JP2015519050A5 - - Google Patents
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- JP2015519050A5 JP2015519050A5 JP2015511658A JP2015511658A JP2015519050A5 JP 2015519050 A5 JP2015519050 A5 JP 2015519050A5 JP 2015511658 A JP2015511658 A JP 2015511658A JP 2015511658 A JP2015511658 A JP 2015511658A JP 2015519050 A5 JP2015519050 A5 JP 2015519050A5
- Authority
- JP
- Japan
- Prior art keywords
- seq
- antibody
- sequence
- antibody fragment
- human pcsk9
- 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.)
- Granted
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- 101001098868 Homo sapiens Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 claims 151
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims 151
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims 151
- 102100038955 Proprotein convertase subtilisin/kexin type 9 Human genes 0.000 claims 145
- 125000003275 alpha amino acid group Chemical group 0.000 claims 98
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 claims 51
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 claims 50
- 102100035361 Cerebellar degeneration-related protein 2 Human genes 0.000 claims 50
- 101000737793 Homo sapiens Cerebellar degeneration-related antigen 1 Proteins 0.000 claims 50
- 101000737796 Homo sapiens Cerebellar degeneration-related protein 2 Proteins 0.000 claims 50
- 239000003795 chemical substances by application Substances 0.000 claims 29
- 239000003814 drug Substances 0.000 claims 28
- 239000000203 mixture Substances 0.000 claims 24
- 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 claims 23
- 229940079593 drug Drugs 0.000 claims 20
- 230000027455 binding Effects 0.000 claims 11
- 108090000765 processed proteins & peptides Proteins 0.000 claims 11
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims 10
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 claims 10
- 102000004196 processed proteins & peptides Human genes 0.000 claims 10
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 claims 10
- 241000235648 Pichia Species 0.000 claims 9
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- 229940097320 beta blocking agent Drugs 0.000 claims 9
- 210000004027 cell Anatomy 0.000 claims 9
- 239000012634 fragment Substances 0.000 claims 9
- MOYKHGMNXAOIAT-JGWLITMVSA-N isosorbide dinitrate Chemical group [O-][N+](=O)O[C@H]1CO[C@@H]2[C@H](O[N+](=O)[O-])CO[C@@H]21 MOYKHGMNXAOIAT-JGWLITMVSA-N 0.000 claims 9
- 150000007523 nucleic acids Chemical class 0.000 claims 9
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 claims 9
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 claims 8
- 239000005541 ACE inhibitor Substances 0.000 claims 8
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical group CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 claims 8
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims 8
- 235000012000 cholesterol Nutrition 0.000 claims 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 8
- 229940124597 therapeutic agent Drugs 0.000 claims 8
- 229940124549 vasodilator Drugs 0.000 claims 8
- 239000003071 vasodilator agent Substances 0.000 claims 8
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 claims 7
- 208000035150 Hypercholesterolemia Diseases 0.000 claims 7
- 239000002934 diuretic Substances 0.000 claims 7
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 claims 7
- 239000005537 C09CA07 - Telmisartan Substances 0.000 claims 6
- GHOSNRCGJFBJIB-UHFFFAOYSA-N Candesartan cilexetil Chemical compound C=12N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)C3=NNN=N3)C(OCC)=NC2=CC=CC=1C(=O)OC(C)OC(=O)OC1CCCCC1 GHOSNRCGJFBJIB-UHFFFAOYSA-N 0.000 claims 6
- 229940097420 Diuretic Drugs 0.000 claims 6
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 claims 6
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims 6
- IYIKLHRQXLHMJQ-UHFFFAOYSA-N amiodarone Chemical compound CCCCC=1OC2=CC=CC=C2C=1C(=O)C1=CC(I)=C(OCCN(CC)CC)C(I)=C1 IYIKLHRQXLHMJQ-UHFFFAOYSA-N 0.000 claims 6
- 229960000528 amlodipine Drugs 0.000 claims 6
- MAEIEVLCKWDQJH-UHFFFAOYSA-N bumetanide Chemical compound CCCCNC1=CC(C(O)=O)=CC(S(N)(=O)=O)=C1OC1=CC=CC=C1 MAEIEVLCKWDQJH-UHFFFAOYSA-N 0.000 claims 6
- 201000010099 disease Diseases 0.000 claims 6
- 230000001882 diuretic effect Effects 0.000 claims 6
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims 6
- 102000053786 human PCSK9 Human genes 0.000 claims 6
- 229960000201 isosorbide dinitrate Drugs 0.000 claims 6
- YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 claims 6
- 108020004707 nucleic acids Proteins 0.000 claims 6
- 102000039446 nucleic acids Human genes 0.000 claims 6
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims 6
- SGUAFYQXFOLMHL-UHFFFAOYSA-N 2-hydroxy-5-{1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl}benzamide Chemical compound C=1C=C(O)C(C(N)=O)=CC=1C(O)CNC(C)CCC1=CC=CC=C1 SGUAFYQXFOLMHL-UHFFFAOYSA-N 0.000 claims 5
- 206010002383 Angina Pectoris Diseases 0.000 claims 5
- 229940127291 Calcium channel antagonist Drugs 0.000 claims 5
- 206010019280 Heart failures Diseases 0.000 claims 5
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 claims 5
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 claims 5
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 claims 5
- NGBFQHCMQULJNZ-UHFFFAOYSA-N Torsemide Chemical compound CC(C)NC(=O)NS(=O)(=O)C1=CN=CC=C1NC1=CC=CC(C)=C1 NGBFQHCMQULJNZ-UHFFFAOYSA-N 0.000 claims 5
- 150000001413 amino acids Chemical class 0.000 claims 5
- 239000003146 anticoagulant agent Substances 0.000 claims 5
- 229940127219 anticoagulant drug Drugs 0.000 claims 5
- 239000000480 calcium channel blocker Substances 0.000 claims 5
- 208000029078 coronary artery disease Diseases 0.000 claims 5
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 claims 5
- YOSHYTLCDANDAN-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2NN=NN=2)C(CCCC)=NC21CCCC2 YOSHYTLCDANDAN-UHFFFAOYSA-N 0.000 claims 5
- 239000002516 radical scavenger Substances 0.000 claims 5
- 229960002256 spironolactone Drugs 0.000 claims 5
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 claims 4
- BIDNLKIUORFRQP-XYGFDPSESA-N (2s,4s)-4-cyclohexyl-1-[2-[[(1s)-2-methyl-1-propanoyloxypropoxy]-(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylic acid Chemical compound C([P@@](=O)(O[C@H](OC(=O)CC)C(C)C)CC(=O)N1[C@@H](C[C@H](C1)C1CCCCC1)C(O)=O)CCCC1=CC=CC=C1 BIDNLKIUORFRQP-XYGFDPSESA-N 0.000 claims 4
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 claims 4
- RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 claims 4
- 241000228212 Aspergillus Species 0.000 claims 4
- 239000002083 C09CA01 - Losartan Substances 0.000 claims 4
- 239000004072 C09CA03 - Valsartan Substances 0.000 claims 4
- 239000002947 C09CA04 - Irbesartan Substances 0.000 claims 4
- 239000002053 C09CA06 - Candesartan Substances 0.000 claims 4
- 229920001268 Cholestyramine Polymers 0.000 claims 4
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 claims 4
- JRWZLRBJNMZMFE-UHFFFAOYSA-N Dobutamine Chemical compound C=1C=C(O)C(O)=CC=1CCNC(C)CCC1=CC=C(O)C=C1 JRWZLRBJNMZMFE-UHFFFAOYSA-N 0.000 claims 4
- RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 claims 4
- 101001051093 Homo sapiens Low-density lipoprotein receptor Proteins 0.000 claims 4
- 108010007859 Lisinopril Proteins 0.000 claims 4
- 208000001145 Metabolic Syndrome Diseases 0.000 claims 4
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 claims 4
- VXFJYXUZANRPDJ-WTNASJBWSA-N Trandopril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@H]2CCCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 VXFJYXUZANRPDJ-WTNASJBWSA-N 0.000 claims 4
- 108010062497 VLDL Lipoproteins Proteins 0.000 claims 4
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims 4
- GOEMGAFJFRBGGG-UHFFFAOYSA-N acebutolol Chemical group CCCC(=O)NC1=CC=C(OCC(O)CNC(C)C)C(C(C)=O)=C1 GOEMGAFJFRBGGG-UHFFFAOYSA-N 0.000 claims 4
- 239000000674 adrenergic antagonist Substances 0.000 claims 4
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- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical group SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 claims 4
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- NPAKNKYSJIDKMW-UHFFFAOYSA-N carvedilol Chemical compound COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=NC3=CC=C[CH]C3=C12 NPAKNKYSJIDKMW-UHFFFAOYSA-N 0.000 claims 4
- 206010012601 diabetes mellitus Diseases 0.000 claims 4
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- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 claims 4
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 claims 4
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 claims 4
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 claims 4
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- RLAWWYSOJDYHDC-BZSNNMDCSA-N lisinopril Chemical compound C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 RLAWWYSOJDYHDC-BZSNNMDCSA-N 0.000 claims 4
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- KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 claims 4
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- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 claims 4
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- REQCZEXYDRLIBE-UHFFFAOYSA-N procainamide Chemical compound CCN(CC)CCNC(=O)C1=CC=C(N)C=C1 REQCZEXYDRLIBE-UHFFFAOYSA-N 0.000 claims 4
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- HMJIYCCIJYRONP-UHFFFAOYSA-N (+-)-Isradipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC2=NON=C12 HMJIYCCIJYRONP-UHFFFAOYSA-N 0.000 claims 2
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2013
- 2013-03-12 US US13/795,674 patent/US9255154B2/en not_active Expired - Fee Related
- 2013-05-08 NZ NZ732652A patent/NZ732652A/en not_active IP Right Cessation
- 2013-05-08 AU AU2013259562A patent/AU2013259562B2/en not_active Ceased
- 2013-05-08 SG SG11201407099WA patent/SG11201407099WA/en unknown
- 2013-05-08 WO PCT/US2013/040112 patent/WO2013169886A1/en not_active Ceased
- 2013-05-08 CN CN201380036215.2A patent/CN104583237B/zh not_active Expired - Fee Related
- 2013-05-08 AR ARP130101583A patent/AR092005A1/es unknown
- 2013-05-08 TW TW102116366A patent/TW201348260A/zh unknown
- 2013-05-08 EP EP13787331.1A patent/EP2844673A4/en not_active Withdrawn
- 2013-05-08 EP EP19218830.8A patent/EP3753950A2/en not_active Withdrawn
- 2013-05-08 CN CN201811305039.9A patent/CN109796533A/zh active Pending
- 2013-05-08 CA CA2872777A patent/CA2872777A1/en not_active Abandoned
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