PL3013959T3 - Antysensowne oligomery i koniugaty ukierunkowane na pcsk9 - Google Patents

Antysensowne oligomery i koniugaty ukierunkowane na pcsk9

Info

Publication number
PL3013959T3
PL3013959T3 PL14739708T PL14739708T PL3013959T3 PL 3013959 T3 PL3013959 T3 PL 3013959T3 PL 14739708 T PL14739708 T PL 14739708T PL 14739708 T PL14739708 T PL 14739708T PL 3013959 T3 PL3013959 T3 PL 3013959T3
Authority
PL
Poland
Prior art keywords
antisense oligomers
targeting pcsk9
conjugates targeting
conjugates
pcsk9
Prior art date
Application number
PL14739708T
Other languages
English (en)
Inventor
Nanna ALBÆK
Maj Hedtjärn
Marie Lindholm
Niels Fisker Nielsen
Andreas Petri
Jacob Ravn
Original Assignee
Roche Innovation Center Copenhagen A/S
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 Center Copenhagen A/S filed Critical Roche Innovation Center Copenhagen A/S
Publication of PL3013959T3 publication Critical patent/PL3013959T3/pl

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1137—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
PL14739708T 2013-06-27 2014-06-27 Antysensowne oligomery i koniugaty ukierunkowane na pcsk9 PL3013959T3 (pl)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
EP13174092 2013-06-27
PCT/EP2013/073858 WO2014076195A1 (en) 2012-11-15 2013-11-14 Oligonucleotide conjugates
EP13192930 2013-11-14
EP13192938 2013-11-14
EP14153253 2014-01-30
EP14168331 2014-05-14
PCT/EP2014/063757 WO2014207232A1 (en) 2013-06-27 2014-06-27 Antisense oligomers and conjugates targeting pcsk9
EP14739708.7A EP3013959B1 (en) 2013-06-27 2014-06-27 Antisense oligomers and conjugates targeting pcsk9

Publications (1)

Publication Number Publication Date
PL3013959T3 true PL3013959T3 (pl) 2020-05-18

Family

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Application Number Title Priority Date Filing Date
PL14739708T PL3013959T3 (pl) 2013-06-27 2014-06-27 Antysensowne oligomery i koniugaty ukierunkowane na pcsk9

Country Status (30)

Country Link
US (7) US9879265B2 (pl)
EP (2) EP3591054A1 (pl)
JP (2) JP6255092B2 (pl)
KR (2) KR101931089B1 (pl)
CN (2) CN105358692B (pl)
AU (1) AU2014300981B2 (pl)
BR (1) BR112015032432B1 (pl)
CA (1) CA2915316C (pl)
CL (1) CL2015003728A1 (pl)
CY (1) CY1122738T1 (pl)
DK (1) DK3013959T3 (pl)
EA (1) EA201592215A1 (pl)
ES (1) ES2770667T3 (pl)
HK (1) HK1221740A1 (pl)
HR (1) HRP20200163T1 (pl)
HU (1) HUE048738T2 (pl)
IL (1) IL242875B (pl)
LT (1) LT3013959T (pl)
MX (2) MX367083B (pl)
MY (1) MY183049A (pl)
NZ (1) NZ715081A (pl)
PE (1) PE20160158A1 (pl)
PH (1) PH12015502761A1 (pl)
PL (1) PL3013959T3 (pl)
PT (1) PT3013959T (pl)
RS (1) RS59986B1 (pl)
SG (2) SG10201908122XA (pl)
SI (1) SI3013959T1 (pl)
UA (1) UA119643C2 (pl)
WO (1) WO2014207232A1 (pl)

Families Citing this family (86)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5645840B2 (ja) 2008-12-02 2014-12-24 株式会社Ｗａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｊａｐａｎ リン原子修飾核酸の合成方法
EP2451461A4 (en) 2009-07-06 2013-05-29 Ontorii Inc NOVEL NUCLEIC ACID PRODRUGS AND METHOD OF USE THEREOF
US11083444B2 (en) 2010-03-11 2021-08-10 Globus Medical, Inc. Tissue retractor and methods of use
EP2620428B1 (en) 2010-09-24 2019-05-22 Wave Life Sciences Ltd. Asymmetric auxiliary group
US9605019B2 (en) 2011-07-19 2017-03-28 Wave Life Sciences Ltd. Methods for the synthesis of functionalized nucleic acids
PL2872147T3 (pl) 2012-07-13 2023-09-25 Wave Life Sciences Ltd. Sposób wytwarzania chiralnych oligonukleotydów
BR112015000784A8 (pt) 2012-07-13 2018-04-03 Wave Life Sciences Japan Grupo auxiliar assimétrico
CN105378085B (zh) 2013-05-01 2019-02-15 Ionis制药公司 用于调节hbv和ttr表达的组合物和方法
CA2915316C (en) * 2013-06-27 2024-01-02 Roche Innovation Center Copenhagen A/S Antisense oligomers and conjugates targeting pcsk9
EP3095459A4 (en) 2014-01-15 2017-08-23 Shin Nippon Biomedical Laboratories, Ltd. Chiral nucleic acid adjuvant having antitumor effect and antitumor agent
US10144933B2 (en) 2014-01-15 2018-12-04 Shin Nippon Biomedical Laboratories, Ltd. Chiral nucleic acid adjuvant having immunity induction activity, and immunity induction activator
CN113278617A (zh) 2014-01-16 2021-08-20 波涛生命科学有限公司 手性设计
PE20190626A1 (es) 2014-05-01 2019-04-26 Ionis Pharmaceuticals Inc Composiciones y metodos para modular la expresion del factor b del complemento
CN106459969B (zh) 2014-05-01 2019-11-15 Ionis制药公司 用于调节生长激素受体表达的组合物和方法
MX2016014102A (es) 2014-05-01 2017-05-03 Ionis Pharmaceuticals Inc Composiciones y metodos para modular la expresion de similar a la angiopoyetina tipo 3.
GB201408623D0 (en) 2014-05-15 2014-07-02 Santaris Pharma As Oligomers and oligomer conjugates
ES2744437T3 (es) 2015-08-06 2020-02-25 Hoffmann La Roche Procedimientos para la preparación de derivados ácidos de GalNAc
WO2017053995A1 (en) * 2015-09-25 2017-03-30 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
IL258230B (en) 2015-10-09 2022-09-01 Wave Life Sciences Ltd Oligonucleotide preparations and methods thereof
WO2017068087A1 (en) 2015-10-22 2017-04-27 Roche Innovation Center Copenhagen A/S Oligonucleotide detection method
US10557137B2 (en) 2015-11-06 2020-02-11 Ionis Pharmaceuticals, Inc. Modulating apolipoprotein (a) expression
AR106683A1 (es) * 2015-11-16 2018-02-07 Hoffmann La Roche FOSFORAMIDITA DE AGRUPACIÓN DE GalNAc
CN114085836B (zh) 2016-03-14 2024-01-26 豪夫迈·罗氏有限公司 用于减少pd-l1表达的寡核苷酸
MA45478A (fr) * 2016-04-11 2019-02-20 Arbutus Biopharma Corp Compositions de conjugués d'acides nucléiques ciblés
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
CN109312403B (zh) 2016-06-17 2023-06-27 豪夫迈·罗氏有限公司 体外肾毒性筛选测定法
WO2018049009A2 (en) 2016-09-07 2018-03-15 Sangamo Therapeutics, Inc. Modulation of liver genes
WO2018067900A1 (en) 2016-10-06 2018-04-12 Ionis Pharmaceuticals, Inc. Method of conjugating oligomeric compounds
EP3568479A1 (en) 2017-01-13 2019-11-20 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating nfkb1 expression
WO2018130584A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating nfkb2 expression
EP3568477A1 (en) 2017-01-13 2019-11-20 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating rela expression
EP3568478A1 (en) 2017-01-13 2019-11-20 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating rel expression
EP3568481A1 (en) 2017-01-13 2019-11-20 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating relb expression
JOP20190215A1 (ar) 2017-03-24 2019-09-19 Ionis Pharmaceuticals Inc مُعدّلات التعبير الوراثي عن pcsk9
SG11201909433XA (en) 2017-04-11 2019-11-28 Arbutus Biopharma Corp Targeted compositions
KR102401796B1 (ko) 2017-04-13 2022-05-25 카딜라 핼쓰캐어 리미티드 신규의 펩타이드 기재 pcsk9 백신
WO2018215049A1 (en) 2017-05-23 2018-11-29 F. Hoffmann-La Roche Ag Process for galnac oligonucleotide conjugates
WO2018216785A1 (ja) 2017-05-26 2018-11-29 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
WO2019030313A2 (en) 2017-08-11 2019-02-14 Roche Innovation Center Copenhagen A/S OLIGONUCLEOTIDES FOR MODULATION OF UBE3C EXPRESSION
WO2019038228A1 (en) 2017-08-22 2019-02-28 Roche Innovation Center Copenhagen A/S OLIGONUCLEOTIDES FOR MODULATION OF TOM1 EXPRESSION
WO2019073018A1 (en) 2017-10-13 2019-04-18 Roche Innovation Center Copenhagen A/S METHODS OF IDENTIFYING ANTISENSE OLIGONUCLEOTIDE IMPROVED OLIGONUCLEOTIDE PHOSPHOROTHIOATE STEREODEFINIS VARIANTS USING PARTIALLY STEREODEFINIS OLIGONUCLEOTIDE SUB LIBRARIES
EP3645723A1 (en) 2017-10-16 2020-05-06 H. Hoffnabb-La Roche Ag NUCLEIC ACID MOLECULE FOR REDUCTION OF PAPD5 AND PAPD7 mRNA FOR TREATING HEPATITIS B INFECTION
EP3724333A2 (en) 2017-12-11 2020-10-21 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
CA3085211A1 (en) 2017-12-21 2019-06-27 F. Hoffmann-La Roche Ag Companion diagnostic for htra1 rna antagonists
BR112020012427A8 (pt) 2017-12-22 2024-04-02 Roche Innovation Ct Copenhagen As Oligonucleotídeos, sal farmaceuticamente aceitável, conjugado, composição farmacêutica e processo para a fabricação de um oligonucleotídeo
EP4092117A1 (en) 2017-12-22 2022-11-23 Roche Innovation Center Copenhagen A/S Gapmer oligonucleotides comprising a phosphorodithioate internucleoside linkage
WO2019122277A1 (en) 2017-12-22 2019-06-27 Roche Innovation Center Copenhagen A/S Novel thiophosphoramidites
CN111699258A (zh) 2018-01-10 2020-09-22 哥本哈根罗氏创新中心 用于调控pias4表达的寡核苷酸
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
AU2019208006A1 (en) 2018-01-12 2020-07-23 Bristol-Myers Squibb Company Antisense oligonucleotides targeting alpha-synuclein and uses thereof
EA202091693A1 (ru) 2018-01-12 2021-04-14 Бристол-Маерс Сквибб Компани Антисмысловые олигонуклеотиды, целенаправленно воздействующие на альфа-синуклеин, и их применения
MX2020006973A (es) 2018-01-12 2020-09-09 Roche Innovation Ct Copenhagen As Oligonucleotidos antisentido para alfa-sinucleina y usos de los mismos.
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
WO2019145386A1 (en) 2018-01-26 2019-08-01 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating csnk1d expression
AU2019237599A1 (en) * 2018-03-20 2020-11-12 Nissan Chemical Corporation Antisense oligonucleotide having reduced toxicity
CN112055749A (zh) 2018-04-05 2020-12-08 豪夫迈·罗氏有限公司 Fubp1抑制剂用于治疗乙型肝炎病毒感染的用途
KR102585973B1 (ko) 2018-07-03 2023-10-10 에프. 호프만-라 로슈 아게 타우 발현을 조절하기 위한 올리고뉴클레오티드
SG11202100348SA (en) 2018-07-13 2021-02-25 Hoffmann La Roche Oligonucleotides for modulating rtel1 expression
CA3098267A1 (en) 2018-07-31 2020-02-06 Roche Innovation Center Copenhagen A/S Oligonucleotides comprising a phosphorotrithioate internucleoside linkage
TW202020155A (zh) 2018-07-31 2020-06-01 丹麥商羅氏創新中心哥本哈根有限公司 含有三硫代磷酸酯核苷間連結之寡核苷酸
AU2020225687A1 (en) 2019-02-20 2021-08-19 Roche Innovation Center Copenhagen A/S Phosphonoacetate gapmer oligonucleotides
CA3129646A1 (en) 2019-02-20 2020-08-27 Roche Innovation Center Copenhagen A/S Novel phosphoramidites
CN113474633A (zh) 2019-02-26 2021-10-01 罗氏创新中心哥本哈根有限公司 寡核苷酸配制方法
EP3947678A1 (en) 2019-04-02 2022-02-09 ProQR Therapeutics II B.V. Antisense oligonucleotides for immunotherapy
MX2021012098A (es) 2019-04-03 2021-11-03 Bristol Myers Squibb Co Oligonucleotidos antisentido del transcrito tipo 2 de angiopoyetina (angptl2) y sus usos.
CN114901821A (zh) 2019-12-19 2022-08-12 豪夫迈·罗氏有限公司 Sept9抑制剂用于治疗乙型肝炎病毒感染的用途
JP2023506547A (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を処置するためのｃｏｐｓ３阻害剤の使用
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
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
JP2023506540A (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を処置するためのｓｃａｍｐ３阻害剤の使用
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
TW202137987A (zh) 2019-12-24 2021-10-16 瑞士商赫孚孟拉羅股份公司 用於治療ｈｂｖ之靶向ｈｂｖ的治療性寡核苷酸及ｔｌｒ７促效劑之醫藥組合
CA3174708A1 (en) 2020-03-04 2021-09-10 Verve Therapeutics, Inc. Compositions and methods for targeted rna delivery
WO2021185765A1 (en) * 2020-03-16 2021-09-23 Argonaute RNA Limited Antagonist of pcsk9
AR122731A1 (es) 2020-06-26 2022-10-05 Hoffmann La Roche Oligonucleótidos mejorados para modular la expresión de fubp1
EP4200419A2 (en) 2020-08-21 2023-06-28 F. Hoffmann-La Roche AG Use of a1cf inhibitors for treating hepatitis b virus infection
CR20230308A (es) * 2020-12-11 2023-09-08 Civi Biopharma Inc Entrega oral de conjugados antisentido que tienen por blanco a pcsk9
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
AU2022234522A1 (en) 2021-03-08 2023-10-26 Les Laboratoires Servier Antisense oligonucleotides for inhibiting alpha-synuclein expression
AU2022349448A1 (en) * 2021-09-23 2024-04-11 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
TW202346587A (zh) 2022-02-21 2023-12-01 瑞士商赫孚孟拉羅股份公司 反義寡核苷酸
US20230372508A1 (en) * 2022-05-19 2023-11-23 Olix Us, Inc. Linkers coupling functional ligands to macromolecules
CN117563009A (zh) * 2023-09-01 2024-02-20 北京悦康科创医药科技股份有限公司 一种含有核糖环或其衍生结构的GalNAc化合物及其寡核苷酸缀合物

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 (ja) 1982-08-09 1984-02-14 Wakunaga Seiyaku Kk 固定化オリゴヌクレオチド
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 (de) 1987-11-12 1989-05-24 Max Planck Gesellschaft Modifizierte oligonukleotide
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
EP0556301B1 (en) 1990-11-08 2001-01-10 Hybridon, Inc. Incorporation of multiple reporter groups on synthetic oligonucleotides
EP0724447B1 (en) 1991-10-24 2003-05-07 Isis Pharmaceuticals, Inc. Derivatized oligonucleotides having improved uptake
NL9201440A (nl) 1992-08-11 1994-03-01 Univ Leiden Triantennaire clusterglycosiden, hun bereiding en toepassing.
JPH06311885A (ja) 1992-08-25 1994-11-08 Mitsubishi Kasei Corp Ｃ型肝炎ウイルス遺伝子に相補的なアンチセンス化合物
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
NZ255578A (en) 1992-09-10 1996-11-26 Chemo Sero Therapeut Res Inst Antisense oligonucleotides complementary and hybridizable to a portion of hepatitis c virus and their use in treating hepatitis c virus associated diseases
JPH08504559A (ja) 1992-12-14 1996-05-14 ハネウエル・インコーポレーテッド 個別に制御される冗長巻線を有するモータシステム
US5574142A (en) 1992-12-15 1996-11-12 Microprobe Corporation Peptide linkers for improved oligonucleotide delivery
JPH10503364A (ja) 1994-05-10 1998-03-31 ザ ジェネラル ホスピタル コーポレーション Ｃ型肝炎ウイルスのアンチセンス阻害
US5580731A (en) 1994-08-25 1996-12-03 Chiron Corporation N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith
JP3307945B2 (ja) 1994-10-06 2002-07-29 アイシス・ファーマシューティカルス・インコーポレーテッド ペプチド核酸コンジュゲート
US5684142A (en) 1995-06-07 1997-11-04 Oncor, Inc. Modified nucleotides for nucleic acid labeling
MX9709914A (es) 1995-06-07 1998-03-31 Pfizer Derivados de acido bifenil-2-carboxilico-tetrahidro-isoquinolin-6-ilo, su preparacion y el uso de los mismos.
CN1120707C (zh) * 1995-11-22 2003-09-10 约翰斯·霍普金斯大学 增强生物分子的细胞摄取的配体
US5656408A (en) 1996-04-29 1997-08-12 Xerox Corporation Coated carrier particles
EP0944602A1 (en) 1996-11-27 1999-09-29 Pfizer Inc. Apo b-secretion/mtp inhibitory amides
PL335721A1 (en) 1997-03-05 2000-05-08 Ribogene Novel methods of screening serving the purpose of identifying the factors of selective hepatitis c virus replication inhibition
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
US6770748B2 (en) 1997-03-07 2004-08-03 Takeshi Imanishi Bicyclonucleoside and oligonucleotide analogue
US5770716A (en) 1997-04-10 1998-06-23 The Perkin-Elmer Corporation Substituted propargylethoxyamido nucleosides, oligonucleotides and methods for using same
GB2341390B (en) 1997-05-21 2000-11-08 Univ Leland Stanford Junior Composition and method for enhancing transport across biological membranes
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
NZ503765A (en) 1997-09-12 2002-04-26 Exiqon As Bi-cyclic and tri-cyclic nucleotide 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
WO2000056748A1 (en) 1999-03-18 2000-09-28 Exiqon A/S Xylo-lna analogues
JP4768132B2 (ja) 1999-03-24 2011-09-07 エクシコン エ／エス ［２．２．１］ビシクロヌクレオシドの改良された製法
CA2372085C (en) 1999-05-04 2009-10-27 Exiqon 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
EP1224280A2 (en) 1999-10-04 2002-07-24 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
AU2001241461A1 (en) 2000-02-07 2001-08-14 Millennium Pharmaceuticals, Inc. Narc-1, novel subtilase-like homologs
EP1334109B1 (en) 2000-10-04 2006-05-10 Santaris Pharma A/S Improved synthesis of purine locked nucleic acid analogues
US20030125241A1 (en) 2001-05-18 2003-07-03 Margit Wissenbach Therapeutic uses of LNA-modified oligonucleotides in infectious diseases
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)
AU2002328792A1 (en) 2001-07-12 2003-01-29 Santaris Pharma A/S Method for preparation of lna phosphoramidites
US7888324B2 (en) 2001-08-01 2011-02-15 Genzyme Corporation Antisense modulation of apolipoprotein B expression
US7407943B2 (en) 2001-08-01 2008-08-05 Isis Pharmaceuticals, Inc. Antisense modulation of apolipoprotein B expression
DK2264172T3 (da) 2002-04-05 2017-11-27 Roche Innovation Ct Copenhagen As Oligomerforbindelser til modulering af HIF-1á-ekspression
CA2484526C (en) 2002-05-08 2009-10-13 Santaris Pharma A/S Synthesis of locked nucleic acid derivatives
UA79300C2 (en) 2002-08-12 2007-06-11 Janssen Pharmaceutica Nv N-aryl piperidine substituted biphenylcarboxamides as inhibitors of apolipoprotein b secretion
AU2003264038A1 (en) 2002-08-12 2004-02-25 Bristol-Myers Squibb Company Combination pharmaceutical agents as inhibitors of hcv replication
US7087229B2 (en) 2003-05-30 2006-08-08 Enzon Pharmaceuticals, Inc. Releasable polymeric conjugates based on aliphatic biodegradable linkers
AU2003291753B2 (en) 2002-11-05 2010-07-08 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
AU2003290596B2 (en) 2002-11-05 2011-05-12 Isis Pharmaceuticals, Inc. Sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
WO2004044141A2 (en) 2002-11-05 2004-05-27 Isis Pharmaceuticals, Inc. Conjugated oligomeric compounds and their use in gene modulation
JP4986109B2 (ja) 2002-11-13 2012-07-25 ジェンザイム・コーポレーション アポリポタンパク質ｂ発現のアンチセンス調節
CA2994089A1 (en) 2002-11-18 2004-06-03 Roche Innovation Center Copenhagen A/S Antisense gapmer oligonucleotides
FR2848572B1 (fr) 2002-12-12 2005-12-09 Univ Joseph Fourier Molecules inhibitrices de la synthese proteique du virus de l'hepatite c et procede de criblage desdites molecules inhibitrices
CA2515623A1 (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 (de) 2003-07-11 2009-03-26 Lbr Medbiotech B.V. Mannose-6-Phosphat Rezeptor vermittelter Gentransfer zu Muskelzellen
US7683036B2 (en) 2003-07-31 2010-03-23 Regulus Therapeutics Inc. Oligomeric compounds and compositions for use in modulation of small non-coding RNAs
ATE555118T1 (de) 2003-08-28 2012-05-15 Takeshi Imanishi Neue synthetische nukleidsäuren vom typ mit quervernetzter n-o-bindung
US20050053981A1 (en) 2003-09-09 2005-03-10 Swayze Eric E. Gapped oligomeric compounds having linked bicyclic sugar moieties at the termini
US8685946B2 (en) 2003-11-26 2014-04-01 Universiy of Massachusetts Sequence-specific inhibition 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
DE602004027163D1 (de) 2003-12-23 2010-06-24 Santaris Pharma As Oligomere verbindungen zur modulation von bcl-2
DK1713912T3 (da) 2004-01-30 2013-12-16 Santaris Pharma As Modificerede Korte Interfererende RNA (Modificerede siRNA)
ATE542918T1 (de) 2004-04-07 2012-02-15 Exiqon As Verfahren zur quantifizierung von mikro-rnas und kleinen interferenz-rnas
US7307067B2 (en) 2004-05-04 2007-12-11 The Board Of Trustees Of The Leland Stanford 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
CA2574088C (en) 2004-07-21 2013-09-17 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising a modified or non-natural nucleobase
FR2873694B1 (fr) 2004-07-27 2006-12-08 Merck Sante Soc Par Actions Si Nouveaux aza-indoles inhibiteurs de la mtp et apob
WO2006112872A2 (en) 2004-08-04 2006-10-26 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising a ligand tethered to a modified or non-natural nucleobase
WO2006020768A2 (en) 2004-08-10 2006-02-23 Alnylam Pharmaceuticals, Inc. Chemically modified oligonucleotides
EP2409713B1 (en) 2004-08-10 2015-07-22 Genzyme Corporation Oligonucleotides for use in modulating lipoprotein and cholesterol levels in humans
WO2006036916A2 (en) 2004-09-24 2006-04-06 Alnylam Pharmaceuticals, Inc. Rnai modulation of apob and uses thereof
EP2199298A1 (en) 2004-11-17 2010-06-23 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
WO2006113910A2 (en) 2005-04-19 2006-10-26 Surface Logix, Inc. Inhibitors of microsomal triglyceride transfer protein and apo-b secretion
EP1931778A2 (en) 2005-09-15 2008-06-18 Santaris Pharma A/S RNA ANTAGONIST COMPOUNDS FOR THE INHIBITION OF APO-Bl00 EXPRESSION
WO2007031091A2 (en) 2005-09-15 2007-03-22 Santaris Pharma A/S Rna antagonist compounds for the modulation of p21 ras expression
EP1984381B1 (en) 2006-01-27 2010-09-29 Isis Pharmaceuticals, Inc. 6-modified bicyclic nucleic acid analogs
CA2649045C (en) 2006-04-03 2019-06-11 Santaris Pharma A/S Pharmaceutical composition comprising anti-mirna antisense oligonucleotides
JP5825754B2 (ja) 2006-05-05 2015-12-02 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 Ａｐｏｂの発現を調節するための化合物および方法
NZ572666A (en) 2006-05-11 2010-11-26 Alnylam Pharmaceuticals Inc Compositions comprising double stranded rna and methods for inhibiting expression of the pcsk9 gene
ES2389737T3 (es) 2006-05-11 2012-10-31 Isis Pharmaceuticals, Inc. Análogos de ácidos nucleicos bicíclicos modificados en 5'
EP2052079A2 (en) 2006-07-17 2009-04-29 Sirna Therapeutics Inc. Rna interference mediated inhibition of proprotein convertase subtilisin kexin 9 (pcsk9) gene expression using short interfering nucleic acid (sina)
AU2007296054B2 (en) 2006-09-15 2013-03-28 Enzon Pharmaceuticals, Inc. Hindered ester-based biodegradable linkers for oligonucleotide delivery
WO2008034123A2 (en) 2006-09-15 2008-03-20 Enzon Pharmaceuticals, Inc. Polymeric conjugates containing positively-charged moieties
US20100216864A1 (en) 2006-10-09 2010-08-26 Ellen Marie Straarup RNA Antagonist Compounds for the Modulation of PCSK9
CA2681568C (en) 2006-11-23 2019-01-08 Querdenker Aps Oligonucleotides for modulating target rna activity
US8093222B2 (en) 2006-11-27 2012-01-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
MX2009005527A (es) 2006-11-27 2009-06-08 Isis Pharmaceuticals Inc Metodos para el tratamiento de hipercolesterolemia.
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
DK2149605T3 (da) 2007-03-22 2013-09-30 Santaris Pharma As Korte RNA antagonist forbindelser til modulering af det ønskede 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
CA2688321A1 (en) 2007-05-30 2008-12-11 Isis Pharmaceuticals, Inc. N-substituted-aminomethylene bridged bicyclic nucleic acid analogs
WO2008154401A2 (en) 2007-06-08 2008-12-18 Isis Pharmaceuticals, Inc. Carbocyclic bicyclic nucleic acid analogs
ATE538127T1 (de) 2007-07-05 2012-01-15 Isis Pharmaceuticals Inc 6-disubstituierte bicyclische nukleinsäureanaloga
CN101816010A (zh) 2007-07-19 2010-08-25 数据匙电子有限公司 Rf令牌和接纳器系统与方法
EP2192914A4 (en) 2007-08-20 2014-05-07 Belrose Pharma Inc POLYMER BINDERS CONTAINING PYRIDYL DISULFIDE GROUPS
WO2009043353A2 (en) 2007-10-04 2009-04-09 Santaris Pharma A/S Micromirs
WO2009067647A1 (en) 2007-11-21 2009-05-28 Isis Pharmaceuticals, Inc. Carbocyclic alpha-l-bicyclic nucleic acid analogs
CA2708173C (en) * 2007-12-04 2016-02-02 Alnylam Pharmaceuticals, Inc. Targeting lipids
WO2009090182A1 (en) 2008-01-14 2009-07-23 Santaris Pharma A/S C4'-substituted - dna nucleotide gapmer oligonucleotides
WO2009134487A2 (en) * 2008-01-31 2009-11-05 Alnylam Pharmaceuticals, Inc. Optimized methods for delivery of dsrna targeting the pcsk9 gene
EP2285819B1 (en) 2008-04-04 2013-10-16 Isis Pharmaceuticals, Inc. Oligomeric compounds comprising neutrally linked terminal bicyclic nucleosides
WO2009126933A2 (en) * 2008-04-11 2009-10-15 Alnylam Pharmaceuticals, Inc. Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
US20110224280A1 (en) 2008-04-16 2011-09-15 Niels Fisker Nielsen Pharmaceutical Composition Comprising Anti PCSK9 Oligomers
WO2009148605A2 (en) * 2008-06-04 2009-12-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
JP2011526494A (ja) * 2008-07-02 2011-10-13 エンゾン ファーマシューティカルズ，インコーポレーテッド Ｈｓｐ２７を標的化するｒｎａアンタゴニスト
AT507215B1 (de) 2009-01-14 2010-03-15 Boehler Edelstahl Gmbh & Co Kg Verschleissbeständiger werkstoff
EP2424521A4 (en) * 2009-04-29 2015-03-04 Amarin Pharmaceuticals Ie Ltd PHARMACEUTICAL COMPOSITIONS COMPRISING EPA AND CARDIOVASCULAR AGENT AND METHODS OF USE
ES2555057T3 (es) 2009-06-12 2015-12-28 Roche Innovation Center Copenhagen A/S Nuevos potentes compuestos antisentido anti-ApoB
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
US20130289094A1 (en) 2010-10-29 2013-10-31 Alnylam Pharmaceuticals, Inc. Compositions and Methods for Inhibition of PCSK9 Genes
EP3843313A1 (en) 2010-12-13 2021-06-30 Telefonaktiebolaget LM Ericsson (publ) Exchange of parameters relating to measurement periods
BR112013013434A2 (pt) * 2010-12-17 2016-08-16 Arrowhead Res Corp metade que tem por alvo modulador fármaco cinético em cacho de galactose para sirna
BR122020024394B1 (pt) 2010-12-29 2021-05-11 F. Hoffmann-La Roche Ag conjugado e composição farmacêutica
EP4269584A3 (en) * 2011-08-11 2024-03-27 Ionis 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
SG11201505387PA (en) 2013-01-30 2015-08-28 Hoffmann La Roche Lna oligonucleotide carbohydrate conjugates
CN105378085B (zh) * 2013-05-01 2019-02-15 Ionis制药公司 用于调节hbv和ttr表达的组合物和方法
CA2915316C (en) 2013-06-27 2024-01-02 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

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US11739332B2 (en) 2023-08-29
US20220025376A1 (en) 2022-01-27
HRP20200163T1 (hr) 2020-08-07
EP3013959A1 (en) 2016-05-04
HUE048738T2 (hu) 2020-08-28
US10385342B2 (en) 2019-08-20
KR20160027042A (ko) 2016-03-09
JP6672245B2 (ja) 2020-03-25
US20160138025A1 (en) 2016-05-19
KR102226110B1 (ko) 2021-03-10
SI3013959T1 (sl) 2020-04-30
ES2770667T3 (es) 2020-07-02
IL242875B (en) 2020-02-27
EA201592215A1 (ru) 2016-05-31
MX2015017601A (es) 2016-04-07
JP2016523094A (ja) 2016-08-08
MX2019006284A (es) 2019-08-29
PE20160158A1 (es) 2016-03-18
BR112015032432B1 (pt) 2023-02-07
US10443058B2 (en) 2019-10-15
RS59986B1 (sr) 2020-03-31
US20240084307A1 (en) 2024-03-14
HK1221740A1 (zh) 2017-06-09
WO2014207232A1 (en) 2014-12-31
SG10201908122XA (en) 2019-10-30
US20200248186A1 (en) 2020-08-06
WO2014207232A4 (en) 2015-03-19
CN112263682A (zh) 2021-01-26
US20180312846A1 (en) 2018-11-01
KR20180136006A (ko) 2018-12-21

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