CA3241870A1 - Splice switcher antisense oligonucleotides with modified backbone chemistries - Google Patents

Splice switcher antisense oligonucleotides with modified backbone chemistries

Info

Publication number
CA3241870A1
CA3241870A1 CA3241870A CA3241870A CA3241870A1 CA 3241870 A1 CA3241870 A1 CA 3241870A1 CA 3241870 A CA3241870 A CA 3241870A CA 3241870 A CA3241870 A CA 3241870A CA 3241870 A1 CA3241870 A1 CA 3241870A1
Authority
CA
Canada
Prior art keywords
oligonucleotide
seq
linkage
nos
spacer
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
CA3241870A
Other languages
English (en)
French (fr)
Inventor
Sandra HINCKLEY
Duncan Brown
Daniel Elbaum
Marisa Elizabeth KAMELGARN
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.)
Quralis Corp
Original Assignee
Quralis Corp
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 Quralis Corp filed Critical Quralis Corp
Publication of CA3241870A1 publication Critical patent/CA3241870A1/en
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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C07H1/02—Phosphorylation
    • 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
    • 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
    • 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
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4702—Regulators; Modulating activity
    • 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
    • C07K14/475—Growth factors; Growth regulators
    • 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
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • 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
    • C12N2310/323—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
    • C12N2310/352—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)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Biophysics (AREA)
  • Biotechnology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Toxicology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Epidemiology (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Immunology (AREA)
  • Cell Biology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
CA3241870A 2021-12-03 2022-12-02 Splice switcher antisense oligonucleotides with modified backbone chemistries Pending CA3241870A1 (en)

Applications Claiming Priority (15)

Application Number Priority Date Filing Date Title
US202163285628P 2021-12-03 2021-12-03
US202163285933P 2021-12-03 2021-12-03
US202163285786P 2021-12-03 2021-12-03
US202163285631P 2021-12-03 2021-12-03
US63/285,631 2021-12-03
US63/285,933 2021-12-03
US63/285,786 2021-12-03
US63/285,628 2021-12-03
US202263350206P 2022-06-08 2022-06-08
US63/350,206 2022-06-08
US202263398987P 2022-08-18 2022-08-18
US202263398992P 2022-08-18 2022-08-18
US63/398,992 2022-08-18
US63/398,987 2022-08-18
PCT/US2022/051740 WO2023102242A2 (en) 2021-12-03 2022-12-02 Splice switcher antisense oligonucleotides with modified backbone chemistries

Publications (1)

Publication Number Publication Date
CA3241870A1 true CA3241870A1 (en) 2023-06-08

Family

ID=86613046

Family Applications (1)

Application Number Title Priority Date Filing Date
CA3241870A Pending CA3241870A1 (en) 2021-12-03 2022-12-02 Splice switcher antisense oligonucleotides with modified backbone chemistries

Country Status (9)

Country Link
EP (1) EP4441226A2 (https=)
JP (1) JP2024545052A (https=)
KR (1) KR20240129626A9 (https=)
CN (1) CN119522282A (https=)
AU (1) AU2022402929A1 (https=)
CA (1) CA3241870A1 (https=)
IL (1) IL313141A (https=)
MX (1) MX2024006612A (https=)
WO (1) WO2023102242A2 (https=)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
GB202315883D0 (en) * 2023-10-17 2023-11-29 Univ Oxford Innovation Ltd Method
WO2025186619A1 (en) * 2024-03-05 2025-09-12 Takeda Pharmaceutical Company Limited Compositions and methods for splicing modulation of unc13a

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2003232071A1 (en) * 2002-05-06 2003-11-17 Genelabs Technologies, Inc. Nucleoside derivatives for treating hepatitis c virus infection
EP3260540A1 (en) * 2010-11-12 2017-12-27 The General Hospital Corporation Polycomb-associated non-coding rnas
WO2020150290A2 (en) * 2019-01-14 2020-07-23 President And Fellows Of Harvard College Methods and compositions for restoring stmn2 levels
JP7795914B2 (ja) * 2019-06-03 2026-01-08 クラリス コーポレーション 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

Also Published As

Publication number Publication date
EP4441226A2 (en) 2024-10-09
IL313141A (en) 2024-07-01
WO2023102242A2 (en) 2023-06-08
JP2024545052A (ja) 2024-12-05
KR20240129626A9 (ko) 2025-12-10
AU2022402929A1 (en) 2024-06-13
MX2024006612A (es) 2024-06-12
WO2023102242A3 (en) 2023-10-12
WO2023102242A9 (en) 2024-10-31
KR20240129626A (ko) 2024-08-27
CN119522282A (zh) 2025-02-25

Similar Documents

Publication Publication Date Title
CA3241870A1 (en) Splice switcher antisense oligonucleotides with modified backbone chemistries
CA2640058C (en) Oligomeric compounds and compositions for the use in modulation of micrornas
JP5441688B2 (ja) ５’修飾二環式核酸類似体
JP7601441B2 (ja) アンジェルマン症候群アンチセンス治療
JP7379387B2 (ja) Ａｔｘｎ２発現を制御するためのオリゴヌクレオチド
CA3239482A1 (en) Treatment of neurological diseases using modulators of unc13a gene transcripts
CA3142526A1 (en) Oligonucleotides and methods of use for treating neurological diseases
JP2001002696A (ja) ギャップを有する２′修飾オリゴヌクレオチド
WO2008154401A2 (en) Carbocyclic bicyclic nucleic acid analogs
CN111373043A (zh) 用于降低snca表达的化合物和方法
WO2021153747A1 (ja) Ａｔｎ１のアンチセンスオリゴヌクレオチド
US20240182889A1 (en) Microrna-27b inhibitors
AU2021284360A1 (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
EA053024B1 (ru) Антисмысловые олигонуклеотиды-переключатели сплайсинга с модифицированной химией скелета
RU2845374C2 (ru) 6'-цианонуклеозид модифицированный замкнутый, нуклеотиды и полимеры нуклеиновых кислот
JP7776420B2 (ja) Ａｔａｘｉｎ ３発現を調節するための化合物、方法及び医薬組成物
HK40121031A (zh) 具有经修饰的主链化学的剪接转换器反义寡核苷酸
JP2025520514A (ja) プログラニュリンを標的とするためのアンチセンスオリゴヌクレオチド
WO2026009916A1 (ja) ２本鎖オリゴヌクレオチド
CN119876147A (zh) 抑制trpv1表达的寡聚核苷酸、组合物及应用
KR20240110595A (ko) 안정화된 rna 제제
WO2024035613A1 (en) Optimized gapmers antisense oligonucleotides for increasing foxg1 expression
JP2023137052A (ja) コンドロイチン硫酸生合成を阻害するアンチセンス核酸

Legal Events

Date Code Title Description
W00 Other event occurred

Free format text: ST27 STATUS EVENT CODE: A-1-1-W00-W00-W160 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: INACTIVE: COVER PAGE PUBLISHED

Effective date: 20240704

P11 Amendment of application requested

Free format text: ST27 STATUS EVENT CODE: A-1-1-P10-P11-P102 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: AMENDMENT DETERMINED COMPLIANT

Effective date: 20250125

W00 Other event occurred

Free format text: ST27 STATUS EVENT CODE: A-1-1-W10-W00-W111 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: CORRESPONDENT DETERMINED COMPLIANT

Effective date: 20250125

MFA Maintenance fee for application paid

Free format text: FEE DESCRIPTION TEXT: MF (APPLICATION, 3RD ANNIV.) - STANDARD

Year of fee payment: 3

U00 Fee paid

Free format text: ST27 STATUS EVENT CODE: A-1-1-U10-U00-U101 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE REQUEST RECEIVED

Effective date: 20251201

U11 Full renewal or maintenance fee paid

Free format text: ST27 STATUS EVENT CODE: A-1-1-U10-U11-U102 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE FEE PAYMENT PAID IN FULL

Effective date: 20251201