プロキューアール セラピューティクス ツー ベスローテン フェンノートシャップ Ａｄａｒ媒介ｒｎａ編集のためのオリゴヌクレオチドおよびその使用
US20260027237A1 (en) 2022-07-15 2026-01-29 Proqr Therapeutics Ii B.V. Chemically modified oligonucleotides for adar-mediated rna editing
GB202215614D0 (en) 2022-10-21 2022-12-07 Proqr Therapeutics Ii Bv Heteroduplex rna editing oligonucleotide complexes
WO2024110565A1 (en) 2022-11-24 2024-05-30 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of hereditary hfe-hemochromatosis
GB202218090D0 (en) 2022-12-01 2023-01-18 Proqr Therapeutics Ii Bv Antisense oligonucleotides for the treatment of aldehyde dehydrogenase 2 deficiency
AU2023390632A1 (en) 2022-12-09 2025-07-10 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of cardiovascular disease
GB202300865D0 (en) 2023-01-20 2023-03-08 Proqr Therapeutics Ii Bv Delivery of oligonucleotides
WO2024175550A1 (en) 2023-02-20 2024-08-29 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of atherosclerotic cardiovascular disease
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GB202304363D0 (en) 2023-03-24 2023-05-10 Proqr Therapeutics Ii Bv Chemically modified antisense oligonucleotides for use in RNA editing
EP4688143A1 (en) 2023-03-27 2026-02-11 ProQR Therapeutics II B.V. Antisense oligonucleotides for the treatment of liver disease
TW202516003A (zh) 2023-06-16 2025-04-16 荷蘭商Ｐｒｏｑｒ治療上市公司Ｉｉ 用於治療神經退化性疾病之反義寡核苷酸
WO2025051946A1 (en) 2023-09-07 2025-03-13 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of metabolic disorders
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WO2025132708A1 (en) 2023-12-20 2025-06-26 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of huntington's disease
GB202404661D0 (en) 2024-04-02 2024-05-15 Proqr Therapeutics Ii Bv Antisense oligoncleotides for the treatment of liver disease
WO2025213142A2 (en) * 2024-04-05 2025-10-09 Wave Life Sciences Ltd. Oligonucleotide compositions and methods thereof
WO2025224230A1 (en) 2024-04-25 2025-10-30 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of fatty liver disease
GB202410081D0 (en) 2024-07-11 2024-08-28 Proqr Therapeutics Ii Bv Antisense oligonucleotides for the treatment of cardiovascular disease
WO2026022136A1 (en) 2024-07-23 2026-01-29 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of metabolic disorders
WO2026060374A2 (en) 2024-09-16 2026-03-19 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of neurological disorders
WO2026068781A1 (en) 2024-09-30 2026-04-02 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of liver disease

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2762326T5 (es) * 2012-10-15 2023-04-27 Ionis Pharmaceuticals Inc Métodos para modular la expresión de C9ORF72
KR20180118111A (ko) * 2015-12-23 2018-10-30 크리스퍼 테라퓨틱스 아게 근위축성 측색 경화증 및/또는 전두측두엽 퇴행의 치료 물질 및 방법
EP3664816A4 (en) * 2017-08-08 2021-05-19 Wave Life Sciences Ltd. OLIGONUCLEOTIDE COMPOSITIONS AND RELATED PROCESSES

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114585370A (zh) * 2019-10-06 2022-06-03 波涛生命科学有限公司 寡核苷酸组合物及其使用方法

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WO2020227691A2 (en) 2020-11-12
JP2022532169A (ja) 2022-07-13
CA3139513A1 (en) 2020-11-12
AU2020267775A1 (en) 2021-12-02
US20220145300A1 (en) 2022-05-12
EP3965780A4 (en) 2023-10-25
EP3965780A2 (en) 2022-03-16
JP2025125554A (ja) 2025-08-27
WO2020227691A3 (en) 2020-12-17

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