HUE050394T2 - Apolipoprotein(a) expressziójának módosítására szolgáló eljárások és készítmények - Google Patents

Apolipoprotein(a) expressziójának módosítására szolgáló eljárások és készítmények

Info

Publication number
HUE050394T2
HUE050394T2 HUE14791187A HUE14791187A HUE050394T2 HU E050394 T2 HUE050394 T2 HU E050394T2 HU E14791187 A HUE14791187 A HU E14791187A HU E14791187 A HUE14791187 A HU E14791187A HU E050394 T2 HUE050394 T2 HU E050394T2
Authority
HU
Hungary
Prior art keywords
apolipoprotein
modifying
expression
compositions
methods
Prior art date
Application number
HUE14791187A
Other languages
English (en)
Hungarian (hu)
Inventor
Thazha Prakash
Punit Seth
Eric Swayze
Mark Graham
Original Assignee
Ionis 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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=51843959&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=HUE050394(T2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Ionis Pharmaceuticals Inc filed Critical Ionis Pharmaceuticals Inc
Publication of HUE050394T2 publication Critical patent/HUE050394T2/hu

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
    • 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
    • A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
    • 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
    • A61K31/7125—Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • 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
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • 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
    • C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
    • 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
    • C12N15/111—General methods applicable to biologically active non-coding nucleic acids
    • 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
    • C12Y301/00—Hydrolases acting on ester bonds (3.1)
    • C12Y301/03—Phosphoric monoester hydrolases (3.1.3)
    • C12Y301/03048—Protein-tyrosine-phosphatase (3.1.3.48)
    • 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
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • C12N2310/113—Antisense targeting other non-coding nucleic acids, e.g. antagomirs
    • 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
    • C12N2310/10—Type of nucleic acid
    • C12N2310/17—Immunomodulatory nucleic acids
    • 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
    • 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
    • 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
    • C12N2310/32—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
    • C12N2310/334—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
    • 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
    • C12N2310/341—Gapmers, i.e. of the type ===---===
    • 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
    • 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
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3511—Conjugate intercalating or cleaving agent
    • 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
    • C12N2310/3513—Protein; Peptide
    • 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
    • C12N2310/30—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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/353—Nature of the modification linked to the nucleic acid via an atom other than carbon
    • 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
    • C12N2320/32—Special delivery means, e.g. tissue-specific

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Virology (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)
  • Polysaccharides And Polysaccharide Derivatives (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Steroid Compounds (AREA)
  • Liquid Crystal Substances (AREA)
HUE14791187A 2013-05-01 2014-05-01 Apolipoprotein(a) expressziójának módosítására szolgáló eljárások és készítmények HUE050394T2 (hu)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US201361818442P 2013-05-01 2013-05-01
US201361823826P 2013-05-15 2013-05-15
US201361843887P 2013-07-08 2013-07-08
US201361871673P 2013-08-29 2013-08-29
US201361880790P 2013-09-20 2013-09-20
US201461976991P 2014-04-08 2014-04-08
US201461986867P 2014-04-30 2014-04-30

Publications (1)

Publication Number Publication Date
HUE050394T2 true HUE050394T2 (hu) 2020-11-30

Family

ID=51843959

Family Applications (2)

Application Number Title Priority Date Filing Date
HUE14791187A HUE050394T2 (hu) 2013-05-01 2014-05-01 Apolipoprotein(a) expressziójának módosítására szolgáló eljárások és készítmények
HUE14791344A HUE043697T2 (hu) 2013-05-01 2014-05-01 Készítmények és eljárások HBV és TTR expressziójának modulálására

Family Applications After (1)

Application Number Title Priority Date Filing Date
HUE14791344A HUE043697T2 (hu) 2013-05-01 2014-05-01 Készítmények és eljárások HBV és TTR expressziójának modulálására

Country Status (40)

Country Link
US (25) US9127276B2 (cg-RX-API-DMAC7.html)
EP (13) EP3828275A1 (cg-RX-API-DMAC7.html)
JP (23) JP6995478B2 (cg-RX-API-DMAC7.html)
KR (17) KR20210014758A (cg-RX-API-DMAC7.html)
CN (13) CN110042098B (cg-RX-API-DMAC7.html)
AU (20) AU2014259757B2 (cg-RX-API-DMAC7.html)
BR (6) BR112015027369B1 (cg-RX-API-DMAC7.html)
CA (5) CA2921509C (cg-RX-API-DMAC7.html)
CL (2) CL2015003217A1 (cg-RX-API-DMAC7.html)
CR (2) CR20190269A (cg-RX-API-DMAC7.html)
CY (2) CY1121879T1 (cg-RX-API-DMAC7.html)
DK (4) DK2991656T3 (cg-RX-API-DMAC7.html)
DO (3) DOP2015000268A (cg-RX-API-DMAC7.html)
EA (2) EA031393B1 (cg-RX-API-DMAC7.html)
ES (4) ES2885174T3 (cg-RX-API-DMAC7.html)
FI (1) FIC20250028I1 (cg-RX-API-DMAC7.html)
FR (1) FR25C1033I1 (cg-RX-API-DMAC7.html)
HR (2) HRP20201378T1 (cg-RX-API-DMAC7.html)
HU (2) HUE050394T2 (cg-RX-API-DMAC7.html)
IL (19) IL296543B2 (cg-RX-API-DMAC7.html)
LT (2) LT2992098T (cg-RX-API-DMAC7.html)
MA (1) MA60161B1 (cg-RX-API-DMAC7.html)
ME (1) ME03390B (cg-RX-API-DMAC7.html)
MX (12) MX373306B (cg-RX-API-DMAC7.html)
MY (2) MY178929A (cg-RX-API-DMAC7.html)
NL (1) NL301341I2 (cg-RX-API-DMAC7.html)
NO (1) NO2025037I1 (cg-RX-API-DMAC7.html)
NZ (5) NZ631552A (cg-RX-API-DMAC7.html)
PE (2) PE20152002A1 (cg-RX-API-DMAC7.html)
PH (3) PH12015502493B1 (cg-RX-API-DMAC7.html)
PL (2) PL2992009T3 (cg-RX-API-DMAC7.html)
PT (3) PT2992009T (cg-RX-API-DMAC7.html)
RS (2) RS58981B1 (cg-RX-API-DMAC7.html)
RU (8) RU2697152C2 (cg-RX-API-DMAC7.html)
SG (5) SG11201508800WA (cg-RX-API-DMAC7.html)
SI (2) SI2992009T1 (cg-RX-API-DMAC7.html)
SM (1) SMT201900316T1 (cg-RX-API-DMAC7.html)
UA (2) UA121017C2 (cg-RX-API-DMAC7.html)
WO (5) WO2014179625A1 (cg-RX-API-DMAC7.html)
ZA (2) ZA201507218B (cg-RX-API-DMAC7.html)

Families Citing this family (508)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2740785C (en) 2008-10-15 2017-06-20 Isis Pharmaceuticals, Inc. Modulation of factor 11 expression
CN102282155B (zh) 2008-12-02 2017-06-09 日本波涛生命科学公司 磷原子修饰的核酸的合成方法
BR112012000828A8 (pt) 2009-07-06 2017-10-10 Ontorii Inc Novas pró-drogas de ácido nucleico e métodos de uso das mesmas
EP2620428B1 (en) 2010-09-24 2019-05-22 Wave Life Sciences Ltd. Asymmetric auxiliary group
CA3077910A1 (en) 2010-11-17 2012-05-24 Ionis Pharmaceuticals, Inc. Modulation of alpha synuclein expression
ES2626488T3 (es) 2011-07-19 2017-07-25 Wave Life Sciences Pte. Ltd. Procedimientos para la síntesis de ácidos nucleicos funcionalizados
EP3640332A1 (en) * 2011-08-29 2020-04-22 Ionis Pharmaceuticals, Inc. Oligomer-conjugate complexes and their use
EP2831231A1 (en) 2012-03-30 2015-02-04 Isis Pharmaceuticals, Inc. Compositions and methods for modulating tau expression for reducing seizure and modifying a neurodegenerative syndrome
EP3336189A1 (en) * 2012-04-20 2018-06-20 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
US9574193B2 (en) 2012-05-17 2017-02-21 Ionis Pharmaceuticals, Inc. Methods and compositions for modulating apolipoprotein (a) expression
WO2013173789A2 (en) 2012-05-17 2013-11-21 Isis Pharmaceuticals, Inc. Antisense oligonucleotide compositions
RU2624028C2 (ru) * 2012-05-24 2017-06-30 Ионис Фармасьютикалз, Инк. Способы и композиции для модулирования экспрессии аполипопротеина (а)
ES2862073T3 (es) 2012-07-13 2021-10-06 Wave Life Sciences Ltd Grupo auxiliar asimétrico
BR112015000723A2 (pt) 2012-07-13 2017-06-27 Shin Nippon Biomedical Laboratories Ltd adjuvante de ácido nucléico quiral
ES2940887T3 (es) 2012-07-13 2023-05-12 Wave Life Sciences Ltd Método de preparación de oligonucleótidos quirales
WO2014076196A1 (en) 2012-11-15 2014-05-22 Santaris Pharma A/S Anti apob antisense conjugate compounds
JP6580993B2 (ja) * 2013-01-30 2019-09-25 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ Ｌｎａオリゴヌクレオチド糖質コンジュゲート
AU2014216137B2 (en) * 2013-02-14 2018-05-10 Ionis Pharmaceuticals, Inc. Modulation of Apolipoprotein C-III (ApoCIII) expression in lipoprotein lipase deficient (LPLD) populations
CN105378080A (zh) 2013-05-01 2016-03-02 莱古路斯治疗法股份有限公司 用于调节mir-122的微小rna化合物和方法
HUE050394T2 (hu) 2013-05-01 2020-11-30 Ionis Pharmaceuticals Inc Apolipoprotein(a) expressziójának módosítására szolgáló eljárások és készítmények
US9506030B2 (en) 2013-05-01 2016-11-29 Regulus Therapeutics Inc. Compounds and methods for enhanced cellular uptake
HRP20200163T1 (hr) 2013-06-27 2020-08-07 Roche Innovation Center Copenhagen A/S Antisens oligomeri i konjugati koji ciljno djeluju na pcsk9
DK3019200T3 (da) * 2013-07-11 2022-06-20 Alnylam Pharmaceuticals Inc Oligonukleotid-ligand-konjugater og fremgangsmåde til fremstiling deraf
JP6617702B2 (ja) 2013-07-15 2019-12-11 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア Ｆｔｙ７２０のアザサイクリック拘束アナログ
TWI657819B (zh) 2013-07-19 2019-05-01 美商Ionis製藥公司 用於調節τ蛋白表現之組合物
WO2015042447A1 (en) 2013-09-20 2015-03-26 Isis Pharmaceuticals, Inc. Targeted therapeutic nucleosides and their use
TWI669393B (zh) * 2013-10-02 2019-08-21 艾爾妮蘭製藥公司 抑制ｌｅｃｔ２基因表現之組合物及方法
US11162096B2 (en) 2013-10-14 2021-11-02 Ionis Pharmaceuticals, Inc Methods for modulating expression of C9ORF72 antisense transcript
WO2015061536A1 (en) * 2013-10-25 2015-04-30 Regulus Therapeutics Inc. Microrna compounds and methods for modulating mir-21 activity
RU2016122168A (ru) * 2013-11-14 2017-12-19 Рош Инновейшен Сентер Копенгаген А/С Антисмысловые конъюгаты, направленные на аполипопротеин b
JP6482475B2 (ja) * 2014-01-07 2019-03-13 レナセラピューティクス株式会社 アンチセンスオリゴヌクレオチド及び糖誘導体を含む二本鎖オリゴヌクレオチド
US10322173B2 (en) 2014-01-15 2019-06-18 Shin Nippon Biomedical Laboratories, Ltd. Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent
JPWO2015108048A1 (ja) 2014-01-15 2017-03-23 株式会社新日本科学 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤
WO2015108047A1 (ja) 2014-01-15 2015-07-23 株式会社新日本科学 免疫誘導活性を有するキラル核酸アジュバンド及び免疫誘導活性剤
CN113278617A (zh) 2014-01-16 2021-08-20 波涛生命科学有限公司 手性设计
EP3105331B1 (en) 2014-02-11 2021-06-23 Alnylam Pharmaceuticals, Inc. Ketohexokinase (khk) irna compositions and methods of use thereof
RU2702838C2 (ru) 2014-03-19 2019-10-11 Ионис Фармасьютикалз, Инк. Композиции для модуляции экспрессии атаксина 2
US10006027B2 (en) 2014-03-19 2018-06-26 Ionis Pharmaceuticals, Inc. Methods for modulating Ataxin 2 expression
SG11201608109TA (en) 2014-04-01 2016-10-28 Ionis Pharmaceuticals Inc Compositions for modulating sod-1 expression
EP3137115B1 (en) * 2014-05-01 2020-10-14 Ionis Pharmaceuticals, Inc. Method for synthesis of reactive conjugate clusters
AU2015252895B2 (en) 2014-05-01 2021-07-15 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating angiopoietin-like 3 expression
CN106232804B (zh) 2014-05-01 2019-10-25 Ionis制药公司 用于调节补体因子b表达的组合物和方法
KR20200102553A (ko) 2014-05-01 2020-08-31 아이오니스 파마수티컬즈, 인코포레이티드 성장 호르몬 수용체 발현을 조절하기 위한 조성물 및 방법
EP4534092A3 (en) 2014-05-01 2025-07-02 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating pkk expression
GB201408623D0 (en) * 2014-05-15 2014-07-02 Santaris Pharma As Oligomers and oligomer conjugates
CA3215908A1 (en) 2014-05-22 2015-11-26 Alnylam Pharmaceuticals, Inc. Angiotensinogen (agt) irna compositions and methods of use thereof
GB201410693D0 (en) 2014-06-16 2014-07-30 Univ Southampton Splicing modulation
US9487783B2 (en) 2014-08-07 2016-11-08 Regulus Therapeutics Inc. Targeting microRNAs for metabolic disorders
US10436802B2 (en) 2014-09-12 2019-10-08 Biogen Ma Inc. Methods for treating spinal muscular atrophy
CN107109411B (zh) 2014-10-03 2022-07-01 冷泉港实验室 核基因输出的定向增加
US20170327524A1 (en) 2014-10-10 2017-11-16 Hoffmann-La Roche, Inc. Galnac phosphoramidites, nucleic acid conjugates thereof and their use
EP3207138B1 (en) * 2014-10-17 2020-07-15 Alnylam Pharmaceuticals, Inc. Polynucleotide agents targeting aminolevulinic acid synthase-1 (alas1) and uses thereof
JOP20200092A1 (ar) 2014-11-10 2017-06-16 Alnylam Pharmaceuticals Inc تركيبات iRNA لفيروس الكبد B (HBV) وطرق لاستخدامها
CN107250362B (zh) * 2014-11-17 2021-10-22 阿尔尼拉姆医药品有限公司 载脂蛋白C3(APOC3)iRNA组合物及其使用方法
US20170369872A1 (en) 2014-12-18 2017-12-28 Alnylam Pharmaceuticals, Inc. Reversir tm compounds
US10793855B2 (en) 2015-01-06 2020-10-06 Ionis Pharmaceuticals, Inc. Compositions for modulating expression of C9ORF72 antisense transcript
US10538763B2 (en) 2015-01-16 2020-01-21 Ionis Pharmaceuticals, Inc. Compounds and methods for modulation of DUX4
CA2976445A1 (en) 2015-02-13 2016-08-18 Alnylam Pharmaceuticals, Inc. Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof
JP6826984B2 (ja) * 2015-02-15 2021-02-10 アークトゥラス・セラピューティクス・インコーポレイテッドＡｒｃｔｕｒｕｓ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． アシル−アミノ−ｌｎａオリゴヌクレオチドおよび／またはヒドロカルビル−アミノ−ｌｎａオリゴヌクレオチド
US11129844B2 (en) 2015-03-03 2021-09-28 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating MECP2 expression
EP3277811B1 (en) 2015-04-03 2020-12-23 University of Massachusetts Fully stabilized asymmetric sirna
EP3277817A4 (en) 2015-04-03 2018-12-05 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating tmprss6 expression
MX2017012610A (es) 2015-04-08 2018-03-16 Alnylam Pharmaceuticals Inc Composiciones y metodos para inhibir la expresion del gen lect2.
WO2016167780A1 (en) 2015-04-16 2016-10-20 Ionis Pharmaceuticals, Inc. Compositions for modulating expression of c9orf72 antisense transcript
WO2016172734A1 (en) 2015-04-24 2016-10-27 California Institute Of Technology Reactivation of x chromosome genes
EP3310918B1 (en) 2015-06-18 2020-08-05 Alnylam Pharmaceuticals, Inc. Polynucleotide agents targeting hydroxyacid oxidase (glycolate oxidase, hao1) and methods of use thereof
WO2016209862A1 (en) 2015-06-23 2016-12-29 Alnylam Pharmaceuticals, Inc. Glucokinase (gck) irna compositions and methods of use thereof
EP3313989B1 (en) 2015-06-29 2024-12-25 Ionis Pharmaceuticals, Inc. Modified crispr rna and modified single crispr rna and uses thereof
AU2016294347B2 (en) 2015-07-10 2022-07-28 Ionis Pharmaceuticals, Inc. Modulators of diacyglycerol acyltransferase 2 (DGAT2)
WO2017011286A1 (en) 2015-07-10 2017-01-19 Alnylam Pharmaceuticals, Inc. Insulin-like growth factor binding protein, acid labile subunit (igfals) and insulin-like growth factor 1 (igf-1) irna compositions and methods of use thereof
US20180193471A1 (en) * 2015-07-16 2018-07-12 Kyowa Hakko Kirin Co., Ltd. ß2GPI GENE EXPRESSION-SUPPRESSING NUCLEIC ACID CONJUGATE
MA43072A (fr) * 2015-07-22 2018-05-30 Wave Life Sciences Ltd Compositions d'oligonucléotides et procédés associés
EP3331892B1 (en) 2015-08-06 2019-07-03 F.Hoffmann-La Roche Ag Processes for the preparation of galnac acid derivatives
CN105111119B (zh) * 2015-08-14 2017-04-12 天津小新医药科技有限公司 一类卤代苯l‑薄荷醇类p2y12受体拮抗剂及其用途
EP3334499A4 (en) 2015-08-14 2019-04-17 University of Massachusetts BIOACTIVE CONJUGATES FOR THE RELEASE OF OLIGONUCLEOTIDES
CN105111118B (zh) * 2015-08-14 2017-04-12 天津小新医药科技有限公司 L‑薄荷醇类p2y12受体拮抗剂、制备方法及其用途
KR20180043819A (ko) 2015-08-24 2018-04-30 로슈 이노베이션 센터 코펜하겐 에이/에스 Lna-g 방법
CN114525280A (zh) 2015-09-02 2022-05-24 阿尔尼拉姆医药品有限公司 程序性细胞死亡1配体1（PD-L1）的iRNA组合物及其使用方法
US10995068B2 (en) 2015-09-24 2021-05-04 The Regents Of The University Of California Synthetic sphingolipid-like molecules, drugs, methods of their synthesis and methods of treatment
RU2018113709A (ru) 2015-09-24 2019-10-30 Айонис Фармасьютикалз, Инк. Модуляторы экспрессии kras
WO2017053720A1 (en) * 2015-09-25 2017-03-30 Tarveda Therapeutics, Inc. RNAi CONJUGATES, PARTICLES AND FORMULATIONS THEREOF
EP3353306A4 (en) 2015-09-25 2019-06-05 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
WO2017053995A1 (en) * 2015-09-25 2017-03-30 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
WO2017053781A1 (en) 2015-09-25 2017-03-30 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating ataxin 3 expression
JOP20210043A1 (ar) * 2015-10-01 2017-06-16 Arrowhead Pharmaceuticals Inc تراكيب وأساليب لتثبيط تعبير جيني للـ lpa
CN108136041B (zh) 2015-10-02 2022-12-30 罗氏创新中心哥本哈根有限公司 寡核苷酸缀合方法
BR122020023854B1 (pt) 2015-10-08 2022-11-29 Ionis Pharmaceuticals, Inc Composto compreendendo oligonucleotídeo modificado e seu uso, uso do oligonucleotídeo modificado, composição e seu uso
KR102422625B1 (ko) 2015-10-09 2022-07-20 유니버시티 오브 사우스앰톤 유전자 발현의 조절 및 탈조절된 단백질 발현의 스크리닝
EP3394258B1 (en) 2015-10-22 2021-09-22 Roche Innovation Center Copenhagen A/S In vitro toxicity screening assay
WO2017068087A1 (en) 2015-10-22 2017-04-27 Roche Innovation Center Copenhagen A/S Oligonucleotide detection method
EP3370708A4 (en) 2015-11-06 2019-06-26 Ionis Pharmaceuticals, Inc. MODULATION OF APOLIPOPROTEIN (A) EXPRESSION
FI4119569T3 (fi) 2015-11-06 2024-08-30 Ionis Pharmaceuticals Inc Konjugoituja antisense-yhdisteitä käytettäviksi hoidossa
JP6649482B2 (ja) * 2015-11-16 2020-02-19 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ ＧａｌＮＡｃクラスターホスホロアミダイト
WO2017096395A1 (en) 2015-12-04 2017-06-08 Ionis Pharmaceuticals, Inc. Methods of treating breast cancer
US11096956B2 (en) 2015-12-14 2021-08-24 Stoke Therapeutics, Inc. Antisense oligomers and uses thereof
KR102604132B1 (ko) 2015-12-14 2023-11-17 콜드스프링하버러보러토리 상염색체 우성 정신 지체 5 및 드라베 증후군의 치료를 위한 안티센스 올리고머
AU2016381174A1 (en) 2015-12-31 2018-05-31 Ionis Pharmaceuticals, Inc. Methods for reducing Ataxin-2 expression
AU2017205462A1 (en) 2016-01-05 2018-06-07 Ionis Pharmaceuticals, Inc. Methods for reducing LRRK2 expression
AU2017207341A1 (en) 2016-01-12 2018-08-02 Interleukin Genetics, Inc. Methods for predicting response to treatment
CN116064544A (zh) 2016-01-26 2023-05-05 日产化学株式会社 单链寡核苷酸
ES2858090T3 (es) 2016-01-29 2021-09-29 Kyowa Kirin Co Ltd Complejo de ácidos nucleicos
US10478503B2 (en) * 2016-01-31 2019-11-19 University Of Massachusetts Branched oligonucleotides
US10246709B2 (en) 2016-03-07 2019-04-02 Arrowhead Pharmaceuticals, Inc. Targeting ligands for therapeutic compounds
AU2017229778A1 (en) 2016-03-09 2018-08-16 Ionis Pharmaceuticals, Inc. Methods and compositions for inhibiting PMP22 expression
MX2018010830A (es) 2016-03-14 2019-02-07 Hoffmann La Roche Oligonucleotidos para reducir la expresion de pd-l1.
AU2017234678A1 (en) 2016-03-16 2018-08-16 Ionis Pharmaceuticals, Inc. Methods of modulating KEAP1
WO2017161168A1 (en) 2016-03-16 2017-09-21 Ionis Pharmaceuticals, Inc. Modulation of dyrk1b expression
EP3228326A1 (en) * 2016-04-05 2017-10-11 Silence Therapeutics GmbH Nucleic acid linked to a trivalent glycoconjugate
MA45478A (fr) * 2016-04-11 2019-02-20 Arbutus Biopharma Corp Compositions de conjugués d'acides nucléiques ciblés
US20190142856A1 (en) 2016-04-13 2019-05-16 Ionis Pharmaceuticals, Inc. Methods for reducing c9orf72 expression
JP6985288B2 (ja) 2016-04-14 2021-12-22 エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft トリチル−モノ−ＧａｌＮＡｃ化合物とその利用
MA45295A (fr) 2016-04-19 2019-02-27 Alnylam Pharmaceuticals Inc Composition d'arni de protéine de liaison de lipoprotéines haute densité (hdlbp/vigiline) et procédés pour les utiliser
US11390867B2 (en) 2016-04-29 2022-07-19 Nanyang Technological University G-quadruplex-containing antisense oligonucleotides
MA45270A (fr) 2016-05-04 2017-11-09 Wave Life Sciences Ltd Compositions d'oligonucléotides et procédés associés
KR102608220B1 (ko) 2016-05-06 2023-11-29 아이오니스 파마수티컬즈, 인코포레이티드 Glp-1 수용체 리간드 모이어티 컨쥬게이트된 올리고뉴클레오티드 및 이의 용도
JP7012033B2 (ja) 2016-06-17 2022-02-10 エフ．ホフマン－ラ ロシュ アーゲー インビトロ腎毒性スクリーニングアッセイ
MA45496A (fr) 2016-06-17 2019-04-24 Hoffmann La Roche Molécules d'acide nucléique pour la réduction de l'arnm de padd5 ou pad7 pour le traitement d'une infection par l'hépatite b
US11105794B2 (en) 2016-06-17 2021-08-31 Hoffmann-La Roche Inc. In vitro nephrotoxicity screening assay
CA3023514A1 (en) 2016-06-17 2017-12-21 Ionis Pharmaceuticals, Inc. Modulation of gys1 expression
WO2017220751A1 (en) 2016-06-22 2017-12-28 Proqr Therapeutics Ii B.V. Single-stranded rna-editing oligonucleotides
ES2952757T3 (es) * 2016-06-30 2023-11-03 Kyowa Kirin Co Ltd Complejo de ácidos nucleicos
WO2018013525A1 (en) 2016-07-11 2018-01-18 Translate Bio Ma, Inc. Nucleic acid conjugates and uses thereof
EP3484908A4 (en) 2016-07-15 2020-04-08 AM Chemicals Llc NON-NUCLEOSIDIC SOLID CARRIERS AND PHOSPHORAMIDITE BUILDING BLOCKS FOR OLIGONUCLEOTID SYNTHESIS
MX2019000619A (es) 2016-07-15 2019-08-01 Ionis Pharmaceuticals Inc Compuestos y metodos para la modulacion de smn2.
US11753638B2 (en) 2016-08-12 2023-09-12 University Of Massachusetts Conjugated oligonucleotides
CA3033867A1 (en) * 2016-08-17 2018-02-22 Solstice Biologics, Ltd. Polynucleotide constructs
DK3507366T3 (da) 2016-09-01 2020-11-02 Proqr Therapeutics Ii Bv Kemisk modificeret, enkeltstrengede rna-modificerende oligonukleotider
CN116942841A (zh) 2016-09-02 2023-10-27 箭头药业股份有限公司 靶向配体
WO2018057837A1 (en) * 2016-09-23 2018-03-29 Ionis Pharmaceuticals, Inc. Gene therapy and targeted delivery of conjugated compounds
JOP20190065A1 (ar) 2016-09-29 2019-03-28 Ionis Pharmaceuticals Inc مركبات وطرق لتقليل التعبير عن tau
WO2018067900A1 (en) * 2016-10-06 2018-04-12 Ionis Pharmaceuticals, Inc. Method of conjugating oligomeric compounds
WO2018081661A1 (en) 2016-10-27 2018-05-03 California Institute Of Technology Hdac inhibitor compositions for reactivation of the x chromosome
JOP20190104A1 (ar) 2016-11-10 2019-05-07 Ionis Pharmaceuticals Inc مركبات وطرق لتقليل التعبير عن atxn3
WO2018089914A1 (en) * 2016-11-11 2018-05-17 Alios Biopharma, Inc. Oligonucleotide targeting strategy for hbv cccdna
TWI788312B (zh) 2016-11-23 2023-01-01 美商阿尼拉製藥公司 絲胺酸蛋白酶抑制因子Ａ１ ｉＲＮＡ組成物及其使用方法
EP3548005A4 (en) 2016-11-29 2020-06-17 Puretech Health LLC Exosomes for delivery of therapeutic agents
EP3548620A4 (en) 2016-12-02 2020-07-22 Cold Spring Harbor Laboratory MODULATION OF THE EXPRESSION OF LNC05
US11033571B2 (en) * 2016-12-13 2021-06-15 Am Sciences Inc Pharmaceutical composition for preventing or treating hepatitis B
TWI865997B (zh) 2016-12-16 2024-12-11 美商阿尼拉製藥公司 使用甲狀腺素運載蛋白（ＴＴＲ）ｉＲＮＡ組成物於治療或預防ＴＴＲ相關疾病之方法
CN108239644B (zh) * 2016-12-23 2021-05-28 苏州瑞博生物技术股份有限公司 一种小干扰核酸和药物组合物及其用途
US10337070B2 (en) 2017-01-12 2019-07-02 Cardioforecast Ltd. Methods and kits for treating cardiovascular disease
EP3568479A1 (en) 2017-01-13 2019-11-20 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating nfkb1 expression
US20190338286A1 (en) 2017-01-13 2019-11-07 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating rel expression
WO2018130581A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating rela expression
US20190345495A1 (en) 2017-01-13 2019-11-14 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating nfkb2 expression
EP3568481A1 (en) 2017-01-13 2019-11-20 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating relb expression
MX2019009305A (es) 2017-02-06 2019-09-19 Nissan Chemical Corp Oligonucleotido de cadena simple.
WO2018165564A1 (en) * 2017-03-09 2018-09-13 Ionis Pharmaceuticals, Inc. Morpholino modified oligomeric compounds
EP3594346A4 (en) 2017-03-10 2020-12-16 National Center For Child Health And Development ANTISENS OLIGONUCLEOTIDE AND COMPOSITION FOR THE PREVENTION OR TREATMENT OF TYPE IA GLYCOGEN STORAGE DISEASE
JOP20190215A1 (ar) 2017-03-24 2019-09-19 Ionis Pharmaceuticals Inc مُعدّلات التعبير الوراثي عن pcsk9
EP3385272A1 (en) 2017-04-05 2018-10-10 Silence Therapeutics GmbH Further novel oligonucleotide-ligand conjugates
US11015198B2 (en) 2017-04-05 2021-05-25 Silence Therapeutics Gmbh Products and compositions
EP3950004A1 (en) 2017-04-11 2022-02-09 Arbutus Biopharma Corporation Targeted compositions
CN118384268A (zh) 2017-04-18 2024-07-26 阿尔尼拉姆医药品有限公司 具有乙肝病毒（hbv）感染的受试者的治疗方法
WO2018215049A1 (en) 2017-05-23 2018-11-29 F. Hoffmann-La Roche Ag Process for galnac oligonucleotide conjugates
JP6952366B2 (ja) * 2017-05-26 2021-10-20 国立研究開発法人国立循環器病研究センター Ｐｃｓｋ９を標的としたアンチセンス核酸
JP2020522510A (ja) 2017-06-02 2020-07-30 ウェイブ ライフ サイエンシズ リミテッドＷａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｌｔｄ． オリゴヌクレオチド組成物及びその使用方法
JP2020522265A (ja) * 2017-06-02 2020-07-30 ウェイブ ライフ サイエンシズ リミテッドＷａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｌｔｄ． オリゴヌクレオチド組成物及びその使用方法
US11401519B2 (en) 2017-06-07 2022-08-02 University Of Massachusetts Anti-ADAM33 oligonucleotides and related methods
EP3642341A4 (en) 2017-06-23 2021-06-16 University Of Massachusetts TWO-DAY SELF-RELEASING SIRNA AND RELATED PROCEDURES
US11597744B2 (en) 2017-06-30 2023-03-07 Sirius Therapeutics, Inc. Chiral phosphoramidite auxiliaries and methods of their use
EP3652317A1 (en) 2017-07-13 2020-05-20 Alnylam Pharmaceuticals, Inc. Lactate dehydrogenase a (ldha) irna compositions and methods of use thereof
US11555188B2 (en) 2017-07-26 2023-01-17 Nissan Chemical Corporation Single-stranded oligonucleotide
TW201909925A (zh) * 2017-08-02 2019-03-16 日商協和醱酵麒麟有限公司 核酸複合體
WO2019027009A1 (ja) * 2017-08-02 2019-02-07 協和発酵キリン株式会社 核酸複合体
WO2019030313A2 (en) 2017-08-11 2019-02-14 Roche Innovation Center Copenhagen A/S OLIGONUCLEOTIDES FOR MODULATION OF UBE3C EXPRESSION
CA3073213A1 (en) 2017-08-17 2019-02-21 Alnylam Pharmaceuticals, Inc. Tunable reversir tm compounds
AU2018318231A1 (en) 2017-08-18 2020-02-13 Ionis Pharmaceuticals, Inc. Modulation of the notch signaling pathway for treatment of respiratory disorders
WO2019038228A1 (en) 2017-08-22 2019-02-28 Roche Innovation Center Copenhagen A/S OLIGONUCLEOTIDES FOR MODULATION OF TOM1 EXPRESSION
CN111278991B (zh) 2017-08-25 2022-04-01 斯托克制药公司 用于治疗病况和疾病的反义寡聚体
WO2019051173A1 (en) 2017-09-08 2019-03-14 Ionis Pharmaceuticals, Inc. MODULATORS OF SMAD7 EXPRESSION
KR20200100601A (ko) * 2017-09-14 2020-08-26 얀센 바이오파마, 인크. GalNAc 유도체
WO2019067875A1 (en) 2017-09-29 2019-04-04 Regeneron Pharmaceuticals, Inc. NON-HUMAN ANIMALS COMPRISING A HUMANIZED TTR LOCUS AND METHODS OF USE
IL311170A (en) 2017-09-29 2024-04-01 Intellia Therapeutics Inc Compositions and methods for ttr gene editing and treating attr amyloidosis
JP2021502059A (ja) 2017-10-13 2021-01-28 ロシュ イノベーション センター コペンハーゲン エーエス 部分的に立体定義されたオリゴヌクレオチドのサブライブラリーを使用することによる、アンチセンスオリゴヌクレオチドの、改良された立体定義されたホスホロチオエートオリゴヌクレオチド変異体を同定するための方法
RU2766360C2 (ru) 2017-10-16 2022-03-15 Ф. Хоффманн-Ля Рош Аг МОЛЕКУЛЫ НУКЛЕИНОВЫХ КИСЛОТ ДЛЯ УМЕНЬШЕНИЯ УРОВНЯ мРНК PAPD5 ИЛИ PAPD7 ДЛЯ ЛЕЧЕНИЯ ИНФЕКЦИОННОГО ГЕПАТИТА В
EP3704252A1 (en) 2017-11-01 2020-09-09 Alnylam Pharmaceuticals, Inc. Complement component c3 irna compositions and methods of use thereof
TWI809004B (zh) 2017-11-09 2023-07-21 美商Ionis製藥公司 用於降低snca表現之化合物及方法
EP3710587A1 (en) 2017-11-16 2020-09-23 Alnylam Pharmaceuticals, Inc. Kisspeptin 1 (kiss1) irna compositions and methods of use thereof
WO2019100039A1 (en) 2017-11-20 2019-05-23 Alnylam Pharmaceuticals, Inc. Serum amyloid p component (apcs) irna compositions and methods of use thereof
CN110997917B (zh) * 2017-12-01 2024-04-09 苏州瑞博生物技术股份有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
CN118291457A (zh) 2017-12-01 2024-07-05 苏州瑞博生物技术股份有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
CN110945131B (zh) * 2017-12-01 2024-05-28 苏州瑞博生物技术股份有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
EP3718572B1 (en) 2017-12-01 2024-07-31 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, composition and conjugate containing nucleic acid, preparation method and use
EP4455285A3 (en) 2017-12-01 2025-02-26 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, composition and conjugate comprising the same, and preparation method and use thereof
CN111050807B (zh) * 2017-12-01 2024-05-28 苏州瑞博生物技术股份有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
AU2018374219C1 (en) 2017-12-01 2023-05-11 Suzhou Ribo Life Science Co., Ltd. Double-stranded oligonucleotide, composition and conjugate comprising double-stranded oligonucleotide, preparation method therefor and use thereof
CN111344408A (zh) 2017-12-11 2020-06-26 哥本哈根罗氏创新中心 用于调控fndc3b表达的寡核苷酸
WO2019115417A2 (en) 2017-12-12 2019-06-20 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating rb1 expression
EP4257691A3 (en) 2017-12-14 2024-01-10 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
EA202091520A1 (ru) 2017-12-18 2020-10-05 Элнилэм Фармасьютикалз, Инк. Композиции на основе irna против бокса-1 высокомобильной группы (hmgb1) и способы их применения
US20200378970A1 (en) 2017-12-21 2020-12-03 Hoffmann-La Roche Inc. Companion diagnostic for htra1 rna antagonists
WO2019126641A2 (en) 2017-12-21 2019-06-27 Ionis Pharmaceuticals, Inc. Modulation of frataxin expression
JP2021508327A (ja) 2017-12-22 2021-03-04 ロシュ イノベーション センター コペンハーゲン エーエス 新規のチオホスホラミダイト
EP3728591B1 (en) 2017-12-22 2025-07-23 Roche Innovation Center Copenhagen A/S Gapmer oligonucleotides comprising a phosphorodithioate internucleoside linkage
KR20200104345A (ko) 2017-12-22 2020-09-03 로슈 이노베이션 센터 코펜하겐 에이/에스 포스포로디티오에이트 뉴클레오시드간 연결을 포함하는 올리고뉴클레오티드
EP3677588A4 (en) * 2017-12-26 2020-11-25 Guangzhou Ribobio Co., Ltd. MODIFIED OLIGONUCLEOTIDES AND COMPOUND WHICH CAN BE USED FOR THE SYNTHESIS OF THEM
CN109957566B (zh) * 2017-12-26 2023-08-25 广州市锐博生物科技有限公司 修饰的寡核苷酸和可用于合成修饰的寡核苷酸的化合物
KR102617947B1 (ko) 2017-12-29 2023-12-27 쑤저우 리보 라이프 사이언스 컴퍼니, 리미티드 접합체와 제조 및 그 용도
WO2019140102A1 (en) 2018-01-10 2019-07-18 Translate Bio Ma, Inc. Compositions and methods for facilitating delivery of synthetic nucleic acids to cells
US20210095274A1 (en) 2018-01-10 2021-04-01 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating pias4 expression
MX2020007439A (es) 2018-01-12 2020-09-14 Bristol Myers Squibb Co Oligonucleotidos antisentido que actuan sobre alfa-sinucleina y usos de estos.
JP2021510295A (ja) 2018-01-12 2021-04-22 ロシュ イノベーション センター コペンハーゲン エーエス Ｇｓｋ３ｂ発現を調節するためのオリゴヌクレオチド
KR20200109338A (ko) 2018-01-12 2020-09-22 로슈 이노베이션 센터 코펜하겐 에이/에스 알파-시누클레인 안티센스 올리고뉴클레오티드 및 이의 용도
US11447775B2 (en) 2018-01-12 2022-09-20 Bristol-Myers Squibb Company Antisense oligonucleotides targeting alpha-synuclein and uses thereof
BR112020014425A2 (pt) 2018-01-15 2020-12-29 Ionis Pharmaceuticals, Inc. Moduladores de expressão de dnm2
JP2021510525A (ja) 2018-01-17 2021-04-30 ロシュ イノベーション センター コペンハーゲン エーエス Ｅｒｃ１発現を調節するためのオリゴヌクレオチド
EP3740573A1 (en) 2018-01-18 2020-11-25 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting srebp1
WO2019145386A1 (en) 2018-01-26 2019-08-01 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating csnk1d expression
WO2019157531A1 (en) 2018-02-12 2019-08-15 Ionis Pharmaceuticals, Inc. Modified compounds and uses thereof
WO2019161105A1 (en) 2018-02-14 2019-08-22 Deep Genomics Incorporated Oligonucleotide therapy for wilson disease
CN112020559A (zh) 2018-02-21 2020-12-01 百时美施贵宝公司 Camk2d反义寡核苷酸及其用途
EP3759127A4 (en) 2018-03-02 2022-03-30 Ionis Pharmaceuticals, Inc. COMPOUNDS AND METHODS FOR MODULATING AMYLOID BETA PRECURSOR PROTEIN
TWI840345B (zh) 2018-03-02 2024-05-01 美商Ionis製藥公司 Irf4表現之調節劑
KR20210130854A (ko) 2018-03-09 2021-11-01 다이이찌 산쿄 가부시키가이샤 당원병 Ia형 치료약
WO2019183440A1 (en) 2018-03-22 2019-09-26 Ionis Pharmaceuticals, Inc. Methods for modulating fmr1 expression
BR112020020220A8 (pt) 2018-04-05 2021-02-17 Centre Leon Berard uso de inibidores da fubp1 para o tratamento de infecção pelo vírus da hepatite b
MX2020010721A (es) 2018-04-11 2020-11-06 Ionis Pharmaceuticals Inc Moduladores de la expresion de ezh2.
EP3788065B1 (en) 2018-04-30 2025-08-27 The Children's Hospital Of Philadelphia Improving anemias by combining agents
US12060558B2 (en) 2018-05-04 2024-08-13 Stoke Therapeutics, Inc. Methods and compositions for treatment of cholesteryl ester storage disease
EP3790990A1 (en) 2018-05-07 2021-03-17 Roche Innovation Center Copenhagen A/S Quality control of lna oligonucleotide therapeutics using massively parallel sequencing
WO2019217369A1 (en) 2018-05-08 2019-11-14 Regulus Therapeutics Inc. Galnac conjugated modified oligonucleotide as mir-122 inhibitor having hcv antiviral activity with reduced hyperbilirubinemia side-effect
CR20200605A (es) * 2018-05-09 2021-01-29 Ionis Pharmaceuticals Inc Compuestos y métodos para la reducción de la expresión de fxi
CR20200604A (es) 2018-05-09 2021-02-09 Ionis Pharmaceuticals Inc Compuestos y métodos para reducir de la expresión de atxn3
US12391942B2 (en) 2018-05-11 2025-08-19 Wave Life Sciences Ltd. Oligonucleotide compositions and methods of use thereof
TWI851574B (zh) 2018-05-14 2024-08-11 美商阿尼拉製藥公司 血管收縮素原（ＡＧＴ）ｉＲＮＡ組成物及其使用方法
GB201808146D0 (en) 2018-05-18 2018-07-11 Proqr Therapeutics Ii Bv Stereospecific Linkages in RNA Editing Oligonucleotides
AU2019287635A1 (en) 2018-06-14 2020-12-17 Ionis Pharmaceuticals, Inc. Compounds and methods for increasing STMN2 expression
TWI833770B (zh) 2018-06-27 2024-03-01 美商Ionis製藥公司 用於減少 lrrk2 表現之化合物及方法
CA3103054A1 (en) 2018-07-03 2020-01-09 F. Hoffmann-La Roche Ag Oligonucleotides for modulating tau expression
WO2020007826A1 (en) 2018-07-05 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting mbtps1
WO2020011744A2 (en) 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting cers5
WO2020011745A2 (en) 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting cers6
JP7616987B2 (ja) 2018-07-13 2025-01-17 エフ． ホフマン－ラ ロシュ アーゲー Ｒｔｅｌ１発現の調節用のオリゴヌクレオチド
WO2020018558A1 (en) 2018-07-17 2020-01-23 Aronora, Inc. Methods for safely reducing thrombopoietin
MX2021000922A (es) 2018-07-25 2021-03-31 Ionis Pharmaceuticals Inc Compuestos y metodos para reducir la expresion de la atxn2.
EP4122943B1 (en) 2018-07-31 2024-05-29 Roche Innovation Center Copenhagen A/S Oligonucleotides comprising a phosphorotrithioate internucleoside linkage
CN119912512A (zh) 2018-07-31 2025-05-02 罗氏创新中心哥本哈根有限公司 包含三硫代磷酸酯核苷间键的寡核苷酸
WO2020033748A1 (en) 2018-08-08 2020-02-13 Arcturus Therapeutics, Inc. Compositions and agents against nonalcoholic steatohepatitis
BR112021002440A2 (pt) 2018-08-10 2021-05-04 University Of Massachusetts oligonucleotídeos modificados visando snps
JP7625512B2 (ja) 2018-08-13 2025-02-03 アルナイラム ファーマシューティカルズ， インコーポレイテッド Ｂ型肝炎ウイルス（ＨＢＶ）ｄｓＲＮＡ物質組成物およびその使用方法
WO2020038377A1 (zh) 2018-08-21 2020-02-27 苏州瑞博生物技术有限公司 一种核酸、含有该核酸的药物组合物和缀合物及其用途
US11279930B2 (en) 2018-08-23 2022-03-22 University Of Massachusetts O-methyl rich fully stabilized oligonucleotides
US20220160870A1 (en) 2018-08-28 2022-05-26 Roche Innovation Center Copenhagen A/S Neoantigen engineering using splice modulating compounds
CA3105385A1 (en) 2018-09-18 2020-03-26 Alnylam Pharmaceuticals, Inc. Ketohexokinase (khk) irna compositions and methods of use thereof
TWI869213B (zh) 2018-09-19 2025-01-01 美商Ionis製藥公司 Pnpla3表現之調節劑
CN111655297A (zh) * 2018-09-30 2020-09-11 苏州瑞博生物技术有限公司 一种siRNA缀合物及其制备方法和用途
WO2020077390A1 (en) * 2018-10-18 2020-04-23 Murdoch University Antisense therapy for ptp1b related conditions
US10913951B2 (en) 2018-10-31 2021-02-09 University of Pittsburgh—of the Commonwealth System of Higher Education Silencing of HNF4A-P2 isoforms with siRNA to improve hepatocyte function in liver failure
CN113286885A (zh) 2018-11-09 2021-08-20 诺华股份有限公司 用靶向apo(a)的经缀合的反义化合物降低心血管事件的风险的方法
TW202028222A (zh) 2018-11-14 2020-08-01 美商Ionis製藥公司 Foxp3表現之調節劑
BR112021008967A2 (pt) 2018-11-15 2021-08-17 Ionis Pharmaceuticals, Inc. moduladores da expressão de irf5
AU2019384181B2 (en) 2018-11-21 2025-04-10 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing prion expression
US12416004B2 (en) 2018-11-23 2025-09-16 Sanofi RNA compositions and methods for inhibiting ANGPTL8
CN113286600A (zh) 2018-11-30 2021-08-20 协和麒麟株式会社 核酸复合物
WO2020117706A1 (en) 2018-12-03 2020-06-11 Triplet Therapeutics, Inc. Methods for the treatment of trinucleotide repeat expansion disorders associated with mlh3 activity
AU2019406186A1 (en) 2018-12-20 2021-07-15 Praxis Precision Medicines, Inc. Compositions and methods for the treatment of KCNT1 related disorders
AU2019403447B2 (en) 2018-12-21 2023-07-27 Ionis Pharmaceuticals, Inc. Modulators of HSD17B13 expression
GB201821269D0 (en) 2018-12-28 2019-02-13 Nippon Shinyaku Co Ltd Myostatin signal inhibitor
EP3903830A4 (en) * 2018-12-28 2023-04-26 Suzhou Ribo Life Science Co., Ltd. NUCLEIC ACID, COMPOSITION AND CONJUGATE WITH NUCLEIC ACID, PROCESS FOR THEIR PREPARATION AND ITS USE
CN111377985B (zh) * 2018-12-29 2023-11-10 苏州瑞博生物技术股份有限公司 化合物和缀合物及其制备方法和用途
CN113330117B (zh) * 2019-01-18 2024-05-28 苏州瑞博生物技术股份有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
JP2022523467A (ja) 2019-01-18 2022-04-25 ユニバーシティ・オブ・マサチューセッツ 動的な薬物動態を修飾するアンカー
WO2020160453A1 (en) 2019-01-31 2020-08-06 Ionis Pharmaceuticals, Inc. Modulators of yap1 expression
TW202102516A (zh) 2019-02-20 2021-01-16 丹麥商羅氏創新中心哥本哈根有限公司 膦醯基乙酸酯間隙子寡核苷酸
CN113474352A (zh) 2019-02-20 2021-10-01 罗氏创新中心哥本哈根有限公司 新型亚磷酰胺
CN109799330B (zh) * 2019-02-22 2021-03-02 华中科技大学同济医学院附属同济医院 神经氨酸及神经氨酸酶抑制剂在慢性心力衰竭中的应用
WO2020173845A1 (en) 2019-02-26 2020-09-03 Roche Innovation Center Copenhagen A/S Oligonucleotide formulation method
US11279932B2 (en) 2019-02-27 2022-03-22 Ionis Pharmaceuticals, Inc. Modulators of MALAT1 expression
US20220145292A1 (en) * 2019-02-28 2022-05-12 Deep Genomics Incorporated Ligand clusters and methods of their use and preparation
CA3133629A1 (en) * 2019-03-21 2020-09-24 Mitotherapeutix Llc Multivalent ligand clusters for targeted delivery of therapeutic agents
MX2021011916A (es) 2019-03-29 2021-10-26 Ionis Pharmaceuticals Inc Compuestos y metodos para modular ube3a-ats.
WO2020201144A1 (en) 2019-04-02 2020-10-08 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for immunotherapy
BR112021019182A2 (pt) 2019-04-03 2022-05-31 Bristol Myers Squibb Co Oligonucleotídeos angptl2 antissenso e seus usos
EP3972983A4 (en) * 2019-05-17 2023-05-24 Ionis Pharmaceuticals, Inc. SYNTHESIS OF OLIGOMERIC COMPOUNDS COMPRISING PHOSPHOROTHIOATE DIESTER AND PHOSPHATE DIESTER BONDS
JP7610268B2 (ja) 2019-05-22 2025-01-08 スーチョウ リボ ライフ サイエンス カンパニー、リミテッド 核酸、薬物組成物及び複合体ならびに調製方法と使用
CN113227376B (zh) * 2019-05-22 2024-04-09 苏州瑞博生物技术股份有限公司 核酸、药物组合物与缀合物及制备方法和用途
US20240200060A1 (en) 2019-05-22 2024-06-20 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, pharmaceutical composition, conjugate, preparation method, and use
WO2020233651A1 (zh) 2019-05-22 2020-11-26 苏州瑞博生物技术股份有限公司 核酸、药物组合物与缀合物及制备方法和用途
EP3992290A4 (en) 2019-05-24 2023-11-15 Suzhou Ribo Life Science Co., Ltd. NUCLEIC ACID, PHARMACEUTICAL COMPOSITION AND CONJUGATE, METHOD FOR THE PRODUCTION THEREOF AND USE THEREOF
US20220186221A1 (en) 2019-05-24 2022-06-16 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, pharmaceutical composition and conjugate, preparation method and use
JP7610849B2 (ja) 2019-05-24 2025-01-09 スーチョウ リボ ライフ サイエンス カンパニー、リミテッド 核酸、薬物組成物及び複合体ならびに調製方法と使用
PT3976791T (pt) 2019-05-28 2025-06-26 Ionis Pharmaceuticals Inc Compostos e métodos para reduzir a expressão da fus
BR112021023488A2 (pt) 2019-05-31 2022-01-18 Aligos Therapeutics Inc Oligonucleotídeos de gapmer modificados e métodos de uso
WO2020247452A1 (en) 2019-06-04 2020-12-10 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized ttr locus with a beta-slip mutation and methods of use
AU2020301419A1 (en) 2019-06-25 2022-01-20 Amgen Inc. Purification methods for carbohydrate-linked oligonucleotides
ES3048358T3 (en) 2019-07-26 2025-12-10 Ionis Pharmaceuticals Inc Compounds and methods for modulating gfap
WO2021022108A2 (en) 2019-08-01 2021-02-04 Alnylam Pharmaceuticals, Inc. CARBOXYPEPTIDASE B2 (CPB2) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
WO2021022109A1 (en) 2019-08-01 2021-02-04 Alnylam Pharmaceuticals, Inc. SERPIN FAMILY F MEMBER 2 (SERPINF2) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
WO2021030213A1 (en) 2019-08-09 2021-02-18 University Of Massachusetts Chemically modified oligonucleotides targeting snps
WO2021030522A1 (en) 2019-08-13 2021-02-18 Alnylam Pharmaceuticals, Inc. SMALL RIBOSOMAL PROTEIN SUBUNIT 25 (RPS25) iRNA AGENT COMPOSITIONS AND METHODS OF USE THEREOF
CN114555621B (zh) * 2019-08-15 2025-10-28 Ionis制药公司 键修饰的寡聚化合物及其用途
US20220290156A1 (en) 2019-08-27 2022-09-15 Sanofi Compositions and methods for inhibiting pcsk9
CN113891892B (zh) 2019-08-29 2024-01-30 苏州瑞博生物技术股份有限公司 化合物和药物缀合物及其制备方法和用途
EP4022062A1 (en) 2019-08-30 2022-07-06 Alnylam Pharmaceuticals, Inc. Neurofilament light chain (nfl) as a biomarker for transthyretin amyloidosis polyneuropathy
US12290567B2 (en) 2019-09-03 2025-05-06 Arcturus Therapeutics, Inc. Asialoglycoprotein Receptor mediated delivery of therapeutically active conjugates
CN119326905A (zh) 2019-09-10 2025-01-21 第一三共株式会社 用于递送至肝脏的GalNAc-寡核苷酸偶联物及其制备方法
US12365894B2 (en) 2019-09-16 2025-07-22 University Of Massachusetts Branched lipid conjugates of siRNA for specific tissue delivery
TW202126304A (zh) 2019-09-20 2021-07-16 瑞士商赫孚孟拉羅股份公司 使用核心蛋白異位調節劑治療hbv感染之方法
WO2021067747A1 (en) 2019-10-04 2021-04-08 Alnylam Pharmaceuticals, Inc. Compositions and methods for silencing ugt1a1 gene expression
CN114728017B (zh) 2019-10-14 2025-10-28 阿斯利康(瑞典)有限公司 Pnpla3表达的调节剂
US12486512B2 (en) 2019-10-18 2025-12-02 Alnylam Pharmaceuticals, Inc. Solute carrier family member iRNA compositions and methods of use thereof
JP7676377B2 (ja) 2019-10-22 2025-05-14 アルナイラム ファーマシューティカルズ， インコーポレイテッド 補体成分Ｃ３ ｉＲＮＡ組成物およびその使用方法
MX2022004388A (es) 2019-11-01 2022-05-06 Alnylam Pharmaceuticals Inc Composiciones de agentes de arni de huntingtina (htt) y metodos de uso de las mismas.
JP7707164B2 (ja) 2019-11-13 2025-07-14 アルナイラム ファーマシューティカルズ， インコーポレイテッド アンギオテンシノーゲン（ａｇｔ）関連障害を処置するための方法および組成物
US20230056569A1 (en) 2019-11-22 2023-02-23 Alnylam Pharmaceuticals, Inc. Ataxin3 (atxn3) rnai agent compositions and methods of use thereof
CN112876534B (zh) * 2019-11-29 2024-02-09 苏州瑞博生物技术股份有限公司 肝靶向化合物及缀合物
MX2022006433A (es) 2019-12-13 2022-06-23 Alnylam Pharmaceuticals Inc Composiciones de agentes de acido ribonucleico de interferencia (arni) del marco de lectura abierto 72 del cromosoma 9 humano (c9orf72) y metodos de uso de los mismos.
WO2021126734A1 (en) 2019-12-16 2021-06-24 Alnylam Pharmaceuticals, Inc. Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof
CN111041025B (zh) * 2019-12-17 2021-06-18 深圳市瑞吉生物科技有限公司 基于结合N-乙酰半乳糖胺多肽的mRNA靶向分子及其制备方法
CN114867856A (zh) 2019-12-19 2022-08-05 豪夫迈·罗氏有限公司 Saraf抑制剂用于治疗乙型肝炎病毒感染的用途
JP2023506550A (ja) 2019-12-19 2023-02-16 エフ． ホフマン－ラ ロシュ エージー． Ｂ型肝炎ウイルス感染症を処置するためのｓｂｄｓ阻害剤の使用
EP4077670A1 (en) 2019-12-19 2022-10-26 F. Hoffmann-La Roche AG Use of cops3 inhibitors for treating hepatitis b virus infection
EP4077667A1 (en) 2019-12-19 2022-10-26 F. Hoffmann-La Roche AG Use of sept9 inhibitors for treating hepatitis b virus infection
CN114829599A (zh) 2019-12-19 2022-07-29 豪夫迈·罗氏有限公司 Scamp3抑制剂用于治疗乙型肝炎病毒感染的用途
CA3163646A1 (en) 2019-12-24 2021-07-01 F. Hoffman-La Roche Ag Pharmaceutical combination of antiviral agents targeting hbv and/or an immune modulator for treatment of hbv
CN115103674A (zh) 2019-12-24 2022-09-23 豪夫迈·罗氏有限公司 使用tlr7激动剂治疗病毒感染的方法
JP2023509870A (ja) 2019-12-24 2023-03-10 エフ． ホフマン－ラ ロシュ アーゲー Ｈｂｖの処置のためのｈｂｖを標的とする治療用オリゴヌクレオチドとｔｌｒ７アゴニストとの医薬組合せ
EP4071163A4 (en) * 2020-01-30 2024-03-20 Eisai R&D Management Co., Ltd. NUCLEIC ACID COMPLEX AND PHARMACEUTICAL COMPOSITION CONTAINING SAME
KR20220140593A (ko) 2020-02-10 2022-10-18 알닐람 파마슈티칼스 인코포레이티드 Vegf-a 발현을 사일런싱하기 위한 조성물 및 방법
KR20220143106A (ko) 2020-02-18 2022-10-24 알닐람 파마슈티칼스 인코포레이티드 아포지질단백질 C3 (APOC3) iRNA 조성물 및 이의 사용 방법
BR112022016238A2 (pt) 2020-02-28 2022-10-11 Ionis Pharmaceuticals Inc Compostos e métodos para modular smn2
GB2627637B (en) 2020-03-04 2024-11-20 Verve Therapeutics Inc A method for reducing the risk of coronary disease
EP4114947A1 (en) 2020-03-05 2023-01-11 Alnylam Pharmaceuticals, Inc. Complement component c3 irna compositions and methods of use thereof for treating or preventing complement component c3-associated diseases
IL296106A (en) 2020-03-06 2022-11-01 Alnylam Pharmaceuticals Inc Compositions and methods for inhibiting expression of transthyretin (ttr)
JP2023516095A (ja) 2020-03-06 2023-04-17 アルナイラム ファーマシューティカルズ， インコーポレイテッド ケトヘキソキナーゼ（ＫＨＫ）ｉＲＮＡ組成物およびその使用方法
EP4121534A1 (en) 2020-03-18 2023-01-25 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating subjects having a heterozygous alanine-glyoxylate aminotransferase gene (agxt) variant
CA3175278A1 (en) 2020-03-23 2021-09-30 Amgen Inc. Monoclonal antibodies to chemically-modified nucleic acids and uses thereof
JP7760130B2 (ja) * 2020-03-26 2025-10-27 国立研究開発法人国立循環器病研究センター Ａｐｏｃ３を標的としたアンチセンス核酸
JP2023519274A (ja) 2020-03-26 2023-05-10 アルナイラム ファーマシューティカルズ， インコーポレイテッド コロナウイルスｉＲＮＡ組成物およびその使用方法
CN117377763A (zh) 2020-04-06 2024-01-09 阿尔尼拉姆医药品有限公司 用于沉默myoc表达的组合物和方法
EP4133079A1 (en) 2020-04-07 2023-02-15 Alnylam Pharmaceuticals, Inc. Compositions and methods for silencing scn9a expression
WO2021206917A1 (en) 2020-04-07 2021-10-14 Alnylam Pharmaceuticals, Inc. ANGIOTENSIN-CONVERTING ENZYME 2 (ACE2) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
EP4133077A1 (en) 2020-04-07 2023-02-15 Alnylam Pharmaceuticals, Inc. Transmembrane serine protease 2 (tmprss2) irna compositions and methods of use thereof
IL297482A (en) 2020-04-21 2022-12-01 Flagship Pioneering Inc Bifunctional molecules and methods of using thereof
CN111575279A (zh) * 2020-04-27 2020-08-25 江苏为真生物医药技术股份有限公司 利用asgpr小分子配体特异性捕获肝细胞外囊泡或循环肿瘤细胞的方法
IL297702A (en) 2020-04-27 2022-12-01 Alnylam Pharmaceuticals Inc Apolipoprotein e (apoe) irna agent compositions and methods of use thereof
WO2021222549A1 (en) 2020-04-30 2021-11-04 Alnylam Pharmaceuticals, Inc. Complement factor b (cfb) irna compositions and methods of use thereof
IL297435A (en) 2020-05-01 2022-12-01 Ionis Pharmaceuticals Inc Compounds and methods for modulating atxn1
CN115867657A (zh) 2020-05-11 2023-03-28 斯托克制药公司 用于治疗疾患和疾病的opa1反义寡聚物
CA3162416C (en) 2020-05-15 2023-07-04 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of argininosuccinate synthetase (ass1)
WO2021231685A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of transmembrane channel-like protein 1 (tmc1)
WO2021231692A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of otoferlin (otof)
EP4150089A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of retinoschisin 1 (rs1)
EP4150086A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of leucine rich repeat kinase 2 (lrrk2)
WO2021231698A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of argininosuccinate lyase (asl)
WO2021231679A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of gap junction protein beta 2 (gjb2)
EP4150076A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of methyl-cpg binding protein 2 (mecp2)
CN113683651A (zh) * 2020-05-19 2021-11-23 上海京新生物医药有限公司 一种GalNAc中间体的制备方法
AR122534A1 (es) 2020-06-03 2022-09-21 Triplet Therapeutics Inc Métodos para el tratamiento de los trastornos de expansión por repetición de nucleótidos asociados con la actividad de msh3
WO2021252557A1 (en) 2020-06-09 2021-12-16 Alnylam Pharmaceuticals, Inc. Rnai compositions and methods of use thereof for delivery by inhalation
EP4649951A2 (en) 2020-06-09 2025-11-19 Alnylam Pharmaceuticals, Inc. Sirna compositions and methods for silencing gpam (glycerol-3-phosphate acyltransferase 1, mitochondrial) expression
US20240033278A9 (en) * 2020-06-10 2024-02-01 Medshine Discovery Inc. Conjugate group and conjugate
BR112022024420A2 (pt) 2020-06-18 2023-01-17 Alnylam Pharmaceuticals Inc Composições de irna de xantina desidrogenase (xdh) e métodos de uso das mesmas
JP2023532040A (ja) * 2020-06-24 2023-07-26 サプリーム テクノロジーズ，ベー．フェー． ＧａｌＮＡｃ及びサポニンのコンジュゲート、前記コンジュゲート及びＧａｌＮＡｃ－オリゴヌクレオチドコンジュゲートを含む治療組成物
AR122731A1 (es) 2020-06-26 2022-10-05 Hoffmann La Roche Oligonucleótidos mejorados para modular la expresión de fubp1
EP4172338A4 (en) 2020-06-29 2025-06-11 Ionis Pharmaceuticals, Inc. COMPOUNDS AND METHODS FOR MODULATING PLP1
CN111744019B (zh) 2020-07-01 2023-08-04 深圳瑞吉生物科技有限公司 基于甘露糖的mRNA靶向递送系统及其应用
CA3177613A1 (en) 2020-07-10 2022-04-13 Inserm (Institut National De La Sante Et De La Recherche Medicale) Methods and compositions for treating epilepsy
WO2022026589A1 (en) 2020-07-28 2022-02-03 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing app expression
EP4192476A4 (en) 2020-08-07 2024-09-18 Ionis Pharmaceuticals, Inc. COMPOUNDS AND METHODS FOR MODULATING SCN2A
PE20230993A1 (es) * 2020-08-13 2023-06-23 Amgen Inc Construcciones de iarn y metodos para inhibir la expresion de marc1
JP2023538630A (ja) 2020-08-21 2023-09-08 エフ． ホフマン－ラ ロシュ アーゲー Ｂ型肝炎ウイルス感染症を処置するためのａ１ｃｆ阻害剤の使用
WO2022066847A1 (en) 2020-09-24 2022-03-31 Alnylam Pharmaceuticals, Inc. Dipeptidyl peptidase 4 (dpp4) irna compositions and methods of use thereof
TW202229552A (zh) 2020-10-05 2022-08-01 美商艾拉倫製藥股份有限公司 Ｇ蛋白－偶合受體７５（ＧＰＲ７５）ｉＲＮＡ組成物及其使用方法
EP4229200A1 (en) 2020-10-16 2023-08-23 Sanofi Novel rna compositions and methods for inhibiting angptl3
US20240035029A1 (en) 2020-10-16 2024-02-01 Sanofi Rna compositions and methods for inhibiting lipoprotein(a)
WO2022087329A1 (en) 2020-10-23 2022-04-28 Alnylam Pharmaceuticals, Inc. Mucin 5b (muc5b) irna compositions and methods of use thereof
AU2021380809A1 (en) 2020-11-13 2023-06-22 Alnylam Pharmaceuticals, Inc. COAGULATION FACTOR V (F5) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
ES2990026T3 (es) 2020-11-18 2024-11-28 Ionis Pharmaceuticals Inc Compuestos y métodos para modular la expresión del angiotensinógeno
US20240002853A1 (en) 2020-11-23 2024-01-04 Alpha Anomeric Sas Nucleic acid duplexes
WO2022125490A1 (en) 2020-12-08 2022-06-16 Alnylam Pharmaceuticals, Inc. Coagulation factor x (f10) irna compositions and methods of use thereof
GB2603454A (en) 2020-12-09 2022-08-10 Ucl Business Ltd Novel therapeutics for the treatment of neurodegenerative disorders
TW202242111A (zh) 2020-12-18 2022-11-01 美商Ionis製藥公司 用於調節因子ｘｉｉ之化合物及方法
US20250304966A1 (en) 2020-12-23 2025-10-02 Argonaute RNA Limited Treatment of cardiovascular disease
US20250320500A1 (en) 2020-12-29 2025-10-16 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, pharmaceutical composition and sirna conjugate containing the nucleic acid, preparation method therefor, and use thereof
EP4274896A1 (en) 2021-01-05 2023-11-15 Alnylam Pharmaceuticals, Inc. Complement component 9 (c9) irna compositions and methods of use thereof
WO2022162161A1 (en) * 2021-01-30 2022-08-04 E-Therapeutics Plc Conjugated oligonucleotide compounds, methods of making and uses thereof
CN116848127A (zh) * 2021-01-30 2023-10-03 e-生物有限公司 缀合寡核苷酸化合物、其制备方法和用途
CA3204317A1 (en) * 2021-01-30 2022-08-04 Ahmad Ali MORTAZAVI Conjugated oligonucleotide compounds, methods of making and uses thereof
WO2022162157A1 (en) * 2021-01-30 2022-08-04 E-Therapeutics Plc Conjugated oligonucleotide compounds, methods of making and uses thereof
AU2022214281A1 (en) 2021-01-30 2023-07-27 E-Therapeutics Plc Conjugated oligonucleotide compounds, methods of making and uses thereof
CN117355534A (zh) * 2021-01-30 2024-01-05 e-生物有限公司 缀合寡核苷酸化合物、其制备方法和用途
TW202246500A (zh) 2021-02-02 2022-12-01 瑞士商赫孚孟拉羅股份公司 用於抑制 ｒｔｅｌ１ 表現之增強型寡核苷酸
IL304880A (en) 2021-02-12 2023-10-01 Alnylam Pharmaceuticals Inc Superoxide dismutase 1 (sod1) irna compositions and methods of use thereof for treating or preventing superoxide dismutase 1- (sod1-) associated neurodegenerative diseases
WO2022175749A1 (en) * 2021-02-18 2022-08-25 Oneglobe Holdings Limited Compositions for conjugating oligonucleotides and carbohydrates
JP2024509783A (ja) 2021-02-25 2024-03-05 アルナイラム ファーマシューティカルズ， インコーポレイテッド プリオンタンパク質（ｐｒｎｐ）ｉｒｎａ組成物およびその使用方法
KR20230150844A (ko) 2021-02-26 2023-10-31 알닐람 파마슈티칼스 인코포레이티드 케토헥소키나아제(KHK) iRNA 조성물 및 이의 사용 방법
AU2022231003A1 (en) 2021-03-04 2023-09-14 Alnylam Pharmaceuticals, Inc. Angiopoietin-like 3 (angptl3) irna compositions and methods of use thereof
WO2022189861A1 (en) 2021-03-08 2022-09-15 Tollys Carbohydrate conjugates of tlr3 ligands and uses thereof
IL305668A (en) 2021-03-08 2023-11-01 Servier Lab Antisense oligonucleotides to inhibit alpha-synuclein expression
EP4305169A1 (en) 2021-03-12 2024-01-17 Alnylam Pharmaceuticals, Inc. Glycogen synthase kinase 3 alpha (gsk3a) irna compositions and methods of use thereof
KR20230162024A (ko) 2021-03-29 2023-11-28 알닐람 파마슈티칼스 인코포레이티드 헌팅틴(HTT) iRNA 제제 조성물 및 이의 사용 방법
EP4314293A1 (en) 2021-04-01 2024-02-07 Alnylam Pharmaceuticals, Inc. Proline dehydrogenase 2 (prodh2) irna compositions and methods of use thereof
MX2023012216A (es) 2021-04-14 2023-10-26 Dicerna Pharmaceuticals Inc Composiciones y metodos para modular la expresion de pnpla3.
CA3216106A1 (en) 2021-04-26 2022-11-03 Alnylam Pharmaceuticals, Inc. Transmembrane protease, serine 6 (tmprss6) irna compositions and methods of use thereof
WO2022232343A1 (en) 2021-04-29 2022-11-03 Alnylam Pharmaceuticals, Inc. Signal transducer and activator of transcription factor 6 (stat6) irna compositions and methods of use thereof
WO2022232650A1 (en) * 2021-04-30 2022-11-03 Ionis Pharmaceuticals, Inc. Methods for reducing agt expression
EP4341401A1 (en) 2021-05-18 2024-03-27 Alnylam Pharmaceuticals, Inc. Sodium-glucose cotransporter-2 (sglt2) irna compositions and methods of use thereof
WO2022246023A1 (en) 2021-05-20 2022-11-24 Korro Bio, Inc. Methods and compositions for adar-mediated editing
WO2022256283A2 (en) 2021-06-01 2022-12-08 Korro Bio, Inc. Methods for restoring protein function using adar
JP2024522996A (ja) 2021-06-02 2024-06-25 アルナイラム ファーマシューティカルズ， インコーポレイテッド パタチン様ホスホリパーゼドメイン含有３（ＰＮＰＬＡ３）ｉＲＮＡ組成物およびその使用方法
AU2022283796A1 (en) 2021-06-04 2023-11-09 Alnylam Pharmaceuticals, Inc. HUMAN CHROMOSOME 9 OPEN READING FRAME 72 (C9ORF72) iRNA AGENT COMPOSITIONS AND METHODS OF USE THEREOF
JP2024523000A (ja) 2021-06-08 2024-06-25 アルナイラム ファーマシューティカルズ， インコーポレイテッド シュタルガルト病及び／又は網膜結合タンパク質４（ｒｂｐ４）関連障害を治療又は予防するための組成物及び方法
BR112023026050A2 (pt) 2021-06-18 2024-03-05 Ionis Pharmaceuticals Inc Compostos e métodos para reduzir expressão de ifnar1
IL309334A (en) 2021-06-23 2024-02-01 Univ Massachusetts Anti-FLT1 optimized oligonucleotide compounds for the treatment of preeclampsia and other angiogenic disorders
MX2024000208A (es) * 2021-06-24 2024-01-29 Lilly Co Eli Restos de administracion terapeutica novedosos y usos de estos.
PE20250353A1 (es) * 2021-06-24 2025-02-06 Lilly Co Eli Terapeutica con arn novedosos y usos de estos
US20230194709A9 (en) 2021-06-29 2023-06-22 Seagate Technology Llc Range information detection using coherent pulse sets with selected waveform characteristics
US20250034564A1 (en) 2021-06-29 2025-01-30 Korro Bio, Inc. Methods and Compositions for ADAR-Mediated Editing
KR20240026203A (ko) 2021-06-30 2024-02-27 알닐람 파마슈티칼스 인코포레이티드 안지오텐시노겐(agt)-관련 장애를 치료하는 방법 및 조성물
JP2024524330A (ja) * 2021-07-02 2024-07-05 上海拓界生物医薬科技有限公司 核酸リガンド及びその複合体、その調製方法と用途
US20240316093A1 (en) 2021-07-08 2024-09-26 Nippon Shinyaku Co., Ltd. Nephrotoxicity reducing agent
IL310001A (en) 2021-07-08 2024-03-01 Nippon Shinyaku Co Ltd Precipitation suppressing agent
TW202308664A (zh) 2021-07-08 2023-03-01 日商日本新藥股份有限公司 腎毒性減輕劑
JP2024528659A (ja) 2021-07-19 2024-07-30 アルナイラム ファーマシューティカルズ， インコーポレイテッド 非原発性高シュウ酸尿症疾患または障害を有するまたは発症するリスクがある対象を治療するための方法および組成物
WO2023003995A1 (en) 2021-07-23 2023-01-26 Alnylam Pharmaceuticals, Inc. Beta-catenin (ctnnb1) irna compositions and methods of use thereof
JP2024529437A (ja) 2021-07-29 2024-08-06 アルナイラム ファーマシューティカルズ， インコーポレイテッド ３－ヒドロキシ－３－メチルグリタル－ＣＯＡレダクターゼ（ＨＭＧＣＲ）ｉＲＮＡ組成物およびその使用方法
AR126675A1 (es) 2021-08-03 2023-11-01 Alnylam Pharmaceuticals Inc COMPOSICIONES DE ARNi CONTRA LA TRANSTIRRETINA (TTR) Y SUS MÉTODOS DE USO
CA3226651A1 (en) * 2021-08-03 2023-02-09 Kallanthottathil G. Rajeev Compositions and methods for targeted rna delivery
PE20241132A1 (es) 2021-08-04 2024-05-24 Alnylam Pharmaceuticals Inc Composiciones de arni y metodos para silenciar el angiotensinogeno (agt)
CA3228733A1 (en) 2021-08-13 2023-02-16 Alnylam Pharmaceuticals, Inc. Factor xii (f12) irna compositions and methods of use thereof
AU2022339821A1 (en) 2021-08-31 2024-03-07 Alnylam Pharmaceuticals, Inc. Cell death-inducing dffa-like effector b (cideb) irna compositions and methods of use thereof
JP2024531728A (ja) 2021-09-14 2024-08-29 アルゴノート アールエヌエー リミテッド 心血管疾患の処置
WO2023044370A2 (en) 2021-09-17 2023-03-23 Alnylam Pharmaceuticals, Inc. Irna compositions and methods for silencing complement component 3 (c3)
CA3232191A1 (en) * 2021-09-18 2023-03-23 Chong Li Lpa inhibitor and use thereof
AU2022345881A1 (en) 2021-09-20 2024-03-21 Alnylam Pharmaceuticals, Inc. Inhibin subunit beta e (inhbe) modulator compositions and methods of use thereof
MX2024003477A (es) * 2021-09-23 2024-04-05 Shanghai Argo Biopharmaceutical Co Ltd Cluster de ligandos multivalentes con andamio de diamina para el suministro dirigido de agentes terapeuticos.
US20250115915A1 (en) 2021-10-01 2025-04-10 Adarx Pharmaceuticals, Inc. Prekallikrein-modulating compositions and methods of use thereof
US20250352667A1 (en) 2021-10-22 2025-11-20 Korro Bio, Inc. Methods and compositions for disrupting nrf2-keap1 protein interaction by adar mediated rna editing
KR20240095325A (ko) 2021-10-29 2024-06-25 알닐람 파마슈티칼스 인코포레이티드 보체 인자 b (cfb) irna 조성물 및 이의 사용 방법
TW202334418A (zh) 2021-10-29 2023-09-01 美商艾拉倫製藥股份有限公司 杭丁頓（ＨＴＴ）ｉＲＮＡ劑組成物及其使用方法
CN118284695A (zh) 2021-11-11 2024-07-02 豪夫迈·罗氏有限公司 用于治疗hbv的药物组合
WO2023102188A1 (en) 2021-12-03 2023-06-08 Quralis Corporation Gapmer antisense oligonucleotides with modified backbone chemistries
GB202117758D0 (en) 2021-12-09 2022-01-26 Ucl Business Ltd Therapeutics for the treatment of neurodegenerative disorders
TW202340466A (zh) * 2021-12-16 2023-10-16 大陸商上海拓界生物醫藥科技有限公司 一種ｄｓｒｎａ、其製備方法及應用
KR20240116539A (ko) * 2021-12-16 2024-07-29 투오지에 바이오텍 (상하이) 컴퍼니 리미티드 LPA를 표적으로 하는 siRNA 및 접합체
CN119095603A (zh) 2021-12-17 2024-12-06 豪夫迈·罗氏有限公司 用于调节rtel1和fubp1的寡核苷酸的组合
CA3243093A1 (en) * 2022-01-20 2025-04-08 Tuojie Biotech (Shanghai) Co., Ltd. DOUBLE-STRANDED RNA, ITS USES AND PREPARATION PROCESS
TW202345865A (zh) * 2022-01-24 2023-12-01 大陸商上海舶望製藥有限公司 抑制LPA(Apo(a))蛋白表達的組合物和方法
WO2023141314A2 (en) 2022-01-24 2023-07-27 Alnylam Pharmaceuticals, Inc. Heparin sulfate biosynthesis pathway enzyme irna agent compositions and methods of use thereof
CN117756866A (zh) * 2022-01-30 2024-03-26 大睿生物医药科技(上海)有限公司 含有n-乙酰半乳糖胺的靶向配体
AR128558A1 (es) 2022-02-21 2024-05-22 Hoffmann La Roche Oligonucleótido antisentido
US20250188469A1 (en) 2022-03-10 2025-06-12 Nippon Shinyaku Co., Ltd. Antiviral antisense oligomer
CN114703184B (zh) * 2022-03-11 2024-06-18 厦门甘宝利生物医药有限公司 Lpa抑制剂及其用途
TW202345867A (zh) 2022-03-16 2023-12-01 日商第一三共股份有限公司 抑制運鐵蛋白受體2表現的siRNA
CN119213005A (zh) 2022-03-16 2024-12-27 艾姆皮瑞克公司 用于提高siRNA生物利用度的GALNAC组合物
WO2023176863A1 (ja) 2022-03-16 2023-09-21 第一三共株式会社 ＲＮＡｉ活性を有する化学修飾オリゴヌクレオチド
TW202403044A (zh) 2022-03-28 2024-01-16 美商安彼瑞可股份有限公司 經修飾之寡核苷酸
CN115028670B (zh) * 2022-06-24 2023-07-28 四川大学华西医院 一种n-乙酰基-d-半乳糖胺三聚体前体的制备方法
CN119654412A (zh) * 2022-06-27 2025-03-18 中美瑞康核酸技术(南通)研究院有限公司 激活补体因子h表达的寡核苷酸调节剂
JP2025524566A (ja) 2022-07-15 2025-07-30 プロキューアール セラピューティクス ツー ベスローテン フェンノートシャップ Ａｄａｒ媒介ｒｎａ編集のためのオリゴヌクレオチドおよびその使用
EP4555085A1 (en) 2022-07-15 2025-05-21 ProQR Therapeutics II B.V. Chemically modified oligonucleotides for adar-mediated rna editing
CN116814621B (zh) * 2022-08-05 2025-09-09 厦门甘宝利生物医药有限公司 一种抑制apoc3基因表达的rna抑制剂及其应用
CN120077130A (zh) 2022-08-18 2025-05-30 阿尔尼拉姆医药品有限公司 通用非靶向sirna组合物及其使用方法
JP2025532593A (ja) 2022-09-15 2025-10-01 リジェネロン・ファーマシューティカルズ・インコーポレイテッド １７ｂ－ヒドロキシステロイドデヒドロゲナーゼ１３型（ｈｓｄ１７ｂ１３）ｉｒｎａ組成物およびその使用方法
CA3268249A1 (en) 2022-09-23 2024-03-28 Ionis Pharmaceuticals, Inc. COMPOUNDS AND METHODS FOR REDUCING MECP2 EXPRESSION
WO2024098061A2 (en) 2022-11-04 2024-05-10 Genkardia Inc. Oligonucleotide-based therapeutics targeting cyclin d2 for the treatment of heart failure
WO2024106539A1 (ja) * 2022-11-18 2024-05-23 株式会社ボナック リガンドコンジュゲート物質及びそれを含む核酸並びにその用途
AU2023383571A1 (en) 2022-11-18 2025-07-03 Genkardia Inc. Methods and compositions for preventing, treating, or reversing cardiac diastolic dysfunction
WO2024112937A2 (en) * 2022-11-23 2024-05-30 Pretzel Therapeutics, Inc. Compositions and methods for treatment of cancer and metabolic disease
KR20250116697A (ko) 2022-12-02 2025-08-01 상하이 아르고 바이오파마슈티칼 씨오., 엘티디. 비시클릭 무염기 핵산 유사체 및 이들로부터 제조된 올리고머 화합물
EP4592432A3 (en) 2022-12-19 2025-10-29 Arnatar Therapeutics Arnatar compounds and methods for enhanced cellular uptake
WO2024137543A1 (en) 2022-12-19 2024-06-27 Arnatar Therapeutics, Inc Advanced rna targeting (arnatar)
AR131419A1 (es) * 2022-12-21 2025-03-19 Lilly Co Eli TERAPÉUTICOS NOVEDOSOS DE iARN DE FAS Y USOS DE ESTOS
EP4649153A1 (en) * 2023-01-10 2025-11-19 Ausperbio Therapeutics Inc. Modified multi-segmented antisense oligonucleotides for use
AU2024217843A1 (en) 2023-02-09 2025-07-31 Alnylam Pharmaceuticals, Inc. Reversir molecules and methods of use thereof
WO2024175113A1 (zh) * 2023-02-24 2024-08-29 南京明德新药研发有限公司 包含R和E的双链siRNA类似物及其缀合物
AU2024258561A1 (en) 2023-04-20 2025-10-30 Adarx Pharmaceuticals, Inc. Mapt-modulating compositions and methods of use thereof
WO2024220746A2 (en) 2023-04-21 2024-10-24 Flagship Pioneering Innovations Vii, Llc Rnai agents targeting fatty acid synthase and related methods
WO2024221135A1 (en) * 2023-04-23 2024-10-31 Ausper Biopharma Co., Ltd. Oligonucleotides for use in modulating immune responses against hepatitis b viral infection
US20240374741A1 (en) * 2023-05-11 2024-11-14 Synerk Biotech Limited Compound, a conjugate and uses thereof
WO2024238396A1 (en) 2023-05-12 2024-11-21 Adarx Pharmaceuticals, Inc. Nmda ligand conjugated compounds and uses thereof
UY40743A (es) * 2023-05-19 2024-12-13 Shanghai Argo Biopharmaceutical Co Ltd COMPOSICIONES Y MÉTODOS PARA INHIBIR LA EXPRESIÓN DEL factor de coagulación XI (FXI)
AU2024279767A1 (en) 2023-05-26 2025-12-04 Adarx Pharmaceuticals, Inc. Sod1-modulating compositions and methods of use thereof
CN121079106A (zh) * 2023-05-31 2025-12-05 上海拓界生物医药科技有限公司 一种靶向LPA的dsRNA及其应用
WO2024255761A1 (zh) * 2023-06-12 2024-12-19 大睿生物 包含糖的寡核苷酸递送配体
AU2024302527A1 (en) 2023-06-13 2025-11-13 Arnatar Therapeutics, Inc Advanced rna targeting (arnatar) for angiotensinogen
WO2024263694A1 (en) 2023-06-20 2024-12-26 Adarx Pharmaceuticals, Inc. Lrrk2-modulating compositions and methods of use thereof
CN119219716A (zh) * 2023-06-30 2024-12-31 上海维申医药有限公司 新型GalNAc的靶向递送片段及其制备和应用
WO2025015338A1 (en) 2023-07-13 2025-01-16 Korro Bio, Inc. Rna-editing oligonucleotides and uses thereof
AU2024287308A1 (en) 2023-07-13 2025-12-18 Korro Bio, Inc. Rna-editing oligonucleotides and uses thereof
WO2025021831A1 (en) * 2023-07-24 2025-01-30 Astrazeneca Ab Multivalent cargo-carrying complexes and uses thereof
GB202311324D0 (en) 2023-07-24 2023-09-06 Astrazeneca Ab Multivalent cargo-carrying complexes and uses thereof
GB202311334D0 (en) 2023-07-24 2023-09-06 Astrazeneca Ab Multivalent cargo-carrying complexes and uses thereof
WO2025034422A1 (en) 2023-08-04 2025-02-13 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating ctnnb1-associated disorders
WO2025036916A1 (en) 2023-08-16 2025-02-20 Les Laboratoires Servier Oligonucleotides for modulating kcnt1 expression
WO2025045194A1 (zh) * 2023-08-31 2025-03-06 正大天晴药业集团股份有限公司 靶向凝血因子xi的双链核糖核酸
TW202526017A (zh) * 2023-09-14 2025-07-01 美商Ionis製藥公司 用於減少ａｐｏｃｉｉｉ表現的化合物及方法
CN116925160B (zh) * 2023-09-15 2023-12-08 天津全和诚科技有限责任公司 一种GalNAc含糖环中间体及其制备方法
WO2025064819A1 (en) * 2023-09-21 2025-03-27 Ionis Pharmaceuticals, Inc. Compounds and methods for inhibiting lpa
US20250215044A1 (en) * 2023-09-21 2025-07-03 Ionis Pharmaceuticals, Inc. Compounds and Methods for Inhibiting LPA
GB202314724D0 (en) 2023-09-26 2023-11-08 Astrazeneca Ab compounds and methods for reducing psd3 expression
WO2025072748A2 (en) * 2023-09-29 2025-04-03 Insitro, Inc. Compositions and methods for treating nonalcoholic fatty liver disease
CN118680948B (zh) * 2023-10-20 2025-08-22 思合基因(北京)生物科技有限公司 寡核苷酸及其在抗乙型肝炎病毒中的应用
AU2024369609A1 (en) 2023-10-31 2025-12-11 Korro Bio, Inc. Oligonucleotides comprising phosphoramidate internucleotide linkages
TW202521133A (zh) * 2023-11-27 2025-06-01 大陸商上海舶望製藥有限公司 抑制甲狀腺素運載蛋白(ttr)表達的組合物和方法
WO2025119212A1 (zh) * 2023-12-05 2025-06-12 广东东阳光药业股份有限公司 一种新型的双链siRNA、其缀合物及其用途
CN120309684A (zh) * 2024-01-15 2025-07-15 武汉人福创新药物研发中心有限公司 靶向化合物及其用途
CN117568313B (zh) * 2024-01-15 2024-04-26 上海贝斯昂科生物科技有限公司 基因编辑组合物及其用途
WO2025155911A1 (en) 2024-01-18 2025-07-24 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of hurler syndrome
EP4671372A2 (en) 2024-01-29 2025-12-31 Arnatar Therapeutics, Inc Translation-enhancing nucleic acid compounds: Upward regulation 1 coupled with ASO (ACT-UP1) and their uses
WO2025165891A1 (en) 2024-01-29 2025-08-07 Arnatar Therapeutics, Inc Translation enhancing nucleic acid compounds: aso coupled translation - upregulation 1 (act-up1) and uses thereof
WO2025196505A2 (en) 2024-03-22 2025-09-25 Takeda Pharmaceutical Company Limited Compositions and methods for inhibiting cytochrome p450 family 7 subfamily a member 1 (cyp7a1) expression
GB202404661D0 (en) 2024-04-02 2024-05-15 Proqr Therapeutics Ii Bv Antisense oligoncleotides for the treatment of liver disease
WO2025224230A1 (en) 2024-04-25 2025-10-30 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of fatty liver disease
CN118146284B (zh) * 2024-05-08 2024-07-26 北京悦康科创医药科技股份有限公司 一种GalNAc化合物、其与寡核苷酸缀合物及制备方法
WO2025242702A1 (en) * 2024-05-23 2025-11-27 Glaxosmithkline Intellectual Property Development Limited Enzymatic process for producing n-acetyl galactosamine clusters

Family Cites Families (379)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3687808A (en) 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
US4458066A (en) 1980-02-29 1984-07-03 University Patents, Inc. Process for preparing polynucleotides
US5132418A (en) 1980-02-29 1992-07-21 University Patents, Inc. Process for preparing polynucleotides
US4500707A (en) 1980-02-29 1985-02-19 University Patents, Inc. Nucleosides useful in the preparation of polynucleotides
US4469863A (en) 1980-11-12 1984-09-04 Ts O Paul O P Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof
US4668777A (en) 1981-03-27 1987-05-26 University Patents, Inc. Phosphoramidite nucleoside compounds
US4415732A (en) 1981-03-27 1983-11-15 University Patents, Inc. Phosphoramidite compounds and processes
US4973679A (en) 1981-03-27 1990-11-27 University Patents, Inc. Process for oligonucleo tide synthesis using phosphormidite intermediates
US5023243A (en) 1981-10-23 1991-06-11 Molecular Biosystems, Inc. Oligonucleotide therapeutic agent and method of making same
US4476301A (en) 1982-04-29 1984-10-09 Centre National De La Recherche Scientifique Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon
DE3329892A1 (de) 1983-08-18 1985-03-07 Köster, Hubert, Prof. Dr., 2000 Hamburg Verfahren zur herstellung von oligonucleotiden
US5118800A (en) 1983-12-20 1992-06-02 California Institute Of Technology Oligonucleotides possessing a primary amino group in the terminal nucleotide
USRE34036E (en) 1984-06-06 1992-08-18 National Research Development Corporation Data transmission using a transparent tone-in band system
US5550111A (en) 1984-07-11 1996-08-27 Temple University-Of The Commonwealth System Of Higher Education Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof
FR2567892B1 (fr) 1984-07-19 1989-02-17 Centre Nat Rech Scient Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons
US5367066A (en) 1984-10-16 1994-11-22 Chiron Corporation Oligonucleotides with selectably cleavable and/or abasic sites
FR2575751B1 (fr) 1985-01-08 1987-04-03 Pasteur Institut Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques
US4751219A (en) 1985-02-05 1988-06-14 Nederlandse Centrale Organisatie Voor Toegepast-Natuur-Wetenschappelijk Onderzoek Synthetic glycolipides, a process for the preparation thereof and several uses for these synthetic glycolipides
US5235033A (en) 1985-03-15 1993-08-10 Anti-Gene Development Group Alpha-morpholino ribonucleoside derivatives and polymers thereof
US5506337A (en) 1985-03-15 1996-04-09 Antivirals Inc. Morpholino-subunit combinatorial library and method
US5166315A (en) 1989-12-20 1992-11-24 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
US5185444A (en) 1985-03-15 1993-02-09 Anti-Gene Deveopment Group Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages
US5405938A (en) 1989-12-20 1995-04-11 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
DE3788914T2 (de) 1986-09-08 1994-08-25 Ajinomoto Kk Verbindungen zur Spaltung von RNS an eine spezifische Position, Oligomere, verwendet bei der Herstellung dieser Verbindungen und Ausgangsprodukte für die Synthese dieser Oligomere.
US5276019A (en) 1987-03-25 1994-01-04 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US5264423A (en) 1987-03-25 1993-11-23 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
GB8712540D0 (en) * 1987-05-28 1987-07-01 Ucb Sa Expression of human proapolipoprotein a-i
CA1340032C (en) 1987-06-24 1998-09-08 Jim Haralambidis Lucleoside derivatives
US5188897A (en) 1987-10-22 1993-02-23 Temple University Of The Commonwealth System Of Higher Education Encapsulated 2',5'-phosphorothioate oligoadenylates
US4924624A (en) 1987-10-22 1990-05-15 Temple University-Of The Commonwealth System Of Higher Education 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof
EP0348458B1 (en) 1987-11-30 1997-04-09 University Of Iowa Research Foundation Dna molecules stabilized by modifications of the 3'-terminal phosphodiester linkage and their use as nucleic acid probes and as therapeutic agents to block the expression of specifically targeted genes
US5403711A (en) 1987-11-30 1995-04-04 University Of Iowa Research Foundation Nucleic acid hybridization and amplification method for detection of specific sequences in which a complementary labeled nucleic acid probe is cleaved
EP0406309A4 (en) 1988-03-25 1992-08-19 The University Of Virginia Alumni Patents Foundation Oligonucleotide n-alkylphosphoramidates
US5278302A (en) 1988-05-26 1994-01-11 University Patents, Inc. Polynucleotide phosphorodithioates
US5216141A (en) 1988-06-06 1993-06-01 Benner Steven A Oligonucleotide analogs containing sulfur linkages
US5175273A (en) 1988-07-01 1992-12-29 Genentech, Inc. Nucleic acid intercalating agents
US5194599A (en) 1988-09-23 1993-03-16 Gilead Sciences, Inc. Hydrogen phosphonodithioate compositions
US5256775A (en) 1989-06-05 1993-10-26 Gilead Sciences, Inc. Exonuclease-resistant oligonucleotides
US5134066A (en) 1989-08-29 1992-07-28 Monsanto Company Improved probes using nucleosides containing 3-dezauracil analogs
US5591722A (en) 1989-09-15 1997-01-07 Southern Research Institute 2'-deoxy-4'-thioribonucleosides and their antiviral activity
US5721218A (en) 1989-10-23 1998-02-24 Gilead Sciences, Inc. Oligonucleotides with inverted polarity
US5399676A (en) 1989-10-23 1995-03-21 Gilead Sciences Oligonucleotides with inverted polarity
US5264562A (en) 1989-10-24 1993-11-23 Gilead Sciences, Inc. Oligonucleotide analogs with novel linkages
US5264564A (en) 1989-10-24 1993-11-23 Gilead Sciences Oligonucleotide analogs with novel linkages
JPH05504552A (ja) 1989-10-24 1993-07-15 ギリアド　サイエンシズ，インコーポレイテッド ２’位が改変されたオリゴヌクレオチド
US5177198A (en) 1989-11-30 1993-01-05 University Of N.C. At Chapel Hill Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates
US5130302A (en) 1989-12-20 1992-07-14 Boron Bilogicals, Inc. Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same
US5587470A (en) 1990-01-11 1996-12-24 Isis Pharmaceuticals, Inc. 3-deazapurines
US5587361A (en) 1991-10-15 1996-12-24 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
US5623065A (en) 1990-08-13 1997-04-22 Isis Pharmaceuticals, Inc. Gapped 2' modified oligonucleotides
US5859221A (en) 1990-01-11 1999-01-12 Isis Pharmaceuticals, Inc. 2'-modified oligonucleotides
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5457191A (en) 1990-01-11 1995-10-10 Isis Pharmaceuticals, Inc. 3-deazapurines
US5670633A (en) 1990-01-11 1997-09-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
US7101993B1 (en) 1990-01-11 2006-09-05 Isis Pharmaceuticals, Inc. Oligonucleotides containing 2′-O-modified purines
US5681941A (en) 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US5646265A (en) 1990-01-11 1997-07-08 Isis Pharmceuticals, Inc. Process for the preparation of 2'-O-alkyl purine phosphoramidites
US6005087A (en) 1995-06-06 1999-12-21 Isis Pharmaceuticals, Inc. 2'-modified oligonucleotides
US5220007A (en) 1990-02-15 1993-06-15 The Worcester Foundation For Experimental Biology Method of site-specific alteration of RNA and production of encoded polypeptides
US5149797A (en) 1990-02-15 1992-09-22 The Worcester Foundation For Experimental Biology Method of site-specific alteration of rna and production of encoded polypeptides
US5321131A (en) 1990-03-08 1994-06-14 Hybridon, Inc. Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling
US5470967A (en) 1990-04-10 1995-11-28 The Dupont Merck Pharmaceutical Company Oligonucleotide analogs with sulfamate linkages
GB9009980D0 (en) 1990-05-03 1990-06-27 Amersham Int Plc Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides
EP0745689A3 (en) 1990-05-11 1996-12-11 Microprobe Corporation A dipstick for a nucleic acid hybridization assay
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
US5378825A (en) 1990-07-27 1995-01-03 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5618704A (en) 1990-07-27 1997-04-08 Isis Pharmacueticals, Inc. Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5623070A (en) 1990-07-27 1997-04-22 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5677437A (en) 1990-07-27 1997-10-14 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
ATE154246T1 (de) 1990-07-27 1997-06-15 Isis Pharmaceuticals Inc Nuklease resistente, pyrimidin modifizierte oligonukleotide, die die gen-expression detektieren und modulieren
US5223618A (en) 1990-08-13 1993-06-29 Isis Pharmaceuticals, Inc. 4'-desmethyl nucleoside analog compounds
US5386023A (en) 1990-07-27 1995-01-31 Isis Pharmaceuticals Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling
FI930455A7 (fi) 1990-08-03 1993-03-24 Sanofi Sa Yhdisteitä ja menetelmiä geeniekspression inhiboimiseksi
US5177196A (en) 1990-08-16 1993-01-05 Microprobe Corporation Oligo (α-arabinofuranosyl nucleotides) and α-arabinofuranosyl precursors thereof
US5214134A (en) 1990-09-12 1993-05-25 Sterling Winthrop Inc. Process of linking nucleosides with a siloxane bridge
US5561225A (en) 1990-09-19 1996-10-01 Southern Research Institute Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages
EP0549686A4 (en) 1990-09-20 1995-01-18 Gilead Sciences Inc Modified internucleoside linkages
US5432272A (en) 1990-10-09 1995-07-11 Benner; Steven A. Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases
US6582908B2 (en) 1990-12-06 2003-06-24 Affymetrix, Inc. Oligonucleotides
US5948903A (en) 1991-01-11 1999-09-07 Isis Pharmaceuticals, Inc. Synthesis of 3-deazapurines
US5672697A (en) 1991-02-08 1997-09-30 Gilead Sciences, Inc. Nucleoside 5'-methylene phosphonates
US7015315B1 (en) 1991-12-24 2006-03-21 Isis Pharmaceuticals, Inc. Gapped oligonucleotides
US5571799A (en) 1991-08-12 1996-11-05 Basco, Ltd. (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response
EP0538194B1 (de) 1991-10-17 1997-06-04 Novartis AG Bicyclische Nukleoside, Oligonukleotide, Verfahren zu deren Herstellung und Zwischenprodukte
US5594121A (en) 1991-11-07 1997-01-14 Gilead Sciences, Inc. Enhanced triple-helix and double-helix formation with oligomers containing modified purines
EP0637965B1 (en) 1991-11-26 2002-10-16 Isis Pharmaceuticals, Inc. Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines
US5484908A (en) 1991-11-26 1996-01-16 Gilead Sciences, Inc. Oligonucleotides containing 5-propynyl pyrimidines
TW393513B (en) 1991-11-26 2000-06-11 Isis Pharmaceuticals Inc Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines
US5792608A (en) 1991-12-12 1998-08-11 Gilead Sciences, Inc. Nuclease stable and binding competent oligomers and methods for their use
US5359044A (en) 1991-12-13 1994-10-25 Isis Pharmaceuticals Cyclobutyl oligonucleotide surrogates
ATE515510T1 (de) * 1991-12-24 2011-07-15 Isis Pharmaceuticals Inc Durch dna-abschnitte unterbrochene modifizierte oligonukleotide
US5700922A (en) 1991-12-24 1997-12-23 Isis Pharmaceuticals, Inc. PNA-DNA-PNA chimeric macromolecules
FR2687679B1 (fr) 1992-02-05 1994-10-28 Centre Nat Rech Scient Oligothionucleotides.
US5633360A (en) 1992-04-14 1997-05-27 Gilead Sciences, Inc. Oligonucleotide analogs capable of passive cell membrane permeation
US5434257A (en) 1992-06-01 1995-07-18 Gilead Sciences, Inc. Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages
EP0577558A2 (de) 1992-07-01 1994-01-05 Ciba-Geigy Ag Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte
US5652355A (en) 1992-07-23 1997-07-29 Worcester Foundation For Experimental Biology Hybrid oligonucleotide phosphorothioates
JPH08502723A (ja) 1992-07-27 1996-03-26 ハイブライドン インコーポレイテッド オリゴヌクレオチド・アルキルホスホノチオエート
WO1994014226A1 (en) 1992-12-14 1994-06-23 Honeywell Inc. Motor system with individually controlled redundant windings
AU6165494A (en) 1993-01-25 1994-08-15 Hybridon, Inc. Oligonucleotide alkylphosphonates and alkylphosphonothioates
US5476925A (en) 1993-02-01 1995-12-19 Northwestern University Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups
GB9304618D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Chemical compounds
GB9304620D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Compounds
EP0691968B1 (en) 1993-03-30 1997-07-16 Sanofi Acyclic nucleoside analogs and oligonucleotide sequences containing them
EP0691977B1 (en) 1993-03-31 1997-11-26 Sanofi Oligonucleotides with amide linkages replacing phosphodiester linkages
US5502177A (en) 1993-09-17 1996-03-26 Gilead Sciences, Inc. Pyrimidine derivatives for labeled binding partners
US5801154A (en) 1993-10-18 1998-09-01 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of multidrug resistance-associated protein
US5457187A (en) 1993-12-08 1995-10-10 Board Of Regents University Of Nebraska Oligonucleotides containing 5-fluorouracil
US5446137B1 (en) 1993-12-09 1998-10-06 Behringwerke Ag Oligonucleotides containing 4'-substituted nucleotides
ES2149962T3 (es) 1993-12-09 2000-11-16 Univ Jefferson Compuestos y metodos para mutaciones dirigidas al sitio en celulas eucarioticas.
US5519134A (en) 1994-01-11 1996-05-21 Isis Pharmaceuticals, Inc. Pyrrolidine-containing monomers and oligomers
US5728518A (en) 1994-01-12 1998-03-17 The Immune Response Corporation Antiviral poly-and oligonucleotides
US5596091A (en) 1994-03-18 1997-01-21 The Regents Of The University Of California Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides
US5627053A (en) 1994-03-29 1997-05-06 Ribozyme Pharmaceuticals, Inc. 2'deoxy-2'-alkylnucleotide containing nucleic acid
US5625050A (en) 1994-03-31 1997-04-29 Amgen Inc. Modified oligonucleotides and intermediates useful in nucleic acid therapeutics
US5646269A (en) 1994-04-28 1997-07-08 Gilead Sciences, Inc. Method for oligonucleotide analog synthesis
US5525711A (en) 1994-05-18 1996-06-11 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Pteridine nucleotide analogs as fluorescent DNA probes
US5597909A (en) 1994-08-25 1997-01-28 Chiron Corporation Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use
US5599706A (en) 1994-09-23 1997-02-04 Stinchcomb; Dan T. Ribozymes targeted to apo(a) mRNA
US5681940A (en) * 1994-11-02 1997-10-28 Icn Pharmaceuticals Sugar modified nucleosides and oligonucleotides
US6172045B1 (en) 1994-12-07 2001-01-09 Neorx Corporation Cluster clearing agents
US6908903B1 (en) 1994-12-07 2005-06-21 Aletheon Pharmaceuticals, Inc. Cluster clearing agents
US5652356A (en) 1995-08-17 1997-07-29 Hybridon, Inc. Inverted chimeric and hybrid oligonucleotides
US20030119724A1 (en) 1995-11-22 2003-06-26 Ts`O Paul O.P. Ligands to enhance cellular uptake of biomolecules
JP2000501414A (ja) 1995-11-22 2000-02-08 ザ・ジョンズ・ホプキンス・ユニバーシティー 生体分子の細胞取り込みを高めるリガンド
US5998203A (en) 1996-04-16 1999-12-07 Ribozyme Pharmaceuticals, Inc. Enzymatic nucleic acids containing 5'-and/or 3'-cap structures
US6620916B1 (en) 1996-09-26 2003-09-16 Ajinomoto Co., Inc. Modified physiologically active proteins and medicinal compositions containing the same
US6770748B2 (en) 1997-03-07 2004-08-03 Takeshi Imanishi Bicyclonucleoside and oligonucleotide analogue
JP3756313B2 (ja) 1997-03-07 2006-03-15 武 今西 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体
USRE44779E1 (en) 1997-03-07 2014-02-25 Santaris Pharma A/S Bicyclonucleoside and oligonucleotide analogues
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
US7572582B2 (en) 1997-09-12 2009-08-11 Exiqon A/S Oligonucleotide analogues
EP2253639A1 (en) 1997-09-12 2010-11-24 Exiqon A/S Bi- and tri-cyclic nucleoside, nucleotide and oligonucleoide analogues
US20040171564A1 (en) 1997-11-20 2004-09-02 Honkanen Richard E. Antisense oligonucleotide modulation of human serine/threonine protein phosphatase gene expression
US20030228597A1 (en) 1998-04-13 2003-12-11 Cowsert Lex M. Identification of genetic targets for modulation by oligonucleotides and generation of oligonucleotides for gene modulation
US6300319B1 (en) 1998-06-16 2001-10-09 Isis Pharmaceuticals, Inc. Targeted oligonucleotide conjugates
US6043352A (en) 1998-08-07 2000-03-28 Isis Pharmaceuticals, Inc. 2'-O-Dimethylaminoethyloxyethyl-modified oligonucleotides
RU2249463C2 (ru) * 1998-08-19 2005-04-10 Бакстер Хелфкэа С.А. Иммуногенный конъюгат бета-пропионамид-связанного полисахарида с белком, использующийся в качестве вакцины
WO2000010599A2 (en) 1998-08-19 2000-03-02 North American Vaccine, Inc. IMMUNOGENIC β-PROPIONAMIDO-LINKED POLYSACCHARIDE PROTEIN CONJUGATE USEFUL AS A VACCINE PRODUCED USING AN N-ACRYLOYLATED POLYSACCHARIDE
US6166239A (en) 1998-09-04 2000-12-26 Isis Pharmaceuticals, Inc. Oligonucleotide protecting groups
EP1152009B2 (en) 1999-02-12 2017-09-06 Daiichi Sankyo Company, Limited Novel nucleosides and oligonucleotide analogues
US20030170249A1 (en) 1999-02-19 2003-09-11 Hakomori Sen-Itiroh Vaccines directed to cancer-associated carbohydrate antigens
US7084125B2 (en) 1999-03-18 2006-08-01 Exiqon A/S Xylo-LNA analogues
US7098192B2 (en) 1999-04-08 2006-08-29 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of STAT3 expression
US6159694A (en) 1999-04-08 2000-12-12 Isis Pharmaceuticals Inc. Antisense modulation of stat3 expression
IL145778A0 (en) 1999-04-21 2002-07-25 American Home Prod Methods and compositions for inhibiting the function of polynucleotide sequences
CN102180924A (zh) 1999-05-04 2011-09-14 桑塔里斯制药公司 L-核糖-lna类似物
US6525191B1 (en) 1999-05-11 2003-02-25 Kanda S. Ramasamy Conformationally constrained L-nucleosides
US6383812B1 (en) 1999-05-28 2002-05-07 Academia Sinica Anti liver disease drug R-YEEE and method of synthesizing branched galactose-terminal glycoproteins
US8541548B2 (en) 1999-06-07 2013-09-24 Arrowhead Madison Inc. Compounds and methods for reversible modification of biologically active molecules
US20080281041A1 (en) 1999-06-07 2008-11-13 Rozema David B Reversibly Masked Polymers
US6656730B1 (en) 1999-06-15 2003-12-02 Isis Pharmaceuticals, Inc. Oligonucleotides conjugated to protein-binding drugs
CA2379152A1 (en) 1999-07-16 2001-01-25 Hyseq, Inc. Novel angiopoietin materials and methods
JP4151751B2 (ja) 1999-07-22 2008-09-17 第一三共株式会社 新規ビシクロヌクレオシド類縁体
DE19935303A1 (de) 1999-07-28 2001-02-08 Aventis Pharma Gmbh Oligonukleotide zur Inhibierung der Expression von humanem eg5
US20020082227A1 (en) 1999-09-30 2002-06-27 Scott Henry Use of oligonucleotides for inhibition of complement activation
US20050112118A1 (en) 1999-12-02 2005-05-26 Myriad Genetics, Incorporated Compositions and methods for treating inflammatory disorders
EP1239050A4 (en) 1999-12-09 2004-07-21 Sankyo Co METHOD FOR TESTING CURATIVE OR PREVENTIVE AGENT OF HYPERLIPEMIA
DE60027203T2 (de) 1999-12-30 2007-01-04 K.U. Leuven Research & Development Cyclohexennukleinsäuren
US20020055479A1 (en) 2000-01-18 2002-05-09 Cowsert Lex M. Antisense modulation of PTP1B expression
US6261840B1 (en) 2000-01-18 2001-07-17 Isis Pharmaceuticals, Inc. Antisense modulation of PTP1B expression
US7179796B2 (en) 2000-01-18 2007-02-20 Isis Pharmaceuticals, Inc. Antisense modulation of PTP1B expression
US6602857B1 (en) 2000-01-18 2003-08-05 Isis Pharmaceuticals, Inc. Antisense modulation of PTP1B expression
US7833992B2 (en) 2001-05-18 2010-11-16 Merck Sharpe & Dohme Conjugates and compositions for cellular delivery
US7491805B2 (en) 2001-05-18 2009-02-17 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
US8202979B2 (en) 2002-02-20 2012-06-19 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid
WO2001060860A2 (en) 2000-02-17 2001-08-23 Millennium Predictive Medicine, Inc. Genes differentially expressed in human prostate cancer and their use
EP1314734A1 (en) 2000-08-29 2003-05-28 Takeshi Imanishi Novel nucleoside analogs and oligonucleotide derivatives containing these analogs
US6426220B1 (en) 2000-10-30 2002-07-30 Isis Pharmaceuticals, Inc. Antisense modulation of calreticulin expression
CN100406065C (zh) * 2000-12-01 2008-07-30 细胞工厂治疗公司 糖基化/半乳糖基化肽、双官能接头和核苷酸单体/多聚体的缀合物以及相关的组合物和使用方法
US20030077829A1 (en) 2001-04-30 2003-04-24 Protiva Biotherapeutics Inc.. Lipid-based formulations
EP1403367A4 (en) 2001-06-08 2005-08-17 Sankyo Co A MEDICAMENT TEST METHOD FOR TREATING OR PREVENTING DISEASES SUCH AS HYPERLIPEMIA
WO2003004602A2 (en) 2001-07-03 2003-01-16 Isis Pharmaceuticals, Inc. Nuclease resistant chimeric oligonucleotides
US20030175906A1 (en) 2001-07-03 2003-09-18 Muthiah Manoharan Nuclease resistant chimeric oligonucleotides
US20030158403A1 (en) 2001-07-03 2003-08-21 Isis Pharmaceuticals, Inc. Nuclease resistant chimeric oligonucleotides
US7425545B2 (en) * 2001-07-25 2008-09-16 Isis Pharmaceuticals, Inc. Modulation of C-reactive protein expression
US6964950B2 (en) 2001-07-25 2005-11-15 Isis Pharmaceuticals, Inc. Antisense modulation of C-reactive protein expression
US7227014B2 (en) 2001-08-07 2007-06-05 Isis Pharmaceuticals, Inc. Antisense modulation of apolipoprotein (a) expression
US7259150B2 (en) 2001-08-07 2007-08-21 Isis Pharmaceuticals, Inc. Modulation of apolipoprotein (a) expression
WO2003014397A1 (en) 2001-08-09 2003-02-20 Biomedlab Corporation Probe for detection of enteric virus detection kit and method for enteric virus with the same
WO2003020739A2 (en) 2001-09-04 2003-03-13 Exiqon A/S Novel lna compositions and uses thereof
US7439043B2 (en) 2001-10-10 2008-10-21 Neose Technologies, Inc. Galactosyl nucleotide sugars
EP1451578B1 (en) 2001-11-16 2013-08-21 Genentech, Inc. Use of angptl3 antagonists for the treatment of liver diseases
US20100240730A1 (en) 2002-02-20 2010-09-23 Merck Sharp And Dohme Corp. RNA Interference Mediated Inhibition of Gene Expression Using Chemically Modified Short Interfering Nucleic Acid (siNA)
WO2004011624A2 (en) 2002-07-31 2004-02-05 Nucleonics, Inc. Double stranded rna structures and constructs, and methods for generating and using the same
WO2004014933A1 (en) 2002-08-07 2004-02-19 University Of Massachusetts Compositions for rna interference and methods of use thereof
EP1543019A2 (en) 2002-09-11 2005-06-22 Santaris Pharma A/S Modified pna molecules
CA2502649A1 (en) 2002-10-18 2004-04-29 Nucleonics Inc. Double-stranded rna structures and constructs, and methods for generating and using the same
AU2003291753B2 (en) 2002-11-05 2010-07-08 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
WO2004044139A2 (en) 2002-11-05 2004-05-27 Isis Parmaceuticals, Inc. Modified oligonucleotides for use in rna interference
US20060009410A1 (en) 2002-11-13 2006-01-12 Crooke Rosanne M Effects of apolipoprotein B inhibition on gene expression profiles in animals
US7511131B2 (en) 2002-11-13 2009-03-31 Genzyme Corporation Antisense modulation of apolipoprotein B expression
WO2004044181A2 (en) 2002-11-13 2004-05-27 Isis Pharmaceuticals, Inc. Antisense modulation of apolipoprotein b expression
US8090542B2 (en) 2002-11-14 2012-01-03 Dharmacon Inc. Functional and hyperfunctional siRNA
EP2474631B1 (en) 2002-12-20 2014-02-12 Celera Corporation Genetic polymorphisms associated with myocardial infarction, methods of detection and uses thereof
US6673661B1 (en) 2002-12-20 2004-01-06 Taiwan Semiconductor Manufacturing Co., Ltd. Self-aligned method for forming dual gate thin film transistor (TFT) device
WO2004063208A1 (en) 2003-01-09 2004-07-29 Postech Foundation New phosphoramidite compounds
WO2004072046A2 (en) 2003-02-12 2004-08-26 Carex S.A. Quinoline derivatives and their use for modulation of lxr activity
US7803781B2 (en) 2003-02-28 2010-09-28 Isis Pharmaceuticals, Inc. Modulation of growth hormone receptor expression and insulin-like growth factor expression
ATE479752T1 (de) * 2003-03-07 2010-09-15 Alnylam Pharmaceuticals Inc Therapeutische zusammensetzungen
JP2006522158A (ja) * 2003-04-03 2006-09-28 アルナイラム ファーマシューティカルズ インコーポレイテッド ｉＲＮＡ複合体
US7598227B2 (en) 2003-04-16 2009-10-06 Isis Pharmaceuticals Inc. Modulation of apolipoprotein C-III expression
US7851615B2 (en) 2003-04-17 2010-12-14 Alnylam Pharmaceuticals, Inc. Lipophilic conjugated iRNA agents
US7723509B2 (en) 2003-04-17 2010-05-25 Alnylam Pharmaceuticals IRNA agents with biocleavable tethers
JP4597976B2 (ja) 2003-04-17 2010-12-15 アルナイラム ファーマシューティカルズ インコーポレイテッド 修飾ｉＲＮＡ剤
US7750142B2 (en) 2003-04-28 2010-07-06 Isis Pharmaceuticals, Inc. Modulation of glucagon receptor expression
US7399853B2 (en) 2003-04-28 2008-07-15 Isis Pharmaceuticals Modulation of glucagon receptor expression
WO2004101619A1 (ja) 2003-05-15 2004-11-25 Shionogi Co., Ltd. 機能的糖ペプチドの合理的設計および合成
WO2004106356A1 (en) 2003-05-27 2004-12-09 Syddansk Universitet Functionalized nucleotide derivatives
DK1661905T3 (da) 2003-08-28 2012-07-23 Takeshi Imanishi Hidtil ukendte syntetiske nukleinsyrer af N-O-krydsbindingstype
WO2005027962A1 (en) 2003-09-18 2005-03-31 Isis Pharmaceuticals, Inc. 4’-thionucleosides and oligomeric compounds
EA009670B1 (ru) * 2003-09-18 2008-02-28 Ай Эс Ай Эс ФАРМАСЬЮТИКАЛЗ, ИНК. МОДУЛИРОВАНИЕ ЭКСПРЕССИИ eIF4E
US8258105B2 (en) * 2003-10-07 2012-09-04 Isis Pharmaceuticals, Inc. Antisense oligonucleotides optimized for kidney targeting
US7959919B2 (en) 2003-11-19 2011-06-14 Novelmed Therapeutics, Inc. Method of inhibiting factor B-mediated complement activation
WO2005065686A1 (en) 2004-01-07 2005-07-21 Adipogen Pharmaceuticals Pty Limited Differentiation modulating agents and uses therefor
WO2005071080A2 (en) 2004-01-20 2005-08-04 Isis Pharmaceuticals, Inc. Modulation of glucocorticoid receptor expression
JP4628960B2 (ja) * 2004-02-05 2011-02-09 独立行政法人科学技術振興機構 リンカー化合物及びリガンド複合体、並びにそれらの製造方法
US20050244869A1 (en) 2004-04-05 2005-11-03 Brown-Driver Vickie L Modulation of transthyretin expression
WO2005097155A1 (ja) 2004-04-08 2005-10-20 Takara Bio Inc. 神経突起伸長誘導剤
CN101052717A (zh) 2004-05-11 2007-10-10 α基因株式会社 诱发rna干扰的多核苷酸以及使用该多核苷酸的基因表达抑制方法
JP2008501694A (ja) 2004-06-03 2008-01-24 アイシス ファーマシューティカルズ、インク． 遺伝子調節の使用のために個別に修飾された鎖を有する二本鎖組成物
PT1771474E (pt) 2004-07-20 2010-05-03 Genentech Inc Inibidores de proteína 4 do tipo angiopoietina, combinações e sua utilização
EP1781698B1 (en) 2004-07-20 2016-07-06 Genentech, Inc. Compositions and methods of using angiopoietin-like 4 protein
DK1786472T3 (da) 2004-08-10 2013-04-15 Genzyme Corp Antisense-modulering af apolipoprotein B-ekspression
US7582744B2 (en) 2004-08-10 2009-09-01 Alnylam Pharmaceuticals, Inc. Chemically modified oligonucleotides
WO2006031461A2 (en) 2004-09-09 2006-03-23 Isis Pharmaceuticals, Inc. Pyrrolidinyl groups for attaching conjugates to oligomeric compounds
JP4944034B2 (ja) 2004-10-13 2012-05-30 アイシス ファーマシューティカルズ， インコーポレーテッド Ｐｔｐ１ｂ発現のアンチセンス調節
US20080261905A1 (en) 2004-11-08 2008-10-23 K.U. Leuven Research And Development Modified Nucleosides for Rna Interference
US20060148740A1 (en) 2005-01-05 2006-07-06 Prosensa B.V. Mannose-6-phosphate receptor mediated gene transfer into muscle cells
JP2008527993A (ja) 2005-01-24 2008-07-31 アヴァリス・アクチエボラーグ 特異性及び送達の改善のためのｓｉＲＮＡ分子、ｓｈＲＮＡ分子又はアンチセンス分子及び機能的実体を含む複合体
EA200800823A1 (ru) * 2005-09-15 2008-10-30 Сантарис Фарма А/С Соединения-антагонисты рнк для ингибирования экспрессии аро-в100
US20070087987A1 (en) 2005-09-19 2007-04-19 Monia Brett P Modulation of glucagon receptor expression
CN101313066A (zh) 2005-09-19 2008-11-26 强生医药研究及开发有限责任公司 糖皮质激素受体表达的调节
EP2161038B1 (en) 2006-01-26 2013-12-25 Isis Pharmaceuticals, Inc. Compositions and their uses directed to Huntingtin
US7569686B1 (en) 2006-01-27 2009-08-04 Isis Pharmaceuticals, Inc. Compounds and methods for synthesis of bicyclic nucleic acid analogs
CN102908630B (zh) 2006-01-27 2014-11-19 Isis制药公司 6-修饰的双环核酸类似物
US20090292006A1 (en) 2006-05-05 2009-11-26 Sanjay Bhanot Compounds and methods for modulating expression of dgat2
ES2366973T3 (es) * 2006-05-05 2011-10-27 Isis Pharmaceuticals, Inc. Compuestos y procedimiento para modular la expresión génica.
US7666854B2 (en) 2006-05-11 2010-02-23 Isis Pharmaceuticals, Inc. Bis-modified bicyclic nucleic acid analogs
JP5441688B2 (ja) 2006-05-11 2014-03-12 アイシス ファーマシューティカルズ， インコーポレーテッド ５’修飾二環式核酸類似体
JP2010500290A (ja) 2006-08-04 2010-01-07 アイシス ファーマシューティカルズ， インコーポレーテッド Ｊｎｋタンパク質を調節するための組成物および方法
KR101133799B1 (ko) 2006-08-18 2012-04-24 에프. 호프만-라 로슈 아게 폴리뉴클레오타이드의 생체내 전달을 위한 다가접합체
US8658211B2 (en) 2006-08-18 2014-02-25 Arrowhead Madison Inc. Polyconjugates for in vivo delivery of polynucleotides
EP2081949B1 (en) 2006-09-22 2014-12-10 GE Healthcare Dharmacon, Inc. Tripartite oligonucleotide complexes and methods for gene silencing by rna interference
WO2008049085A1 (en) 2006-10-18 2008-04-24 Isis Pharmaceuticals, Inc. Antisense compounds
US8084437B2 (en) 2006-11-27 2011-12-27 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
US8093222B2 (en) 2006-11-27 2012-01-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
KR101503937B1 (ko) 2006-12-08 2015-03-18 렉시컨 파마슈티컬스 인코퍼레이티드 Ａｎｇｐｔｌ３ 에 대한 단일클론 항체
CN101616690B (zh) * 2006-12-20 2015-11-25 爱克索马美国有限责任公司 用于治疗IL-1β相关疾病的方法
EP2125852B1 (en) 2007-02-15 2016-04-06 Ionis Pharmaceuticals, Inc. 5'-substituted-2'-f modified nucleosides and oligomeric compounds prepared therefrom
EP2604283A1 (en) 2007-02-16 2013-06-19 KTB Tumorforschungsgesellschaft mbH Receptor And Antigen Targeted Prodrug
AU2008221287A1 (en) 2007-03-01 2008-09-04 Wellstat Immunotherapeutics, Llc Treatment of diseases characterized by inflammation
CA2679244A1 (en) 2007-03-02 2009-03-05 Mdrna, Inc. Nucleic acid compounds for inhibiting myc gene expression and uses thereof
WO2008131419A2 (en) 2007-04-23 2008-10-30 Alnylam Pharmaceuticals, Inc. Glycoconjugates of rna interference agents
DK2170917T3 (da) 2007-05-30 2012-10-08 Isis Pharmaceuticals Inc N-Substituerede bicycliske nukleinsyreanaloge med aminomethylenbro
ES2386492T3 (es) 2007-06-08 2012-08-21 Isis Pharmaceuticals, Inc. Análogos de ácidos nucleicos bicíclicos carbocíclicos
WO2009003009A1 (en) 2007-06-26 2008-12-31 Enanta Pharmaceuticals, Inc. Substituted pyrrolidine as anti-infectives
ES2376507T5 (es) 2007-07-05 2015-08-31 Isis Pharmaceuticals, Inc. Análogos de ácidos nucleicos bicíclicos 6-disustituidos
EP2188298B1 (en) 2007-08-15 2013-09-18 Isis Pharmaceuticals, Inc. Tetrahydropyran nucleic acid analogs
BRPI0815324A2 (pt) * 2007-08-20 2015-07-14 Protalix Ltd "conjugado protêico que contém sacarídeos, processo de separação do conjugado protêico que contém sacarídeos, composição farmacêutica do conjugado protêico que contém sacarídeos, uso do conjugado protêico que contém sacarídeos e composto do conjugado protêico que contém sacarídeos"
JP5792955B2 (ja) * 2007-10-01 2015-10-14 アイシス ファーマシューティカルズ， インコーポレーテッド 線維芽細胞増殖因子受容体４発現のアンチセンスモジュレーション
US9029337B2 (en) 2007-11-09 2015-05-12 Isis Pharmaceuticals, Inc. Modulation of factor 7 expression
WO2009067647A1 (en) 2007-11-21 2009-05-28 Isis Pharmaceuticals, Inc. Carbocyclic alpha-l-bicyclic nucleic acid analogs
WO2009073809A2 (en) * 2007-12-04 2009-06-11 Alnylam Pharmaceuticals, Inc. Carbohydrate conjugates as delivery agents for oligonucleotides
EP3673910B1 (en) 2007-12-27 2023-11-22 Stelic Institute & Co., Inc. Sugar chain-related gene and use thereof
AU2009241591A1 (en) 2008-01-31 2009-11-05 Alnylam Pharmaceuticals, Inc. Optimized methods for delivery of DSRNA targeting the PCSK9 gene
US8530640B2 (en) 2008-02-07 2013-09-10 Isis Pharmaceuticals, Inc. Bicyclic cyclohexitol nucleic acid analogs
WO2009142822A2 (en) 2008-03-26 2009-11-26 Alnylam Pharmaceuticals, Inc. 2-f modified rna interference agents
CA3044980A1 (en) * 2008-04-11 2009-10-15 Alnylam Pharmaceuticals, Inc. Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
WO2009143369A2 (en) 2008-05-22 2009-11-26 Isis Pharmaceuticals, Inc. Method of preparing nucleosides and analogs thereof without using chromatography
WO2009148605A2 (en) 2008-06-04 2009-12-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
WO2010006215A1 (en) 2008-07-09 2010-01-14 Celera Corporation Genetic polymorphisms associated with cardiovascular diseases, methods of detection and uses thereof
EP2323667A4 (en) 2008-08-07 2012-07-25 Isis Pharmaceuticals Inc MODULATION OF TRANSTHYRETIN EXPRESSION BY TREATMENT OF CNS DISEASES
WO2010039548A2 (en) 2008-09-23 2010-04-08 Alnylam Pharmaceuticals, Inc. Chemical modifications of monomers and oligonucleotides with cycloaddition
WO2010036696A1 (en) 2008-09-24 2010-04-01 Isis Pharmaceuticals, Inc. Cyclohexenyl nucleic acid analogs
EP2356129B1 (en) 2008-09-24 2013-04-03 Isis Pharmaceuticals, Inc. Substituted alpha-l-bicyclic nucleosides
CA2740785C (en) 2008-10-15 2017-06-20 Isis Pharmaceuticals, Inc. Modulation of factor 11 expression
PL2937418T3 (pl) * 2008-10-20 2018-04-30 Alnylam Pharmaceuticals, Inc. Kompozycje i sposoby hamowania ekspresji transtyretyny
EP2447274B1 (en) 2008-10-24 2017-10-04 Ionis Pharmaceuticals, Inc. Oligomeric compounds and methods
WO2010048552A2 (en) 2008-10-24 2010-04-29 Isis Pharmaceuticals, Inc. Methods of using oligomeric compounds comprising 2'-substituted nucleosides
PL2355851T3 (pl) 2008-11-10 2018-08-31 Arbutus Biopharma Corporation Nowe lipidy i kompozycje do dostarczania środków terapeutycznych
CA2750561C (en) 2009-01-26 2017-10-10 Protiva Biotherapeutics, Inc. Compositions and methods for silencing apolipoprotein c-iii expression
EP3243504A1 (en) 2009-01-29 2017-11-15 Arbutus Biopharma Corporation Improved lipid formulation
WO2010101951A1 (en) 2009-03-02 2010-09-10 Alnylam Pharmaceuticals, Inc. Nucleic acid chemical modifications
FR2943060B1 (fr) 2009-03-13 2013-01-04 Commissariat Energie Atomique Agents chelatants d'ions metalliques, leurs procedes de preparation et leurs applications
NZ595891A (en) 2009-04-15 2013-06-28 Isis Pharmaceuticals Inc Modulation of inflammatory responses by factor xi
US8883202B2 (en) 2009-05-05 2014-11-11 Tekmira Pharmaceuticals Corporation Lipid compositions
CA2764158A1 (en) 2009-06-01 2010-12-09 Halo-Bio Rnai Therapeutics, Inc. Polynucleotides for multivalent rna interference, compositions and methods of use thereof
LT2440183T (lt) 2009-06-10 2018-08-10 Arbutus Biopharma Corporation Patobulinta lipido kompozicija
MX2011013421A (es) 2009-06-15 2012-03-16 Alnylam Pharmaceuticals Inc Arnds formulado con lipido de direccionamiento del gen pcsk9.
CA2767225A1 (en) 2009-07-06 2011-01-13 Alnylam Pharmaceuticals, Inc. Compositions and methods for enhancing production of a biological product
WO2011005861A1 (en) 2009-07-07 2011-01-13 Alnylam Pharmaceuticals, Inc. Oligonucleotide end caps
WO2011005860A2 (en) 2009-07-07 2011-01-13 Alnylam Pharmaceuticals, Inc. 5' phosphate mimics
WO2011008995A1 (en) 2009-07-16 2011-01-20 Isis Pharmaceuticals, Inc. Modulation of factor 7 expression
US9012421B2 (en) 2009-08-06 2015-04-21 Isis Pharmaceuticals, Inc. Bicyclic cyclohexose nucleic acid analogs
US8901072B2 (en) * 2009-08-12 2014-12-02 The Medicines Company Glycopeptide and lipoglycopeptide antibiotics with improved solubility
US8552163B2 (en) 2009-09-25 2013-10-08 Johns Hopkins University Liver-targeting agents and their synthesis
JP5892938B2 (ja) 2009-10-16 2016-03-30 グラクソ グループ リミテッドＧｌａｘｏ Ｇｒｏｕｐ Ｌｉｍｉｔｅｄ Ｈｂｖアンチセンス阻害剤
TWI388338B (zh) 2009-10-26 2013-03-11 Iner Aec Executive Yuan 對聚合醣鏈進行放射標誌以作為肝受體造影劑之方法
TWI391144B (zh) 2009-10-26 2013-04-01 Iner Aec Executive Yuan 一種定量肝殘餘功能的檢驗方法與其新穎肝受體造影檢驗藥劑
WO2011056883A1 (en) * 2009-11-03 2011-05-12 Alnylam Pharmaceuticals, Inc. Lipid formulated compositions and methods for inhibiting expression of transthyretin (ttr)
WO2011072290A2 (en) 2009-12-11 2011-06-16 The Regents Of The University Of Michigan Targeted dendrimer-drug conjugates
CA2786071C (en) 2010-01-08 2021-01-12 Isis Pharmaceuticals, Inc. Modulation of angiopoietin-like 3 expression
US9198972B2 (en) 2010-01-28 2015-12-01 Alnylam Pharmaceuticals, Inc. Monomers and oligonucleotides comprising cycloaddition adduct(s)
WO2011104169A1 (en) 2010-02-24 2011-09-01 F. Hoffmann-La Roche Ag Compositions for targeted delivery of sirna
WO2011115818A1 (en) 2010-03-17 2011-09-22 Isis Pharmaceuticals, Inc. 5'-substituted bicyclic nucleosides and oligomeric compounds prepared therefrom
US20130109817A1 (en) 2010-03-26 2013-05-02 Mersana Therapeutics, Inc. Modified Polymers for Delivery of Polynucleotides, Method of Manufacture, and Methods of Use Thereof
WO2011120053A1 (en) 2010-03-26 2011-09-29 Mersana Therapeutics, Inc. Modified polymers for delivery of polynucleotides, method of manufacture, and methods of use thereof
US9102938B2 (en) 2010-04-01 2015-08-11 Alnylam Pharmaceuticals, Inc. 2′ and 5′ modified monomers and oligonucleotides
US9725479B2 (en) 2010-04-22 2017-08-08 Ionis Pharmaceuticals, Inc. 5′-end derivatives
WO2011133876A2 (en) 2010-04-22 2011-10-27 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising acyclic and abasic nucleosides and analogs
EP2625186B1 (en) 2010-04-28 2016-07-27 Ionis Pharmaceuticals, Inc. 5' modified nucleosides and oligomeric compounds prepared therefrom
US8993738B2 (en) 2010-04-28 2015-03-31 Isis Pharmaceuticals, Inc. Modified nucleosides, analogs thereof and oligomeric compounds prepared therefrom
RS56011B1 (sr) 2010-04-29 2017-09-29 Ionis Pharmaceuticals Inc Modulacija ekspresije transtiretina
WO2011163121A1 (en) 2010-06-21 2011-12-29 Alnylam Pharmaceuticals, Inc. Multifunctional copolymers for nucleic acid delivery
WO2012037254A1 (en) * 2010-09-15 2012-03-22 Alnylam Pharmaceuticals, Inc. MODIFIED iRNA AGENTS
WO2012067970A2 (en) 2010-11-11 2012-05-24 Ted M Dawson Transcriptional repression leading to parkinson's disease
WO2012068187A1 (en) 2010-11-19 2012-05-24 Merck Sharp & Dohme Corp. Poly(amide) polymers for the delivery of oligonucleotides
CN103492568B (zh) 2010-12-17 2017-04-12 箭头研究公司 用于siRNA的半乳糖簇‑药代动力学调节剂靶向部分
US8501930B2 (en) 2010-12-17 2013-08-06 Arrowhead Madison Inc. Peptide-based in vivo siRNA delivery system
KR20130108655A (ko) 2010-12-29 2013-10-04 에프. 호프만-라 로슈 아게 핵산의 세포내 전달을 위한 소분자 접합체
EP3467109A1 (en) 2011-02-08 2019-04-10 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
PE20142463A1 (es) 2011-04-01 2015-01-22 Isis Pharmaceuticals Inc Modulacion de la expresion del transductor de senales y activador de la transcripcion 3 (stat3)
EP2697244B1 (en) * 2011-04-13 2017-05-17 Ionis Pharmaceuticals, Inc. Antisense modulation of ptp1b expression
KR102055331B1 (ko) 2011-04-21 2019-12-12 아이오니스 파마수티컬즈, 인코포레이티드 B형 간염 바이러스(hbv) 발현 조절
US20120295961A1 (en) 2011-04-21 2012-11-22 Swayze Eric E Modulation of hepatitis b virus (hbv) expression
SG194671A1 (en) 2011-04-27 2013-12-30 Isis Pharmaceuticals Inc Modulation of apolipoprotein ciii (apociii) expression
WO2012174154A1 (en) 2011-06-13 2012-12-20 Isis Pharmaceuticals, Inc. Modulation of inflammatory responses by factor vii
AU2012271357A1 (en) * 2011-06-16 2013-05-02 Ionis Pharmaceuticals, Inc. Antisense modulation of fibroblast growth factor receptor 4 expression
BR112013032645A2 (pt) 2011-06-21 2016-11-22 Alnylam Pharmaceuticals composições e métodos para inibição de expressão de apolipoproteína c-iii (apoc3)
EP3444348A1 (en) * 2011-06-21 2019-02-20 Alnylam Pharmaceuticals, Inc. Angiopoietin-like 3 (angptl3) irna compositions and methods of use thereof
WO2012177639A2 (en) 2011-06-22 2012-12-27 Alnylam Pharmaceuticals, Inc. Bioprocessing and bioproduction using avian cell lines
US20130017250A1 (en) * 2011-07-15 2013-01-17 The Trustees Of Columbia University In The City Of New York Methods For High Density Lipoprotein Cholesterol Regulation
HK1199736A1 (en) 2011-08-26 2015-07-17 箭头研究公司 Poly(vinyl ester) polymers for in vivo nucleic acid delivery
EP3640332A1 (en) 2011-08-29 2020-04-22 Ionis Pharmaceuticals, Inc. Oligomer-conjugate complexes and their use
RU2598709C2 (ru) 2011-09-20 2016-09-27 Айсис Фармасьютикалс, Инк. Антисмысловая регуляция экспрессии gcgr
WO2013063313A1 (en) 2011-10-25 2013-05-02 Isis Pharmaceuticals, Inc. Antisense modulation of gccr expression
AU2012340159B2 (en) 2011-11-18 2017-09-07 Alnylam Pharmaceuticals, Inc. RNAi agents, compositions and methods of use thereof for treating transthyretin (TTR) associated diseases
US20150031747A1 (en) 2012-02-08 2015-01-29 Isis Pharmaceuticals, Inc. Methods and compositions for modulating factor vii expression
WO2013142514A1 (en) 2012-03-19 2013-09-26 Isis Pharmaceuticals, Inc. Methods and compositions for modulating alpha-1-antitrypsin expression
WO2013142571A2 (en) 2012-03-20 2013-09-26 Cornell University Assays for the identification of compounds that modulate lipid homeostasis
US9133461B2 (en) 2012-04-10 2015-09-15 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the ALAS1 gene
EP3336189A1 (en) 2012-04-20 2018-06-20 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
WO2013159109A1 (en) 2012-04-20 2013-10-24 Isis Pharmaceuticals, Inc. Modulation of hepatitis b virus (hbv) expression
EP3453762B1 (en) 2012-05-02 2021-04-21 Sirna Therapeutics, Inc. Short interfering nucleic acid (sina) compositions
TW201808342A (zh) 2012-05-02 2018-03-16 喜納製藥公司 包含四ｇａｌｎａｃ之新穎結合物及傳送寡核苷酸之方法
WO2013173789A2 (en) 2012-05-17 2013-11-21 Isis Pharmaceuticals, Inc. Antisense oligonucleotide compositions
US9574193B2 (en) 2012-05-17 2017-02-21 Ionis Pharmaceuticals, Inc. Methods and compositions for modulating apolipoprotein (a) expression
RU2624028C2 (ru) 2012-05-24 2017-06-30 Ионис Фармасьютикалз, Инк. Способы и композиции для модулирования экспрессии аполипопротеина (а)
US20150322428A1 (en) 2012-06-18 2015-11-12 Isis Pharmaceuticals, Inc. Compounds and methods for improved cellular uptake of antisense compounds
DK2879718T3 (da) 2012-08-06 2023-06-19 Alnylam Pharmaceuticals Inc Proces til fremstilling af kulhydratkonjugerede RNA-stoffer
WO2014059353A2 (en) 2012-10-11 2014-04-17 Isis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleosides and uses thereof
WO2014076196A1 (en) 2012-11-15 2014-05-22 Santaris Pharma A/S Anti apob antisense conjugate compounds
WO2014118272A1 (en) 2013-01-30 2014-08-07 Santaris Pharma A/S Antimir-122 oligonucleotide carbohydrate conjugates
JP6580993B2 (ja) 2013-01-30 2019-09-25 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ Ｌｎａオリゴヌクレオチド糖質コンジュゲート
HUE050394T2 (hu) * 2013-05-01 2020-11-30 Ionis Pharmaceuticals Inc Apolipoprotein(a) expressziójának módosítására szolgáló eljárások és készítmények
AU2013389474B2 (en) 2013-05-16 2018-11-15 Racthera Co., Ltd. Transplantation adjuvant in cell therapy using neural progenitor cells
EP3011028B1 (en) 2013-06-21 2019-06-12 Ionis Pharmaceuticals, Inc. Compositions and methods for modulation of target nucleic acids
HRP20200163T1 (hr) 2013-06-27 2020-08-07 Roche Innovation Center Copenhagen A/S Antisens oligomeri i konjugati koji ciljno djeluju na pcsk9
US20170073689A1 (en) 2013-07-02 2017-03-16 Ionis Pharmaceuticals, Inc. Modulators of growth hormone receptor
DK3019200T3 (da) 2013-07-11 2022-06-20 Alnylam Pharmaceuticals Inc Oligonukleotid-ligand-konjugater og fremgangsmåde til fremstiling deraf
LT3043827T (lt) 2013-09-13 2019-08-12 Ionis Pharmaceuticals, Inc. Komplemento faktoriaus b moduliatoriai
WO2015042447A1 (en) 2013-09-20 2015-03-26 Isis Pharmaceuticals, Inc. Targeted therapeutic nucleosides and their use
RU2016122168A (ru) 2013-11-14 2017-12-19 Рош Инновейшен Сентер Копенгаген А/С Антисмысловые конъюгаты, направленные на аполипопротеин b
CA2932904A1 (en) 2013-12-06 2015-06-11 Dicerna Pharmaceuticals, Inc. Methods and compositions for the specific inhibition of transthyretin (ttr) by double-stranded rna
KR20200102553A (ko) 2014-05-01 2020-08-31 아이오니스 파마수티컬즈, 인코포레이티드 성장 호르몬 수용체 발현을 조절하기 위한 조성물 및 방법
EP4534092A3 (en) 2014-05-01 2025-07-02 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating pkk expression
AU2015252895B2 (en) 2014-05-01 2021-07-15 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating angiopoietin-like 3 expression
EP3137115B1 (en) 2014-05-01 2020-10-14 Ionis Pharmaceuticals, Inc. Method for synthesis of reactive conjugate clusters
CN106232804B (zh) 2014-05-01 2019-10-25 Ionis制药公司 用于调节补体因子b表达的组合物和方法
WO2015179693A1 (en) 2014-05-22 2015-11-26 Isis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
US20170145424A1 (en) 2014-06-06 2017-05-25 Ionis Pharmaceuticals, Inc. Compositions and methods for enhanced intestinal absorption of conjugated oligomeric compounds
FI4119569T3 (fi) * 2015-11-06 2024-08-30 Ionis Pharmaceuticals Inc Konjugoituja antisense-yhdisteitä käytettäviksi hoidossa
EP3370708A4 (en) * 2015-11-06 2019-06-26 Ionis Pharmaceuticals, Inc. MODULATION OF APOLIPOPROTEIN (A) EXPRESSION

Also Published As

Publication number Publication date
MX2019010443A (es) 2019-10-17
EP3524680A1 (en) 2019-08-14
KR20160002975A (ko) 2016-01-08
RU2015151202A (ru) 2017-06-06
KR102651423B1 (ko) 2024-03-27
AU2014259757A1 (en) 2015-10-22
EP2992009A4 (en) 2016-12-28
WO2014179625A1 (en) 2014-11-06
CN105378085B (zh) 2019-02-15
EP2991661B1 (en) 2019-03-13
NZ631512A (en) 2016-10-28
MX2021008899A (es) 2021-08-19
EP2992009A1 (en) 2016-03-09
SI2992098T1 (sl) 2019-06-28
PH12018501963A1 (en) 2020-07-20
WO2014179627A9 (en) 2015-02-26
JP6769866B2 (ja) 2020-10-14
EP4529927A3 (en) 2025-06-18
IL261901A (en) 2018-10-31
IL242132B (en) 2018-10-31
EP2992097A4 (en) 2017-01-04
PL2992009T3 (pl) 2020-11-30
RU2018112167A (ru) 2019-03-07
RU2015151204A3 (cg-RX-API-DMAC7.html) 2018-03-27
EP2992098A2 (en) 2016-03-09
AU2020207820A1 (en) 2020-08-06
RU2018136140A3 (cg-RX-API-DMAC7.html) 2022-04-27
US10844379B2 (en) 2020-11-24
AU2019204784C1 (en) 2022-11-03
BR112015027377A2 (pt) 2017-08-29
DOP2016000287A (es) 2017-02-15
IL264241A (en) 2019-02-28
NZ631537A (en) 2017-05-26
MX381034B (es) 2025-04-01
RU2015151204A (ru) 2017-06-02
AU2019200820B2 (en) 2020-04-30
WO2014179627A3 (en) 2015-04-16
JP2022017514A (ja) 2022-01-25
US9163239B2 (en) 2015-10-20
BR112015027369A8 (pt) 2018-01-02
KR20210151260A (ko) 2021-12-13
EP2991661A1 (en) 2016-03-09
NZ740338A (en) 2022-04-29
CN110079524A (zh) 2019-08-02
AU2014259750B2 (en) 2019-02-28
MA60161B1 (fr) 2025-02-28
KR102138781B1 (ko) 2020-07-28
US20220275365A9 (en) 2022-09-01
BR112015027369A2 (pt) 2017-09-26
KR20210129257A (ko) 2021-10-27
WO2014179626A3 (en) 2015-02-26
US20160090595A1 (en) 2016-03-31
EP2991656A2 (en) 2016-03-09
JP2016522683A (ja) 2016-08-04
US20240401038A1 (en) 2024-12-05
JP2021074021A (ja) 2021-05-20
RU2015151203A (ru) 2017-06-02
WO2014179626A2 (en) 2014-11-06
HUE043697T2 (hu) 2019-09-30
KR20240042220A (ko) 2024-04-01
WO2014179627A2 (en) 2014-11-06
CR20150612A (es) 2016-03-03
AU2019200820A1 (en) 2019-02-28
BR112015027322A2 (pt) 2017-09-26
IL283660A (en) 2021-07-29
PH12015502493B1 (en) 2019-09-25
RU2019124314A (ru) 2019-08-21
LT2992009T (lt) 2020-11-10
IL263843B (en) 2020-03-31
KR20160003723A (ko) 2016-01-11
JP7177127B2 (ja) 2022-11-22
JP6639629B2 (ja) 2020-02-05
BR112015027321A8 (pt) 2018-01-02
EP4529927A2 (en) 2025-04-02
BR112015027319A8 (pt) 2018-01-02
AU2022202770B2 (en) 2024-10-03
RU2015151200A (ru) 2019-01-14
CN114058617A (zh) 2022-02-18
US20160090596A1 (en) 2016-03-31
ZA201507218B (en) 2023-09-27
KR20210037752A (ko) 2021-04-06
EP3828275A1 (en) 2021-06-02
RS60796B1 (sr) 2020-10-30
MX373334B (es) 2020-05-04
US20180002693A1 (en) 2018-01-04
KR20180051678A (ko) 2018-05-16
ME03390B (me) 2020-01-20
CY1121879T1 (el) 2020-10-14
AU2024266799A1 (en) 2024-12-12
CL2015003217A1 (es) 2016-07-08
CN108064162B (zh) 2021-12-03
IL273184A (en) 2020-04-30
US20250346899A1 (en) 2025-11-13
KR20200090966A (ko) 2020-07-29
BR112015027377A8 (pt) 2017-10-03
US20150126720A1 (en) 2015-05-07
HK1221475A1 (en) 2017-06-02
EP2992098B1 (en) 2019-03-27
RU2015151202A3 (cg-RX-API-DMAC7.html) 2018-03-27
CA2921509A1 (en) 2014-11-06
IL270464B (en) 2021-07-29
NL301341I2 (nl) 2025-10-02
LT2992098T (lt) 2019-07-10
MX2015015264A (es) 2016-08-12
IL274064B (en) 2021-06-30
MX2019010441A (es) 2019-10-17
EA201592093A1 (ru) 2016-06-30
BR112015027322A8 (pt) 2018-01-02
EP2992098A4 (en) 2017-01-11
ZA201507216B (en) 2017-08-30
BR112015027319A2 (pt) 2017-09-26
US20210130823A1 (en) 2021-05-06
KR20160002974A (ko) 2016-01-08
CA2921509C (en) 2025-10-07
AU2019203674B2 (en) 2021-03-25
US11851655B2 (en) 2023-12-26
RU2018136140A (ru) 2018-12-17
HRP20201378T1 (hr) 2020-11-27
US20200224198A1 (en) 2020-07-16
KR102212275B1 (ko) 2021-02-05
JP2018183184A (ja) 2018-11-22
MX2015015234A (es) 2016-10-03
HK1221485A1 (en) 2017-06-02
JP2020007361A (ja) 2020-01-16
SG11201508800WA (en) 2015-11-27
EP3524680B1 (en) 2020-11-11
CA2921162A1 (en) 2014-11-06
US20140343123A1 (en) 2014-11-20
RU2686080C2 (ru) 2019-04-24
FIC20250028I1 (fi) 2025-08-18
EA031393B1 (ru) 2018-12-28
AU2014259759A1 (en) 2015-10-22
KR20220108195A (ko) 2022-08-02
ES2819213T3 (es) 2021-04-15
CN105377887A (zh) 2016-03-02
NZ725538A (en) 2021-02-26
KR102558571B1 (ko) 2023-07-21
HK1221486A1 (en) 2017-06-02
US20150126719A1 (en) 2015-05-07
HRP20190987T1 (hr) 2019-09-20
IL296543B1 (en) 2024-10-01
US20160017323A1 (en) 2016-01-21
IL273312A (en) 2020-04-30
RU2699985C2 (ru) 2019-09-11
JP6592486B2 (ja) 2019-10-16
RU2697152C2 (ru) 2019-08-12
BR112015027377B1 (pt) 2023-01-10
MX373306B (es) 2020-05-20
MY178929A (en) 2020-10-23
IL264580B (en) 2020-04-30
RU2015151199A3 (cg-RX-API-DMAC7.html) 2018-03-27
AU2018267625B2 (en) 2020-09-10
BR122018009831B1 (pt) 2021-12-21
PH12019501191A1 (en) 2021-03-01
CN110066795A (zh) 2019-07-30
AU2019202598A1 (en) 2019-05-02
IL284593B (en) 2022-10-01
IL315582A (en) 2024-11-01
MX2015015239A (es) 2016-10-03
EP2992009B1 (en) 2020-06-24
UA120287C2 (uk) 2019-11-11
US12291709B2 (en) 2025-05-06
HK1221403A1 (en) 2017-06-02
IL242125B (en) 2019-02-28
CN105378082B (zh) 2020-06-09
EP4155403A1 (en) 2023-03-29
AU2014259750A1 (en) 2015-10-22
KR20230113835A (ko) 2023-08-01
CA2921514C (en) 2023-10-24
US20190367914A1 (en) 2019-12-05
WO2014179629A3 (en) 2015-01-22
KR102482890B1 (ko) 2022-12-30
US9932580B2 (en) 2018-04-03
CN105377887B (zh) 2020-11-03
RU2019110030A (ru) 2019-05-06
US20210087566A1 (en) 2021-03-25
CN111593051A (zh) 2020-08-28
RS58981B1 (sr) 2019-08-30
IL274064A (en) 2020-06-30
AU2017200365C1 (en) 2019-04-18
MX2015015220A (es) 2016-01-12
MY198359A (en) 2023-08-28
KR102235678B1 (ko) 2021-04-05
SI2992009T1 (sl) 2020-10-30
CN110079524B (zh) 2024-09-24
SMT201900316T1 (it) 2019-07-11
KR20190084138A (ko) 2019-07-15
KR20160002976A (ko) 2016-01-08
DOP2021000095A (es) 2021-09-15
AU2017203436A1 (en) 2017-06-08
US20180044676A1 (en) 2018-02-15
MX2020002184A (es) 2020-07-14
US20210024923A1 (en) 2021-01-28
US11299736B1 (en) 2022-04-12
DOP2015000268A (es) 2015-11-30
EP2992097B1 (en) 2019-11-06
JP7339294B2 (ja) 2023-09-05
EP2991656B1 (en) 2019-12-18
JP2023012548A (ja) 2023-01-25
DK3524680T3 (da) 2020-12-14
CN105378082A (zh) 2016-03-02
DK2992009T3 (da) 2020-09-14
US20150176007A1 (en) 2015-06-25
AU2017203436B2 (en) 2018-10-18
MX2015015263A (es) 2016-12-16
SG10201906382QA (en) 2019-08-27
JP2023113843A (ja) 2023-08-16
US10927372B2 (en) 2021-02-23
AU2021204244A1 (en) 2021-07-22
UA121017C2 (uk) 2020-03-25
AU2019204784B2 (en) 2022-01-27
IL273205A (en) 2020-04-30
CN105378085A (zh) 2016-03-02
NO2025037I1 (no) 2025-08-13
US20210395734A1 (en) 2021-12-23
SG10201801813YA (en) 2018-04-27
AU2019204784A1 (en) 2019-07-25
EP3690049A1 (en) 2020-08-05
IL273184B (en) 2021-07-29
US20240352455A1 (en) 2024-10-24
JP2024116224A (ja) 2024-08-27
PE20152002A1 (es) 2016-01-21
AU2017200950A1 (en) 2017-03-02
AU2018267625A1 (en) 2018-12-13
AU2020217347A1 (en) 2020-08-27
EA201891479A1 (ru) 2018-11-30
AU2014259756B2 (en) 2017-02-23
DK2992098T3 (da) 2019-06-17
RU2650510C2 (ru) 2018-04-16
US20230151365A1 (en) 2023-05-18
AU2017200950B2 (en) 2019-01-17
MX2020004209A (es) 2020-08-13
DK2991656T3 (da) 2020-03-23
KR20210014758A (ko) 2021-02-09
WO2014179620A1 (en) 2014-11-06
IL242126B (en) 2019-01-31
AU2014259759B2 (en) 2020-06-18
CN110042098A (zh) 2019-07-23
KR20230006933A (ko) 2023-01-11
JP2021020901A (ja) 2021-02-18
EP2991656A4 (en) 2017-02-22
US9957504B2 (en) 2018-05-01
KR102424855B1 (ko) 2022-07-26
US20180273953A1 (en) 2018-09-27
AU2014259756A1 (en) 2015-10-22
JP2021107408A (ja) 2021-07-29
IL264241B (en) 2020-04-30
ES2885174T3 (es) 2021-12-13
PT2992098T (pt) 2019-07-05
BR112015027369B1 (pt) 2021-06-08
US9145558B2 (en) 2015-09-29
US9714421B2 (en) 2017-07-25
KR20240147701A (ko) 2024-10-08
WO2014179629A8 (en) 2016-06-02
BR112015027321A2 (pt) 2017-09-26
JP2019056001A (ja) 2019-04-11
PE20161430A1 (es) 2017-01-06
RU2670614C9 (ru) 2018-11-23
CN108064162A (zh) 2018-05-22
US9932581B2 (en) 2018-04-03
EP2992097A2 (en) 2016-03-09
EP3633039A1 (en) 2020-04-08
IL264580A (en) 2019-02-28
JP6216444B2 (ja) 2017-10-18
ES2778442T3 (es) 2020-08-10
JP2020074787A (ja) 2020-05-21
RU2015151199A (ru) 2017-06-05
JP2025072530A (ja) 2025-05-09
US9127276B2 (en) 2015-09-08
US10683499B2 (en) 2020-06-16
JP6387084B2 (ja) 2018-09-05
CA2921518A1 (en) 2014-11-06
CR20190269A (es) 2019-09-13
RU2015151200A3 (cg-RX-API-DMAC7.html) 2019-01-14
IL272617A (en) 2020-03-31
JP2020058370A (ja) 2020-04-16
PL2992098T3 (pl) 2019-09-30
US20160076032A1 (en) 2016-03-17
NZ631552A (en) 2017-02-24
JP6652602B2 (ja) 2020-02-26
PT3524680T (pt) 2021-01-04
IL242124B (en) 2019-02-28
NZ712737A (en) 2021-08-27
PT2992009T (pt) 2020-09-21
CN110042098B (zh) 2023-02-24
JP2016526874A (ja) 2016-09-08
CA2921167C (en) 2025-05-20
JP7429103B2 (ja) 2024-02-07
US20190055554A1 (en) 2019-02-21
RU2670614C2 (ru) 2018-10-24
SG11201508870VA (en) 2015-11-27
JP2020039355A (ja) 2020-03-19
MA60161A1 (fr) 2024-09-30
AU2017200365B2 (en) 2018-11-08
AU2020233603A1 (en) 2020-10-01
IL284593B2 (en) 2023-02-01
ES2730015T3 (es) 2019-11-07
IL296543B2 (en) 2025-02-01
CA2921514A1 (en) 2014-11-06
CN112921036B (zh) 2025-08-19
CN112921036A (zh) 2021-06-08
IL284000A (en) 2021-07-29
CL2016002262A1 (es) 2017-06-09
JP2020039354A (ja) 2020-03-19
MX2021008901A (es) 2021-08-19
SG10201801507RA (en) 2018-03-28
US9181550B2 (en) 2015-11-10
KR102315836B1 (ko) 2021-10-22
CN119913147A (zh) 2025-05-02
EP4438129A3 (en) 2025-01-15
AU2021204244B2 (en) 2023-10-19
AU2014259755A1 (en) 2015-10-22
JP6866459B2 (ja) 2021-04-28
JP7633311B2 (ja) 2025-02-19
CA2921167A1 (en) 2014-11-06
IL261901B (en) 2020-05-31
JP2025174962A (ja) 2025-11-28
JP2024010070A (ja) 2024-01-23
FR25C1033I1 (fr) 2025-11-21
NZ753018A (en) 2022-01-28
CN105392488B (zh) 2021-04-30
US20160076030A1 (en) 2016-03-17
US20180273952A1 (en) 2018-09-27
KR102712053B1 (ko) 2024-10-02
IL284593A (en) 2021-08-31
US20150126718A1 (en) 2015-05-07
US9181549B2 (en) 2015-11-10
AU2017200365A1 (en) 2017-02-23
KR20160002977A (ko) 2016-01-08
CY1123369T1 (el) 2021-12-31
CN113293163A (zh) 2021-08-24
EP2991661A4 (en) 2017-02-15
AU2014259757B2 (en) 2017-03-02
JP6995478B2 (ja) 2022-01-14
JP2016526018A (ja) 2016-09-01
JP2018027091A (ja) 2018-02-22
US20240247260A1 (en) 2024-07-25
HK1221404A1 (en) 2017-06-02
IL296543A (en) 2022-11-01
AU2019203674A1 (en) 2019-06-27
EP4438129A2 (en) 2024-10-02
PH12015502493A1 (en) 2016-02-22
EA036584B1 (ru) 2020-11-26
JP6456362B2 (ja) 2019-01-23
IL263843A (en) 2019-01-31
CN105392488A (zh) 2016-03-09
AU2024200296A1 (en) 2024-02-08
JP2016523515A (ja) 2016-08-12
WO2014179629A2 (en) 2014-11-06
AU2014259755B2 (en) 2018-08-30
KR101857707B1 (ko) 2018-05-14
MX384824B (es) 2025-04-01
JP2016522817A (ja) 2016-08-04
AU2022202770A1 (en) 2022-05-19
US10883104B2 (en) 2021-01-05
NZ728517A (en) 2021-12-24
EP3546579A1 (en) 2019-10-02

Similar Documents

Publication Publication Date Title
HUE050394T2 (hu) Apolipoprotein(a) expressziójának módosítására szolgáló eljárások és készítmények
HUE051680T2 (hu) Apolipoprotein(a) expressziójának módosítására szolgáló eljárások és készítmények
IL241112B (en) Methods and compositions for modification of hla
LT3080100T (lt) Lizinui specifinės demetilazės-1 inhibitoriai
HUE057734T2 (hu) Heterociklusos vegyületek és alkalmazásuk
HUE043103T2 (hu) Fokozott transzgén expresszió és processzálás
HUE042466T2 (hu) Eljárás és köztitermékek JAK inhibitor elõállítására
DK3494985T3 (da) Vaccinesammensætning omfattende mutant calreticulin
UA29014S (uk) Комп'ютер
HUE049233T2 (hu) C9ORF72-expresszió módosítására szolgáló készítmények
HUE053410T2 (hu) Alkalmazási eljárás és alkalmazási berendezés
EP2979681A4 (en) HARDENING COMPOSITION
HUE045274T2 (hu) Eljárás helyettesített oxiránok és triazolok elõállítására
DK2986722T3 (da) Manipulerede phenylalaninammoniak-lyasepolypeptider
DE112014000689A5 (de) Al-Gusslegierung
DK2992104T3 (da) Fremgangsmåde til ekspression
HUE037370T2 (hu) Eljárás instant tészta elõállítására és instant tészta
EP2958994A4 (en) Vaccine composition
FR3015434B1 (fr) Suspension de turbomachine
DOS2013000177S (es) Capsulas
HUE053033T2 (hu) Hidrolázoknak ellenálló kapszidokat alkalmazó készítmények és eljárások
DK3256462T3 (da) Substituerede 2-thioimidazolyl-carboxamider som skadedyrsbekæmpelsesmiddel
DK2943561T3 (da) Fotobioreaktor
DK3371050T3 (da) Vingeløst luftfartøj
HRP20181307T1 (hr) Postupak izrade zubne proteze