EA202090717A1 - RNAi MEANS AND COMPOSITIONS FOR INHIBITING EXPRESSION OF ANGIOPOETIN-LIKE PROTEIN 3 (ANGPTL3) AND METHODS OF APPLICATION - Google Patents

RNAi MEANS AND COMPOSITIONS FOR INHIBITING EXPRESSION OF ANGIOPOETIN-LIKE PROTEIN 3 (ANGPTL3) AND METHODS OF APPLICATION

Info

Publication number
EA202090717A1
EA202090717A1 EA202090717A EA202090717A EA202090717A1 EA 202090717 A1 EA202090717 A1 EA 202090717A1 EA 202090717 A EA202090717 A EA 202090717A EA 202090717 A EA202090717 A EA 202090717A EA 202090717 A1 EA202090717 A1 EA 202090717A1
Authority
EA
Eurasian Patent Office
Prior art keywords
angptl3
rnai agents
compositions
methods
rnai
Prior art date
Application number
EA202090717A
Other languages
Russian (ru)
Inventor
Чжэнь Ли
Жуй Чжу
Со Вонг
Original Assignee
Эрроухед Фармасьютикалс, Инк.
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 Эрроухед Фармасьютикалс, Инк. filed Critical Эрроухед Фармасьютикалс, Инк.
Priority claimed from PCT/US2018/050848 external-priority patent/WO2019055633A1/en
Publication of EA202090717A1 publication Critical patent/EA202090717A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • 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
    • 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
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/317—Chemical structure of the backbone with an inverted bond, e.g. a cap structure
    • 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
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/343—Spatial arrangement of the modifications having patterns, e.g. ==--==--==--
    • 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

Landscapes

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

Abstract

Настоящее изобретение относится к средствам РНКи, например двухцепочечным средствам РНКи, которые способны ингибировать экспрессию гена ангиопоэтин-подобный 3 (также называемого ANGPTL3, ANGPL3, ангиопоэтин-подобным белком 3), и композициям, которые включают средств РНКи к ANGPTL3. Также раскрыты способы применения средств РНКи к ANGPTL3 и их композиций. Средства РНКи к ANGPTL3, раскрытые в настоящем документе, могут быть конъюгированы с направляющими лигандами для облегчения доставки в клетки, в том числе в гепатоциты. Описаны фармацевтические композиции, которые включают одно или более средств РНКи к ANGPTL3, необязательно с одним или более дополнительными терапевтическими средствами. Доставка средств РНКи к ANGPTL3 in vivo обеспечивает ингибирование экспрессии гена ANGPTL3 и может приводить к снижению уровней триглицеридов и/или холестерина у субъекта. Средства РНКи могут применяться в способах лечения ANGPTL3-ассоциированных заболеваний и нарушений, включая кардиометаболические заболевания, такие как гипертриглицеридемия и гиперлипидемия.The present invention relates to RNAi agents, for example, double-stranded RNAi agents that are capable of inhibiting the expression of an angiopoietin-like 3 gene (also called ANGPTL3, ANGPL3, angiopoietin-like protein 3), and compositions that include ANGPTL3 RNAi agents. Methods of applying RNAi agents to ANGPTL3 and their compositions are also disclosed. ANGPTL3 RNAi agents disclosed herein can be conjugated to guide ligands to facilitate delivery to cells, including hepatocytes. Pharmaceutical compositions are described that include one or more ANGPTL3 RNAs, optionally with one or more additional therapeutic agents. In vivo delivery of RNAi to ANGPTL3 provides inhibition of the expression of the ANGPTL3 gene and can lead to a decrease in the level of triglycerides and / or cholesterol in a subject. RNAi agents can be used in methods of treating ANGPTL3-associated diseases and disorders, including cardiometabolic diseases such as hypertriglyceridemia and hyperlipidemia.

EA202090717A 2018-07-07 2018-09-13 RNAi MEANS AND COMPOSITIONS FOR INHIBITING EXPRESSION OF ANGIOPOETIN-LIKE PROTEIN 3 (ANGPTL3) AND METHODS OF APPLICATION EA202090717A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201862694976P 2018-07-07 2018-07-07
PCT/US2018/050848 WO2019055633A1 (en) 2017-09-14 2018-09-13 Rnai agents and compositions for inhibiting expression of angiopoietin-like 3 (angptl3), and methods of use

Publications (1)

Publication Number Publication Date
EA202090717A1 true EA202090717A1 (en) 2020-06-11

Family

ID=71138820

Family Applications (1)

Application Number Title Priority Date Filing Date
EA202090717A EA202090717A1 (en) 2018-07-07 2018-09-13 RNAi MEANS AND COMPOSITIONS FOR INHIBITING EXPRESSION OF ANGIOPOETIN-LIKE PROTEIN 3 (ANGPTL3) AND METHODS OF APPLICATION

Country Status (1)

Country Link
EA (1) EA202090717A1 (en)

Similar Documents

Publication Publication Date Title
PH12020500309A1 (en) Rnai agents and compositions for inhibiting expression of angiopoietin-like 3 (angptl3), and methods of use
PH12020500332A1 (en) Rnai agents and compositions for inhibiting expression of apolipoprotein c-iii (apoc3)
CY1125263T1 (en) COMPOSITIONS AND METHODS FOR INHIBITING GENE EXPRESSION OF LPA
EA202191313A1 (en) COMPOSITIONS BASED ON LIPID NANOPARTICLES
WO2015106128A3 (en) Rnai agents modified at the 4'-c-position
WO2016106404A3 (en) Methods and compositions for treating malignant tumors associated with kras mutation
EA202191630A1 (en) CHEMICALLY MODIFIED CONSTRUCTIONS FOR RNAi AND WAYS OF THEIR APPLICATION
MA40240A (en) HETERARYL KINASE INHIBITION COMPOUNDS
EA201792103A1 (en) COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF HIF2ALPH GENES
EA033448B1 (en) Modified release composition of orlistat and acarbose for the treatment of obesity and related metabolic disorders
EA201692318A1 (en) COMPOSITIONS AND METHODS FOR INHIBITING THE EXPRESSION OF THE ALPHA-1-ANTITRIPSINE GENE
MX2022002198A (en) Compositions and methods for modulating splicing and protein expression.
EA201791535A1 (en) NEW CONNECTION 4'-TIONOUCLEOSIDE, AND ALSO THE WAY OF ITS OBTAINING, ITS PHARMACEUTICAL COMPOSITION AND APPLICATION
EP4124346A3 (en) Compositions and methods for treating diseases
WO2019217397A3 (en) Compositions and methods for improving strand biased
EA202090717A1 (en) RNAi MEANS AND COMPOSITIONS FOR INHIBITING EXPRESSION OF ANGIOPOETIN-LIKE PROTEIN 3 (ANGPTL3) AND METHODS OF APPLICATION
CR20200117A (en) Rnai agents and compositions for inhibiting expression of angiopoietin-like 3 (angptl3), and methods of use
EA202090687A1 (en) RNAi AGENTS AND COMPOSITIONS FOR INHIBITING EXPRESSION OF APOLIPOPROTEIN C-III (APOC3)
EP4257128A3 (en) Methods and compounds for the treatment of genetic disease
EA202090234A1 (en) RNAi MEANS FOR INHIBITING ALPHA-ENaC EXPRESSION AND METHODS OF APPLICATION
AR113014A1 (en) IRNA AGENTS AND COMPOSITIONS TO INHIBIT THE EXPRESSION OF APOLIPOPROTEIN C-III (APOC3)
EA202190800A1 (en) RNA AGENTS FOR INHIBITING EXPRESSION 17beta-HSD TYPE 13 (HSD17B13), THEIR COMPOSITIONS AND METHODS OF APPLICATION
AR113454A1 (en) IARN AGENTS AND COMPOSITIONS TO INHIBIT RECIPIENT EXPRESSION OF ASIALOGLYCOPROTEIN 1
EA202190660A1 (en) PHARNESOID X-RECEPTOR AGONISTS AND THEIR APPLICATION
EA201990427A1 (en) RNAi AGENTS AGAINST INFECTION CAUSED BY HEPATITIS B VIRUS