ES2724853T3 - Conjugados de oligonucleótidos - Google Patents

Conjugados de oligonucleótidos Download PDF

Info

Publication number
ES2724853T3
ES2724853T3 ES13791808T ES13791808T ES2724853T3 ES 2724853 T3 ES2724853 T3 ES 2724853T3 ES 13791808 T ES13791808 T ES 13791808T ES 13791808 T ES13791808 T ES 13791808T ES 2724853 T3 ES2724853 T3 ES 2724853T3
Authority
ES
Spain
Prior art keywords
region
group
oligomer
lna
conjugate
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
ES13791808T
Other languages
English (en)
Spanish (es)
Inventor
Nanna Albæk
Henrik Frydenlund Hansen
Susanne Kammler
Jacob Ravn
HENRIK øRUM
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Roche Innovation Center Copenhagen AS
Original Assignee
Roche Innovation Center 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
Application filed by Roche Innovation Center Copenhagen AS filed Critical Roche Innovation Center Copenhagen AS
Application granted granted Critical
Publication of ES2724853T3 publication Critical patent/ES2724853T3/es
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113Non-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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/04Anorexiants; Antiobesity agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/06Antihyperlipidemics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06Antianaemics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs 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
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/111General methods applicable to biologically active non-coding nucleic acids
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/11Antisense
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/31Chemical structure of the backbone
    • C12N2310/314Phosphoramidates
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/31Chemical structure of the backbone
    • C12N2310/315Phosphorothioates
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/32Chemical structure of the sugar
    • C12N2310/323Chemical structure of the sugar modified ring structure
    • C12N2310/3231Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/34Spatial arrangement of the modifications
    • C12N2310/341Gapmers, i.e. of the type ===---===
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/35Nature of the modification
    • C12N2310/351Conjugate
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/35Nature of the modification
    • C12N2310/351Conjugate
    • C12N2310/3515Lipophilic moiety, e.g. cholesterol
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/35Nature of the modification
    • C12N2310/351Conjugate
    • C12N2310/3517Marker; Tag
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00Applications; Uses
    • C12N2320/30Special therapeutic applications
    • C12N2320/32Special delivery means, e.g. tissue-specific
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2330/00Production
    • C12N2330/30Production chemically synthesised

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Obesity (AREA)
  • Virology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Emergency Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
ES13791808T 2012-11-15 2013-11-14 Conjugados de oligonucleótidos Active ES2724853T3 (es)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
EP12192773 2012-11-15
EP13153296 2013-01-30
EP13157237 2013-02-28
EP13174092 2013-06-27
PCT/EP2013/073858 WO2014076195A1 (en) 2012-11-15 2013-11-14 Oligonucleotide conjugates

Publications (1)

Publication Number Publication Date
ES2724853T3 true ES2724853T3 (es) 2019-09-16

Family

ID=49584733

Family Applications (1)

Application Number Title Priority Date Filing Date
ES13791808T Active ES2724853T3 (es) 2012-11-15 2013-11-14 Conjugados de oligonucleótidos

Country Status (22)

Country Link
US (4) US20150291958A1 (enExample)
EP (3) EP2920304B1 (enExample)
JP (3) JP6452614B2 (enExample)
KR (2) KR20150083920A (enExample)
CN (3) CN117126846A (enExample)
AU (2) AU2013346767B2 (enExample)
BR (2) BR112015010116A2 (enExample)
CA (2) CA2889596C (enExample)
DK (2) DK2920304T3 (enExample)
ES (1) ES2724853T3 (enExample)
HK (2) HK1210213A1 (enExample)
HR (1) HRP20190826T1 (enExample)
IL (2) IL238448B (enExample)
MX (2) MX2015005792A (enExample)
MY (1) MY173826A (enExample)
NZ (1) NZ708171A (enExample)
PL (1) PL2920304T3 (enExample)
RU (3) RU2015119411A (enExample)
SG (2) SG10201804331TA (enExample)
SI (1) SI2920304T1 (enExample)
WO (2) WO2014076196A1 (enExample)
ZA (1) ZA201503375B (enExample)

Families Citing this family (297)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE60329220D1 (de) 2002-11-18 2009-10-22 Santaris Pharma As Antisense-entwurf
US8334372B2 (en) 2008-10-15 2012-12-18 Isis Pharmaceuticals, Inc. Modulation of factor 11 expression
WO2010064146A2 (en) 2008-12-02 2010-06-10 Chiralgen, Ltd. Method for the synthesis of phosphorus atom modified nucleic acids
CA2767253A1 (en) 2009-07-06 2011-01-13 Ontorii, Inc. Novel nucleic acid prodrugs and methods of use thereof
WO2012039448A1 (ja) 2010-09-24 2012-03-29 株式会社キラルジェン 不斉補助基
JP6126009B2 (ja) 2010-11-17 2017-05-10 アイオーニス ファーマシューティカルズ, インコーポレーテッドIonis Pharmaceuticals,Inc. α−シヌクレイン発現の調節
CN103796657B (zh) 2011-07-19 2017-07-11 波涛生命科学有限公司 合成官能化核酸的方法
EP3533873A1 (en) 2011-09-14 2019-09-04 Translate Bio MA, Inc. Multimeric oligonucleotide compounds
CA2873797A1 (en) 2012-05-16 2013-11-21 Rana Therapeutics Inc. Compositions and methods for modulating utrn expression
BR112014028631A2 (pt) 2012-05-16 2017-10-17 Rana Therapeutics Inc composições e métodos para modulação da expressão da família de genes da hemoglobina
US10837014B2 (en) 2012-05-16 2020-11-17 Translate Bio Ma, Inc. Compositions and methods for modulating SMN gene family expression
DK2850186T3 (en) 2012-05-16 2019-04-08 Translate Bio Ma Inc COMPOSITIONS AND PROCEDURES FOR MODULATING SMN GENFAMILY EXPRESSION
CA2873779A1 (en) 2012-05-16 2013-11-21 Rana Therapeutics Inc. Compositions and methods for modulating mecp2 expression
AU2013262699A1 (en) 2012-05-16 2015-01-22 Rana Therapeutics, Inc. Compositions and methods for modulating ATP2A2 expression
JP6453212B2 (ja) 2012-07-13 2019-01-16 ウェイブ ライフ サイエンシズ リミテッドWave Life Sciences Ltd. キラル制御
WO2014010250A1 (en) 2012-07-13 2014-01-16 Chiralgen, Ltd. Asymmetric auxiliary group
JP2015529469A (ja) 2012-09-14 2015-10-08 ラナ セラピューティクス インコーポレイテッド 多量体オリゴヌクレオチド化合物
WO2014076196A1 (en) 2012-11-15 2014-05-22 Santaris Pharma A/S Anti apob antisense conjugate compounds
CA2893801A1 (en) * 2013-01-30 2014-08-07 F. Hoffmann-La Roche Ag Lna oligonucleotide carbohydrate conjugates
RU2670614C9 (ru) 2013-05-01 2018-11-23 Ионис Фармасьютикалз, Инк. Композиции и способы модулирования экспрессии hbv и ttr
WO2014179445A1 (en) 2013-05-01 2014-11-06 Regulus Therapeutics Inc. Compounds and methods for enhanced cellular uptake
US9309513B2 (en) 2013-05-01 2016-04-12 Regulus Therapeutics Inc. MicroRNA compounds and methods for modulating miR-122
WO2015042447A1 (en) 2013-09-20 2015-03-26 Isis Pharmaceuticals, Inc. Targeted therapeutic nucleosides and their use
US11162096B2 (en) 2013-10-14 2021-11-02 Ionis Pharmaceuticals, Inc Methods for modulating expression of C9ORF72 antisense transcript
US9994846B2 (en) 2013-10-25 2018-06-12 Regulus Therapeutics Inc. MicroRNA compounds and methods for modulating miR-21 activity
WO2015108047A1 (ja) 2014-01-15 2015-07-23 株式会社新日本科学 免疫誘導活性を有するキラル核酸アジュバンド及び免疫誘導活性剤
JPWO2015108048A1 (ja) 2014-01-15 2017-03-23 株式会社新日本科学 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤
KR20230152178A (ko) 2014-01-16 2023-11-02 웨이브 라이프 사이언시스 리미티드 키랄 디자인
US10358643B2 (en) 2014-01-30 2019-07-23 Hoffmann-La Roche, Inc. Poly oligomer compound with biocleavable conjugates
ES2890677T3 (es) 2014-03-19 2022-01-21 Ionis Pharmaceuticals Inc Composiciones para modular la expresión de ataxina 2
WO2015143245A1 (en) 2014-03-19 2015-09-24 Isis Pharmaceuticals, Inc. Methods for modulating ataxin 2 expression
NZ724100A (en) 2014-04-01 2022-12-23 Biogen Ma Inc Compositions for modulating sod-1 expression
JP6667453B2 (ja) 2014-05-01 2020-03-18 アイオーニス ファーマシューティカルズ, インコーポレーテッドIonis Pharmaceuticals,Inc. 成長ホルモン受容体発現を調節するための組成物及び方法
US9382540B2 (en) 2014-05-01 2016-07-05 Isis Pharmaceuticals, Inc Compositions and methods for modulating angiopoietin-like 3 expression
CA2943894A1 (en) 2014-05-01 2015-11-05 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating complement factor b expression
ES2849600T3 (es) 2014-05-01 2021-08-19 Ionis Pharmaceuticals Inc Conjugados de oligonucleótidos antisentido modificados y su uso para modular la expresión de PKK
GB201408623D0 (en) 2014-05-15 2014-07-02 Santaris Pharma As Oligomers and oligomer conjugates
US9487783B2 (en) 2014-08-07 2016-11-08 Regulus Therapeutics Inc. Targeting microRNAs for metabolic disorders
BR112017004056A2 (pt) 2014-09-12 2017-12-05 Biogen Ma Inc composições e métodos para detecção da proteína smn em um indivíduo e tratamento de um indivíduo
RU2017114156A (ru) 2014-10-10 2018-11-15 Ф. Хоффманн-Ля Рош Аг N-ацетилгалактозаминовые (galnac) фосфорамитиды, их конъюгаты с нуклеиновыми кислотами и их применение
BR112017009504A2 (pt) * 2014-11-10 2018-02-06 Glaxosmithkline Ip No 2 Ltd métodos para tratar e para curar uma infecção por hcv, e, composição farmacêutica.
CN107208092B (zh) 2014-12-16 2021-09-10 罗氏创新中心哥本哈根有限公司 手性毒性筛选方法
EP3234141A4 (en) * 2014-12-18 2018-06-20 Alnylam Pharmaceuticals, Inc. Reversir tm compounds
WO2016112132A1 (en) 2015-01-06 2016-07-14 Ionis Pharmaceuticals, Inc. Compositions for modulating expression of c9orf72 antisense transcript
US10538763B2 (en) 2015-01-16 2020-01-21 Ionis Pharmaceuticals, Inc. Compounds and methods for modulation of DUX4
WO2016130943A1 (en) * 2015-02-13 2016-08-18 Rana Therapeutics, Inc. Hybrid oligonucleotides and uses thereof
US11129844B2 (en) 2015-03-03 2021-09-28 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating MECP2 expression
WO2016161378A1 (en) 2015-04-03 2016-10-06 University Of Massachusetts Oligonucleotide compounds for treatment of preeclampsia and other angiogenic disorders
EP3929293A3 (en) 2015-04-03 2022-03-16 University Of Massachusetts Fully stabilized asymmetric sirna
EP3766973A1 (en) 2015-04-03 2021-01-20 University Of Massachusetts Oligonucleotide compounds for targeting huntingtin mrna
US10407678B2 (en) 2015-04-16 2019-09-10 Ionis Pharmaceuticals, Inc. Compositions for modulating expression of C9ORF72 antisense transcript
US10633653B2 (en) 2015-08-14 2020-04-28 University Of Massachusetts Bioactive conjugates for oligonucleotide delivery
JP6835826B2 (ja) * 2015-08-24 2021-02-24 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 Lna−gプロセス
EP3353305A4 (en) * 2015-09-25 2019-09-18 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
CN108136041B (zh) 2015-10-02 2022-12-30 罗氏创新中心哥本哈根有限公司 寡核苷酸缀合方法
CN108137492B (zh) 2015-10-09 2021-12-21 波涛生命科学有限公司 寡核苷酸组合物及其方法
WO2017068087A1 (en) 2015-10-22 2017-04-27 Roche Innovation Center Copenhagen A/S Oligonucleotide detection method
CN113952353A (zh) 2015-11-06 2022-01-21 Ionis制药公司 调节载脂蛋白(a)表达
ES2989704T3 (es) * 2015-11-06 2024-11-27 Ionis Pharmaceuticals Inc Compuestos antisentido conjugados para uso terapéutico
PE20181157A1 (es) 2015-11-12 2018-07-19 Hoffmann La Roche Oligonucleotidos para inducir la expresion paterna de ube3a
EP3389670A4 (en) 2015-12-04 2020-01-08 Ionis Pharmaceuticals, Inc. METHODS OF TREATING BREAST CANCER
US20190002887A1 (en) 2015-12-31 2019-01-03 Ionis Pharmaceuticals, Inc. Methods for reducing ataxin-2 expression
WO2017120365A1 (en) 2016-01-05 2017-07-13 Ionis Pharmaceuticals, Inc. Methods for reducing lrrk2 expression
CA3012967A1 (en) * 2016-01-29 2017-08-03 Kyowa Hakko Kirin Co., Ltd. Nucleic acid conjugate
EP3408391A4 (en) 2016-01-31 2019-08-28 University of Massachusetts BRANCHED OLIGONUCLEOTIDES
US10246709B2 (en) 2016-03-07 2019-04-02 Arrowhead Pharmaceuticals, Inc. Targeting ligands for therapeutic compounds
PE20230157A1 (es) 2016-03-14 2023-02-01 Hoffmann La Roche Oligonucleotidos para reducir la expresion de pd-l1
WO2017161168A1 (en) 2016-03-16 2017-09-21 Ionis Pharmaceuticals, Inc. Modulation of dyrk1b expression
AU2017234678A1 (en) 2016-03-16 2018-08-16 Ionis Pharmaceuticals, Inc. Methods of modulating KEAP1
MA45328A (fr) 2016-04-01 2019-02-06 Avidity Biosciences Llc Compositions acide nucléique-polypeptide et utilisations de celles-ci
EP3228326A1 (en) * 2016-04-05 2017-10-11 Silence Therapeutics GmbH Nucleic acid linked to a trivalent glycoconjugate
EP3440206B1 (en) * 2016-04-08 2020-10-28 Translate Bio, Inc. Multimeric coding nucleic acid and uses thereof
WO2017178656A1 (en) 2016-04-14 2017-10-19 Roche Innovation Center Copenhagen A/S TRITYL-MONO-GalNAc COMPOUNDS AND THEIR USE
AU2017260003B2 (en) * 2016-05-06 2019-12-05 Astrazeneca Ab GLP-1 receptor ligand moiety conjugated oligonucleotides and uses thereof
US11236339B2 (en) 2016-06-17 2022-02-01 Ionis Pharmaceuticals, Inc. Modulation of GYS1 expression
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
JP7074345B2 (ja) 2016-06-22 2022-05-24 プロキューアール セラピューティクス ツー ベスローテン フェンノートシャップ 一本鎖rna編集オリゴヌクレオチド
BR112018077321A2 (pt) 2016-07-01 2019-04-24 F. Hoffmann-La Roche Ag oligonucleotídeos anti-sentido para modular a expressão de htra1
EP3496758A4 (en) 2016-08-12 2020-11-11 University of Massachusetts CONJUGATE OLIGONUCLEOTIDES
CA3035293A1 (en) 2016-09-01 2018-03-08 Proqr Therapeutics Ii B.V. Chemically modified single-stranded rna-editing oligonucleotides
CA3011668A1 (en) 2016-09-02 2018-03-08 Arrowhead Pharmaceuticals, Inc. Targeting ligands
WO2018067900A1 (en) 2016-10-06 2018-04-12 Ionis Pharmaceuticals, Inc. Method of conjugating oligomeric compounds
JOP20190104A1 (ar) 2016-11-10 2019-05-07 Ionis Pharmaceuticals Inc مركبات وطرق لتقليل التعبير عن atxn3
US11033570B2 (en) 2016-12-02 2021-06-15 Cold Spring Harbor Laboratory Modulation of Lnc05 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
US20190345495A1 (en) 2017-01-13 2019-11-14 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating nfkb2 expression
US20190338286A1 (en) 2017-01-13 2019-11-07 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating rel expression
US20190345496A1 (en) 2017-01-13 2019-11-14 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating relb expression
JP7048574B2 (ja) 2017-03-10 2022-04-05 国立研究開発法人国立成育医療研究センター アンチセンスオリゴヌクレオチドおよび糖原病Ia型予防または治療用組成物
WO2018165541A1 (en) 2017-03-10 2018-09-13 The Board Of Regents Of The University Of Texas System Treatment of fuchs' endothelial corneal dystrophy
MX2019012280A (es) * 2017-04-11 2020-01-23 Arbutus Biopharma Corp Composiciones dirigidas.
WO2018215049A1 (en) * 2017-05-23 2018-11-29 F. Hoffmann-La Roche Ag Process for galnac oligonucleotide conjugates
EP3633036A4 (en) 2017-05-26 2021-03-17 National Cerebral and Cardiovascular Center NUCLEIC ACID TARGETING ANTI-SENSES PCSK9
US20190055564A1 (en) 2017-06-01 2019-02-21 F. Hoffmann-La Roche Ag Antisense oligonucleotides for modulating htra1 expression
EP3630788A4 (en) * 2017-06-02 2021-04-28 Wave Life Sciences Ltd. OLIGONUCLEOTIDE COMPOSITIONS AND METHODS FOR THEIR USE
US11401519B2 (en) 2017-06-07 2022-08-02 University Of Massachusetts Anti-ADAM33 oligonucleotides and related methods
CA3064590A1 (en) 2017-06-23 2018-12-27 University Of Massachusetts Two-tailed self-delivering sirna and related methods
US20190048049A1 (en) 2017-08-10 2019-02-14 Cerenis Therapeutics Holding Sa Cargomers
WO2019030313A2 (en) 2017-08-11 2019-02-14 Roche Innovation Center Copenhagen A/S OLIGONUCLEOTIDES FOR MODULATION OF UBE3C EXPRESSION
EP3668981A4 (en) 2017-08-17 2021-05-26 Alnylam Pharmaceuticals, Inc. ADJUSTABLE REVERSIRTM COMPOUNDS
CA3071033A1 (en) 2017-08-18 2019-02-21 Ionis Pharmaceuticals, Inc. Modulation of the notch signaling pathway for treatment of respiratory disorders
WO2019038228A1 (en) 2017-08-22 2019-02-28 Roche Innovation Center Copenhagen A/S OLIGONUCLEOTIDES FOR MODULATION OF TOM1 EXPRESSION
WO2019051173A1 (en) 2017-09-08 2019-03-14 Ionis Pharmaceuticals, Inc. MODULATORS OF SMAD7 EXPRESSION
EP3694530A4 (en) * 2017-10-12 2021-06-30 Wave Life Sciences Ltd. COMPOSITIONS OF OLIGONUCLEOTIDES AND RELATED PROCESSES
EP3694995A1 (en) 2017-10-13 2020-08-19 Roche Innovation Center Copenhagen A/S Methods for identifying improved stereodefined phosphorothioate oligonucleotide variants of antisense oligonucleotides utilising sub-libraries of partially stereodefined oligonucleotides
KR102585898B1 (ko) 2017-10-16 2023-10-10 에프. 호프만-라 로슈 아게 B형 간염 감염을 치료하기 위한 PAPD5 및 PAPD7 mRNA의 감소용 핵산 분자
CA3081758A1 (en) 2017-11-06 2019-05-09 Nitto Denko Corporation Fusogenic compounds for delivery of biologically active molecules
TWI809004B (zh) 2017-11-09 2023-07-21 美商Ionis製藥公司 用於降低snca表現之化合物及方法
US12083142B2 (en) 2017-12-01 2024-09-10 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, composition and conjugate comprising the same, and preparation method and use thereof
WO2019105435A1 (zh) 2017-12-01 2019-06-06 苏州瑞博生物技术有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
WO2019105419A1 (zh) 2017-12-01 2019-06-06 苏州瑞博生物技术有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
JP7261494B2 (ja) 2017-12-01 2023-04-20 スーチョウ リボ ライフ サイエンス カンパニー、リミテッド 核酸、当該核酸を含む組成物及び複合体ならびに調製方法と使用
KR102756073B1 (ko) 2017-12-01 2025-01-20 쑤저우 리보 라이프 사이언스 컴퍼니, 리미티드 이중-가닥 올리고뉴클레오티드, 조성물 및 이중-가닥 올리고뉴클레오티드를 포함하는 접합체, 그의 제조 방법 및 그의 용도
IL319835A (en) 2017-12-06 2025-05-01 Avidity Biosciences Inc Compositions and methods for treating muscular dystrophy and myotonic dystrophy
JP2021505175A (ja) 2017-12-11 2021-02-18 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 Fndc3bの発現を調節するためのオリゴヌクレオチド
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
WO2019126641A2 (en) 2017-12-21 2019-06-27 Ionis Pharmaceuticals, Inc. Modulation of frataxin expression
EP3728591B1 (en) 2017-12-22 2025-07-23 Roche Innovation Center Copenhagen A/S Gapmer oligonucleotides comprising a phosphorodithioate internucleoside linkage
JP2021508327A (ja) 2017-12-22 2021-03-04 ロシュ イノベーション センター コペンハーゲン エーエス 新規のチオホスホラミダイト
AU2018386524A1 (en) 2017-12-22 2020-07-02 Roche Innovation Center Copenhagen A/S Oligonucleotides comprising a phosphorodithioate internucleoside linkage
HRP20250408T1 (hr) 2017-12-29 2025-06-06 Suzhou Ribo Life Science Co., Ltd. Kojugati i njihova priprema i uporaba
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
JP7547201B2 (ja) 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 アルファ-シヌクレインを標的とするアンチセンスオリゴヌクレオチドおよびその使用
PE20201501A1 (es) 2018-01-12 2020-12-29 Bristol Myers Squibb Co Oligonucleotidos antisentido que actuan sobre alfa-sinucleina, y usos de estos
PE20210172A1 (es) 2018-01-12 2021-01-29 Roche Innovation Ct Copenhagen As Oligonucleotidos antisentido para alfa-sinucleina y usos de los mismos
US20210095275A1 (en) 2018-01-12 2021-04-01 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating gsk3b expression
CN111902537A (zh) 2018-01-15 2020-11-06 Ionis制药公司 Dnm2表达的调节剂
WO2019141656A1 (en) 2018-01-17 2019-07-25 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating erc1 expression
JP2021511029A (ja) 2018-01-18 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 Srebp1を標的とするアンチセンス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
JP7383618B2 (ja) * 2018-01-26 2023-11-20 エフ. ホフマン-ラ ロシュ アーゲー 放射標識オリゴヌクレオチドおよびその調製のための方法
AU2019219194A1 (en) 2018-02-09 2020-08-06 Genentech, Inc. Oligonucleotides for modulating TMEM106B expression
JP7500426B2 (ja) 2018-02-21 2024-06-17 ブリストル-マイヤーズ スクイブ カンパニー Camk2dアンチセンスオリゴヌクレオチドおよびその使用
TWI840345B (zh) 2018-03-02 2024-05-01 美商Ionis製藥公司 Irf4表現之調節劑
EP3759127A4 (en) 2018-03-02 2022-03-30 Ionis Pharmaceuticals, Inc. COMPOUNDS AND METHODS FOR MODULATING AMYLOID BETA PRECURSOR PROTEIN
KR20210130854A (ko) 2018-03-09 2021-11-01 다이이찌 산쿄 가부시키가이샤 당원병 Ia형 치료약
EP3768694A4 (en) 2018-03-22 2021-12-29 Ionis Pharmaceuticals, Inc. Methods for modulating fmr1 expression
EP3775208A1 (en) 2018-04-05 2021-02-17 F. Hoffmann-La Roche AG Use of fubp1 inhibitors for treating hepatitis b virus infection
EP3775204A4 (en) 2018-04-11 2021-12-29 Ionis Pharmaceuticals, Inc. Modulators of ezh2 expression
CN112105745A (zh) 2018-05-07 2020-12-18 罗氏创新中心哥本哈根有限公司 用于寡核苷酸治疗剂的大规模平行发现方法
US20210371860A1 (en) 2018-05-08 2021-12-02 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating myh7 expression
JP7279081B2 (ja) 2018-05-08 2023-05-22 レグルス セラピューティクス インコーポレイテッド Mir-122を調節するためのマイクロrna化合物及び方法
CA3098136A1 (en) 2018-05-09 2019-11-14 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing fxi expression
JOP20200283A1 (ar) 2018-05-09 2020-11-08 Ionis Pharmaceuticals Inc مركبات وطرق لتقليل التعبير الوراثي عن atxn3
SG11202010841QA (en) * 2018-05-11 2020-11-27 Alpha Anomeric Sas Oligonucleotides conjugates comprising 7'-5'-alpha-anomeric-bicyclic sugar nucleosides
TWI844541B (zh) 2018-05-11 2024-06-11 新加坡商波濤生命科學有限公司 寡核苷酸組成物及其使用方法
GB201808146D0 (en) 2018-05-18 2018-07-11 Proqr Therapeutics Ii Bv Stereospecific Linkages in RNA Editing Oligonucleotides
WO2019233922A1 (en) 2018-06-05 2019-12-12 F. Hoffmann-La Roche Ag Oligonucleotides for modulating atxn2 expression
US11833168B2 (en) 2018-06-14 2023-12-05 Ionis Pharmaceuticals, Inc. Compounds and methods for increasing STMN2 expression
TWI833770B (zh) 2018-06-27 2024-03-01 美商Ionis製藥公司 用於減少 lrrk2 表現之化合物及方法
WO2020007772A1 (en) 2018-07-02 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting gbp-1
WO2020007700A1 (en) 2018-07-02 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting spi1
WO2020007702A1 (en) 2018-07-02 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting bcl2l11
AU2019297391B2 (en) 2018-07-03 2023-01-12 F. Hoffmann-La Roche Ag Oligonucleotides for modulating Tau expression
WO2020007889A1 (en) 2018-07-05 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting stat1
WO2020007826A1 (en) 2018-07-05 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting mbtps1
WO2020011653A1 (en) 2018-07-09 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting kynu
WO2020011743A1 (en) 2018-07-09 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting mafb
WO2020011869A2 (en) 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting tlr2
WO2020011745A2 (en) 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting cers6
WO2020011744A2 (en) 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting cers5
MX2021000404A (es) 2018-07-13 2021-03-25 Hoffmann La Roche Oligonucleotidos para modular la expresion de rtel1.
MX2021000922A (es) 2018-07-25 2021-03-31 Ionis Pharmaceuticals Inc Compuestos y metodos para reducir la expresion de la atxn2.
EP4122943B1 (en) 2018-07-31 2024-05-29 Roche Innovation Center Copenhagen A/S Oligonucleotides comprising a phosphorotrithioate internucleoside linkage
AU2019313443A1 (en) 2018-07-31 2020-11-26 Roche Innovation Center Copenhagen A/S Oligonucleotides comprising a phosphorotrithioate internucleoside linkage
WO2020033899A1 (en) 2018-08-10 2020-02-13 University Of Massachusetts Modified oligonucleotides targeting snps
US11918600B2 (en) 2018-08-21 2024-03-05 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, pharmaceutical composition and conjugate containing nucleic acid, and use thereof
US11279930B2 (en) 2018-08-23 2022-03-22 University Of Massachusetts O-methyl rich fully stabilized oligonucleotides
WO2020038976A1 (en) 2018-08-23 2020-02-27 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting usp8
EP3841220A1 (en) 2018-08-23 2021-06-30 Roche Innovation Center Copenhagen A/S Microrna-134 biomarker
WO2020038973A1 (en) 2018-08-23 2020-02-27 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting sptlc1
WO2020038971A1 (en) 2018-08-23 2020-02-27 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting vcan
US20220160870A1 (en) 2018-08-28 2022-05-26 Roche Innovation Center Copenhagen A/S Neoantigen engineering using splice modulating compounds
EP3620519A1 (en) 2018-09-04 2020-03-11 F. Hoffmann-La Roche AG Use of isolated milk extracellular vesicles for delivering oligonucleotides orally
WO2020051398A1 (en) * 2018-09-06 2020-03-12 Aptamir Therapeutics, Inc. Metabolic benefits of short mir-22 mirna antagomir therapies
CN111655297A (zh) 2018-09-30 2020-09-11 苏州瑞博生物技术有限公司 一种siRNA缀合物及其制备方法和用途
EP3873920A1 (en) 2018-11-01 2021-09-08 F. Hoffmann-La Roche AG Antisense oligonucleotides targeting tia1
TW202028222A (zh) 2018-11-14 2020-08-01 美商Ionis製藥公司 Foxp3表現之調節劑
CA3119456A1 (en) 2018-11-15 2020-05-22 Ionis Pharmaceuticals, Inc. Modulators of irf5 expression
US12281305B2 (en) 2018-11-21 2025-04-22 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing prion expression
WO2020117706A1 (en) 2018-12-03 2020-06-11 Triplet Therapeutics, Inc. Methods for the treatment of trinucleotide repeat expansion disorders associated with mlh3 activity
CA3123617A1 (en) 2018-12-20 2020-06-25 Praxis Precision Medicines, Inc. Compositions and methods for the treatment of kcnt1 related disorders
EP3898975A2 (en) 2018-12-21 2021-10-27 Boehringer Ingelheim International GmbH Antisense oligonucleotides targeting card9
WO2020150636A1 (en) * 2019-01-18 2020-07-23 University Of Massachusetts Dynamic pharmacokinetic-modifying anchors
WO2020152303A1 (en) 2019-01-25 2020-07-30 F. Hoffmann-La Roche Ag Lipid vesicle for oral drug delivery
MX2021008918A (es) 2019-01-31 2021-08-24 Ionis Pharmaceuticals Inc Moduladores de expresion yap1.
TW202045521A (zh) 2019-02-20 2020-12-16 丹麥商羅氏創新中心哥本哈根有限公司 新穎亞磷醯胺化物
JP2022521510A (ja) 2019-02-20 2022-04-08 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 ホスホノアセテートギャップマー型オリゴヌクレオチド
WO2020173845A1 (en) 2019-02-26 2020-09-03 Roche Innovation Center Copenhagen A/S Oligonucleotide formulation method
SG11202108450SA (en) 2019-02-27 2021-09-29 Ionis Pharmaceuticals Inc Modulators of malat1 expression
WO2020178258A1 (en) * 2019-03-05 2020-09-10 F. Hoffmann-La Roche Ag Intracellular targeting of molecules
CN117431244A (zh) 2019-03-29 2024-01-23 Ionis制药公司 用于调节ube3a-ats的化合物和方法
EP3947678A1 (en) 2019-04-02 2022-02-09 ProQR Therapeutics II B.V. Antisense oligonucleotides for immunotherapy
SG11202110745VA (en) 2019-04-03 2021-10-28 Bristol Myers Squibb Co Angptl2 antisense oligonucleotides and uses thereof
US11286485B2 (en) 2019-04-04 2022-03-29 Hoffmann-La Roche Inc. Oligonucleotides for modulating ATXN2 expression
EP3947677A1 (en) 2019-04-04 2022-02-09 F. Hoffmann-La Roche AG Oligonucleotides for modulating atxn2 expression
WO2020243490A2 (en) 2019-05-31 2020-12-03 Aligos Therapeutics, Inc. Modified gapmer oligonucleotides and methods of use
EP3980539A1 (en) 2019-06-06 2022-04-13 F. Hoffmann-La Roche AG Antisense oligonucleotides targeting atxn3
HRP20251033T1 (hr) 2019-07-26 2025-10-24 Ionis Pharmaceuticals, Inc. Spojevi i postupci za moduliranje gfap
CN114466929A (zh) * 2019-07-30 2022-05-10 Mpeg La有限责任公司 具有增强的生物活性的多聚体寡核苷酸的皮下递送
US12024706B2 (en) 2019-08-09 2024-07-02 University Of Massachusetts Modified oligonucleotides targeting SNPs
CA3150715A1 (en) 2019-09-10 2021-03-18 Makoto Koizumi Conjugate of galnac-oligonucleotide for delivery to liver and manufacturing method thereof
US12365894B2 (en) 2019-09-16 2025-07-22 University Of Massachusetts Branched lipid conjugates of siRNA for specific tissue delivery
BR112022006476A2 (pt) * 2019-10-02 2022-07-05 Sirnaomics Inc Oligonucleotídeos com análogos de nucleosídeos
WO2021122921A1 (en) 2019-12-19 2021-06-24 F. Hoffmann-La Roche Ag Use of cops3 inhibitors for treating hepatitis b virus infection
WO2021122910A1 (en) 2019-12-19 2021-06-24 F. Hoffmann-La Roche Ag Use of sbds inhibitors for treating hepatitis b virus infection
WO2021122869A1 (en) 2019-12-19 2021-06-24 F. Hoffmann-La Roche Ag Use of scamp3 inhibitors for treating hepatitis b virus infection
WO2021122735A1 (en) 2019-12-19 2021-06-24 F. Hoffmann-La Roche Ag Use of sept9 inhibitors for treating hepatitis b virus infection
WO2021122993A1 (en) 2019-12-19 2021-06-24 F. Hoffmann-La Roche Ag Use of saraf inhibitors for treating hepatitis b virus infection
EP4058032A4 (en) * 2019-12-19 2024-01-10 Entrada Therapeutics, Inc. Compositions for delivery of antisense compounds
CN114829603A (zh) 2019-12-20 2022-07-29 豪夫迈·罗氏有限公司 用于抑制scn9a表达的增强寡核苷酸
MX2022007909A (es) 2019-12-24 2022-07-21 Hoffmann La Roche Combinacion farmaceutica de agentes antivirales que actuan sobre hbv y/o un inmunomodulador para el tratamiento de hbv.
WO2021130266A1 (en) 2019-12-24 2021-07-01 F. Hoffmann-La Roche Ag Pharmaceutical combination of a therapeutic oligonucleotide targeting hbv and a tlr7 agonist for treatment of hbv
US20230090446A1 (en) 2020-01-28 2023-03-23 Universite De Strasbourg Antisense oligonucleotide targeting linc00518 for treating melanoma
WO2021158810A1 (en) 2020-02-05 2021-08-12 Bristol-Myers Squibb Company Oligonucleotides for splice modulation of camk2d
AR121446A1 (es) 2020-02-28 2022-06-08 Ionis Pharmaceuticals Inc Compuestos y métodos para modular smn2
JP2023516142A (ja) 2020-02-28 2023-04-18 エフ・ホフマン-ラ・ロシュ・アクチェンゲゼルシャフト Cd73エクソン7スプライシングを調節するためのオリゴヌクレオチド
MX2022010980A (es) 2020-03-04 2022-12-02 Verve Therapeutics Inc Composiciones y metodos para el suministro de arn dirigido.
IL296387B2 (en) 2020-03-19 2024-08-01 Avidity Biosciences Inc Preparations and methods for the treatment of facial, back and arm muscle atrophy
CN115916262A (zh) * 2020-04-21 2023-04-04 旗舰创业股份有限公司 双官能分子及其使用方法
WO2021222768A2 (en) 2020-05-01 2021-11-04 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating atxn1
WO2021231204A1 (en) 2020-05-11 2021-11-18 Genentech, Inc. Complement component 4 inhibitors for treating neurological diseases, and related compositons, systems and methods of using same
JP2023527684A (ja) 2020-05-11 2023-06-30 ジェネンテック, インコーポレイテッド 神経疾患を治療するための補体成分c1s阻害剤、並びにそれを使用する関連組成物、システム及び方法
WO2021231210A1 (en) 2020-05-11 2021-11-18 Genentech, Inc. Complement component c1r inhibitors for treating a neurological disease, and related compositions, systems and methods of using same
TW202208628A (zh) 2020-05-13 2022-03-01 瑞士商赫孚孟拉羅股份公司 靶向顆粒蛋白前體之寡核苷酸促效劑
EP4150089A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of retinoschisin 1 (rs1)
EP4150088A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of argininosuccinate synthetase (ass1)
EP4150086A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of leucine rich repeat kinase 2 (lrrk2)
WO2021231685A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of transmembrane channel-like protein 1 (tmc1)
EP4150078A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of argininosuccinate lyase (asl)
EP4150090A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of otoferlin (otof)
WO2021231680A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of methyl-cpg binding protein 2 (mecp2)
EP4150087A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of gap junction protein beta 2 (gjb2)
JP2023526096A (ja) 2020-05-22 2023-06-20 エフ. ホフマン-ラ ロシュ アーゲー Card9のスプライス調節のためのオリゴヌクレオチド
US11408000B2 (en) 2020-06-03 2022-08-09 Triplet Therapeutics, Inc. Oligonucleotides for the treatment of nucleotide repeat expansion disorders associated with MSH3 activity
CN115702243A (zh) 2020-06-09 2023-02-14 罗氏创新中心哥本哈根有限公司 用于治疗性多核苷酸的鸟苷类似物
AR122731A1 (es) 2020-06-26 2022-10-05 Hoffmann La Roche Oligonucleótidos mejorados para modular la expresión de fubp1
BR112022024206A2 (pt) 2020-06-29 2023-01-03 Ionis Pharmaceuticals Inc Compostos e métodos para modular plp1
WO2022018155A1 (en) 2020-07-23 2022-01-27 F. Hoffmann-La Roche Ag Lna oligonucleotides for splice modulation of stmn2
CN116209761A (zh) 2020-07-23 2023-06-02 豪夫迈·罗氏有限公司 靶向rna结合蛋白位点的寡核苷酸
UY39344A (es) 2020-07-28 2022-02-25 Ionis Pharmaceuticals Inc Compuestos y métodos para reducir la expresión de app
CN111671913B (zh) * 2020-07-30 2022-02-08 四川大学 一种量子点-小核酸偶联物及其用途
TW202221123A (zh) 2020-08-07 2022-06-01 美商Ionis製藥公司 調節scn2a之化合物及方法
EP4200419A2 (en) 2020-08-21 2023-06-28 F. Hoffmann-La Roche AG Use of a1cf inhibitors for treating hepatitis b virus infection
CA3194161A1 (en) * 2020-10-02 2022-04-07 David M. Evans Nucleoside containing sirnas for treating viral diseases
MX2023005736A (es) 2020-11-18 2023-05-25 Ionis Pharmaceuticals Inc Compuestos y metodos para modular la expresion de angiotensinogeno.
TW202237842A (zh) 2020-12-03 2022-10-01 瑞士商赫孚孟拉羅股份公司 靶向atxn3之反義寡核苷酸
US20230060373A1 (en) 2020-12-03 2023-03-02 Hoffmann-La Roche Inc. Antisense Oligonucleotides Targeting ATXN3
IL303800A (en) 2020-12-18 2023-08-01 Ionis Pharmaceuticals Inc Compounds and methods for modulating factor xii
JP2023553710A (ja) 2020-12-18 2023-12-25 エフ. ホフマン-ラ ロシュ アーゲー プログラニュリンを標的とするためのアンチセンスオリゴヌクレオチド
JP2024501662A (ja) 2020-12-22 2024-01-15 エフ. ホフマン-ラ ロシュ アーゲー Xbp1を標的とするオリゴヌクレオチド
CN114716518A (zh) * 2021-01-06 2022-07-08 圣诺制药公司 一种能够抑制pcsk9表达的分子构造及药物组合物
WO2022162015A1 (en) 2021-01-26 2022-08-04 Universite Brest Bretagne Occidentale Novel stim1 splicing variants and uses thereof
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
EP4305168A1 (en) 2021-03-08 2024-01-17 Les Laboratoires Servier Antisense oligonucleotides for inhibiting alpha-synuclein expression
WO2022232650A1 (en) * 2021-04-30 2022-11-03 Ionis Pharmaceuticals, Inc. Methods for reducing agt expression
WO2022246023A1 (en) 2021-05-20 2022-11-24 Korro Bio, Inc. Methods and compositions for adar-mediated editing
WO2022256283A2 (en) 2021-06-01 2022-12-08 Korro Bio, Inc. Methods for restoring protein function using adar
KR20240019228A (ko) 2021-06-08 2024-02-14 에프. 호프만-라 로슈 아게 올리고뉴클레오티드 프로그래눌린 효현제
US12378267B2 (en) 2021-06-17 2025-08-05 Entrada Therapeutics, Inc. Synthesis of FMOC-protected morpholino monomers and oligomers
AU2022293556A1 (en) 2021-06-18 2024-01-18 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing ifnar1 expression
IL309334A (en) 2021-06-23 2024-02-01 Univ Massachusetts Anti-FLT1 optimized oligonucleotide compounds for the treatment of preeclampsia and other angiogenic disorders
US20230194709A9 (en) 2021-06-29 2023-06-22 Seagate Technology Llc Range information detection using coherent pulse sets with selected waveform characteristics
US20250034564A1 (en) 2021-06-29 2025-01-30 Korro Bio, Inc. Methods and Compositions for ADAR-Mediated Editing
US20250188455A1 (en) * 2021-09-02 2025-06-12 Vanderbilt University Lipophilic oligonucleotide conjugates
KR20240055874A (ko) 2021-09-16 2024-04-29 어비디티 바이오사이언시스 인크. 안면견갑상완 근이영양증을 치료하는 조성물 및 방법
EP4419683A1 (en) 2021-10-22 2024-08-28 Korro Bio, Inc. Methods and compositions for disrupting nrf2-keap1 protein interaction by adar mediated rna editing
CN118318042A (zh) 2021-11-03 2024-07-09 豪夫迈·罗氏有限公司 用于调节载脂蛋白e4表达的寡核苷酸
JP2024544532A (ja) 2021-11-11 2024-12-03 エフ. ホフマン-ラ ロシュ アーゲー Hbvの処置のための医薬組合せ
WO2023102188A1 (en) * 2021-12-03 2023-06-08 Quralis Corporation Gapmer antisense oligonucleotides with modified backbone chemistries
CN118434858A (zh) 2021-12-07 2024-08-02 豪夫迈·罗氏有限公司 靶向actl6b的反义寡核苷酸
CN118489009A (zh) 2021-12-17 2024-08-13 豪夫迈·罗氏有限公司 寡核苷酸gba激动剂
WO2023111210A1 (en) 2021-12-17 2023-06-22 F. Hoffmann-La Roche Ag Combination of oligonucleotides for modulating rtel1 and fubp1
WO2023117738A1 (en) 2021-12-20 2023-06-29 F. Hoffmann-La Roche Ag Threose nucleic acid antisense oligonucleotides and methods thereof
EP4465994A1 (en) 2022-01-20 2024-11-27 Genentech, Inc. Antisense oligonucleotides for modulating tmem106b expression
AR128558A1 (es) 2022-02-21 2024-05-22 Hoffmann La Roche Oligonucleótido antisentido
TW202400786A (zh) 2022-03-16 2024-01-01 日商第一三共股份有限公司 具有RNAi活性的化學修飾寡核苷酸
JPWO2023176862A1 (enExample) 2022-03-16 2023-09-21
CN119173632A (zh) 2022-05-10 2024-12-20 豪夫迈·罗氏有限公司 靶向cfp-elk1基因间区域的反义寡核苷酸
WO2023222858A1 (en) 2022-05-18 2023-11-23 F. Hoffmann-La Roche Ag Improved oligonucleotides targeting rna binding protein sites
EP4282964A1 (en) * 2022-05-23 2023-11-29 Universitat de Valéncia Oligonucleotides conjugated to oleic acid and uses thereof
JP2025520514A (ja) 2022-06-17 2025-07-03 エフ. ホフマン-ラ ロシュ アーゲー プログラニュリンを標的とするためのアンチセンスオリゴヌクレオチド
EP4332221A1 (en) 2022-08-29 2024-03-06 Roche Innovation Center Copenhagen A/S Threose nucleic acid antisense oligonucleotides and methods thereof
IL318655A (en) 2022-09-06 2025-03-01 Hoffmann La Roche Double RNA molecule for ocular administration
KR20250075637A (ko) 2022-09-23 2025-05-28 아이오니스 파마수티컬즈, 인코포레이티드 Mecp2 발현을 감소시키기 위한 화합물 및 방법(compounds and methods for reducing mecp2 expression)
AU2023385867A1 (en) * 2022-11-21 2025-06-05 Pepgen Inc. Cell-penetrating peptides, conjugates thereof, and methods of their use
WO2024126654A1 (en) 2022-12-14 2024-06-20 F. Hoffmann-La Roche Ag Antisense oligonucleotides targeting actl6b
WO2024153586A1 (en) 2023-01-16 2024-07-25 Institut National De Recherche Pour L'agriculture, L'alimentation Et L'environnement Antisense molecules and their uses for the treatment of coronavirus infection, in particular the treatment of covid-19 related to sars-cov-2 infection
EP4652262A1 (en) 2023-01-19 2025-11-26 Altos Labs, Inc. Use of regeneration factors in organ transplantation
WO2024196893A1 (en) * 2023-03-17 2024-09-26 Camford Labs Inc. Chemically modified nucleotides
CN121002179A (zh) * 2023-03-30 2025-11-21 中美瑞康核酸技术(南通)研究院有限公司 寡核苷酸的递送载体及其使用方法
WO2024227765A2 (en) 2023-05-04 2024-11-07 F. Hoffmann-La Roche Ag Oligonucleotides capable of upregulating glucocerebrosidase expression
TW202508607A (zh) * 2023-05-19 2025-03-01 大陸商北京炫景瑞醫藥科技有限公司 雙股寡核苷酸及其共軛物和用途
WO2024256707A1 (en) 2023-06-16 2024-12-19 F. Hoffmann-La Roche Ag Double stranded oligonucleotide for modulating jak1 expression
WO2025036916A1 (en) 2023-08-16 2025-02-20 Les Laboratoires Servier Oligonucleotides for modulating kcnt1 expression

Family Cites Families (207)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US603095A (en) 1898-04-26 Machine for dishing metal
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
US4904582A (en) 1987-06-11 1990-02-27 Synthetic Genetics Novel amphiphilic nucleic acid conjugates
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
US5354844A (en) 1989-03-16 1994-10-11 Boehringer Ingelheim International Gmbh Protein-polycation conjugates
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
CA2095212A1 (en) 1990-11-08 1992-05-09 Sudhir Agrawal Incorporation of multiple reporter groups on synthetic oligonucleotides
DE4104186A1 (de) 1991-02-12 1992-08-13 Genentech Inc Neue, ueber endozytose in hoehere eukaryotische zellen aufnehmbare, nukleinsaeure enthaltende komplexe
DE4110409C2 (de) 1991-03-29 1999-05-27 Boehringer Ingelheim Int Neue Protein-Polykation-Konjugate
KR950014915B1 (ko) 1991-06-19 1995-12-18 주식회사녹십자 탈시알로당단백-포함화합물
EP0724447B1 (en) 1991-10-24 2003-05-07 Isis Pharmaceuticals, Inc. Derivatized oligonucleotides having improved uptake
US5272250A (en) 1992-07-10 1993-12-21 Spielvogel Bernard F Boronated phosphoramidate compounds
NL9201440A (nl) 1992-08-11 1994-03-01 Univ Leiden Triantennaire clusterglycosiden, hun bereiding en toepassing.
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
AU679566B2 (en) 1993-09-03 1997-07-03 Isis Pharmaceuticals, Inc. Amine-derivatized nucleosides and oligonucleosides
DE699079T1 (de) 1994-03-07 1997-09-25 Dendritech Inc Bioaktive und/oder gezielte dendrimere-konjugate
US5646262A (en) 1994-07-28 1997-07-08 Georgetown University Antisense oligonucleotides against hepatitis B viral replication
US5580731A (en) 1994-08-25 1996-12-03 Chiron Corporation N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith
DE69527857T2 (de) 1994-10-06 2003-05-28 Buchardt, Dorte Peptid-nukleinsäure-konjugate
US5684142A (en) 1995-06-07 1997-11-04 Oncor, Inc. Modified nucleotides for nucleic acid labeling
US5672662A (en) 1995-07-07 1997-09-30 Shearwater Polymers, Inc. Poly(ethylene glycol) and related polymers monosubstituted with propionic or butanoic acids and functional derivatives thereof for biotechnical applications
US5985662A (en) 1995-07-13 1999-11-16 Isis Pharmaceuticals Inc. Antisense inhibition of hepatitis B virus replication
EP0862439A4 (en) 1995-11-22 2001-01-10 O Paul O P Ts LIGANDS FOR INCREASING THE CELLULAR UPtake OF BIOMOLECULES
US6344436B1 (en) 1996-01-08 2002-02-05 Baylor College Of Medicine Lipophilic peptides for macromolecule delivery
US5656408A (en) 1996-04-29 1997-08-12 Xerox Corporation Coated carrier particles
US5776907A (en) 1996-05-20 1998-07-07 Texas Biotechnology Corporation Mitomycin oligonucleotide conjugates
US6001991A (en) 1996-10-04 1999-12-14 Isis Pharmaceuticals Inc. Antisense oligonucleotide modulation of MDR P-glycoprotein gene expression
US20030014318A1 (en) 1996-11-08 2003-01-16 Matthew Byrne International trading system and method
US6770748B2 (en) 1997-03-07 2004-08-03 Takeshi Imanishi Bicyclonucleoside and oligonucleotide analogue
JP3756313B2 (ja) 1997-03-07 2006-03-15 武 今西 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体
US5770716A (en) 1997-04-10 1998-06-23 The Perkin-Elmer Corporation Substituted propargylethoxyamido nucleosides, oligonucleotides and methods for using same
CN1304572C (zh) * 1997-05-05 2007-03-14 萨诺费-阿文蒂斯德国有限公司 与人Ha-ras基因片段互补的经修饰的反义核苷酸
IL132941A0 (en) 1997-05-21 2001-03-19 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
ATE293123T1 (de) 1997-09-12 2005-04-15 Exiqon As Bi- und tri-zyklische - nukleosid, nukleotid und oligonukleotid-analoga
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
US6365379B1 (en) 1998-10-06 2002-04-02 Isis Pharmaceuticals, Inc. Zinc finger peptide cleavage of nucleic acids
EP1135481B1 (en) 1998-12-02 2004-02-25 I.D.M. Immuno-Designed Molecules New oligomeric conjugates liable to transfer biological molecules into cells
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
US6656730B1 (en) * 1999-06-15 2003-12-02 Isis Pharmaceuticals, Inc. Oligonucleotides conjugated to protein-binding drugs
US20040146516A1 (en) 1999-06-17 2004-07-29 Utah Ventures Ii L.P. Lumen-exposed molecules and methods for targeted delivery
US6617442B1 (en) 1999-09-30 2003-09-09 Isis Pharmaceuticals, Inc. Human Rnase H1 and oligonucleotide compositions thereof
IL148916A0 (en) 1999-10-04 2002-09-12 Exiqon As Design of high affinity rnase h recruiting oligonucleotide
US20080039414A1 (en) 2002-02-20 2008-02-14 Sima Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US6559279B1 (en) 2000-09-08 2003-05-06 Isis Pharmaceuticals, Inc. Process for preparing peptide derivatized oligomeric compounds
EP1383782A1 (en) 2001-03-26 2004-01-28 Sirna Therpeutics, Inc. Oligonucleotide mediated inhibition of hepatitis b virus and hepatitis c virus replication
EP3231445A1 (en) 2001-05-18 2017-10-18 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
US7407943B2 (en) 2001-08-01 2008-08-05 Isis Pharmaceuticals, Inc. Antisense modulation of apolipoprotein B expression
US7227014B2 (en) 2001-08-07 2007-06-05 Isis Pharmaceuticals, Inc. Antisense modulation of apolipoprotein (a) expression
US7259150B2 (en) 2001-08-07 2007-08-21 Isis Pharmaceuticals, Inc. Modulation of apolipoprotein (a) expression
US20030191075A1 (en) 2002-02-22 2003-10-09 Cook Phillip Dan Method of using modified oligonucleotides for hepatic delivery
AU2003237875A1 (en) 2002-05-15 2003-12-02 Isis Pharmaceuticals, Inc. Antisense modulation of apolipoprotein b expression
GB2389824B (en) 2002-06-21 2005-08-24 Paul Sinclair Improvements in or relating to funeral vehicles
US7655790B2 (en) * 2002-07-12 2010-02-02 Sirna Therapeutics, Inc. Deprotection and purification of oligonucleotides and their derivatives
US7087229B2 (en) 2003-05-30 2006-08-08 Enzon Pharmaceuticals, Inc. Releasable polymeric conjugates based on aliphatic biodegradable linkers
US6878805B2 (en) 2002-08-16 2005-04-12 Isis Pharmaceuticals, Inc. Peptide-conjugated oligomeric compounds
CA2504694C (en) 2002-11-05 2013-10-01 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
US8604183B2 (en) 2002-11-05 2013-12-10 Isis Pharmaceuticals, Inc. Compositions comprising alternating 2′-modified nucleosides for use in gene modulation
AU2003295389A1 (en) 2002-11-05 2004-06-03 Isis Pharmaceuticals, Inc. Conjugated oligomeric compounds and their use in gene modulation
CA2505801A1 (en) 2002-11-13 2004-05-27 Rosanne Crooke Antisense modulation of apolipoprotein b expression
US7511131B2 (en) 2002-11-13 2009-03-31 Genzyme Corporation Antisense modulation of apolipoprotein B expression
DE60329220D1 (de) 2002-11-18 2009-10-22 Santaris Pharma As Antisense-entwurf
US7816337B2 (en) 2003-02-18 2010-10-19 Roche Madison Inc. Reversible attachment of a membrane active polymer to a polynucleotide
WO2004087931A1 (en) 2003-04-03 2004-10-14 Korea Advanced Institute Of Science And Technology Conjugate for gene transfer comprising oligonucleotide and hydrophilic polymer, polyelectrolyte complex micelles formed from the conjugate, and methods for preparation thereof
US7723509B2 (en) 2003-04-17 2010-05-25 Alnylam Pharmaceuticals IRNA agents with biocleavable tethers
WO2004106356A1 (en) 2003-05-27 2004-12-09 Syddansk Universitet Functionalized nucleotide derivatives
CA2524495A1 (en) * 2003-06-03 2005-01-13 Eli Lilly And Company Modulation of survivin expression
DE60319354T2 (de) 2003-07-11 2009-03-26 Lbr Medbiotech B.V. Mannose-6-Phosphat Rezeptor vermittelter Gentransfer zu Muskelzellen
CA2533701A1 (en) 2003-07-31 2005-02-17 Isis Pharmaceuticals, Inc. Oligomeric compounds and compositions for use in modulation of small non-coding rnas
US7825235B2 (en) 2003-08-18 2010-11-02 Isis Pharmaceuticals, Inc. Modulation of diacylglycerol acyltransferase 2 expression
JP4731324B2 (ja) 2003-08-28 2011-07-20 武 今西 N−o結合性架橋構造型新規人工核酸
WO2005027962A1 (en) 2003-09-18 2005-03-31 Isis Pharmaceuticals, Inc. 4’-thionucleosides and oligomeric compounds
EP1663316A2 (en) * 2003-09-25 2006-06-07 Coley Pharmaceutical Group, Inc. Nucleic acid lipophilic conjugates
EP1706489B9 (en) 2003-12-23 2011-01-05 Santaris Pharma A/S Oligomeric compounds for the modulation of bcl-2
US20050261170A1 (en) 2004-01-22 2005-11-24 Immunomedics, Inc. Folate conjugates and complexes
DK1713912T3 (da) 2004-01-30 2013-12-16 Santaris Pharma As Modificerede Korte Interfererende RNA (Modificerede siRNA)
US20050244869A1 (en) 2004-04-05 2005-11-03 Brown-Driver Vickie L Modulation of transthyretin expression
WO2005111238A2 (en) 2004-04-19 2005-11-24 Archemix Corporation Aptamer-mediated intracellular delivery of therapeutic oligonucleotides
US20050288246A1 (en) 2004-05-24 2005-12-29 Iversen Patrick L Peptide conjugated, inosine-substituted antisense oligomer compound and method
WO2006112872A2 (en) 2004-08-04 2006-10-26 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising a ligand tethered to a modified or non-natural nucleobase
DK1786472T3 (da) 2004-08-10 2013-04-15 Genzyme Corp Antisense-modulering af apolipoprotein B-ekspression
NZ554214A (en) 2004-09-24 2009-10-30 Alnylam Pharmaceuticals Inc Rnai modulation of apob and uses thereof
WO2006050734A2 (en) * 2004-11-09 2006-05-18 Santaris Pharma A/S Potent lna oligonucleotides for the inhibition of hif-1a expression
AU2005304110B2 (en) * 2004-11-09 2009-06-11 Enzon Pharmaceuticals, Inc. LNA oligonucleotides and the treatment of cancer
US20120122801A1 (en) 2005-01-05 2012-05-17 Prosensa B.V. Mannose-6-phosphate receptor mediated gene transfer into muscle cells
EP1841867A1 (en) 2005-01-24 2007-10-10 Avaris AB COMPLEX CONTAINING SiRNA, ShRNA OR ANTISENSE MOLECULE AND FUNCTIONAL ENTITY, FOR IMPROVED SPECIFICITY AND DELIVERY
US20070213292A1 (en) 2005-08-10 2007-09-13 The Rockefeller University Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof
EP2338992A3 (en) 2005-08-29 2011-10-12 Regulus Therapeutics, Inc Antisense compounds having enhanced anti-microRNA activity
WO2007027775A2 (en) 2005-08-29 2007-03-08 Isis Pharmaceuticals, Inc. Methods for use in modulating mir-122a
WO2007031091A2 (en) 2005-09-15 2007-03-22 Santaris Pharma A/S Rna antagonist compounds for the modulation of p21 ras expression
CA2622583A1 (en) * 2005-09-15 2007-03-22 Henrik Frydenlund Hansen Rna antagonist compounds for the inhibition of apo-b100 expression
JP2009508527A (ja) 2005-09-19 2009-03-05 ジヨンソン・アンド・ジヨンソン・フアーマシユーチカル・リサーチ・アンド・デベロツプメント・エルエルシー グルココルチコイド受容体発現の調節
CA2629323A1 (en) 2005-11-10 2007-05-24 The University Of North Carolina At Chapel Hill Splice switching oligomers for tnf superfamily receptors and their use in treatment of disease
US20090176977A1 (en) 2006-01-27 2009-07-09 Joacim Elmen Lna modified phosphorothiolated oligonucleotides
EP1984381B1 (en) 2006-01-27 2010-09-29 Isis Pharmaceuticals, Inc. 6-modified bicyclic nucleic acid analogs
JP5244087B2 (ja) 2006-03-23 2013-07-24 サンタリス ファーマ アー/エス 低分子内部セグメント化干渉rna
GB0606415D0 (en) 2006-03-31 2006-05-10 Univ Southampton Topical drug delivery
AU2007234191B2 (en) 2006-04-03 2012-07-12 Roche Innovation Center Copenhagen A/S Pharmaceutical composition comprising anti-miRNA antisense oligonucleotides
SG10201406016SA (en) * 2006-04-03 2014-11-27 Stella Aps Pharmaceutical composition comprising anti-mirna antisense oligonucleotides
EP2023940B1 (en) 2006-05-05 2011-06-22 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of sglt2
DK2066684T3 (da) 2006-05-11 2012-10-22 Isis Pharmaceuticals Inc 5´-Modificerede bicycliske nukleinsyreanaloge
EP2076257A4 (en) 2006-09-15 2014-04-16 Belrose Pharma Inc POLYMER CONJUGATES WITH POSITIVELY LOADED PARTS
MX2009002859A (es) 2006-09-15 2009-03-30 Enzon Pharmaceuticals Inc Enlazadores biodegradables a base de ester impedido para suministro de oligonucleotidos.
MX2009003398A (es) 2006-09-27 2009-08-12 Coley Pharm Gmbh Analogos de oligonucleotidos cpg que contienen analogos t hidrofobos con actividad inmunoestimuladora mejorada.
WO2008040355A2 (en) 2006-10-06 2008-04-10 Exiqon A/S Novel methods for quantification of micrornas and small interfering rnas
CA2666191C (en) 2006-10-09 2017-07-11 Santaris Pharma A/S Rna antagonist compounds for the modulation of pcsk9
CA2666981A1 (en) 2006-10-20 2008-05-02 Ercole Biotech, Inc. Soluble tnf receptors and their use in treatment of disease
EP2455471A3 (en) 2006-11-27 2012-09-12 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
EP2125852B1 (en) 2007-02-15 2016-04-06 Ionis Pharmaceuticals, Inc. 5'-substituted-2'-f modified nucleosides and oligomeric compounds prepared therefrom
WO2008109369A2 (en) 2007-03-02 2008-09-12 Mdrna, Inc. Nucleic acid compounds for inhibiting tnf gene expression and uses thereof
DE102007012908A1 (de) 2007-03-19 2008-09-25 Momentive Performance Materials Gmbh Neue Polyamid-Polysiloxan-Verbindungen
US8580756B2 (en) 2007-03-22 2013-11-12 Santaris Pharma A/S Short oligomer antagonist compounds for the modulation of target mRNA
AU2008228243B2 (en) 2007-03-22 2014-05-15 Santaris Pharma A/S RNA antagonist compounds for the inhibition of Apo-B100 expression
KR20090128494A (ko) 2007-03-24 2009-12-15 겐자임 코포레이션 인간 아포리포프로틴 b에 상보적인 안티센스 올리고뉴클레오타이드 투여
CA3072221A1 (en) 2007-05-01 2008-11-06 Santaris Pharma A/S Splice switching oligomers for tnf superfamily receptors and their use in treatment of disease
EP2152879B1 (en) 2007-05-01 2012-11-14 Santaris Pharma A/S Rna antagonist compounds for the modulation of beta-catenin
AU2008260277C1 (en) 2007-05-30 2014-04-17 Isis Pharmaceuticals, Inc. N-substituted-aminomethylene bridged bicyclic nucleic acid analogs
DK2173760T4 (en) 2007-06-08 2016-02-08 Isis Pharmaceuticals Inc Carbocyclic bicyclic nukleinsyreanaloge
EP2170363B1 (en) 2007-06-29 2018-08-08 Sarepta Therapeutics, Inc. Tissue specific peptide conjugates and methods
CN101796062B (zh) 2007-07-05 2014-07-30 Isis制药公司 6-双取代双环核酸类似物
EP2171648A4 (en) 2007-07-19 2011-06-29 Datakey Electronics Inc HF TOKEN AND RECORDING SYSTEM AND METHOD
JP2010536986A (ja) 2007-08-20 2010-12-02 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 ピリジルジスルフィド部分を含有するポリマーリンカー
US8486904B2 (en) 2007-10-01 2013-07-16 Isis Pharmaceuticals, Inc. Antisense modulation of fibroblast growth factor receptor 4 expression
MY156951A (en) 2007-10-04 2016-04-15 Santaris Pharma As Micromirs
WO2009045536A2 (en) 2007-10-05 2009-04-09 The University Of North Carolina At Chapel Hill Receptor targeted oligonucleotides
JP5872162B2 (ja) 2007-11-26 2016-03-01 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 アンドロゲン受容体を標的化するlnaアンタゴニスト
MX2010006039A (es) 2007-12-03 2010-06-23 Enzon Pharmaceuticals Inc Compuestos antagonistas del acido ribonucleico para la modulacion de la expresion de la fosfoinositida-3-cinasa catalitica.
AU2008340355B2 (en) * 2007-12-04 2015-01-22 Tekmira Pharmaceuticals Corporation Targeting lipids
WO2009090182A1 (en) 2008-01-14 2009-07-23 Santaris Pharma A/S C4'-substituted - dna nucleotide gapmer oligonucleotides
EP2265627A2 (en) 2008-02-07 2010-12-29 Isis Pharmaceuticals, Inc. Bicyclic cyclohexitol nucleic acid analogs
CA2717792A1 (en) 2008-03-07 2009-09-11 Santaris Pharma A/S Pharmaceutical compositions for treatment of microrna related diseases
WO2009124238A1 (en) 2008-04-04 2009-10-08 Isis Pharmaceuticals, Inc. Oligomeric compounds comprising neutrally linked terminal bicyclic nucleosides
JP5788312B2 (ja) 2008-04-11 2015-09-30 アルニラム ファーマスーティカルズ インコーポレイテッドAlnylam Pharmaceuticals, Inc. 標的リガンドをエンドソーム分解性成分と組み合わせることによる核酸の部位特異的送達
WO2009148605A2 (en) 2008-06-04 2009-12-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
JP2011526482A (ja) 2008-07-03 2011-10-13 サンタリス ファーマ アー/エス ミトコンドリアグリセロール−3−リン酸アシルトランスフェラーゼ1(mtgpat1)の発現を阻害するためのrnaアンタゴニスト化合物
CN102149390A (zh) 2008-07-10 2011-08-10 阿姆斯特丹大学附属医院 补体拮抗剂及其应用
US9033197B2 (en) 2008-07-17 2015-05-19 Nir Bar Spool holder
US7932256B2 (en) 2008-07-31 2011-04-26 Bristol-Myers Squibb Company (S)-4-(1-cyclopropyl-2-methoxyethyl)-6-(6-(difluoromethoxy)-2,5-dimethylpyridin-3-ylamino)-5-oxo-4,5-dihydropyrazine-2-carbonitrile: a pyrazinone modulator of corticotropin-releasing factor receptor activity
EP2323667A4 (en) 2008-08-07 2012-07-25 Isis Pharmaceuticals Inc MODULATION OF TRANSTHYRETIN EXPRESSION BY TREATMENT OF CNS DISEASES
WO2010045584A1 (en) 2008-10-17 2010-04-22 Endocyte, Inc. Folate targeting of nucleotides
WO2010076248A1 (en) 2008-12-31 2010-07-08 Santaris Pharma A/S Use of lna apob antisense oligomers for the treatment of acute coronary syndromes
AT507215B1 (de) 2009-01-14 2010-03-15 Boehler Edelstahl Gmbh & Co Kg Verschleissbeständiger werkstoff
EP2414521B1 (en) 2009-03-31 2016-10-26 The General Hospital Corporation Regulation of mir-33 micrornas in the treatment of cholesterol-related disorders
EP2421970B1 (en) * 2009-04-24 2016-09-07 Roche Innovation Center Copenhagen A/S Pharmaceutical compositions for treatment of hcv patients that are non-responders to interferon
CA2764822A1 (en) 2009-06-12 2010-12-16 Santaris Pharma A/S New potent anti apob antisense compounds
WO2011009697A1 (en) 2009-07-21 2011-01-27 Santaris Pharma A/S Antisense oligomers targeting pcsk9
EP2512491B1 (en) 2009-10-16 2017-10-11 Glaxo Group Limited Hbv antisense inhibitors
KR101663617B1 (ko) 2009-10-29 2016-10-07 엘지전자 주식회사 하향링크 기준신호 송수신 방법 및, 이를 이용한 기지국 및 사용자기기
US20130023578A1 (en) * 2009-12-31 2013-01-24 Samyang Biopharmaceuticals Corporation siRNA for inhibition of c-Met expression and anticancer composition containing the same
CA2786071C (en) 2010-01-08 2021-01-12 Isis Pharmaceuticals, Inc. Modulation of angiopoietin-like 3 expression
US8846631B2 (en) 2010-01-14 2014-09-30 Regulus Therapeutics Inc. MicroRNA compositions and methods
ES2562817T3 (es) 2010-02-24 2016-03-08 Arrowhead Research Corporation Composiciones para el suministro dirigido de ARNip
WO2011123621A2 (en) 2010-04-01 2011-10-06 Alnylam Pharmaceuticals Inc. 2' and 5' modified monomers and oligonucleotides
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
WO2011130458A2 (en) 2010-04-13 2011-10-20 John Rossi Rna aptamers against baff-r as cell-type specific delivery agents and methods for their use
EP2560687B1 (en) 2010-04-19 2017-05-24 Nlife Therapeutics S.L. Compositions and methods for selective delivery of oligonucleotide molecules to specific neuron types
WO2011133871A2 (en) 2010-04-22 2011-10-27 Alnylam Pharmaceuticals, Inc. 5'-end derivatives
WO2011139917A1 (en) 2010-04-29 2011-11-10 Isis Pharmaceuticals, Inc. Modulation of transthyretin expression
WO2012012716A2 (en) 2010-07-23 2012-01-26 Regulus Therapeutics, Inc. Targeting micrornas for the treatment of fibrosis
US9127280B2 (en) 2010-08-31 2015-09-08 Osaka University Oligonucleotide, and therapeutic agent for dyslipidemia containing oligonucleotide as active ingredient
WO2012078637A2 (en) 2010-12-06 2012-06-14 Immune Disease Institute, Inc. Composition and method for oligonucleotide delivery
EP3843313A1 (en) 2010-12-13 2021-06-30 Telefonaktiebolaget LM Ericsson (publ) Exchange of parameters relating to measurement periods
CA2816155C (en) 2010-12-17 2020-10-27 Arrowhead Research Corporation Galactose cluster-pharmacokinetic modulator targeting moiety for sirna
KR20130108655A (ko) 2010-12-29 2013-10-04 에프. 호프만-라 로슈 아게 핵산의 세포내 전달을 위한 소분자 접합체
CA2816041C (en) 2010-12-29 2019-01-08 Arrowhead Research Corporation In vivo polynucleotide delivery conjugates having enzyme sensitive linkages
WO2012099755A1 (en) 2011-01-11 2012-07-26 Alnylam Pharmaceuticals, Inc. Pegylated lipids and their use for drug delivery
US20120295961A1 (en) 2011-04-21 2012-11-22 Swayze Eric E Modulation of hepatitis b virus (hbv) expression
CR20190207A (es) 2011-04-21 2019-06-26 Ionis Pharmaceuticals Inc MODULACIÓN DE LA EXPRESIÓN DEL VIRUS DE LA HEPATITIS B (VHB) (Divisional 2013-0551)
ES2868950T3 (es) 2011-04-25 2021-10-22 Sanofi Sa Compuestos de microARN y métodos para modular la actividad de miR-21
CN102226185A (zh) * 2011-05-09 2011-10-26 华中科技大学同济医学院附属同济医院 靶向肝细胞的rna适配子及其核苷酸序列
WO2012174154A1 (en) 2011-06-13 2012-12-20 Isis Pharmaceuticals, Inc. Modulation of inflammatory responses by factor vii
EP2721156B1 (en) 2011-06-16 2016-12-21 Ionis Pharmaceuticals, Inc. Antisense modulation of fibroblast growth factor receptor 4 expression
SI2726613T1 (sl) 2011-06-30 2018-10-30 Arrowhead Pharmaceuticals, Inc. Sestavki in postopki za zaviranje izražanja gena virusa hepatitisa B
US10023861B2 (en) 2011-08-29 2018-07-17 Ionis Pharmaceuticals, Inc. Oligomer-conjugate complexes and their use
EP3533873A1 (en) * 2011-09-14 2019-09-04 Translate Bio MA, Inc. Multimeric oligonucleotide compounds
AU2012327227A1 (en) 2011-11-07 2013-05-23 Isis Pharmaceuticals, Inc. Administration of Factor XI antisense oligonucleotides
WO2013068348A1 (en) 2011-11-07 2013-05-16 Santaris Pharma A/S Lna oligomers for improvement in hepatic function
WO2013119979A1 (en) 2012-02-08 2013-08-15 Isis Pharmaceuticals, Inc. Methods and compositions for modulating factor vii expression
US9340784B2 (en) 2012-03-19 2016-05-17 Ionis Pharmaceuticals, Inc. Methods and compositions for modulating alpha-1-antitrypsin expression
US9221864B2 (en) 2012-04-09 2015-12-29 Isis Pharmaceuticals, Inc. Tricyclic nucleic acid analogs
WO2013159109A1 (en) 2012-04-20 2013-10-24 Isis Pharmaceuticals, Inc. Modulation of hepatitis b virus (hbv) expression
US9984408B1 (en) 2012-05-30 2018-05-29 Amazon Technologies, Inc. Method, medium, and system for live video cooperative shopping
WO2014076196A1 (en) 2012-11-15 2014-05-22 Santaris Pharma A/S Anti apob antisense conjugate compounds
CA2893801A1 (en) 2013-01-30 2014-08-07 F. Hoffmann-La Roche Ag Lna oligonucleotide carbohydrate conjugates
RU2670614C9 (ru) 2013-05-01 2018-11-23 Ионис Фармасьютикалз, Инк. Композиции и способы модулирования экспрессии hbv и ttr
CA2928349A1 (en) 2013-11-14 2015-05-21 Roche Innovation Center Copenhagen A/S Apob antisense conjugate compounds
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
CN104837996A (zh) 2015-08-12
WO2014076196A1 (en) 2014-05-22
PL2920304T3 (pl) 2019-07-31
RU2015119411A (ru) 2017-01-10
EP2920304A1 (en) 2015-09-23
US20150291958A1 (en) 2015-10-15
MX363068B (es) 2019-03-07
RU2015119409A (ru) 2017-01-10
AU2013346767B2 (en) 2019-04-11
JP2016501195A (ja) 2016-01-18
MX2015005794A (es) 2016-01-12
JP2016503300A (ja) 2016-02-04
CN104884618A (zh) 2015-09-02
MY173826A (en) 2020-02-24
EP3406718A1 (en) 2018-11-28
US11155816B2 (en) 2021-10-26
DK2920307T3 (en) 2018-07-16
CA2889596A1 (en) 2014-05-22
KR20150082643A (ko) 2015-07-15
BR112015010116A2 (pt) 2017-08-22
SI2920304T1 (sl) 2019-06-28
RU2653438C2 (ru) 2018-05-08
JP2019055995A (ja) 2019-04-11
US20180251764A1 (en) 2018-09-06
RU2018112970A3 (enExample) 2020-05-27
AU2013346767A2 (en) 2015-06-18
EP2920307A1 (en) 2015-09-23
US20210238601A1 (en) 2021-08-05
SG11201503821YA (en) 2015-06-29
CA2889596C (en) 2022-08-23
SG10201804331TA (en) 2018-07-30
ZA201503375B (en) 2016-02-24
US10077443B2 (en) 2018-09-18
JP6452614B2 (ja) 2019-01-16
CA2889044A1 (en) 2014-05-22
EP2920307B1 (en) 2018-05-02
MX2015005792A (es) 2015-12-17
IL268420A (en) 2019-09-26
EP2920304B1 (en) 2019-03-06
CN117126846A (zh) 2023-11-28
AU2019202288A1 (en) 2019-04-18
NZ708171A (en) 2019-11-29
IL238448B (en) 2019-09-26
RU2018112970A (ru) 2019-03-01
HK1214297A1 (zh) 2016-07-22
WO2014076195A1 (en) 2014-05-22
US20150275212A1 (en) 2015-10-01
IL238448A0 (en) 2015-06-30
DK2920304T3 (da) 2019-05-13
AU2013346767A1 (en) 2015-05-28
KR102112892B1 (ko) 2020-05-19
KR20150083920A (ko) 2015-07-20
HK1210213A1 (en) 2016-04-15
BR112015011112A2 (pt) 2018-11-06
HRP20190826T1 (hr) 2019-06-28

Similar Documents

Publication Publication Date Title
ES2724853T3 (es) Conjugados de oligonucleótidos
KR102287532B1 (ko) 생분해성 컨쥬게이트를 갖는 폴리 올리고머 화합물
EP2951305B1 (en) Lna oligonucleotide carbohydrate conjugates
ES2770667T3 (es) Oligómeros antisentido y conjugados que se dirigen a PCSK9