ES2657679T3 - Modulación del factor de expresión 11 - Google Patents

Modulación del factor de expresión 11 Download PDF

Info

Publication number
ES2657679T3
ES2657679T3 ES09821293.9T ES09821293T ES2657679T3 ES 2657679 T3 ES2657679 T3 ES 2657679T3 ES 09821293 T ES09821293 T ES 09821293T ES 2657679 T3 ES2657679 T3 ES 2657679T3
Authority
ES
Spain
Prior art keywords
isis
antisense
seq
factor
nucleotide
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
ES09821293.9T
Other languages
English (en)
Spanish (es)
Inventor
Susan M. Freier
Brett P. Monia
Hong Zhang
Chenguang Zhao
Jeffrey R. Crosby
Andrew M. Siwkowski
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.)
Ionis Pharmaceuticals Inc
Original Assignee
Ionis Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ionis Pharmaceuticals Inc filed Critical Ionis Pharmaceuticals Inc
Application granted granted Critical
Publication of ES2657679T3 publication Critical patent/ES2657679T3/es
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/7125—Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/727—Heparin; Heparan
    • 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
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/737—Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • 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
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • 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
    • 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
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1137—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against enzymes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21—Serine endopeptidases (3.4.21)
    • C12Y304/21027—Coagulation factor XIa (3.4.21.27)
    • 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
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/33—Chemical structure of the base
    • C12N2310/334—Modified C
    • C12N2310/3341—5-Methylcytosine
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/341—Gapmers, i.e. of the type ===---===
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Biochemistry (AREA)
  • Biomedical Technology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Cardiology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Dermatology (AREA)
  • Virology (AREA)
  • Hematology (AREA)
  • Vascular Medicine (AREA)
  • Diabetes (AREA)
  • Urology & Nephrology (AREA)
  • Hospice & Palliative Care (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pulmonology (AREA)
ES09821293.9T 2008-10-15 2009-10-15 Modulación del factor de expresión 11 Active ES2657679T3 (es)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US10577208P 2008-10-15 2008-10-15
US105772P 2008-10-15
US17446109P 2009-04-30 2009-04-30
US174461P 2009-04-30
PCT/US2009/060922 WO2010045509A2 (en) 2008-10-15 2009-10-15 Modulation of factor 11 expression

Publications (1)

Publication Number Publication Date
ES2657679T3 true ES2657679T3 (es) 2018-03-06

Family

ID=42107256

Family Applications (1)

Application Number Title Priority Date Filing Date
ES09821293.9T Active ES2657679T3 (es) 2008-10-15 2009-10-15 Modulación del factor de expresión 11

Country Status (23)

Country Link
US (7) US8334372B2 (enExample)
EP (2) EP2379084B1 (enExample)
JP (4) JP5809058B2 (enExample)
KR (2) KR101773551B1 (enExample)
CN (4) CN102245186B (enExample)
AU (2) AU2009305636A1 (enExample)
BR (1) BRPI0920263B1 (enExample)
CA (2) CA2966011C (enExample)
CY (1) CY1119909T1 (enExample)
DK (1) DK2379084T3 (enExample)
ES (1) ES2657679T3 (enExample)
HR (1) HRP20171969T1 (enExample)
HU (1) HUE035888T2 (enExample)
IL (2) IL212267A (enExample)
LT (1) LT2379084T (enExample)
MX (1) MX2011004097A (enExample)
NO (1) NO2379084T3 (enExample)
NZ (2) NZ603603A (enExample)
PL (1) PL2379084T3 (enExample)
PT (1) PT2379084T (enExample)
RU (2) RU2535964C2 (enExample)
SI (1) SI2379084T1 (enExample)
WO (1) WO2010045509A2 (enExample)

Families Citing this family (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8334372B2 (en) 2008-10-15 2012-12-18 Isis Pharmaceuticals, Inc. Modulation of factor 11 expression
BRPI1015236A2 (pt) * 2009-04-15 2019-09-24 Isis Pharmaceuticals Inc métodos para modular uma resposta inflamatória, apra melhorar uma doença, distúrbio ou condição inflamatórios em um animal, para tratar um animal em risco para uma doença, distúrbio ou condição inflamatórios, para inibir a expressão de fator xi em um animal, para reduzir o risco de doença, distúrbio ou condição inflamatórios, em um animal, para tratar um animal em risco para uma doença inflamatória, e para tratar um animal tendo uma doença inflamatória, e, uso de um composto marcado para fator xi
WO2012064758A2 (en) * 2010-11-08 2012-05-18 Isis Pharmaceuticals, Inc. Methods for modulating factor 12 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)
US20120295961A1 (en) * 2011-04-21 2012-11-22 Swayze Eric E Modulation of hepatitis b virus (hbv) expression
WO2012170947A2 (en) 2011-06-10 2012-12-13 Isis Pharmaceuticals, Inc. Methods for modulating factor 12 expression
AU2012327227A1 (en) * 2011-11-07 2013-05-23 Isis Pharmaceuticals, Inc. Administration of Factor XI antisense oligonucleotides
US10502737B2 (en) 2012-05-25 2019-12-10 The University Of Vermont And State Agriculture College Anti-thrombotic compositions and methods for assaying platelet reactivity and treatment selection
RU2670614C9 (ru) 2013-05-01 2018-11-23 Ионис Фармасьютикалз, Инк. Композиции и способы модулирования экспрессии hbv и ttr
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
WO2015179693A1 (en) 2014-05-22 2015-11-26 Isis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
TWI675043B (zh) 2014-08-07 2019-10-21 瑞士商諾華公司 血管生成素樣４抗體及其使用方法
US9988443B2 (en) 2014-08-07 2018-06-05 Novartis Ag Angiopoetin-like 4 (ANGPTL4) antibodies and methods of use
JOP20200312A1 (ar) 2015-06-26 2017-06-16 Novartis Ag الأجسام المضادة للعامل xi وطرق الاستخدام
TW201802121A (zh) 2016-05-25 2018-01-16 諾華公司 抗因子XI/XIa抗體之逆轉結合劑及其用途
WO2018067900A1 (en) 2016-10-06 2018-04-12 Ionis Pharmaceuticals, Inc. Method of conjugating oligomeric compounds
JP2019535839A (ja) 2016-11-29 2019-12-12 ピュアテック ヘルス エルエルシー 治療剤の送達のためのエクソソーム
IL308980A (en) 2016-12-23 2024-01-01 Novartis Ag Antibodies against factor XI and methods of their use
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
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
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
HRP20250408T1 (hr) 2017-12-29 2025-06-06 Suzhou Ribo Life Science Co., Ltd. Kojugati i njihova priprema i uporaba
CA3097718A1 (en) * 2018-04-20 2019-10-24 The University Of Vermont And State Agriculture College Compositions and methods for treating cardiovascular disease in selected patients
CA3098136A1 (en) * 2018-05-09 2019-11-14 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing fxi expression
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
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
AU2020280438B2 (en) * 2019-05-22 2025-03-06 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, pharmaceutical composition, conjugate, preparation method, and use
TW202229549A (zh) * 2020-08-04 2022-08-01 大陸商上海拓界生物醫藥科技有限公司 抑制凝血因子ｘｉ表達的ｓｉｒｎａ、組成物及其醫藥用途
IL303800A (en) 2020-12-18 2023-08-01 Ionis Pharmaceuticals Inc Compounds and methods for modulating factor xii
WO2022221441A2 (en) * 2021-04-13 2022-10-20 Sirnaomics, Inc. Products and compositions
TW202333751A (zh) * 2021-12-16 2023-09-01 大陸商上海拓界生物醫藥科技有限公司 一種ｄｓｒｎａ、其製備方法及應用
JP2025500860A (ja) * 2021-12-16 2025-01-15 上海拓界生物医薬科技有限公司 ｄｓＲＮＡ、その調製方法及び使用
UY40743A (es) * 2023-05-19 2024-12-13 Shanghai Argo Biopharmaceutical Co Ltd COMPOSICIONES Y MÉTODOS PARA INHIBIR LA EXPRESIÓN DEL factor de coagulación XI (FXI)
WO2025045194A1 (zh) * 2023-08-31 2025-03-06 正大天晴药业集团股份有限公司 靶向凝血因子xi的双链核糖核酸
CN120712356A (zh) * 2024-01-26 2025-09-26 石药集团中奇制药技术（石家庄）有限公司 一种抑制f11基因表达的核酸分子
WO2025199356A1 (en) * 2024-03-22 2025-09-25 Sirius Therapeutics, Inc. Polynucleic acid molecules for inhibiting expression of fxi, pharmaceutical compositions, and uses thereof

Family Cites Families (193)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3687808A (en) 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
US4500707A (en) 1980-02-29 1985-02-19 University Patents, Inc. Nucleosides useful in the preparation of polynucleotides
US5132418A (en) 1980-02-29 1992-07-21 University Patents, Inc. Process for preparing polynucleotides
US4469863A (en) 1980-11-12 1984-09-04 Ts O Paul O P Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof
US4415732A (en) 1981-03-27 1983-11-15 University Patents, Inc. Phosphoramidite compounds and processes
US4973679A (en) 1981-03-27 1990-11-27 University Patents, Inc. Process for oligonucleo tide synthesis using phosphormidite intermediates
US5023243A (en) 1981-10-23 1991-06-11 Molecular Biosystems, Inc. Oligonucleotide therapeutic agent and method of making same
US4476301A (en) 1982-04-29 1984-10-09 Centre National De La Recherche Scientifique Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon
DE3329892A1 (de) 1983-08-18 1985-03-07 Köster, Hubert, Prof. Dr., 2000 Hamburg Verfahren zur herstellung von oligonucleotiden
US5118800A (en) 1983-12-20 1992-06-02 California Institute Of Technology Oligonucleotides possessing a primary amino group in the terminal nucleotide
USRE34036E (en) 1984-06-06 1992-08-18 National Research Development Corporation Data transmission using a transparent tone-in band system
US5550111A (en) 1984-07-11 1996-08-27 Temple University-Of The Commonwealth System Of Higher Education Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof
FR2567892B1 (fr) 1984-07-19 1989-02-17 Centre Nat Rech Scient Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons
US5367066A (en) 1984-10-16 1994-11-22 Chiron Corporation Oligonucleotides with selectably cleavable and/or abasic sites
FR2575751B1 (fr) 1985-01-08 1987-04-03 Pasteur Institut Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
US5166315A (en) 1989-12-20 1992-11-24 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5185444A (en) 1985-03-15 1993-02-09 Anti-Gene Deveopment Group Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages
US5405938A (en) 1989-12-20 1995-04-11 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5235033A (en) 1985-03-15 1993-08-10 Anti-Gene Development Group Alpha-morpholino ribonucleoside derivatives and polymers thereof
US5506337A (en) 1985-03-15 1996-04-09 Antivirals Inc. Morpholino-subunit combinatorial library and method
DE3788914T2 (de) 1986-09-08 1994-08-25 Ajinomoto Kk Verbindungen zur Spaltung von RNS an eine spezifische Position, Oligomere, verwendet bei der Herstellung dieser Verbindungen und Ausgangsprodukte für die Synthese dieser Oligomere.
US5264423A (en) 1987-03-25 1993-11-23 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US5276019A (en) 1987-03-25 1994-01-04 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
JP2828642B2 (ja) 1987-06-24 1998-11-25 ハワード フローレイ インスティテュト オブ イクスペリメンタル フィジオロジー アンド メディシン ヌクレオシド誘導体
US4924624A (en) 1987-10-22 1990-05-15 Temple University-Of The Commonwealth System Of Higher Education 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof
US5188897A (en) 1987-10-22 1993-02-23 Temple University Of The Commonwealth System Of Higher Education Encapsulated 2',5'-phosphorothioate oligoadenylates
US5403711A (en) 1987-11-30 1995-04-04 University Of Iowa Research Foundation Nucleic acid hybridization and amplification method for detection of specific sequences in which a complementary labeled nucleic acid probe is cleaved
ATE151467T1 (de) 1987-11-30 1997-04-15 Univ Iowa Res Found Durch modifikationen an der 3'-terminalen phosphodiesterbindung stabilisierte dna moleküle, ihre verwendung als nukleinsäuresonden sowie als therapeutische mittel zur hemmung der expression spezifischer zielgene
WO1989009221A1 (en) 1988-03-25 1989-10-05 University Of Virginia Alumni Patents Foundation Oligonucleotide n-alkylphosphoramidates
US5278302A (en) 1988-05-26 1994-01-11 University Patents, Inc. Polynucleotide phosphorodithioates
US5216141A (en) 1988-06-06 1993-06-01 Benner Steven A Oligonucleotide analogs containing sulfur linkages
US5175273A (en) 1988-07-01 1992-12-29 Genentech, Inc. Nucleic acid intercalating agents
US5194599A (en) 1988-09-23 1993-03-16 Gilead Sciences, Inc. Hydrogen phosphonodithioate compositions
US5256775A (en) 1989-06-05 1993-10-26 Gilead Sciences, Inc. Exonuclease-resistant oligonucleotides
US5134066A (en) 1989-08-29 1992-07-28 Monsanto Company Improved probes using nucleosides containing 3-dezauracil analogs
US5591722A (en) 1989-09-15 1997-01-07 Southern Research Institute 2'-deoxy-4'-thioribonucleosides and their antiviral activity
US5399676A (en) 1989-10-23 1995-03-21 Gilead Sciences Oligonucleotides with inverted polarity
US5721218A (en) 1989-10-23 1998-02-24 Gilead Sciences, Inc. Oligonucleotides with inverted polarity
US5264562A (en) 1989-10-24 1993-11-23 Gilead Sciences, Inc. Oligonucleotide analogs with novel linkages
EP0497875B1 (en) 1989-10-24 2000-03-22 Isis Pharmaceuticals, Inc. 2' modified oligonucleotides
US5264564A (en) 1989-10-24 1993-11-23 Gilead Sciences Oligonucleotide analogs with novel linkages
US5177198A (en) 1989-11-30 1993-01-05 University Of N.C. At Chapel Hill Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates
US5130302A (en) 1989-12-20 1992-07-14 Boron Bilogicals, Inc. Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same
US5670633A (en) 1990-01-11 1997-09-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
US7101993B1 (en) 1990-01-11 2006-09-05 Isis Pharmaceuticals, Inc. Oligonucleotides containing 2′-O-modified purines
US5623065A (en) 1990-08-13 1997-04-22 Isis Pharmaceuticals, Inc. Gapped 2' modified oligonucleotides
US5587361A (en) 1991-10-15 1996-12-24 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
US5646265A (en) 1990-01-11 1997-07-08 Isis Pharmceuticals, Inc. Process for the preparation of 2'-O-alkyl purine phosphoramidites
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US6005087A (en) 1995-06-06 1999-12-21 Isis Pharmaceuticals, Inc. 2'-modified oligonucleotides
US5457191A (en) 1990-01-11 1995-10-10 Isis Pharmaceuticals, Inc. 3-deazapurines
US5681941A (en) 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US5859221A (en) 1990-01-11 1999-01-12 Isis Pharmaceuticals, Inc. 2'-modified oligonucleotides
US5587470A (en) 1990-01-11 1996-12-24 Isis Pharmaceuticals, Inc. 3-deazapurines
US5149797A (en) 1990-02-15 1992-09-22 The Worcester Foundation For Experimental Biology Method of site-specific alteration of rna and production of encoded polypeptides
US5220007A (en) 1990-02-15 1993-06-15 The Worcester Foundation For Experimental Biology Method of site-specific alteration of RNA and production of encoded polypeptides
US5321131A (en) 1990-03-08 1994-06-14 Hybridon, Inc. Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling
US5470967A (en) 1990-04-10 1995-11-28 The Dupont Merck Pharmaceutical Company Oligonucleotide analogs with sulfamate linkages
GB9009980D0 (en) 1990-05-03 1990-06-27 Amersham Int Plc Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides
ATE167523T1 (de) 1990-05-11 1998-07-15 Microprobe Corp Teststreifen zum eintauchen für nukleinsäure- hybridisierungsassays und verfahren zur kovalenten immobilisierung von oligonucleotiden
US5378825A (en) 1990-07-27 1995-01-03 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs
US5386023A (en) 1990-07-27 1995-01-31 Isis Pharmaceuticals Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling
US5223618A (en) 1990-08-13 1993-06-29 Isis Pharmaceuticals, Inc. 4'-desmethyl nucleoside analog compounds
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
BR9106702A (pt) 1990-07-27 1993-06-08 Isis Pharmaceuticals Inc Analogo de oligonucleotideos e processos para modular a producao de uma proteina por um organismo e para tratar um organismo
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5677437A (en) 1990-07-27 1997-10-14 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5618704A (en) 1990-07-27 1997-04-08 Isis Pharmacueticals, Inc. Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling
US5623070A (en) 1990-07-27 1997-04-22 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
IL99066A (en) 1990-08-03 1996-01-31 Sterling Winthrop Inc Nuclease resistant compounds comprising an oligonucleotide sequence having a diol at either or both termini and compositions containing them
US5177196A (en) 1990-08-16 1993-01-05 Microprobe Corporation Oligo (α-arabinofuranosyl nucleotides) and α-arabinofuranosyl precursors thereof
US5214134A (en) 1990-09-12 1993-05-25 Sterling Winthrop Inc. Process of linking nucleosides with a siloxane bridge
US5561225A (en) 1990-09-19 1996-10-01 Southern Research Institute Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages
WO1992005186A1 (en) 1990-09-20 1992-04-02 Gilead Sciences Modified internucleoside linkages
US5432272A (en) 1990-10-09 1995-07-11 Benner; Steven A. Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases
US6582908B2 (en) * 1990-12-06 2003-06-24 Affymetrix, Inc. Oligonucleotides
US5948903A (en) 1991-01-11 1999-09-07 Isis Pharmaceuticals, Inc. Synthesis of 3-deazapurines
US5672697A (en) 1991-02-08 1997-09-30 Gilead Sciences, Inc. Nucleoside 5'-methylene phosphonates
FR2676231A1 (fr) * 1991-05-07 1992-11-13 Aetsrn Concentre de facteur xi de la coagulation sanguine a haute activite specifique, approprie a usage therapeutique et son procede de preparation.
US7015315B1 (en) 1991-12-24 2006-03-21 Isis Pharmaceuticals, Inc. Gapped oligonucleotides
US5571799A (en) 1991-08-12 1996-11-05 Basco, Ltd. (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response
DE59208572D1 (de) 1991-10-17 1997-07-10 Ciba Geigy Ag Bicyclische Nukleoside, Oligonukleotide, Verfahren zu deren Herstellung und Zwischenprodukte
US5594121A (en) 1991-11-07 1997-01-14 Gilead Sciences, Inc. Enhanced triple-helix and double-helix formation with oligomers containing modified purines
US5484908A (en) 1991-11-26 1996-01-16 Gilead Sciences, Inc. Oligonucleotides containing 5-propynyl pyrimidines
EP1256589A3 (en) 1991-11-26 2003-09-17 Isis Pharmaceuticals, Inc. Oligomers containing modified pyrimidines
TW393513B (en) 1991-11-26 2000-06-11 Isis Pharmaceuticals Inc Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines
US5792608A (en) 1991-12-12 1998-08-11 Gilead Sciences, Inc. Nuclease stable and binding competent oligomers and methods for their use
US5359044A (en) 1991-12-13 1994-10-25 Isis Pharmaceuticals Cyclobutyl oligonucleotide surrogates
US5700922A (en) 1991-12-24 1997-12-23 Isis Pharmaceuticals, Inc. PNA-DNA-PNA chimeric macromolecules
FR2687679B1 (fr) 1992-02-05 1994-10-28 Centre Nat Rech Scient Oligothionucleotides.
US5633360A (en) 1992-04-14 1997-05-27 Gilead Sciences, Inc. Oligonucleotide analogs capable of passive cell membrane permeation
US5434257A (en) 1992-06-01 1995-07-18 Gilead Sciences, Inc. Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages
EP0577558A2 (de) 1992-07-01 1994-01-05 Ciba-Geigy Ag Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte
US5652355A (en) 1992-07-23 1997-07-29 Worcester Foundation For Experimental Biology Hybrid oligonucleotide phosphorothioates
US5476925A (en) 1993-02-01 1995-12-19 Northwestern University Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups
GB9304618D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Chemical compounds
GB9304620D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Compounds
ATE155467T1 (de) 1993-03-30 1997-08-15 Sanofi Sa Acyclische nucleosid analoge und sie enthaltende oligonucleotidsequenzen
EP0691977B1 (en) 1993-03-31 1997-11-26 Sanofi Oligonucleotides with amide linkages replacing phosphodiester linkages
US5502177A (en) 1993-09-17 1996-03-26 Gilead Sciences, Inc. Pyrimidine derivatives for labeled binding partners
US5801154A (en) * 1993-10-18 1998-09-01 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of multidrug resistance-associated protein
US5457187A (en) 1993-12-08 1995-10-10 Board Of Regents University Of Nebraska Oligonucleotides containing 5-fluorouracil
US5446137B1 (en) 1993-12-09 1998-10-06 Behringwerke Ag Oligonucleotides containing 4'-substituted nucleotides
NZ278490A (en) 1993-12-09 1998-03-25 Univ Jefferson Chimeric polynucleotide with both ribo- and deoxyribonucleotides in one strand and deoxyribonucleotides in a second strand
WO1995017420A1 (en) * 1993-12-22 1995-06-29 Temple University - Of The Commonwealth System Of Higher Education Peptide analogs of the activated platelet binding site on factor xi
US5519134A (en) 1994-01-11 1996-05-21 Isis Pharmaceuticals, Inc. Pyrrolidine-containing monomers and oligomers
US5596091A (en) 1994-03-18 1997-01-21 The Regents Of The University Of California Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides
US5627053A (en) 1994-03-29 1997-05-06 Ribozyme Pharmaceuticals, Inc. 2'deoxy-2'-alkylnucleotide containing nucleic acid
US5625050A (en) 1994-03-31 1997-04-29 Amgen Inc. Modified oligonucleotides and intermediates useful in nucleic acid therapeutics
US5646269A (en) 1994-04-28 1997-07-08 Gilead Sciences, Inc. Method for oligonucleotide analog synthesis
US5525711A (en) 1994-05-18 1996-06-11 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Pteridine nucleotide analogs as fluorescent DNA probes
US5597909A (en) 1994-08-25 1997-01-28 Chiron Corporation Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use
US5652356A (en) 1995-08-17 1997-07-29 Hybridon, Inc. Inverted chimeric and hybrid oligonucleotides
EP0862439A4 (en) 1995-11-22 2001-01-10 O Paul O P Ts LIGANDS FOR INCREASING THE CELLULAR UPtake OF BIOMOLECULES
US6770748B2 (en) 1997-03-07 2004-08-03 Takeshi Imanishi Bicyclonucleoside and oligonucleotide analogue
USRE44779E1 (en) 1997-03-07 2014-02-25 Santaris Pharma A/S Bicyclonucleoside and oligonucleotide analogues
ATE293123T1 (de) 1997-09-12 2005-04-15 Exiqon As Bi- und tri-zyklische - nukleosid, nukleotid und oligonukleotid-analoga
US7572582B2 (en) 1997-09-12 2009-08-11 Exiqon A/S Oligonucleotide analogues
US20030228597A1 (en) * 1998-04-13 2003-12-11 Cowsert Lex M. Identification of genetic targets for modulation by oligonucleotides and generation of oligonucleotides for gene modulation
ATE274600T1 (de) 1998-06-08 2004-09-15 Univ Vermont Verfahren zur bestimmung der blutgerinnung in plasma
US6300319B1 (en) 1998-06-16 2001-10-09 Isis Pharmaceuticals, Inc. Targeted oligonucleotide conjugates
US6043352A (en) 1998-08-07 2000-03-28 Isis Pharmaceuticals, Inc. 2'-O-Dimethylaminoethyloxyethyl-modified oligonucleotides
AU767172B2 (en) * 1999-03-18 2003-11-06 Merck Patent Gmbh Protein for blocking platelet adhesion
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
US7491805B2 (en) 2001-05-18 2009-02-17 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
US6426220B1 (en) 2000-10-30 2002-07-30 Isis Pharmaceuticals, Inc. Antisense modulation of calreticulin expression
CN100406065C (zh) 2000-12-01 2008-07-30 细胞工厂治疗公司 糖基化/半乳糖基化肽、双官能接头和核苷酸单体/多聚体的缀合物以及相关的组合物和使用方法
DE10111925A1 (de) * 2001-03-13 2002-10-02 Ogham Gmbh Herzchip
US20030175906A1 (en) 2001-07-03 2003-09-18 Muthiah Manoharan Nuclease resistant chimeric oligonucleotides
CA2452458A1 (en) 2001-07-03 2003-01-16 Isis Pharmaceuticals, Inc. Nuclease resistant chimeric oligonucleotides
US20030158403A1 (en) 2001-07-03 2003-08-21 Isis Pharmaceuticals, Inc. Nuclease resistant chimeric oligonucleotides
US20030040480A1 (en) * 2001-07-20 2003-02-27 Rasmus Rojkjaer Pharmaceutical composition comprising factor VII polypeptides and factor XI polypeptides
WO2003013423A2 (en) * 2001-08-05 2003-02-20 Gvg, Inc. Antithrombotic agent
US20040142325A1 (en) 2001-09-14 2004-07-22 Liat Mintz Methods and systems for annotating biomolecular sequences
US7176303B2 (en) 2003-11-06 2007-02-13 Isis Pharmaceuticals, Inc. Modulation of STAT5 expression
US8604183B2 (en) 2002-11-05 2013-12-10 Isis Pharmaceuticals, Inc. Compositions comprising alternating 2′-modified nucleosides for use in gene modulation
CA2504694C (en) 2002-11-05 2013-10-01 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
EP2213738B1 (en) * 2002-11-14 2012-10-10 Dharmacon, Inc. siRNA molecules targeting Bcl-2
US7144999B2 (en) * 2002-11-23 2006-12-05 Isis Pharmaceuticals, Inc. Modulation of hypoxia-inducible factor 1 alpha expression
US20040180855A1 (en) 2003-02-19 2004-09-16 Schumacher William A. Methods of treating thrombosis with reduced risk of increased bleeding times
US7723509B2 (en) 2003-04-17 2010-05-25 Alnylam Pharmaceuticals IRNA agents with biocleavable tethers
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
US20050181978A1 (en) * 2003-11-20 2005-08-18 Rasmus Rojkjaer Therapeutic use of factor XI
DK1745062T3 (da) 2004-04-22 2014-08-11 Regado Biosciences Inc Forbedrede modulatorer af koagulationsfaktorer
KR20070085113A (ko) * 2004-05-11 2007-08-27 가부시키가이샤 알파젠 Rna간섭을 생기게 하는 폴리뉴클레오티드, 및 이를 이용한유전자발현억제 방법
US8394947B2 (en) * 2004-06-03 2013-03-12 Isis Pharmaceuticals, Inc. Positionally modified siRNA constructs
WO2006034348A2 (en) * 2004-09-17 2006-03-30 Isis Pharmaceuticals, Inc. Enhanced antisense oligonucleotides
JP2008518610A (ja) 2004-11-03 2008-06-05 アルマック ダイアグノスティックス リミテッド トランスクリプトームマイクロアレイ技法およびそれを使用する方法
US20060148740A1 (en) 2005-01-05 2006-07-06 Prosensa B.V. Mannose-6-phosphate receptor mediated gene transfer into muscle cells
US7512842B2 (en) * 2005-08-29 2009-03-31 Searete Llc Multi-voltage synchronous systems
EP2338992A3 (en) * 2005-08-29 2011-10-12 Regulus Therapeutics, Inc Antisense compounds having enhanced anti-microRNA activity
WO2007059966A1 (en) * 2005-11-23 2007-05-31 Georg Dewald Detection and treatment of drug associated angioedema
WO2007089611A2 (en) * 2006-01-26 2007-08-09 Isis Pharmaceuticals Inc. Compositions and their uses directed to huntingtin
US7569686B1 (en) 2006-01-27 2009-08-04 Isis Pharmaceuticals, Inc. Compounds and methods for synthesis of bicyclic nucleic acid analogs
EP1984381B1 (en) 2006-01-27 2010-09-29 Isis Pharmaceuticals, Inc. 6-modified bicyclic nucleic acid analogs
EP2023940B1 (en) 2006-05-05 2011-06-22 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of sglt2
US7666854B2 (en) 2006-05-11 2010-02-23 Isis Pharmaceuticals, Inc. Bis-modified bicyclic nucleic acid analogs
DK2066684T3 (da) 2006-05-11 2012-10-22 Isis Pharmaceuticals Inc 5´-Modificerede bicycliske nukleinsyreanaloge
US20080021999A1 (en) * 2006-07-18 2008-01-24 Aspect Software, Inc. Remote expert screen pop via data message
US20080021998A1 (en) 2006-07-20 2008-01-24 Rachel Wentink Presence-based resource locator
ES2377327T5 (es) 2006-10-18 2020-04-28 Ionis Pharmaceuticals Inc Compuestos antisentido
EP2455471A3 (en) * 2006-11-27 2012-09-12 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
US7521213B2 (en) 2006-12-01 2009-04-21 Quest Diagnostics Investments Incorporated Sample processing for nucleic acid amplification
EP2125852B1 (en) 2007-02-15 2016-04-06 Ionis Pharmaceuticals, Inc. 5'-substituted-2'-f modified nucleosides and oligomeric compounds prepared therefrom
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
CN101796062B (zh) 2007-07-05 2014-07-30 Isis制药公司 6-双取代双环核酸类似物
EP2188298B1 (en) 2007-08-15 2013-09-18 Isis Pharmaceuticals, Inc. Tetrahydropyran nucleic acid analogs
WO2009067647A1 (en) 2007-11-21 2009-05-28 Isis Pharmaceuticals, Inc. Carbocyclic alpha-l-bicyclic nucleic acid analogs
WO2009067660A2 (en) 2007-11-21 2009-05-28 Oregon Health & Science University Anti-factor xi monoclonal antibodies and methods of use thereof
AU2008340355B2 (en) 2007-12-04 2015-01-22 Tekmira Pharmaceuticals Corporation Targeting lipids
EP2265627A2 (en) 2008-02-07 2010-12-29 Isis Pharmaceuticals, Inc. Bicyclic cyclohexitol nucleic acid analogs
WO2010036698A1 (en) 2008-09-24 2010-04-01 Isis Pharmaceuticals, Inc. Substituted alpha-l-bicyclic nucleosides
US8334372B2 (en) 2008-10-15 2012-12-18 Isis Pharmaceuticals, Inc. Modulation of factor 11 expression
BRPI1015236A2 (pt) * 2009-04-15 2019-09-24 Isis Pharmaceuticals Inc métodos para modular uma resposta inflamatória, apra melhorar uma doença, distúrbio ou condição inflamatórios em um animal, para tratar um animal em risco para uma doença, distúrbio ou condição inflamatórios, para inibir a expressão de fator xi em um animal, para reduzir o risco de doença, distúrbio ou condição inflamatórios, em um animal, para tratar um animal em risco para uma doença inflamatória, e para tratar um animal tendo uma doença inflamatória, e, uso de um composto marcado para fator xi
US9012421B2 (en) 2009-08-06 2015-04-21 Isis Pharmaceuticals, Inc. Bicyclic cyclohexose nucleic acid analogs
US10913767B2 (en) 2010-04-22 2021-02-09 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising acyclic and abasic nucleosides and analogs
JP2013541334A (ja) 2010-09-15 2013-11-14 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 修飾されたｉＲＮＡ剤
EP3067421B1 (en) 2011-02-08 2018-10-10 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
US10023861B2 (en) 2011-08-29 2018-07-17 Ionis Pharmaceuticals, Inc. Oligomer-conjugate complexes and their use
AU2012327227A1 (en) 2011-11-07 2013-05-23 Isis Pharmaceuticals, Inc. Administration of Factor XI antisense oligonucleotides
US9914922B2 (en) 2012-04-20 2018-03-13 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
WO2014059353A2 (en) 2012-10-11 2014-04-17 Isis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleosides and uses thereof
WO2014076196A1 (en) 2012-11-15 2014-05-22 Santaris Pharma A/S Anti apob antisense conjugate compounds
RU2670614C9 (ru) 2013-05-01 2018-11-23 Ионис Фармасьютикалз, Инк. Композиции и способы модулирования экспрессии hbv и ttr
US20170145424A1 (en) 2014-06-06 2017-05-25 Ionis Pharmaceuticals, Inc. Compositions and methods for enhanced intestinal absorption of conjugated oligomeric compounds
CA3098136A1 (en) 2018-05-09 2019-11-14 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing fxi expression

Also Published As

Publication number Publication date
CA2740785A1 (en) 2010-04-22
EP2379084A4 (en) 2012-06-06
AU2017202862A1 (en) 2017-05-18
EP2379084B1 (en) 2017-11-22
CN104212799B (zh) 2018-11-23
HUE035888T2 (en) 2018-05-28
CN104212799A (zh) 2014-12-17
CN109797150A (zh) 2019-05-24
US20130274308A1 (en) 2013-10-17
US20200000839A1 (en) 2020-01-02
SI2379084T1 (en) 2018-04-30
EP3335715A3 (en) 2018-08-08
US8334372B2 (en) 2012-12-18
HRP20171969T1 (hr) 2018-04-06
NZ603603A (en) 2014-06-27
CA2966011C (en) 2021-10-19
US20100137414A1 (en) 2010-06-03
JP6397517B2 (ja) 2018-09-26
NZ592203A (en) 2013-01-25
JP6633155B2 (ja) 2020-01-22
US10772906B2 (en) 2020-09-15
PT2379084T (pt) 2018-02-19
KR101979134B1 (ko) 2019-05-15
RU2011119479A (ru) 2012-11-27
CN102245186B (zh) 2014-08-27
PL2379084T3 (pl) 2018-04-30
DK2379084T3 (en) 2018-01-22
EP2379084A2 (en) 2011-10-26
CA2966011A1 (en) 2010-04-22
CN103820450A (zh) 2014-05-28
IL212267A (en) 2016-02-29
KR20110081294A (ko) 2011-07-13
EP3335715A2 (en) 2018-06-20
AU2009305636A1 (en) 2010-04-22
WO2010045509A3 (en) 2010-07-15
US11376273B2 (en) 2022-07-05
JP2017099395A (ja) 2017-06-08
JP6084255B2 (ja) 2017-02-22
US20230263822A1 (en) 2023-08-24
US20170035798A1 (en) 2017-02-09
IL212267A0 (en) 2011-06-30
RU2739594C2 (ru) 2020-12-28
KR101773551B1 (ko) 2017-08-31
IL244116A0 (en) 2016-04-21
RU2535964C2 (ru) 2014-12-20
US20130190384A1 (en) 2013-07-25
CN102245186A (zh) 2011-11-16
AU2017202862B2 (en) 2018-09-20
CY1119909T1 (el) 2018-06-27
JP2018199700A (ja) 2018-12-20
BRPI0920263A2 (pt) 2016-07-12
US20210169921A1 (en) 2021-06-10
NO2379084T3 (enExample) 2018-04-21
BRPI0920263B1 (pt) 2021-09-21
IL244116B (en) 2019-03-31
US8735370B2 (en) 2014-05-27
MX2011004097A (es) 2011-07-28
JP2015211685A (ja) 2015-11-26
CA2740785C (en) 2017-06-20
KR20170101324A (ko) 2017-09-05
JP2012505660A (ja) 2012-03-08
RU2014134408A (ru) 2016-03-20
WO2010045509A2 (en) 2010-04-22
LT2379084T (lt) 2018-03-26
JP5809058B2 (ja) 2015-11-10
CN103820450B (zh) 2018-08-21

Similar Documents

Publication Publication Date Title
ES2657679T3 (es) Modulación del factor de expresión 11
US11535849B2 (en) Modulation of transthyretin expression
ES2567132T3 (es) Modulación de la expresión del receptor de la hormona de crecimiento y de IGF-I
AU2006336624B2 (en) Modulation of gene expression by oligomers targeted to chromosomal DNA
EP3126499B1 (en) Compositions for modulating sod-1 expression
ES2733708T3 (es) Reducción selectiva de variantes alélicas
EP3043827B1 (en) Modulators of complement factor b
RU2700244C2 (ru) Модуляторы рецептора гормона роста
AU2013216852A1 (en) Methods and compositions for modulating Factor VII expression
AU2014337506A1 (en) Methods for modulating expression of C9ORF72 antisense transcript
KR20040085150A (ko) 아이지에프비피-2 및 아이지에프비피-5를 억제하는양특이성 안티센스 올리고뉴클레오티드 및 그 사용방법
JP2006502243A5 (enExample)
AU6259396A (en) Therapeutic oligonucleotides targeting the human MDR1 and MRP genes
CN103597075A (zh) 用于选择性地杀伤细胞的生物活性核苷酸分子、其用途及应用试剂盒
AU2016203300B2 (en) Modulation of transthyretin expression
WO2025045130A1 (zh) 一种抑制sod1基因表达的dsrna分子及其应用
NZ715151B2 (en) Modulators of growth hormone receptor
HK1180005A (en) Modulation of transthyretin expression
HK1180005B (en) Modulation of transthyretin expression
HK1233301B (en) Compositions for modulating sod-1 expression
HK1233301A1 (en) Compositions for modulating sod-1 expression
HK1225638B (en) Modulators of complement factor b
AU2011248467A1 (en) Modulation of transthyretin expression