CA3091979A1 - Modified oligonucleotides and methods of use in tauopathies - Google Patents

Modified oligonucleotides and methods of use in tauopathies Download PDF

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Publication number
CA3091979A1
CA3091979A1 CA3091979A CA3091979A CA3091979A1 CA 3091979 A1 CA3091979 A1 CA 3091979A1 CA 3091979 A CA3091979 A CA 3091979A CA 3091979 A CA3091979 A CA 3091979A CA 3091979 A1 CA3091979 A1 CA 3091979A1
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Canada
Prior art keywords
oligonucleotide
modified
nucleotides
formula
nucleosides
Prior art date
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Pending
Application number
CA3091979A
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English (en)
French (fr)
Inventor
Andreas Ebneth
Constantin Van Outryve D'ydewalle
Sergei Gryaznov
Saul Martinez Montero
Vivek Kumar Rajnanshi
Leonid Beigelman
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Janssen Pharmaceutica NV
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Janssen Pharmaceutica NV
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Publication of CA3091979A1 publication Critical patent/CA3091979A1/en
Pending legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • 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
    • 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
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • 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
    • C12N2310/315—Phosphorothioates
    • 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
    • C12N2310/33—Chemical structure of the base
    • C12N2310/334—Modified C
    • C12N2310/3341—5-Methylcytosine
    • 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
    • C12N2310/33—Chemical structure of the base
    • C12N2310/335—Modified T or U
    • 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
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/341—Gapmers, i.e. of the type ===---===
    • 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
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/345—Spatial arrangement of the modifications having at least two different backbone modifications
    • 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
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
    • 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
    • C12N2310/352—Nature of the modification linked to the nucleic acid via a carbon atom
    • C12N2310/3521—Methyl
    • 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
    • C12N2310/352—Nature of the modification linked to the nucleic acid via a carbon atom
    • C12N2310/3525—MOE, methoxyethoxy
    • 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
    • C12N2320/50—Methods for regulating/modulating their activity

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Zoology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Psychiatry (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Hospice & Palliative Care (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
CA3091979A 2018-03-13 2019-03-13 Modified oligonucleotides and methods of use in tauopathies Pending CA3091979A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201862642499P 2018-03-13 2018-03-13
US62/642,499 2018-03-13
PCT/EP2019/056312 WO2019175260A2 (en) 2018-03-13 2019-03-13 Modified oligonucleotides and methods of use in tauopathies

Publications (1)

Publication Number Publication Date
CA3091979A1 true CA3091979A1 (en) 2019-09-19

Family

ID=65861258

Family Applications (1)

Application Number Title Priority Date Filing Date
CA3091979A Pending CA3091979A1 (en) 2018-03-13 2019-03-13 Modified oligonucleotides and methods of use in tauopathies

Country Status (15)

Country Link
US (2) US11453881B2 (https=)
EP (2) EP3765476B1 (https=)
JP (1) JP2021515784A (https=)
KR (1) KR20200131263A (https=)
CN (1) CN111868068A (https=)
AU (1) AU2019233612A1 (https=)
BR (1) BR112020018365A2 (https=)
CA (1) CA3091979A1 (https=)
EA (1) EA202092156A1 (https=)
ES (1) ES3063421T3 (https=)
IL (1) IL277238A (https=)
MA (1) MA52149A (https=)
MX (1) MX2020009532A (https=)
SG (1) SG11202008895WA (https=)
WO (1) WO2019175260A2 (https=)

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Publication number Priority date Publication date Assignee Title
AU2013203395A1 (en) 2012-03-30 2013-10-17 Isis Pharmaceuticals, Inc. Compositions and methods for modulating TAU expression for reducing seizure and modifying a neurodegenerative syndrome
TWI772856B (zh) 2013-07-19 2022-08-01 美商百健Ｍａ公司 用於調節τ蛋白表現之組合物
WO2021198958A1 (en) * 2020-04-01 2021-10-07 Janssen Biopharma, Inc. Nucleic acid polymers
PE20240648A1 (es) * 2021-07-23 2024-04-04 Biogen Ma Inc Metodos para reducir la expresion de tau
AU2024313057A1 (en) * 2023-06-22 2025-10-30 Denali Therapeutics Inc. Compositions and methods for modulating tau expression
US12551569B2 (en) 2024-03-31 2026-02-17 Arrowhead Pharmaceuticals, Inc. RNAi agents for inhibiting expression of microtubule associated protein tau (MAPT), compositions thereof, and methods of use
WO2026025082A1 (en) * 2024-07-25 2026-01-29 Biogen Ma Inc. Methods for treating alzheimer's disease

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JP3756313B2 (ja) 1997-03-07 2006-03-15 武 今西 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体
US6770748B2 (en) 1997-03-07 2004-08-03 Takeshi Imanishi Bicyclonucleoside and oligonucleotide analogue
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
CZ296576B6 (cs) 1999-02-12 2006-04-12 Sankyo Company Limited Nukleosidový analog a oligonukleotidový analog a farmaceutický prostredek, sonda a primer s jeho obsahem
US7084125B2 (en) 1999-03-18 2006-08-01 Exiqon A/S Xylo-LNA analogues
EP1178999B1 (en) 1999-05-04 2007-03-14 Santaris Pharma A/S L-ribo-lna analogues
US6525191B1 (en) 1999-05-11 2003-02-25 Kanda S. Ramasamy Conformationally constrained L-nucleosides
JP4151751B2 (ja) 1999-07-22 2008-09-17 第一三共株式会社 新規ビシクロヌクレオシド類縁体
CN1317291C (zh) * 1999-09-10 2007-05-23 杰龙公司 寡核苷酸n3′→p5′硫代氨基磷酸酯,其合成及应用
US7569575B2 (en) 2002-05-08 2009-08-04 Santaris Pharma A/S Synthesis of locked nucleic acid derivatives
CA2504694C (en) 2002-11-05 2013-10-01 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
DK1794313T3 (da) * 2004-06-21 2013-07-22 Proteome Sciences Plc Fremgangsmåde til screeninger der anvender C-ABL, FYN og SYK i kombination med tau-protein
GB0605337D0 (en) 2006-03-17 2006-04-26 Genomica Sau Treatment of CNS conditions
CN109810977A (zh) * 2012-05-26 2019-05-28 株式会社博纳克 具有递送功能的基因表达调控用单链核酸分子
US9228189B2 (en) * 2012-10-26 2016-01-05 Geron Corporation C-myc antisense oligonucleotides and methods for using the same to treat cell-proliferative disorders
ES2807379T3 (es) * 2013-03-14 2021-02-22 Ionis Pharmaceuticals Inc Composiciones y métodos para regular la expresión de Tau
TWI772856B (zh) * 2013-07-19 2022-08-01 美商百健Ｍａ公司 用於調節τ蛋白表現之組合物
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Also Published As

Publication number Publication date
WO2019175260A3 (en) 2019-11-14
KR20200131263A (ko) 2020-11-23
EA202092156A1 (ru) 2021-04-01
US20210095284A1 (en) 2021-04-01
EP3765476A2 (en) 2021-01-20
EP3765476B1 (en) 2025-11-26
EP3922637A1 (en) 2021-12-15
MX2020009532A (es) 2020-10-05
MA52149A (fr) 2021-01-20
EP3765476C0 (en) 2025-11-26
ES3063421T3 (en) 2026-04-16
BR112020018365A2 (pt) 2020-12-29
SG11202008895WA (en) 2020-10-29
WO2019175260A2 (en) 2019-09-19
AU2019233612A1 (en) 2020-09-10
IL277238A (en) 2020-10-29
CN111868068A (zh) 2020-10-30
JP2021515784A (ja) 2021-06-24
US20240011029A1 (en) 2024-01-11
US11453881B2 (en) 2022-09-27

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