CA3214439A1 - Compositions and methods for inhibiting ketohexokinase (khk) - Google Patents

Compositions and methods for inhibiting ketohexokinase (khk) Download PDF

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Publication number
CA3214439A1
CA3214439A1 CA3214439A CA3214439A CA3214439A1 CA 3214439 A1 CA3214439 A1 CA 3214439A1 CA 3214439 A CA3214439 A CA 3214439A CA 3214439 A CA3214439 A CA 3214439A CA 3214439 A1 CA3214439 A1 CA 3214439A1
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CA
Canada
Prior art keywords
seq
nucleotides
nos
oligonucleotide
antisense strand
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
CA3214439A
Other languages
English (en)
French (fr)
Inventor
Bob Dale Brown
Henryk T. Dudek
Utsav SAXENA
JiHye PARK
Marc Abrams
Martin Lee KOSER
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.)
Boehringer Ingelheim International GmbH
Original Assignee
Boehringer Ingelheim International GmbH
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 Boehringer Ingelheim International GmbH filed Critical Boehringer Ingelheim International GmbH
Publication of CA3214439A1 publication Critical patent/CA3214439A1/en
Pending legal-status Critical Current

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    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • 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 nucleic acids [NA]
    • 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
    • C12N2310/34—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
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    • 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
    • C12N2310/50—Physical structure
    • C12N2310/53—Physical structure partially self-complementary or closed
    • C12N2310/531—Stem-loop; Hairpin

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Biophysics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Virology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Detergent Compositions (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CA3214439A 2021-04-12 2022-04-11 Compositions and methods for inhibiting ketohexokinase (khk) Pending CA3214439A1 (en)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US202163173775P 2021-04-12 2021-04-12
US63/173,775 2021-04-12
US202163182277P 2021-04-30 2021-04-30
US63/182,277 2021-04-30
EP21196784 2021-09-15
EP21196784.9 2021-09-15
PCT/EP2022/059663 WO2022218941A2 (en) 2021-04-12 2022-04-11 Compositions and methods for inhibiting ketohexokinase (khk)

Publications (1)

Publication Number Publication Date
CA3214439A1 true CA3214439A1 (en) 2022-10-20

Family

ID=81448852

Family Applications (1)

Application Number Title Priority Date Filing Date
CA3214439A Pending CA3214439A1 (en) 2021-04-12 2022-04-11 Compositions and methods for inhibiting ketohexokinase (khk)

Country Status (20)

Country Link
US (2) US20220340909A1 (enExample)
EP (1) EP4323518A2 (enExample)
JP (1) JP2024516356A (enExample)
KR (1) KR20230170732A (enExample)
CN (1) CN117120612A (enExample)
AU (1) AU2022256742A1 (enExample)
BR (1) BR112023017367A2 (enExample)
CA (1) CA3214439A1 (enExample)
CL (1) CL2023003017A1 (enExample)
CO (1) CO2023013465A2 (enExample)
CR (1) CR20230482A (enExample)
DO (1) DOP2023000223A (enExample)
EC (1) ECSP23076906A (enExample)
IL (1) IL307315A (enExample)
JO (1) JOP20230250A1 (enExample)
MX (1) MX2023012048A (enExample)
PE (1) PE20250400A1 (enExample)
PH (1) PH12023552830A1 (enExample)
TW (1) TW202305135A (enExample)
WO (1) WO2022218941A2 (enExample)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA3211059A1 (en) * 2021-02-26 2022-09-01 Alnylam Pharmaceuticals, Inc. Ketohexokinase (khk) irna compositions and methods of use thereof
TW202430191A (zh) 2022-10-11 2024-08-01 德商百靈佳殷格翰國際股份有限公司 用於治療伴有晚期纖維化及/或硬化之nash的方法
TW202430192A (zh) 2022-10-11 2024-08-01 德商百靈佳殷格翰國際股份有限公司 用於治療nash之劑量方案
WO2024175062A1 (zh) * 2023-02-23 2024-08-29 大睿生物医药科技(上海)有限公司 调控KHK基因活性的dsRNA分子
WO2024260379A1 (zh) * 2023-06-20 2024-12-26 施能康医药科技(苏州)有限公司 靶向已酮糖激酶的核酸及其用途
CN118703500B (zh) * 2024-01-30 2025-06-17 大连医科大学 一种果糖激酶khk的小干扰和短发夹rna序列组合及其应用
WO2025184876A1 (zh) * 2024-03-07 2025-09-12 竣莅医药科技（无锡）有限公司 一种rna干扰触发分子与对应核酸干扰药物制剂及其用途
WO2026149467A1 (zh) * 2025-01-09 2026-07-16 云合智药（苏州）生物科技有限公司 用于抑制己酮糖激酶表达的RNAi剂及其应用

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US5977343A (en) 1992-05-14 1999-11-02 Ribozyme Pharmaceuticals, Inc. Synthesis, deprotection, analysis and purification of RNA and ribozymes
US5804683A (en) 1992-05-14 1998-09-08 Ribozyme Pharmaceuticals, Inc. Deprotection of RNA with alkylamine
EP1253199A1 (en) 1993-09-02 2002-10-30 Ribozyme Pharmaceuticals, Inc. Abasic moieties containing enzymatic nucleic acids
US5889136A (en) 1995-06-09 1999-03-30 The Regents Of The University Of Colorado Orthoester protecting groups in RNA synthesis
US5998203A (en) 1996-04-16 1999-12-07 Ribozyme Pharmaceuticals, Inc. Enzymatic nucleic acids containing 5'-and/or 3'-cap structures
US6111086A (en) 1998-02-27 2000-08-29 Scaringe; Stephen A. Orthoester protecting groups
KR20080023768A (ko) 2000-03-30 2008-03-14 화이트헤드 인스티튜트 포 바이오메디칼 리서치 Ｒｎａ 간섭의 ｒｎａ 서열 특이적인 매개체
CN100523215C (zh) 2000-12-01 2009-08-05 马普科技促进协会 介导rna干涉的小rna分子
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MX2022011009A (es) * 2020-03-06 2022-10-07 Alnylam Pharmaceuticals Inc Composiciones de acido ribonucleico de interferencia (arni) de ketohexocinasa (khk) y metodos de uso de las mismas.
CA3211059A1 (en) * 2021-02-26 2022-09-01 Alnylam Pharmaceuticals, Inc. Ketohexokinase (khk) irna compositions and methods of use thereof

Also Published As

Publication number Publication date
US20220340909A1 (en) 2022-10-27
IL307315A (en) 2023-11-01
BR112023017367A2 (pt) 2023-12-12
TW202305135A (zh) 2023-02-01
CL2023003017A1 (es) 2024-05-03
DOP2023000223A (es) 2023-11-15
US20250092403A1 (en) 2025-03-20
JP2024516356A (ja) 2024-04-15
KR20230170732A (ko) 2023-12-19
MX2023012048A (es) 2023-10-23
WO2022218941A2 (en) 2022-10-20
PE20250400A1 (es) 2025-02-11
CR20230482A (es) 2023-12-07
WO2022218941A3 (en) 2023-02-23
PH12023552830A1 (en) 2024-05-20
JOP20230250A1 (ar) 2023-10-12
CN117120612A (zh) 2023-11-24
EP4323518A2 (en) 2024-02-21
CO2023013465A2 (es) 2023-10-30
ECSP23076906A (es) 2023-11-30
AU2022256742A1 (en) 2023-09-07

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