WO2023081500A2 - Conjugués oligonucleotides/arni - Google Patents

Conjugués oligonucleotides/arni Download PDF

Info

Publication number
WO2023081500A2
WO2023081500A2 PCT/US2022/049230 US2022049230W WO2023081500A2 WO 2023081500 A2 WO2023081500 A2 WO 2023081500A2 US 2022049230 W US2022049230 W US 2022049230W WO 2023081500 A2 WO2023081500 A2 WO 2023081500A2
Authority
WO
WIPO (PCT)
Prior art keywords
nucleotides
oligonucleotide
sense strand
nucleotide
positions
Prior art date
Application number
PCT/US2022/049230
Other languages
English (en)
Other versions
WO2023081500A3 (fr
Inventor
Bob Dale Brown
Maire JUNG
Travis GRIM
Matthew COSTALES
Marc Abrams
Martin Lee KOSER
Beata KAMINSKA
Jessica LAPIERRE
Original Assignee
Dicerna 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 Dicerna Pharmaceuticals, Inc. filed Critical Dicerna Pharmaceuticals, Inc.
Publication of WO2023081500A2 publication Critical patent/WO2023081500A2/fr
Publication of WO2023081500A3 publication Critical patent/WO2023081500A3/fr

Links

Classifications

    • 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
    • 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
    • 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
    • C12N15/1137—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 enzymes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y102/00—Oxidoreductases acting on the aldehyde or oxo group of donors (1.2)
    • C12Y102/01—Oxidoreductases acting on the aldehyde or oxo group of donors (1.2) with NAD+ or NADP+ as acceptor (1.2.1)
    • C12Y102/01003—Aldehyde dehydrogenase (NAD+) (1.2.1.3)
    • 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
    • C12N2310/14—Type of nucleic acid interfering N.A.
    • 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
    • C12N2310/323—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
    • C12N2310/35—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
    • C12N2310/50—Physical structure
    • C12N2310/53—Physical structure partially self-complementary or closed
    • C12N2310/531—Stem-loop; Hairpin

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Virology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne des oligonucléotides conjugués avec des lipides qui inhibent ou réduisent l'expression de gènes cibles. L'invention concerne également des compositions les comprenant et leurs utilisations, en particulier des utilisations se rapportant au traitement de maladies, de troubles et/ou d'états associés à une diminution induite par un déclencheur d'ARNi de l'expression génique cible.
PCT/US2022/049230 2021-11-08 2022-11-08 Conjugués oligonucleotides/arni WO2023081500A2 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US202163277097P 2021-11-08 2021-11-08
US63/277,097 2021-11-08
US202263340291P 2022-05-10 2022-05-10
US63/340,291 2022-05-10

Publications (2)

Publication Number Publication Date
WO2023081500A2 true WO2023081500A2 (fr) 2023-05-11
WO2023081500A3 WO2023081500A3 (fr) 2023-08-03

Family

ID=86242133

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2022/049230 WO2023081500A2 (fr) 2021-11-08 2022-11-08 Conjugués oligonucleotides/arni

Country Status (2)

Country Link
TW (1) TW202333750A (fr)
WO (1) WO2023081500A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024040041A1 (fr) * 2022-08-15 2024-02-22 Dicerna Pharmaceuticals, Inc. Régulation de l'activité de molécules d'arni

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101147147B1 (ko) * 2004-04-01 2012-05-25 머크 샤프 앤드 돔 코포레이션 Ｒｎａ 간섭의 오프 타겟 효과 감소를 위한 변형된폴리뉴클레오타이드
CN101842381A (zh) * 2007-08-27 2010-09-22 波士顿生物医药公司 作为微小rna模拟物或抑制剂的不对称rna双链体的组合物
AU2019405783A1 (en) * 2018-12-19 2021-07-01 Alnylam Pharmaceuticals, Inc. Amyloid precursor protein (APP) RNAi agent compositions and methods of use thereof
CN113795581A (zh) * 2019-05-03 2021-12-14 迪克纳制药公司 具有缩短的有义链的双链核酸抑制剂分子

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024040041A1 (fr) * 2022-08-15 2024-02-22 Dicerna Pharmaceuticals, Inc. Régulation de l'activité de molécules d'arni

Also Published As

Publication number Publication date
TW202333750A (zh) 2023-09-01
WO2023081500A3 (fr) 2023-08-03

Similar Documents

Publication Publication Date Title
CN106795200B (zh) Galnac亚磷酰胺、其核酸缀合物及其用途
JP2022171811A (ja) キメラ２重鎖核酸
JP6440170B2 (ja) キメラ一本鎖アンチセンスポリヌクレオチドおよび二本鎖アンチセンス剤
CN113166759A (zh) 经化学修饰的RNAi构建体及其用途
KR20120104381A (ko) Ｈｓｆ1-관련 질환을 치료하기 위한 유기 조성물
JP2022551269A (ja) 最小フッ素含有量を用いた低分子干渉ｒｎａの化学修飾
AU2022256742A1 (en) Compositions and methods for inhibiting ketohexokinase (khk)
WO2023081500A2 (fr) Conjugués oligonucleotides/arni
US20240117351A1 (en) Compositions and methods for inhibiting gene expression in the central nervous system
WO2023081823A1 (fr) Conjugaison de lipides pour le ciblage d'astrocytes du système nerveux central
US20230416742A1 (en) Compositions and methods for inhibiting mapt expression
WO2023081822A1 (fr) Conjugaison de lipides pour le ciblage d'oligodendrocytes du système nerveux central
WO2022240952A1 (fr) Conjugaison de lipides pour le ciblage de neurones du système nerveux central
WO2024040041A1 (fr) Régulation de l'activité de molécules d'arni
CN117597444A (zh) 用于靶向中枢神经系统的神经元的脂质缀合
US20230272393A1 (en) Compositions and methods for modulating apoc3 expression
TW202409275A (zh) 用於抑制ｓｎｃａ表現之組合物及方法
WO2023220351A1 (fr) Compositions et procédés d'inhibition de l'expression de snca
US20240124875A1 (en) Rnai conjugates and uses thereof
WO2022221430A1 (fr) Compositions et procédés de modulation de l'expression de pnpla3
TW202345873A (zh) 調節ｓｃａｐ活性之組合物及方法
WO2023178141A2 (fr) Combinaison d'oligonucléotides de ciblage de stat3 et d'inhibiteurs de pd-l1
CN117280031A (zh) 用于抑制核受体亚家族1组h成员3（nr1h3）表达的组合物和方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22890908

Country of ref document: EP

Kind code of ref document: A2