CA2713379A1 - Optimized methods for delivery of dsrna targeting the pcsk9 gene - Google Patents
Optimized methods for delivery of dsrna targeting the pcsk9 gene Download PDFInfo
- Publication number
- CA2713379A1 CA2713379A1 CA2713379A CA2713379A CA2713379A1 CA 2713379 A1 CA2713379 A1 CA 2713379A1 CA 2713379 A CA2713379 A CA 2713379A CA 2713379 A CA2713379 A CA 2713379A CA 2713379 A1 CA2713379 A1 CA 2713379A1
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- Prior art keywords
- dsrna
- pcsk9
- nucleotide
- cholesterol
- days
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- OABYVIYXWMZFFJ-ZUHYDKSRSA-M sodium glycocholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 OABYVIYXWMZFFJ-ZUHYDKSRSA-M 0.000 description 1
- VMSNAUAEKXEYGP-YEUHZSMFSA-M sodium glycodeoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 VMSNAUAEKXEYGP-YEUHZSMFSA-M 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- 150000003522 tetracyclines Chemical class 0.000 description 1
- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
- JYKSTGLAIMQDRA-UHFFFAOYSA-N tetraglycerol Chemical compound OCC(O)CO.OCC(O)CO.OCC(O)CO.OCC(O)CO JYKSTGLAIMQDRA-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 229940028869 ticlid Drugs 0.000 description 1
- 229960005001 ticlopidine Drugs 0.000 description 1
- MTKNGOHFNXIVOS-UHFFFAOYSA-N ticlopidine hydrochloride Chemical compound [H+].[Cl-].ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 MTKNGOHFNXIVOS-UHFFFAOYSA-N 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
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- 125000002640 tocopherol group Chemical class 0.000 description 1
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- 229950004514 torcetrapib Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
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- 230000010474 transient expression Effects 0.000 description 1
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- ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 230000010415 tropism Effects 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 description 1
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- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1137—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against enzymes
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- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
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- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
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- Engineering & Computer Science (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2496808P | 2008-01-31 | 2008-01-31 | |
| US61/024,968 | 2008-01-31 | ||
| US3908308P | 2008-03-24 | 2008-03-24 | |
| US61/039,083 | 2008-03-24 | ||
| US7654808P | 2008-06-27 | 2008-06-27 | |
| US61/076,548 | 2008-06-27 | ||
| US18876508P | 2008-08-11 | 2008-08-11 | |
| US61/188,765 | 2008-08-11 | ||
| PCT/US2009/032743 WO2009134487A2 (en) | 2008-01-31 | 2009-01-30 | Optimized methods for delivery of dsrna targeting the pcsk9 gene |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2713379A1 true CA2713379A1 (en) | 2009-11-05 |
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Family Applications (1)
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|---|---|---|---|
| CA2713379A Abandoned CA2713379A1 (en) | 2008-01-31 | 2009-01-30 | Optimized methods for delivery of dsrna targeting the pcsk9 gene |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US20100010066A1 (enExample) |
| EP (1) | EP2245039A4 (enExample) |
| JP (1) | JP2011511004A (enExample) |
| AU (1) | AU2009241591A1 (enExample) |
| BR (1) | BRPI0907008A2 (enExample) |
| CA (1) | CA2713379A1 (enExample) |
| MX (1) | MX2010008394A (enExample) |
| WO (1) | WO2009134487A2 (enExample) |
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| AU2005222902B2 (en) | 2004-03-12 | 2010-06-10 | Alnylam Pharmaceuticals, Inc. | iRNA agents targeting VEGF |
| SG171676A1 (en) | 2006-05-11 | 2011-06-29 | Alnylam Pharmaceuticals Inc | Compositions and methods for inhibiting expression of the pcsk9 gene |
| 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 |
| HRP20150796T1 (hr) | 2008-10-20 | 2015-09-11 | Alnylam Pharmaceuticals, Inc. | Pripravci i postupci za inhibiciju ekspresije transtiretina |
| 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 |
| EP2442792A4 (en) | 2009-06-15 | 2015-12-23 | Alnylam Pharmaceuticals Inc | TESTING GENE PCSK9 LIPID-FORMULATED DSRNA |
| WO2010147992A1 (en) | 2009-06-15 | 2010-12-23 | Alnylam Pharmaceuticals, Inc. | Methods for increasing efficacy of lipid formulated sirna |
| WO2011038031A1 (en) | 2009-09-22 | 2011-03-31 | Alnylam Pharmaceuticals, Inc. | Dual targeting sirna agents |
| US8846631B2 (en) | 2010-01-14 | 2014-09-30 | Regulus Therapeutics Inc. | MicroRNA compositions and methods |
| KR102453078B1 (ko) | 2010-03-24 | 2022-10-11 | 피오 파마슈티칼스 코프. | 진피 및 섬유증성 적응증에서의 ｒｎａ 간섭 |
| CN103200945B (zh) | 2010-03-24 | 2016-07-06 | 雷克西制药公司 | 眼部症候中的rna干扰 |
| EP2616543A1 (en) * | 2010-09-15 | 2013-07-24 | Alnylam Pharmaceuticals, Inc. | MODIFIED iRNA AGENTS |
| US9260471B2 (en) * | 2010-10-29 | 2016-02-16 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using short interfering nucleic acids (siNA) |
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