Nothing Special   »   [go: up one dir, main page]

SG10201908122XA - Antisense oligomers and conjugates targeting pcsk9 - Google Patents

Antisense oligomers and conjugates targeting pcsk9

Info

Publication number
SG10201908122XA
SG10201908122XA SG10201908122XA SG10201908122XA SG 10201908122X A SG10201908122X A SG 10201908122XA SG 10201908122X A SG10201908122X A SG 10201908122XA SG 10201908122X A SG10201908122X A SG 10201908122XA
Authority
SG
Singapore
Prior art keywords
pcsk9
antisense oligomers
conjugates
conjugates targeting
targeting pcsk9
Prior art date
Application number
Inventor
Nanna Albæk
Maj Hedtjärn
Marie Lindholm
Niels Fisker Nielsen
Andreas Petri
Jacob Ravn
Original Assignee
Roche Innovation Ct Copenhagen As
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
Priority claimed from PCT/EP2013/073858 external-priority patent/WO2014076195A1/en
Application filed by Roche Innovation Ct Copenhagen As filed Critical Roche Innovation Ct Copenhagen As
Publication of SG10201908122XA publication Critical patent/SG10201908122XA/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1137—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K47/545—Heterocyclic compounds
    • 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
    • A61K47/54—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
    • A61K47/554—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 the modifying agent being a steroid plant sterol, glycyrrhetic acid, enoxolone or bile acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • A61K31/712—Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
    • 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
    • C12N2310/30—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
    • C12N2310/34—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
    • C12N2310/35—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
    • C12N2310/3515—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
    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C12N2320/32—Special delivery means, e.g. tissue-specific
    • 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
    • C12N2330/00—Production
    • C12N2330/30—Production chemically synthesised

Landscapes

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

Abstract

ANTISENSE OLIGOMERS AND CONJUGATES TARGETING PCSK9 The present invention relates to oligomeric compounds and conjugates thereof that target Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) PCSK9 mRNA in a cell, leading to reduced expression of PCSK9. Reduction of PCSK9 expression is beneficial for a range of medical disorders, such as hypercholesterolemia and related disorders. [No suitable figure]
SG10201908122X 2013-06-27 2014-06-27 Antisense oligomers and conjugates targeting pcsk9 SG10201908122XA (en)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
EP13174092 2013-06-27
EP13192938 2013-11-14
PCT/EP2013/073858 WO2014076195A1 (en) 2012-11-15 2013-11-14 Oligonucleotide conjugates
EP13192930 2013-11-14
EP14153253 2014-01-30
EP14168331 2014-05-14

Publications (1)

Publication Number Publication Date
SG10201908122XA true SG10201908122XA (en) 2019-10-30

Family

ID=52141126

Family Applications (2)

Application Number Title Priority Date Filing Date
SG10201908122X SG10201908122XA (en) 2013-06-27 2014-06-27 Antisense oligomers and conjugates targeting pcsk9
SG11201510656PA SG11201510656PA (en) 2013-06-27 2014-06-27 Antisense oligomers and conjugates targeting pcsk9

Family Applications After (1)

Application Number Title Priority Date Filing Date
SG11201510656PA SG11201510656PA (en) 2013-06-27 2014-06-27 Antisense oligomers and conjugates targeting pcsk9

Country Status (30)

Country Link
US (7) US9879265B2 (en)
EP (2) EP3591054A1 (en)
JP (2) JP6255092B2 (en)
KR (2) KR101931089B1 (en)
CN (2) CN112263682B (en)
AU (1) AU2014300981B2 (en)
BR (1) BR112015032432B1 (en)
CA (1) CA2915316C (en)
CL (1) CL2015003728A1 (en)
CY (1) CY1122738T1 (en)
DK (1) DK3013959T3 (en)
EA (1) EA201592215A1 (en)
ES (1) ES2770667T3 (en)
HK (1) HK1221740A1 (en)
HR (1) HRP20200163T1 (en)
HU (1) HUE048738T2 (en)
IL (1) IL242875B (en)
LT (1) LT3013959T (en)
MX (2) MX367083B (en)
MY (1) MY183049A (en)
NZ (1) NZ715081A (en)
PE (1) PE20160158A1 (en)
PH (1) PH12015502761A1 (en)
PL (1) PL3013959T3 (en)
PT (1) PT3013959T (en)
RS (1) RS59986B1 (en)
SG (2) SG10201908122XA (en)
SI (1) SI3013959T1 (en)
UA (1) UA119643C2 (en)
WO (1) WO2014207232A1 (en)

Families Citing this family (91)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9394333B2 (en) 2008-12-02 2016-07-19 Wave Life Sciences Japan Method for the synthesis of phosphorus atom modified nucleic acids
AU2010270714B2 (en) 2009-07-06 2015-08-13 Wave Life Sciences Ltd. Novel nucleic acid prodrugs and methods use thereof
WO2012039448A1 (en) 2010-09-24 2012-03-29 株式会社キラルジェン Asymmetric auxiliary group
US9605019B2 (en) 2011-07-19 2017-03-28 Wave Life Sciences Ltd. Methods for the synthesis of functionalized nucleic acids
US9598458B2 (en) 2012-07-13 2017-03-21 Wave Life Sciences Japan, Inc. Asymmetric auxiliary group
KR102712879B1 (en) 2012-07-13 2024-10-04 웨이브 라이프 사이언시스 리미티드 Chiral control
CA2921518A1 (en) 2013-05-01 2014-11-06 Ionis Pharmaceuticals, Inc. Compositions and methods
SI3013959T1 (en) 2013-06-27 2020-04-30 Roche Innovation Center Copenhagen A/S Antisense oligomers and conjugates targeting pcsk9
JPWO2015108047A1 (en) 2014-01-15 2017-03-23 株式会社新日本科学 Chiral nucleic acid adjuvant having immunity induction activity and immunity induction activator
EP3095459A4 (en) 2014-01-15 2017-08-23 Shin Nippon Biomedical Laboratories, Ltd. Chiral nucleic acid adjuvant having antitumor effect and antitumor agent
EP3094728B1 (en) 2014-01-16 2022-03-09 Wave Life Sciences Ltd. Chiral design
US9994855B2 (en) 2014-05-01 2018-06-12 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating growth hormone receptor expression
RU2734658C2 (en) 2014-05-01 2020-10-21 Ионис Фармасьютикалз, Инк. Compositions and methods for modulating the expression of angiopoietin-like protein 3
AU2015252858C1 (en) 2014-05-01 2021-09-16 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating Complement Factor B expression
GB201408623D0 (en) 2014-05-15 2014-07-02 Santaris Pharma As Oligomers and oligomer conjugates
CN107709342B (en) 2015-08-06 2021-09-03 豪夫迈·罗氏有限公司 Process for preparing acetylgalactosamine acid derivatives
US20210052631A1 (en) * 2015-09-25 2021-02-25 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
CN114533900A (en) 2015-10-09 2022-05-27 波涛生命科学有限公司 Oligonucleotide compositions and methods thereof
WO2017068087A1 (en) 2015-10-22 2017-04-27 Roche Innovation Center Copenhagen A/S Oligonucleotide detection method
BR122023026882A2 (en) 2015-11-06 2024-01-23 Ionis Pharmaceuticals, Inc USE OF AN OLIGOMERIC COMPOUND
CA2994787A1 (en) 2015-11-16 2017-05-26 F. Hoffmann-La Roche Ag Galnac cluster phosphoramidite
PE20181892A1 (en) 2016-03-14 2018-12-11 Hoffmann La Roche OLIGONUCLEOTIDES TO REDUCE THE EXPRESSION OF PD-L1
MA45478A (en) * 2016-04-11 2019-02-20 Arbutus Biopharma Corp TARGETED NUCLEIC ACID CONJUGATE COMPOSITIONS
MA45496A (en) 2016-06-17 2019-04-24 Hoffmann La Roche NUCLEIC ACID MOLECULES FOR PADD5 OR PAD7 MRNA REDUCTION FOR TREATMENT OF HEPATITIS B INFECTION
EP3472348B1 (en) * 2016-06-17 2022-06-29 F. Hoffmann-La Roche AG In vitro nephrotoxicity screening assay
JP7012033B2 (en) 2016-06-17 2022-02-10 エフ．ホフマン－ラ ロシュ アーゲー In vitro nephrotoxicity screening assay
CA3024944A1 (en) 2016-06-22 2017-12-28 Proqr Therapeutics Ii B.V. Single-stranded rna-editing oligonucleotides
EP3509645A4 (en) * 2016-09-07 2020-06-17 Sangamo Therapeutics, Inc. Modulation of liver genes
KR20190065341A (en) 2016-10-06 2019-06-11 아이오니스 파마수티컬즈, 인코포레이티드 Method of joining oligomeric compounds
WO2018130585A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating relb expression
WO2018130584A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating nfkb2 expression
WO2018130581A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating rela expression
WO2018130583A1 (en) 2017-01-13 2018-07-19 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
EP3594346A4 (en) 2017-03-10 2020-12-16 National Center For Child Health And Development Antisense oligonucleotide and composition for prevention or treatment of glycogen storage disease type ia
JOP20190215A1 (en) * 2017-03-24 2019-09-19 Ionis Pharmaceuticals Inc Modulators of pcsk9 expression
KR102656438B1 (en) 2017-04-11 2024-04-12 아뷰터스 바이오파마 코포레이션 targeting composition
WO2018189705A1 (en) 2017-04-13 2018-10-18 Cadila Healthcare Limited Novel peptide based pcsk9 vaccine
WO2018215049A1 (en) 2017-05-23 2018-11-29 F. Hoffmann-La Roche Ag Process for galnac oligonucleotide conjugates
JP6952366B2 (en) * 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 Antisense nucleic acid targeting PCSK9
WO2019030313A2 (en) 2017-08-11 2019-02-14 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating ube3c expression
WO2019038228A1 (en) 2017-08-22 2019-02-28 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating tom1 expression
WO2019073018A1 (en) 2017-10-13 2019-04-18 Roche Innovation Center Copenhagen A/S Methods for identifying improved stereodefined phosphorothioate oligonucleotide variants of antisense oligonucleotides utilising sub-libraries of partially stereodefined oligonucleotides
BR112020007417A2 (en) 2017-10-16 2021-01-26 F. Hoffmann-La Roche Ag nucleic acid molecule for reduction of papd5 and papd7 of mrna for the treatment of hepatitis b infection
WO2019115416A2 (en) 2017-12-11 2019-06-20 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating fndc3b expression
WO2019115417A2 (en) 2017-12-12 2019-06-20 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating rb1 expression
BR112020012523A2 (en) 2017-12-21 2020-11-24 F. Hoffmann-La Roche Ag complementary diagnosis for htra1 rna antagonists
EP4074724A1 (en) 2017-12-22 2022-10-19 Roche Innovation Center Copenhagen A/S Oligonucleotides comprising a phosphorodithioate internucleoside linkage
JP2021508327A (en) 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 New thiophosphoramidite
US20200332289A1 (en) 2017-12-22 2020-10-22 Roche Innovation Center Copenhagen A/S Gapmer oligonucleotides comprising a phosphorodithioate internucleoside linkage
JP2021511022A (en) 2018-01-10 2021-05-06 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 Oligonucleotides for regulating PIAS4 expression
JP7547201B2 (en) 2018-01-12 2024-09-09 ブリストル－マイヤーズ スクイブ カンパニー Antisense oligonucleotides targeting alpha-synuclein and uses thereof - Patents.com
WO2019138057A1 (en) 2018-01-12 2019-07-18 Roche Innovation Center Copenhagen A/S Alpha-synuclein antisense oligonucleotides and uses thereof
US20210095275A1 (en) 2018-01-12 2021-04-01 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating gsk3b expression
BR112020013994A2 (en) 2018-01-12 2020-12-08 Bristol-Myers Squibb Company ANTISENSE OLIGONUCLEOTIDS THAT DRIVE ALPHA-SYNUCLEIN AND THEIR USES
WO2019141656A1 (en) 2018-01-17 2019-07-25 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating erc1 expression
WO2019145386A1 (en) 2018-01-26 2019-08-01 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating csnk1d expression
US11058767B2 (en) * 2018-02-21 2021-07-13 Bristol-Myers Squibb Company CAMK2D antisense oligonucleotides and uses thereof
US20210054377A1 (en) * 2018-03-20 2021-02-25 Tokyo Institute Of Technology Antisense oligonucleotide reduced in toxicity
CA3097544A1 (en) 2018-04-05 2019-10-10 F. Hoffmann-La Roche Ag Use of fubp1 inhibitors for treating hepatitis b virus infection
MX2020013366A (en) 2018-07-03 2021-03-09 Hoffmann La Roche Oligonucleotides for modulating tau expression.
CN112534055A (en) 2018-07-13 2021-03-19 豪夫迈·罗氏有限公司 Oligonucleotides for modulating expression of RTEL1
US20210221837A1 (en) 2018-07-31 2021-07-22 Roche Innovation Center Copenhagen A/S Oligonucleotides comprising a phosphorotrithioate internucleoside linkage
EP4122943B1 (en) 2018-07-31 2024-05-29 Roche Innovation Center Copenhagen A/S Oligonucleotides comprising a phosphorotrithioate internucleoside linkage
BR112021016460A2 (en) 2019-02-20 2021-10-13 Roche Innovation Center Copenhagen A/S SINGLE RIBBON ANTISSENSE GAPMER OLIGONUCLEOTIDE, PHARMACEUTICALLY ACCEPTABLE SALT OF AN OLIGONUCLEOTIDE, CONJUGATED, PHARMACEUTICAL COMPOSITION AND INVENTION
EP3927716A1 (en) 2019-02-20 2021-12-29 Roche Innovation Center Copenhagen A/S Novel phosphoramidites
CN113474633A (en) 2019-02-26 2021-10-01 罗氏创新中心哥本哈根有限公司 Process for preparing oligonucleotide
US20220177894A1 (en) 2019-04-02 2022-06-09 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for immunotherapy
EA202192733A1 (en) 2019-04-03 2022-03-14 Бристол-Маерс Сквибб Компани ANGPTL2 ANTISENSE OLIGONUCLEOTIDES AND THEIR APPLICATIONS
WO2021122993A1 (en) 2019-12-19 2021-06-24 F. Hoffmann-La Roche Ag Use of saraf inhibitors for treating hepatitis b virus infection
EP4077669A1 (en) 2019-12-19 2022-10-26 F. Hoffmann-La Roche AG Use of sbds 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
EP4077668A1 (en) 2019-12-19 2022-10-26 F. Hoffmann-La Roche AG Use of scamp3 inhibitors for treating hepatitis b virus infection
EP4077670A1 (en) 2019-12-19 2022-10-26 F. Hoffmann-La Roche AG Use of cops3 inhibitors for treating hepatitis b virus infection
CA3163490A1 (en) 2019-12-24 2021-07-01 F. Hoffman-La Roche Ag Pharmaceutical combination of a therapeutic oligonucleotide targeting hbv and a tlr7 agonist for treatment of hbv
EP4081217A1 (en) 2019-12-24 2022-11-02 F. Hoffmann-La Roche AG Pharmaceutical combination of antiviral agents targeting hbv and/or an immune modulator for treatment of hbv
JP2023516759A (en) * 2020-03-04 2023-04-20 ヴァーヴ・セラピューティクス，インコーポレーテッド Compositions and methods for targeted RNA delivery
EP4081642A1 (en) * 2020-03-16 2022-11-02 Argonaute Rna Limited Antagonist of pcsk9
AR122731A1 (en) 2020-06-26 2022-10-05 Hoffmann La Roche IMPROVED OLIGONUCLEOTIDES TO MODULATE FUBP1 EXPRESSION
WO2022038211A2 (en) 2020-08-21 2022-02-24 F. Hoffmann-La Roche Ag Use of a1cf inhibitors for treating hepatitis b virus infection
CR20230308A (en) * 2020-12-11 2023-09-08 Civi Biopharma Inc ORAL DELIVERY OF ANTISENSE CONJUGATES TARGETTING PCSK9
TW202246500A (en) 2021-02-02 2022-12-01 瑞士商赫孚孟拉羅股份公司 Enhanced oligonucleotides for inhibiting rtel1 expression
CA3212650A1 (en) 2021-03-08 2022-09-15 Les Laboratoires Servier Antisense oligonucleotides for inhibiting alpha-synuclein expression
WO2023049294A2 (en) * 2021-09-23 2023-03-30 Sirius Therapeutics, Inc. Polynucleic acid molecules targeting pcsk9 and uses thereof
WO2023111210A1 (en) 2021-12-17 2023-06-22 F. Hoffmann-La Roche Ag Combination of oligonucleotides for modulating rtel1 and fubp1
AR128558A1 (en) 2022-02-21 2024-05-22 Hoffmann La Roche ANTISENSE OLIGONUCLEOTIDE
WO2023225650A1 (en) * 2022-05-19 2023-11-23 Olix Us, Inc. Linkers coupling functional ligands to macromolecules
GB2629617A (en) * 2023-05-04 2024-11-06 Argonaute Rna Ltd Dual silencing
GB2629679A (en) * 2023-05-04 2024-11-06 Argonaute Rna Ltd Dual silencing
CN117563009A (en) * 2023-09-01 2024-02-20 北京悦康科创医药科技股份有限公司 GalNAc compound containing ribose ring or derivative structure thereof and oligonucleotide conjugate thereof
CN118546935B (en) * 2024-07-25 2024-10-22 深圳大学 Method for preparing enhanced CAR-T cells based on interference or knocked-out human PCSK9 gene and application

Family Cites Families (146)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2699808A (en) 1944-10-06 1955-01-18 Mark W Lowe Apparatus for peeling tomatoes
US2699508A (en) 1951-12-21 1955-01-11 Selectronics Inc Method of mounting and construction of mounting for low frequency piezoelectric crystals
JPS5927900A (en) 1982-08-09 1984-02-14 Wakunaga Seiyaku Kk Oligonucleotide derivative and its preparation
US4948882A (en) 1983-02-22 1990-08-14 Syngene, Inc. Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis
US4587044A (en) 1983-09-01 1986-05-06 The Johns Hopkins University Linkage of proteins to nucleic acids
US5430136A (en) 1984-10-16 1995-07-04 Chiron Corporation Oligonucleotides having selectably cleavable and/or abasic sites
US4914210A (en) 1987-10-02 1990-04-03 Cetus Corporation Oligonucleotide functionalizing reagents
US4962029A (en) 1987-10-02 1990-10-09 Cetus Corporation Covalent oligonucleotide-horseradish peroxidase conjugate
US5525465A (en) 1987-10-28 1996-06-11 Howard Florey Institute Of Experimental Physiology And Medicine Oligonucleotide-polyamide conjugates and methods of production and applications of the same
DE3738460A1 (en) 1987-11-12 1989-05-24 Max Planck Gesellschaft MODIFIED OLIGONUCLEOTIDS
US5391723A (en) 1989-05-31 1995-02-21 Neorx Corporation Oligonucleotide conjugates
US4958013A (en) 1989-06-06 1990-09-18 Northwestern University Cholesteryl modified oligonucleotides
US5254469A (en) 1989-09-12 1993-10-19 Eastman Kodak Company Oligonucleotide-enzyme conjugate that can be used as a probe in hybridization assays and polymerase chain reaction procedures
US5486603A (en) 1990-01-08 1996-01-23 Gilead Sciences, Inc. Oligonucleotide having enhanced binding affinity
US6395492B1 (en) 1990-01-11 2002-05-28 Isis Pharmaceuticals, Inc. Derivatized oligonucleotides having improved uptake and other properties
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5245022A (en) 1990-08-03 1993-09-14 Sterling Drug, Inc. Exonuclease resistant terminally substituted oligonucleotides
US5512667A (en) 1990-08-28 1996-04-30 Reed; Michael W. Trifunctional intermediates for preparing 3'-tailed oligonucleotides
WO1992008728A1 (en) 1990-11-08 1992-05-29 Hybridon, Inc. Incorporation of multiple reporter groups on synthetic oligonucleotides
DE69233046T2 (en) 1991-10-24 2004-03-04 Isis Pharmaceuticals, Inc., Carlsfeld DERIVATIZED OLIGONUCLEOTIDS WITH IMPROVED CAPACITY
NL9201440A (en) 1992-08-11 1994-03-01 Univ Leiden Triantennary cluster glycosides, their preparation and application.
JPH06311885A (en) 1992-08-25 1994-11-08 Mitsubishi Kasei Corp Anti-sense compound complementary with gene of hepatitis c virus
DK0662157T3 (en) 1992-09-10 2001-08-27 Isis Pharmaceuticals Inc Preparations and Methods for the Treatment of Hepatitis C Virus-Associated Diseases
US6423489B1 (en) 1992-09-10 2002-07-23 Isis Pharmaceuticals, Inc. Compositions and methods for treatment of Hepatitis C virus-associated diseases
US6433159B1 (en) 1992-09-10 2002-08-13 Isis Pharmaceuticals, Inc. Compositions and methods for treatment of Hepatitis C virus associated diseases
EP0673559A1 (en) 1992-12-14 1995-09-27 Honeywell Inc. Motor system with individually controlled redundant windings
US5574142A (en) 1992-12-15 1996-11-12 Microprobe Corporation Peptide linkers for improved oligonucleotide delivery
EP0759979A4 (en) 1994-05-10 1999-10-20 Gen Hospital Corp Antisense inhibition of hepatitis c virus
US5580731A (en) 1994-08-25 1996-12-03 Chiron Corporation N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith
DE69527857T2 (en) 1994-10-06 2003-05-28 Buchardt, Dorte Peptide Nucleic Acid CONJUGATES
MX9709914A (en) 1995-06-07 1998-03-31 Pfizer BIPHENYL-2-CARBOXYLIC ACID-TETRAHYDRO-ISOQUINOLIN-6-YL AMIDE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS INHIBITORS OF MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN AND/OR APOLIPOPROTEIN B (Apo B) SECRETION.
US5684142A (en) 1995-06-07 1997-11-04 Oncor, Inc. Modified nucleotides for nucleic acid labeling
TW520293B (en) * 1995-11-22 2003-02-11 Univ Johns Hopkins Med Delivery system to enhance cellular uptake of biomolecules
US5656408A (en) 1996-04-29 1997-08-12 Xerox Corporation Coated carrier particles
TR199901180T2 (en) 1996-11-27 1999-08-23 Pfizer Inc. Apo B-Salg�lama / MTP inhibitor amides.
HUP0001395A3 (en) 1997-03-05 2001-09-28 Univ Washington Seattle Novel screening methods to identify agents that selectively inhibit hepatitis c virus replication
US6770748B2 (en) 1997-03-07 2004-08-03 Takeshi Imanishi Bicyclonucleoside and oligonucleotide analogue
JP3756313B2 (en) 1997-03-07 2006-03-15 武 今西 Novel bicyclonucleosides and oligonucleotide analogues
US5770716A (en) 1997-04-10 1998-06-23 The Perkin-Elmer Corporation Substituted propargylethoxyamido nucleosides, oligonucleotides and methods for using same
IL132941A0 (en) 1997-05-21 2001-03-19 Univ Leland Stanford Junior Composition and method for enhancing transport across biological membranes
NZ503765A (en) 1997-09-12 2002-04-26 Exiqon As Bi-cyclic and tri-cyclic nucleotide analogues
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
US6096875A (en) 1998-05-29 2000-08-01 The Perlein-Elmer Corporation Nucleotide compounds including a rigid linker
US6300319B1 (en) 1998-06-16 2001-10-09 Isis Pharmaceuticals, Inc. Targeted oligonucleotide conjugates
US6335432B1 (en) 1998-08-07 2002-01-01 Bio-Red Laboratories, Inc. Structural analogs of amine bases and nucleosides
US6335437B1 (en) 1998-09-07 2002-01-01 Isis Pharmaceuticals, Inc. Methods for the preparation of conjugated oligomers
US6410323B1 (en) 1999-08-31 2002-06-25 Isis Pharmaceuticals, Inc. Antisense modulation of human Rho family gene expression
EP1161439B1 (en) 1999-03-18 2010-04-21 Exiqon A/S Xylo-lna analogues
ES2269113T3 (en) 1999-03-24 2007-04-01 Exiqon A/S IMPROVED SYNTHESIS OF -2.2.1 / BICICLO-NUCLEOSIDOS.
AU776362B2 (en) 1999-05-04 2004-09-09 Roche Innovation Center Copenhagen A/S L-ribo-LNA analogues
US6525191B1 (en) 1999-05-11 2003-02-25 Kanda S. Ramasamy Conformationally constrained L-nucleosides
US20040146516A1 (en) 1999-06-17 2004-07-29 Utah Ventures Ii L.P. Lumen-exposed molecules and methods for targeted delivery
US7029895B2 (en) 1999-09-27 2006-04-18 Millennium Pharmaceuticals, Inc. 27411, a novel human PGP synthase
US6617442B1 (en) 1999-09-30 2003-09-09 Isis Pharmaceuticals, Inc. Human Rnase H1 and oligonucleotide compositions thereof
AU7406700A (en) 1999-10-04 2001-05-10 Exiqon A/S Design of high affinity rnase h recruiting oligonucleotide
IL139450A0 (en) 1999-11-10 2001-11-25 Pfizer Prod Inc Methods of administering apo b-secretion/mtp inhibitors
US20020068709A1 (en) 1999-12-23 2002-06-06 Henrik Orum Therapeutic uses of LNA-modified oligonucleotides
WO2001057081A2 (en) 2000-02-07 2001-08-09 Millennium Pharmaceuticals, Inc. Narc-1, subtilase-like homologs
WO2002028875A2 (en) 2000-10-04 2002-04-11 Cureon A/S Improved synthesis of purine locked nucleic acid analogues
US20070173473A1 (en) 2001-05-18 2007-07-26 Sirna Therapeutics, Inc. RNA interference mediated inhibition of proprotein convertase subtilisin Kexin 9 (PCSK9) gene expression using short interfering nucleic acid (siNA)
AU2002317437A1 (en) 2001-05-18 2002-12-03 Cureon A/S Therapeutic uses of lna-modified oligonucleotides in infectious diseases
ATE287413T1 (en) 2001-07-12 2005-02-15 Santaris Pharma As METHOD FOR PRODUCING THE LNA PHOSPHORAMIDITE
US7407943B2 (en) 2001-08-01 2008-08-05 Isis Pharmaceuticals, Inc. Antisense modulation of apolipoprotein B expression
US7888324B2 (en) 2001-08-01 2011-02-15 Genzyme Corporation Antisense modulation of apolipoprotein B expression
AU2003225495B2 (en) 2002-04-05 2009-01-15 Roche Innovation Center Copenhagen A/S Oligomeric compounds for the modulation HIF-1alpha expression
DE60315444T2 (en) 2002-05-08 2008-04-30 Santaris Pharma A/S SYNTHESIS OF LOCKED NUCLEIC ACID DERIVATIVES
AU2003261434A1 (en) 2002-08-12 2004-02-25 Bristol-Myers Squibb Company Iminothiazolidinones as inhibitors of hcv replication
UA79300C2 (en) 2002-08-12 2007-06-11 Janssen Pharmaceutica Nv N-aryl piperidine substituted biphenylcarboxamides as inhibitors of apolipoprotein b secretion
US7087229B2 (en) 2003-05-30 2006-08-08 Enzon Pharmaceuticals, Inc. Releasable polymeric conjugates based on aliphatic biodegradable linkers
AU2003295389A1 (en) 2002-11-05 2004-06-03 Isis Pharmaceuticals, Inc. Conjugated oligomeric compounds and their use in gene modulation
US7696345B2 (en) 2002-11-05 2010-04-13 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
AU2003295387A1 (en) 2002-11-05 2004-06-03 Isis Parmaceuticals, Inc. Modified oligonucleotides for use in rna interference
EP2336318B1 (en) 2002-11-13 2013-04-24 Genzyme Corporation Antisense modulation of apolipoprotein b expression
AU2003281969B2 (en) 2002-11-18 2011-01-27 Roche Innovation Center Copenhagen A/S Amino-LNA, thio-LNA and alpha-L-oxy-LN
FR2848572B1 (en) 2002-12-12 2005-12-09 Univ Joseph Fourier INHIBITOR MOLECULES OF PROTEIN SYNTHESIS OF HEPATITIS C VIRUS AND METHOD FOR SCREENING THESE INHIBITORY MOLECULES
WO2004069991A2 (en) 2003-02-10 2004-08-19 Santaris Pharma A/S Oligomeric compounds for the modulation of survivin expression
EP1471152A1 (en) 2003-04-25 2004-10-27 Institut National De La Sante Et De La Recherche Medicale (Inserm) Mutations in the human PCSK9 gene associated to hypercholesterolemia
WO2004106356A1 (en) 2003-05-27 2004-12-09 Syddansk Universitet Functionalized nucleotide derivatives
DE60319354T2 (en) 2003-07-11 2009-03-26 Lbr Medbiotech B.V. Mannose-6-phosphate receptor mediated gene transfer to muscle cells
CA2533701A1 (en) 2003-07-31 2005-02-17 Isis Pharmaceuticals, Inc. Oligomeric compounds and compositions for use in modulation of small non-coding rnas
ATE555118T1 (en) 2003-08-28 2012-05-15 Takeshi Imanishi NEW SYNTHETIC NUCLEIC ACIDS OF THE CROSS-LINKED N-O BOND TYPE
US20050053981A1 (en) 2003-09-09 2005-03-10 Swayze Eric E. Gapped oligomeric compounds having linked bicyclic sugar moieties at the termini
EP1793674B1 (en) 2003-11-26 2018-05-30 University of Massachusetts Sequence-specific inhibtion of small rna function
UA83510C2 (en) 2003-12-09 2008-07-25 Янссен Фармацевтика Н.В. N-aryl piperidine substituted biphenylcarboxamides as inhibitors of apolipoprotein b
RU2377301C2 (en) 2003-12-23 2009-12-27 Сантарис Фарма А/С OLIGOMER COMPOUND REDUCING EXPRESSION OF HUMAN GENE Bcl-2, CONJUGATE, PHARMACEUTICAL COMPOSITION AND APPLICATION OF OLIGOMER COMPOUND IN CANCER TREATMENT
DK1713912T3 (en) 2004-01-30 2013-12-16 Santaris Pharma As Modified Short Interfering RNA (Modified siRNA)
EP1735459B1 (en) 2004-04-07 2012-01-25 Exiqon A/S Methods for quantification of micrornas and small interfering rnas
WO2005107816A2 (en) 2004-05-04 2005-11-17 The Board Of Trustees Of The Leland Stanford Junior University Methods and compositions for reducing viral genome amounts in a target cell
US20080213891A1 (en) 2004-07-21 2008-09-04 Alnylam Pharmaceuticals, Inc. RNAi Agents Comprising Universal Nucleobases
AU2005328382C1 (en) 2004-07-21 2013-01-24 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising a modified or non-natural nucleobase
FR2873694B1 (en) 2004-07-27 2006-12-08 Merck Sante Soc Par Actions Si NEW AZA-INDOLES INHIBITORS OF MTP AND APOB
US7632932B2 (en) 2004-08-04 2009-12-15 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising a ligand tethered to a modified or non-natural nucleobase
US7582744B2 (en) 2004-08-10 2009-09-01 Alnylam Pharmaceuticals, Inc. Chemically modified oligonucleotides
WO2006020676A2 (en) 2004-08-10 2006-02-23 Isis Pharmaceuticals, Inc. Antisense modulation of apolipoprotein b expression
EP1802644B1 (en) 2004-09-24 2012-11-07 Alnylam Pharmaceuticals Inc. Rnai modulation of apob and uses thereof
WO2006053430A1 (en) 2004-11-17 2006-05-26 Protiva Biotherapeutics, Inc. Sirna silencing of apolipoprotein b
US20060185027A1 (en) 2004-12-23 2006-08-17 David Bartel Systems and methods for identifying miRNA targets and for altering miRNA and target expression
GEP20104878B (en) 2005-04-19 2010-01-11 Surface Logix Inc Inhibitors of microsomal triglyceride transfer protein and apo-b secretion
WO2007031091A2 (en) 2005-09-15 2007-03-22 Santaris Pharma A/S Rna antagonist compounds for the modulation of p21 ras expression
KR20080068019A (en) 2005-09-15 2008-07-22 산타리스 팔마 에이/에스 Rna antagonist compounds for the inhibition of apo-b100 expression
PL2314594T3 (en) 2006-01-27 2014-12-31 Isis Pharmaceuticals Inc 6-modified bicyclic nucleic acid analogs
ES2715625T3 (en) 2006-04-03 2019-06-05 Roche Innovation Ct Copenhagen As Pharmaceutical composition comprising anti-miRNA antisense oligonucleotides
EP2458006B1 (en) 2006-05-05 2018-06-20 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating expression APOB
EP3249052B1 (en) * 2006-05-11 2019-04-10 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the pcsk9 gene
US7547684B2 (en) 2006-05-11 2009-06-16 Isis Pharmaceuticals, Inc. 5′-modified bicyclic nucleic acid analogs
AU2007275365A1 (en) 2006-07-17 2008-01-24 Sirna Therapeutics Inc. RNA interference mediated inhibition of Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene expression using short interfering nucleic acid (siNA)
CA2662520A1 (en) 2006-09-15 2008-03-20 Enzon Pharmaceuticals, Inc. Polymeric conjugates containing positively-charged moieties
EP2063709A2 (en) 2006-09-15 2009-06-03 Enzon Pharmaceuticals, Inc. Hindered ester-based biodegradable linkers for oligonucleotide delivery
EP2076597A2 (en) 2006-10-09 2009-07-08 Santaris Pharma A/S Rna antagonist compounds for the modulation of pcsk9
WO2008061537A2 (en) 2006-11-23 2008-05-29 Querdenker Aps Oligonucleotides for modulating target rna activity
US8093222B2 (en) 2006-11-27 2012-01-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
US8084437B2 (en) 2006-11-27 2011-12-27 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
WO2008089767A1 (en) 2007-01-26 2008-07-31 Diramo A/S Stacking of optic sensor and microfluidic-chips with optically communication through windows
WO2008109369A2 (en) 2007-03-02 2008-09-12 Mdrna, Inc. Nucleic acid compounds for inhibiting tnf gene expression and uses thereof
US8580756B2 (en) 2007-03-22 2013-11-12 Santaris Pharma A/S Short oligomer antagonist compounds for the modulation of target mRNA
WO2008124384A2 (en) 2007-04-03 2008-10-16 Aegerion Pharmaceuticals, Inc. Combinations of mtp inhibitors with cholesterol absorption inhibitors or interferon for treating hepatitis c
ES2388590T3 (en) 2007-05-30 2012-10-16 Isis Pharmaceuticals, Inc. Analogs of bicyclic nucleic acids with N-substituted aminomethylene bridge.
US8278426B2 (en) 2007-06-08 2012-10-02 Isis Pharmaceuticals, Inc. Carbocyclic bicyclic nucleic acid analogs
ES2376507T5 (en) 2007-07-05 2015-08-31 Isis Pharmaceuticals, Inc. 6-disubstituted bicyclic nucleic acid analogs
EP2171648A4 (en) 2007-07-19 2011-06-29 Datakey Electronics Inc Rf token and receptacle system and method
US20100203066A1 (en) 2007-08-20 2010-08-12 Enzon Pharmaceuticals, Inc. Polymeric linkers containing pyridyl disulfide moieties
EP2623599B1 (en) 2007-10-04 2019-01-02 Roche Innovation Center Copenhagen A/S Micromirs
US8546556B2 (en) 2007-11-21 2013-10-01 Isis Pharmaceuticals, Inc Carbocyclic alpha-L-bicyclic nucleic acid analogs
US8106022B2 (en) 2007-12-04 2012-01-31 Alnylam Pharmaceuticals, Inc. Carbohydrate conjugates as delivery agents for oligonucleotides
WO2009090182A1 (en) 2008-01-14 2009-07-23 Santaris Pharma A/S C4'-substituted - dna nucleotide gapmer oligonucleotides
BRPI0907008A2 (en) 2008-01-31 2015-07-07 Alnylam Pharmaceuticals Inc Optimized methods for dsrna release by targeting the pcsk9 gene
US9290534B2 (en) 2008-04-04 2016-03-22 Ionis Pharmaceuticals, Inc. Oligomeric compounds having at least one neutrally linked terminal bicyclic nucleoside
AU2009234266B2 (en) * 2008-04-11 2015-08-06 Tekmira Pharmaceuticals Corporation Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
WO2009127680A1 (en) * 2008-04-16 2009-10-22 Santaris Pharma A/S Pharmaceutical composition comprising anti pcsk9 oligomers
WO2009148605A2 (en) * 2008-06-04 2009-12-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
US8440809B2 (en) * 2008-07-02 2013-05-14 Santaris Pharma A/S RNA antagonists targeting Hsp27
AT507215B1 (en) 2009-01-14 2010-03-15 Boehler Edelstahl Gmbh & Co Kg WEAR-RESISTANT MATERIAL
NZ720946A (en) * 2009-04-29 2017-09-29 Amarin Pharmaceuticals Ie Ltd Pharmaceutical compositions comprising epa and a cardiovascular agent and methods of using the same
EP2440215B1 (en) 2009-06-12 2015-10-21 Roche Innovation Center Copenhagen A/S New potent anti apob antisense compounds
EP2456870A1 (en) * 2009-07-21 2012-05-30 Santaris Pharma A/S Antisense oligomers targeting pcsk9
WO2011126937A1 (en) 2010-04-06 2011-10-13 The University Of North Carolina At Chapel Hill Targeted intracellular delivery of oligonucleotides via conjugation with small molecule ligands
WO2012058693A2 (en) * 2010-10-29 2012-05-03 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibition of pcsk9 genes
WO2012082046A1 (en) 2010-12-13 2012-06-21 Telefonaktiebolaget L M Ericsson (Publ) Exchange of parameters relating to measurement periods
KR20130132475A (en) * 2010-12-17 2013-12-04 애로우헤드 리서치 코오포레이션 Galactose cluster-pharmacokinetic modulator targeting moiety for sirna
WO2012089352A1 (en) 2010-12-29 2012-07-05 F. Hoffmann-La Roche Ag Small molecule conjugates for intracellular delivery of nucleic acids
WO2013022984A1 (en) * 2011-08-11 2013-02-14 Isis Pharmaceuticals, Inc. Selective antisense compounds and uses thereof
US9984408B1 (en) 2012-05-30 2018-05-29 Amazon Technologies, Inc. Method, medium, and system for live video cooperative shopping
AU2014211406B2 (en) 2013-01-30 2019-07-18 Roche Innovation Center Copenhagen A/S LNA oligonucleotide carbohydrate conjugates
CA2921518A1 (en) * 2013-05-01 2014-11-06 Ionis Pharmaceuticals, Inc. Compositions and methods
SI3013959T1 (en) 2013-06-27 2020-04-30 Roche Innovation Center Copenhagen A/S Antisense oligomers and conjugates targeting pcsk9
US9778708B1 (en) 2016-07-18 2017-10-03 Lenovo Enterprise Solutions (Singapore) Pte. Ltd. Dual sided latching retainer for computer modules

Also Published As

Publication number Publication date
EP3591054A1 (en) 2020-01-08
CL2015003728A1 (en) 2016-08-26
PE20160158A1 (en) 2016-03-18
PT3013959T (en) 2020-02-04
KR20180136006A (en) 2018-12-21
WO2014207232A1 (en) 2014-12-31
CY1122738T1 (en) 2021-03-12
CN112263682B (en) 2024-08-20
PH12015502761A1 (en) 2016-03-21
DK3013959T3 (en) 2020-02-17
ES2770667T3 (en) 2020-07-02
US20220025376A1 (en) 2022-01-27
MX2019006284A (en) 2019-08-29
EP3013959B1 (en) 2019-12-04
EP3013959A1 (en) 2016-05-04
RS59986B1 (en) 2020-03-31
US20200248186A1 (en) 2020-08-06
US10370668B2 (en) 2019-08-06
JP2018064575A (en) 2018-04-26
KR102226110B1 (en) 2021-03-10
MX367083B (en) 2019-08-05
CN105358692B (en) 2020-08-21
JP2016523094A (en) 2016-08-08
SG11201510656PA (en) 2016-01-28
CN105358692A (en) 2016-02-24
HK1221740A1 (en) 2017-06-09
CN112263682A (en) 2021-01-26
AU2014300981A1 (en) 2016-01-21
US11091764B2 (en) 2021-08-17
MX2015017601A (en) 2016-04-07
KR20160027042A (en) 2016-03-09
US10385342B2 (en) 2019-08-20
BR112015032432B1 (en) 2023-02-07
US20160138025A1 (en) 2016-05-19
HRP20200163T1 (en) 2020-08-07
CA2915316A1 (en) 2014-12-31
NZ715081A (en) 2022-02-25
US9879265B2 (en) 2018-01-30
CA2915316C (en) 2024-01-02
US20180312847A1 (en) 2018-11-01
PL3013959T3 (en) 2020-05-18
WO2014207232A4 (en) 2015-03-19
US10443058B2 (en) 2019-10-15
IL242875B (en) 2020-02-27
SI3013959T1 (en) 2020-04-30
US20240084307A1 (en) 2024-03-14
UA119643C2 (en) 2019-07-25
US11739332B2 (en) 2023-08-29
EA201592215A1 (en) 2016-05-31
HUE048738T2 (en) 2020-08-28
JP6672245B2 (en) 2020-03-25
MY183049A (en) 2021-02-09
JP6255092B2 (en) 2017-12-27
US20180216116A1 (en) 2018-08-02
BR112015032432A2 (en) 2017-08-29
AU2014300981B2 (en) 2017-08-10
US20180312846A1 (en) 2018-11-01
LT3013959T (en) 2020-03-10
KR101931089B1 (en) 2019-03-14

Similar Documents

Publication Publication Date Title
SG10201908122XA (en) Antisense oligomers and conjugates targeting pcsk9
PH12019501274A1 (en) Methods of treating or preventing cholesterol related disorders
MX2023000251A (en) Methods and compositions for treating a proprotein convertase subtilisin kexin (pcsk9) gene-associated disorder.
TN2013000467A1 (en) Methods of treating or preventing cholesterol related disorders
MY168961A (en) Antibodies to pcsk9 and uses thereof
HK1243075A1 (en) Methods of lowering proprotein convertase subtilisin/kexin type 9 (pcsk9)
WO2012170607A3 (en) Use of pcsk9 antagonists
MX2015005963A (en) Heterocyclic glutaminase inhibitors.
ZA201409210B (en) Methods and uses for proprotein convertase subtilisin kexin 9 (pcsk9) inhibitors
MX346883B (en) Vaccine.
AU347707S (en) Diaphragm pump
MX2016006226A (en) Dosing regimens for use with pcsk9 inhibitors.
MX2016000794A (en) High potency pancreatin pharmaceutical compositions.
PH12014502187A1 (en) Cdr-modified anti-siglec-15 antibody
MX2016000480A (en) High potency pancreatin pharmaceutical compositions.
GR1008167B (en) Pharmaceutical gluconic iron-containing composition - preparation method of same
EA201990125A1 (en) ANTISMYSIBLE OLIGOMERS AND THEIR CONJUGATES AIMED AT PROPROTEIN CONVERTASE SUBTILYSINE / KEKSIN TYPE 9 (PCSK9)
MA38717B1 (en) Antisense oligomers and conjugates targeting pcsk9