CN119709746A - 肝外递送 - Google Patents

肝外递送 Download PDF

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Publication number
CN119709746A
CN119709746A CN202411905986.7A CN202411905986A CN119709746A CN 119709746 A CN119709746 A CN 119709746A CN 202411905986 A CN202411905986 A CN 202411905986A CN 119709746 A CN119709746 A CN 119709746A
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CN
China
Prior art keywords
compound
antisense strand
strand
lipophilic
nucleotides
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202411905986.7A
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English (en)
Chinese (zh)
Inventor
J·K·奈尔
M·A·迈尔
J·C·萨利纳斯
松田茂夫
A·V·凯尔因
S·P·兰蒂尼
何果
M·H·郑
J·M·皮尔森
M·马诺哈兰
D·C·冈瑟
I·兹拉特夫
C·S·锡尔
V·R·贾达夫
S·米尔斯坦
M·贾纳斯
D·达塔
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Alnylam Pharmaceuticals Inc
Original Assignee
Alnylam Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Alnylam Pharmaceuticals Inc filed Critical Alnylam Pharmaceuticals Inc
Publication of CN119709746A publication Critical patent/CN119709746A/zh
Pending legal-status Critical Current

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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
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • 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
    • A61K48/0075—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the delivery route, e.g. oral, subcutaneous
    • 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
    • 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
    • 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
    • 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
    • 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
    • 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
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/322—2'-R Modification
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3515—Lipophilic moiety, e.g. cholesterol
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/353—Nature of the modification linked to the nucleic acid via an atom other than carbon
    • C12N2310/3535—Nitrogen
    • 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
    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Epidemiology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
CN202411905986.7A 2019-11-06 2020-11-06 肝外递送 Pending CN119709746A (zh)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201962931631P 2019-11-06 2019-11-06
US62/931,631 2019-11-06
PCT/US2020/059399 WO2021092371A2 (en) 2019-11-06 2020-11-06 Extrahepatic delivery
CN202080093231.5A CN114945669B (zh) 2019-11-06 2020-11-06 肝外递送

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
CN202080093231.5A Division CN114945669B (zh) 2019-11-06 2020-11-06 肝外递送

Publications (1)

Publication Number Publication Date
CN119709746A true CN119709746A (zh) 2025-03-28

Family

ID=73646550

Family Applications (2)

Application Number Title Priority Date Filing Date
CN202411905986.7A Pending CN119709746A (zh) 2019-11-06 2020-11-06 肝外递送
CN202080093231.5A Active CN114945669B (zh) 2019-11-06 2020-11-06 肝外递送

Family Applications After (1)

Application Number Title Priority Date Filing Date
CN202080093231.5A Active CN114945669B (zh) 2019-11-06 2020-11-06 肝外递送

Country Status (10)

Country Link
US (1) US20230016929A1 (https=)
EP (1) EP4055166A2 (https=)
JP (2) JP7780428B2 (https=)
KR (1) KR20220110749A (https=)
CN (2) CN119709746A (https=)
AU (1) AU2020378414A1 (https=)
BR (1) BR112022007795A2 (https=)
CA (1) CA3160329A1 (https=)
MX (1) MX2022005220A (https=)
WO (1) WO2021092371A2 (https=)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20220062517A (ko) 2019-08-15 2022-05-17 아이오니스 파마수티컬즈, 인코포레이티드 결합 변형된 올리고머 화합물 및 이의 용도
EP4291654A2 (en) 2021-02-12 2023-12-20 Alnylam Pharmaceuticals, Inc. Superoxide dismutase 1 (sod1) irna compositions and methods of use thereof for treating or preventing superoxide dismutase 1- (sod1-) associated neurodegenerative diseases
AR126070A1 (es) * 2021-06-08 2023-09-06 Alnylam Pharmaceuticals Inc Composiciones y métodos para tratar o prevenir la enfermedad de stargardt y/o trastornos asociados con la proteína transportadora de retinol 4 (rbp4)
TW202328449A (zh) 2021-09-24 2023-07-16 美商艾拉倫製藥公司 微管相關蛋白ＴＡＵ（ＭＡＰＴ）ｉＲＮＡ試劑組合物及其使用方法
CN114891509B (zh) * 2021-12-14 2023-05-05 湖北兴福电子材料股份有限公司 一种高选择性的缓冲氧化物蚀刻液
AU2023245603A1 (en) * 2022-03-28 2024-11-07 Empirico Inc. Modified oligonucleotides
WO2024073732A1 (en) 2022-09-30 2024-04-04 Alnylam Pharmaceuticals, Inc. Modified double-stranded rna agents
KR20260009305A (ko) 2023-04-12 2026-01-19 알닐람 파마슈티칼스 인코포레이티드 이중 가닥 rna 제제의 간외 전달
CN121358748A (zh) * 2023-06-12 2026-01-16 大睿生物医药科技(上海)有限公司 包含糖的寡核苷酸递送配体
TW202517784A (zh) 2023-07-14 2025-05-01 大陸商云合智藥（蘇州）生物科技有限公司 用於抑制己酮糖激酶表達的ＲＮＡｉ劑及其應用
AU2024318590A1 (en) * 2023-07-31 2026-02-26 Basecure Therapeutics Inc. Conjugates of n-acetyl-galactosamine (galnac) and oligonucleotides and uses thereof
WO2025040139A1 (zh) 2023-08-23 2025-02-27 云合智药（苏州）生物科技有限公司 用于抑制二酰甘油-O-酰基转移酶2表达的RNAi剂及其应用
WO2025054459A1 (en) * 2023-09-08 2025-03-13 Dicerna Pharmaceuticals, Inc. Rnai oligonucleotide conjugates
WO2025073871A1 (en) 2023-10-03 2025-04-10 Bicycletx Limited Bicyclic peptide ligand complexes specific for tfr1
WO2026082078A1 (zh) * 2024-10-15 2026-04-23 成都先衍生物技术有限公司 一种亚磷酰胺脂质分子及其在RNAi分子中的用途

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