MX2018013398A - Composiciones y metodos para inhibir la expresion de transtiretina. - Google Patents

Composiciones y metodos para inhibir la expresion de transtiretina.

Info

Publication number
MX2018013398A
MX2018013398A MX2018013398A MX2018013398A MX2018013398A MX 2018013398 A MX2018013398 A MX 2018013398A MX 2018013398 A MX2018013398 A MX 2018013398A MX 2018013398 A MX2018013398 A MX 2018013398A MX 2018013398 A MX2018013398 A MX 2018013398A
Authority
MX
Mexico
Prior art keywords
transthyretin
methods
compositions
inhibiting expression
ttr
Prior art date
Application number
MX2018013398A
Other languages
English (en)
Inventor
Gregory Hinkle
Stuart Milstein
Dinah Wenyee Sah
Rene Alvarez
Qingmin Chen
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 MX2018013398A publication Critical patent/MX2018013398A/es

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
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • 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
    • 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
    • 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—Liposomes
    • 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 N.A.
    • 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)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Epidemiology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Dermatology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Psychiatry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Hospice & Palliative Care (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Urology & Nephrology (AREA)
  • Endocrinology (AREA)
  • Diabetes (AREA)

Abstract

La invención se refiere a un ácido ribonucleico de hebra doble (ARNds) que tiene como objetivo un gen de transtiretina (TTR), y métodos para usar el ARNds para inhibir la expresión de la TTR.
MX2018013398A 2008-10-20 2011-04-20 Composiciones y metodos para inhibir la expresion de transtiretina. MX2018013398A (es)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US10695608P 2008-10-20 2008-10-20
US11573808P 2008-11-18 2008-11-18
US15667009P 2009-03-02 2009-03-02
US18554509P 2009-06-09 2009-06-09
US24278309P 2009-09-15 2009-09-15
US24479409P 2009-09-22 2009-09-22

Publications (1)

Publication Number Publication Date
MX2018013398A true MX2018013398A (es) 2023-01-05

Family

ID=42062316

Family Applications (4)

Application Number Title Priority Date Filing Date
MX2013008747A MX344354B (es) 2008-10-20 2009-10-20 Composiciones y metodos para inhibir la expresion de transtiretina.
MX2011004268A MX2011004268A (es) 2008-10-20 2009-10-20 Composiciones y metodos para inhibir la expresion de transtiretina.
MX2016002209A MX360460B (es) 2008-10-20 2009-10-20 Composiciones y metodos para inhibir la expresion de transtiretina.
MX2018013398A MX2018013398A (es) 2008-10-20 2011-04-20 Composiciones y metodos para inhibir la expresion de transtiretina.

Family Applications Before (3)

Application Number Title Priority Date Filing Date
MX2013008747A MX344354B (es) 2008-10-20 2009-10-20 Composiciones y metodos para inhibir la expresion de transtiretina.
MX2011004268A MX2011004268A (es) 2008-10-20 2009-10-20 Composiciones y metodos para inhibir la expresion de transtiretina.
MX2016002209A MX360460B (es) 2008-10-20 2009-10-20 Composiciones y metodos para inhibir la expresion de transtiretina.

Country Status (28)

Country Link
US (8) US8168775B2 (es)
EP (4) EP2344639B1 (es)
JP (6) JP5791505B2 (es)
KR (6) KR102031027B1 (es)
CN (3) CN106834291B (es)
AU (1) AU2009307677C1 (es)
CA (3) CA2739895C (es)
CY (3) CY1116944T1 (es)
DK (2) DK2344639T3 (es)
EA (3) EA020312B1 (es)
ES (2) ES2656516T3 (es)
HK (3) HK1156348A1 (es)
HR (2) HRP20150796T1 (es)
HU (3) HUE037875T2 (es)
IL (5) IL310600A (es)
LT (2) LT2937418T (es)
LU (1) LUC00098I2 (es)
MX (4) MX344354B (es)
NL (1) NL300965I2 (es)
NO (2) NO2937418T3 (es)
NZ (2) NZ602404A (es)
PL (2) PL2937418T3 (es)
PT (2) PT2937418T (es)
SG (3) SG10201809460SA (es)
SI (2) SI2937418T1 (es)
SM (1) SMT201500176B (es)
WO (1) WO2010048228A2 (es)
ZA (1) ZA201102876B (es)

Families Citing this family (106)

* 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
WO2007134161A2 (en) * 2006-05-11 2007-11-22 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the pcsk9 gene
DK2279254T3 (en) 2008-04-15 2017-09-18 Protiva Biotherapeutics Inc PRESENT UNKNOWN LIPID FORMS FOR NUCLEIC ACID ADMINISTRATION
CA2739895C (en) 2008-10-20 2018-09-25 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of transthyretin
US8324368B2 (en) * 2008-12-10 2012-12-04 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
CA2764832A1 (en) * 2009-06-15 2010-12-23 Alnylam Pharmaceuticals, Inc. Lipid formulated dsrna targeting the pcsk9 gene
US9051567B2 (en) 2009-06-15 2015-06-09 Tekmira Pharmaceuticals Corporation Methods for increasing efficacy of lipid formulated siRNA
IL292615B2 (en) 2009-07-01 2023-11-01 Protiva Biotherapeutics Inc Nucleic acid-lipid particles, preparations containing them and their uses
WO2011020023A2 (en) * 2009-08-14 2011-02-17 Alnylam Pharmaceuticals, Inc. Lipid formulated compositions and methods for inhibiting expression of a gene from the ebola virus
JP5723378B2 (ja) * 2009-11-03 2015-05-27 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
ES2893199T3 (es) * 2010-03-29 2022-02-08 Alnylam Pharmaceuticals Inc Terapia de ARNbc para amiloidosis ocular relacionada con transtiretina (TTR)
JP5896175B2 (ja) * 2010-04-29 2016-03-30 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． トランスサイレチン発現の調節
WO2011141705A1 (en) * 2010-05-12 2011-11-17 Protiva Biotherapeutics, Inc. Novel cationic lipids and methods of use thereof
EP3456827A3 (en) * 2010-06-02 2019-05-08 Alnylam Pharmaceuticals, Inc. Compositions and methods directed to treating liver fibrosis
WO2012000104A1 (en) 2010-06-30 2012-01-05 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
WO2012068176A1 (en) 2010-11-15 2012-05-24 Life Technologies Corporation Amine-containing transfection reagents and methods for making and using same
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.
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
CN107287202B (zh) 2011-06-21 2021-03-16 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
EP2723865B1 (en) * 2011-06-21 2019-03-27 Alnylam Pharmaceuticals, Inc. METHODS FOR DETERMINING ACTIVITY OF RNAi IN A SUBJECT
US9399775B2 (en) * 2011-11-18 2016-07-26 Alnylam Pharmaceuticals, Inc. RNAi agents, compositions and methods of use thereof for treating transthyretin (TTR) associated diseases
US9061063B2 (en) 2011-12-07 2015-06-23 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
US20140200261A1 (en) 2013-01-17 2014-07-17 Moderna Therapeutics, Inc. Signal-sensor polynucleotides for the alteration of cellular phenotypes
WO2014124334A2 (en) 2013-02-08 2014-08-14 Misfolding Diagnostics, Inc. Transthyretin antibodies and uses thereof
CN115261411A (zh) 2013-04-04 2022-11-01 哈佛学院校长同事会 利用CRISPR/Cas系统的基因组编辑的治疗性用途
SG10201801813YA (en) 2013-05-01 2018-04-27 Ionis Pharmaceuticals Inc Compositions and methods for modulating apolipoprotein c-iii expression
WO2014204726A1 (en) * 2013-06-17 2014-12-24 The Broad Institute Inc. Delivery and use of the crispr-cas systems, vectors and compositions for hepatic targeting and therapy
JP2016528890A (ja) 2013-07-09 2016-09-23 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系を用いるゲノム編集の治療用の使用
AR097738A1 (es) * 2013-09-23 2016-04-13 Alnylam Pharmaceuticals Inc Métodos para tratar o prevenir enfermedades asociadas con la transtiretina (ttr)
CA2925107A1 (en) * 2013-10-02 2015-04-09 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the lect2 gene
WO2015085158A1 (en) 2013-12-06 2015-06-11 Dicerna Pharmaceuticals, Inc. Methods and compositions for the specific inhibition of transthyretin (ttr) by double-stranded rna
EP3122365B1 (en) * 2014-03-25 2023-05-03 Arcturus Therapeutics, Inc. Transthyretin allele selective una oligomers for gene silencing
AU2015236215B2 (en) 2014-03-25 2020-03-19 Arcturus Therapeutics, Inc. UNA oligomers having reduced off-target effects in gene silencing
US9856475B2 (en) 2014-03-25 2018-01-02 Arcturus Therapeutics, Inc. Formulations for treating amyloidosis
CA2943894A1 (en) 2014-05-01 2015-11-05 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating complement factor b expression
KR102410072B1 (ko) 2014-08-29 2022-06-20 알닐람 파마슈티칼스 인코포레이티드 트랜스타이레틴(ttr) 매개 아밀로이드증의 치료 방법
JP6830441B2 (ja) * 2015-04-01 2021-02-17 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． 治療上のｕｎａオリゴマーおよびその使用
WO2016164746A1 (en) 2015-04-08 2016-10-13 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the lect2 gene
BR112017021053A2 (pt) 2015-04-13 2018-08-14 Alnylam Pharmaceuticals Inc composições de irna de angiopoietina do tipo 3 (angptl3) e métodos de uso do mesmo
US10968426B2 (en) 2015-05-08 2021-04-06 President And Fellows Of Harvard College Universal donor stem cells and related methods
WO2017015671A1 (en) * 2015-07-23 2017-01-26 Arcturus Therapeutics, Inc. Compositions for treating amyloidosis
SG10201912341SA (en) 2015-07-31 2020-02-27 Alnylam Pharmaceuticals Inc TRANSTHYRETIN (TTR) iRNA COMPOSITIONS AND METHODS OF USE THEREOF FOR TREATING OR PREVENTING TTR-ASSOCIATED DISEASES
KR102515329B1 (ko) 2016-03-07 2023-03-29 애로우헤드 파마슈티컬스 인코포레이티드 치료용 화합물을 위한 표적화 리간드
TW202320855A (zh) 2016-09-02 2023-06-01 美商愛羅海德製藥公司 標靶性配體
CN109661233A (zh) 2016-10-06 2019-04-19 Ionis 制药公司 缀合低聚化合物的方法
WO2018102397A1 (en) 2016-11-29 2018-06-07 PureTech Health LLC Exosomes for delivery of therapeutic agents
CN110381940B (zh) 2017-02-17 2023-07-21 文涵治疗有限公司 Ag-10的制备方法、其中间体及其盐
US11806360B2 (en) 2017-09-19 2023-11-07 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating transthyretin (TTR) mediated amyloidosis
SG11202002565YA (en) 2017-09-29 2020-04-29 Intellia Therapeutics Inc Compositions and methods for ttr gene editing and treating attr amyloidosis
MX2020003589A (es) 2017-09-29 2020-07-22 Regeneron Pharma Animales no humanos que comprenden un locus ttr humanizado y metodos de uso.
WO2019183463A1 (en) * 2018-03-23 2019-09-26 Eidos Therapeutics, Inc. Methods of treating ttr amyloidosis using ag10
CN112804998A (zh) 2018-08-17 2021-05-14 文涵治疗有限公司 Ag10的制剂
CN113166783A (zh) 2018-10-09 2021-07-23 不列颠哥伦比亚大学 包含无有机溶剂和去污剂的转染活性囊泡的组合物和系统以及与之相关的方法
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
CN113874510A (zh) 2019-06-04 2021-12-31 瑞泽恩制药公司 包括具有β滑移突变的人源化TTR基因座的非人动物和使用方法
JP2022542839A (ja) 2019-07-19 2022-10-07 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 リコンビナーゼ組成物及び使用方法
WO2021041884A1 (en) 2019-08-30 2021-03-04 Alnylam Pharmaceuticals, Inc. Neurofilament light chain (nfl) as a biomarker for transthyretin amyloidosis polyneuropathy
AU2020378414A1 (en) * 2019-11-06 2022-05-26 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery
AU2021232029A1 (en) 2020-03-06 2022-10-06 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of transthyretin (TTR)
EP4153223A1 (en) 2020-05-20 2023-03-29 Flagship Pioneering Innovations VI, LLC Immunogenic compositions and uses thereof
EP4153224A1 (en) 2020-05-20 2023-03-29 Flagship Pioneering Innovations VI, LLC Coronavirus antigen compositions and their uses
EP4158031A1 (en) 2020-05-29 2023-04-05 Flagship Pioneering Innovations VI, LLC Trem compositions and methods relating thereto
AU2021281453A1 (en) 2020-05-29 2022-11-17 Flagship Pioneering Innovations Vi, Llc. Trem compositions and methods relating thereto
AU2021336976A1 (en) 2020-09-03 2023-03-23 Flagship Pioneering Innovations Vi, Llc Immunogenic compositions and uses thereof
IL303195A (en) 2020-11-25 2023-07-01 Akagera Medicines Inc Lipid nanoparticles for delivery of nucleic acids and related methods of use
WO2022112919A1 (en) 2020-11-25 2022-06-02 Pfizer Inc. (aza)benzothiazolyl substituted pyrazole compounds
BR112023012377A2 (pt) 2020-12-23 2023-10-24 Flagship Pioneering Innovations Vi Llc Composições de trems modificadas e usos das mesmas
WO2022178411A1 (en) * 2021-02-22 2022-08-25 Alnylam Pharmaceuticals, Inc. Folliculin irna compositions and methods thereof
IL305442A (en) 2021-03-04 2023-10-01 Alnylam Pharmaceuticals Inc Angiopoietin-like 3 (ANGPTL3) IRNA compositions and methods of using them
AU2022246895A1 (en) 2021-03-31 2023-10-19 Flagship Pioneering Innovations V, Inc. Thanotransmission polypeptides and their use in treating cancer
WO2022235537A1 (en) 2021-05-03 2022-11-10 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating transthyretin (ttr) mediated amyloidosis
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
AU2022323090A1 (en) * 2021-08-03 2024-02-01 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof
AU2022343268A1 (en) 2021-09-08 2024-03-28 Flagship Pioneering Innovations Vi, Llc Methods and compositions for modulating a genome
AR127073A1 (es) 2021-09-17 2023-12-13 Flagship Pioneering Innovations Vi Llc Composiciones y métodos para producir polirribonucleótidos circulares
WO2023069397A1 (en) 2021-10-18 2023-04-27 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
IL312799A (en) 2021-11-24 2024-07-01 Flagship Pioneering Innovations Vi Llc Immunogenic compositions of varicella-zoster virus and uses thereof
WO2023096990A1 (en) 2021-11-24 2023-06-01 Flagship Pioneering Innovation Vi, Llc Coronavirus immunogen compositions and their uses
AU2022397300A1 (en) 2021-11-24 2024-06-27 Flagship Pioneering Innovations Vi, Llc Immunogenic compositions and their uses
TW202340461A (zh) 2021-12-22 2023-10-16 美商旗艦先鋒創新有限責任公司 用於純化多核糖核苷酸之組成物和方法
WO2023122789A1 (en) 2021-12-23 2023-06-29 Flagship Pioneering Innovations Vi, Llc Circular polyribonucleotides encoding antifusogenic polypeptides
WO2023196634A2 (en) 2022-04-08 2023-10-12 Flagship Pioneering Innovations Vii, Llc Vaccines and related methods
WO2023220083A1 (en) 2022-05-09 2023-11-16 Flagship Pioneering Innovations Vi, Llc Trem compositions and methods of use for treating proliferative disorders
TW202409283A (zh) 2022-05-13 2024-03-01 美商旗艦先鋒創新有限責任（Ｖｉｉ）公司 雙股ｄｎａ組合物及相關方法
WO2023250112A1 (en) 2022-06-22 2023-12-28 Flagship Pioneering Innovations Vi, Llc Compositions of modified trems and uses thereof
WO2024030856A2 (en) 2022-08-01 2024-02-08 Flagship Pioneering Innovations Vii, Llc Immunomodulatory proteins and related methods
WO2024035952A1 (en) 2022-08-12 2024-02-15 Remix Therapeutics Inc. Methods and compositions for modulating splicing at alternative splice sites
WO2024077191A1 (en) 2022-10-05 2024-04-11 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
WO2024102799A1 (en) 2022-11-08 2024-05-16 Flagship Pioneering Innovations Vi, Llc Compositions and methods for producing circular polyribonucleotides
WO2024108217A1 (en) 2022-11-18 2024-05-23 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
WO2024129988A1 (en) 2022-12-14 2024-06-20 Flagship Pioneering Innovations Vii, Llc Compositions and methods for delivery of therapeutic agents to bone
WO2024151685A1 (en) 2023-01-09 2024-07-18 Beth Israel Deaconess Medical Center, Inc. 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
US20240238473A1 (en) 2023-01-09 2024-07-18 Beth Israel Deaconess Medical Center, Inc. Recombinant nucleic acid molecules and their use in wound healing

Family Cites Families (218)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US513030A (en) 1894-01-16 Machine for waxing or coating paper
US564562A (en) 1896-07-21 Joseph p
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
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
US5118800A (en) 1983-12-20 1992-06-02 California Institute Of Technology Oligonucleotides possessing a primary amino group in the terminal nucleotide
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
US5258506A (en) 1984-10-16 1993-11-02 Chiron Corporation Photolabile reagents for incorporation into oligonucleotide chains
US5367066A (en) 1984-10-16 1994-11-22 Chiron Corporation Oligonucleotides with selectably cleavable and/or abasic sites
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
US5166315A (en) 1989-12-20 1992-11-24 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5405938A (en) 1989-12-20 1995-04-11 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
US5235033A (en) 1985-03-15 1993-08-10 Anti-Gene Development Group Alpha-morpholino ribonucleoside derivatives and polymers thereof
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
ATE68013T1 (de) 1985-07-05 1991-10-15 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
US4837028A (en) 1986-12-24 1989-06-06 Liposome Technology, Inc. Liposomes with enhanced circulation time
US4920016A (en) 1986-12-24 1990-04-24 Linear Technology, Inc. Liposomes with enhanced circulation time
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
US4904582A (en) 1987-06-11 1990-02-27 Synthetic Genetics Novel amphiphilic nucleic acid conjugates
DE3851889T2 (de) 1987-06-24 1995-04-13 Florey Howard Inst Nukleosid-derivate.
ATE117375T1 (de) 1987-09-11 1995-02-15 Whitehead Biomedical Inst Transduktionsveränderte fibroblasten und ihre anwendung.
US5585481A (en) 1987-09-21 1996-12-17 Gen-Probe Incorporated Linking reagents for nucleotide probes
US5188897A (en) 1987-10-22 1993-02-23 Temple University Of The Commonwealth System Of Higher Education Encapsulated 2',5'-phosphorothioate oligoadenylates
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
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
EP0391960B1 (en) 1987-12-11 1994-08-17 Whitehead Institute For Biomedical Research Genetic modification of endothelial cells
ATE152169T1 (de) 1988-02-05 1997-05-15 Whitehead Biomedical 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
US5599923A (en) 1989-03-06 1997-02-04 Board Of Regents, University Of Tx Texaphyrin metal complexes having improved functionalization
US5457183A (en) 1989-03-06 1995-10-10 Board Of Regents, The University Of Texas System Hydroxylated texaphyrins
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
US5013556A (en) 1989-10-20 1991-05-07 Liposome Technology, Inc. Liposomes with enhanced circulation time
US5225212A (en) 1989-10-20 1993-07-06 Liposome Technology, Inc. Microreservoir liposome composition and method
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
DK0942000T3 (da) 1989-10-24 2004-11-01 Isis Pharmaceuticals Inc 2'-modificerede oligonukleotider
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
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
US5587470A (en) 1990-01-11 1996-12-24 Isis Pharmaceuticals, Inc. 3-deazapurines
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5578718A (en) 1990-01-11 1996-11-26 Isis Pharmaceuticals, Inc. Thiol-derivatized nucleosides
US5681941A (en) 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US5670633A (en) 1990-01-11 1997-09-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
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
EP0745689A3 (en) 1990-05-11 1996-12-11 Microprobe Corporation A dipstick for a nucleic acid hybridization assay
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5623070A (en) 1990-07-27 1997-04-22 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5688941A (en) 1990-07-27 1997-11-18 Isis Pharmaceuticals, Inc. Methods of making conjugated 4' desmethyl nucleoside analog compounds
US5618704A (en) 1990-07-27 1997-04-08 Isis Pharmacueticals, Inc. Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling
US5138045A (en) 1990-07-27 1992-08-11 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
EP0544824B1 (en) 1990-07-27 1997-06-11 Isis Pharmaceuticals, Inc. Nuclease resistant, pyrimidine modified oligonucleotides that detect and modulate gene expression
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5677437A (en) 1990-07-27 1997-10-14 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5218105A (en) 1990-07-27 1993-06-08 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5245022A (en) 1990-08-03 1993-09-14 Sterling Drug, Inc. Exonuclease resistant terminally substituted oligonucleotides
BR9106729A (pt) 1990-08-03 1993-07-20 Sterling Winthrop Inc Composto,processos para inibir a degradacao por nuclease de compostos e para estabilizar sequencias de nicleotideos ou oligonucleosideos,composicao utilizavel para inibir expressao de genes e processo para inibir expressao de genes em um mamifero necessitando de tal tratamento
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
EP0556345B2 (en) 1990-10-31 2005-10-12 Cell Genesys, Inc. Retroviral vectors useful for gene therapy
EP0556301B1 (en) 1990-11-08 2001-01-10 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
US5714331A (en) 1991-05-24 1998-02-03 Buchardt, Deceased; Ole Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility
US5539082A (en) 1993-04-26 1996-07-23 Nielsen; Peter E. Peptide nucleic acids
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
US5565552A (en) 1992-01-21 1996-10-15 Pharmacyclics, Inc. Method of expanded porphyrin-oligonucleotide conjugate synthesis
US5595726A (en) 1992-01-21 1997-01-21 Pharmacyclics, Inc. Chromophore probe for detection of nucleic acid
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
ATE155467T1 (de) 1993-03-30 1997-08-15 Sanofi Sa Acyclische nucleosid analoge und sie enthaltende oligonucleotidsequenzen
JPH08508491A (ja) 1993-03-31 1996-09-10 スターリング ウインスロップ インコーポレイティド ホスホジエステル結合をアミド結合に置き換えたオリゴヌクレオチド
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
AU5545596A (en) 1995-04-28 1996-11-18 Medtronic, Inc. Intraparenchymal infusion catheter system
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
IL122290A0 (en) 1995-06-07 1998-04-05 Inex Pharmaceuticals Corp Lipid-nucleic acid complex its preparation and use
US5981501A (en) 1995-06-07 1999-11-09 Inex Pharmaceuticals Corp. Methods for encapsulating plasmids in lipid bilayers
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
AU705644B2 (en) 1995-08-01 1999-05-27 Novartis Ag 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
ATE321882T1 (de) 1997-07-01 2006-04-15 Isis Pharmaceuticals Inc Zusammensetzungen und verfahren zur verabreichung von oligonukleotiden über die speiseröhre
US6506559B1 (en) 1997-12-23 2003-01-14 Carnegie Institute Of Washington Genetic inhibition by double-stranded RNA
ATE507299T1 (de) 1998-04-08 2011-05-15 Commw Scient Ind Res Org Verfahren und mittel zum erhalt von veränderten phänotypen
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
JP2002520038A (ja) 1998-07-20 2002-07-09 アイネックス ファーマシューティカルズ コーポレイション リポソームカプセル化核酸複合体
MXPA01003642A (es) 1998-10-09 2003-07-21 Ingene Inc Sintesis enzimatica de adnss.
CA2345936A1 (en) 1998-10-09 2000-04-20 Ingene, Inc. Production of ssdna in a cell
DE19956568A1 (de) 1999-01-30 2000-08-17 Roland Kreutzer Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens
EP1156812A4 (en) 1999-02-23 2004-09-29 Isis Pharmaceuticals Inc MULTIPARTICULAR FORMULATION
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
RU2322500C2 (ru) * 2000-12-01 2008-04-20 Макс-Планк-Гезелльшафт Цур Фердерунг Дер Виссеншафтен Е.Ф. Малые молекулы рнк, опосредующие интерференцию рнк
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)
US7956176B2 (en) * 2002-09-05 2011-06-07 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
EP2305812A3 (en) * 2002-11-14 2012-06-06 Dharmacon, Inc. Fuctional 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
EP1605978B1 (en) 2003-03-07 2010-09-01 Alnylam Pharmaceuticals Inc. Therapeutic compositions
JP2006522158A (ja) 2003-04-03 2006-09-28 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 ｉＲＮＡ複合体
CA2532228C (en) 2003-07-16 2017-02-14 Protiva Biotherapeutics, Inc. Lipid encapsulated interfering rna
US20050244869A1 (en) 2004-04-05 2005-11-03 Brown-Driver Vickie L Modulation of transthyretin expression
US7799565B2 (en) 2004-06-07 2010-09-21 Protiva Biotherapeutics, Inc. Lipid encapsulated interfering RNA
WO2005120152A2 (en) 2004-06-07 2005-12-22 Protiva Biotherapeutics, Inc. Cationic lipids and methods of use
US7838561B2 (en) * 2004-06-14 2010-11-23 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
WO2007086883A2 (en) * 2005-02-14 2007-08-02 Sirna Therapeutics, Inc. Cationic lipids and formulated molecular compositions containing them
EP1866414B9 (en) 2005-03-31 2012-10-03 Calando Pharmaceuticals, Inc. Inhibitors of ribonucleotide reductase subunit 2 and uses thereof
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
CN101267805A (zh) 2005-07-27 2008-09-17 普洛体维生物治疗公司 制造脂质体的系统和方法
EP2395012B8 (en) 2005-11-02 2018-06-06 Arbutus Biopharma Corporation Modified siRNA molecules and uses thereof
US7718629B2 (en) 2006-03-31 2010-05-18 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of Eg5 gene
US8598333B2 (en) 2006-05-26 2013-12-03 Alnylam Pharmaceuticals, Inc. SiRNA silencing of genes expressed in cancer
CA2665225C (en) * 2006-10-03 2015-06-30 Alnylam Pharmaceuticals, Inc. Lipid containing formulations
EP3705125B1 (en) * 2007-12-04 2023-07-05 Alnylam Pharmaceuticals, Inc. Carbohydrate conjugates as delivery agents for oligonucleotides
ES2535419T3 (es) * 2007-12-27 2015-05-11 Protiva Biotherapeutics Inc. Silenciamiento de expresión de quinasa tipo polo usando ARN interferente
CA3044134A1 (en) 2008-01-02 2009-07-09 Arbutus Biopharma Corporation Improved compositions and methods for the delivery of nucleic acids
DK2279254T3 (en) * 2008-04-15 2017-09-18 Protiva Biotherapeutics Inc PRESENT UNKNOWN LIPID FORMS FOR NUCLEIC ACID ADMINISTRATION
US20110237646A1 (en) 2008-08-07 2011-09-29 Isis Pharmaceuticals, Inc. Modulation of transthyretin expression for the treatment of cns related disorders
CN102245590B (zh) * 2008-10-09 2014-03-19 泰米拉制药公司 改善的氨基脂质和递送核酸的方法
CA2739895C (en) 2008-10-20 2018-09-25 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of transthyretin
EP2365962B1 (en) 2008-11-07 2017-07-05 Massachusetts Institute of Technology Aminoalcohol lipidoids and uses thereof
MX359674B (es) 2008-11-10 2018-10-05 Alnylam Pharmaceuticals Inc Lipidos y composiciones novedosas para el suministro de terapeuticos.
US20120101148A1 (en) 2009-01-29 2012-04-26 Alnylam Pharmaceuticals, Inc. lipid formulation
WO2010129709A1 (en) 2009-05-05 2010-11-11 Alnylam Pharmaceuticals, Inc. Lipid compositions
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
JP5723378B2 (ja) 2009-11-03 2015-05-27 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
JP5896175B2 (ja) 2010-04-29 2016-03-30 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． トランスサイレチン発現の調節
KR102005337B1 (ko) * 2014-01-09 2019-07-30 에스케이하이닉스 주식회사 전압 변환 장치
US10799808B2 (en) 2018-09-13 2020-10-13 Nina Davis Interactive storytelling kit

Also Published As

Publication number Publication date
HUS1900004I1 (hu) 2019-03-28
IL281434B1 (en) 2023-05-01
KR102354558B1 (ko) 2022-01-25
PL2937418T3 (pl) 2018-04-30
HK1258859A1 (zh) 2019-11-22
HUE037875T2 (hu) 2018-09-28
CA3222620A1 (en) 2010-04-29
EP2937418A1 (en) 2015-10-28
NZ602404A (en) 2014-04-30
US20230257740A1 (en) 2023-08-17
IL212428A0 (en) 2011-06-30
CY1120174T1 (el) 2018-12-12
CN102186978B (zh) 2014-03-12
HK1156348A1 (en) 2012-06-08
HRP20180093T1 (hr) 2018-02-23
MX2011004268A (es) 2011-06-01
CA2739895C (en) 2018-09-25
KR101635436B1 (ko) 2016-07-01
HK1216652A1 (zh) 2016-11-25
EA201792626A1 (ru) 2018-08-31
MX344354B (es) 2016-12-14
IL302142B1 (en) 2024-03-01
US20160264963A1 (en) 2016-09-15
IL302142A (en) 2023-06-01
EP2344639A2 (en) 2011-07-20
US20170321213A1 (en) 2017-11-09
CY1116944T1 (el) 2017-04-05
CN103937793A (zh) 2014-07-23
US10240152B2 (en) 2019-03-26
IL302142B2 (en) 2024-07-01
IL281434A (en) 2021-04-29
AU2009307677C1 (en) 2022-09-22
SG10201912276XA (en) 2020-02-27
EP3848461A1 (en) 2021-07-14
EA020312B1 (ru) 2014-10-30
US20100120893A1 (en) 2010-05-13
DK2937418T3 (en) 2018-01-22
NL300965I2 (nl) 2020-07-28
HUE026604T2 (hu) 2016-06-28
SMT201500176B (it) 2015-09-07
EA201400170A1 (ru) 2015-03-31
KR20160079921A (ko) 2016-07-06
EP2937418B1 (en) 2017-10-18
CY2019005I2 (el) 2019-11-27
MX360460B (es) 2018-11-05
KR20190116553A (ko) 2019-10-14
JP5791505B2 (ja) 2015-10-07
AU2009307677B2 (en) 2015-07-30
EP2344639B1 (en) 2015-04-22
IL243178A0 (en) 2016-02-29
PT2344639E (pt) 2015-09-07
JP2019205442A (ja) 2019-12-05
KR20220012422A (ko) 2022-02-03
NO2019004I1 (no) 2019-01-29
NO2937418T3 (es) 2018-03-17
ES2656516T3 (es) 2018-02-27
EP3354733B1 (en) 2020-12-09
BRPI0919732A2 (pt) 2015-12-08
EA036772B1 (ru) 2020-12-18
EP3354733A1 (en) 2018-08-01
IL281434B2 (en) 2023-09-01
SG10201703242XA (en) 2017-06-29
ES2543004T3 (es) 2015-08-13
JP7500658B2 (ja) 2024-06-17
US20190309293A1 (en) 2019-10-10
IL310600A (en) 2024-04-01
AU2009307677A1 (en) 2010-04-29
JP2018007666A (ja) 2018-01-18
US20140194493A1 (en) 2014-07-10
EA029762B1 (ru) 2018-05-31
LT2937418T (lt) 2018-02-12
JP2018171072A (ja) 2018-11-08
JP6371446B2 (ja) 2018-08-08
KR20110073592A (ko) 2011-06-29
EA201170591A1 (ru) 2011-12-30
SI2344639T1 (sl) 2015-09-30
CN103937793B (zh) 2017-08-11
US20200283766A1 (en) 2020-09-10
KR102031027B1 (ko) 2019-10-14
LTC2937418I2 (lt) 2019-12-27
CN102186978A (zh) 2011-09-14
JP6553780B2 (ja) 2019-07-31
KR101624869B1 (ko) 2016-05-30
PT2937418T (pt) 2018-01-23
SI2937418T1 (en) 2018-02-28
CA3018487A1 (en) 2010-04-29
CN106834291B (zh) 2020-09-29
KR20150007359A (ko) 2015-01-20
US8741866B2 (en) 2014-06-03
CN106834291A (zh) 2017-06-13
CY2019005I1 (el) 2019-11-27
DK2344639T3 (en) 2015-07-27
NZ592867A (en) 2013-05-31
PL2344639T3 (pl) 2015-10-30
LUC00098I1 (es) 2019-01-31
IL243178B (en) 2021-03-25
LUC00098I2 (es) 2019-12-24
HRP20150796T1 (hr) 2015-09-11
JP2022160408A (ja) 2022-10-19
JP2015062420A (ja) 2015-04-09
JP2012506254A (ja) 2012-03-15
SG10201809460SA (en) 2018-11-29
US9234196B2 (en) 2016-01-12
LTPA2019501I1 (lt) 2019-02-25
US8168775B2 (en) 2012-05-01
KR102578331B1 (ko) 2023-09-15
WO2010048228A2 (en) 2010-04-29
ZA201102876B (en) 2015-06-24
KR20180017245A (ko) 2018-02-20
NL300965I1 (nl) 2019-02-06
US20120225927A1 (en) 2012-09-06
CA2739895A1 (en) 2010-04-29
WO2010048228A3 (en) 2010-09-16

Similar Documents

Publication Publication Date Title
MX2018013398A (es) Composiciones y metodos para inhibir la expresion de transtiretina.
EP2496238A4 (en) FORMULATED LIPID COMPOSITIONS AND METHODS FOR INHIBITING TRANSTHYRETIN EXPRESSION (TTR)
MX2018013216A (es) Composiciones y metodos para inhibir la expresion del gen de proteasa transmembrana, serina 6 (tmprss6).
MX2021015290A (es) Composiciones y metodos para inhibicion de genes para apolipoproteina c-iii (apoc3).
WO2009129465A3 (en) Compositions and methods for inhibiting expression of xbp-1 gene
WO2009076400A3 (en) Compositions and methods for inhibiting expression of factor vii gene
MX2021009118A (es) Composiciones y metodos para inhibir la expresion del gen alas1.
CA2792561C (en) Compositions and methods for inhibiting expression of cd274/pd-l1 gene
EP2464336A4 (en) COMPOSITIONS FORMULATED IN LIPIDS AND METHODS OF INHIBITING THE EXPRESSION OF EBOLA VIRUS GENE
WO2013163430A3 (en) Serpinc1 irna compositions and methods of use thereof
AU2012272970A8 (en) Angiopoietin-like 3 (ANGPTL3) iRNA compositions and methods of use thereof
WO2008121604A3 (en) Compositions and methods for inhibiting expression of a gene from the ebola
WO2012027713A3 (en) Compositions and methods for inhibition of snca
WO2012079046A3 (en) Compositions and methods for inhibiting expression of klf-1 and bcl11a genes
WO2010028054A8 (en) Compositions and methods for inhibiting expression of mutant egfr gene
WO2012177921A3 (en) Compositions and methods for inhibiting hepcidin antimicrobial peptide (hamp) or hamp-related gene expression
MX2022001017A (es) Composiciones y metodos para inhibir la expresion del gen de sintasa de acido 5'-aminolevulinico 1 (alas1).
WO2010006342A9 (en) Compositions and methods for inhibiting expression of gsk-3 genes
WO2009137128A3 (en) Compositions and methods for inhibiting expression of cd45 gene
EA202092118A2 (ru) Композиции и способы для ингибирования экспрессии транстиретина
NZ748858A (en) Compositions and methods for inhibiting expression of transthyretin