TW202043472A - 用於減少ａｐｐ表現之化合物及方法 - Google Patents

用於減少ａｐｐ表現之化合物及方法 Download PDF

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TW202043472A
TW202043472A TW109102899A TW109102899A TW202043472A TW 202043472 A TW202043472 A TW 202043472A TW 109102899 A TW109102899 A TW 109102899A TW 109102899 A TW109102899 A TW 109102899A TW 202043472 A TW202043472 A TW 202043472A
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Taiwan
Prior art keywords
modified
oligonucleotide
nucleobases
rnai
nucleosides
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TW109102899A
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English (en)
Chinese (zh)
Inventor
蘇珊 M 弗瑞爾
賀恩 荷亞 比伊
賀利 科達席微茲
艾瑞克 E 史瓦瑟
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美商Ionis製藥公司
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Publication of TW202043472A publication Critical patent/TW202043472A/zh

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    • 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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    • C12N15/09—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
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    • C12N2310/00—Structure or type of the nucleic acid
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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
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    • C12N2310/00—Structure or type of the nucleic acid
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/323—Chemical structure of the sugar modified ring structure
    • C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
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    • C12N2310/00—Structure or type of the nucleic acid
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    • C12N2310/334—Modified C
    • C12N2310/3341—5-Methylcytosine
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    • 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
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/345—Spatial arrangement of the modifications having at least two different backbone modifications
    • 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
    • C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Molecular Biology (AREA)
  • Wood Science & Technology (AREA)
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  • Biochemistry (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
TW109102899A 2019-01-29 2020-01-30 用於減少ａｐｐ表現之化合物及方法 TW202043472A (zh)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US201962798353P 2019-01-29 2019-01-29
US62/798,353 2019-01-29
US201962841169P 2019-04-30 2019-04-30
US62/841,169 2019-04-30
US201962915764P 2019-10-16 2019-10-16
US62/915,764 2019-10-16

Publications (1)

Publication Number Publication Date
TW202043472A true TW202043472A (zh) 2020-12-01

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TW109102899A TW202043472A (zh) 2019-01-29 2020-01-30 用於減少ａｐｐ表現之化合物及方法

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US (1) US20220380773A1 (enExample)
EP (1) EP3918073A4 (enExample)
JP (2) JP7557469B2 (enExample)
TW (1) TW202043472A (enExample)
UY (1) UY38562A (enExample)
WO (1) WO2020160163A1 (enExample)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SG11202006528XA (en) 2018-01-12 2020-08-28 Bristol Myers Squibb Co Antisense oligonucleotides targeting alpha-synuclein and uses thereof
CN120310791A (zh) 2018-01-12 2025-07-15 百时美施贵宝公司 靶向α-突触核蛋白的反义寡核苷酸及其用途
US11732260B2 (en) 2018-03-02 2023-08-22 Ionis Pharmaceuticals, Inc. Compounds and methods for the modulation of amyloid-β precursor protein
MX2021007570A (es) * 2018-12-19 2021-08-24 Alnylam Pharmaceuticals Inc Composiciones de agente de arni de la proteina precursora del amiloide (app) y metodos de uso de las mismas.
KR20210149107A (ko) * 2019-04-03 2021-12-08 브리스톨-마이어스 스큅 컴퍼니 Angptl2 안티센스 올리고뉴클레오티드 및 그의 용도
KR20220062517A (ko) 2019-08-15 2022-05-17 아이오니스 파마수티컬즈, 인코포레이티드 결합 변형된 올리고머 화합물 및 이의 용도
BR112023001624A2 (pt) 2020-07-28 2023-02-23 Ionis Pharmaceuticals Inc Compostos e métodos para reduzir a expressão de app
US20240117349A1 (en) * 2021-01-29 2024-04-11 Alnylam Pharmaceuticals, Inc. iRNA COMPOSITIONS AND METHODS FOR SILENCING AMYLOID PRECURSOR PROTEIN (APP)
CN118369427A (zh) * 2021-10-15 2024-07-19 阿尔尼拉姆医药品有限公司 肝外递送irna组合物及其使用方法
TW202511488A (zh) * 2023-08-31 2025-03-16 大陸商上海拓界生物醫藥科技有限公司 靶向ＡＰＰ的ＲＮＡｉ劑及其醫藥用途
WO2025228429A1 (zh) * 2024-04-30 2025-11-06 北京安龙生物医药有限公司 靶向淀粉样前体蛋白基因的寡核苷酸及其用途

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2126451A1 (en) * 1991-12-24 1993-07-08 Brett P. Monia Compositions and methods for modulating .beta.-amyloid
US20030232435A1 (en) * 2002-06-14 2003-12-18 Isis Pharmaceuticals Inc. Antisense modulation of amyloid beta protein precursor expression
GB0324854D0 (en) * 2003-10-24 2003-11-26 Expresson Biosystems Ltd App/ena antisense
WO2009105572A2 (en) * 2008-02-19 2009-08-27 Edunn Biotechonology Inc. Antisense modulation of amyloid beta protein expression
US20100190807A1 (en) * 2008-08-26 2010-07-29 Senex Biotechnology, Inc. CDKI Pathway inhibitors and uses thereof to regulate expression to TAU protein
US20110301052A1 (en) * 2010-04-16 2011-12-08 Mcneel Douglas G Diagnostic evaluation of antibody responses to commonly recognized prostate cancer-associated antigens
EP3004354A4 (en) * 2013-06-07 2017-01-11 Rana Therapeutics, Inc. Compositions and methods for modulating foxp3 expression
WO2015023941A1 (en) * 2013-08-16 2015-02-19 Rana Therapeutics, Inc. Oligonucleotides targeting euchromatin regions of genes
BR112016007751A2 (pt) * 2013-10-11 2017-09-12 Ionis Pharmaceuticals Inc composições para modulação de expressão de c9orf72
US9926556B2 (en) * 2014-04-28 2018-03-27 Ionis Pharmaceuticals, Inc. Linkage modified oligomeric compounds
US11732260B2 (en) * 2018-03-02 2023-08-22 Ionis Pharmaceuticals, Inc. Compounds and methods for the modulation of amyloid-β precursor protein

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Publication number Publication date
EP3918073A4 (en) 2023-11-22
JP2025000693A (ja) 2025-01-07
US20220380773A1 (en) 2022-12-01
WO2020160163A1 (en) 2020-08-06
JP7557469B2 (ja) 2024-09-27
UY38562A (es) 2020-08-31
EP3918073A1 (en) 2021-12-08
JP2022518929A (ja) 2022-03-17

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