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
    • 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
    • C12N2310/50—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)
  • Plant Pathology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Microbiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Physics & Mathematics (AREA)
  • Virology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Detergent Compositions (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
EP21196784.9 2021-09-15
EP21196784 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 (https=)
EP (1) EP4323518A2 (https=)
JP (1) JP2024516356A (https=)
KR (1) KR20230170732A (https=)
CN (1) CN117120612A (https=)
AU (1) AU2022256742A1 (https=)
BR (1) BR112023017367A2 (https=)
CA (1) CA3214439A1 (https=)
CL (1) CL2023003017A1 (https=)
CO (1) CO2023013465A2 (https=)
CR (1) CR20230482A (https=)
DO (1) DOP2023000223A (https=)
EC (1) ECSP23076906A (https=)
IL (1) IL307315A (https=)
JO (1) JOP20230250A1 (https=)
MX (1) MX2023012048A (https=)
PE (1) PE20250400A1 (https=)
PH (1) PH12023552830A1 (https=)
TW (1) TW202305135A (https=)
WO (1) WO2022218941A2 (https=)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2022226098A1 (en) * 2021-02-26 2023-08-24 Alnylam Pharmaceuticals, Inc. KETOHEXOKINASE (KHK) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
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
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
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
CN117925620B (zh) * 2024-01-30 2024-09-03 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

Family Cites Families (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6469158B1 (en) 1992-05-14 2002-10-22 Ribozyme Pharmaceuticals, Incorporated Synthesis, deprotection, analysis and purification of RNA and ribozymes
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
ATE227342T1 (de) 1993-09-02 2002-11-15 Ribozyme Pharm Inc Enzymatische nukleiksaüre die nicht-nukleotide enthaltet
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
ES2336887T5 (es) 2000-03-30 2019-03-06 Whitehead Inst Biomedical Res Mediadores de interferencia por ARN específicos de secuencias de ARN
CA2429814C (en) 2000-12-01 2014-02-18 Thomas Tuschl Rna interference mediating small rna molecules
US20050159378A1 (en) 2001-05-18 2005-07-21 Sirna Therapeutics, Inc. RNA interference mediated inhibition of Myc and/or Myb gene expression using short interfering nucleic acid (siNA)
WO2003040395A2 (en) 2001-11-07 2003-05-15 Applera Corporation Universal nucleotides for nucleic acid analysis
US20070265220A1 (en) 2004-03-15 2007-11-15 City Of Hope Methods and compositions for the specific inhibition of gene expression by double-stranded RNA
WO2007030167A1 (en) 2005-09-02 2007-03-15 Nastech Pharmaceutical Company Inc. Modification of double-stranded ribonucleic acid molecules
DK2341943T3 (en) 2008-09-22 2019-02-25 Dicerna Pharmaceuticals Inc COMPOSITIONS AND METHODS OF SPECIFIC INHIBITION OF DSRNA REPRINT WITH MODIFICATIONS
KR101728655B1 (ko) 2008-12-18 2017-04-19 다이서나 파마수이티컬, 인크. 유전자 발현의 특이적 억제를 위한 연장된 다이서 기질 제제 및 방법
US20100249214A1 (en) 2009-02-11 2010-09-30 Dicerna Pharmaceuticals Multiplex dicer substrate rna interference molecules having joining sequences
WO2011005860A2 (en) 2009-07-07 2011-01-13 Alnylam Pharmaceuticals, Inc. 5' phosphate mimics
WO2011133871A2 (en) 2010-04-22 2011-10-27 Alnylam Pharmaceuticals, Inc. 5'-end derivatives
AU2012328680A1 (en) 2011-10-25 2014-05-01 Ionis Pharmaceuticals, Inc. Antisense modulation of GCCR expression
CN113057959B (zh) * 2014-02-11 2024-07-16 阿尔尼拉姆医药品有限公司 己酮糖激酶（KHK）iRNA组合物及其使用方法
AU2015330670B2 (en) * 2014-10-10 2022-01-06 Novo Nordisk Health Care Ag Therapeutic inhibition of lactate dehydrogenase and agents therefor
DK3569711T3 (da) * 2014-12-15 2021-02-22 Dicerna Pharmaceuticals Inc Ligandmodificerede dobbeltstrengede nukleinsyrer
HUE059718T2 (hu) 2016-09-02 2022-12-28 Dicerna Pharmaceuticals Inc 4'-foszfát analógok és azokat tartalmazó oligonukleotidok
US20210332367A1 (en) * 2018-09-18 2021-10-28 Alnylam Pharmaceuticals, Inc. KETOHEXOKINASE (KHK) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
AU2020358016A1 (en) * 2019-10-02 2022-04-21 Dicerna Pharmaceuticals, Inc. Chemical modifications of small interfering RNA with minimal fluorine content
BR112022017822A2 (pt) * 2020-03-06 2022-11-08 Alnylam Pharmaceuticals Inc Composições de irna de cetoexocinase (khk) e métodos de uso das mesmas
AU2022226098A1 (en) * 2021-02-26 2023-08-24 Alnylam Pharmaceuticals, Inc. KETOHEXOKINASE (KHK) iRNA COMPOSITIONS AND METHODS OF USE THEREOF

Also Published As

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

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