CA2559161C - Irna agents targeting vegf - Google Patents

Irna agents targeting vegf Download PDF

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Publication number
CA2559161C
CA2559161C CA2559161A CA2559161A CA2559161C CA 2559161 C CA2559161 C CA 2559161C CA 2559161 A CA2559161 A CA 2559161A CA 2559161 A CA2559161 A CA 2559161A CA 2559161 C CA2559161 C CA 2559161C
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CA
Canada
Prior art keywords
irna agent
sequence
irna
rna
vegf
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.)
Expired - Fee Related
Application number
CA2559161A
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English (en)
French (fr)
Other versions
CA2559161A1 (en
Inventor
Antonin De Fougerolles
Maria Frank-Kamenetsky
Muthiah Manoharan
Kallanthottathil G. Rajeev
Philipp Hadwiger
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
Priority to CA2815554A priority Critical patent/CA2815554A1/en
Publication of CA2559161A1 publication Critical patent/CA2559161A1/en
Application granted granted Critical
Publication of CA2559161C publication Critical patent/CA2559161C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1136—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against growth factors, growth regulators, cytokines, lymphokines or hormones
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    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
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    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/712—Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
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    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
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    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/55—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
    • A61K47/551—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds one of the codrug's components being a vitamin, e.g. niacinamide, vitamin B3, cobalamin, vitamin B12, folate, vitamin A or retinoic acid
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    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
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    • A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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    • 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
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    • 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
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    • C12N2310/351—Conjugate
    • C12N2310/3515—Lipophilic moiety, e.g. cholesterol
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    • C12N2310/53—Physical structure partially self-complementary or closed
    • C12N2310/533—Physical structure partially self-complementary or closed having a mismatch or nick in at least one of the strands
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    • C12N2320/00—Applications; Uses
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    • C12N2320/30—Special therapeutic applications
    • C12N2320/32—Special delivery means, e.g. tissue-specific

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  • Health & Medical Sciences (AREA)
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  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
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  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Biomedical Technology (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Biophysics (AREA)
  • Immunology (AREA)
  • Endocrinology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Pulmonology (AREA)
  • Diabetes (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Rheumatology (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
CA2559161A 2004-03-12 2005-03-11 Irna agents targeting vegf Expired - Fee Related CA2559161C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA2815554A CA2815554A1 (en) 2004-03-12 2005-03-11 Irna agents targeting vegf

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US55262004P 2004-03-12 2004-03-12
US60/552,620 2004-03-12
US55982404P 2004-04-05 2004-04-05
US60/559,824 2004-04-05
US64719105P 2005-01-25 2005-01-25
US60/647,191 2005-01-25
PCT/US2005/008182 WO2005089224A2 (en) 2004-03-12 2005-03-11 iRNA AGENTS TARGETING VEGF

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CA2815554A Division CA2815554A1 (en) 2004-03-12 2005-03-11 Irna agents targeting vegf

Publications (2)

Publication Number Publication Date
CA2559161A1 CA2559161A1 (en) 2005-09-29
CA2559161C true CA2559161C (en) 2013-06-11

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CA2559161A Expired - Fee Related CA2559161C (en) 2004-03-12 2005-03-11 Irna agents targeting vegf

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US (5) US7947659B2 (enExample)
EP (4) EP2636739B1 (enExample)
JP (4) JP4937899B2 (enExample)
AU (2) AU2005222902B2 (enExample)
CA (1) CA2559161C (enExample)
ES (1) ES2423060T3 (enExample)
WO (1) WO2005089224A2 (enExample)

Families Citing this family (119)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2832154B1 (fr) 2001-11-09 2007-03-16 Centre Nat Rech Scient Oligonucleotides inhibiteurs et leur utilisation pour reprimer specifiquement un gene
EP1495120B1 (en) * 2002-04-18 2012-10-10 Acuity Pharmaceuticals, Inc Means and methods for the specific modulation of target genes in the eye
US7148342B2 (en) * 2002-07-24 2006-12-12 The Trustees Of The University Of Pennyslvania Compositions and methods for sirna inhibition of angiogenesis
DK1527176T4 (en) 2002-08-05 2017-07-03 Silence Therapeutics Gmbh ADDITIONAL NEW FORMS OF INTERFERRING RNA MOLECULES
US9879266B2 (en) 2002-11-14 2018-01-30 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
US10011836B2 (en) 2002-11-14 2018-07-03 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
US7592442B2 (en) 2002-11-14 2009-09-22 Dharmacon, Inc. siRNA targeting ribonucleotide reductase M2 polypeptide (RRM2 or RNR-R2)
US9839649B2 (en) 2002-11-14 2017-12-12 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
US7635770B2 (en) 2002-11-14 2009-12-22 Dharmacon, Inc. siRNA targeting protein kinase N-3 (PKN-3)
US8198427B1 (en) 2002-11-14 2012-06-12 Dharmacon, Inc. SiRNA targeting catenin, beta-1 (CTNNB1)
EP1560931B1 (en) 2002-11-14 2011-07-27 Dharmacon, Inc. Functional and hyperfunctional sirna
US9719094B2 (en) 2002-11-14 2017-08-01 Thermo Fisher Scientific Inc. RNAi targeting SEC61G
US7619081B2 (en) 2002-11-14 2009-11-17 Dharmacon, Inc. siRNA targeting coatomer protein complex, subunit beta 2 (COPB2)
US7977471B2 (en) 2002-11-14 2011-07-12 Dharmacon, Inc. siRNA targeting TNFα
US7781575B2 (en) 2002-11-14 2010-08-24 Dharmacon, Inc. siRNA targeting tumor protein 53 (p53)
US7691998B2 (en) 2002-11-14 2010-04-06 Dharmacon, Inc. siRNA targeting nucleoporin 62kDa (Nup62)
WO2006006948A2 (en) 2002-11-14 2006-01-19 Dharmacon, Inc. METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY
US9228186B2 (en) 2002-11-14 2016-01-05 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
US9719092B2 (en) 2002-11-14 2017-08-01 Thermo Fisher Scientific Inc. RNAi targeting CNTD2
US7951935B2 (en) 2002-11-14 2011-05-31 Dharmacon, Inc. siRNA targeting v-myc myelocytomatosis viral oncogene homolog (MYC)
US9771586B2 (en) 2002-11-14 2017-09-26 Thermo Fisher Scientific Inc. RNAi targeting ZNF205
US7612196B2 (en) 2002-11-14 2009-11-03 Dharmacon, Inc. siRNA targeting cyclin-dependent kinase inhibitor 1B (p27, Kip1) (CDKN1B)
US20090280567A1 (en) * 2004-02-06 2009-11-12 Dharmacon, Inc. Stabilized sirnas as transfection controls and silencing reagents
EP2636739B1 (en) 2004-03-12 2014-12-10 Alnylam Pharmaceuticals Inc. iRNA agents targeting VEGF
KR101147147B1 (ko) * 2004-04-01 2012-05-25 머크 샤프 앤드 돔 코포레이션 Ｒｎａ 간섭의 오프 타겟 효과 감소를 위한 변형된폴리뉴클레오타이드
US7605250B2 (en) 2004-05-12 2009-10-20 Dharmacon, Inc. siRNA targeting cAMP-specific phosphodiesterase 4D
EP2292757A3 (en) 2004-08-23 2011-11-16 Sylentis S.A.U. Treatment of eye disorders characterized by an elevated intraocular pressure by siRNAs
US20060223777A1 (en) * 2005-03-29 2006-10-05 Dharmacon, Inc. Highly functional short hairpin RNA
CA2604441A1 (en) * 2005-04-12 2006-10-19 Intradigm Corporation Composition and methods of rnai therapeutics for treatment of cancer and other neovascularization diseases
US7893244B2 (en) * 2005-04-12 2011-02-22 Intradigm Corporation Composition and methods of RNAi therapeutics for treatment of cancer and other neovascularization diseases
US8669236B2 (en) * 2005-05-12 2014-03-11 The General Hospital Corporation Biotinylated compositions
GB0521351D0 (en) * 2005-10-20 2005-11-30 Genomica Sau Modulation of TRPV expression levels
GB0521716D0 (en) * 2005-10-25 2005-11-30 Genomica Sau Modulation of 11beta-hydroxysteriod dehydrogenase 1 expression for the treatment of ocular diseases
JP5111385B2 (ja) * 2005-10-28 2013-01-09 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 ハンチンチン遺伝子の発現を抑制するための組成物および方法
CN101448849B (zh) * 2006-03-31 2013-08-21 阿尔尼拉姆医药品有限公司 抑制Eg5基因表达的组合物和方法
US20090130212A1 (en) * 2006-05-15 2009-05-21 Physical Pharmaceutica, Llc Composition and improved method for preparation of small particles
US8598333B2 (en) * 2006-05-26 2013-12-03 Alnylam Pharmaceuticals, Inc. SiRNA silencing of genes expressed in cancer
ES2390499T3 (es) * 2006-06-12 2012-11-13 Opko Pharmaceuticals, Llc Composiciones y métodos para la inhibición de la angiogénesis por sirna
US7872118B2 (en) * 2006-09-08 2011-01-18 Opko Ophthalmics, Llc siRNA and methods of manufacture
AU2007299705B2 (en) * 2006-09-22 2012-09-06 Dharmacon, Inc. Duplex oligonucleotide complexes and methods for gene silencing by RNA interference
EP2121924A1 (en) * 2007-03-02 2009-11-25 MDRNA, Inc. Nucleic acid compounds for inhibiting vegf family gene expression and uses thereof
US20100112687A1 (en) * 2007-03-02 2010-05-06 Mdrna, Inc. Nucleic acid compounds for inhibiting erbb family gene expression and uses thereof
US20110046206A1 (en) * 2007-06-22 2011-02-24 Isis Pharmaceuticals, Inc. Double strand compositions comprising differentially modified strands for use in gene modulation
CN101795714B (zh) * 2007-09-07 2014-05-14 国立大学法人德岛大学 p53的表达促进方法和该方法中使用的p53表达促进剂
US8188060B2 (en) 2008-02-11 2012-05-29 Dharmacon, Inc. Duplex oligonucleotides with enhanced functionality in gene regulation
BRPI0909779A2 (pt) * 2008-03-05 2019-09-24 Alnylam Pharmaceuticals Inc composições e processos para a inibição da expressão dos genes eg5 e vegf
DE102008014318B4 (de) * 2008-03-14 2021-02-04 Premark Feg L.L.C. Transportspülmaschine und Verfahren zum Betreiben einer Transportspülmaschine
WO2009146417A1 (en) * 2008-05-30 2009-12-03 Sigma-Aldrich Co. Compositions and methods for specifically silencing a target nucleic acid
SG10201510586PA (en) 2008-06-30 2016-01-28 Mesoblast Inc Treatment of Eye Diseases And Excessive Neovascularization Using A Combined Therapy
WO2010042751A2 (en) * 2008-10-08 2010-04-15 Chimeros Inc. Chimeric therapeutics, compositions, and methods for using same
ES2794401T3 (es) * 2008-10-15 2020-11-18 Axolabs Gmbh Método de detección de oligonucleótidos
MX2011005851A (es) * 2008-12-04 2011-07-29 Opko Opthalmics Llc Composiciones y metodos para la inhibicion selectiva de isoformas vegf proangiogenicas.
ES2804764T3 (es) 2009-06-01 2021-02-09 Halo Bio Rnai Therapeutics Inc Polinucleótidos para la interferencia de ARN multivalente, composiciones y métodos de uso de los mismos
WO2011017548A1 (en) * 2009-08-05 2011-02-10 Alnylam Pharmaceuticals, Inc. Lipid formulated compositions and methods for inhibiting expression of eg5 and vegf genes
CN102639115A (zh) 2009-09-15 2012-08-15 阿尔尼拉姆医药品有限公司 脂质配制的组合物及抑制eg5和vegf基因的表达的方法
US20110104154A1 (en) * 2009-10-30 2011-05-05 Alcon Research, Ltd. Single nucleotide polymorphisms and genes associated with age-related macular degeneration
WO2011073521A1 (en) 2009-12-15 2011-06-23 Petri Salven Methods for enriching adult-derived endothelial progenitor cells and uses thereof
EP3578183B1 (en) 2010-03-24 2021-09-08 Phio Pharmaceuticals Corp. Rna interference in ocular indications
RU2615143C2 (ru) 2010-03-24 2017-04-04 Адвирна Самодоставляющие PHKi соединения уменьшенного размера
ES2979168T3 (es) 2010-07-23 2024-09-24 Univ Boston Inhibidores anti-DEspR como productos terapéuticos para inhibición de angiogénesis patológica e invasividad de células tumorales y para imagenología molecular y administración dirigida
JP2013541334A (ja) * 2010-09-15 2013-11-14 アルニラム ファーマスーティカルズ インコーポレイテッド 修飾されたｉＲＮＡ剤
EP2622075B1 (en) * 2010-09-27 2016-03-02 Sabanci Universitesi Use of mirnas for the diagnosis, prophylaxis, treatment and follow-up of diseases involving macroautophagy abnormalities
EP2631291B1 (en) 2010-10-22 2019-05-15 OliX Pharmaceuticals, Inc. Nucleic acid molecules inducing rna interference, and uses thereof
WO2012064824A1 (en) 2010-11-09 2012-05-18 Alnylam Pharmaceuticals, Inc. Lipid formulated compositions and methods for inhibiting expression of eg5 and vegf genes
SMT202400520T1 (it) 2011-04-22 2025-01-14 Univ California Virioni di virus adeno-associato con capside variante e relativi metodi di utilizzo
US9255927B2 (en) 2011-05-05 2016-02-09 Duke University Methods of developing a prognosis for pancreatic cancer and predicting responsiveness to cancer therapeutics
EP3358013B1 (en) 2012-05-02 2020-06-24 Sirna Therapeutics, Inc. Short interfering nucleic acid (sina) compositions
KR101567576B1 (ko) * 2012-05-22 2015-11-10 올릭스 주식회사 세포 내 관통능을 가지고 ｒｎａ 간섭을 유도하는 핵산 분자 및 그 용도
US9655977B2 (en) 2012-08-31 2017-05-23 The General Hospital Corporation Biotin complexes for treatment and diagnosis of alzheimer's disease
IN2015DN02699A (enExample) 2012-09-05 2015-09-04 Sylentis Sau
GB201215857D0 (en) 2012-09-05 2012-10-24 Sylentis Sau siRNA and their use in methods and compositions for the treatment and/or prevention of eye conditions
HK1218656A1 (zh) * 2013-01-08 2017-03-03 贝尼泰克生物制药有限公司 年龄相关性黄斑变性治疗
EP2994167B1 (en) 2013-05-06 2020-05-06 Alnylam Pharmaceuticals, Inc. Dosages and methods for delivering lipid formulated nucleic acid molecules
EP2865756A1 (en) * 2013-10-22 2015-04-29 Sylentis, S.A.U. siRNA and their use in methods and compositions for inhibiting the expression of the FLAP gene.
EA201691587A1 (ru) 2014-02-11 2017-01-30 Элнилэм Фармасьютикалз, Инк. КОМПОЗИЦИИ НА ОСНОВЕ iRNA ДЛЯ КЕТОГЕКСОКИНАЗЫ (KHK) И СПОСОБЫ ИХ ПРИМЕНЕНИЯ
GB201403684D0 (en) 2014-03-03 2014-04-16 King S College London Vector
WO2015132303A1 (en) 2014-03-04 2015-09-11 Sylentis Sau Sirnas and their use in methods and compositions for the treatment and/or prevention of eye conditions
CN104038000B (zh) * 2014-07-03 2016-08-24 雷勃电气（无锡）有限公司 可拆装铜笼转子铁心叠压热套工艺
WO2016037162A1 (en) 2014-09-07 2016-03-10 Selecta Biosciences, Inc. Methods and compositions for attenuating anti-viral transfer vector immune responses
DK3277814T3 (da) 2015-04-03 2020-08-24 Univ Massachusetts Oligonukleotidforbindelser til målretning mod huntingtin-mrna
JP6892433B2 (ja) 2015-04-03 2021-06-23 ユニバーシティ・オブ・マサチューセッツＵｎｉｖｅｒｓｉｔｙ Ｏｆ Ｍａｓｓａｃｈｕｓｅｔｔｓ 十分に安定化された非対称ｓｉｒｎａ
DK3277815T3 (da) 2015-04-03 2021-12-13 Univ Massachusetts Oligonukleotidforbindelser til behandling af præeklampsi og andre angiogene lidelser
EP3315608B1 (en) * 2015-06-26 2020-09-16 Suzhou Ribo Life Science Co., Ltd. Sirna, pharmaceutical composition and conjugate which contain sirna, and uses thereof
US10633653B2 (en) 2015-08-14 2020-04-28 University Of Massachusetts Bioactive conjugates for oligonucleotide delivery
CA2995995A1 (en) 2015-08-24 2017-03-02 Halo-Bio Rnai Therapeutics, Inc. Polynucleotide nanoparticles for the modulation of gene expression and uses thereof
WO2017085550A1 (en) 2015-11-16 2017-05-26 Olix Pharmaceuticals, Inc. Treatment of age-related macular degeneration using rna complexes that target myd88 or tlr3
AU2016371624B2 (en) * 2015-12-13 2020-08-27 Nitto Denko Corporation siRNA structures for high activity and reduced off target
JP7749201B6 (ja) 2016-01-31 2025-10-21 ユニバーシティー オブ マサチューセッツ 分岐オリゴヌクレオチド
US10358648B2 (en) 2016-02-02 2019-07-23 Olix Pharmaceuticals, Inc. Treatment of atopic dermatitis and asthma using RNA complexes that target IL4Rα, TRPA1, or F2RL1
CN108779464B (zh) 2016-02-02 2022-05-17 奥利克斯医药有限公司 使用靶向angpt2和pdgfb的rna复合物治疗血管生成相关性疾病
KR102339886B1 (ko) 2016-04-11 2021-12-17 올릭스 주식회사 연결 조직 성장 인자를 표적화하는 rna 복합체를 사용한 특발성 폐 섬유증의 치료 방법
CA3022600A1 (en) 2016-04-29 2017-11-02 Adverum Biotechnologies, Inc. Evasion of neutralizing antibodies by a recombinant adeno-associated virus
WO2017201166A1 (en) 2016-05-17 2017-11-23 Duke University Methods of predicting responsiveness of a cancer to a vegf targeting agent and methods of prognosing and treating cancer
KR101916652B1 (ko) 2016-06-29 2018-11-08 올릭스 주식회사 작은 간섭 rna의 rna 간섭효과 증진용 화합물 및 이의 용도
JP6875500B2 (ja) * 2016-07-28 2021-05-26 インスティテュート フォー ベーシック サイエンスＩｎｓｔｉｔｕｔｅ Ｆｏｒ Ｂａｓｉｃ Ｓｃｉｅｎｃｅ Ｃａｓ９タンパク質およびガイドＲＮＡを含む眼疾患治療用薬学組成物
KR20230039779A (ko) 2016-07-29 2023-03-21 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 변이체 캡시드를 갖는 아데노-관련된 바이러스 비리온 및 이의 사용 방법
WO2018031933A2 (en) 2016-08-12 2018-02-15 University Of Massachusetts Conjugated oligonucleotides
JP7050215B2 (ja) * 2016-08-19 2022-04-08 ツールゲン インコーポレイテッド 人工的に操作された血管新生調節系
CA3040179A1 (en) 2016-10-19 2018-04-26 Adverum Biotechnologies, Inc. Modified aav capsids and uses thereof
CN110121558B (zh) * 2016-11-28 2023-06-13 日商那帕洁制药股份有限公司 化学修饰siRNA
WO2018146557A2 (en) 2017-02-10 2018-08-16 Dong Ki Lee Long double-stranded rna for rna interference
US10844377B2 (en) 2017-06-23 2020-11-24 University Of Massachusetts Two-tailed self-delivering siRNA
BR112019019015A2 (pt) 2017-06-30 2020-04-14 Univ California vírions de vírus adeno-associado com capsídeos variantes e seus métodos de uso
WO2019022250A1 (ja) * 2017-07-28 2019-01-31 国立大学法人九州大学 水溶性有効成分の放出が制御された経皮吸収組成物
MX2020003838A (es) 2017-10-13 2020-08-06 Selecta Biosciences Inc Metodos y composiciones para atenuar las respuestas de inmunoglobulina m del vector de transferencia antiviral.
KR20210093227A (ko) 2018-08-10 2021-07-27 유니버시티 오브 매사추세츠 Snp를 표적화하는 변형된 올리고뉴클레오티드
WO2020041769A1 (en) 2018-08-23 2020-02-27 University Of Massachusetts O-methyl rich fully stabilized oligonucleotides
WO2020150636A1 (en) 2019-01-18 2020-07-23 University Of Massachusetts Dynamic pharmacokinetic-modifying anchors
CN114206396A (zh) 2019-05-28 2022-03-18 西莱克塔生物科技公司 用于减弱抗病毒转移载体免疫应答的方法和组合物
CN114096280A (zh) * 2019-07-12 2022-02-25 俄勒冈健康与科学大学 用于共同递送有丝分裂激酶抑制剂和免疫检查点抑制剂的治疗构建体
MX2022001710A (es) 2019-08-09 2022-05-10 Univ Massachusetts Oligonucleótidos modificados químicamente dirigidos a los snp.
US12365894B2 (en) 2019-09-16 2025-07-22 University Of Massachusetts Branched lipid conjugates of siRNA for specific tissue delivery
CN115515968A (zh) * 2019-12-11 2022-12-23 阿维利诺美国实验室股份有限公司 使用短干扰RNA对具有R124H突变的转化生长因子β诱导基因的等位基因特异性沉默
KR102324428B1 (ko) * 2020-04-16 2021-11-09 건국대학교 산학협력단 혈관내피 성장인자 발현을 억제하는 shRNA 및 이의 용도
WO2021214282A1 (en) 2020-04-24 2021-10-28 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for preventing induction of immune responses to the transduced cells expressing a transgene product after ocular gene therapy
IL309334A (en) 2021-06-23 2024-02-01 Univ Massachusetts Anti-FLT1 optimized oligonucleotide compounds for the treatment of preeclampsia and other angiogenic disorders
US20230141563A1 (en) 2021-10-12 2023-05-11 Selecta Biosciences, Inc. Methods and compositions for attenuating anti-viral transfer vector igm responses
US20230357437A1 (en) 2022-03-09 2023-11-09 Selecta Biosciences, Inc. Immunosuppressants in combination with anti-igm agents and related dosing
EP4622992A1 (en) 2022-11-24 2025-10-01 Amyndas Pharmaceuticals US LLC Compstatin analogs for vector-based therapy

Family Cites Families (132)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
KR840001915A (ko) * 1981-10-13 1984-06-07 그레이험 워커 존 자동 조절 돛 세트
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
IL79289A (en) * 1985-07-05 1992-01-15 Whitehead Biomedical Inst Introduction and expression of foreign genetic material into keratinocytes using a recombinant retrovirus
US5139941A (en) * 1985-10-31 1992-08-18 University Of Florida Research Foundation, Inc. AAV transduction vectors
US4837028A (en) * 1986-12-24 1989-06-06 Liposome Technology, Inc. Liposomes with enhanced circulation time
US4888116A (en) * 1987-01-15 1989-12-19 The Dow Chemical Company Method of improving membrane properties via reaction of diazonium compounds or precursors
EP0378576B1 (en) 1987-09-11 1995-01-18 Whitehead Institute For Biomedical Research Transduced fibroblasts and uses therefor
JP2914692B2 (ja) 1987-12-11 1999-07-05 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 内皮細胞の遺伝子修飾
EP0400047B1 (en) 1988-02-05 1997-04-23 Whitehead Institute For Biomedical Research Modified hepatocytes and uses therefor
GB8824593D0 (en) 1988-10-20 1988-11-23 Royal Free Hosp School Med Liposomes
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
AU637800B2 (en) 1989-08-31 1993-06-10 City Of Hope Chimeric dna-rna catalytic sequences
US5225212A (en) * 1989-10-20 1993-07-06 Liposome Technology, Inc. Microreservoir liposome composition and method
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
US5665710A (en) * 1990-04-30 1997-09-09 Georgetown University Method of making liposomal oligodeoxynucleotide compositions
US5962219A (en) 1990-06-11 1999-10-05 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: chemi-selex
PL169576B1 (pl) 1990-10-12 1996-08-30 Max Planck Gesellschaft Sposób wytwarzania czasteczki RNA o aktywnosci katalitycznej PL PL
DE69128893T2 (de) 1990-10-31 1998-09-10 Brigham & Womens Hospital Genetische veränderung von endothelzellen
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
DE4216134A1 (de) * 1991-06-20 1992-12-24 Europ Lab Molekularbiolog Synthetische katalytische oligonukleotidstrukturen
US5252479A (en) * 1991-11-08 1993-10-12 Research Corporation Technologies, Inc. Safe vector for gene therapy
US5652094A (en) 1992-01-31 1997-07-29 University Of Montreal Nucleozymes
EP0642589A4 (en) 1992-05-11 1997-05-21 Ribozyme Pharm Inc METHOD AND REAGENT TO INHIBIT VIRAL REPLICATION.
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
CA2140343A1 (en) 1992-07-17 1994-02-03 Sean M. Sullivan Method and reagent for treatment of animal diseases
US5478745A (en) 1992-12-04 1995-12-26 University Of Pittsburgh Recombinant viral vector system
US5672659A (en) 1993-01-06 1997-09-30 Kinerton Limited Ionic molecular conjugates of biodegradable polyesters and bioactive polypeptides
CA2154363A1 (en) 1993-01-22 1994-08-04 Bruce A. Sullenger Localization of therapeutic agents
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
DE69424406T2 (de) * 1993-02-19 2000-10-26 Nippon Shinyaku Co., Ltd. Arzneistoffzusammensetzung, die ein nukleinsäurecopolymer enthält
US5395619A (en) 1993-03-03 1995-03-07 Liposome Technology, Inc. Lipid-polymer conjugates and liposomes
US5731294A (en) * 1993-07-27 1998-03-24 Hybridon, Inc. Inhibition of neovasularization using VEGF-specific oligonucleotides
CA2137297C (en) * 1993-12-06 2000-04-18 Tsuyoshi Miyazaki Reactive vesicle and functional substance-fixed vesicle
US5902880A (en) * 1994-08-19 1999-05-11 Ribozyme Pharmaceuticals, Inc. RNA polymerase III-based expression of therapeutic RNAs
US5627053A (en) 1994-03-29 1997-05-06 Ribozyme Pharmaceuticals, Inc. 2'deoxy-2'-alkylnucleotide containing nucleic acid
US6054299A (en) * 1994-04-29 2000-04-25 Conrad; Charles A. Stem-loop cloning vector and method
WO2000022114A1 (en) 1998-10-09 2000-04-20 Ingene, Inc. PRODUCTION OF ssDNA $i(IN VIVO)
US5543152A (en) * 1994-06-20 1996-08-06 Inex Pharmaceuticals Corporation Sphingosomes for enhanced drug delivery
US6150092A (en) * 1994-06-27 2000-11-21 Taogosei Company, Ltd. Antisense nucleic acid compound targeted to VEGF
US6146886A (en) 1994-08-19 2000-11-14 Ribozyme Pharmaceuticals, Inc. RNA polymerase III-based expression of therapeutic RNAs
US5595760A (en) * 1994-09-02 1997-01-21 Delab Sustained release of peptides from pharmaceutical compositions
US5820873A (en) 1994-09-30 1998-10-13 The University Of British Columbia Polyethylene glycol modified ceramide lipids and liposome uses thereof
US5885613A (en) 1994-09-30 1999-03-23 The University Of British Columbia Bilayer stabilizing components and their use in forming programmable fusogenic liposomes
US5753613A (en) 1994-09-30 1998-05-19 Inex Pharmaceuticals Corporation Compositions for the introduction of polyanionic materials into cells
US5716824A (en) * 1995-04-20 1998-02-10 Ribozyme Pharmaceuticals, Inc. 2'-O-alkylthioalkyl and 2-C-alkylthioalkyl-containing enzymatic nucleic acids (ribozymes)
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
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
US6096720A (en) 1995-08-01 2000-08-01 Novartis Ag Liposomal oligonucleotide compositions
US5858397A (en) 1995-10-11 1999-01-12 University Of British Columbia Liposomal formulations of mitoxantrone
AU1430097A (en) 1996-01-16 1997-08-11 Ribozyme Pharmaceuticals, Inc. Synthesis of methoxy nucleosides and enzymatic nucleic acid molecules
US5994316A (en) 1996-02-21 1999-11-30 The Immune Response Corporation Method of preparing polynucleotide-carrier complexes for delivery to cells
US5849902A (en) 1996-09-26 1998-12-15 Oligos Etc. Inc. Three component chimeric antisense oligonucleotides
US6001311A (en) 1997-02-05 1999-12-14 Protogene Laboratories, Inc. Apparatus for diverse chemical synthesis using two-dimensional array
US6127533A (en) * 1997-02-14 2000-10-03 Isis Pharmaceuticals, Inc. 2'-O-aminooxy-modified oligonucleotides
US6395713B1 (en) 1997-07-23 2002-05-28 Ribozyme Pharmaceuticals, Inc. Compositions for the delivery of negatively charged molecules
US6506559B1 (en) 1997-12-23 2003-01-14 Carnegie Institute Of Washington Genetic inhibition by double-stranded RNA
DK1068311T3 (da) 1998-04-08 2011-08-08 Commw Scient Ind Res Org Fremgangsmåder og midler til opnåelse af modificerede fænotyper
EP1071753A2 (en) 1998-04-20 2001-01-31 Ribozyme Pharmaceuticals, Inc. Nucleic acid molecules with novel chemical compositions capable of modulating gene expression
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
EP1096921B1 (en) 1998-07-20 2003-04-16 Protiva Biotherapeutics Inc. Liposomal encapsulated nucleic acid-complexes
KR20010099682A (ko) 1998-10-09 2001-11-09 추후보충 단일가닥 ｄｎａ의 효소 합성
DE19956568A1 (de) 1999-01-30 2000-08-17 Roland Kreutzer Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens
ATE408699T1 (de) 1999-03-10 2008-10-15 Phogen Ltd Verabreichung von nukleinsäuren und proteinen an zellen
US20050112141A1 (en) * 2000-08-30 2005-05-26 Terman David S. Compositions and methods for treatment of neoplastic disease
DE10100586C1 (de) 2001-01-09 2002-04-11 Ribopharma Ag Verfahren zur Hemmung der Expression eines Ziegens
WO2001053345A1 (en) * 2000-01-20 2001-07-26 North Bristol Nhs Trust Vegf148 isoform, a truncated splice variant of vegf. vegf heterodimers and therapeutical uses thereof
AU2001247951A1 (en) 2000-02-07 2001-08-14 Roche Diagnostics Corporation Novel cationic amphiphiles
WO2003070918A2 (en) 2002-02-20 2003-08-28 Ribozyme Pharmaceuticals, Incorporated Rna interference by modified short interfering nucleic acid
WO2002081628A2 (en) 2001-04-05 2002-10-17 Ribozyme Pharmaceuticals, Incorporated Modulation of gene expression associated with inflammation proliferation and neurite outgrowth, using nucleic acid based technologies
SE0003665D0 (sv) 2000-10-11 2000-10-11 Astrazeneca Ab A delivery device
CA2426384A1 (en) * 2000-10-19 2003-04-17 Kyowa Hakko Kogyo Co., Ltd. Antibody inhibiting vplf activity
CZ302719B6 (cs) 2000-12-01 2011-09-21 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Izolovaná molekula dvouretezcové RNA, zpusob její výroby a její použití
US20040209832A1 (en) * 2001-11-30 2004-10-21 Mcswiggen James RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA)
WO2003070917A2 (en) 2002-02-20 2003-08-28 Sirna Therapeutics, Inc. Rna interference mediated inhibition of myc and myb genes or genes of their respective pathways
WO2003070910A2 (en) * 2002-02-20 2003-08-28 Ribozyme Pharmaceuticals, Incorporated INHIBITION OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) AND VEGF RECEPTOR GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
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)
US7981863B2 (en) * 2001-09-19 2011-07-19 Neuronova Ab Treatment of Parkinson's disease with PDGF
FR2832154B1 (fr) * 2001-11-09 2007-03-16 Centre Nat Rech Scient Oligonucleotides inhibiteurs et leur utilisation pour reprimer specifiquement un gene
EP1432724A4 (en) * 2002-02-20 2006-02-01 Sirna Therapeutics Inc INTERFERENCE MEDIATION INHIBITION OF GENE RNA FROM MAP KINASE
US7199107B2 (en) * 2002-05-23 2007-04-03 Isis Pharmaceuticals, Inc. Antisense modulation of kinesin-like 1 expression
NO315435B1 (no) 2002-06-21 2003-09-01 Hydralift Asa Kompenseringsanordning
JP4222792B2 (ja) 2002-06-26 2009-02-12 シャープ株式会社 測距センサおよびそれを用いた電子機器ならびに測距センサの製造方法
CN1156336C (zh) 2002-07-12 2004-07-07 清华大学 柔性基底材料表面负载二氧化钛薄膜光催化剂的制备方法
US6679120B1 (en) 2002-07-15 2004-01-20 Gas Research Institute System and method for guided boring obstacle detection
US7148342B2 (en) * 2002-07-24 2006-12-12 The Trustees Of The University Of Pennyslvania Compositions and methods for sirna inhibition of angiogenesis
BR0313079A (pt) 2002-07-29 2005-08-16 Gates Corp Correia
US7036793B2 (en) 2002-07-31 2006-05-02 Brass-Craft Manufacturing Company Stop valve
EP1546173A4 (en) * 2002-08-06 2006-05-31 Intradigm Corp METHOD FOR DOWNSTREGULATING THE EXPRESSION OF TARGET GENES IN VIVO BY INCLUDING INTERFERING 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)
US20040115201A1 (en) * 2002-09-25 2004-06-17 Paz Einat Mitotic kinesin-like protein-1, MKLP1, and uses thereof
EP1560931B1 (en) * 2002-11-14 2011-07-27 Dharmacon, Inc. Functional and hyperfunctional sirna
WO2004064737A2 (en) 2003-01-17 2004-08-05 Alnylam Pharmaceuticals Therapeutics compositions
DE10302421A1 (de) 2003-01-21 2004-07-29 Ribopharma Ag Doppelsträngige Ribonukleinsäure mit verbesserter Wirksamkeit
AR050920A1 (es) * 2003-03-07 2006-12-06 Astrazeneca Ab Enantiomeros de heterociclos fusionados seleccionados y usos de los mismos
EP2216407B1 (en) 2003-03-07 2016-01-13 Alnylam Pharmaceuticals, Inc. Therapeutic compositions
CA2488224A1 (en) 2003-04-03 2004-10-21 Alnylam Pharmaceuticals, Inc. Irna conjugates
EP1625138A4 (en) 2003-04-17 2010-06-23 Alnylam Pharmaceuticals Inc PROTECTED MONOMERS
AU2004233092C9 (en) 2003-04-17 2010-10-28 Alnylam Pharmaceuticals, Inc. Modified iRNA agents
EP2497485A1 (en) * 2003-05-09 2012-09-12 Transfert Plus Compound and method for regulating plasminogen activation and cell migration
ES2761262T3 (es) 2003-06-13 2020-05-19 Alnylam Europe Ag Acido ribonucleico bicatenario con elevada eficacia en un organismo
ES2559828T3 (es) 2003-07-16 2016-02-16 Protiva Biotherapeutics Inc. ARN de interferencia encapsulado en lípidos
CA2539651A1 (en) 2003-09-22 2005-04-07 Rosetta Inpharmatics Llc Synthetic lethal screen using rna interference
EP2636739B1 (en) 2004-03-12 2014-12-10 Alnylam Pharmaceuticals Inc. iRNA agents targeting VEGF
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
WO2007086883A2 (en) 2005-02-14 2007-08-02 Sirna Therapeutics, Inc. Cationic lipids and formulated molecular compositions containing them
ATE541928T1 (de) * 2005-03-31 2012-02-15 Calando Pharmaceuticals Inc Inhibitoren der untereinheit 2 der ribonukleotidreduktase und ihre verwendungen
US7915230B2 (en) 2005-05-17 2011-03-29 Molecular Transfer, Inc. Reagents for transfection of eukaryotic cells
US8344132B2 (en) 2005-06-22 2013-01-01 BioCryst Pharmaceticals, Inc. Methods for the preparation of 9-deazapurine derivatives
EP1937213B1 (en) 2005-07-27 2017-10-25 Protiva Biotherapeutics Inc. Systems and methods for manufacturing liposomes
CA2628300C (en) 2005-11-02 2018-04-17 Protiva Biotherapeutics, Inc. Modified sirna molecules and uses thereof
CN101448849B (zh) 2006-03-31 2013-08-21 阿尔尼拉姆医药品有限公司 抑制Eg5基因表达的组合物和方法
US8598333B2 (en) 2006-05-26 2013-12-03 Alnylam Pharmaceuticals, Inc. SiRNA silencing of genes expressed in cancer
MX2009003548A (es) 2006-10-03 2009-04-15 Alnylam Pharmaceuticals Inc Formulaciones que contienen lipidos.
US20080213350A1 (en) 2007-02-20 2008-09-04 Texas Tech University System Encapsulation of nucleic acids in liposomes
US7858592B2 (en) 2007-02-26 2010-12-28 The Board Of Regents Of The University Of Texas System Interfering RNAs against the promoter region of P53
ES2535419T3 (es) 2007-12-27 2015-05-11 Protiva Biotherapeutics Inc. Silenciamiento de expresión de quinasa tipo polo usando ARN interferente
JP2011511004A (ja) 2008-01-31 2011-04-07 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 ＰＣＳＫ９遺伝子を標的とするｄｓＲＮＡを送達するための最適化された方法
BRPI0909779A2 (pt) 2008-03-05 2019-09-24 Alnylam Pharmaceuticals Inc composições e processos para a inibição da expressão dos genes eg5 e vegf
ES2638448T3 (es) 2008-04-15 2017-10-20 Protiva Biotherapeutics Inc. Novedosas formulaciones de lípidos para la administración de ácidos nucleicos
EA037404B1 (ru) 2008-11-10 2021-03-24 Арбутус Биофарма Корпорэйшн Липиды и композиции для доставки лекарственных средств
EP2391343B1 (en) 2009-01-29 2017-03-01 Arbutus Biopharma Corporation Improved lipid formulation for the delivery of nucleic acids
NZ594995A (en) 2009-03-12 2013-06-28 Alnylam Pharmaceuticals Inc LIPID FORMULATED COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF HUMAN KINESIN FAMILY MEMBER 11 (Eg5) AND VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) GENES
CA3042927C (en) 2009-05-05 2022-05-17 Arbutus Biopharma Corporation Lipid compositions for the delivery of therapeutic agents
HRP20211619T1 (hr) 2009-06-10 2022-02-04 Arbutus Biopharma Corporation Poboljšana formulacija lipida
WO2011017548A1 (en) 2009-08-05 2011-02-10 Alnylam Pharmaceuticals, Inc. Lipid formulated compositions and methods for inhibiting expression of eg5 and vegf genes
CN102639115A (zh) 2009-09-15 2012-08-15 阿尔尼拉姆医药品有限公司 脂质配制的组合物及抑制eg5和vegf基因的表达的方法

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