ES2603379T3 - Compuestos antagonistas de ARN para la modulación de PCSK9 - Google Patents
Compuestos antagonistas de ARN para la modulación de PCSK9 Download PDFInfo
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- ES2603379T3 ES2603379T3 ES11181596.5T ES11181596T ES2603379T3 ES 2603379 T3 ES2603379 T3 ES 2603379T3 ES 11181596 T ES11181596 T ES 11181596T ES 2603379 T3 ES2603379 T3 ES 2603379T3
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Families Citing this family (71)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007131237A2 (en) | 2006-05-05 | 2007-11-15 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating expression of ptp1b |
| US8093222B2 (en) | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| KR20090103894A (ko) | 2006-11-27 | 2009-10-01 | 아이시스 파마수티컬즈 인코포레이티드 | 고콜레스테롤혈증을 치료하는 방법 |
| US8470791B2 (en) | 2007-03-22 | 2013-06-25 | Santaris Pharma A/S | RNA antagonist compounds for the inhibition of Apo-B100 expression |
| EP2198024A2 (en) * | 2007-08-30 | 2010-06-23 | Santaris Pharma A/S | Rna antagonist compounds for the modulation of fabp4/ap2 |
| US20110224280A1 (en) * | 2008-04-16 | 2011-09-15 | Niels Fisker Nielsen | Pharmaceutical Composition Comprising Anti PCSK9 Oligomers |
| EP2285399A2 (en) * | 2008-05-22 | 2011-02-23 | Schering Corporation | Egf-a domain-mediated modulation of pcsk9 for treating lipid disorders |
| WO2009148605A2 (en) * | 2008-06-04 | 2009-12-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| EP2456870A1 (en) | 2009-07-21 | 2012-05-30 | Santaris Pharma A/S | Antisense oligomers targeting pcsk9 |
| US9364495B2 (en) | 2009-10-20 | 2016-06-14 | Roche Innovation Center Copenhagen A/S | Oral delivery of therapeutically effective LNA oligonucleotides |
| GB2481373A (en) * | 2010-06-21 | 2011-12-28 | Weiming Xu | Treatment of hypercholesterolaemia by ubiquitination of PCSK9 |
| WO2012029870A1 (ja) * | 2010-08-31 | 2012-03-08 | 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 |
| EP2638163B1 (en) | 2010-11-12 | 2017-05-17 | The General Hospital Corporation | Polycomb-associated non-coding rnas |
| EP3521451A1 (en) | 2010-11-17 | 2019-08-07 | Ionis Pharmaceuticals, Inc. | Modulation of alpha synuclein expression |
| US8911729B2 (en) | 2011-01-10 | 2014-12-16 | The Regents Of The University Of Michigan | Stem cell factor inhibitor |
| WO2013001372A2 (en) | 2011-06-30 | 2013-01-03 | University Of Oslo | Methods and compositions for inhibition of activation of regulatory t cells |
| LT2729173T (lt) | 2011-07-06 | 2016-10-10 | Sykehuset Sorlandet Hf | Egfr taikinių terapija |
| EP2756080B1 (en) | 2011-09-14 | 2019-02-20 | Translate Bio MA, Inc. | Multimeric oligonucleotide compounds |
| ES2707232T3 (es) | 2011-12-16 | 2019-04-03 | Univ Nat Corp Tokyo Medical & Dental | Acido nucleico bicatenario quimérico |
| US9255154B2 (en) | 2012-05-08 | 2016-02-09 | Alderbio Holdings, Llc | Anti-PCSK9 antibodies and use thereof |
| CN104583398A (zh) | 2012-05-16 | 2015-04-29 | Rana医疗有限公司 | 用于调节基因表达的组合物和方法 |
| WO2013184209A1 (en) | 2012-06-04 | 2013-12-12 | Ludwig Institute For Cancer Research Ltd. | Mif for use in methods of treating subjects with a neurodegenerative disorder |
| 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 |
| EP2906696B2 (en) | 2012-10-15 | 2022-12-14 | Ionis Pharmaceuticals, Inc. | Methods for modulating c9orf72 expression |
| EP2906697A4 (en) | 2012-10-15 | 2016-06-22 | Ionis Pharmaceuticals Inc | METHOD FOR MONITORING THE C9ORF72 EXPRESSION |
| RU2730677C2 (ru) | 2012-10-15 | 2020-08-24 | Ионис Фармасьютикалз, Инк. | Соединение для модуляции экспрессии гена c9orf72 и его применение |
| US10058630B2 (en) | 2012-10-22 | 2018-08-28 | Concievalve, Llc | Methods for inhibiting stenosis, obstruction, or calcification of a stented heart valve or bioprosthesis |
| CA2889044A1 (en) | 2012-11-15 | 2014-05-22 | Roche Innovation Center Copenhagen A/S | Anti apob antisense conjugate compounds |
| US20150320861A1 (en) | 2012-12-21 | 2015-11-12 | Sykehuset Sørlandet Hf | Egfr targeted therapy of neurological disorders and pain |
| MX2015009056A (es) | 2013-01-30 | 2015-10-05 | Hoffmann La Roche | Conjugados de oligonucleotidos de acido nucleico bloqueado y carbohidratos. |
| US20160108395A1 (en) | 2013-03-01 | 2016-04-21 | National University Corporation Tokyo Medical And Dental University | Chimeric single-stranded antisense polynucleotides and double-stranded antisense agent |
| CA2913499A1 (en) | 2013-05-30 | 2014-12-04 | National University Corporation Tokyo Medical And Dental University | Double-stranded agents for delivering therapeutic oligonucleotides |
| CN105324119A (zh) | 2013-06-16 | 2016-02-10 | 国立大学法人东京医科齿科大学 | 具有外显子跳跃效应的双链反义核酸 |
| MX391977B (es) * | 2013-06-27 | 2025-03-21 | Roche Innovation Ct Copenhagen As | Oligómeros antisentido y conjugados con diana en la proteína-convertasa subtilisina/kexina tipo 9(pcsk9). |
| WO2015006554A1 (en) | 2013-07-10 | 2015-01-15 | The Regents Of The University Of Michigan | Therapeutic antibodies and uses thereof |
| BR112016007751A2 (pt) | 2013-10-11 | 2017-09-12 | Ionis Pharmaceuticals Inc | composições para modulação de expressão de c9orf72 |
| EP3760208B1 (en) | 2014-06-25 | 2024-05-29 | The General Hospital Corporation | Targeting human satellite ii (hsatii) |
| AU2016235662B2 (en) * | 2015-03-20 | 2020-07-30 | Aarhus Universitet | Inhibitors of PCSK9 for treatment of lipoprotein metabolism disorders |
| CN107635512A (zh) * | 2015-04-15 | 2018-01-26 | 康斯瓦维有限责任公司 | 用于抑制天然心脏瓣膜、被支撑的心脏瓣膜或生物假体的狭窄、阻塞或钙化的装置和方法 |
| MX366128B (es) | 2015-04-16 | 2019-06-28 | Ionis Pharmaceuticals Inc | Composiciones para modular la expresion de c90rf72. |
| US11260073B2 (en) | 2015-11-02 | 2022-03-01 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating C90RF72 |
| US11384112B2 (en) | 2016-02-17 | 2022-07-12 | Tokyo Institute Of Technology | Artificial nucleoside and artificial nucleotide, and artificial oligonucleotide |
| US11260134B2 (en) | 2016-09-29 | 2022-03-01 | National University Corporation Tokyo Medical And Dental University | Double-stranded nucleic acid complex having overhang |
| US11572558B2 (en) | 2017-02-06 | 2023-02-07 | Nissan Chemical Corporation | Single-stranded oligonucleotide |
| JP6952366B2 (ja) * | 2017-05-26 | 2021-10-20 | 国立研究開発法人国立循環器病研究センター | Pcsk9を標的としたアンチセンス核酸 |
| WO2019004420A1 (ja) | 2017-06-30 | 2019-01-03 | 国立大学法人東京医科歯科大学 | ヘテロ二本鎖型antimiR |
| CN110997918A (zh) | 2017-07-26 | 2020-04-10 | 日产化学株式会社 | 单链寡核苷酸 |
| WO2019167995A1 (ja) | 2018-02-28 | 2019-09-06 | 国立大学法人東京医科歯科大学 | 虚血病変部位特異的な遺伝子治療法 |
| EP3766972B1 (en) | 2018-03-14 | 2025-04-23 | Institute of Science Tokyo | Nucleic acid complex |
| WO2019181946A1 (ja) | 2018-03-19 | 2019-09-26 | 国立大学法人東京医科歯科大学 | 毒性が軽減した核酸 |
| CA3094303A1 (en) | 2018-03-20 | 2019-09-26 | Tokyo Institute Of Technology | Antisense oligonucleotide reduced in toxicity |
| JP7262816B2 (ja) | 2018-03-22 | 2023-04-24 | 国立大学法人 東京医科歯科大学 | ヘテロ核酸のbbb通過脂質リガンド |
| EP3831408A4 (en) | 2018-07-27 | 2021-11-17 | Osaka University | COMPOSITION TO INHIBIT AGING, PREVENT, IMPROVE, OR TREAT AGE-RELATED DISEASES, OR EXTEND LIFE |
| US12492399B2 (en) | 2019-03-14 | 2025-12-09 | Rena Therapeutics Inc. | Nucleic acid complex for regulating IHH expression |
| WO2020209285A1 (ja) | 2019-04-08 | 2020-10-15 | 国立大学法人東京医科歯科大学 | 筋疾患治療用医薬組成物 |
| JP7737667B2 (ja) | 2019-09-18 | 2025-09-11 | 国立大学法人東京科学大学 | 核酸複合体 |
| US20240117346A1 (en) | 2019-10-11 | 2024-04-11 | National University Corporation Tokyo Medical And Dental University | Modified hetero nucleic acids |
| CA3169474A1 (en) | 2020-01-31 | 2021-08-05 | Sanwa Kagaku Kenkyusho Co., Ltd. | Antisense oligonucleotide of atn1 |
| JPWO2021177418A1 (OSRAM) | 2020-03-04 | 2021-09-10 | ||
| US20230174981A1 (en) | 2020-03-16 | 2023-06-08 | National University Corporation Tokyo Medical And Dental University | Heteronucleic acid containing morpholino nucleic acid |
| IL304048A (en) | 2020-12-31 | 2023-08-01 | Dyne Therapeutics Inc | Muscle targeting complexes and uses thereof for treating myotonic dystrophy |
| US20240240183A1 (en) | 2021-05-25 | 2024-07-18 | National University Corporation Tokyo Medical And Dental University | Heteronucleic acid containing scpBNA or AmNA |
| CA3222167A1 (en) | 2021-05-31 | 2022-12-08 | Rena Therapeutics Inc. | Ligand-binding nucleic acid complex |
| JPWO2023022229A1 (OSRAM) | 2021-08-19 | 2023-02-23 | ||
| US20240390508A1 (en) | 2021-08-21 | 2024-11-28 | Takeda Pharmaceutical Company Limited | Human transferrin receptor binding peptide-drug conjugate |
| EP4403191A1 (en) | 2021-09-15 | 2024-07-24 | National University Corporation Tokyo Medical and Dental University | Heteronucleic acid including 2'-modified nucleoside |
| WO2023080159A1 (ja) | 2021-11-02 | 2023-05-11 | レナセラピューティクス株式会社 | リガンド結合核酸複合体 |
| CN120659627A (zh) | 2022-07-29 | 2025-09-16 | 瑞泽恩制药公司 | 用于转铁蛋白受体(tfr)介导的脑和肌肉递送的组合物和方法 |
| JPWO2024071099A1 (OSRAM) | 2022-09-29 | 2024-04-04 | ||
| US20240182561A1 (en) | 2022-11-04 | 2024-06-06 | Regeneron Pharmaceuticals, Inc. | Calcium voltage-gated channel auxiliary subunit gamma 1 (cacng1) binding proteins and cacng1-mediated delivery to skeletal muscle |
| JP2025538220A (ja) | 2022-11-14 | 2025-11-26 | 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 | アストロサイトへの線維芽細胞増殖因子受容体3媒介送達のための組成物および方法 |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3719766A1 (de) * | 1987-06-13 | 1988-12-22 | Heidelberger Druckmasch Ag | Registermesssystem |
| US4914210A (en) * | 1987-10-02 | 1990-04-03 | Cetus Corporation | Oligonucleotide functionalizing reagents |
| US6433159B1 (en) * | 1992-09-10 | 2002-08-13 | Isis Pharmaceuticals, Inc. | Compositions and methods for treatment of Hepatitis C virus associated diseases |
| US6423489B1 (en) * | 1992-09-10 | 2002-07-23 | Isis Pharmaceuticals, Inc. | Compositions and methods for treatment of Hepatitis C virus-associated diseases |
| AU680435B2 (en) * | 1992-09-10 | 1997-07-31 | Isis Pharmaceuticals, Inc. | Compositions and methods for treatment of hepatitis C virus-associated diseases |
| DK0832069T3 (da) * | 1995-06-07 | 2003-04-22 | Pfizer | Biphenyl-2-carboxylsyre-tetrahydroisoquinolin-6-ylamidderivater, deres fremstilling og deres anvendelse som inhibitorer af sekretion af mikrosomalt triglyceridoverførselsprotein og/eller apolipoprotein B (Apo B) |
| EP0944602A1 (en) * | 1996-11-27 | 1999-09-29 | Pfizer Inc. | Apo b-secretion/mtp inhibitory amides |
| PL335721A1 (en) * | 1997-03-05 | 2000-05-08 | Ribogene | Novel methods of screening serving the purpose of identifying the factors of selective hepatitis c virus replication inhibition |
| US6410323B1 (en) * | 1999-08-31 | 2002-06-25 | Isis Pharmaceuticals, Inc. | Antisense modulation of human Rho family gene expression |
| US7029895B2 (en) * | 1999-09-27 | 2006-04-18 | Millennium Pharmaceuticals, Inc. | 27411, a novel human PGP synthase |
| US6617442B1 (en) | 1999-09-30 | 2003-09-09 | Isis Pharmaceuticals, Inc. | Human Rnase H1 and oligonucleotide compositions thereof |
| WO2001057081A2 (en) | 2000-02-07 | 2001-08-09 | Millennium Pharmaceuticals, Inc. | Narc-1, subtilase-like homologs |
| US7407943B2 (en) | 2001-08-01 | 2008-08-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein B expression |
| PT2264172T (pt) * | 2002-04-05 | 2017-12-06 | Roche Innovation Ct Copenhagen As | Compostos oligoméricos para a modulação da expressão do hif-1α. |
| WO2003097662A1 (en) | 2002-05-15 | 2003-11-27 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein b expression |
| US7183302B2 (en) * | 2002-08-12 | 2007-02-27 | Bristol-Myers Squibb Company | Iminothiazolidinones as inhibitors of HCV replication |
| US7087229B2 (en) * | 2003-05-30 | 2006-08-08 | Enzon Pharmaceuticals, Inc. | Releasable polymeric conjugates based on aliphatic biodegradable linkers |
| WO2004044181A2 (en) | 2002-11-13 | 2004-05-27 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein b expression |
| DK2284269T3 (en) | 2002-11-18 | 2017-10-23 | Roche Innovation Ct Copenhagen As | Antisense design |
| FR2848572B1 (fr) * | 2002-12-12 | 2005-12-09 | Univ Joseph Fourier | Molecules inhibitrices de la synthese proteique du virus de l'hepatite c et procede de criblage desdites molecules inhibitrices |
| 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 |
| EP1648914A4 (en) * | 2003-07-31 | 2009-12-16 | Regulus Therapeutics Inc | OLIGOMERIC COMPOUNDS AND COMPOSITIONS USEFUL FOR MODULATING SMALL NON-CODING RNA |
| EP1713912B1 (en) | 2004-01-30 | 2013-09-18 | Santaris Pharma A/S | Modified short interfering rna (modified sirna) |
| ES2663810T3 (es) * | 2004-08-10 | 2018-04-17 | Kastle Therapeutics, Llc | Métodos para modular los niveles de lipoproteínas y colesterol en humanos |
| US20060185027A1 (en) * | 2004-12-23 | 2006-08-17 | David Bartel | Systems and methods for identifying miRNA targets and for altering miRNA and target expression |
| WO2008011431A2 (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) |
-
2007
- 2007-10-09 CA CA2666191A patent/CA2666191C/en active Active
- 2007-10-09 EP EP07821072A patent/EP2076597A2/en not_active Withdrawn
- 2007-10-09 JP JP2009531824A patent/JP2010505432A/ja not_active Withdrawn
- 2007-10-09 WO PCT/EP2007/060703 patent/WO2008043753A2/en not_active Ceased
- 2007-10-09 AU AU2007306361A patent/AU2007306361A1/en not_active Abandoned
- 2007-10-09 MX MX2009003729A patent/MX2009003729A/es not_active Application Discontinuation
- 2007-10-09 US US12/444,806 patent/US20100216864A1/en not_active Abandoned
- 2007-10-09 ES ES11181596.5T patent/ES2603379T3/es active Active
- 2007-10-09 EP EP11181596.5A patent/EP2444494B1/en active Active
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2009
- 2009-03-18 IL IL197668A patent/IL197668A0/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| MX2009003729A (es) | 2009-04-22 |
| CA2666191A1 (en) | 2008-04-17 |
| AU2007306361A1 (en) | 2008-04-17 |
| EP2444494B1 (en) | 2016-09-28 |
| IL197668A0 (en) | 2011-08-01 |
| EP2076597A2 (en) | 2009-07-08 |
| WO2008043753A8 (en) | 2008-06-26 |
| US20100216864A1 (en) | 2010-08-26 |
| JP2010505432A (ja) | 2010-02-25 |
| EP2444494A1 (en) | 2012-04-25 |
| WO2008043753A2 (en) | 2008-04-17 |
| WO2008043753A3 (en) | 2008-09-25 |
| CA2666191C (en) | 2017-07-11 |
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