JP2010510807A5 - - Google Patents
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- JP2010510807A5 JP2010510807A5 JP2009539274A JP2009539274A JP2010510807A5 JP 2010510807 A5 JP2010510807 A5 JP 2010510807A5 JP 2009539274 A JP2009539274 A JP 2009539274A JP 2009539274 A JP2009539274 A JP 2009539274A JP 2010510807 A5 JP2010510807 A5 JP 2010510807A5
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- compound
- seq
- modified
- modified oligonucleotide
- complementary
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- 150000001875 compounds Chemical class 0.000 claims description 106
- 108091034117 Oligonucleotide Proteins 0.000 claims description 86
- 101001098868 Homo sapiens Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 claims description 50
- 230000000692 anti-sense effect Effects 0.000 claims description 25
- 102000053786 human PCSK9 Human genes 0.000 claims description 12
- 239000002777 nucleoside Substances 0.000 claims 75
- 230000000295 complement effect Effects 0.000 claims 48
- 125000003835 nucleoside group Chemical group 0.000 claims 43
- 150000003833 nucleoside derivatives Chemical class 0.000 claims 32
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 21
- 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 Chemical class 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 claims 19
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims 13
- 150000007523 nucleic acids Chemical group 0.000 claims 12
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 6
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical group CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims 4
- 125000002619 bicyclic group Chemical group 0.000 claims 4
- 239000003085 diluting agent Substances 0.000 claims 4
- 239000003937 drug carrier Substances 0.000 claims 4
- 150000003839 salts Chemical class 0.000 claims 4
- 102100038955 Proprotein convertase subtilisin/kexin type 9 Human genes 0.000 description 38
- 210000004027 cell Anatomy 0.000 description 21
- 108020004999 messenger RNA Proteins 0.000 description 19
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 16
- 239000000074 antisense oligonucleotide Substances 0.000 description 16
- 238000012230 antisense oligonucleotides Methods 0.000 description 16
- 230000005764 inhibitory process Effects 0.000 description 16
- 210000003494 hepatocyte Anatomy 0.000 description 14
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 10
- 230000008685 targeting Effects 0.000 description 10
- 239000002245 particle Substances 0.000 description 8
- 108010007622 LDL Lipoproteins Proteins 0.000 description 7
- 231100000673 dose–response relationship Toxicity 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- 208000029078 coronary artery disease Diseases 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 238000003753 real-time PCR Methods 0.000 description 4
- 208000032928 Dyslipidaemia Diseases 0.000 description 3
- 208000017170 Lipid metabolism disease Diseases 0.000 description 3
- 238000011529 RT qPCR Methods 0.000 description 3
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- 108010027006 Apolipoproteins B Proteins 0.000 description 1
- 102000018616 Apolipoproteins B Human genes 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- 108010023302 HDL Cholesterol Proteins 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 241000764238 Isis Species 0.000 description 1
- 108010028554 LDL Cholesterol Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 208000010706 fatty liver disease Diseases 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US86739506P | 2006-11-27 | 2006-11-27 | |
| US91289207P | 2007-04-19 | 2007-04-19 | |
| US98628607P | 2007-11-07 | 2007-11-07 | |
| US98807407P | 2007-11-14 | 2007-11-14 | |
| PCT/US2007/024369 WO2008066776A2 (en) | 2006-11-27 | 2007-11-27 | Methods for treating hypercholesterolemia |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2010510807A JP2010510807A (ja) | 2010-04-08 |
| JP2010510807A5 true JP2010510807A5 (enExample) | 2011-01-20 |
Family
ID=39276232
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009539274A Pending JP2010510807A (ja) | 2006-11-27 | 2007-11-27 | 高コレステロール血症を治療するための方法 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US8084437B2 (enExample) |
| EP (3) | EP2453016A1 (enExample) |
| JP (1) | JP2010510807A (enExample) |
| KR (1) | KR20090103894A (enExample) |
| AU (1) | AU2007325767A1 (enExample) |
| CA (1) | CA2670563A1 (enExample) |
| CO (1) | CO6241169A2 (enExample) |
| EA (1) | EA200900741A1 (enExample) |
| IL (1) | IL198851A0 (enExample) |
| MX (1) | MX2009005527A (enExample) |
| NO (1) | NO20092150L (enExample) |
| TW (1) | TW200838551A (enExample) |
| WO (1) | WO2008066776A2 (enExample) |
Families Citing this family (56)
| Publication number | Priority date | Publication date | Assignee | Title |
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| EP2194128B1 (en) | 2006-05-11 | 2012-08-01 | Alnylam Pharmaceuticals Inc. | Compositions and methods for inhibiting expression of the PCSK9 gene |
| US8093222B2 (en) | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| EP2453016A1 (en) | 2006-11-27 | 2012-05-16 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| JOP20080381B1 (ar) | 2007-08-23 | 2023-03-28 | Amgen Inc | بروتينات مرتبطة بمولدات مضادات تتفاعل مع بروبروتين كونفيرتاز سيتيليزين ككسين من النوع 9 (pcsk9) |
| US10131904B2 (en) | 2008-02-11 | 2018-11-20 | Rxi Pharmaceuticals Corporation | Modified RNAi polynucleotides and uses thereof |
| WO2009148605A2 (en) * | 2008-06-04 | 2009-12-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| HRP20171969T1 (hr) * | 2008-10-15 | 2018-04-06 | Ionis Pharmaceuticals, Inc. | Modulacija ekspresije faktora 11 |
| US9394333B2 (en) | 2008-12-02 | 2016-07-19 | Wave Life Sciences Japan | Method for the synthesis of phosphorus atom modified nucleic acids |
| 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). |
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| NZ595891A (en) * | 2009-04-15 | 2013-06-28 | Isis Pharmaceuticals Inc | Modulation of inflammatory responses by factor xi |
| US9051567B2 (en) | 2009-06-15 | 2015-06-09 | Tekmira Pharmaceuticals Corporation | Methods for increasing efficacy of lipid formulated siRNA |
| KR20120050429A (ko) | 2009-06-15 | 2012-05-18 | 알닐람 파마슈티칼스 인코포레이티드 | Ｐｃｓｋ9 유전자를 표적으로 하는 지질 제형된 ｄｓｒｎａ |
| MX342945B (es) | 2009-07-06 | 2016-10-18 | Ontorii Inc * | Profármacos de ácido nucleico novedosos y métodos de uso de los mismos. |
| EP2456870A1 (en) | 2009-07-21 | 2012-05-30 | Santaris Pharma A/S | Antisense oligomers targeting pcsk9 |
| EP3561060A1 (en) * | 2010-02-08 | 2019-10-30 | Ionis Pharmaceuticals, Inc. | Selective reduction of allelic variants |
| WO2011097644A2 (en) | 2010-02-08 | 2011-08-11 | Isis Pharmaceuticals, Inc. | Selective reduction of allelic variants |
| GB2481373A (en) * | 2010-06-21 | 2011-12-28 | Weiming Xu | Treatment of hypercholesterolaemia by ubiquitination of PCSK9 |
| DK2620428T3 (da) | 2010-09-24 | 2019-07-01 | Wave Life Sciences Ltd | Asymmetrisk hjælpegruppe |
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| BR112013018740A2 (pt) | 2011-01-28 | 2019-01-08 | Sanofi Sa | anticorpos humanos para pcsk9 para uso em métodos de tratamento de grupos específicos de indivíduos |
| US9605019B2 (en) | 2011-07-19 | 2017-03-28 | Wave Life Sciences Ltd. | Methods for the synthesis of functionalized nucleic acids |
| AR087305A1 (es) | 2011-07-28 | 2014-03-12 | Regeneron Pharma | Formulaciones estabilizadas que contienen anticuerpos anti-pcsk9, metodo de preparacion y kit |
| EP2742056B2 (en) | 2011-08-11 | 2020-06-10 | Ionis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
| CN103930444B (zh) | 2011-09-16 | 2020-08-04 | 瑞泽恩制药公司 | 用前蛋白转化酶枯草溶菌素-9(PCSK9)抑制剂降低脂蛋白(a)水平的方法 |
| JP2015530867A (ja) | 2012-06-15 | 2015-10-29 | ジェネンテック， インコーポレイテッド | 抗ｐｃｓｋ９抗体、製剤、投薬、及び使用方法 |
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| JP6452614B2 (ja) | 2012-11-15 | 2019-01-16 | ロシュ イノベーション センター コペンハーゲン エーエス | オリゴヌクレオチドコンジュゲート |
| PT2929031T (pt) | 2012-12-05 | 2018-01-19 | Alnylam Pharmaceuticals Inc | Composições de irna de pcsk9 e métodos de seu uso |
| DK2951305T3 (en) | 2013-01-30 | 2018-10-29 | Hoffmann La Roche | LNA oligonucleotide KULHYDRATKONJUGATER |
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| BR112015026513A2 (pt) | 2013-04-17 | 2017-07-25 | Pfizer | derivados de n-piperidin-3-ilbenzamida para tratar as doenças cardiovasculares |
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| JP2018523684A (ja) | 2015-08-18 | 2018-08-23 | 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Ｒｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | リポタンパク質アフェレーシスを受けている高脂血症の患者を治療するための抗ｐｃｓｋ９阻害抗体 |
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| EP3765611A4 (en) | 2018-04-18 | 2022-05-04 | Dicerna Pharmaceuticals, Inc. | PCSK9 TARGETED OLIGONUCLEOTIDES FOR THE TREATMENT OF HYPERCHOLESTEROLEMIA AND RELATED DISORDERS |
| SG11202010012PA (en) | 2018-05-09 | 2020-11-27 | Ionis Pharmaceuticals Inc | Compounds and methods for reducing fxi expression |
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-
2007
- 2007-11-27 EP EP11192464A patent/EP2453016A1/en not_active Withdrawn
- 2007-11-27 TW TW096145015A patent/TW200838551A/zh unknown
- 2007-11-27 EA EA200900741A patent/EA200900741A1/ru unknown
- 2007-11-27 KR KR1020097013295A patent/KR20090103894A/ko not_active Withdrawn
- 2007-11-27 JP JP2009539274A patent/JP2010510807A/ja active Pending
- 2007-11-27 MX MX2009005527A patent/MX2009005527A/es not_active Application Discontinuation
- 2007-11-27 EP EP11192458A patent/EP2455471A3/en not_active Withdrawn
- 2007-11-27 CA CA002670563A patent/CA2670563A1/en not_active Abandoned
- 2007-11-27 AU AU2007325767A patent/AU2007325767A1/en not_active Abandoned
- 2007-11-27 US US12/516,457 patent/US8084437B2/en active Active
- 2007-11-27 WO PCT/US2007/024369 patent/WO2008066776A2/en not_active Ceased
- 2007-11-27 EP EP07862213A patent/EP2102340A2/en not_active Withdrawn
-
2009
- 2009-05-20 IL IL198851A patent/IL198851A0/en unknown
- 2009-06-03 NO NO20092150A patent/NO20092150L/no not_active Application Discontinuation
- 2009-06-26 CO CO09066682A patent/CO6241169A2/es not_active Application Discontinuation
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