JP5791505B2 - トランスチレチンの発現を阻害するための組成物および方法 - Google Patents

トランスチレチンの発現を阻害するための組成物および方法 Download PDF

Info

Publication number
JP5791505B2
JP5791505B2 JP2011533279A JP2011533279A JP5791505B2 JP 5791505 B2 JP5791505 B2 JP 5791505B2 JP 2011533279 A JP2011533279 A JP 2011533279A JP 2011533279 A JP2011533279 A JP 2011533279A JP 5791505 B2 JP5791505 B2 JP 5791505B2
Authority
JP
Japan
Prior art keywords
dsrna
ttr
seq
nucleotides
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
JP2011533279A
Other languages
English (en)
Japanese (ja)
Other versions
JP2012506254A5 (enExample
JP2012506254A (ja
Inventor
ダイナ・ウェン−イー・サー
グレゴリー・ヒンクル
レネ・アルバレズ
スチュアート・ミルスタイン
チェン・キンミン
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.)
Alnylam Pharmaceuticals Inc
Original Assignee
Alnylam 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 Alnylam Pharmaceuticals Inc filed Critical Alnylam Pharmaceuticals Inc
Publication of JP2012506254A publication Critical patent/JP2012506254A/ja
Publication of JP2012506254A5 publication Critical patent/JP2012506254A5/ja
Application granted granted Critical
Publication of JP5791505B2 publication Critical patent/JP5791505B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/02—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—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
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • 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
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6527—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07F9/6533—Six-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/111—General methods applicable to biologically active non-coding nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—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
    • C12N2310/335—Modified T or U
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3515—Lipophilic moiety, e.g. cholesterol
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/352—Nature of the modification linked to the nucleic acid via a carbon atom
    • C12N2310/3521—Methyl
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C12N2320/32—Special delivery means, e.g. tissue-specific

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Epidemiology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Dermatology (AREA)
  • Cardiology (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Endocrinology (AREA)
  • Diabetes (AREA)
  • Gastroenterology & Hepatology (AREA)
JP2011533279A 2008-10-20 2009-10-20 トランスチレチンの発現を阻害するための組成物および方法 Active JP5791505B2 (ja)

Applications Claiming Priority (13)

Application Number Priority Date Filing Date Title
US10695608P 2008-10-20 2008-10-20
US61/106,956 2008-10-20
US11573808P 2008-11-18 2008-11-18
US61/115,738 2008-11-18
US15667009P 2009-03-02 2009-03-02
US61/156,670 2009-03-02
US18554509P 2009-06-09 2009-06-09
US61/185,545 2009-06-09
US24278309P 2009-09-15 2009-09-15
US61/242,783 2009-09-15
US24479409P 2009-09-22 2009-09-22
US61/244,794 2009-09-22
PCT/US2009/061381 WO2010048228A2 (en) 2008-10-20 2009-10-20 Compositions and methods for inhibiting expression of transthyretin

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2014214774A Division JP2015062420A (ja) 2008-10-20 2014-10-21 トランスチレチンの発現を阻害するための組成物および方法

Publications (3)

Publication Number Publication Date
JP2012506254A JP2012506254A (ja) 2012-03-15
JP2012506254A5 JP2012506254A5 (enExample) 2012-12-06
JP5791505B2 true JP5791505B2 (ja) 2015-10-07

Family

ID=42062316

Family Applications (7)

Application Number Title Priority Date Filing Date
JP2011533279A Active JP5791505B2 (ja) 2008-10-20 2009-10-20 トランスチレチンの発現を阻害するための組成物および方法
JP2014214774A Pending JP2015062420A (ja) 2008-10-20 2014-10-21 トランスチレチンの発現を阻害するための組成物および方法
JP2017132506A Active JP6371446B2 (ja) 2008-10-20 2017-07-06 トランスチレチンの発現を阻害するための組成物および方法
JP2018132510A Active JP6553780B2 (ja) 2008-10-20 2018-07-12 トランスチレチンの発現を阻害するための組成物および方法
JP2019125381A Pending JP2019205442A (ja) 2008-10-20 2019-07-04 トランスチレチンの発現を阻害するための組成物および方法
JP2022106180A Active JP7500658B2 (ja) 2008-10-20 2022-06-30 トランスチレチンの発現を阻害するための組成物および方法
JP2024091123A Active JP7806130B2 (ja) 2008-10-20 2024-06-05 トランスチレチンの発現を阻害するための組成物および方法

Family Applications After (6)

Application Number Title Priority Date Filing Date
JP2014214774A Pending JP2015062420A (ja) 2008-10-20 2014-10-21 トランスチレチンの発現を阻害するための組成物および方法
JP2017132506A Active JP6371446B2 (ja) 2008-10-20 2017-07-06 トランスチレチンの発現を阻害するための組成物および方法
JP2018132510A Active JP6553780B2 (ja) 2008-10-20 2018-07-12 トランスチレチンの発現を阻害するための組成物および方法
JP2019125381A Pending JP2019205442A (ja) 2008-10-20 2019-07-04 トランスチレチンの発現を阻害するための組成物および方法
JP2022106180A Active JP7500658B2 (ja) 2008-10-20 2022-06-30 トランスチレチンの発現を阻害するための組成物および方法
JP2024091123A Active JP7806130B2 (ja) 2008-10-20 2024-06-05 トランスチレチンの発現を阻害するための組成物および方法

Country Status (27)

Country Link
US (9) US8168775B2 (enExample)
EP (4) EP3354733B1 (enExample)
JP (7) JP5791505B2 (enExample)
KR (6) KR102354558B1 (enExample)
CN (3) CN106834291B (enExample)
AU (1) AU2009307677C1 (enExample)
CA (3) CA2739895C (enExample)
CY (3) CY1116944T1 (enExample)
DK (2) DK2344639T3 (enExample)
EA (3) EA029762B1 (enExample)
ES (2) ES2543004T3 (enExample)
HR (2) HRP20150796T1 (enExample)
HU (3) HUE026604T2 (enExample)
IL (5) IL302142B2 (enExample)
LT (2) LT2937418T (enExample)
LU (1) LUC00098I2 (enExample)
MX (4) MX344354B (enExample)
NL (1) NL300965I2 (enExample)
NO (2) NO2937418T3 (enExample)
NZ (2) NZ592867A (enExample)
PL (2) PL2344639T3 (enExample)
PT (2) PT2937418T (enExample)
SG (3) SG10201809460SA (enExample)
SI (2) SI2344639T1 (enExample)
SM (2) SMT201800027T1 (enExample)
WO (1) WO2010048228A2 (enExample)
ZA (1) ZA201102876B (enExample)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2017071616A (ja) * 2009-11-03 2017-04-13 アルナイラム ファーマシューティカルズ， インコーポレイテッドＡｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． トランスサイレチン（ｔｔｒ）を阻害する脂質製剤化組成物及び方法

Families Citing this family (136)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9228186B2 (en) 2002-11-14 2016-01-05 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
US20050244869A1 (en) * 2004-04-05 2005-11-03 Brown-Driver Vickie L Modulation of transthyretin expression
EP2194128B1 (en) 2006-05-11 2012-08-01 Alnylam Pharmaceuticals Inc. Compositions and methods for inhibiting expression of the PCSK9 gene
CA2721333C (en) 2008-04-15 2020-12-01 Protiva Biotherapeutics, Inc. Novel lipid formulations for nucleic acid delivery
SG10201809460SA (en) * 2008-10-20 2018-11-29 Alnylam Pharmaceuticals Inc Compositions and methods for inhibiting expression of transthyretin
DK2355851T3 (en) 2008-11-10 2018-06-25 Arbutus Biopharma Corp Newly known lipids and compositions for release of therapeutic agents
CA2746514C (en) 2008-12-10 2018-11-27 Alnylam Pharmaceuticals, Inc. Gnaq targeted dsrna compositions and methods for inhibiting expression
US20120101148A1 (en) * 2009-01-29 2012-04-26 Alnylam Pharmaceuticals, Inc. lipid formulation
CA2764609C (en) * 2009-06-10 2018-10-02 Alnylam Pharmaceuticals, Inc. Improved cationic lipid of formula i
US9051567B2 (en) 2009-06-15 2015-06-09 Tekmira Pharmaceuticals Corporation Methods for increasing efficacy of lipid formulated siRNA
KR20120050429A (ko) * 2009-06-15 2012-05-18 알닐람 파마슈티칼스 인코포레이티드 Ｐｃｓｋ9 유전자를 표적으로 하는 지질 제형된 ｄｓｒｎａ
JP5766188B2 (ja) 2009-07-01 2015-08-19 プロチバ バイオセラピューティクス インコーポレイティッド 固形腫瘍に治療剤を送達するための脂質製剤
AP2015008874A0 (en) * 2009-08-14 2015-11-30 Alnylam Pharmaceuticals Inc Lipid formulated compositions and methods for inhibiting expression of a gene from the ebola virus
US20130281510A1 (en) * 2010-03-29 2013-10-24 Kumamoto University siRNA Therapy for Transthyretin (TTR) Related Ocular Amyloidosis
US20230340473A1 (en) * 2010-03-29 2023-10-26 Alnylam Pharmaceuticals, Inc. Sirna therapy for transthyretin (ttr) related ocular amyloidosis
ES2625689T3 (es) * 2010-04-29 2017-07-20 Ionis Pharmaceuticals, Inc. Modulación de la expresión de transtiretina
EP2569276B1 (en) * 2010-05-12 2021-02-24 Arbutus Biopharma Corporation Novel cationic lipids and methods of use thereof
AU2011261434B2 (en) * 2010-06-02 2015-11-26 Alnylam Pharmaceuticals, Inc. Compositions and methods directed to treating liver fibrosis
US9006417B2 (en) 2010-06-30 2015-04-14 Protiva Biotherapeutics, Inc. Non-liposomal systems for nucleic acid delivery
EP3485913A1 (en) 2010-10-21 2019-05-22 Sirna Therapeutics, Inc. Low molecular weight cationic lipids for oligonucleotide delivery
BR122022001262B1 (pt) * 2010-11-15 2022-09-27 Life Technologies Corporation Compostos de transfecção contendo amina e complexo de transfecção
US9127275B2 (en) * 2010-12-10 2015-09-08 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of klf-1 and bcl11a genes
EP2525223A1 (en) * 2011-05-19 2012-11-21 Universiteit Maastricht In vitro method for predicting in vivo genotoxicity of chemical compounds.
EP3564393A1 (en) * 2011-06-21 2019-11-06 Alnylam Pharmaceuticals, Inc. Assays and methods for determining activity of a therapeutic agent in a subject
CN103890000B (zh) 2011-06-21 2017-09-01 阿尔尼拉姆医药品有限公司 血管生成素样3(ANGPTL3)iRNA组合物及其使用方法
WO2012177921A2 (en) * 2011-06-21 2012-12-27 Alnylam Pharmaceuticals, Inc Compositions and methods for inhibiting hepcidin antimicrobial peptide (hamp) or hamp-related gene expression
WO2013075035A1 (en) * 2011-11-18 2013-05-23 Alnylam Pharmaceuticals Rnai agents, compositions and methods of use thereof for treating transthyretin (ttr) associated diseases
EP3988537A1 (en) 2011-12-07 2022-04-27 Alnylam Pharmaceuticals, Inc. Biodegradable lipids for the delivery of active agents
US9035039B2 (en) * 2011-12-22 2015-05-19 Protiva Biotherapeutics, Inc. Compositions and methods for silencing SMAD4
US9597380B2 (en) 2012-11-26 2017-03-21 Modernatx, Inc. Terminally modified RNA
PT2929031T (pt) 2012-12-05 2018-01-19 Alnylam Pharmaceuticals Inc Composições de irna de pcsk9 e métodos de seu uso
WO2014093622A2 (en) 2012-12-12 2014-06-19 The Broad Institute, Inc. Delivery, engineering and optimization of systems, methods and compositions for sequence manipulation and therapeutic applications
WO2014093701A1 (en) 2012-12-12 2014-06-19 The Broad Institute, Inc. Functional genomics using crispr-cas systems, compositions, methods, knock out libraries and applications thereof
JP2016504050A (ja) 2013-01-17 2016-02-12 モデルナ セラピューティクス インコーポレイテッドＭｏｄｅｒｎａ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． 細胞表現型の改変のためのシグナルセンサーポリヌクレオチド
EP2953970A4 (en) 2013-02-08 2016-06-29 Misfolding Diagnostics Inc TRANSTYRETIN ANTIBODIES AND USES THEREOF
JP2016522679A (ja) 2013-04-04 2016-08-04 プレジデント アンド フェローズ オブ ハーバード カレッジ ＣＲＩＳＰＲ／Ｃａｓ系を用いたゲノム編集の治療的使用
PE20152002A1 (es) 2013-05-01 2016-01-21 Isis Pharmaceuticals Inc Composiciones y metodos para modular la expresion de ttr y vhb
KR20240172759A (ko) 2013-06-17 2024-12-10 더 브로드 인스티튜트, 인코퍼레이티드 간의 표적화 및 치료를 위한 ＣＲＩＳＰＲ­Ｃａｓ 시스템, 벡터 및 조성물의 전달 및 용도
EP3011033B1 (en) 2013-06-17 2020-02-19 The Broad Institute, Inc. Functional genomics using crispr-cas systems, compositions methods, screens and applications thereof
CA2915837A1 (en) 2013-06-17 2014-12-24 The Broad Institute, Inc. Optimized crispr-cas double nickase systems, methods and compositions for sequence manipulation
EP3019595A4 (en) 2013-07-09 2016-11-30 THERAPEUTIC USES OF A GENERIC CHANGE WITH CRISPR / CAS SYSTEMS
TW201610151A (zh) * 2013-09-23 2016-03-16 阿尼拉製藥公司 治療或預防與甲狀腺素運載蛋白相關疾病之方法
TWI669393B (zh) * 2013-10-02 2019-08-21 艾爾妮蘭製藥公司 抑制ｌｅｃｔ２基因表現之組合物及方法
AU2014360314B2 (en) 2013-12-06 2018-04-26 Dicerna Pharmaceuticals, Inc. Methods and compositions for the specific inhibition of transthyretin (TTR) by double-stranded RNA
EP3080271B1 (en) 2013-12-12 2020-02-12 The Broad Institute, Inc. Systems, methods and compositions for sequence manipulation with optimized functional crispr-cas systems
WO2015089354A1 (en) 2013-12-12 2015-06-18 The Broad Institute Inc. Compositions and methods of use of crispr-cas systems in nucleotide repeat disorders
EP3080259B1 (en) 2013-12-12 2023-02-01 The Broad Institute, Inc. Engineering of systems, methods and optimized guide compositions with new architectures for sequence manipulation
CN105899658B (zh) 2013-12-12 2020-02-18 布罗德研究所有限公司 针对hbv和病毒性疾病以及障碍的crispr-cas系统和组合物的递送、用途和治疗应用
JP6771387B2 (ja) * 2014-03-25 2020-10-21 アークトゥラス・セラピューティクス・インコーポレイテッドＡｒｃｔｕｒｕｓ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． 遺伝子サイレンシング用トランスサイレチン対立遺伝子選択的ｕｎａオリゴマー
US9856475B2 (en) 2014-03-25 2018-01-02 Arcturus Therapeutics, Inc. Formulations for treating amyloidosis
CA2946719C (en) * 2014-03-25 2023-09-26 Arcturus Therapeutics, Inc. Una oligomers having reduced off-target effects in gene silencing
RS59182B1 (sr) 2014-05-01 2019-10-31 Ionis Pharmaceuticals Inc Kompozicije i postupci za modulaciju ekspresije faktora b komplementa
LT3185957T (lt) * 2014-08-29 2022-09-26 Alnylam Pharmaceuticals, Inc. Patisiranas, skirtas naudoti transtiretino amiloidozei gydyti
US12180263B2 (en) 2014-11-06 2024-12-31 President And Fellows Of Harvard College Cells lacking B2M surface expression and methods for allogeneic administration of such cells
EP3889260A1 (en) 2014-12-12 2021-10-06 The Broad Institute, Inc. Protected guide rnas (pgrnas)
CA2970370A1 (en) 2014-12-24 2016-06-30 Massachusetts Institute Of Technology Crispr having or associated with destabilization domains
US10519447B2 (en) 2015-04-01 2019-12-31 Arcturus Therapeutics, Inc. Therapeutic UNA oligomers and uses thereof
WO2016164746A1 (en) 2015-04-08 2016-10-13 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the lect2 gene
KR20250005546A (ko) 2015-04-13 2025-01-09 알닐람 파마슈티칼스 인코포레이티드 안지오포이에틴-유사 3(angptl3) irna 조성물 및 이의 이용 방법
CN107921148A (zh) 2015-05-08 2018-04-17 哈佛学院校长同事会 通用供体干细胞和相关方法
WO2016205759A1 (en) 2015-06-18 2016-12-22 The Broad Institute Inc. Engineering and optimization of systems, methods, enzymes and guide scaffolds of cas9 orthologs and variants for sequence manipulation
MX392008B (es) 2015-06-18 2025-03-21 Broad Inst Inc Mutaciones de la enzima crispr que reducen los efectos fuera del blanco
WO2017015671A1 (en) * 2015-07-23 2017-01-26 Arcturus Therapeutics, Inc. Compositions for treating amyloidosis
PL3329002T3 (pl) 2015-07-31 2021-04-19 Alnylam Pharmaceuticals, Inc. Kompozycje irna transtyretyny (ttr) i sposoby ich zastosowania do leczenia lub zapobiegania chorobom związanym z ttr
MX2018009854A (es) 2016-03-07 2018-11-09 Arrowhead Pharmaceuticals Inc Ligandos dirigidos para compuestos terapeuticos.
CN116832169A (zh) 2016-09-02 2023-10-03 箭头药业股份有限公司 靶向配体
KR20190065341A (ko) 2016-10-06 2019-06-11 아이오니스 파마수티컬즈, 인코포레이티드 올리고머 화합물들의 접합 방법
WO2018102397A1 (en) 2016-11-29 2018-06-07 PureTech Health LLC Exosomes for delivery of therapeutic agents
CN116730921A (zh) 2017-02-17 2023-09-12 文涵治疗有限公司 Ag-10的制备方法、其中间体及其盐
BR112020005230A2 (pt) 2017-09-19 2020-09-24 Alnylam Pharmaceuticals, Inc. composições e métodos para o tratamento da amiloidose mediada por transtiretina (ttr)
MX2020003608A (es) 2017-09-29 2020-09-25 Intellia Therapeutics Inc Composiciones y métodos para la edición del gen ttr y el tratamiento de la amiloidosis attr.
ES2962277T3 (es) 2017-09-29 2024-03-18 Regeneron Pharma Roedores que comprenden un locus Ttr humanizado y métodos de uso
MA52137A (fr) * 2018-03-23 2021-01-27 Eidos Therapeutics Inc Méthodes de traitement de l'amylose ttr à l'aide d'ag10
JP7469293B2 (ja) 2018-08-17 2024-04-16 エイドス セラピューティクス，インコーポレイティド Ａｇ１０の製剤
JP7555123B2 (ja) 2018-10-09 2024-09-24 ザ ユニヴァーシティ オブ ブリティッシュ コロンビア 有機溶媒不含かつ劣化剤不含のトランスフェクション・コンピテント・ベシクルを含む組成物及びシステム並びにそれらに関連する方法
WO2020128816A2 (en) 2018-12-20 2020-06-25 Pfizer Inc. Pharmaceutical compositions and methods comprising a combination of a benzoxazole transthyretin stabilizer and an additional therapeutic agent
EP3801011A1 (en) 2019-06-04 2021-04-14 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized ttr locus with a beta-slip mutation and methods of use
CN114423869A (zh) 2019-07-19 2022-04-29 旗舰先锋创新Vi有限责任公司 重组酶组合物和使用方法
WO2021041884A1 (en) 2019-08-30 2021-03-04 Alnylam Pharmaceuticals, Inc. Neurofilament light chain (nfl) as a biomarker for transthyretin amyloidosis polyneuropathy
US12378560B2 (en) 2019-10-29 2025-08-05 Northwestern University Sequence multiplicity within spherical nucleic acids
EP4055166A2 (en) * 2019-11-06 2022-09-14 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery
IL296024A (en) 2020-03-04 2022-10-01 Flagship Pioneering Innovations Vi Llc Methods and compositions for modulating a genome
KR20220152270A (ko) 2020-03-06 2022-11-15 알닐람 파마슈티칼스 인코포레이티드 트랜스티레틴 (ttr)의 발현을 억제하기 위한 조성물 및 방법
EP4153223A1 (en) 2020-05-20 2023-03-29 Flagship Pioneering Innovations VI, LLC Immunogenic compositions and uses thereof
JP2023526422A (ja) 2020-05-20 2023-06-21 フラッグシップ パイオニアリング イノベーションズ シックス，エルエルシー コロナウイルス抗原組成物及びそれらの使用
CN116018405A (zh) 2020-05-29 2023-04-25 旗舰先锋创新Vi有限责任公司 Trem组合物及其相关方法
AU2021281453A1 (en) 2020-05-29 2022-11-17 Flagship Pioneering Innovations Vi, Llc. Trem compositions and methods relating thereto
MX2023002439A (es) 2020-09-03 2023-05-09 Flagship Pioneering Innovations Vi Llc Composiciones immunogénicas y usos de las mismas.
WO2022112919A1 (en) 2020-11-25 2022-06-02 Pfizer Inc. (aza)benzothiazolyl substituted pyrazole compounds
US11591544B2 (en) 2020-11-25 2023-02-28 Akagera Medicines, Inc. Ionizable cationic lipids
KR20230135585A (ko) 2020-12-23 2023-09-25 플래그쉽 파이어니어링 이노베이션스 브이아이, 엘엘씨 변형된 trem의 조성물 및 이의 용도
WO2022178411A1 (en) * 2021-02-22 2022-08-25 Alnylam Pharmaceuticals, Inc. Folliculin irna compositions and methods thereof
IL305418A (en) 2021-03-04 2023-10-01 Alnylam Pharmaceuticals Inc Angiopoietin-like 3 (ANGPTL3) IRNA compositions and methods of using them
CA3214085A1 (en) 2021-03-31 2022-10-06 Darby Rye Schmidt Thanotransmission polypeptides and their use in treating cancer
JP2024518374A (ja) 2021-05-03 2024-05-01 アルナイラム ファーマシューティカルズ， インコーポレイテッド トランスサイレチン（ｔｔｒ）媒介性アミロイドーシスを治療するための組成物および方法
EP4351541A2 (en) 2021-06-08 2024-04-17 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating or preventing stargardt's disease and/or retinal binding protein 4 (rbp4)-associated disorders
EP4377457A1 (en) 2021-07-26 2024-06-05 Flagship Pioneering Innovations VI, LLC Trem compositions and uses thereof
CA3227852A1 (en) 2021-08-03 2023-02-09 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof
JP2024533311A (ja) 2021-09-08 2024-09-12 フラッグシップ パイオニアリング イノベーションズ シックス，エルエルシー ゲノムを調節するための方法及び組成物
AR127073A1 (es) 2021-09-17 2023-12-13 Flagship Pioneering Innovations Vi Llc Composiciones y métodos para producir polirribonucleótidos circulares
AU2022370530A1 (en) 2021-10-18 2024-05-02 Flagship Pioneering Innovations Vi, Llc Compositions and methods for purifying polyribonucleotides
CN114058636A (zh) * 2021-11-16 2022-02-18 大连润生康泰医学检验实验室有限公司 一种转甲状腺素蛋白基因的克隆、表达与纯化方法
JP2024541466A (ja) 2021-11-24 2024-11-08 フラッグシップ パイオニアリング イノベーションズ シックス，エルエルシー 水痘帯状疱疹ウイルス免疫原組成物及びその使用
JP2024541467A (ja) 2021-11-24 2024-11-08 フラッグシップ パイオニアリング イノベーションズ シックス，エルエルシー コロナウイルス免疫原組成物及びそれらの使用
IL312965A (en) 2021-11-24 2024-07-01 Flagship Pioneering Innovations Vi Llc Immunogenic compositions and their uses
EP4453201A1 (en) 2021-12-22 2024-10-30 Flagship Pioneering Innovations VI, LLC Compositions and methods for purifying polyribonucleotides
JP2025500358A (ja) 2021-12-23 2025-01-09 フラッグシップ パイオニアリング イノベーションズ シックス，エルエルシー 抗膜融合ポリペプチドをコードする環状ポリリボヌクレオチド
JP2025511756A (ja) 2022-04-08 2025-04-16 フラッグシップ パイオニアリング イノベーションズ セブン，エルエルシー ワクチン及び関連する方法
CA3257006A1 (en) 2022-05-09 2023-11-16 Flagship Pioneering Innovations Vi, Llc TREM COMPOSITIONS AND METHODS OF USE FOR TREATING PROLIFERATIVE DISORDERS
CN119487196A (zh) 2022-05-13 2025-02-18 旗舰创业创新七公司 双链dna组合物及相关方法
KR20250031230A (ko) 2022-05-25 2025-03-06 아카제라 메디신즈, 인크. 핵산 전달을 위한 지질 나노입자 및 이의 사용 방법
EP4544043A1 (en) 2022-06-22 2025-04-30 Flagship Pioneering Innovations VI, LLC Compositions of modified trems and uses thereof
CA3261283A1 (en) 2022-08-01 2024-02-08 Flagship Pioneering Innovations Vii, Llc Immunomodulatory Proteins and Associated Methods
WO2024035952A1 (en) 2022-08-12 2024-02-15 Remix Therapeutics Inc. Methods and compositions for modulating splicing at alternative splice sites
EP4598946A1 (en) 2022-10-05 2025-08-13 Flagship Pioneering Innovations V, Inc. Nucleic acid molecules encoding trif and additionalpolypeptides and their use in treating cancer
WO2024097664A1 (en) 2022-10-31 2024-05-10 Flagship Pioneering Innovations Vi, Llc Compositions and methods for purifying polyribonucleotides
WO2024098061A2 (en) 2022-11-04 2024-05-10 Genkardia Inc. Oligonucleotide-based therapeutics targeting cyclin d2 for the treatment of heart failure
TW202434728A (zh) 2022-11-08 2024-09-01 美商旗艦先鋒創新有限責任公司 用於產生環狀多核糖核苷酸的組成物和方法
EP4619524A1 (en) 2022-11-18 2025-09-24 Genkardia Inc. Methods and compositions for preventing, treating, or reversing cardiac diastolic dysfunction
WO2024129874A1 (en) * 2022-12-13 2024-06-20 Sirnaomics, Inc. Products and compositions
TW202430215A (zh) 2022-12-14 2024-08-01 美商旗艦先鋒創新有限責任（Ｖｉｉ）公司 用於將治療劑遞送至骨之組成物和方法
US20240252520A1 (en) 2023-01-09 2024-08-01 Beth Israel Deaconess Medical Center, Inc. Therapeutic agents and their use for treating chronic wounds
WO2024151673A2 (en) 2023-01-09 2024-07-18 President And Fellows Of Harvard College Recombinant nucleic acid molecules and their use in wound healing
WO2024151687A1 (en) 2023-01-09 2024-07-18 Flagship Pioneering Innovations V, Inc. Genetic switches and their use in treating cancer
IL322468A (en) 2023-02-13 2025-09-01 Flagship Pioneering Innovations Vii Llc Ionizable lipids containing degradable crosslinkers and lipid carriers for therapeutic compositions
IL322201A (en) 2023-02-17 2025-09-01 Flagship Pioneering Innovations Vii Llc DNA structures containing modified uracil
WO2024173836A2 (en) 2023-02-17 2024-08-22 Flagship Pioneering Innovations Vii, Llc Dna compositions comprising modified cytosine
KR20250162610A (ko) 2023-03-15 2025-11-18 플래그쉽 파이어니어링 이노베이션스 브이아이, 엘엘씨 폴리리보뉴클레오티드를 포함하는 조성물 및 이의 용도
CN121358494A (zh) 2023-03-15 2026-01-16 旗舰创业创新第六有限责任公司 免疫原性组合物及其用途
WO2024216128A1 (en) 2023-04-12 2024-10-17 Flagship Pioneering Innovations Vi, Llc Trems for use in correction of missense mutations
WO2025006684A1 (en) 2023-06-28 2025-01-02 Flagship Pioneering Innovations Vi, Llc Circular polyribonucleotides encoding antifusogenic polypeptides
WO2025042786A1 (en) 2023-08-18 2025-02-27 Flagship Pioneering Innovations Vi, Llc Compositions comprising circular polyribonucleotides and uses thereof
TW202525266A (zh) 2023-09-18 2025-07-01 美商旗艦先鋒創新有限責任（Ｖｉｉ）公司 可電離類脂質組成物及其治療用途
WO2025098117A1 (zh) * 2023-11-06 2025-05-15 成都倍特药业股份有限公司 一种抑制甲状腺素转运蛋白(TTR)表达的RNAi试剂、组合物及应用
WO2025106670A1 (en) 2023-11-14 2025-05-22 Flagship Pioneering Innovations Vii, Llc Ionizable lipidoid compositions and therapeutic uses thereof
WO2025210133A1 (en) 2024-04-03 2025-10-09 Deep Piction Gmbh Hybrid lipid nanoparticles for targeted delivery

Family Cites Families (256)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US564562A (en) 1896-07-21 Joseph p
US513030A (en) 1894-01-16 Machine for waxing or coating paper
US3687808A (en) 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
US4522808A (en) 1980-08-15 1985-06-11 Societe Anonyme Dite: L'oreal Anti-sunburn compositions containing 2-phenyl-indole derivatives
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
US4426330A (en) 1981-07-20 1984-01-17 Lipid Specialties, Inc. Synthetic phospholipid compounds
US4534899A (en) 1981-07-20 1985-08-13 Lipid Specialties, Inc. Synthetic phospholipid compounds
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
JPS5927900A (ja) 1982-08-09 1984-02-14 Wakunaga Seiyaku Kk 固定化オリゴヌクレオチド
FR2540122B1 (fr) 1983-01-27 1985-11-29 Centre Nat Rech Scient Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation, leur procede de synthese et leur application
US4605735A (en) 1983-02-14 1986-08-12 Wakunaga Seiyaku Kabushiki Kaisha Oligonucleotide derivatives
US4948882A (en) 1983-02-22 1990-08-14 Syngene, Inc. Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis
US4824941A (en) 1983-03-10 1989-04-25 Julian Gordon Specific antibody to the native form of 2'5'-oligonucleotides, the method of preparation and the use as reagents in immunoassays or for binding 2'5'-oligonucleotides in biological systems
US4587044A (en) 1983-09-01 1986-05-06 The Johns Hopkins University Linkage of proteins to nucleic acids
US5118800A (en) 1983-12-20 1992-06-02 California Institute Of Technology Oligonucleotides possessing a primary amino group in the terminal nucleotide
US5118802A (en) 1983-12-20 1992-06-02 California Institute Of Technology DNA-reporter conjugates linked via the 2' or 5'-primary amino group of the 5'-terminal nucleoside
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
US5430136A (en) 1984-10-16 1995-07-04 Chiron Corporation Oligonucleotides having selectably cleavable and/or abasic sites
US5367066A (en) 1984-10-16 1994-11-22 Chiron Corporation Oligonucleotides with selectably cleavable and/or abasic sites
US5258506A (en) 1984-10-16 1993-11-02 Chiron Corporation Photolabile reagents for incorporation into oligonucleotide chains
US4828979A (en) 1984-11-08 1989-05-09 Life Technologies, Inc. Nucleotide analogs for nucleic acid labeling and detection
FR2575751B1 (fr) 1985-01-08 1987-04-03 Pasteur Institut Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques
US5185444A (en) 1985-03-15 1993-02-09 Anti-Gene Deveopment Group Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages
US5235033A (en) 1985-03-15 1993-08-10 Anti-Gene Development Group Alpha-morpholino ribonucleoside derivatives and polymers thereof
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
US5405938A (en) 1989-12-20 1995-04-11 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5166315A (en) 1989-12-20 1992-11-24 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US4762779A (en) 1985-06-13 1988-08-09 Amgen Inc. Compositions and methods for functionalizing nucleic acids
US4980286A (en) 1985-07-05 1990-12-25 Whitehead Institute For Biomedical Research In vivo introduction and expression of foreign genetic material in epithelial cells
DE3681787D1 (de) 1985-07-05 1991-11-07 Whitehead Biomedical Inst Expression von fremdem genetischem material in epithelzellen.
US5139941A (en) 1985-10-31 1992-08-18 University Of Florida Research Foundation, Inc. AAV transduction vectors
US5317098A (en) 1986-03-17 1994-05-31 Hiroaki Shizuya Non-radioisotope tagging of fragments
JPS638396A (ja) 1986-06-30 1988-01-14 Wakunaga Pharmaceut Co Ltd ポリ標識化オリゴヌクレオチド誘導体
US4920016A (en) 1986-12-24 1990-04-24 Linear Technology, Inc. Liposomes with enhanced circulation time
US4837028A (en) 1986-12-24 1989-06-06 Liposome Technology, Inc. Liposomes with enhanced circulation time
US5276019A (en) 1987-03-25 1994-01-04 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US5264423A (en) 1987-03-25 1993-11-23 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US4904582A (en) 1987-06-11 1990-02-27 Synthetic Genetics Novel amphiphilic nucleic acid conjugates
EP0366685B1 (en) 1987-06-24 1994-10-19 Howard Florey Institute Of Experimental Physiology And Medicine Nucleoside derivatives
JP3015383B2 (ja) 1987-09-11 2000-03-06 ホワイトヘツド・インスチチユート・フオー・バイオメデイカル・リサーチ 形質導入した線維芽およびそれらの使用
US5585481A (en) 1987-09-21 1996-12-17 Gen-Probe Incorporated Linking reagents for nucleotide probes
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
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
DE3851153T2 (de) 1987-12-11 1995-01-05 Hughes Howard Med Inst Genetische modifizierung von endothelialen zellen.
DE68927996T2 (de) 1988-02-05 1997-12-04 Hughes Howard Med Inst Modifizierte hepatozyten und deren anwendung
US5082830A (en) 1988-02-26 1992-01-21 Enzo Biochem, Inc. End labeled nucleotide probe
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
US5109124A (en) 1988-06-01 1992-04-28 Biogen, Inc. Nucleic acid probe linked to a label having a terminal cysteine
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
US5262536A (en) 1988-09-15 1993-11-16 E. I. Du Pont De Nemours And Company Reagents for the preparation of 5'-tagged oligonucleotides
GB8824593D0 (en) 1988-10-20 1988-11-23 Royal Free Hosp School Med Liposomes
US5512439A (en) 1988-11-21 1996-04-30 Dynal As Oligonucleotide-linked magnetic particles and uses thereof
US5457183A (en) 1989-03-06 1995-10-10 Board Of Regents, The University Of Texas System Hydroxylated texaphyrins
US5599923A (en) 1989-03-06 1997-02-04 Board Of Regents, University Of Tx Texaphyrin metal complexes having improved functionalization
US5328470A (en) 1989-03-31 1994-07-12 The Regents Of The University Of Michigan Treatment of diseases by site-specific instillation of cells or site-specific transformation of cells and kits therefor
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
US5451463A (en) 1989-08-28 1995-09-19 Clontech Laboratories, Inc. Non-nucleoside 1,3-diol reagents for labeling synthetic oligonucleotides
US5134066A (en) 1989-08-29 1992-07-28 Monsanto Company Improved probes using nucleosides containing 3-dezauracil analogs
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
US5591722A (en) 1989-09-15 1997-01-07 Southern Research Institute 2'-deoxy-4'-thioribonucleosides and their antiviral activity
US5356633A (en) 1989-10-20 1994-10-18 Liposome Technology, Inc. Method of treatment of inflamed tissues
US5225212A (en) 1989-10-20 1993-07-06 Liposome Technology, Inc. Microreservoir liposome composition and method
US5013556A (en) 1989-10-20 1991-05-07 Liposome Technology, Inc. Liposomes with enhanced circulation time
US5399676A (en) 1989-10-23 1995-03-21 Gilead Sciences Oligonucleotides with inverted polarity
US5264564A (en) 1989-10-24 1993-11-23 Gilead Sciences Oligonucleotide analogs with novel linkages
EP0497875B1 (en) 1989-10-24 2000-03-22 Isis Pharmaceuticals, Inc. 2' modified oligonucleotides
US5292873A (en) 1989-11-29 1994-03-08 The Research Foundation Of State University Of New York Nucleic acids labeled with naphthoquinone probe
US5177198A (en) 1989-11-30 1993-01-05 University Of N.C. At Chapel Hill Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates
US5486603A (en) 1990-01-08 1996-01-23 Gilead Sciences, Inc. Oligonucleotide having enhanced binding affinity
US5681941A (en) 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5670633A (en) 1990-01-11 1997-09-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
US5587470A (en) 1990-01-11 1996-12-24 Isis Pharmaceuticals, Inc. 3-deazapurines
US5578718A (en) 1990-01-11 1996-11-26 Isis Pharmaceuticals, Inc. Thiol-derivatized nucleosides
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
US5214136A (en) 1990-02-20 1993-05-25 Gilead Sciences, Inc. Anthraquinone-derivatives oligonucleotides
WO1991013080A1 (en) 1990-02-20 1991-09-05 Gilead Sciences, Inc. Pseudonucleosides and pseudonucleotides and their polymers
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
US5665710A (en) 1990-04-30 1997-09-09 Georgetown University Method of making liposomal oligodeoxynucleotide compositions
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
DE69032425T2 (de) 1990-05-11 1998-11-26 Microprobe Corp., Bothell, Wash. Teststreifen zum Eintauchen für Nukleinsäure-Hybridisierungsassays und Verfahren zur kovalenten Immobilisierung von Oligonucleotiden
US5218105A (en) 1990-07-27 1993-06-08 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5138045A (en) 1990-07-27 1992-08-11 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5688941A (en) 1990-07-27 1997-11-18 Isis Pharmaceuticals, Inc. Methods of making conjugated 4' desmethyl nucleoside analog compounds
US5677437A (en) 1990-07-27 1997-10-14 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
EP0544824B1 (en) 1990-07-27 1997-06-11 Isis Pharmaceuticals, Inc. Nuclease resistant, pyrimidine modified oligonucleotides that detect and modulate gene expression
US5623070A (en) 1990-07-27 1997-04-22 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5618704A (en) 1990-07-27 1997-04-08 Isis Pharmacueticals, Inc. Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
ES2083593T3 (es) 1990-08-03 1996-04-16 Sterling Winthrop Inc Compuestos y metodos para inhibir la expresion de genes.
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
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
JPH06505704A (ja) 1990-09-20 1994-06-30 ギリアド　サイエンシズ，インコーポレイテッド 改変ヌクレオシド間結合
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
ATE163046T1 (de) 1990-10-31 1998-02-15 Somatix Therapy Corp Genetische veränderung von endothelzellen
CA2095212A1 (en) 1990-11-08 1992-05-09 Hybridon, Inc. Incorporation of multiple reporter groups on synthetic oligonucleotides
GB9100304D0 (en) 1991-01-08 1991-02-20 Ici Plc Compound
JP3220180B2 (ja) 1991-05-23 2001-10-22 三菱化学株式会社 薬剤含有タンパク質結合リポソーム
US5539082A (en) 1993-04-26 1996-07-23 Nielsen; Peter E. Peptide nucleic acids
US5714331A (en) 1991-05-24 1998-02-03 Buchardt, Deceased; Ole Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility
US5719262A (en) 1993-11-22 1998-02-17 Buchardt, Deceased; Ole Peptide nucleic acids having amino acid side chains
US5371241A (en) 1991-07-19 1994-12-06 Pharmacia P-L Biochemicals Inc. Fluorescein labelled phosphoramidites
US5571799A (en) 1991-08-12 1996-11-05 Basco, Ltd. (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response
ES2103918T3 (es) 1991-10-17 1997-10-01 Ciba Geigy Ag Nucleosidos biciclicos, oligonucleotidos, procedimiento para su obtencion y productos intermedios.
US5594121A (en) 1991-11-07 1997-01-14 Gilead Sciences, Inc. Enhanced triple-helix and double-helix formation with oligomers containing modified purines
US5252479A (en) 1991-11-08 1993-10-12 Research Corporation Technologies, Inc. Safe vector for gene therapy
US5484908A (en) 1991-11-26 1996-01-16 Gilead Sciences, Inc. Oligonucleotides containing 5-propynyl pyrimidines
US5359044A (en) 1991-12-13 1994-10-25 Isis Pharmaceuticals Cyclobutyl oligonucleotide surrogates
US5595726A (en) 1992-01-21 1997-01-21 Pharmacyclics, Inc. Chromophore probe for detection of nucleic acid
US5565552A (en) 1992-01-21 1996-10-15 Pharmacyclics, Inc. Method of expanded porphyrin-oligonucleotide conjugate synthesis
FR2687679B1 (fr) 1992-02-05 1994-10-28 Centre Nat Rech Scient Oligothionucleotides.
DE4203923A1 (de) 1992-02-11 1993-08-12 Henkel Kgaa Verfahren zur herstellung von polycarboxylaten auf polysaccharid-basis
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
US5587308A (en) 1992-06-02 1996-12-24 The United States Of America As Represented By The Department Of Health & Human Services Modified adeno-associated virus vector capable of expression from a novel promoter
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
US5272250A (en) 1992-07-10 1993-12-21 Spielvogel Bernard F Boronated phosphoramidate compounds
US5478745A (en) 1992-12-04 1995-12-26 University Of Pittsburgh Recombinant viral vector system
US5574142A (en) 1992-12-15 1996-11-12 Microprobe Corporation Peptide linkers for improved oligonucleotide delivery
JP3351476B2 (ja) 1993-01-22 2002-11-25 三菱化学株式会社 リン脂質誘導体及びそれを含有するリポソーム
US5476925A (en) 1993-02-01 1995-12-19 Northwestern University Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups
US5395619A (en) 1993-03-03 1995-03-07 Liposome Technology, Inc. Lipid-polymer conjugates and liposomes
GB9304618D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Chemical compounds
AU6449394A (en) 1993-03-30 1994-10-24 Sterling Winthrop Inc. Acyclic nucleoside analogs and oligonucleotide sequences containing them
AU6412794A (en) 1993-03-31 1994-10-24 Sterling Winthrop Inc. Oligonucleotides with amide linkages replacing phosphodiester linkages
DE4311944A1 (de) 1993-04-10 1994-10-13 Degussa Umhüllte Natriumpercarbonatpartikel, Verfahren zu deren Herstellung und sie enthaltende Wasch-, Reinigungs- und Bleichmittelzusammensetzungen
US5502177A (en) 1993-09-17 1996-03-26 Gilead Sciences, Inc. Pyrimidine derivatives for labeled binding partners
CA2137297C (en) 1993-12-06 2000-04-18 Tsuyoshi Miyazaki Reactive vesicle and functional substance-fixed vesicle
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
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
US6054299A (en) 1994-04-29 2000-04-25 Conrad; Charles A. Stem-loop cloning vector and method
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
US5543152A (en) 1994-06-20 1996-08-06 Inex Pharmaceuticals Corporation Sphingosomes for enhanced drug delivery
US5597696A (en) 1994-07-18 1997-01-28 Becton Dickinson And Company Covalent cyanine dye oligonucleotide conjugates
US5597909A (en) 1994-08-25 1997-01-28 Chiron Corporation Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use
US5580731A (en) 1994-08-25 1996-12-03 Chiron Corporation N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith
US5820873A (en) 1994-09-30 1998-10-13 The University Of British Columbia Polyethylene glycol modified ceramide lipids and liposome uses thereof
WO1996033761A1 (en) 1995-04-28 1996-10-31 Medtronic, Inc. Intraparenchymal infusion catheter system
US20030027216A1 (en) 2001-07-02 2003-02-06 Kiernan Urban A. Analysis of proteins from biological fluids using mass spectrometric immunoassay
US5981501A (en) 1995-06-07 1999-11-09 Inex Pharmaceuticals Corp. Methods for encapsulating plasmids in lipid bilayers
US7422902B1 (en) 1995-06-07 2008-09-09 The University Of British Columbia Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer
ATE285477T1 (de) 1995-06-07 2005-01-15 Inex Pharmaceutical Corp Herstellung von lipid-nukleinsäure partikeln duch ein hydrophobische lipid-nukleinsäuree komplexe zwischenprodukt und zur verwendung in der gentransfer
US5756122A (en) 1995-06-07 1998-05-26 Georgetown University Liposomally encapsulated nucleic acids having high entrapment efficiencies, method of manufacturer and use thereof for transfection of targeted cells
EP0843555B1 (en) 1995-08-01 2003-08-27 Isis Pharmaceuticals, Inc. Liposomal oligonucleotide compositions
US5858397A (en) 1995-10-11 1999-01-12 University Of British Columbia Liposomal formulations of mitoxantrone
US5735814A (en) 1996-04-30 1998-04-07 Medtronic, Inc. Techniques of treating neurodegenerative disorders by brain infusion
EP1012331B1 (en) 1997-07-01 2006-03-29 Isis Pharmaceuticals, Inc. Compositions and methods for the delivery of oligonucleotides via the alimentary canal
US6506559B1 (en) 1997-12-23 2003-01-14 Carnegie Institute Of Washington Genetic inhibition by double-stranded RNA
EP2267138B1 (en) 1998-04-08 2016-06-08 Commonwealth Scientific and Industrial Research Organization Methods and means for obtaining modified phenotypes
AR020078A1 (es) 1998-05-26 2002-04-10 Syngenta Participations Ag Metodo para alterar la expresion de un gen objetivo en una celula de planta
WO2000003683A2 (en) 1998-07-20 2000-01-27 Inex Pharmaceuticals Corporation Liposomal encapsulated nucleic acid-complexes
AU6430599A (en) 1998-10-09 2000-05-01 Cytogenix, Inc. Enzymatic synthesis of ssdna
AU6298899A (en) 1998-10-09 2000-05-01 Ingene, Inc. Production of ssdna (in vivo)
DE19956568A1 (de) 1999-01-30 2000-08-17 Roland Kreutzer Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens
JP2002537343A (ja) 1999-02-23 2002-11-05 アイシス・ファーマシューティカルス・インコーポレーテッド 多重粒子製剤
DE10100586C1 (de) 2001-01-09 2002-04-11 Ribopharma Ag Verfahren zur Hemmung der Expression eines Ziegens
AU2001247951A1 (en) * 2000-02-07 2001-08-14 Roche Diagnostics Corporation Novel cationic amphiphiles
US20070026394A1 (en) * 2000-02-11 2007-02-01 Lawrence Blatt Modulation of gene expression associated with inflammation proliferation and neurite outgrowth using nucleic acid based technologies
US20030072794A1 (en) * 2000-06-09 2003-04-17 Teni Boulikas Encapsulation of plasmid DNA (lipogenes™) and therapeutic agents with nuclear localization signal/fusogenic peptide conjugates into targeted liposome complexes
KR100909681B1 (ko) * 2000-12-01 2009-07-29 막스-플랑크-게젤샤프트 츄어 푀르더룽 데어 비쎈샤프텐 에.파우. Ｒｎａ 간섭을 매개하는 작은 ｒｎａ 분자
WO2002059621A2 (en) 2001-01-24 2002-08-01 Bayer Corporation Regulation of transthyretin to treat obesity
US7514099B2 (en) * 2005-02-14 2009-04-07 Sirna Therapeutics, Inc. Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules
US20030170891A1 (en) 2001-06-06 2003-09-11 Mcswiggen James A. RNA interference mediated inhibition of epidermal growth factor receptor gene expression using short interfering nucleic acid (siNA)
US20030124616A1 (en) 2001-06-21 2003-07-03 Jacobsen Donald W. Homocysteinylated transthyretin
US20030191056A1 (en) 2002-04-04 2003-10-09 Kenneth Walker Use of transthyretin peptide/protein fusions to increase the serum half-life of pharmacologically active peptides/proteins
BRPI0313202A8 (pt) 2002-08-05 2016-08-16 Atugen Ag Formas adicionais para interferir com as moléculas de rna
US7923547B2 (en) * 2002-09-05 2011-04-12 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
EP1556684A4 (en) 2002-11-01 2008-01-23 Univ Colorado Regents QUANTITATIVE ANALYSIS OF PROTEIN ISOFORMS USING FLIGHT TIME MASS SPECTROMETRY BY MATRIX ASSISTED LASER DESORPTION / IONIZATION
US9228186B2 (en) 2002-11-14 2016-01-05 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
US8090542B2 (en) * 2002-11-14 2012-01-03 Dharmacon Inc. Functional and hyperfunctional siRNA
US7250496B2 (en) 2002-11-14 2007-07-31 Rosetta Genomics Ltd. Bioinformatically detectable group of novel regulatory genes and uses thereof
DE10302421A1 (de) 2003-01-21 2004-07-29 Ribopharma Ag Doppelsträngige Ribonukleinsäure mit verbesserter Wirksamkeit
AU2004220556B2 (en) 2003-03-07 2009-05-07 Alnylam Pharmaceuticals, Inc. Therapeutic compositions
EP1608735A4 (en) 2003-04-03 2008-11-05 Alnylam Pharmaceuticals RNAI CONJUGATES
CN101291653B (zh) 2003-07-16 2012-06-27 普洛体维生物治疗公司 脂质包封的干扰rna
US20050244869A1 (en) 2004-04-05 2005-11-03 Brown-Driver Vickie L Modulation of transthyretin expression
CA2569419A1 (en) 2004-06-03 2005-12-22 Isis Pharmaceuticals, Inc. Double strand compositions comprising differentially modified strands for use in gene modulation
EP1781593B1 (en) * 2004-06-07 2011-12-14 Protiva Biotherapeutics Inc. Cationic lipids and methods of use
EP1766035B1 (en) 2004-06-07 2011-12-07 Protiva Biotherapeutics Inc. Lipid encapsulated interfering rna
WO2005120583A2 (en) * 2004-06-14 2005-12-22 Wisconsin Alumni Research Foundation Method for preventing or treating cardiac hypertrophy
ES2246715B1 (es) * 2004-08-04 2007-05-01 Consejo Superior Investig. Cientificas Modelo animal de enfermedades neurodegenerativas, procedimiento de obtencion y aplicaciones.
CN101189343B (zh) * 2004-08-23 2011-11-16 阿尔尼拉姆药物公司 多rna聚合酶ⅲ启动子表达构建体
BRPI0520207A2 (pt) 2004-12-08 2012-09-25 Revision Therapeutics Inc uso de uma quantidade eficaz de um primeiro composto, e, medicamento sistemicamente formulado
JP2008537551A (ja) 2005-03-31 2008-09-18 カランド ファーマシューティカルズ， インコーポレイテッド リボヌクレオチドレダクターゼサブユニット２の阻害剤およびその使用
US7915230B2 (en) * 2005-05-17 2011-03-29 Molecular Transfer, Inc. Reagents for transfection of eukaryotic cells
WO2007008652A2 (en) * 2005-07-08 2007-01-18 The University Of North Carolina At Chapel Hill Methods and compositions directed to dj-1 as regulator of the anti-oxidant transcription factor nrf2
WO2007012191A1 (en) 2005-07-27 2007-02-01 Protiva Biotherapeutics, Inc. Systems and methods for manufacturing liposomes
CN101346393B (zh) 2005-11-02 2015-07-22 普洛体维生物治疗公司 修饰的siRNA分子及其应用
JP5704741B2 (ja) 2006-03-31 2015-04-22 アルナイラム ファーマシューティカルズ， インコーポレイテッドＡｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． Ｅｇ５遺伝子発現の抑制のための組成物および方法
US8598333B2 (en) 2006-05-26 2013-12-03 Alnylam Pharmaceuticals, Inc. SiRNA silencing of genes expressed in cancer
EP2695608B1 (en) * 2006-10-03 2016-11-23 Arbutus Biopharma Corporation Lipid containing formulations
GB0704764D0 (en) 2007-03-12 2007-04-18 Electrophoretics Ltd Isobarically labelled reagents and methods of their use
EP2173358B1 (en) 2007-06-22 2015-10-21 Isis Pharmaceuticals, Inc. Double strand compositions comprising differentially modified strands for use in gene modulation
CA2910760C (en) 2007-12-04 2019-07-09 Muthiah Manoharan Targeting lipids
EP2238251B1 (en) * 2007-12-27 2015-02-11 Protiva Biotherapeutics Inc. Silencing of polo-like kinase expression using interfering rna
EP2224912B1 (en) 2008-01-02 2016-05-11 TEKMIRA Pharmaceuticals Corporation Improved compositions and methods for the delivery of nucleic acids
WO2009134487A2 (en) 2008-01-31 2009-11-05 Alnylam Pharmaceuticals, Inc. Optimized methods for delivery of dsrna targeting the pcsk9 gene
WO2009100390A2 (en) 2008-02-08 2009-08-13 Mayo Foundation For Medical Education And Research Classifying amyloidosis
CA2721333C (en) * 2008-04-15 2020-12-01 Protiva Biotherapeutics, Inc. Novel lipid formulations for nucleic acid delivery
TWI455944B (zh) 2008-07-01 2014-10-11 Daiichi Sankyo Co Ltd 雙股多核苷酸
US20110237646A1 (en) 2008-08-07 2011-09-29 Isis Pharmaceuticals, Inc. Modulation of transthyretin expression for the treatment of cns related disorders
JP5777519B2 (ja) * 2008-10-09 2015-09-09 テクミラ ファーマシューティカルズ コーポレイション 改良されたアミノ脂質および核酸の送達方法
SG10201809460SA (en) 2008-10-20 2018-11-29 Alnylam Pharmaceuticals Inc Compositions and methods for inhibiting expression of transthyretin
WO2010053572A2 (en) 2008-11-07 2010-05-14 Massachusetts Institute Of Technology Aminoalcohol lipidoids and uses thereof
DK2355851T3 (en) 2008-11-10 2018-06-25 Arbutus Biopharma Corp Newly known lipids and compositions for release of therapeutic agents
US9493774B2 (en) 2009-01-05 2016-11-15 Rxi Pharmaceuticals Corporation Inhibition of PCSK9 through RNAi
US20120101148A1 (en) 2009-01-29 2012-04-26 Alnylam Pharmaceuticals, Inc. lipid formulation
CA2760776C (en) 2009-05-05 2019-07-09 Alnylam Pharmaceuticals, Inc. Lipid compositions for the delivery of therapeutic agents
CA2764609C (en) * 2009-06-10 2018-10-02 Alnylam Pharmaceuticals, Inc. Improved cationic lipid of formula i
KR20120050429A (ko) 2009-06-15 2012-05-18 알닐람 파마슈티칼스 인코포레이티드 Ｐｃｓｋ9 유전자를 표적으로 하는 지질 제형된 ｄｓｒｎａ
US9051567B2 (en) 2009-06-15 2015-06-09 Tekmira Pharmaceuticals Corporation Methods for increasing efficacy of lipid formulated siRNA
WO2011056883A1 (en) 2009-11-03 2011-05-12 Alnylam Pharmaceuticals, Inc. Lipid formulated compositions and methods for inhibiting expression of transthyretin (ttr)
US20130281510A1 (en) 2010-03-29 2013-10-24 Kumamoto University siRNA Therapy for Transthyretin (TTR) Related Ocular Amyloidosis
ES2625689T3 (es) 2010-04-29 2017-07-20 Ionis Pharmaceuticals, Inc. Modulación de la expresión de transtiretina
AU2011302152B2 (en) 2010-09-15 2015-06-11 Alnylam Pharmaceuticals, Inc. Modified iRNA agents
DK2632472T3 (en) 2010-10-29 2018-03-19 Sirna Therapeutics Inc RNA INTERFERENCE-MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERRING NUCLEIC ACIDS (SINA)
CN110123830A (zh) 2010-11-09 2019-08-16 阿尔尼拉姆医药品有限公司 用于抑制Eg5和VEGF基因的表达的脂质配制的组合物和方法
EP3564393A1 (en) 2011-06-21 2019-11-06 Alnylam Pharmaceuticals, Inc. Assays and methods for determining activity of a therapeutic agent in a subject
WO2013075035A1 (en) 2011-11-18 2013-05-23 Alnylam Pharmaceuticals Rnai agents, compositions and methods of use thereof for treating transthyretin (ttr) associated diseases
HK1200191A1 (en) 2011-11-18 2015-07-31 Alnylam Pharmaceuticals, Inc. Modified rnai agents
CA2879683C (en) 2012-08-03 2023-02-14 Alnylam Pharmaceuticals, Inc. Modified rnai agents
TW201610151A (zh) 2013-09-23 2016-03-16 阿尼拉製藥公司 治療或預防與甲狀腺素運載蛋白相關疾病之方法
AU2014360314B2 (en) 2013-12-06 2018-04-26 Dicerna Pharmaceuticals, Inc. Methods and compositions for the specific inhibition of transthyretin (TTR) by double-stranded RNA
KR102005337B1 (ko) * 2014-01-09 2019-07-30 에스케이하이닉스 주식회사 전압 변환 장치
IL316808A (en) 2014-08-20 2025-01-01 Alnylam Pharmaceuticals Inc Modified double-stranded RNA materials and their uses
LT3185957T (lt) 2014-08-29 2022-09-26 Alnylam Pharmaceuticals, Inc. Patisiranas, skirtas naudoti transtiretino amiloidozei gydyti
PL3329002T3 (pl) 2015-07-31 2021-04-19 Alnylam Pharmaceuticals, Inc. Kompozycje irna transtyretyny (ttr) i sposoby ich zastosowania do leczenia lub zapobiegania chorobom związanym z ttr
SG10201913552UA (en) 2016-12-16 2020-03-30 Alnylam Pharmaceuticals Inc Methods for treating or preventing ttr-associated diseases using transthyretin (ttr) irna compositions
BR112020005230A2 (pt) 2017-09-19 2020-09-24 Alnylam Pharmaceuticals, Inc. composições e métodos para o tratamento da amiloidose mediada por transtiretina (ttr)
US10799808B2 (en) 2018-09-13 2020-10-13 Nina Davis Interactive storytelling kit
WO2020069055A1 (en) 2018-09-28 2020-04-02 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof for treating or preventing ttr-associated ocular diseases
WO2021041884A1 (en) 2019-08-30 2021-03-04 Alnylam Pharmaceuticals, Inc. Neurofilament light chain (nfl) as a biomarker for transthyretin amyloidosis polyneuropathy
EP4055165A1 (en) 2019-11-06 2022-09-14 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof for treating or preventing ttr-associated ocular diseases
KR20220152270A (ko) 2020-03-06 2022-11-15 알닐람 파마슈티칼스 인코포레이티드 트랜스티레틴 (ttr)의 발현을 억제하기 위한 조성물 및 방법
JP2024518374A (ja) 2021-05-03 2024-05-01 アルナイラム ファーマシューティカルズ， インコーポレイテッド トランスサイレチン（ｔｔｒ）媒介性アミロイドーシスを治療するための組成物および方法
EP4351541A2 (en) 2021-06-08 2024-04-17 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating or preventing stargardt's disease and/or retinal binding protein 4 (rbp4)-associated disorders
CA3227852A1 (en) 2021-08-03 2023-02-09 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2017071616A (ja) * 2009-11-03 2017-04-13 アルナイラム ファーマシューティカルズ， インコーポレイテッドＡｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． トランスサイレチン（ｔｔｒ）を阻害する脂質製剤化組成物及び方法

Also Published As

Publication number Publication date
KR20180017245A (ko) 2018-02-20
NL300965I1 (nl) 2019-02-06
US10240152B2 (en) 2019-03-26
EP2344639A2 (en) 2011-07-20
JP2024116226A (ja) 2024-08-27
EP3848461A1 (en) 2021-07-14
MX2018013398A (es) 2023-01-05
JP2022160408A (ja) 2022-10-19
IL281434B1 (en) 2023-05-01
US20250376682A1 (en) 2025-12-11
CN102186978A (zh) 2011-09-14
EP2344639B1 (en) 2015-04-22
HUS1900004I1 (hu) 2019-03-28
LT2937418T (lt) 2018-02-12
MX360460B (es) 2018-11-05
HRP20180093T1 (hr) 2018-02-23
JP2015062420A (ja) 2015-04-09
JP2019205442A (ja) 2019-12-05
CN102186978B (zh) 2014-03-12
EA029762B1 (ru) 2018-05-31
HK1156348A1 (en) 2012-06-08
CY1120174T1 (el) 2018-12-12
SG10201809460SA (en) 2018-11-29
US8741866B2 (en) 2014-06-03
CN106834291A (zh) 2017-06-13
KR102578331B1 (ko) 2023-09-15
EA020312B1 (ru) 2014-10-30
IL243178B (en) 2021-03-25
CY2019005I1 (el) 2019-11-27
KR20150007359A (ko) 2015-01-20
JP6553780B2 (ja) 2019-07-31
DK2937418T3 (en) 2018-01-22
PL2937418T3 (pl) 2018-04-30
KR101635436B1 (ko) 2016-07-01
CA2739895A1 (en) 2010-04-29
AU2009307677A1 (en) 2010-04-29
SMT201800027T1 (it) 2018-03-08
ES2543004T3 (es) 2015-08-13
BRPI0919732A2 (pt) 2015-12-08
US20140194493A1 (en) 2014-07-10
IL281434A (en) 2021-04-29
EA201400170A1 (ru) 2015-03-31
SMT201500176B (it) 2015-09-07
IL212428A0 (en) 2011-06-30
KR101624869B1 (ko) 2016-05-30
CN103937793A (zh) 2014-07-23
SI2344639T1 (sl) 2015-09-30
HK1216652A1 (en) 2016-11-25
LTPA2019501I1 (lt) 2019-02-25
KR102031027B1 (ko) 2019-10-14
AU2009307677C1 (en) 2022-09-22
US20100120893A1 (en) 2010-05-13
EA201170591A1 (ru) 2011-12-30
WO2010048228A2 (en) 2010-04-29
IL310600A (en) 2024-04-01
PT2344639E (pt) 2015-09-07
SG10201703242XA (en) 2017-06-29
LUC00098I1 (enExample) 2019-01-31
JP7806130B2 (ja) 2026-01-26
SG10201912276XA (en) 2020-02-27
US20120225927A1 (en) 2012-09-06
CA2739895C (en) 2018-09-25
CY2019005I2 (el) 2019-11-27
KR20190116553A (ko) 2019-10-14
HRP20150796T1 (hr) 2015-09-11
US20230257740A1 (en) 2023-08-17
NZ592867A (en) 2013-05-31
PL2344639T3 (pl) 2015-10-30
KR20160079921A (ko) 2016-07-06
LTC2937418I2 (lt) 2019-12-27
EP3354733B1 (en) 2020-12-09
CY1116944T1 (el) 2017-04-05
IL302142B1 (en) 2024-03-01
MX2011004268A (es) 2011-06-01
LUC00098I2 (enExample) 2019-12-24
NL300965I2 (nl) 2020-07-28
CA3018487A1 (en) 2010-04-29
US9234196B2 (en) 2016-01-12
JP6371446B2 (ja) 2018-08-08
EP2937418A1 (en) 2015-10-28
IL302142B2 (en) 2024-07-01
KR20110073592A (ko) 2011-06-29
US8168775B2 (en) 2012-05-01
JP2018171072A (ja) 2018-11-08
KR102354558B1 (ko) 2022-01-25
US12227744B2 (en) 2025-02-18
IL302142A (en) 2023-06-01
ES2656516T3 (es) 2018-02-27
JP7500658B2 (ja) 2024-06-17
NZ602404A (en) 2014-04-30
DK2344639T3 (en) 2015-07-27
CN106834291B (zh) 2020-09-29
WO2010048228A3 (en) 2010-09-16
US20200283766A1 (en) 2020-09-10
EP2937418B1 (en) 2017-10-18
NO2019004I1 (no) 2019-01-29
US20190309293A1 (en) 2019-10-10
EP3354733A1 (en) 2018-08-01
ZA201102876B (en) 2015-06-24
AU2009307677B2 (en) 2015-07-30
NO2937418T3 (enExample) 2018-03-17
US20170321213A1 (en) 2017-11-09
HUE026604T2 (hu) 2016-06-28
MX344354B (es) 2016-12-14
EA201792626A1 (ru) 2018-08-31
HK1258859A1 (en) 2019-11-22
IL243178A0 (en) 2016-02-29
CN103937793B (zh) 2017-08-11
HUE037875T2 (hu) 2018-09-28
US20160264963A1 (en) 2016-09-15
JP2012506254A (ja) 2012-03-15
NZ797298A (en) 2024-08-30
CA3222620A1 (en) 2010-04-29
JP2018007666A (ja) 2018-01-18
EA036772B1 (ru) 2020-12-18
PT2937418T (pt) 2018-01-23
SI2937418T1 (en) 2018-02-28
KR20220012422A (ko) 2022-02-03
IL281434B2 (en) 2023-09-01

Similar Documents

Publication Publication Date Title
JP7806130B2 (ja) トランスチレチンの発現を阻害するための組成物および方法
JP6669905B2 (ja) トランスチレチン（ＴＴＲ）関連眼アミロイドーシスのためのｓｉＲＮＡ療法
JP5723378B2 (ja) トランスサイレチン（ｔｔｒ）を阻害する脂質製剤化組成物及び方法
AU2021203272B2 (en) Compositions and methods for inhibiting expression of transthyretin

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20121016

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20121016

RD04 Notification of resignation of power of attorney

Free format text: JAPANESE INTERMEDIATE CODE: A7424

Effective date: 20140120

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20140422

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20140722

A602 Written permission of extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A602

Effective date: 20140729

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20140821

A602 Written permission of extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A602

Effective date: 20140828

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20140919

A602 Written permission of extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A602

Effective date: 20140929

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20150331

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20150624

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20150721

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20150804

R150 Certificate of patent or registration of utility model

Ref document number: 5791505

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R153 Grant of patent term extension

Free format text: JAPANESE INTERMEDIATE CODE: R153

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250