AU2007325767A1 - Methods for treating hypercholesterolemia - Google Patents
Methods for treating hypercholesterolemia Download PDFInfo
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- AU2007325767A1 AU2007325767A1 AU2007325767A AU2007325767A AU2007325767A1 AU 2007325767 A1 AU2007325767 A1 AU 2007325767A1 AU 2007325767 A AU2007325767 A AU 2007325767A AU 2007325767 A AU2007325767 A AU 2007325767A AU 2007325767 A1 AU2007325767 A1 AU 2007325767A1
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- seq
- compound
- cholesterol
- modified oligonucleotide
- certain embodiments
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Families Citing this family (56)
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| SG171676A1 (en) | 2006-05-11 | 2011-06-29 | Alnylam Pharmaceuticals Inc | Compositions and methods for inhibiting expression of the pcsk9 gene |
| US8093222B2 (en) | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| JP2010510807A (ja) | 2006-11-27 | 2010-04-08 | アイシス ファーマシューティカルズ， インコーポレーテッド | 高コレステロール血症を治療するための方法 |
| JOP20080381B1 (ar) | 2007-08-23 | 2023-03-28 | Amgen Inc | بروتينات مرتبطة بمولدات مضادات تتفاعل مع بروبروتين كونفيرتاز سيتيليزين ككسين من النوع 9 (pcsk9) |
| EP3643782A1 (en) | 2008-02-11 | 2020-04-29 | Phio Pharmaceuticals Corp. | Modified rnai polynucleotides and uses thereof |
| WO2009148605A2 (en) * | 2008-06-04 | 2009-12-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| CN104212799B (zh) | 2008-10-15 | 2018-11-23 | Ionis制药公司 | 因子11表达的调节 |
| RU2015151857A (ru) | 2008-12-02 | 2019-01-15 | Уэйв Лайф Сайенсес Джапан, Инк. | Способ синтеза модифицированных по атому фосфора нуклеиновых кислот |
| JO3672B1 (ar) | 2008-12-15 | 2020-08-27 | Regeneron Pharma | أجسام مضادة بشرية عالية التفاعل الكيماوي بالنسبة لإنزيم سبتيليسين كنفرتيز بروبروتين / كيكسين نوع 9 (pcsk9). |
| WO2010078536A1 (en) | 2009-01-05 | 2010-07-08 | Rxi Pharmaceuticals Corporation | Inhibition of pcsk9 through rnai |
| CN102421900B (zh) * | 2009-03-12 | 2015-07-22 | 阿尔尼拉姆医药品有限公司 | 用于抑制Eg5和VEGF基因表达的脂质配制的组合物以及方法 |
| EP2419146A4 (en) * | 2009-04-15 | 2013-11-27 | Isis Pharmaceuticals Inc | MODULATION OF IGNITION REACTIONS BY FACTOR XI |
| WO2010147992A1 (en) | 2009-06-15 | 2010-12-23 | Alnylam Pharmaceuticals, Inc. | Methods for increasing efficacy of lipid formulated sirna |
| EP2442792A4 (en) | 2009-06-15 | 2015-12-23 | Alnylam Pharmaceuticals Inc | TESTING GENE PCSK9 LIPID-FORMULATED DSRNA |
| MX342945B (es) | 2009-07-06 | 2016-10-18 | Ontorii Inc * | Profármacos de ácido nucleico novedosos y métodos de uso de los mismos. |
| WO2011009697A1 (en) * | 2009-07-21 | 2011-01-27 | Santaris Pharma A/S | Antisense oligomers targeting pcsk9 |
| JP6006120B2 (ja) * | 2010-02-08 | 2016-10-12 | アイオーニス ファーマシューティカルズ， インコーポレーテッドＩｏｎｉｓ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． | 対立遺伝子多様体の選択的低減 |
| CA2789038A1 (en) | 2010-02-08 | 2011-08-11 | Isis Pharmaceuticals, Inc. | Selective reduction of allelic variants |
| GB2481373A (en) * | 2010-06-21 | 2011-12-28 | Weiming Xu | Treatment of hypercholesterolaemia by ubiquitination of PCSK9 |
| US10428019B2 (en) | 2010-09-24 | 2019-10-01 | Wave Life Sciences Ltd. | Chiral auxiliaries |
| WO2012058693A2 (en) * | 2010-10-29 | 2012-05-03 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibition of pcsk9 genes |
| HRP20180959T1 (hr) | 2011-01-28 | 2018-07-27 | Sanofi Biotechnology | Ljudska protutijela za pcsk9 za uporabu u postupcima liječenja određenih skupina subjekata |
| EP3248982A1 (en) | 2011-07-19 | 2017-11-29 | Wave Life Sciences Ltd. | Thiosulfonate reagents for the synthesis of functionalized nucleic acids |
| AR087305A1 (es) | 2011-07-28 | 2014-03-12 | Regeneron Pharma | Formulaciones estabilizadas que contienen anticuerpos anti-pcsk9, metodo de preparacion y kit |
| WO2013022967A1 (en) | 2011-08-11 | 2013-02-14 | Isis Pharmaceuticals, Inc. | Gapped oligomeric compounds comprising 5'-modified deoxyribonucleosides in the gap and uses thereof |
| CA2848201C (en) | 2011-09-16 | 2020-10-27 | Regeneron Pharmaceuticals, Inc. | Methods for reducing lipoprotein(a) levels by administering an inhibitor of proprotein convertase subtilisin kexin-9 (pcsk9) |
| RU2015101113A (ru) | 2012-06-15 | 2016-08-10 | Дженентек, Инк. | Антитела против pcsk9, составы, дозы и способы применения |
| JP2015165772A (ja) * | 2012-07-04 | 2015-09-24 | 国立大学法人大阪大学 | オリゴヌクレオチド、およびオリゴヌクレオチドを有効成分として含有する脂質異常症治療剤 |
| CA2879066C (en) | 2012-07-13 | 2019-08-13 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant |
| CN104661664B (zh) | 2012-07-13 | 2020-07-03 | 波涛生命科学有限公司 | 手性控制 |
| CA2879023C (en) | 2012-07-13 | 2017-03-28 | Wave Life Sciences Japan | Asymmetric auxiliary group |
| EP4086347A3 (en) | 2012-10-12 | 2023-01-11 | Ionis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
| SG11201503821YA (en) | 2012-11-15 | 2015-06-29 | Roche Innovation Ct Copenhagen As | Oligonucleotide conjugates |
| HUE035887T2 (en) | 2012-12-05 | 2018-05-28 | Alnylam Pharmaceuticals Inc | PCSK9 iRNA preparations and methods for their use |
| RU2649367C2 (ru) | 2013-01-30 | 2018-04-02 | Ф. Хоффманн-Ля Рош Аг | Конъюгаты углевода и lna-олигонуклеотида |
| GB2523527A (en) * | 2013-04-05 | 2015-09-02 | Weiming Xu | Screen compounds for the modulation of proprotein convertase subtilisin/kexin type 9(PCSK9) |
| MX2015014666A (es) | 2013-04-17 | 2016-03-01 | Pfizer | Derivados de n-piperidin-3-ilbenzamida para tratar enfermedades cardiovasculares. |
| KR102482890B1 (ko) | 2013-05-01 | 2022-12-30 | 아이오니스 파마수티컬즈, 인코포레이티드 | 아포지질단백질 (a) 발현을 조절하는 조성물 및 방법 |
| US10111953B2 (en) * | 2013-05-30 | 2018-10-30 | Regeneron Pharmaceuticals, Inc. | Methods for reducing remnant cholesterol and other lipoprotein fractions by administering an inhibitor of proprotein convertase subtilisin kexin-9 (PCSK9) |
| DK3013959T3 (da) | 2013-06-27 | 2020-02-17 | Roche Innovation Ct Copenhagen As | Antisense-oligomerer og konjugater målrettet pcsk9 |
| EP3730614A3 (en) * | 2013-07-02 | 2020-12-30 | Ionis Pharmaceuticals, Inc. | Modulators of growth hormone receptor |
| US10322173B2 (en) | 2014-01-15 | 2019-06-18 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent |
| JPWO2015108048A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤 |
| US10144933B2 (en) | 2014-01-15 | 2018-12-04 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having immunity induction activity, and immunity induction activator |
| MX2016009290A (es) | 2014-01-16 | 2017-02-28 | Wave Life Sciences Ltd | Diseño quiral. |
| WO2015179693A1 (en) | 2014-05-22 | 2015-11-26 | Isis Pharmaceuticals, Inc. | Conjugated antisense compounds and their use |
| PE20180800A1 (es) * | 2015-07-10 | 2018-05-09 | Ionis Pharmaceuticals Inc | Moduladores de diaciglicerol aciltransferasa 2 (dgat2) |
| IL314925A (en) | 2015-08-18 | 2024-10-01 | Regeneron Pharma | Antibodies against PCSK9 for the treatment of patients with hyperlipidemia undergoing lipoprotein-lowering therapy |
| CN108348541A (zh) | 2015-08-25 | 2018-07-31 | 阿尔尼拉姆医药品有限公司 | 用于治疗前蛋白转化酶枯草杆菌蛋白酶kexin(pcsk9)基因相关障碍的方法和组合物 |
| CN109661233A (zh) | 2016-10-06 | 2019-04-19 | Ionis 制药公司 | 缀合低聚化合物的方法 |
| AU2017368050A1 (en) | 2016-11-29 | 2019-06-20 | Puretech Lyt, Inc. | Exosomes for delivery of therapeutic agents |
| JOP20190215A1 (ar) | 2017-03-24 | 2019-09-19 | Ionis Pharmaceuticals Inc | مُعدّلات التعبير الوراثي عن pcsk9 |
| CA3097585A1 (en) * | 2018-04-18 | 2019-10-24 | Dicerna Pharmaceuticals, Inc. | Pcsk9 targeting oligonucleotides for treating hypercholesterolemia and related conditions |
| US20210355497A1 (en) | 2018-05-09 | 2021-11-18 | Ionis Pharmaceuticals, Inc. | Compounds and methods for reducing fxi expression |
| KR20180087217A (ko) | 2018-07-20 | 2018-08-01 | 주식회사 유진바이오텍 | 귀리산화 베타-글루칸을 유효성분으로 포함하는 비만, 이상지방혈증(dyslipidemia) 또는 지방간의 예방 또는 치료용 조성물 |
| WO2024229020A2 (en) * | 2023-05-01 | 2024-11-07 | Chroma Medicine, Inc. | Compositions and methods for epigenetic regulation of pcsk9 expression |
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|---|---|---|---|---|
| US604360A (en) * | 1898-05-24 | Safety device for elevators | ||
| US5023243A (en) * | 1981-10-23 | 1991-06-11 | Molecular Biosystems, Inc. | Oligonucleotide therapeutic agent and method of making same |
| US5118800A (en) * | 1983-12-20 | 1992-06-02 | California Institute Of Technology | Oligonucleotides possessing a primary amino group in the terminal nucleotide |
| FR2567892B1 (fr) * | 1984-07-19 | 1989-02-17 | Centre Nat Rech Scient | Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons |
| US5591722A (en) * | 1989-09-15 | 1997-01-07 | Southern Research Institute | 2'-deoxy-4'-thioribonucleosides and their antiviral activity |
| DE69033495T2 (de) * | 1989-10-24 | 2000-07-20 | Isis Pharmaceuticals, Inc. | 2'-modifizierte nukleotide |
| US5670633A (en) | 1990-01-11 | 1997-09-23 | Isis Pharmaceuticals, Inc. | Sugar modified oligonucleotides that detect and modulate gene expression |
| US6005087A (en) * | 1995-06-06 | 1999-12-21 | Isis Pharmaceuticals, Inc. | 2'-modified oligonucleotides |
| US5646265A (en) * | 1990-01-11 | 1997-07-08 | Isis Pharmceuticals, Inc. | Process for the preparation of 2'-O-alkyl purine phosphoramidites |
| US5681941A (en) * | 1990-01-11 | 1997-10-28 | Isis Pharmaceuticals, Inc. | Substituted purines and oligonucleotide cross-linking |
| GB9009980D0 (en) | 1990-05-03 | 1990-06-27 | Amersham Int Plc | Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides |
| EP0455905B1 (en) * | 1990-05-11 | 1998-06-17 | Microprobe Corporation | Dipsticks for nucleic acid hybridization assays and methods for covalently immobilizing oligonucleotides |
| US5677437A (en) * | 1990-07-27 | 1997-10-14 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
| KR100211552B1 (ko) * | 1990-08-03 | 1999-08-02 | 디. 꼬쉬 | 유전자 발현 억제용 화합물 및 방법 |
| US6582908B2 (en) * | 1990-12-06 | 2003-06-24 | Affymetrix, Inc. | Oligonucleotides |
| DE59208572D1 (de) * | 1991-10-17 | 1997-07-10 | Ciba Geigy Ag | Bicyclische Nukleoside, Oligonukleotide, Verfahren zu deren Herstellung und Zwischenprodukte |
| TW393513B (en) * | 1991-11-26 | 2000-06-11 | Isis Pharmaceuticals Inc | Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines |
| US5359044A (en) * | 1991-12-13 | 1994-10-25 | Isis Pharmaceuticals | Cyclobutyl oligonucleotide surrogates |
| FR2687679B1 (fr) * | 1992-02-05 | 1994-10-28 | Centre Nat Rech Scient | Oligothionucleotides. |
| US5633360A (en) * | 1992-04-14 | 1997-05-27 | Gilead Sciences, Inc. | Oligonucleotide analogs capable of passive cell membrane permeation |
| EP0577558A2 (de) * | 1992-07-01 | 1994-01-05 | Ciba-Geigy Ag | Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte |
| WO1994001093A1 (en) | 1992-07-09 | 1994-01-20 | Merck & Co., Inc. | Controlled porosity osmotic enalapril pump |
| US5652355A (en) * | 1992-07-23 | 1997-07-29 | Worcester Foundation For Experimental Biology | Hybrid oligonucleotide phosphorothioates |
| CA2159631A1 (en) | 1993-03-30 | 1994-10-13 | Sanofi | Acyclic nucleoside analogs and oligonucleotide sequences containing them |
| WO1994022891A1 (en) * | 1993-03-31 | 1994-10-13 | Sterling Winthrop Inc. | Oligonucleotides with amide linkages replacing phosphodiester linkages |
| AU6449294A (en) | 1993-03-31 | 1994-10-24 | Sterling Winthrop Inc. | Novel 5'-substituted nucleosides and oligomers produced therefrom |
| DE4311944A1 (de) * | 1993-04-10 | 1994-10-13 | Degussa | Umhüllte Natriumpercarbonatpartikel, Verfahren zu deren Herstellung und sie enthaltende Wasch-, Reinigungs- und Bleichmittelzusammensetzungen |
| US5801154A (en) * | 1993-10-18 | 1998-09-01 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of multidrug resistance-associated protein |
| US5457187A (en) * | 1993-12-08 | 1995-10-10 | Board Of Regents University Of Nebraska | Oligonucleotides containing 5-fluorouracil |
| US5446137B1 (en) * | 1993-12-09 | 1998-10-06 | Behringwerke Ag | Oligonucleotides containing 4'-substituted nucleotides |
| US5519134A (en) * | 1994-01-11 | 1996-05-21 | Isis Pharmaceuticals, Inc. | Pyrrolidine-containing monomers and oligomers |
| US5627053A (en) * | 1994-03-29 | 1997-05-06 | Ribozyme Pharmaceuticals, Inc. | 2'deoxy-2'-alkylnucleotide containing nucleic acid |
| US5625050A (en) * | 1994-03-31 | 1997-04-29 | Amgen Inc. | Modified oligonucleotides and intermediates useful in nucleic acid therapeutics |
| US5597909A (en) * | 1994-08-25 | 1997-01-28 | Chiron Corporation | Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use |
| US5792747A (en) * | 1995-01-24 | 1998-08-11 | The Administrators Of The Tulane Educational Fund | Highly potent agonists of growth hormone releasing hormone |
| US5567427A (en) * | 1995-03-17 | 1996-10-22 | Helene Curtis, Inc. | Emulsified, low ph cosmetic compositions having improved stability |
| US5673633A (en) * | 1995-05-31 | 1997-10-07 | Pfister; Joel W. | Table leg system |
| US6043060A (en) | 1996-11-18 | 2000-03-28 | Imanishi; Takeshi | Nucleotide analogues |
| JP3756313B2 (ja) | 1997-03-07 | 2006-03-15 | 武 今西 | 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体 |
| US6770748B2 (en) * | 1997-03-07 | 2004-08-03 | Takeshi Imanishi | Bicyclonucleoside and oligonucleotide analogue |
| KR100414936B1 (ko) | 1997-09-12 | 2004-01-13 | 엑시콘 에이/에스 | 이환 및 삼환 뉴클레오시드, 뉴클레오타이드 및올리고뉴클레오타이드 동족체 |
| US6794499B2 (en) * | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
| US20030228597A1 (en) * | 1998-04-13 | 2003-12-11 | Cowsert Lex M. | Identification of genetic targets for modulation by oligonucleotides and generation of oligonucleotides for gene modulation |
| US6043352A (en) * | 1998-08-07 | 2000-03-28 | Isis Pharmaceuticals, Inc. | 2'-O-Dimethylaminoethyloxyethyl-modified oligonucleotides |
| US6410323B1 (en) * | 1999-08-31 | 2002-06-25 | Isis Pharmaceuticals, Inc. | Antisense modulation of human Rho family gene expression |
| NZ513402A (en) * | 1999-02-12 | 2003-06-30 | Sankyo Co | Novel nucleosides and oligonucleotide analogues |
| US7084125B2 (en) * | 1999-03-18 | 2006-08-01 | Exiqon A/S | Xylo-LNA analogues |
| PT1178999E (pt) * | 1999-05-04 | 2007-06-26 | Santaris Pharma As | Análogos de l-ribo-lna |
| US6525191B1 (en) * | 1999-05-11 | 2003-02-25 | Kanda S. Ramasamy | Conformationally constrained L-nucleosides |
| JP4151751B2 (ja) * | 1999-07-22 | 2008-09-17 | 第一三共株式会社 | 新規ビシクロヌクレオシド類縁体 |
| US7053199B2 (en) * | 2000-08-29 | 2006-05-30 | Takeshi Imanishi | Nucleoside analogs and oligonucleotide derivatives containing these analogs |
| US6426220B1 (en) | 2000-10-30 | 2002-07-30 | Isis Pharmaceuticals, Inc. | Antisense modulation of calreticulin expression |
| CA2452458A1 (en) | 2001-07-03 | 2003-01-16 | Isis Pharmaceuticals, Inc. | Nuclease resistant chimeric oligonucleotides |
| US7407943B2 (en) * | 2001-08-01 | 2008-08-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein B expression |
| WO2003020739A2 (en) * | 2001-09-04 | 2003-03-13 | Exiqon A/S | Novel lna compositions and uses thereof |
| ES2649817T3 (es) * | 2002-04-05 | 2018-01-15 | Roche Innovation Center Copenhagen A/S | Compuestos oligom¿¿ricos para la modulaci¿®n de la expresi¿®n de HIF-1¿Á |
| US7569575B2 (en) * | 2002-05-08 | 2009-08-04 | Santaris Pharma A/S | Synthesis of locked nucleic acid derivatives |
| US20040219565A1 (en) * | 2002-10-21 | 2004-11-04 | Sakari Kauppinen | Oligonucleotides useful for detecting and analyzing nucleic acids of interest |
| CA2504694C (en) * | 2002-11-05 | 2013-10-01 | Isis Pharmaceuticals, Inc. | Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation |
| US7511131B2 (en) * | 2002-11-13 | 2009-03-31 | Genzyme Corporation | Antisense modulation of apolipoprotein B expression |
| DK2284266T3 (da) * | 2002-11-14 | 2014-01-13 | Thermo Fisher Scient Biosciences Inc | sIRNA-MOLEKYLE MOD TP53 |
| US7655785B1 (en) * | 2002-11-14 | 2010-02-02 | Rosetta Genomics Ltd. | Bioinformatically detectable group of novel regulatory oligonucleotides and uses thereof |
| DK2752488T3 (da) * | 2002-11-18 | 2020-04-20 | Roche Innovation Ct Copenhagen As | Antisense-design |
| JP2004357715A (ja) * | 2003-01-21 | 2004-12-24 | Research Association For Biotechnology | 全長ｃＤＮＡ |
| EP1471152A1 (en) * | 2003-04-25 | 2004-10-27 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Mutations in the human PCSK9 gene associated to hypercholesterolemia |
| JP2005060664A (ja) | 2003-07-31 | 2005-03-10 | Asahi Glass Co Ltd | 含フッ素化合物、含フッ素ポリマーとその製造方法およびそれを含むレジスト組成物 |
| JP4731324B2 (ja) * | 2003-08-28 | 2011-07-20 | 武 今西 | Ｎ−ｏ結合性架橋構造型新規人工核酸 |
| CA2568735A1 (en) | 2004-06-03 | 2005-12-22 | Isis Pharmaceuticals, Inc. | Double strand compositions comprising differentially modified strands for use in gene modulation |
| CA2875436A1 (en) * | 2004-07-02 | 2006-08-17 | Sarepta Therapeutics, Inc. | Antisense antibacterial method and compound |
| WO2006126040A1 (en) | 2005-05-25 | 2006-11-30 | Rosetta Genomics Ltd. | Bacterial and bacterial associated mirnas and uses thereof |
| US20070068404A1 (en) | 2005-09-29 | 2007-03-29 | Edwin Hirahara | Systems and methods for additive deposition of materials onto a substrate |
| JP5128796B2 (ja) | 2006-01-20 | 2013-01-23 | Ｇ＆Ｇサイエンス株式会社 | 脳血管障害の遺伝的リスク検出法 |
| ES2516815T3 (es) * | 2006-01-27 | 2014-10-31 | Isis Pharmaceuticals, Inc. | Análogos de ácidos nucleicos bicíclicos modificados en la posición 6 |
| WO2007136989A2 (en) | 2006-05-05 | 2007-11-29 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating expression of dgat2 |
| SG171676A1 (en) * | 2006-05-11 | 2011-06-29 | Alnylam Pharmaceuticals Inc | Compositions and methods for inhibiting expression of the pcsk9 gene |
| US7572618B2 (en) * | 2006-06-30 | 2009-08-11 | Bristol-Myers Squibb Company | Polynucleotides encoding novel PCSK9 variants |
| AU2007275365A1 (en) | 2006-07-17 | 2008-01-24 | Sirna Therapeutics Inc. | RNA interference mediated inhibition of Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene expression using short interfering nucleic acid (siNA) |
| MX2009003729A (es) | 2006-10-09 | 2009-04-22 | Santaris Pharma As | Copuestos antagonistas de acido ribonucleico para la modulacion de proproteina convertasa subtilisina/kexina tipo 9a. |
| WO2008043561A2 (en) | 2006-10-11 | 2008-04-17 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Influenza targets |
| JP2010510807A (ja) | 2006-11-27 | 2010-04-08 | アイシス ファーマシューティカルズ， インコーポレーテッド | 高コレステロール血症を治療するための方法 |
| US8093222B2 (en) * | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| WO2008109369A2 (en) | 2007-03-02 | 2008-09-12 | Mdrna, Inc. | Nucleic acid compounds for inhibiting tnf gene expression and uses thereof |
| US20100105134A1 (en) * | 2007-03-02 | 2010-04-29 | Mdrna, Inc. | Nucleic acid compounds for inhibiting gene expression and uses thereof |
| WO2009148605A2 (en) | 2008-06-04 | 2009-12-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
-
2007
- 2007-11-27 JP JP2009539274A patent/JP2010510807A/ja active Pending
- 2007-11-27 AU AU2007325767A patent/AU2007325767A1/en not_active Abandoned
- 2007-11-27 EP EP11192458A patent/EP2455471A3/en not_active Withdrawn
- 2007-11-27 EP EP07862213A patent/EP2102340A2/en not_active Withdrawn
- 2007-11-27 US US12/516,457 patent/US8084437B2/en active Active
- 2007-11-27 WO PCT/US2007/024369 patent/WO2008066776A2/en not_active Ceased
- 2007-11-27 TW TW096145015A patent/TW200838551A/zh unknown
- 2007-11-27 CA CA002670563A patent/CA2670563A1/en not_active Abandoned
- 2007-11-27 EA EA200900741A patent/EA200900741A1/ru unknown
- 2007-11-27 KR KR1020097013295A patent/KR20090103894A/ko not_active Withdrawn
- 2007-11-27 EP EP11192464A patent/EP2453016A1/en not_active Withdrawn
- 2007-11-27 MX MX2009005527A patent/MX2009005527A/es not_active Application Discontinuation
-
2009
- 2009-05-20 IL IL198851A patent/IL198851A0/en unknown
- 2009-06-03 NO NO20092150A patent/NO20092150L/no not_active Application Discontinuation
- 2009-06-26 CO CO09066682A patent/CO6241169A2/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| AU2007325767A2 (en) | 2009-07-09 |
| EP2455471A3 (en) | 2012-09-12 |
| US20100144834A1 (en) | 2010-06-10 |
| EP2455471A2 (en) | 2012-05-23 |
| IL198851A0 (en) | 2011-08-01 |
| JP2010510807A (ja) | 2010-04-08 |
| NO20092150L (no) | 2009-07-31 |
| KR20090103894A (ko) | 2009-10-01 |
| EP2102340A2 (en) | 2009-09-23 |
| US8084437B2 (en) | 2011-12-27 |
| CA2670563A1 (en) | 2008-06-05 |
| EP2453016A1 (en) | 2012-05-16 |
| CO6241169A2 (es) | 2011-01-20 |
| EA200900741A1 (ru) | 2010-04-30 |
| MX2009005527A (es) | 2009-06-08 |
| TW200838551A (en) | 2008-10-01 |
| WO2008066776A2 (en) | 2008-06-05 |
| WO2008066776A3 (en) | 2008-09-25 |
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