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
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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 (cg-RX-API-DMAC7.html) | 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 (cg-RX-API-DMAC7.html) |
| EP (3) | EP2455471A3 (cg-RX-API-DMAC7.html) |
| JP (1) | JP2010510807A (cg-RX-API-DMAC7.html) |
| KR (1) | KR20090103894A (cg-RX-API-DMAC7.html) |
| AU (1) | AU2007325767A1 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2670563A1 (cg-RX-API-DMAC7.html) |
| CO (1) | CO6241169A2 (cg-RX-API-DMAC7.html) |
| EA (1) | EA200900741A1 (cg-RX-API-DMAC7.html) |
| IL (1) | IL198851A0 (cg-RX-API-DMAC7.html) |
| MX (1) | MX2009005527A (cg-RX-API-DMAC7.html) |
| NO (1) | NO20092150L (cg-RX-API-DMAC7.html) |
| TW (1) | TW200838551A (cg-RX-API-DMAC7.html) |
| WO (1) | WO2008066776A2 (cg-RX-API-DMAC7.html) |
Families Citing this family (56)
| Publication number | Priority date | Publication date | Assignee | Title |
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| EP2835429B1 (en) | 2006-05-11 | 2017-12-13 | Alnylam Pharmaceuticals Inc. | Compositions and methods for inhibiting expression of the PCSK9 gene |
| US8084437B2 (en) | 2006-11-27 | 2011-12-27 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| US8093222B2 (en) | 2006-11-27 | 2012-01-10 | 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) |
| AU2009213147A1 (en) | 2008-02-11 | 2009-08-20 | Rxi Pharmaceuticals Corp. | Modified RNAi polynucleotides and uses thereof |
| WO2009148605A2 (en) * | 2008-06-04 | 2009-12-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| DK2379084T3 (en) * | 2008-10-15 | 2018-01-22 | Ionis Pharmaceuticals Inc | MODULATION OF FACTOR 11 EXPRESSION |
| AU2009323766B2 (en) | 2008-12-02 | 2016-10-06 | Wave Life Sciences Ltd. | 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). |
| US9493774B2 (en) * | 2009-01-05 | 2016-11-15 | Rxi Pharmaceuticals Corporation | Inhibition of PCSK9 through RNAi |
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| BRPI1015236A2 (pt) * | 2009-04-15 | 2019-09-24 | Isis Pharmaceuticals Inc | métodos para modular uma resposta inflamatória, apra melhorar uma doença, distúrbio ou condição inflamatórios em um animal, para tratar um animal em risco para uma doença, distúrbio ou condição inflamatórios, para inibir a expressão de fator xi em um animal, para reduzir o risco de doença, distúrbio ou condição inflamatórios, em um animal, para tratar um animal em risco para uma doença inflamatória, e para tratar um animal tendo uma doença inflamatória, e, uso de um composto marcado para fator xi |
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| US9051567B2 (en) | 2009-06-15 | 2015-06-09 | Tekmira Pharmaceuticals Corporation | Methods for increasing efficacy of lipid formulated siRNA |
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| US9605019B2 (en) | 2011-07-19 | 2017-03-28 | Wave Life Sciences Ltd. | Methods for the synthesis of functionalized nucleic acids |
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| DK2742135T4 (da) | 2011-08-11 | 2020-07-13 | Ionis Pharmaceuticals Inc | Bindingsmodificerede gapped oligomeriske forbindelser og anvendelser deraf |
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| 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 |
| JP6268157B2 (ja) | 2012-07-13 | 2018-01-24 | 株式会社Ｗａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｊａｐａｎ | 不斉補助基 |
| JP6246121B2 (ja) | 2012-07-13 | 2017-12-13 | 株式会社新日本科学 | キラル核酸アジュバント |
| SG10201912895PA (en) | 2012-07-13 | 2020-02-27 | Wave Life Sciences Ltd | Chiral control |
| EP3459549B1 (en) | 2012-10-12 | 2022-04-06 | Ionis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
| ES2724853T3 (es) | 2012-11-15 | 2019-09-16 | Roche Innovation Ct Copenhagen As | Conjugados de oligonucleótidos |
| PT2929031T (pt) | 2012-12-05 | 2018-01-19 | Alnylam Pharmaceuticals Inc | Composições de irna de pcsk9 e métodos de seu uso |
| MY177989A (en) | 2013-01-30 | 2020-09-28 | Hoffmann La Roche | Lna oligonucleotide carbohydrate conjugates |
| GB2523527A (en) * | 2013-04-05 | 2015-09-02 | Weiming Xu | Screen compounds for the modulation of proprotein convertase subtilisin/kexin type 9(PCSK9) |
| MX2015014666A (es) | 2013-04-17 | 2016-03-01 | Pfizer | Derivados de n-piperidin-3-ilbenzamida para tratar enfermedades cardiovasculares. |
| KR102138781B1 (ko) | 2013-05-01 | 2020-07-28 | 아이오니스 파마수티컬즈, 인코포레이티드 | 아포지질단백질 c-iii 발현을 조절하는 조성물 및 방법 |
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| JP6487913B2 (ja) * | 2013-07-02 | 2019-03-20 | アイオーニス ファーマシューティカルズ， インコーポレーテッドＩｏｎｉｓ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． | 成長ホルモン受容体のモジュレータ |
| JPWO2015108047A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 免疫誘導活性を有するキラル核酸アジュバンド及び免疫誘導活性剤 |
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| CN109477106B (zh) * | 2015-07-10 | 2022-10-04 | Ionis制药公司 | 二酰基甘油酰基转移酶2(dgat2)的调节剂 |
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| KR102793532B1 (ko) | 2015-08-25 | 2025-04-14 | 알닐람 파마슈티칼스 인코포레이티드 | 전구단백질 컨버타제 서브틸리신 켁신 (pcsk9) 유전자-관련 장애를 치료하기 위한 방법 및 조성물 |
| US11400161B2 (en) | 2016-10-06 | 2022-08-02 | Ionis Pharmaceuticals, Inc. | Method of conjugating oligomeric compounds |
| JP2019535839A (ja) | 2016-11-29 | 2019-12-12 | ピュアテック ヘルス エルエルシー | 治療剤の送達のためのエクソソーム |
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| KR102749200B1 (ko) * | 2018-04-18 | 2025-01-03 | 다이서나 파마수이티컬, 인크. | 고콜레스테롤혈증 및 관련 상태를 치료하기 위한 pcsk9 표적화 올리고뉴클레오티드 |
| CR20200605A (es) | 2018-05-09 | 2021-01-29 | Ionis Pharmaceuticals Inc | Compuestos y métodos para la reducción de la expresión de fxi |
| KR20180087217A (ko) | 2018-07-20 | 2018-08-01 | 주식회사 유진바이오텍 | 귀리산화 베타-글루칸을 유효성분으로 포함하는 비만, 이상지방혈증(dyslipidemia) 또는 지방간의 예방 또는 치료용 조성물 |
| WO2024229020A2 (en) * | 2023-05-01 | 2024-11-07 | Chroma Medicine, Inc. | Compositions and methods for epigenetic regulation of pcsk9 expression |
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-
2007
- 2007-11-27 US US12/516,457 patent/US8084437B2/en active Active
- 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 EA EA200900741A patent/EA200900741A1/ru unknown
- 2007-11-27 EP EP07862213A patent/EP2102340A2/en not_active Withdrawn
- 2007-11-27 AU AU2007325767A patent/AU2007325767A1/en not_active Abandoned
- 2007-11-27 WO PCT/US2007/024369 patent/WO2008066776A2/en not_active Ceased
- 2007-11-27 TW TW096145015A patent/TW200838551A/zh unknown
- 2007-11-27 EP EP11192464A patent/EP2453016A1/en not_active Withdrawn
- 2007-11-27 KR KR1020097013295A patent/KR20090103894A/ko not_active Withdrawn
- 2007-11-27 JP JP2009539274A patent/JP2010510807A/ja active Pending
-
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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