JP2010503382A5 - - Google Patents
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- JP2010503382A5 JP2010503382A5 JP2009520964A JP2009520964A JP2010503382A5 JP 2010503382 A5 JP2010503382 A5 JP 2010503382A5 JP 2009520964 A JP2009520964 A JP 2009520964A JP 2009520964 A JP2009520964 A JP 2009520964A JP 2010503382 A5 JP2010503382 A5 JP 2010503382A5
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- 125000003729 nucleotide group Chemical group 0.000 claims description 155
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- NAGJZTKCGNOGPW-UHFFFAOYSA-N dithiophosphoric acid Chemical class OP(O)(S)=S NAGJZTKCGNOGPW-UHFFFAOYSA-N 0.000 description 2
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/487,788 US20070173473A1 (en) | 2001-05-18 | 2006-07-17 | RNA interference mediated inhibition of proprotein convertase subtilisin Kexin 9 (PCSK9) gene expression using short interfering nucleic acid (siNA) |
| US86136906P | 2006-11-28 | 2006-11-28 | |
| PCT/US2007/073723 WO2008011431A2 (en) | 2006-07-17 | 2007-07-17 | Rna interference mediated inhibition of proprotein convertase subtilisin kexin 9 (pcsk9) gene expression using short interfering nucleic acid (sina) |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2010503382A JP2010503382A (ja) | 2010-02-04 |
| JP2010503382A5 true JP2010503382A5 (OSRAM) | 2010-03-25 |
Family
ID=38957565
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009520964A Withdrawn JP2010503382A (ja) | 2006-07-17 | 2007-07-17 | 低分子干渉核酸（ｓｉＮＡ）を用いたプロタンパク質転換酵素サブチリシンケクシン９（ＰＣＳＫ９）遺伝子発現のＲＮＡ干渉媒介性阻害 |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP2052079A2 (OSRAM) |
| JP (1) | JP2010503382A (OSRAM) |
| CN (1) | CN102124107A (OSRAM) |
| AU (1) | AU2007275365A1 (OSRAM) |
| CA (1) | CA2658183A1 (OSRAM) |
| WO (1) | WO2008011431A2 (OSRAM) |
Families Citing this family (62)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7935812B2 (en) | 2002-02-20 | 2011-05-03 | Merck Sharp & Dohme Corp. | RNA interference mediated inhibition of hepatitis C virus (HCV) expression using short interfering nucleic acid (siNA) |
| WO2007086883A2 (en) | 2005-02-14 | 2007-08-02 | Sirna Therapeutics, Inc. | Cationic lipids and formulated molecular compositions containing them |
| US7404969B2 (en) * | 2005-02-14 | 2008-07-29 | Sirna Therapeutics, Inc. | Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules |
| WO2007134161A2 (en) * | 2006-05-11 | 2007-11-22 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the pcsk9 gene |
| CA2666191C (en) * | 2006-10-09 | 2017-07-11 | Santaris Pharma A/S | Rna antagonist compounds for the modulation of pcsk9 |
| EP2455471A3 (en) * | 2006-11-27 | 2012-09-12 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| US8093222B2 (en) | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| 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 |
| WO2009114475A2 (en) * | 2008-03-09 | 2009-09-17 | Intradigm Corporation | Compositions comprising human pcsk9 and apolipoprotein b sirna and methods of use |
| US20110224280A1 (en) * | 2008-04-16 | 2011-09-15 | Niels Fisker Nielsen | Pharmaceutical Composition Comprising Anti PCSK9 Oligomers |
| CA2635187A1 (en) | 2008-06-05 | 2009-12-05 | The Royal Institution For The Advancement Of Learning/Mcgill University | Oligonucleotide duplexes and uses thereof |
| US8790664B2 (en) | 2008-09-05 | 2014-07-29 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Multimodular assembly useful for intracellular delivery |
| US9051567B2 (en) | 2009-06-15 | 2015-06-09 | Tekmira Pharmaceuticals Corporation | Methods for increasing efficacy of lipid formulated siRNA |
| NZ597504A (en) * | 2009-06-15 | 2013-10-25 | Alnylam Pharmaceuticals Inc | Lipid formulated dsrna targeting the pcsk9 gene |
| US8563528B2 (en) | 2009-07-21 | 2013-10-22 | Santaris Pharma A/S | Antisense oligomers targeting PCSK9 |
| US9187746B2 (en) | 2009-09-22 | 2015-11-17 | Alnylam Pharmaceuticals, Inc. | Dual targeting siRNA agents |
| SG181904A1 (en) * | 2009-12-23 | 2012-07-30 | Novartis Ag | Lipids, lipid compositions, and methods of using them |
| WO2012138416A1 (en) * | 2011-04-08 | 2012-10-11 | Bio-Rad Laboratories, Inc. | Pcr reaction mixtures with decreased non-specific activity |
| DK3366775T4 (da) * | 2011-11-18 | 2025-10-27 | Alnylam Pharmaceuticals Inc | Modificerede rnai-midler |
| JP6002382B2 (ja) * | 2011-12-07 | 2016-10-05 | 株式会社バイオシンクタンク | 遺伝子発現阻害剤及び阻害方法 |
| ES2552371T3 (es) * | 2012-05-25 | 2015-11-27 | Zora Biosciences Oy | Biomarcadores sensibles, eficaces e inocuos, para la inhibición de la Proproteína Convertasa Subtilisina/Kexina de tipo 9 (PCSK9) |
| CN104854242B (zh) | 2012-12-05 | 2018-03-16 | 阿尔尼拉姆医药品有限公司 | PCSK9 iRNA组合物及其使用方法 |
| SG10201908122XA (en) | 2013-06-27 | 2019-10-30 | Roche Innovation Ct Copenhagen As | Antisense oligomers and conjugates targeting pcsk9 |
| US9034332B1 (en) | 2014-07-15 | 2015-05-19 | Kymab Limited | Precision medicine by targeting rare human PCSK9 variants for cholesterol treatment |
| US8883157B1 (en) | 2013-12-17 | 2014-11-11 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
| FR3014695A1 (OSRAM) * | 2013-12-17 | 2015-06-19 | Kymab Ltd | |
| US9023359B1 (en) | 2014-07-15 | 2015-05-05 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
| US9051378B1 (en) | 2014-07-15 | 2015-06-09 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
| US9045548B1 (en) | 2014-07-15 | 2015-06-02 | Kymab Limited | Precision Medicine by targeting rare human PCSK9 variants for cholesterol treatment |
| US9914769B2 (en) | 2014-07-15 | 2018-03-13 | Kymab Limited | Precision medicine for cholesterol treatment |
| US9139648B1 (en) | 2014-07-15 | 2015-09-22 | Kymab Limited | Precision medicine by targeting human NAV1.9 variants for treatment of pain |
| GB2537614A (en) * | 2015-04-20 | 2016-10-26 | Heart Biotech Ltd | Formulations for inhibition of PCSK9 for the treatment of hypercholesterolemia |
| KR20250107273A (ko) * | 2015-05-06 | 2025-07-11 | 알닐람 파마슈티칼스 인코포레이티드 | 인자 ＸＩＩ(하게만 인자)(Ｆ12), 칼리크레인 Ｂ, 혈장(플레처 인자) 1(ＫＬＫＢ1) 및 키니노겐 1(ＫＮＧ1) ｉＲＮＡ 조성물 및 그의 이용 방법 |
| KR102793532B1 (ko) | 2015-08-25 | 2025-04-14 | 알닐람 파마슈티칼스 인코포레이티드 | 전구단백질 컨버타제 서브틸리신 켁신 (pcsk9) 유전자-관련 장애를 치료하기 위한 방법 및 조성물 |
| MX2018009090A (es) * | 2016-01-26 | 2019-03-28 | Nissan Chemical Corp | Oligonucleótido de cadena simple. |
| CN109312341B (zh) * | 2016-03-07 | 2024-02-27 | 美国政府(由卫生和人类服务部的部长所代表) | 微小rna及其使用方法 |
| EP3440463B1 (en) * | 2016-04-05 | 2020-07-08 | Université de Strasbourg | Intra-droplet surface engineering to capture a molecular target |
| US11260134B2 (en) | 2016-09-29 | 2022-03-01 | National University Corporation Tokyo Medical And Dental University | Double-stranded nucleic acid complex having overhang |
| CA3081910A1 (en) * | 2017-11-13 | 2019-05-16 | Silence Therapeutics Gmbh | Nucleic acids for inhibiting expression of a target gene comprising phosphorodithioate linkages |
| AU2018374219C1 (en) | 2017-12-01 | 2023-05-11 | Suzhou Ribo Life Science Co., Ltd. | Double-stranded oligonucleotide, composition and conjugate comprising double-stranded oligonucleotide, preparation method therefor and use thereof |
| JP7365052B2 (ja) | 2017-12-01 | 2023-10-19 | スーチョウ リボ ライフ サイエンス カンパニー、リミテッド | 核酸、当該核酸を含む組成物及び複合体ならびに調製方法と使用 |
| US11414661B2 (en) | 2017-12-01 | 2022-08-16 | Suzhou Ribo Life Science Co., Ltd. | Nucleic acid, composition and conjugate containing nucleic acid, preparation method therefor and use thereof |
| EP3718572B1 (en) | 2017-12-01 | 2024-07-31 | Suzhou Ribo Life Science Co., Ltd. | Nucleic acid, composition and conjugate containing nucleic acid, preparation method and use |
| KR102834361B1 (ko) | 2017-12-01 | 2025-07-17 | 쑤저우 리보 라이프 사이언스 컴퍼니, 리미티드 | 핵산, 이를 포함하는 조성물과 컨쥬게이트, 및 그의 제조 방법과 용도 |
| CN109957565B (zh) * | 2017-12-26 | 2023-04-07 | 广州市锐博生物科技有限公司 | 一种修饰的siRNA分子及其应用 |
| CN109957567B (zh) * | 2017-12-26 | 2022-09-23 | 阿格纳生物制药有限公司 | 一种抑制PCSK9基因表达的siRNA分子及其应用 |
| JP7191101B2 (ja) * | 2017-12-26 | 2022-12-16 | アーゴーナ ファーマシューティカルズ リミテッド | ＰＣＳＫ９遺伝子の発現を抑制するｓｉＲＮＡ分子及びその応用 |
| EP3732185B1 (en) | 2017-12-29 | 2025-02-26 | Suzhou Ribo Life Science Co., Ltd. | Conjugates and preparation and use thereof |
| EP3765611A4 (en) * | 2018-04-18 | 2022-05-04 | Dicerna Pharmaceuticals, Inc. | PCSK9 TARGETED OLIGONUCLEOTIDES FOR THE TREATMENT OF HYPERCHOLESTEROLEMIA AND RELATED DISORDERS |
| EP3842534A4 (en) | 2018-08-21 | 2022-07-06 | Suzhou Ribo Life Science Co., Ltd. | NUCLEIC ACID, COMPOSITION AND CONJUGATE CONTAINING NUCLEIC ACID AND METHOD OF USE THEREOF |
| CN111655297A (zh) | 2018-09-30 | 2020-09-11 | 苏州瑞博生物技术有限公司 | 一种siRNA缀合物及其制备方法和用途 |
| KR20210110839A (ko) | 2018-12-28 | 2021-09-09 | 쑤저우 리보 라이프 사이언스 컴퍼니, 리미티드 | 핵산, 핵산을 함유하는 조성물 및 접합체, 이의 제조 방법 및 용도 |
| CN109666727B (zh) * | 2018-12-29 | 2020-11-06 | 中国药科大学 | 一种高活性抑制pcsk9表达的微小rna的用途 |
| JP7574206B2 (ja) * | 2019-03-20 | 2024-10-28 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | ステロール調節エレメント結合転写因子１（ｓｒｅｂｆ１）阻害剤による上昇した脂質レベルの治療 |
| CN117701564A (zh) * | 2019-05-22 | 2024-03-15 | 苏州瑞博生物技术股份有限公司 | 核酸、药物组合物与缀合物及制备方法和用途 |
| CA3139195A1 (en) | 2019-05-22 | 2020-11-26 | Suzhou Ribo Life Science Co., Ltd. | Nucleic acid, pharmaceutical composition, conjugate, preparation method, and use |
| EP4022061A1 (en) * | 2019-08-27 | 2022-07-06 | Sanofi | Compositions and methods for inhibiting pcsk9 |
| CA3167849A1 (en) | 2020-03-16 | 2021-09-23 | Daniel Mitchell | Antagonist of pcsk9 |
| JP2024528634A (ja) * | 2021-07-16 | 2024-07-30 | スーチョウ リボ ライフ サイエンス カンパニー、リミテッド | 二本鎖オリゴヌクレオチド、二本鎖オリゴヌクレオチドを含む組成物及び複合体並びに調製方法と使用 |
| EP4402263A2 (en) * | 2021-09-14 | 2024-07-24 | Argonaute Rna Limited | Treatment of cardiovascular disease |
| CN117757790A (zh) * | 2022-11-17 | 2024-03-26 | 北京福元医药股份有限公司 | 抑制SCAP基因表达的siRNA、其缀合物和药物组合物及用途 |
| WO2024228030A2 (en) * | 2023-05-04 | 2024-11-07 | Argonaute RNA Limited | Dual silencing |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070173473A1 (en) * | 2001-05-18 | 2007-07-26 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of proprotein convertase subtilisin Kexin 9 (PCSK9) gene expression using short interfering nucleic acid (siNA) |
| US20060148743A1 (en) * | 2001-05-18 | 2006-07-06 | Vasant Jadhav | RNA interference mediated inhibition of histone deacetylase (HDAC) gene expression using short interfering nucleic acid (siNA) |
| ES2761262T3 (es) * | 2003-06-13 | 2020-05-19 | Alnylam Europe Ag | Acido ribonucleico bicatenario con elevada eficacia en un organismo |
| WO2007030937A2 (en) * | 2005-09-16 | 2007-03-22 | Institut De Recherches Cliniques De Montreal/I.R.C.M. | Screening proteinase modulators using a chimeric protein and ski-i proprotein convertase substrates and inhibitors |
| EP2505646A1 (en) * | 2006-05-05 | 2012-10-03 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating expression of CRP |
-
2007
- 2007-07-17 EP EP07813032A patent/EP2052079A2/en not_active Withdrawn
- 2007-07-17 WO PCT/US2007/073723 patent/WO2008011431A2/en not_active Ceased
- 2007-07-17 CA CA002658183A patent/CA2658183A1/en not_active Abandoned
- 2007-07-17 AU AU2007275365A patent/AU2007275365A1/en not_active Abandoned
- 2007-07-17 CN CN2007800269961A patent/CN102124107A/zh active Pending
- 2007-07-17 JP JP2009520964A patent/JP2010503382A/ja not_active Withdrawn
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