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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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 (enExample) | 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| JP2009520964A Withdrawn JP2010503382A (ja) | 2006-07-17 | 2007-07-17 | 低分子干渉核酸(siNA)を用いたプロタンパク質転換酵素サブチリシンケクシン9(PCSK9)遺伝子発現のRNA干渉媒介性阻害 |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 (enExample) |
| JP (1) | JP2010503382A (enExample) |
| CN (1) | CN102124107A (enExample) |
| AU (1) | AU2007275365A1 (enExample) |
| CA (1) | CA2658183A1 (enExample) |
| WO (1) | WO2008011431A2 (enExample) |
Families Citing this family (60)
| 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) |
| US7404969B2 (en) * | 2005-02-14 | 2008-07-29 | Sirna Therapeutics, Inc. | Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules |
| WO2007086883A2 (en) | 2005-02-14 | 2007-08-02 | Sirna Therapeutics, Inc. | Cationic lipids and formulated molecular compositions containing them |
| SG171676A1 (en) * | 2006-05-11 | 2011-06-29 | Alnylam Pharmaceuticals Inc | Compositions and methods for inhibiting expression of the pcsk9 gene |
| 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. |
| 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 |
| EP2245039A4 (en) * | 2008-01-31 | 2012-06-06 | Alnylam Pharmaceuticals Inc | OPTIMIZED METHODS FOR EXPORING DSRNA TO TARGET THE PCSK9 GEN |
| US20110065644A1 (en) * | 2008-03-09 | 2011-03-17 | Intradigm Corporation | Compositions comprising human pcsk9 and apolipoprotein b sirna and methods of use |
| WO2009127680A1 (en) * | 2008-04-16 | 2009-10-22 | Santaris Pharma A/S | 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 |
| 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 |
| WO2011009697A1 (en) | 2009-07-21 | 2011-01-27 | Santaris Pharma A/S | Antisense oligomers targeting pcsk9 |
| WO2011038031A1 (en) | 2009-09-22 | 2011-03-31 | Alnylam Pharmaceuticals, Inc. | Dual targeting sirna agents |
| EP3721943A1 (en) * | 2009-12-23 | 2020-10-14 | Novartis AG | Lipids, lipid compositions and methods of using them |
| EP2694670B1 (en) | 2011-04-08 | 2017-07-19 | Bio-Rad Laboratories, Inc. | Pcr reaction mixtures with decreased non-specific activity |
| KR20250133484A (ko) * | 2011-11-18 | 2025-09-05 | 알닐람 파마슈티칼스 인코포레이티드 | 변형된 RNAi 제제 |
| 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) |
| HUE035887T2 (en) | 2012-12-05 | 2018-05-28 | Alnylam Pharmaceuticals Inc | PCSK9 iRNA preparations and methods for their use |
| DK3013959T3 (da) | 2013-06-27 | 2020-02-17 | Roche Innovation Ct Copenhagen As | Antisense-oligomerer og konjugater målrettet pcsk9 |
| US9051378B1 (en) | 2014-07-15 | 2015-06-09 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
| US9023359B1 (en) | 2014-07-15 | 2015-05-05 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
| US9914769B2 (en) | 2014-07-15 | 2018-03-13 | Kymab Limited | Precision medicine for cholesterol treatment |
| US9045548B1 (en) | 2014-07-15 | 2015-06-02 | Kymab Limited | Precision Medicine by targeting rare human PCSK9 variants for cholesterol treatment |
| US9034332B1 (en) | 2014-07-15 | 2015-05-19 | Kymab Limited | Precision medicine by targeting rare human PCSK9 variants for cholesterol treatment |
| FR3014695A1 (enExample) * | 2013-12-17 | 2015-06-19 | Kymab Ltd | |
| US8883157B1 (en) | 2013-12-17 | 2014-11-11 | Kymab Limited | Targeting rare human PCSK9 variants 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 |
| TWI806034B (zh) * | 2015-05-06 | 2023-06-21 | 美商阿尼拉製藥公司 | 第十二因子(哈格曼因子)(F12)、激肽釋放素B、血漿(夫列契因子)1(KLKB1)及激肽原1(KNG1)iRNA組成物及其使用方法 |
| 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 |
| BR112018015164A2 (pt) * | 2016-01-26 | 2018-12-26 | Nissan Chemical Corp | oligonucleotídeo de fita simples |
| CN117757794A (zh) * | 2016-03-07 | 2024-03-26 | 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 |
| JP7129702B2 (ja) * | 2016-09-29 | 2022-09-02 | 国立大学法人 東京医科歯科大学 | オーバーハングを有する二本鎖核酸複合体 |
| JP7461886B2 (ja) * | 2017-11-13 | 2024-04-04 | サイレンス・セラピューティクス・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 標的遺伝子の発現を抑制するためのジチオリン酸結合を含む核酸 |
| KR102834361B1 (ko) | 2017-12-01 | 2025-07-17 | 쑤저우 리보 라이프 사이언스 컴퍼니, 리미티드 | 핵산, 이를 포함하는 조성물과 컨쥬게이트, 및 그의 제조 방법과 용도 |
| US11414665B2 (en) | 2017-12-01 | 2022-08-16 | Suzhou Ribo Life Science Co., Ltd. | Nucleic acid, composition and conjugate comprising the same, and preparation method 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 |
| WO2019105418A1 (zh) | 2017-12-01 | 2019-06-06 | 苏州瑞博生物技术有限公司 | 双链寡核苷酸、含双链寡核苷酸的组合物与缀合物及制备方法和用途 |
| WO2019126990A1 (zh) * | 2017-12-26 | 2019-07-04 | 广州市锐博生物科技有限公司 | 一种抑制PCSK9基因表达的siRNA分子及其应用 |
| 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 |
| CA3087106A1 (en) | 2017-12-29 | 2019-07-04 | Suzhou Ribo Life Science Co., Ltd. | Conjugates and preparation and use thereof |
| CA3097585A1 (en) * | 2018-04-18 | 2019-10-24 | Dicerna Pharmaceuticals, Inc. | Pcsk9 targeting oligonucleotides for treating hypercholesterolemia and related conditions |
| JP2021533800A (ja) | 2018-08-21 | 2021-12-09 | 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Suzhou Ribo Life Science Co., Ltd. | 核酸、当該核酸を含む薬物組成物及び複合体ならびにその使用 |
| 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 |
| 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 |
| US11504390B2 (en) * | 2019-03-20 | 2022-11-22 | Regeneron Pharmaceuticals, Inc. | Treatment of increased lipid levels with sterol regulatory element binding transcription factor 1 (SREBF1) inhibitors |
| EP3974530A4 (en) * | 2019-05-22 | 2023-07-12 | Suzhou Ribo Life Science Co., Ltd. | NUCLEIC ACID, PHARMACEUTICAL COMPOSITION, CONJUGATE, METHOD FOR PREPARATION AND USE |
| EP4022061A1 (en) * | 2019-08-27 | 2022-07-06 | Sanofi | Compositions and methods for inhibiting pcsk9 |
| WO2021185765A1 (en) | 2020-03-16 | 2021-09-23 | Argonaute RNA Limited | Antagonist of pcsk9 |
| WO2023284763A1 (zh) * | 2021-07-16 | 2023-01-19 | 苏州瑞博生物技术股份有限公司 | 双链寡核苷酸、含双链寡核苷酸的组合物与缀合物及制备方法和用途 |
| JP2024531728A (ja) * | 2021-09-14 | 2024-08-29 | アルゴノート アールエヌエー リミテッド | 心血管疾患の処置 |
| 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) |
| EP2336317B1 (en) * | 2003-06-13 | 2019-09-11 | Alnylam Europe AG | Double-stranded ribonucleic acid with increased effectiveness in an organism |
| US20090130691A1 (en) * | 2005-09-16 | 2009-05-21 | Institut De Recherches Cliniques De Montreal | Screening proteinase modulators using a chimeric protein and ski-i proprotein convertase substrates and inhibitors |
| WO2007136989A2 (en) * | 2006-05-05 | 2007-11-29 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating expression of dgat2 |
-
2007
- 2007-07-17 AU AU2007275365A patent/AU2007275365A1/en not_active Abandoned
- 2007-07-17 CN CN2007800269961A patent/CN102124107A/zh active Pending
- 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 JP JP2009520964A patent/JP2010503382A/ja not_active Withdrawn
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