CN119790152A - 使用unc13a基因转录本的调节剂治疗神经系统疾病 - Google Patents

使用unc13a基因转录本的调节剂治疗神经系统疾病 Download PDF

Info

Publication number
CN119790152A
CN119790152A CN202280090919.7A CN202280090919A CN119790152A CN 119790152 A CN119790152 A CN 119790152A CN 202280090919 A CN202280090919 A CN 202280090919A CN 119790152 A CN119790152 A CN 119790152A
Authority
CN
China
Prior art keywords
oligonucleotide
spacer
seq
nos
compound
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
CN202280090919.7A
Other languages
English (en)
Chinese (zh)
Inventor
S·欣克利
D·布朗
D·艾尔鲍姆
M·E·卡梅尔加恩
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.)
Quelis Co
Original Assignee
Quelis Co
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 Quelis Co filed Critical Quelis Co
Publication of CN119790152A publication Critical patent/CN119790152A/zh
Pending legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/712—Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • 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
    • 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
    • C12N2310/323—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
    • 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
    • C12N2310/332—Abasic residue
    • 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
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/344—Position-specific modifications, e.g. on every purine, at the 3'-end
    • 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
    • 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
    • C12N2320/30—Special therapeutic applications
    • C12N2320/33—Alteration of splicing

Landscapes

  • 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)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biochemistry (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Neurosurgery (AREA)
  • Epidemiology (AREA)
  • Neurology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CN202280090919.7A 2021-12-03 2022-12-02 使用unc13a基因转录本的调节剂治疗神经系统疾病 Pending CN119790152A (zh)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US202163285786P 2021-12-03 2021-12-03
US63/285,786 2021-12-03
US202263350206P 2022-06-08 2022-06-08
US63/350,206 2022-06-08
US202263398987P 2022-08-18 2022-08-18
US63/398,987 2022-08-18
PCT/US2022/051713 WO2023102225A2 (en) 2021-12-03 2022-12-02 Treatment of neurological diseases using modulators of unc13a gene transcripts

Publications (1)

Publication Number Publication Date
CN119790152A true CN119790152A (zh) 2025-04-08

Family

ID=86613080

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202280090919.7A Pending CN119790152A (zh) 2021-12-03 2022-12-02 使用unc13a基因转录本的调节剂治疗神经系统疾病

Country Status (16)

Country Link
US (1) US20250051766A1 (https=)
EP (1) EP4441225A4 (https=)
JP (1) JP2024543214A (https=)
KR (1) KR20240129627A9 (https=)
CN (1) CN119790152A (https=)
AU (1) AU2022400851A1 (https=)
CA (1) CA3239482A1 (https=)
CL (1) CL2024001657A1 (https=)
CO (1) CO2024008076A2 (https=)
CR (1) CR20240269A (https=)
DO (1) DOP2024000107A (https=)
IL (1) IL313203A (https=)
JO (1) JOP20240125A1 (https=)
MX (1) MX2024006763A (https=)
PE (1) PE20250677A1 (https=)
WO (1) WO2023102225A2 (https=)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2603454A (en) 2020-12-09 2022-08-10 Ucl Business Ltd Novel therapeutics for the treatment of neurodegenerative disorders
AU2023356317A1 (en) * 2022-10-05 2025-05-15 Trace Neuroscience, Inc. Unc13a antisense oligonucleotides and uses thereof
WO2024178223A1 (en) * 2023-02-24 2024-08-29 Northwestern University Antisense oligonucleotides for preventing unc13a misplicing
WO2025186619A1 (en) * 2024-03-05 2025-09-12 Takeda Pharmaceutical Company Limited Compositions and methods for splicing modulation of unc13a
WO2025255388A1 (en) * 2024-06-05 2025-12-11 Camp4 Therapeutics Corporation Modulation of syngap1 gene transcription using antisense oligonucleotides targeting regulatory rnas
WO2026080323A1 (en) 2024-10-09 2026-04-16 Quralis Corporation Treatment of neurological diseases using modulators of unc13a gene transcripts

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060008800A1 (en) * 2001-11-05 2006-01-12 Christian Rosenmund Unc-13 in the modulation of neurotransmission and secretion events
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
DK3155101T3 (da) * 2014-06-16 2020-05-04 Univ Johns Hopkins Sammensætninger og fremgangsmåder til ekspression af CRISPR-leder-RNA´er under anvendelse af H1-promotoren
WO2020102472A1 (en) * 2018-11-15 2020-05-22 President And Fellows Of Harvard College Methods and compositions related to targeting ffar2 and ilc3 populations for the treatment of a gastrointestinal disease
AU2022255175A1 (en) * 2021-04-06 2023-11-23 Trace Neuroscience, Inc. Compositions and methods for treating tdp-43 proteinopathy

Also Published As

Publication number Publication date
EP4441225A2 (en) 2024-10-09
AU2022400851A1 (en) 2024-06-20
IL313203A (en) 2024-07-01
EP4441225A4 (en) 2026-03-11
WO2023102225A2 (en) 2023-06-08
JOP20240125A1 (ar) 2024-06-02
CR20240269A (es) 2024-09-13
CO2024008076A2 (es) 2024-11-18
WO2023102225A3 (en) 2024-03-28
US20250051766A1 (en) 2025-02-13
KR20240129627A (ko) 2024-08-27
CA3239482A1 (en) 2023-06-08
MX2024006763A (es) 2024-08-15
CL2024001657A1 (es) 2024-12-20
PE20250677A1 (es) 2025-03-04
KR20240129627A9 (ko) 2025-12-10
JP2024543214A (ja) 2024-11-19
DOP2024000107A (es) 2024-09-30

Similar Documents

Publication Publication Date Title
JP7795914B2 (ja) 神経学的疾患を処置するためのオリゴヌクレオチドおよびその使用方法
US20250051766A1 (en) Treatment of neurological diseases using modulators of unc13a gene transcripts
KR20240129626A (ko) 변형된 백본 화학을 갖는 스플라이스 스위처 안티센스 올리고뉴클레오티드
IL313205A (en) Microbial consortia
AU2020296104A1 (en) PPM1A inhibitors and methods of using same
US20230235332A1 (en) Treatment of neurological diseases using modulators of gene transcripts
WO2023102548A1 (en) Treatment of neurological diseases using modulators of kcnq2 gene transcripts
CN119452086A (zh) 具有修饰的主链化学的gapmer反义寡核苷酸
KR20260022373A (ko) 변형된 unc13a 올리고뉴클레오티드
IL313204A (en) Methods for the synthesis of factor D complement inhibitors
WO2023102227A2 (en) Treatment of neurological diseases using modulators of smn2 gene transcripts
CN116528878A (zh) 使用基因转录物调控剂治疗神经学疾病
HK40121031A (zh) 具有经修饰的主链化学的剪接转换器反义寡核苷酸
HK40097883A (zh) 使用基因转录物调控剂治疗神经学疾病
HK40121931A (zh) 具有修饰的主链化学的gapmer反义寡核苷酸

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination