JP2009536827A5 - - Google Patents
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- JP2009536827A5 JP2009536827A5 JP2009510173A JP2009510173A JP2009536827A5 JP 2009536827 A5 JP2009536827 A5 JP 2009536827A5 JP 2009510173 A JP2009510173 A JP 2009510173A JP 2009510173 A JP2009510173 A JP 2009510173A JP 2009536827 A5 JP2009536827 A5 JP 2009536827A5
- Authority
- JP
- Japan
- Prior art keywords
- dsrna
- sequence
- pcsk9
- cell
- expression
- Prior art date
- Legal status (The legal status 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 status listed.)
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- 125000003729 nucleotide group Chemical group 0.000 claims description 39
- 230000000295 complement effect Effects 0.000 claims description 36
- 230000014509 gene expression Effects 0.000 claims description 30
- 101150094724 PCSK9 gene Proteins 0.000 claims description 28
- 239000002773 nucleotide Substances 0.000 claims description 28
- 101001098868 Homo sapiens Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 claims description 27
- 102100038955 Proprotein convertase subtilisin/kexin type 9 Human genes 0.000 claims description 27
- 230000002401 inhibitory effect Effects 0.000 claims description 14
- 108091081021 Sense strand Proteins 0.000 claims description 12
- 108020004999 messenger RNA Proteins 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 230000000692 anti-sense effect Effects 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 229920002477 rna polymer Polymers 0.000 claims description 8
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 4
- 102000040650 (ribonucleotides)n+m Human genes 0.000 claims description 4
- 101100135844 Homo sapiens PCSK9 gene Proteins 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 208000035657 Abasia Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 3
- 230000001105 regulatory effect Effects 0.000 claims description 3
- 208000037273 Pathologic Processes Diseases 0.000 claims description 2
- 230000015556 catabolic process Effects 0.000 claims description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol group Chemical group [C@@H]1(CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)[C@H](C)CCCC(C)C HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 2
- 238000006731 degradation reaction Methods 0.000 claims description 2
- 230000002222 downregulating effect Effects 0.000 claims description 2
- 238000000338 in vitro Methods 0.000 claims description 2
- 125000001921 locked nucleotide group Chemical group 0.000 claims description 2
- 230000001404 mediated effect Effects 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- ONKSSDKXDIVIHK-UHFFFAOYSA-N n,n-didecyldodecanamide Chemical group CCCCCCCCCCCC(=O)N(CCCCCCCCCC)CCCCCCCCCC ONKSSDKXDIVIHK-UHFFFAOYSA-N 0.000 claims description 2
- 230000009054 pathological process Effects 0.000 claims description 2
- 150000008298 phosphoramidates Chemical class 0.000 claims description 2
- 108091028664 Ribonucleotide Proteins 0.000 description 5
- 239000002336 ribonucleotide Substances 0.000 description 5
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 4
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- 150000004713 phosphodiesters Chemical group 0.000 description 2
- 125000002652 ribonucleotide group Chemical group 0.000 description 2
- YIMATHOGWXZHFX-WCTZXXKLSA-N (2r,3r,4r,5r)-5-(hydroxymethyl)-3-(2-methoxyethoxy)oxolane-2,4-diol Chemical class COCCO[C@H]1[C@H](O)O[C@H](CO)[C@H]1O YIMATHOGWXZHFX-WCTZXXKLSA-N 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US79945806P | 2006-05-11 | 2006-05-11 | |
| US60/799,458 | 2006-05-11 | ||
| US81720306P | 2006-06-27 | 2006-06-27 | |
| US60/817,203 | 2006-06-27 | ||
| US84008906P | 2006-08-25 | 2006-08-25 | |
| US60/840,089 | 2006-08-25 | ||
| US82991406P | 2006-10-18 | 2006-10-18 | |
| US60/829,914 | 2006-10-18 | ||
| US90113407P | 2007-02-13 | 2007-02-13 | |
| US60/901,134 | 2007-02-13 | ||
| PCT/US2007/068655 WO2007134161A2 (en) | 2006-05-11 | 2007-05-10 | Compositions and methods for inhibiting expression of the pcsk9 gene |
Related Child Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010108836A Division JP2010246544A (ja) | 2006-05-11 | 2010-05-10 | Ｐｃｓｋ９遺伝子の発現を阻害するための組成物および方法 |
| JP2014018817A Division JP6034316B2 (ja) | 2006-05-11 | 2014-02-03 | Ｐｃｓｋ９遺伝子の発現を阻害するための組成物および方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2009536827A JP2009536827A (ja) | 2009-10-22 |
| JP2009536827A5 true JP2009536827A5 (enExample) | 2010-07-01 |
| JP5570806B2 JP5570806B2 (ja) | 2014-08-13 |
Family
ID=38694697
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009510173A Expired - Fee Related JP5570806B2 (ja) | 2006-05-11 | 2007-05-10 | Ｐｃｓｋ９遺伝子の発現を阻害するための組成物および方法 |
| JP2010108836A Pending JP2010246544A (ja) | 2006-05-11 | 2010-05-10 | Ｐｃｓｋ９遺伝子の発現を阻害するための組成物および方法 |
| JP2014018817A Expired - Fee Related JP6034316B2 (ja) | 2006-05-11 | 2014-02-03 | Ｐｃｓｋ９遺伝子の発現を阻害するための組成物および方法 |
| JP2015226712A Pending JP2016027830A (ja) | 2006-05-11 | 2015-11-19 | Ｐｃｓｋ９遺伝子の発現を阻害するための組成物および方法 |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010108836A Pending JP2010246544A (ja) | 2006-05-11 | 2010-05-10 | Ｐｃｓｋ９遺伝子の発現を阻害するための組成物および方法 |
| JP2014018817A Expired - Fee Related JP6034316B2 (ja) | 2006-05-11 | 2014-02-03 | Ｐｃｓｋ９遺伝子の発現を阻害するための組成物および方法 |
| JP2015226712A Pending JP2016027830A (ja) | 2006-05-11 | 2015-11-19 | Ｐｃｓｋ９遺伝子の発現を阻害するための組成物および方法 |
Country Status (14)
| Country | Link |
|---|---|
| US (10) | US7605251B2 (enExample) |
| EP (8) | EP3249052B1 (enExample) |
| JP (4) | JP5570806B2 (enExample) |
| KR (2) | KR101320916B1 (enExample) |
| CN (2) | CN101484588B (enExample) |
| AU (2) | AU2007249329C1 (enExample) |
| CA (2) | CA2915441A1 (enExample) |
| EA (2) | EA015676B1 (enExample) |
| ES (2) | ES2874149T3 (enExample) |
| IL (3) | IL195181A (enExample) |
| NZ (2) | NZ572666A (enExample) |
| PL (2) | PL3578656T3 (enExample) |
| SG (1) | SG171676A1 (enExample) |
| WO (1) | WO2007134161A2 (enExample) |
Families Citing this family (174)
| 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) |
| EP3037105B1 (en) * | 2003-06-27 | 2021-03-17 | Amgen Fremont Inc. | Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof |
| US8288354B2 (en) | 2005-12-28 | 2012-10-16 | The Scripps Research Institute | Natural antisense and non-coding RNA transcripts as drug targets |
| KR101320916B1 (ko) | 2006-05-11 | 2013-10-23 | 알닐람 파마슈티칼스 인코포레이티드 | Ｐｃｓｋ9 유전자의 발현을 억제하기 위한 조성물 및 방법 |
| AU2007322265B2 (en) | 2006-11-07 | 2013-06-20 | Merck Sharp & Dohme Corp. | Antagonists of PCSK9 |
| DK2548438T3 (en) * | 2006-11-08 | 2015-10-19 | Veritas Bio LLC | IN VIVO SUBMITTING DOUBLE-STRENGTH RNA TO A CELL |
| KR20090103894A (ko) * | 2006-11-27 | 2009-10-01 | 아이시스 파마수티컬즈 인코포레이티드 | 고콜레스테롤혈증을 치료하는 방법 |
| US8093222B2 (en) * | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| US7910722B2 (en) | 2007-07-05 | 2011-03-22 | Florida State University Research Foundation | RNAi therapeutic for treatment of hepatitis C infection |
| JOP20080381B1 (ar) | 2007-08-23 | 2023-03-28 | Amgen Inc | بروتينات مرتبطة بمولدات مضادات تتفاعل مع بروبروتين كونفيرتاز سيتيليزين ككسين من النوع 9 (pcsk9) |
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| CN102016036B (zh) | 2008-02-11 | 2015-04-08 | 阿克赛医药公司 | 经修饰的RNAi多核苷酸及其用途 |
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| CN102405286A (zh) | 2008-09-22 | 2012-04-04 | 阿克赛医药公司 | 减小大小的自递送RNAi化合物 |
| MX339820B (es) | 2008-10-03 | 2016-06-13 | Curna Inc | Compuestos oligonucleottidos designados para inhibir el transcrito antisentido natrual apra apolipoproteina-a1. |
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| CN102317458B (zh) | 2008-12-04 | 2018-01-02 | 库尔纳公司 | 通过红细胞生成素(epo)天然反义转录物的抑制对epo相关疾病的治疗 |
| KR101866152B1 (ko) | 2008-12-04 | 2018-06-08 | 큐알엔에이, 인크. | 종양 억제 유전자에 대한 천연 안티센스 전사체의 억제에 의해 종양 억제 유전자 관련된 질환의 치료 |
| 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). |
| US9493774B2 (en) | 2009-01-05 | 2016-11-15 | Rxi Pharmaceuticals Corporation | Inhibition of PCSK9 through RNAi |
| WO2010090762A1 (en) | 2009-02-04 | 2010-08-12 | Rxi Pharmaceuticals Corporation | Rna duplexes with single stranded phosphorothioate nucleotide regions for additional functionality |
| EP3009150B1 (en) | 2009-02-12 | 2019-11-13 | CuRNA, Inc. | Treatment of brain derived neurotrophic factor (bdnf) related diseases by inhibition of natural antisense transcript to bdnf |
| WO2010107733A2 (en) | 2009-03-16 | 2010-09-23 | Curna, Inc. | Treatment of nuclear factor (erythroid-derived 2)-like 2 (nrf2) related diseases by inhibition of natural antisense transcript to nrf2 |
| WO2010107740A2 (en) | 2009-03-17 | 2010-09-23 | Curna, Inc. | Treatment of delta-like 1 homolog (dlk1) related diseases by inhibition of natural antisense transcript to dlk1 |
| EP2427552B1 (en) | 2009-05-06 | 2016-11-16 | CuRNA, Inc. | Treatment of tristetraproline (ttp) related diseases by inhibition of natural antisense transcript to ttp |
| CN103223177B (zh) | 2009-05-06 | 2016-08-10 | 库尔纳公司 | 通过针对脂质转运和代谢基因的天然反义转录物的抑制治疗脂质转运和代谢基因相关疾病 |
| EP2427554B1 (en) | 2009-05-08 | 2016-11-16 | CuRNA, Inc. | Treatment of dystrophin family related diseases by inhibition of natural antisense transcript to dmd family |
| EP2432881B1 (en) | 2009-05-18 | 2017-11-15 | CuRNA, Inc. | Treatment of reprogramming factor related diseases by inhibition of natural antisense transcript to a reprogramming factor |
| US8895527B2 (en) | 2009-05-22 | 2014-11-25 | Curna, Inc. | Treatment of transcription factor E3 (TFE3) and insulin receptor substrate 2(IRS2) related diseases by inhibition of natural antisense transcript to TFE3 |
| JP5960049B2 (ja) | 2009-05-28 | 2016-08-02 | クルナ・インコーポレーテッド | 抗ウイルス遺伝子に対する天然アンチセンス転写物の抑制による抗ウイルス遺伝子関連疾患の治療 |
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| US9051567B2 (en) | 2009-06-15 | 2015-06-09 | Tekmira Pharmaceuticals Corporation | 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 |
| CN102695797B (zh) | 2009-06-16 | 2018-05-25 | 库尔纳公司 | 通过抑制针对胶原基因的天然反义转录物来治疗胶原基因相关的疾病 |
| US8951981B2 (en) | 2009-06-16 | 2015-02-10 | Curna, Inc. | Treatment of paraoxonase 1 (PON1) related diseases by inhibition of natural antisense transcript to PON1 |
| CA2765889A1 (en) | 2009-06-24 | 2010-12-29 | Opko Curna, Llc | Treatment of tumor necrosis factor receptor 2 (tnfr2) related diseases by inhibition of natural antisense transcript to tnfr2 |
| CA2765815A1 (en) | 2009-06-26 | 2010-12-29 | Opko Curna, Llc | Treatment of down syndrome gene related diseases by inhibition of natural antisense transcript to a down syndrome gene |
| JP5766188B2 (ja) | 2009-07-01 | 2015-08-19 | プロチバ バイオセラピューティクス インコーポレイティッド | 固形腫瘍に治療剤を送達するための脂質製剤 |
| US8563528B2 (en) | 2009-07-21 | 2013-10-22 | Santaris Pharma A/S | Antisense oligomers targeting PCSK9 |
| KR101801407B1 (ko) | 2009-07-24 | 2017-11-24 | 큐알엔에이, 인크. | 시르투인 (ｓｉｒｔ)에 대한 천연 안티센스 전사체의 억제에 의한 시르투인 관련된 질환의 치료 |
| JP6128848B2 (ja) | 2009-08-05 | 2017-05-17 | クルナ・インコーポレーテッド | インスリン遺伝子（ｉｎｓ）に対する天然アンチセンス転写物の抑制によるインスリン遺伝子（ｉｎｓ）関連疾患の治療 |
| CA2770104C (en) | 2009-08-11 | 2019-03-19 | Opko Curna, Llc | Treatment of adiponectin (adipoq) related diseases by inhibition of natural antisense transcript to an adiponectin (adipoq) |
| WO2011022606A2 (en) | 2009-08-21 | 2011-02-24 | Curna, Inc. | Treatment of 'c terminus of hsp70-interacting protein' (chip) related diseases by inhibition of natural antisense transcript to chip |
| CN102482671B (zh) | 2009-08-25 | 2017-12-01 | 库尔纳公司 | 通过抑制‘含有iq模体的gtp酶激活蛋白’(iqgap)的天然反义转录物而治疗iqgap相关疾病 |
| WO2011028938A1 (en) * | 2009-09-02 | 2011-03-10 | Alnylam Pharmaceuticals, Inc. | Methods for lowering serum cholestrol in a subject using inhibition of pcsk9 |
| US9187746B2 (en) | 2009-09-22 | 2015-11-17 | Alnylam Pharmaceuticals, Inc. | Dual targeting siRNA agents |
| US20120295952A1 (en) | 2009-09-25 | 2012-11-22 | Curna, Inc. | Treatment of filaggrin (flg) related diseases by modulation of flg expression and activity |
| CA2780741C (en) | 2009-10-12 | 2023-04-04 | Smith Holdings, Llc | Methods and compositions for modulating gene expression using oligonucleotide based drugs administered in vivo or in vitro |
| AR079336A1 (es) * | 2009-12-11 | 2012-01-18 | Irm Llc | Antagonistas de la pro-proteina convertasa-subtilisina/quexina tipo 9 (pcsk9) |
| RU2639550C2 (ru) | 2009-12-16 | 2017-12-21 | Курна, Инк. | Лечение заболеваний, связанных с сайт-1 мембраносвязанной пептидазой транскрипционных факторов (mbtps1), путем ингибирования природного антисмыслового транскрипта к mbtps1 |
| US20110152343A1 (en) * | 2009-12-22 | 2011-06-23 | Functional Genetics, Inc. | Protease inhibitors and broad-spectrum antiviral |
| US8940708B2 (en) | 2009-12-23 | 2015-01-27 | Curna, Inc. | Treatment of hepatocyte growth factor (HGF) related diseases by inhibition of natural antisense transcript to HGF |
| CN102781480B (zh) | 2009-12-23 | 2018-07-27 | 库尔纳公司 | 通过抑制解偶联蛋白2(ucp2)的天然反义转录物而治疗ucp2相关疾病 |
| EP2519633B1 (en) | 2009-12-29 | 2017-10-25 | CuRNA, Inc. | Treatment of nuclear respiratory factor 1 (nrf1) related diseases by inhibition of natural antisense transcript to nrf1 |
| JP5982288B2 (ja) | 2009-12-29 | 2016-08-31 | カッパーアールエヌエー，インコーポレイテッド | 腫瘍タンパク質６３（ｐ６３）に対する天然アンチセンス転写物の阻害による腫瘍タンパク質６３関連疾患の治療 |
| EP2519632B1 (en) | 2009-12-31 | 2018-04-11 | CuRNA, Inc. | Treatment of insulin receptor substrate 2 (irs2) related diseases by inhibition of natural antisense transcript to irs2 and transcription factor e3 (tfe3) |
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