ATE541928T1 - Inhibitoren der untereinheit 2 der ribonukleotidreduktase und ihre verwendungen - Google Patents

Inhibitoren der untereinheit 2 der ribonukleotidreduktase und ihre verwendungen

Info

Publication number
ATE541928T1
ATE541928T1 AT06758231T AT06758231T ATE541928T1 AT E541928 T1 ATE541928 T1 AT E541928T1 AT 06758231 T AT06758231 T AT 06758231T AT 06758231 T AT06758231 T AT 06758231T AT E541928 T1 ATE541928 T1 AT E541928T1
Authority
AT
Austria
Prior art keywords
inhibitors
ribonucleotide reductase
subunity
certain embodiments
present application
Prior art date
Application number
AT06758231T
Other languages
English (en)
Inventor
Mark Davis
Jeremy Heidel
John Roosi
Original Assignee
Calando 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 Calando Pharmaceuticals Inc filed Critical Calando Pharmaceuticals Inc
Application granted granted Critical
Publication of ATE541928T1 publication Critical patent/ATE541928T1/de

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1137Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against enzymes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51Nanocapsules; Nanoparticles
    • A61K9/5107Excipients; Inactive ingredients
    • A61K9/5123Organic compounds, e.g. fats, sugars
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10Antimycotics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/11Antisense
    • C12N2310/111Antisense spanning the whole gene, or a large part of it
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/14Type of nucleic acid interfering N.A.
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/50Physical structure
    • C12N2310/53Physical structure partially self-complementary or closed
AT06758231T 2005-03-31 2006-03-31 Inhibitoren der untereinheit 2 der ribonukleotidreduktase und ihre verwendungen ATE541928T1 (de)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US66736205P 2005-03-31 2005-03-31
US69593105P 2005-06-30 2005-06-30
US74210005P 2005-12-02 2005-12-02
PCT/US2006/011812 WO2006105361A2 (en) 2005-03-31 2006-03-31 Inhibitors of ribonucleotide reductase subunit 2 and uses thereof

Publications (1)

Publication Number Publication Date
ATE541928T1 true ATE541928T1 (de) 2012-02-15

Family

ID=37054157

Family Applications (1)

Application Number Title Priority Date Filing Date
AT06758231T ATE541928T1 (de) 2005-03-31 2006-03-31 Inhibitoren der untereinheit 2 der ribonukleotidreduktase und ihre verwendungen

Country Status (13)

Country Link
US (2) US7427605B2 (de)
EP (2) EP1866414B9 (de)
JP (3) JP2008537551A (de)
AT (1) ATE541928T1 (de)
AU (1) AU2006230436B2 (de)
CA (1) CA2603730A1 (de)
DK (1) DK1866414T3 (de)
ES (1) ES2381201T3 (de)
HK (1) HK1112486A1 (de)
IL (1) IL186129A0 (de)
PL (1) PL1866414T3 (de)
TW (1) TWI335352B (de)
WO (1) WO2006105361A2 (de)

Families Citing this family (251)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8546143B2 (en) 2001-01-09 2013-10-01 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of a target gene
EP2277551B1 (de) 2002-09-06 2013-05-08 Cerulean Pharma Inc. Polymere auf basis von cyclodextrin zur verabreichung von an diese kovalent gebundene arzneimittel
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
US9228186B2 (en) 2002-11-14 2016-01-05 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
US9839649B2 (en) 2002-11-14 2017-12-12 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
EP2365077B1 (de) * 2004-03-12 2013-05-08 Alnylam Pharmaceuticals, Inc. iRNA-Agenten zum VEGF-Targeting
CA2577036A1 (en) * 2004-08-18 2006-02-23 Genesense Technologies Inc. Small interfering rna molecules against ribonucleotide reductase and uses thereof
WO2006036916A2 (en) * 2004-09-24 2006-04-06 Alnylam Pharmaceuticals, Inc. Rnai modulation of apob and uses thereof
US7790878B2 (en) * 2004-10-22 2010-09-07 Alnylam Pharmaceuticals, Inc. RNAi modulation of RSV, PIV and other respiratory viruses and uses thereof
EA201201356A1 (ru) 2005-01-07 2013-07-30 Элнилэм Фармасьютикалз, Инк. Композиция для лечения респираторных синцитиальных вирусов
US20060217324A1 (en) * 2005-01-24 2006-09-28 Juergen Soutschek RNAi modulation of the Nogo-L or Nogo-R gene and uses thereof
US7427605B2 (en) * 2005-03-31 2008-09-23 Calando Pharmaceuticals, Inc. Inhibitors of ribonucleotide reductase subunit 2 and uses thereof
AU2006261732B2 (en) * 2005-06-27 2011-09-15 Alnylam Pharmaceuticals, Inc. RNAi modulation of HIF-1 and theraputic uses thereof
US20070082845A1 (en) * 2005-07-15 2007-04-12 The Penn State Research Foundation Ferritin as a therapeutic target in abnormal cells
JP2009502138A (ja) * 2005-07-21 2009-01-29 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 RhoA遺伝子のRNAi調節及びその使用法
EP1941059A4 (de) 2005-10-28 2010-11-03 Alnylam Pharmaceuticals Inc Zusammensetzungen und verfahren zur hemmung der expression des huntingtin-gens
EP1945270B1 (de) 2005-11-09 2011-05-25 Alnylam Pharmaceuticals Inc. Zusammensetzungen und verfahren zur hemmung der expression von faktor v leiden mutationsgen
US8229398B2 (en) * 2006-01-30 2012-07-24 Qualcomm Incorporated GSM authentication in a CDMA network
WO2008029276A2 (en) * 2006-02-02 2008-03-13 Allergan, Inc. Compositions and methods for the treatment of ophthalmic disease
EP1999260A2 (de) * 2006-03-24 2008-12-10 Novartis AG Dsrna-zusammensetzungen und verfahren zur behandlung von hpv-infektionen
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
WO2007127919A2 (en) 2006-04-28 2007-11-08 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of a gene from the jc virus
NZ572666A (en) 2006-05-11 2010-11-26 Alnylam Pharmaceuticals Inc Compositions comprising double stranded rna and methods for inhibiting expression of the pcsk9 gene
WO2007137220A2 (en) * 2006-05-22 2007-11-29 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of ikk-b gene
US8598333B2 (en) * 2006-05-26 2013-12-03 Alnylam Pharmaceuticals, Inc. SiRNA silencing of genes expressed in cancer
EP3342415B1 (de) 2006-08-08 2022-01-26 Rheinische Friedrich-Wilhelms-Universität Bonn Struktur und verwendung von 5´-phosphat-oligonukleotiden
WO2008026946A2 (en) * 2006-08-30 2008-03-06 Genesis Research And Development Corporation Limited Compositions and methods for the treatment and prevention of neoplastic disorders
US20090209478A1 (en) 2006-09-21 2009-08-20 Tomoko Nakayama Compositions and methods for inhibiting expression of the hamp gene
EP2087115B1 (de) * 2006-09-27 2012-11-21 Novarx Blockierung von genexpressionen in eukaryotischen zellen
EP2125031B1 (de) 2006-12-19 2017-11-01 Marina Biotech, Inc. Lipide und lipidanordnungen mit transfektionsverstärkungselementen
WO2008086556A1 (en) 2007-01-16 2008-07-24 The University Of Queensland Method of inducing an immune response
JP2010516625A (ja) 2007-01-24 2010-05-20 インサート セラピューティクス, インコーポレイテッド 制御された薬物送達のためのテザー基を有するポリマー−薬物コンジュゲート
PE20090064A1 (es) * 2007-03-26 2009-03-02 Novartis Ag Acido ribonucleico de doble cadena para inhibir la expresion del gen e6ap humano y composicion farmaceutica que lo comprende
AP2014007971A0 (en) 2007-03-29 2014-09-30 Alnylam Pharmaceuticals Inc Compositions and methods for inhibiting expressionof a gene from the ebola
WO2008144365A2 (en) * 2007-05-17 2008-11-27 Novartis Ag Method for making dry powder compositions containing ds-rna based on supercritical fluid technology
US7871985B2 (en) 2007-12-10 2011-01-18 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of factor VII gene
US20100204305A1 (en) * 2007-12-11 2010-08-12 Lorus Therapeutics Inc. Small interfering rna molecules against ribonucleotide reductase and uses thereof
WO2009076679A2 (en) 2007-12-13 2009-06-18 Alnylam Pharmaceuticals Inc. Methods and compositions for prevention or treatment of rsv infection
EP2250266A2 (de) 2008-02-12 2010-11-17 Alnylam Pharmaceuticals Inc. Zusammensetzungen und verfahren zur hemmung der cd45-genexpression
JP2009203173A (ja) * 2008-02-26 2009-09-10 Hokkaido Univ siRNA−ポリカチオン複合体を含有するイオントフォレーシス用組成物
CA2716793A1 (en) 2008-03-05 2009-09-11 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of eg5 and vegf genes
CA2718869C (en) 2008-03-19 2018-10-30 China Synthetic Rubber Corporation Methods and agents for the diagnosis and treatment of hepatocellular carcinoma
AU2009232355A1 (en) 2008-04-04 2009-10-08 Calando Pharmaceuticals, Inc. Compositions and use of EPAS1 inhibitors
WO2009129465A2 (en) 2008-04-17 2009-10-22 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of xbp-1 gene
EP2279011B1 (de) 2008-04-30 2017-10-25 Siemens Medical Solutions USA, Inc. Auf substrat basierende pet-kontrastmittel
JP5689413B2 (ja) 2008-05-21 2015-03-25 ライニッシュ フリードリッヒ−ウィルヘルムズ−ユニバーシタット ボン 平滑末端を有する5’三リン酸オリゴヌクレオチドおよびその使用
US20110184046A1 (en) 2008-07-11 2011-07-28 Dinah Wen-Yee Sah Compositions And Methods For Inhibiting Expression Of GSK-3 Genes
US8309791B2 (en) * 2008-07-16 2012-11-13 Recombinectics, Inc. Method for producing a transgenic pig using a hyper-methylated transposon
US20100056475A1 (en) * 2008-08-06 2010-03-04 Alexander Chucholowski Cyclodextrin conjugates
US8557292B2 (en) 2008-08-13 2013-10-15 California Institute Of Technology Carrier nanoparticles and related compositions, methods and systems
US20100068737A1 (en) * 2008-09-16 2010-03-18 University Of Tennessee Research Foundation Enzyme-linked Immunosorbent Assay (ELISA) for Canine Hepcidin
EP2166076A1 (de) * 2008-09-23 2010-03-24 The Procter & Gamble Company Reinigungszusammensetzung
CA2739170A1 (en) 2008-09-25 2010-04-01 Alnylam Pharmaceuticals, Inc. Lipid formulated compositions and methods for inhibiting expression of serum amyloid a gene
WO2010042547A1 (en) 2008-10-06 2010-04-15 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of an rna from west nile virus
US8168775B2 (en) 2008-10-20 2012-05-01 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of transthyretin
EP2355848A2 (de) * 2008-10-22 2011-08-17 Universität Zürich Prorektorat MNW Lichtblocker ltalpha1beta2 und ltalpha2beta1 oder deren rezeptor ltbetar zur vorbeugung und behandlung chronischer hepatitis und anderer leberkrankheiten
EP2346904B1 (de) 2008-10-29 2017-04-12 China Synthetic Rubber Corporation Methoden und mittel zur diagnose und behandlung von hepatozellulärem karzinom
CA2746514C (en) 2008-12-10 2018-11-27 Alnylam Pharmaceuticals, Inc. Gnaq targeted dsrna compositions and methods for inhibiting expression
CA2753703A1 (en) 2009-03-04 2010-09-10 Hirofumi Takeuchi Nucleic acid complex and nucleic acid-delivering composition
CN104922699B (zh) * 2009-03-12 2020-07-24 阿尔尼拉姆医药品有限公司 脂质配制的组合物以及用于抑制Eg5和VEGF基因表达的方法
JP2012521762A (ja) * 2009-03-27 2012-09-20 メルク・シャープ・エンド・ドーム・コーポレイション 低分子干渉核酸(siNA)を用いた神経成長因子β鎖(NGFβ)遺伝子発現のRNA干渉媒介性阻害
WO2010147992A1 (en) 2009-06-15 2010-12-23 Alnylam Pharmaceuticals, Inc. Methods for increasing efficacy of lipid formulated sirna
EA201270019A1 (ru) * 2009-06-15 2012-06-29 Элнилэм Фармасьютикалз, Инк. Двуцепочечная рнк, включенная в липидный состав и мишенью которой является ген pcsk9
EP2464336A4 (de) 2009-08-14 2013-11-20 Alnylam Pharmaceuticals Inc Zusammensetzungen aus lipidformulierungen und verfahren zur hemmung der expression eines gens aus dem ebolavirus
US8859516B2 (en) 2009-09-15 2014-10-14 Alnylam Pharmaceuticals, Inc. Lipid formulated compositions and methods for inhibiting expression of Eg5 and VEGF genes
WO2011034583A2 (en) 2009-09-16 2011-03-24 Duke University Inhibition of endosomal toll-like receptor activation
US9187746B2 (en) 2009-09-22 2015-11-17 Alnylam Pharmaceuticals, Inc. Dual targeting siRNA agents
WO2011056883A1 (en) 2009-11-03 2011-05-12 Alnylam Pharmaceuticals, Inc. Lipid formulated compositions and methods for inhibiting expression of transthyretin (ttr)
US20110237686A1 (en) 2010-03-26 2011-09-29 Cerulean Pharma Inc Formulations and methods of use
CA2801066C (en) 2010-06-02 2021-02-09 Alnylam Pharmaceuticals, Inc. Compositions and methods directed to treating liver fibrosis
JP2013223426A (ja) * 2010-08-12 2013-10-31 Chugai Pharmaceut Co Ltd Rrm2のアンタゴニストを有効成分として含有するc型肝炎治療剤
WO2012056441A1 (en) * 2010-10-28 2012-05-03 Nanodoc Ltd. Compositions and methods for specific cleavage of exogenous rna in a cell
US9193973B2 (en) 2010-12-10 2015-11-24 Alynylam Pharmaceuticals, Inc. Compositions and methods for increasing erythropoietin (EPO) production
US9127275B2 (en) 2010-12-10 2015-09-08 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of klf-1 and bcl11a genes
US8501930B2 (en) 2010-12-17 2013-08-06 Arrowhead Madison Inc. Peptide-based in vivo siRNA delivery system
EP2508530A1 (de) 2011-03-28 2012-10-10 Rheinische Friedrich-Wilhelms-Universität Bonn Reinigung von triphosphorylierten Oligonucleotiden mit Einfang-Tags
MX360349B (es) 2011-03-29 2018-10-30 Alnylam Pharmaceuticals Inc Composiciones y metodos para inhibir la expresion del gen de proteasa transmembrana, serina 6 (tmprss6).
WO2012174224A2 (en) * 2011-06-17 2012-12-20 Calando Pharmaceuticals, Inc. Methods for administering nucleic acid-based therapeutics
CA2839896A1 (en) 2011-06-21 2012-12-27 Alnylam Pharmaceuticals, Inc. Assays and methods for determining activity of a therapeutic agent in a subject
EP2723861A4 (de) 2011-06-21 2014-12-10 Alnylam Pharmaceuticals Inc Zusammensetzungen und verfahren zur hemmung des hepcidin-antimikrobiellen peptids (hamp) oder der damit zusammenhängenden genexpression
MX360782B (es) 2011-06-21 2018-11-16 Alnylam Pharmaceuticals Inc Composiciones de arni similares a angiopoyetina 3 (angptl3) y metodos para su uso.
US9068184B2 (en) 2011-06-21 2015-06-30 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibition of expression of protein C (PROC) genes
AU2012272860A1 (en) 2011-06-21 2013-12-19 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibition of expression of apolipoprotein C-III (APOC3) genes
EP3597750B1 (de) 2011-06-23 2022-05-04 Alnylam Pharmaceuticals, Inc. Serpina1-sirnas: materialzusammensetzungen und behandlungsverfahren
WO2013003697A1 (en) 2011-06-30 2013-01-03 Trustees Of Boston University Method for controlling tumor growth, angiogenesis and metastasis using immunoglobulin containing and proline rich receptor-1 (igpr-1)
WO2013019857A2 (en) 2011-08-01 2013-02-07 Alnylam Pharmaceuticals, Inc. Method for improving the success rate of hematopoietic stem cell transplants
ES2800065T3 (es) 2011-11-18 2020-12-23 Alnylam Pharmaceuticals Inc Agentes de iARN, composiciones y métodos de uso de los mismos para tratar enfermedades asociadas con transtiretina (TTR)
US9133461B2 (en) 2012-04-10 2015-09-15 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the ALAS1 gene
US9127274B2 (en) 2012-04-26 2015-09-08 Alnylam Pharmaceuticals, Inc. Serpinc1 iRNA compositions and methods of use thereof
EP2712870A1 (de) 2012-09-27 2014-04-02 Rheinische Friedrich-Wilhelms-Universität Bonn Neuartige RIG-I-Liganden und Herstellungsverfahren dafür
WO2014055493A1 (en) 2012-10-02 2014-04-10 Cerulean Pharma Inc. Methods and systems for polymer precipitation and generation of particles
ES2657608T3 (es) 2012-12-05 2018-03-06 Alnylam Pharmaceuticals, Inc. Composiciones de arni de pcsk9 y métodos de uso de las mismas
US20150366890A1 (en) 2013-02-25 2015-12-24 Trustees Of Boston University Compositions and methods for treating fungal infections
US9132097B2 (en) 2013-03-01 2015-09-15 California Institute Of Technology Nanoparticles stabilized with nitrophenylboronic acid compositions
US9468681B2 (en) 2013-03-01 2016-10-18 California Institute Of Technology Targeted nanoparticles
RS56663B1 (sr) 2013-03-14 2018-03-30 Alnylam Pharmaceuticals Inc Irnk sastavi komponente komplementa c5 i metode za njihovu upotrebu
EP3708184A1 (de) 2013-03-27 2020-09-16 The General Hospital Corporation Verfahren und mittel zur behandlung von morbus alzheimer
AU2014268529C1 (en) 2013-05-22 2020-10-01 Alnylam Pharmaceuticals, Inc. TMPRSS6 iRNA compositions and methods of use thereof
SG10201804472YA (en) 2013-05-22 2018-07-30 Alnylam Pharmaceuticals Inc SERPINA1 iRNA COMPOSITIONS AND METHODS OF USE THEREOF
TW202003849A (zh) 2013-10-02 2020-01-16 美商艾爾妮蘭製藥公司 抑制lect2基因表現之組合物及方法
NZ757749A (en) 2013-10-04 2022-07-01 Icahn School Med Mount Sinai Compositions and methods for inhibiting expression of the alas1 gene
US9493552B2 (en) 2013-11-15 2016-11-15 China Synthetic Rubber Corporation Therapeutic biologic for treatment of hepatocellular carcinoma
CA3107872A1 (en) 2013-12-12 2015-06-18 Alnylam Pharmaceuticals, Inc. Complement component irna compositions and methods of use thereof
EP3960860A3 (de) 2014-02-11 2022-06-08 Alnylam Pharmaceuticals, Inc. Ketohexokinase (khk)-irna-zusammensetzungen und verfahren zur verwendung davon
WO2015175510A1 (en) 2014-05-12 2015-11-19 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating a serpinc1-associated disorder
CN112852809A (zh) 2014-05-22 2021-05-28 阿尔尼拉姆医药品有限公司 血管紧张素原(AGT)iRNA组合物及其使用方法
WO2016033326A2 (en) 2014-08-29 2016-03-03 Alnylam Pharmaceuticals, Inc. Methods of treating transthyretin (ttr) mediated amyloidosis
EP3191591A1 (de) 2014-09-12 2017-07-19 Alnylam Pharmaceuticals, Inc. Gegen komplementkomponente c5 gerichtete polynukleotidwirkstoffe und verfahren zur verwendung davon
JOP20200115A1 (ar) 2014-10-10 2017-06-16 Alnylam Pharmaceuticals Inc تركيبات وطرق لتثبيط التعبير الجيني عن hao1 (حمض أوكسيداز هيدروكسيلي 1 (أوكسيداز جليكولات))
WO2016061487A1 (en) 2014-10-17 2016-04-21 Alnylam Pharmaceuticals, Inc. Polynucleotide agents targeting aminolevulinic acid synthase-1 (alas1) and uses thereof
EP3904519A1 (de) 2014-10-30 2021-11-03 Genzyme Corporation Polynukleotidwirkstoffe mit abzielung auf serpinc1 (at3) und verfahren zur verwendung davon
JOP20200092A1 (ar) 2014-11-10 2017-06-16 Alnylam Pharmaceuticals Inc تركيبات iRNA لفيروس الكبد B (HBV) وطرق لاستخدامها
CA2968114A1 (en) 2014-11-17 2016-05-26 Alnylam Pharmaceuticals, Inc. Apolipoprotein c3 (apoc3) irna compositions and methods of use thereof
EP3256587A2 (de) 2015-02-13 2017-12-20 Alnylam Pharmaceuticals, Inc. Patatin-like phospholipase domain containing-3 (pnpla3)-irna-zusammensetzungen und verfahren zur verwendung davon
MX2017012610A (es) 2015-04-08 2018-03-16 Alnylam Pharmaceuticals Inc Composiciones y metodos para inhibir la expresion del gen lect2.
WO2016168286A1 (en) 2015-04-13 2016-10-20 Alnylam Pharmaceuticals, Inc. Angiopoietin-like 3 (angptl3) irna compositions and methods of use thereof
EP3307316A1 (de) 2015-06-12 2018-04-18 Alnylam Pharmaceuticals, Inc. Gegen komplementkomponente c5 gerichtete irna-zusammensetzungen und verfahren zur verwendung davon
WO2016205323A1 (en) 2015-06-18 2016-12-22 Alnylam Pharmaceuticals, Inc. Polynucleotde agents targeting hydroxyacid oxidase (glycolate oxidase, hao1) and methods of use thereof
WO2016209862A1 (en) 2015-06-23 2016-12-29 Alnylam Pharmaceuticals, Inc. Glucokinase (gck) irna compositions and methods of use thereof
WO2017003668A1 (en) 2015-07-01 2017-01-05 California Institute Of Technology Cationic mucic acid polymer-based delivery systems
WO2017011286A1 (en) 2015-07-10 2017-01-19 Alnylam Pharmaceuticals, Inc. Insulin-like growth factor binding protein, acid labile subunit (igfals) and insulin-like growth factor 1 (igf-1) irna compositions and methods of use thereof
EP3329002B1 (de) 2015-07-31 2020-10-07 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr)-irna-zusammensetzungen und verfahren zur verwendung davon zur behandlung oder praevention ttr-assoziierter erkrankungen
WO2017027350A2 (en) 2015-08-07 2017-02-16 Arrowhead Pharmaceuticals, Inc. Rnai therapy for hepatitis b virus infection
EP3340994A1 (de) 2015-08-25 2018-07-04 Alnylam Pharmaceuticals, Inc. Verfahren und zusammensetzungen zur behandlung einer mit dem proprotein-konvertase-subtilisin-kexin (pcsk9)-gen assoziierte störung
EP3344769B1 (de) 2015-09-02 2024-04-17 Alnylam Pharmaceuticals, Inc. Programmed cell death 1 ligand 1 (pd-l1) irna-kompositionen und methoden zu deren verwendung
WO2017069958A2 (en) 2015-10-09 2017-04-27 The Brigham And Women's Hospital, Inc. Modulation of novel immune checkpoint targets
WO2017075478A2 (en) 2015-10-28 2017-05-04 The Broad Institute Inc. Compositions and methods for evaluating and modulating immune responses by use of immune cell gene signatures
WO2017075451A1 (en) 2015-10-28 2017-05-04 The Broad Institute Inc. Compositions and methods for evaluating and modulating immune responses by detecting and targeting pou2af1
WO2017075465A1 (en) 2015-10-28 2017-05-04 The Broad Institute Inc. Compositions and methods for evaluating and modulating immune responses by detecting and targeting gata3
CA3009154A1 (en) * 2015-12-25 2017-06-29 Sbi Biotech Co., Ltd. Tlr inhibitory oligonucleotides and their use
US9732303B2 (en) 2016-01-06 2017-08-15 The Procter & Gamble Company Microcapsules formed from phosphate esters and compositions containing same
US9730867B2 (en) 2016-01-06 2017-08-15 The Procter & Gamble Company Methods of forming a slurry with microcapsules formed from phosphate esters
US10154947B2 (en) 2016-01-06 2018-12-18 The Procter & Gamble Company Antiperspirant composition
MA45295A (fr) 2016-04-19 2019-02-27 Alnylam Pharmaceuticals Inc Composition d'arni de protéine de liaison de lipoprotéines haute densité (hdlbp/vigiline) et procédés pour les utiliser
EP3469083A1 (de) 2016-06-10 2019-04-17 Alnylam Pharmaceuticals, Inc. Gegen komplementkomponente c5 gerichtete irna-zusammensetzungen und verfahren zur verwendung davon zur behandlung von paroxysmaler nächtlicher hämoglobinurie (pnh)
JOP20170161A1 (ar) 2016-08-04 2019-01-30 Arrowhead Pharmaceuticals Inc عوامل RNAi للعدوى بفيروس التهاب الكبد ب
US20190262399A1 (en) 2016-09-07 2019-08-29 The Broad Institute, Inc. Compositions and methods for evaluating and modulating immune responses
WO2018067991A1 (en) 2016-10-07 2018-04-12 The Brigham And Women's Hospital, Inc. Modulation of novel immune checkpoint targets
TWI788312B (zh) 2016-11-23 2023-01-01 美商阿尼拉製藥公司 絲胺酸蛋白酶抑制因子A1 iRNA組成物及其使用方法
WO2018112320A1 (en) 2016-12-16 2018-06-21 Alnylam Pharmaceuticals, Inc. Methods for treating or preventing ttr-associated diseases using transthyretin (ttr) irna compositions
WO2018129261A1 (en) 2017-01-05 2018-07-12 Brown University Methods and compositions relating to anti-chi3l1 antibody reagents
CN111148760A (zh) 2017-02-27 2020-05-12 卡拉斯医疗有限公司 抗体构建体和治疗癌症的方法
BR112019021852A2 (pt) 2017-04-18 2020-06-02 Alnylam Pharmaceuticals, Inc. Agente de rnai e uma vacina contra hbv, uso ou método e kit para tratamento
WO2018204303A1 (en) 2017-05-01 2018-11-08 The Children's Medical Center Coporation Methods and compositions relating to anti-pd1 antibody reagents
CA3069868A1 (en) 2017-07-13 2019-01-17 Alnylam Pharmaceuticals Inc. Lactate dehydrogenase a (ldha) irna compositions and methods of use thereof
WO2019014491A1 (en) 2017-07-13 2019-01-17 Alnylam Pharmaceuticals, Inc. METHODS OF INHIBITING GENE EXPRESSION OF HAO1 (HYDROXYACID OXIDASE 1 (GLYCOLATE OXIDASE))
KR20200089656A (ko) 2017-09-19 2020-07-27 알닐람 파마슈티칼스 인코포레이티드 트랜스타이레틴(ttr) 매개 아밀로이드증을 치료하기 위한 조성물 및 방법
WO2019089922A1 (en) 2017-11-01 2019-05-09 Alnylam Pharmaceuticals, Inc. Complement component c3 irna compositions and methods of use thereof
EP3710587A1 (de) 2017-11-16 2020-09-23 Alnylam Pharmaceuticals, Inc. Apolipoprotein-c3 kisspeptin 1 (kiss1)-irna-zusammensetzungen und verfahren zur verwendung davon
WO2019100039A1 (en) 2017-11-20 2019-05-23 Alnylam Pharmaceuticals, Inc. Serum amyloid p component (apcs) irna compositions and methods of use thereof
CA3086343A1 (en) 2017-12-18 2019-06-27 Alnylam Pharmaceuticals, Inc. High mobility group box-1 (hmgb1) irna compositions and methods of use thereof
KR102083478B1 (ko) * 2017-12-28 2020-04-28 한양대학교 산학협력단 Chi3l1 억제제를 유효성분으로 하는 암의 폐 전이 예방 또는 치료용 약학 조성물
TW202016304A (zh) 2018-05-14 2020-05-01 美商阿尼拉製藥公司 血管收縮素原(AGT)iRNA組成物及其使用方法
US20210348162A1 (en) 2018-08-16 2021-11-11 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the lect2 gene
AU2019344776A1 (en) 2018-09-18 2021-01-21 Alnylam Pharmaceuticals, Inc. Ketohexokinase (KHK) iRNA compositions and methods of use thereof
US10913951B2 (en) 2018-10-31 2021-02-09 University of Pittsburgh—of the Commonwealth System of Higher Education Silencing of HNF4A-P2 isoforms with siRNA to improve hepatocyte function in liver failure
CA3122402A1 (en) 2018-12-20 2020-06-25 Vir Biotechnology, Inc. Combination hbv therapy
US20220056455A1 (en) 2018-12-20 2022-02-24 Praxis Precision Medicines, Inc. Compositions and methods for the treatment of kcnt1 related disorders
EP4007812A1 (de) 2019-08-01 2022-06-08 Alnylam Pharmaceuticals, Inc. Irna-zusammensetzungen der serpinfamilie f element 2 (serpinf2) und verfahren zu deren verwendung
EP4007811A2 (de) 2019-08-01 2022-06-08 Alnylam Pharmaceuticals, Inc. Carboxypeptidase-b2(cpb2)-irna-zusammensetzungen und verfahren zur verwendung davon
WO2021030522A1 (en) 2019-08-13 2021-02-18 Alnylam Pharmaceuticals, Inc. SMALL RIBOSOMAL PROTEIN SUBUNIT 25 (RPS25) iRNA AGENT COMPOSITIONS AND METHODS OF USE THEREOF
BR112022003860A2 (pt) 2019-09-03 2022-08-16 Alnylam Pharmaceuticals Inc Composições e métodos para inibir a expressão do gene lect2
JP2022548320A (ja) 2019-09-23 2022-11-17 オメガ セラピューティクス, インコーポレイテッド アポリポタンパク質b(apob)遺伝子発現をモジュレートするための組成物および方法
JP2022548399A (ja) 2019-09-23 2022-11-18 オメガ セラピューティクス, インコーポレイテッド 肝細胞核因子4-アルファ(HNF4α)遺伝子発現をモジュレートするための組成物および方法
US20220389429A1 (en) 2019-10-04 2022-12-08 Alnylam Pharmaceuticals, Inc. Compositions and methods for silencing ugt1a1 gene expression
AU2020363372A1 (en) 2019-10-07 2022-05-19 University Of Virginia Patent Foundation Modulating lymphatic vessels in neurological disease
WO2021076828A1 (en) 2019-10-18 2021-04-22 Alnylam Pharmaceuticals, Inc. Solute carrier family member irna compositions and methods of use thereof
EP4048793A1 (de) 2019-10-22 2022-08-31 Alnylam Pharmaceuticals, Inc. Gegen komplementkomponente c3 gerichtete irna-zusammensetzungen und verfahren zur verwendung davon
CA3155921A1 (en) 2019-11-01 2021-05-06 Alnylam Pharmaceuticals, Inc. HUNTINGTINE (HTT) TARGETING RNAI AGENT COMPOSITIONS AND METHODS OF USE THEREOF
EP4051796A1 (de) 2019-11-01 2022-09-07 Alnylam Pharmaceuticals, Inc. Zusammensetzungen und verfahren zum unterdrücken der dnajb1-prkaca-fusionsgenexpression
KR20220115946A (ko) 2019-11-13 2022-08-19 알닐람 파마슈티칼스 인코포레이티드 안지오텐시노겐 (agt) 관련 장애를 치료하기 위한 방법 및 조성물
WO2021102373A1 (en) 2019-11-22 2021-05-27 Alnylam Pharmaceuticals, Inc. Ataxin3 (atxn3) rnai agent compositions and methods of use thereof
CN115151641A (zh) 2019-12-13 2022-10-04 阿尔尼拉姆医药品有限公司 人类染色体9开放阅读框72(C9ORF72)iRNA剂组合物及其使用方法
WO2021126734A1 (en) 2019-12-16 2021-06-24 Alnylam Pharmaceuticals, Inc. Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof
US20230067811A1 (en) 2020-01-24 2023-03-02 University Of Virginia Patent Foundation Modulating lymphatic vessels in neurological disease
WO2021154941A1 (en) 2020-01-31 2021-08-05 Alnylam Pharmaceuticals, Inc. Complement component c5 irna compositions for use in the treatment of amyotrophic lateral sclerosis (als)
BR112022015770A2 (pt) 2020-02-10 2022-10-11 Alnylam Pharmaceuticals Inc Composições e métodos para silenciar a expressão de vegf-a
IL295496A (en) 2020-02-18 2022-10-01 Alnylam Pharmaceuticals Inc Apolipoprotein c3 (apoc3) irna preparations and methods of using them
JP2023516095A (ja) 2020-03-06 2023-04-17 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 ケトヘキソキナーゼ(KHK)iRNA組成物およびその使用方法
CA3173528A1 (en) 2020-03-11 2021-09-16 Omega Therapeutics, Inc. Compositions and methods for modulating forkhead box p3 (foxp3) gene expression
WO2021188611A1 (en) 2020-03-18 2021-09-23 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating subjects having a heterozygous alanine-glyoxylate aminotransferase gene (agxt) variant
TW202204615A (zh) 2020-03-26 2022-02-01 美商阿尼拉製藥公司 冠狀病毒iRNA組成物及其使用方法
EP4127171A2 (de) 2020-03-30 2023-02-08 Alnylam Pharmaceuticals, Inc. Zusammensetzungen und verfahren zur ausschaltung der dnajc15-genexpression
TW202204618A (zh) 2020-04-06 2022-02-01 美商艾爾妮蘭製藥公司 用於靜默myoc表現之組合物及方法
WO2021206917A1 (en) 2020-04-07 2021-10-14 Alnylam Pharmaceuticals, Inc. ANGIOTENSIN-CONVERTING ENZYME 2 (ACE2) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
EP4133077A1 (de) 2020-04-07 2023-02-15 Alnylam Pharmaceuticals, Inc. Irna-zusammensetzungen mit transmembran-serinprotease 2 (tmprss2) und verfahren zur verwendung davon
CA3179678A1 (en) 2020-04-07 2021-10-14 Alnylam Pharmaceuticals, Inc. Compositions and methods for silencing scn9a expression
WO2021222065A1 (en) 2020-04-27 2021-11-04 Alnylam Pharmaceuticals, Inc. Apolipoprotein e (apoe) irna agent compositions and methods of use thereof
JP2023523790A (ja) 2020-04-30 2023-06-07 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 補体因子B(CFB)iRNA組成物およびその使用方法
WO2021231679A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of gap junction protein beta 2 (gjb2)
EP4150088A1 (de) 2020-05-15 2023-03-22 Korro Bio, Inc. Verfahren und zusammensetzungen zur adar-vermittelten bearbeitung von argininosuccinat-synthetase (ass1)
WO2021231698A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of argininosuccinate lyase (asl)
WO2021231685A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of transmembrane channel-like protein 1 (tmc1)
EP4150076A1 (de) 2020-05-15 2023-03-22 Korro Bio, Inc. Verfahren und zusammensetzungen zur adar-vermittelten bearbeitung von methyl-cpg-bindendem protein 2 (mecp2)
WO2021231691A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of retinoschisin 1 (rsi)
EP4150086A1 (de) 2020-05-15 2023-03-22 Korro Bio, Inc. Verfahren und zusammensetzungen zur adar-vermittelten bearbeitung von leucinreicher repeat-kinase 2 (lrrk2)
EP4150090A1 (de) 2020-05-15 2023-03-22 Korro Bio, Inc. Verfahren und zusammensetzungen zur adar-vermittelten bearbeitung von otoflin (otof)
EP4153746A1 (de) 2020-05-21 2023-03-29 Alnylam Pharmaceuticals, Inc. Zusammensetzungen und verfahren zur hemmung der marc1-genexpression
US11408000B2 (en) 2020-06-03 2022-08-09 Triplet Therapeutics, Inc. Oligonucleotides for the treatment of nucleotide repeat expansion disorders associated with MSH3 activity
EP4162050A1 (de) 2020-06-09 2023-04-12 Alnylam Pharmaceuticals, Inc. Rnai-zusammensetzungen und verfahren zur verwendung davon zur verabreichung durch inhalation
JP2023530461A (ja) 2020-06-18 2023-07-18 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 キサンチンデヒドロゲナーゼ(XDH)iRNA組成物およびその使用方法
WO2021262840A1 (en) 2020-06-24 2021-12-30 Vir Biotechnology, Inc. Engineered hepatitis b virus neutralizing antibodies and uses thereof
EP4217489A1 (de) 2020-09-24 2023-08-02 Alnylam Pharmaceuticals, Inc. Dipeptidylpeptidase 4 (dpp4)-irna-zusammensetzungen und verfahren zur verwendung davon
WO2022076291A1 (en) 2020-10-05 2022-04-14 Alnylam Pharmaceuticals, Inc. G protein-coupled receptor 75 (gpr75) irna compositions and methods of use thereof
AU2021365822A1 (en) 2020-10-21 2023-06-08 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating primary hyperoxaluria
EP4232582A1 (de) 2020-10-23 2023-08-30 Alnylam Pharmaceuticals, Inc. Mucin-5b (muc5b)-irna-zusammensetzungen und verfahren zur verwendung davon
IL302709A (en) 2020-11-13 2023-07-01 Alnylam Pharmaceuticals Inc Coagulation factor iRNA compositions (F5) and methods of using them
WO2022119873A1 (en) 2020-12-01 2022-06-09 Alnylam Pharmaceuticals, Inc. Methods and compositions for inhibition of hao1 (hydroxyacid oxidase 1 (glycolate oxidase)) gene expression
EP4259795A1 (de) 2020-12-08 2023-10-18 Alnylam Pharmaceuticals, Inc. Gerinnungsfaktor x (f10)-irna-zusammensetzungen und verfahren zur verwendung davon
AU2021414121A1 (en) * 2020-12-29 2023-06-29 Precise-Therapeutics Llc Compositions and associated methods for sustained-release of radioactive agents and their applications
WO2022150260A1 (en) 2021-01-05 2022-07-14 Alnylam Pharmaceuticals, Inc. COMPLEMENT COMPONENT 9 (C9) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
US20240117033A1 (en) 2021-01-15 2024-04-11 President And Fellows Of Harvard College Methods and compositions relating to anti-mfsd2a antibodies
TW202305131A (zh) 2021-02-12 2023-02-01 美商艾拉倫製藥股份有限公司 用於治療或預防超氧歧化酶1-(SOD1-)相關的神經退化疾病的超氧歧化酶1(SOD1)iRNA組成物及其使用方法
JP2024509783A (ja) 2021-02-25 2024-03-05 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 プリオンタンパク質(prnp)irna組成物およびその使用方法
BR112023016645A2 (pt) 2021-02-26 2023-11-14 Alnylam Pharmaceuticals Inc Composições de irna de ceto-hexoquinase (khk) e métodos de uso das mesmas
TW202302849A (zh) 2021-03-04 2023-01-16 美商艾拉倫製藥股份有限公司 類血管生成素3(ANGPTL3)iRNA組成物及其使用方法
EP4305169A1 (de) 2021-03-12 2024-01-17 Alnylam Pharmaceuticals, Inc. Glykogensynthasekinase-3-alpha (gsk3a)-irna-zusammensetzungen und verfahren zur verwendung davon
AR125230A1 (es) 2021-03-29 2023-06-28 Alnylam Pharmaceuticals Inc COMPOSICIONES DE AGENTES DE ARNi CONTRA HUNTINGTINA (HTT) Y SUS MÉTODOS DE USO
EP4314293A1 (de) 2021-04-01 2024-02-07 Alnylam Pharmaceuticals, Inc. Prolindehydrogenase 2 (prodh2)-irna-zusammensetzungen und verfahren zur verwendung davon
TW202309280A (zh) 2021-04-26 2023-03-01 美商艾拉倫製藥股份有限公司 跨膜絲胺酸蛋白酶6(TMPRSS6)iRNA組成物及其使用方法
EP4330396A1 (de) 2021-04-29 2024-03-06 Alnylam Pharmaceuticals, Inc. Signalwandler und aktivator von transkriptionsfaktor 6 (stat6)-irna-zusammensetzungen und verfahren zur verwendung davon
EP4341401A1 (de) 2021-05-18 2024-03-27 Alnylam Pharmaceuticals, Inc. Natriumglucose-cotransporter-2-(sglt2)-irna-zusammensetzungen und verfahren zur verwendung davon
WO2022246023A1 (en) 2021-05-20 2022-11-24 Korro Bio, Inc. Methods and compositions for adar-mediated editing
WO2022256283A2 (en) 2021-06-01 2022-12-08 Korro Bio, Inc. Methods for restoring protein function using adar
WO2022256395A1 (en) 2021-06-02 2022-12-08 Alnylam Pharmaceuticals, Inc. Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof
AU2022283796A1 (en) 2021-06-04 2023-11-09 Alnylam Pharmaceuticals, Inc. HUMAN CHROMOSOME 9 OPEN READING FRAME 72 (C9ORF72) iRNA AGENT COMPOSITIONS AND METHODS OF USE THEREOF
AR126070A1 (es) 2021-06-08 2023-09-06 Alnylam Pharmaceuticals Inc Composiciones y métodos para tratar o prevenir la enfermedad de stargardt y/o trastornos asociados con la proteína transportadora de retinol 4 (rbp4)
US20230194709A9 (en) 2021-06-29 2023-06-22 Seagate Technology Llc Range information detection using coherent pulse sets with selected waveform characteristics
WO2023278410A1 (en) 2021-06-29 2023-01-05 Korro Bio, Inc. Methods and compositions for adar-mediated editing
KR20240026203A (ko) 2021-06-30 2024-02-27 알닐람 파마슈티칼스 인코포레이티드 안지오텐시노겐(agt)-관련 장애를 치료하는 방법 및 조성물
WO2023283359A2 (en) 2021-07-07 2023-01-12 Omega Therapeutics, Inc. Compositions and methods for modulating secreted frizzled receptor protein 1 (sfrp1) gene expression
TW202333748A (zh) 2021-07-19 2023-09-01 美商艾拉倫製藥股份有限公司 用於處置具有或有風險發展非原發性高草酸鹽尿疾病或病症的個體的方法及組成物
IL309897A (en) 2021-07-21 2024-03-01 Alnylam Pharmaceuticals Inc Target gene IRNA compositions associated with a metabolic disorder and methods of using them
WO2023003995A1 (en) 2021-07-23 2023-01-26 Alnylam Pharmaceuticals, Inc. Beta-catenin (ctnnb1) irna compositions and methods of use thereof
WO2023009687A1 (en) 2021-07-29 2023-02-02 Alnylam Pharmaceuticals, Inc. 3-hydroxy-3-methylglutaryl-coa reductase (hmgcr) irna compositions and methods of use thereof
TW202328445A (zh) 2021-08-03 2023-07-16 美商艾拉倫製藥股份有限公司 甲狀腺素運載蛋白(TTR)iRNA組成物及其使用方法
CA3228255A1 (en) 2021-08-04 2023-02-09 Alnylam Pharmaceuticals, Inc. Irna compositions and methods for silencing angiotensinogen (agt)
AU2022328347A1 (en) 2021-08-13 2024-02-08 Alnylam Pharmaceuticals, Inc. Factor xii (f12) irna compositions and methods of use thereof
WO2023044370A2 (en) 2021-09-17 2023-03-23 Alnylam Pharmaceuticals, Inc. Irna compositions and methods for silencing complement component 3 (c3)
AU2022345881A1 (en) 2021-09-20 2024-03-21 Alnylam Pharmaceuticals, Inc. Inhibin subunit beta e (inhbe) modulator compositions and methods of use thereof
AU2022364838A1 (en) 2021-10-15 2024-04-11 Alnylam Pharmaceuticals, Inc. Extra-hepatic delivery irna compositions and methods of use thereof
CA3234835A1 (en) 2021-10-22 2023-04-27 Korro Bio, Inc. Methods and compositions for disrupting nrf2-keap1 protein interaction by adar mediated rna editing
CA3234636A1 (en) 2021-10-29 2023-05-04 Alnylam Pharmaceuticals, Inc. Complement factor b (cfb) irna compositions and methods of use thereof
WO2023076450A2 (en) 2021-10-29 2023-05-04 Alnylam Pharmaceuticals, Inc. HUNTINGTIN (HTT) iRNA AGENT COMPOSITIONS AND METHODS OF USE THEREOF
WO2023122762A1 (en) 2021-12-22 2023-06-29 Camp4 Therapeutics Corporation Modulation of gene transcription using antisense oligonucleotides targeting regulatory rnas
WO2023138211A1 (zh) * 2022-01-21 2023-07-27 苏州万维生命科学技术有限公司 星型β-抗菌糖肽、其制备方法及应用
WO2023141314A2 (en) 2022-01-24 2023-07-27 Alnylam Pharmaceuticals, Inc. Heparin sulfate biosynthesis pathway enzyme irna agent compositions and methods of use thereof
WO2023240277A2 (en) 2022-06-10 2023-12-14 Camp4 Therapeutics Corporation Methods of modulating progranulin expression using antisense oligonucleotides targeting regulatory rnas
WO2024039776A2 (en) 2022-08-18 2024-02-22 Alnylam Pharmaceuticals, Inc. Universal non-targeting sirna compositions and methods of use thereof
WO2024059165A1 (en) 2022-09-15 2024-03-21 Alnylam Pharmaceuticals, Inc. 17b-hydroxysteroid dehydrogenase type 13 (hsd17b13) irna compositions and methods of use thereof

Family Cites Families (101)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4534899A (en) 1981-07-20 1985-08-13 Lipid Specialties, Inc. Synthetic phospholipid compounds
US4426330A (en) 1981-07-20 1984-01-17 Lipid Specialties, Inc. Synthetic phospholipid compounds
EP0269520A3 (de) 1986-11-21 1988-08-24 Institut Pasteur Zum Hervorrufen von AIDS geeignetes Retrovirus vom HIV-2-Typ sowie seine Antigen- und Nukleinsäurebestandteile
US4987071A (en) 1986-12-03 1991-01-22 University Patents, Inc. RNA ribozyme polymerases, dephosphorylases, restriction endoribonucleases and methods
US5116742A (en) 1986-12-03 1992-05-26 University Patents, Inc. RNA ribozyme restriction endoribonucleases and methods
US4845195A (en) * 1987-05-22 1989-07-04 Merck & Co., Inc. Inhibitor of ribonucleotide reductase
CA1340747C (en) 1988-06-14 1999-09-14 Karsten Henco Hiv-2 virus variants
US5354844A (en) 1989-03-16 1994-10-11 Boehringer Ingelheim International Gmbh Protein-polycation conjugates
US4945195A (en) 1989-03-20 1990-07-31 C & K Components, Inc. Rotary switch
US5108921A (en) 1989-04-03 1992-04-28 Purdue Research Foundation Method for enhanced transmembrane transport of exogenous molecules
US5227170A (en) 1989-06-22 1993-07-13 Vestar, Inc. Encapsulation process
US5356633A (en) 1989-10-20 1994-10-18 Liposome Technology, Inc. Method of treatment of inflamed tissues
US5527528A (en) 1989-10-20 1996-06-18 Sequus Pharmaceuticals, Inc. Solid-tumor treatment method
US5013556A (en) 1989-10-20 1991-05-07 Liposome Technology, Inc. Liposomes with enhanced circulation time
US5469854A (en) 1989-12-22 1995-11-28 Imarx Pharmaceutical Corp. Methods of preparing gas-filled liposomes
US5580575A (en) 1989-12-22 1996-12-03 Imarx Pharmaceutical Corp. Therapeutic drug delivery systems
US5264618A (en) 1990-04-19 1993-11-23 Vical, Inc. Cationic lipids for intracellular delivery of biologically active molecules
ES2061416T3 (es) 1990-10-12 1997-03-01 Max Planck Gesellschaft Ribozimas modificadas.
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
NZ244306A (en) 1991-09-30 1995-07-26 Boehringer Ingelheim Int Composition for introducing nucleic acid complexes into eucaryotic cells, complex containing nucleic acid and endosomolytic agent, peptide with endosomolytic domain and nucleic acid binding domain and preparation
US5521291A (en) 1991-09-30 1996-05-28 Boehringer Ingelheim International, Gmbh Conjugates for introducing nucleic acid into higher eucaryotic cells
US5756353A (en) 1991-12-17 1998-05-26 The Regents Of The University Of California Expression of cloned genes in the lung by aerosol-and liposome-based delivery
US5858784A (en) 1991-12-17 1999-01-12 The Regents Of The University Of California Expression of cloned genes in the lung by aerosol- and liposome-based delivery
US5652094A (en) 1992-01-31 1997-07-29 University Of Montreal Nucleozymes
EP0642589A4 (de) 1992-05-11 1997-05-21 Ribozyme Pharm Inc Methode und reagenz zur inhibierung der viralen replikation.
WO1994000562A1 (en) 1992-06-24 1994-01-06 The Mt. Sinai School Of Medicine Of The City University Of New York A novel human immunodeficiency virus
EP0786522A2 (de) 1992-07-17 1997-07-30 Ribozyme Pharmaceuticals, Inc. Enzymatische RNA-Moleküle zur Behandlung von stenotischen Zuständen
US5583020A (en) 1992-11-24 1996-12-10 Ribozyme Pharmaceuticals, Inc. Permeability enhancers for negatively charged polynucleotides
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
US5395619A (en) 1993-03-03 1995-03-07 Liposome Technology, Inc. Lipid-polymer conjugates and liposomes
US5462854A (en) 1993-04-19 1995-10-31 Beckman Instruments, Inc. Inverse linkage oligonucleotides for chemical and enzymatic processes
US5534259A (en) 1993-07-08 1996-07-09 Liposome Technology, Inc. Polymer compound and coated particle composition
US5543158A (en) 1993-07-23 1996-08-06 Massachusetts Institute Of Technology Biodegradable injectable nanoparticles
US5417978A (en) 1993-07-29 1995-05-23 Board Of Regents, The University Of Texas System Liposomal antisense methyl phosphonate oligonucleotides and methods for their preparation and use
FR2711523B1 (fr) 1993-10-26 1996-02-16 Transgene Sa Procédé de préparation d'un aérosol viral.
US5595756A (en) 1993-12-22 1997-01-21 Inex Pharmaceuticals Corporation Liposomal compositions for enhanced retention of bioactive agents
US5627053A (en) 1994-03-29 1997-05-06 Ribozyme Pharmaceuticals, Inc. 2'deoxy-2'-alkylnucleotide containing nucleic acid
EP0755454B1 (de) 1994-04-13 2008-02-13 The Rockefeller University Aav-vermittelte überbringung von dna in zellen des nervensystems
US5543152A (en) 1994-06-20 1996-08-06 Inex Pharmaceuticals Corporation Sphingosomes for enhanced drug delivery
US5591721A (en) 1994-10-25 1997-01-07 Hybridon, Inc. Method of down-regulating gene expression
US5512295A (en) 1994-11-10 1996-04-30 The Board Of Trustees Of The Leland Stanford Junior University Synthetic liposomes for enhanced uptake and delivery
US5716824A (en) 1995-04-20 1998-02-10 Ribozyme Pharmaceuticals, Inc. 2'-O-alkylthioalkyl and 2-C-alkylthioalkyl-containing enzymatic nucleic acids (ribozymes)
US6428771B1 (en) 1995-05-15 2002-08-06 Pharmaceutical Discovery Corporation Method for drug delivery to the pulmonary system
US5542760A (en) 1995-09-26 1996-08-06 Becton Dickinson And Company Syringe filler for mixing insulins
AU1430097A (en) 1996-01-16 1997-08-11 Ribozyme Pharmaceuticals, Inc. Synthesis of methoxy nucleosides and enzymatic nucleic acid molecules
JP4301576B2 (ja) * 1996-08-02 2009-07-22 ローラス セラピューティクス インコーポレイテッド リボヌクレオチドレダクターゼのr1およびr2成分に対して指向される抗腫瘍アンチセンス配列
US6030942A (en) 1996-08-30 2000-02-29 The Trustees Of The University Of Pennsylvania Peptides peptide analogs peptidomimetics and other small molecules useful for inhibiting the activity of ribonucleotide reductase
CA2265838A1 (en) 1996-09-12 1998-03-19 Alain Rolland Compositions and methods for pulmonary gene delivery
US5849902A (en) 1996-09-26 1998-12-15 Oligos Etc. Inc. Three component chimeric antisense oligonucleotides
DE69732306T2 (de) 1997-01-16 2006-01-12 Massachusetts Institute Of Technology, Cambridge Zubereitung von partikelhaltigen arzneimitteln zur inhalation
US6001311A (en) 1997-02-05 1999-12-14 Protogene Laboratories, Inc. Apparatus for diverse chemical synthesis using two-dimensional array
US6395713B1 (en) 1997-07-23 2002-05-28 Ribozyme Pharmaceuticals, Inc. Compositions for the delivery of negatively charged molecules
WO1999004819A1 (en) 1997-07-24 1999-02-04 Inex Pharmaceuticals Corporation Liposomal compositions for the delivery of nucleic acid catalysts
AR013269A1 (es) 1997-08-04 2000-12-13 Scras Producto que contiene por lo menos un rna de doble filamento combinado con por lo menos un agente anti-viral, para la utilizacion terapeutica en eltratamiento de una enfermedad viral, en especial de la hepatitis viral
NZ503765A (en) 1997-09-12 2002-04-26 Exiqon As Bi-cyclic and tri-cyclic nucleotide analogues
US6506559B1 (en) 1997-12-23 2003-01-14 Carnegie Institute Of Washington Genetic inhibition by double-stranded RNA
AU3751299A (en) 1998-04-20 1999-11-08 Ribozyme Pharmaceuticals, Inc. Nucleic acid molecules with novel chemical compositions capable of modulating gene expression
US7091192B1 (en) 1998-07-01 2006-08-15 California Institute Of Technology Linear cyclodextrin copolymers
US6509323B1 (en) 1998-07-01 2003-01-21 California Institute Of Technology Linear cyclodextrin copolymers
GB9827152D0 (en) 1998-07-03 1999-02-03 Devgen Nv Characterisation of gene function using double stranded rna inhibition
DE69935154T2 (de) 1998-11-12 2007-10-25 Inc. Transave Inhalationssystem
WO2000032765A2 (en) * 1998-12-04 2000-06-08 Immusol, Inc. Ribozyme therapy for the treatment and/or prevention of restenosis
US6294153B1 (en) 1998-12-21 2001-09-25 Generex Pharmaceuticals, Inc. Aerosol pharmaceutical formulation for pulmonary and nasal delivery
EP1147204A1 (de) 1999-01-28 2001-10-24 Medical College Of Georgia Research Institute, Inc. Zusammensetzung und verfahren zur in vivo und in vitro abschwächung der genexpression mittels dobbelsträngigem rna
DE19956568A1 (de) 1999-01-30 2000-08-17 Roland Kreutzer Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens
US6110462A (en) 1999-03-03 2000-08-29 The Scripps Research Institute Enzymatic DNA molecules that contain modified nucleotides
US6503481B1 (en) 1999-05-03 2003-01-07 Battellepharma, Inc. Compositions for aerosolization and inhalation
CA2372085C (en) 1999-05-04 2009-10-27 Exiqon A/S L-ribo-lna analogues
CA2386270A1 (en) 1999-10-15 2001-04-26 University Of Massachusetts Rna interference pathway genes as tools for targeted genetic interference
US6770633B1 (en) * 1999-10-26 2004-08-03 Immusol, Inc. Ribozyme therapy for the treatment of proliferative skin and eye diseases
AU781151B2 (en) * 1999-10-26 2005-05-12 Immusol Incorporated Ribozyme therapy for the treatment of proliferative skin and eye diseases
GB9927444D0 (en) 1999-11-19 2000-01-19 Cancer Res Campaign Tech Inhibiting gene expression
US7098030B2 (en) * 1999-12-31 2006-08-29 Mirus Bio Corporation Polyampholytes for delivering polyions to a cell
US6585957B1 (en) 2000-01-25 2003-07-01 Aeropharm Technology Incorporated Medicinal aerosol formulation
US6596261B1 (en) 2000-01-25 2003-07-22 Aeropharm Technology Incorporated Method of administering a medicinal aerosol formulation
WO2001077350A2 (en) 2000-04-07 2001-10-18 Large Scale Biology Corporation Compositions and methods for inhibiting gene expression
US6503756B1 (en) * 2000-09-22 2003-01-07 Isis Pharmaceuticals, Inc. Antisense modulation of syntaxin 4 interacting protein expression
ES2728168T3 (es) * 2000-12-01 2019-10-22 Max Planck Gesellschaft Moléculas pequeñas de ARN que median en la interferencia de ARN
TWI321054B (en) 2000-12-19 2010-03-01 California Inst Of Techn Compositions containing inclusion complexes
WO2002053190A2 (en) 2000-12-29 2002-07-11 Advanced Inhalation Research, Inc. Particles for inhalation having sustained release properties
EP1355628A2 (de) 2001-02-01 2003-10-29 Board of Regents, The University of Texas System Stabilisierte aerosollösungen von polymeren zur verabreichung von genen an die lunge
US6475468B2 (en) 2001-02-15 2002-11-05 Aeropharm Technology Incorporated Modulated release particles for aerosol delivery
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)
US20040063654A1 (en) 2001-11-02 2004-04-01 Davis Mark E. Methods and compositions for therapeutic use of RNA interference
US6816784B1 (en) * 2002-03-08 2004-11-09 Navteq North America, Llc Method and system using delivery trucks to collect address location data
WO2003103581A2 (en) 2002-06-05 2003-12-18 Genentech, Inc. Compositions and methods for liver growth and liver protection
EP2277551B1 (de) 2002-09-06 2013-05-08 Cerulean Pharma Inc. Polymere auf basis von cyclodextrin zur verabreichung von an diese kovalent gebundene arzneimittel
US20040053289A1 (en) * 2002-09-09 2004-03-18 The Regents Of The University Of California Short interfering nucleic acid hybrids and methods thereof
BR0315198A (pt) 2002-10-09 2005-08-30 Insert Therapeutics Inc Materiais e composições à base de ciclodextrina e usos relacionados aos mesmos
US7250496B2 (en) * 2002-11-14 2007-07-31 Rosetta Genomics Ltd. Bioinformatically detectable group of novel regulatory genes and uses thereof
US7592442B2 (en) * 2002-11-14 2009-09-22 Dharmacon, Inc. siRNA targeting ribonucleotide reductase M2 polypeptide (RRM2 or RNR-R2)
EP2213738B1 (de) * 2002-11-14 2012-10-10 Dharmacon, Inc. siRNA moleküle gegen Bcl-2
US7250289B2 (en) * 2002-11-20 2007-07-31 Affymetrix, Inc. Methods of genetic analysis of mouse
US20040241657A1 (en) 2003-05-28 2004-12-02 Perlegen Sciences, Inc. Liver related disease compositions and methods
US7482156B2 (en) 2003-10-15 2009-01-27 Cell Genesys, Inc. Hepatocellular carcinoma specific promoter and uses thereof
CA2577036A1 (en) * 2004-08-18 2006-02-23 Genesense Technologies Inc. Small interfering rna molecules against ribonucleotide reductase and uses thereof
US7427605B2 (en) * 2005-03-31 2008-09-23 Calando Pharmaceuticals, Inc. Inhibitors of ribonucleotide reductase subunit 2 and uses thereof
KR100794956B1 (ko) * 2006-07-25 2008-01-15 주식회사 만도 고리형 서포트 요크를 구비하는 조향장치
US8240498B2 (en) 2006-10-31 2012-08-14 Crown Packaging Technology, Inc. Resealable closure

Also Published As

Publication number Publication date
DK1866414T3 (da) 2012-04-23
ES2381201T3 (es) 2012-05-24
US7427605B2 (en) 2008-09-23
JP2008537551A (ja) 2008-09-18
EP1866414B9 (de) 2012-10-03
US20060263435A1 (en) 2006-11-23
EP1866414B1 (de) 2012-01-18
CA2603730A1 (en) 2006-10-05
HK1112486A1 (en) 2008-09-05
TWI335352B (en) 2011-01-01
PL1866414T3 (pl) 2012-10-31
IL186129A0 (en) 2008-01-20
EP1866414A2 (de) 2007-12-19
AU2006230436A1 (en) 2006-10-05
EP2360249A1 (de) 2011-08-24
WO2006105361A2 (en) 2006-10-05
AU2006230436B2 (en) 2011-11-24
JP2012153732A (ja) 2012-08-16
JP2012157368A (ja) 2012-08-23
TW200714294A (en) 2007-04-16
WO2006105361A3 (en) 2007-04-05
US20090169638A1 (en) 2009-07-02

Similar Documents

Publication Publication Date Title
ATE541928T1 (de) Inhibitoren der untereinheit 2 der ribonukleotidreduktase und ihre verwendungen
EA200800240A1 (ru) Производные тиазола в качестве активатора амфк
TW200716584A (en) Dihydrobenzofuran derivatives and uses thereof
GEP20094785B (en) Pyrrolopyrazoles, potent kinase inhibitors
EA200701396A1 (ru) Триазолофталазины в качестве ингибиторов pde-2
WO2009123764A3 (en) Compositions and use of epas1 inhibitors
WO2006072612A3 (en) Triazolophthalazines as pde2- inhibitors
ATE548374T1 (de) 2'-fluor-2'-desoxytetrahydrouridine als cytidindeaminaseinhibitoren
WO2009006389A8 (en) Pyrimidine derivatives useful as raf kinase inhibitors
IL197161A (en) Derivatives 4- (n-azacycloalkyl) anilides Preparations containing and using them
ATE432323T1 (de) Bitumenzusammensetzung
CY1109916T1 (el) Βενζιμιδαζολο-θειοφαινικες ενωσεις ως plk αναστολεις
DK1789398T3 (da) 2-amino-quinazolin derivater anvendelige som inhibitorer af B-sekretase (BACE)
WO2007092645A3 (en) Novel hcv inhibitor combinations and methods
NO20073368L (no) Amid-promedikament av gemcitabin, sammensetninger og anvendelse derav
MX2008001538A (es) Aril piridinas y metodos para su uso.
MY147790A (en) Stable emulsion composition
PL1922128T3 (pl) Element do zmniejszania zawartości drobnego pyłu w powietrzu, za pomocą mchów i/lub porostów
MX2008001541A (es) Metodos para la preparacion de inhibidores de polimerasa del vhc.
MXPA06000986A (es) Compuestos.
NO20074528L (no) Substituerte pyrroler, sammensetninger, fremgangsmate for fremstilling og anvendelse av samme
MXPA06000987A (es) Derivados de nicotinamida utiles como inhibidores de pde4.
ATE491764T1 (de) Auto-adhäsiver klebstoff
DK1819704T3 (da) Pyrrolopyridin-2-carboxylsyre-amid-derivat anvendelig som inhibitor af glycogenphosphorylase
WO2005075457A8 (en) Phthalazinone-derivatives as pde4 inhibitors