JP2020522544A5 - - Google Patents
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- JP2020522544A5 JP2020522544A5 JP2019567608A JP2019567608A JP2020522544A5 JP 2020522544 A5 JP2020522544 A5 JP 2020522544A5 JP 2019567608 A JP2019567608 A JP 2019567608A JP 2019567608 A JP2019567608 A JP 2019567608A JP 2020522544 A5 JP2020522544 A5 JP 2020522544A5
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- Prior art keywords
- patient
- pharmaceutical composition
- antigen
- antibody
- binding fragment
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 claims 23
- 102000004965 antibodies Human genes 0.000 claims 21
- 108090001123 antibodies Proteins 0.000 claims 21
- 239000000427 antigen Substances 0.000 claims 21
- 102000038129 antigens Human genes 0.000 claims 21
- 108091007172 antigens Proteins 0.000 claims 21
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims 18
- 238000002560 therapeutic procedure Methods 0.000 claims 13
- 239000000556 agonist Substances 0.000 claims 10
- 108090001061 Insulin Proteins 0.000 claims 9
- 102000004877 Insulin Human genes 0.000 claims 9
- 208000009576 Hypercholesterolemia Diseases 0.000 claims 6
- 102100005352 PCSK9 Human genes 0.000 claims 6
- 101700000651 PCSK9 Proteins 0.000 claims 6
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 6
- 239000003112 inhibitor Substances 0.000 claims 6
- 230000002401 inhibitory effect Effects 0.000 claims 6
- 150000001413 amino acids Chemical group 0.000 claims 4
- 206010003210 Arteriosclerosis Diseases 0.000 claims 3
- 208000004981 Coronary Disease Diseases 0.000 claims 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N D-Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims 3
- 230000000271 cardiovascular Effects 0.000 claims 3
- 201000008739 coronary artery disease Diseases 0.000 claims 3
- 239000008103 glucose Substances 0.000 claims 3
- DTHNMHAUYICORS-KTKZVXAJSA-N 107444-51-9 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 claims 2
- 206010012601 Diabetes mellitus Diseases 0.000 claims 2
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- 102100003818 GCG Human genes 0.000 claims 2
- 101710042131 GCG Proteins 0.000 claims 2
- 102000036849 Islet amyloid polypeptide Human genes 0.000 claims 2
- 108010041872 Islet amyloid polypeptide Proteins 0.000 claims 2
- 208000001072 Type 2 Diabetes Mellitus Diseases 0.000 claims 2
- 230000003178 anti-diabetic Effects 0.000 claims 2
- 239000003472 antidiabetic agent Substances 0.000 claims 2
- 230000001419 dependent Effects 0.000 claims 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims 2
- 150000002632 lipids Chemical class 0.000 claims 2
- 230000000051 modifying Effects 0.000 claims 2
- 239000000018 receptor agonist Substances 0.000 claims 2
- 102000005962 receptors Human genes 0.000 claims 2
- 108020003175 receptors Proteins 0.000 claims 2
- IDHVLSACPFUBDY-QCDLPZBNSA-N xenin Chemical compound C([C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CN=CN1 IDHVLSACPFUBDY-QCDLPZBNSA-N 0.000 claims 2
- FJLGEFLZQAZZCD-JUFISIKESA-N (3S,5R)-fluvastatin Chemical compound C12=CC=CC=C2N(C(C)C)C(\C=C\[C@H](O)C[C@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 FJLGEFLZQAZZCD-JUFISIKESA-N 0.000 claims 1
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims 1
- IGRCWJPBLWGNPX-UHFFFAOYSA-N 3-(2-chlorophenyl)-N-(4-chlorophenyl)-N,5-dimethyl-1,2-oxazole-4-carboxamide Chemical compound C=1C=C(Cl)C=CC=1N(C)C(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl IGRCWJPBLWGNPX-UHFFFAOYSA-N 0.000 claims 1
- SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 claims 1
- OIRDTQYFTABQOQ-GAWUUDPSSA-N 9-β-D-XYLOFURANOSYL-ADENINE Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@H](O)[C@H]1O OIRDTQYFTABQOQ-GAWUUDPSSA-N 0.000 claims 1
- 206010000891 Acute myocardial infarction Diseases 0.000 claims 1
- OIRDTQYFTABQOQ-SXVXDFOESA-N Adenosine Natural products Nc1ncnc2c1ncn2[C@@H]3O[C@@H](CO)[C@H](O)[C@@H]3O OIRDTQYFTABQOQ-SXVXDFOESA-N 0.000 claims 1
- 206010002388 Angina unstable Diseases 0.000 claims 1
- RCHHVVGSTHAVPF-ZPHPLDECSA-N Apidra Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3N=CNC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CNC=N1 RCHHVVGSTHAVPF-ZPHPLDECSA-N 0.000 claims 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 claims 1
- 102100008845 COPA Human genes 0.000 claims 1
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- 102100009019 FFAR1 Human genes 0.000 claims 1
- 102100009021 FFAR4 Human genes 0.000 claims 1
- 101700008340 FFAR4 Proteins 0.000 claims 1
- 102000018711 Facilitative Glucose Transport Proteins Human genes 0.000 claims 1
- 108091006011 G proteins Proteins 0.000 claims 1
- 102100016463 GPBAR1 Human genes 0.000 claims 1
- 101710045222 GPBAR1 Proteins 0.000 claims 1
- 102000025873 GPCR, family 2, glucagon receptor Human genes 0.000 claims 1
- 108010063919 GPCR, family 2, glucagon receptor Proteins 0.000 claims 1
- 102100018511 GPR142 Human genes 0.000 claims 1
- 101710030445 GPR142 Proteins 0.000 claims 1
- 102000030007 GTP-Binding Proteins Human genes 0.000 claims 1
- 108091000058 GTP-Binding Proteins Proteins 0.000 claims 1
- COCFEDIXXNGUNL-RFKWWTKHSA-N Glargine Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(=O)NCC(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 COCFEDIXXNGUNL-RFKWWTKHSA-N 0.000 claims 1
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- 208000005764 Peripheral Arterial Disease Diseases 0.000 claims 1
- 206010062585 Peripheral arterial occlusive disease Diseases 0.000 claims 1
- VGYFMXBACGZSIL-MCBHFWOFSA-N Pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 claims 1
- 210000002381 Plasma Anatomy 0.000 claims 1
- 229960002965 Pravastatin Drugs 0.000 claims 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N Pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims 1
- 102000001253 Protein Kinases Human genes 0.000 claims 1
- 108060006633 Protein Kinases Proteins 0.000 claims 1
- BPRHUIZQVSMCRT-VEUZHWNKSA-N Rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 claims 1
- RYMZZMVNJRMUDD-HGQWONQESA-N Simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims 1
- 102000004117 Somatostatin receptor 3 Human genes 0.000 claims 1
- 108090000674 Somatostatin receptor 3 Proteins 0.000 claims 1
- 208000007814 Unstable Angina Diseases 0.000 claims 1
- 101700086325 WRN Proteins 0.000 claims 1
- 238000010521 absorption reaction Methods 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 239000012190 activator Substances 0.000 claims 1
- 229960005305 adenosine Drugs 0.000 claims 1
- 239000003888 alpha glucosidase inhibitor Substances 0.000 claims 1
- 230000003042 antagnostic Effects 0.000 claims 1
- 239000005557 antagonist Substances 0.000 claims 1
- 239000002260 anti-inflammatory agent Substances 0.000 claims 1
- 229940121363 anti-inflammatory agents Drugs 0.000 claims 1
- 229960005370 atorvastatin Drugs 0.000 claims 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims 1
- 239000003613 bile acid Substances 0.000 claims 1
- 230000001906 cholesterol absorption Effects 0.000 claims 1
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N diguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 claims 1
- 235000020828 fasting Nutrition 0.000 claims 1
- 229960003765 fluvastatin Drugs 0.000 claims 1
- 230000002496 gastric Effects 0.000 claims 1
- 239000003102 growth factor Substances 0.000 claims 1
- 239000002955 immunomodulating agent Substances 0.000 claims 1
- 229960004717 insulin aspart Drugs 0.000 claims 1
- 108010050259 insulin degludec Proteins 0.000 claims 1
- 229960004225 insulin degludec Drugs 0.000 claims 1
- 229960003948 insulin detemir Drugs 0.000 claims 1
- 229960000696 insulin glulisine Drugs 0.000 claims 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 230000004048 modification Effects 0.000 claims 1
- 238000006011 modification reaction Methods 0.000 claims 1
- 150000002814 niacins Chemical class 0.000 claims 1
- 235000001968 nicotinic acid Nutrition 0.000 claims 1
- 235000020660 omega-3 fatty acid Nutrition 0.000 claims 1
- 239000006014 omega-3 oil Substances 0.000 claims 1
- 239000002245 particle Substances 0.000 claims 1
- 229960002797 pitavastatin Drugs 0.000 claims 1
- 229940096700 plain lipid modifying drugs Fibrates Drugs 0.000 claims 1
- 229920001184 polypeptide Polymers 0.000 claims 1
- 102000004196 processed proteins & peptides Human genes 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
- 239000002464 receptor antagonist Substances 0.000 claims 1
- 239000003638 reducing agent Substances 0.000 claims 1
- -1 robastatin Chemical compound 0.000 claims 1
- 229960000672 rosuvastatin Drugs 0.000 claims 1
- 230000003248 secreting Effects 0.000 claims 1
- 229960002855 simvastatin Drugs 0.000 claims 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical compound OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims 1
- 108010006643 xenin 25 Proteins 0.000 claims 1
Claims (20)
該方法は、それを必要としている患者に、該抗体またはその抗原結合断片を、約２週間ごとまたは約４週間ごとに、７５ｍｇ、１５０ｍｇまたは３００ｍｇ投与する工程を含み、
該抗体またはその抗原結合断片は、配列番号２、３、および４に記載の３つの重鎖ＣＤＲ、ならびに配列番号７、８、および１０に記載の３つの軽鎖ＣＤＲを含み、ならびに
該患者は、（ｉ）１型真性糖尿病（Ｔ１ＤＭ）および（ｉｉ）高コレステロール血症を有する、インスリン療法を受けている心血管リスクの高い患者である、
前記医薬組成物。 A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that specifically binds to the human proprotein convertase subtilisin / kexin type 9 (PCSK9) for use in methods of treating hypercholesterolemia.
The method comprises administering 75 mg, 150 mg or 300 mg of the antibody or antigen-binding fragment thereof to a patient in need thereof about every 2 weeks or about every 4 weeks.
The antibody or antigen-binding fragment thereof comprises the three heavy chain CDRs set forth in SEQ ID NOs: 2, 3 and 4, and the three light chain CDRs set forth in SEQ ID NOs: 7, 8 and 10. , (I) Type 1 diabetes mellitus (T1DM) and (ii) hypercholesterolemia, patients at high cardiovascular risk receiving insulin therapy.
The pharmaceutical composition.
該方法は、それを必要としている患者に、該抗体またはその抗原結合断片を、７５ｍｇ、１５０ｍｇまたは３００ｍｇ投与する工程を含み、
該抗体またはその抗原結合断片は、配列番号２、３、および４に記載の３つの重鎖ＣＤＲ、ならびに配列番号７、８、および１０に記載の３つの軽鎖ＣＤＲを含み、ならびに
該患者は、（ｉ）１型真性糖尿病（Ｔ１ＤＭ）および（ｉｉ）高コレステロール血症を有する、インスリン療法を受けている心血管リスクの高い患者である、
前記医薬組成物。 A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that specifically binds to the human proprotein convertase subtilisin / kexin type 9 (PCSK9) for use in methods of treating hypercholesterolemia.
The method comprises administering 75 mg, 150 mg or 300 mg of the antibody or antigen-binding fragment thereof to a patient in need thereof.
The antibody or antigen-binding fragment thereof comprises the three heavy chain CDRs set forth in SEQ ID NOs: 2, 3 and 4, and the three light chain CDRs set forth in SEQ ID NOs: 7, 8 and 10. , (I) Type 1 diabetes mellitus (T1DM) and (ii) hypercholesterolemia, patients at high cardiovascular risk receiving insulin therapy.
The pharmaceutical composition.
（ｂ）１５０ｍｇの抗体または抗原結合断片が２週間ごとに患者に投与される；または
（ｃ）３００ｍｇの抗体または抗原結合断片が４週間ごとに患者に投与される；
請求項１〜５のいずれか一項に記載の医薬組成物。 (A) 75 mg of antibody or antigen binding fragment is administered to the patient every 2 weeks;
(B) 150 mg of antibody or antigen-binding fragment is administered to the patient every 2 weeks; or (c) 300 mg of antibody or antigen-binding fragment is administered to the patient every 4 weeks;
The pharmaceutical composition according to any one of claims 1 to 5.
（ａ）該スタチンが、アトルバスタチン、ロスバスタチン、シンバスタチン、プラバスタチン、ロバスタチン、フルバスタチン、ピタバスタチン、およびセリバスタチンからなる群から選択される；および／または
（ｂ）該スタチン療法が、最大耐性量のスタチン療法である、
請求項１４に記載の医薬組成物。 LMT is a statin therapy
(A) The statin is selected from the group consisting of atorvastatin, rosuvastatin, simvastatin, pravastatin, robastatin, fluvastatin, pitavastatin, and serivastatin; be,
The pharmaceutical composition according to claim 14.
インスリンデテミル、インスリンリスプロ、インスリンデグルデック、インスリンアスパルト、および基礎インスリンからなる群から選択される、請求項１〜１６のいずれか一項に記載の医薬組成物。 Insulin therapy includes human insulin, insulin glargine, insulin glulisine,
The pharmaceutical composition according to any one of claims 1 to 16, selected from the group consisting of insulin detemir, insulin lispro, insulin degludec, insulin aspart, and basal insulin.
（ａ）患者のＬＤＬ−Ｃレベルを少なくとも４０％減少させる；
（ｂ）患者の非ＨＤＬ−Ｃレベルを少なくとも３５％減少させる；
（ｃ）患者のＡｐｏＣ３レベルを減少させる；
（ｄ）患者におけるリポタンパク質粒子の数および／またはサイズを減少させる；
（ｅ）患者のヘモグロビンＡ１ｃ（ＨｂＡ１ｃ）レベルに影響を及ぼさない；および／または
（ｆ）患者の空腹時血漿グルコース（ＦＰＧ）レベルに影響を及ぼさない
請求項１〜１８のいずれか一項に記載の医薬組成物。 Antibodies or antigen-binding fragments thereof:
(A) Reduces LDL-C levels in patients by at least 40%;
(B) Reduce patient non-HDL-C levels by at least 35%;
(C) Decrease ApoC3 levels in patients;
(D) Reduce the number and / or size of lipoprotein particles in patients;
(E) The patient's hemoglobin A1c (HbA1c) level is not affected; and / or (f) the patient's fasting plasma glucose (FPG) level is not affected. Pharmaceutical composition.
それを必要としている患者に、該抗体またはその抗原結合断片を、約２週間ごとに７５ｍｇ投与する工程；および
該患者におけるＬＤＬ−Ｃレベルが７０ｍｇ／ｄＬより低い場合、約２週間ごとに１回またはそれ以上の次の投薬量の７５ｍｇの抗体もしくはその抗原結合断片を患者に投与するか、または患者におけるＬＤＬ−Ｃレベルが７０ｍｇ／ｄＬ以上の場合、約２週間ごとに１回またはそれ以上の次の投薬量の１５０ｍｇの抗体もしくはその抗原結合断片を投与する工程
を含み、
抗体またはその抗原結合断片は、配列番号１のアミノ酸配列を有する重鎖可変領域（ＨＣＶＲ）、および配列番号６のアミノ酸配列を有する軽鎖可変領域（ＬＣＶＲ）を含み、
該患者は、付随するインスリン療法を受け、ならびに
該患者は、（ｉ）１型真性糖尿病（Ｔ１ＤＭ）または２型真性糖尿病（Ｔ２ＤＭ）および（ｉｉ）最大耐性のスタチン療法によっては適切に制御されない高コレステロール血症を有する、インスリン療法を受けている心血管リスクの高い患者である、
前記医薬組成物。 A pharmaceutical composition comprising an antibody that specifically binds to the human proprotein convertase subtilisin / kexin type 9 (PCSK9) or an antigen-binding fragment thereof for use in a method for treating hypercholesterolemia. teeth:
The step of administering 75 mg of the antibody or antigen-binding fragment thereof to a patient in need thereof about every 2 weeks; and if the LDL-C level in the patient is lower than 70 mg / dL, about once every 2 weeks. Or a higher dose of 75 mg antibody or antigen-binding fragment thereof is administered to the patient, or if the LDL-C level in the patient is 70 mg / dL or higher, once or more about every two weeks. Including the step of administering the next dosage of 150 mg antibody or antigen-binding fragment thereof.
The antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR) having the amino acid sequence of SEQ ID NO: 1 and a light chain variable region (LCVR) having the amino acid sequence of SEQ ID NO: 6.
The patient receives concomitant insulin therapy, and the patient is not properly controlled by (i) type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) and (ii) maximally resistant statin therapy. Patients with cholesterolemia who are on high cardiovascular risk receiving insulin therapy,
The pharmaceutical composition.
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| US201762532162P | 2017-07-13 | 2017-07-13 | |
| US62/532,162 | 2017-07-13 | ||
| EP18305565 | 2018-05-04 | ||
| EP18305565.6 | 2018-05-04 | ||
| PCT/IB2018/054182 WO2018225041A1 (en) | 2017-06-09 | 2018-06-09 | Methods for treating hyperlipidemia in diabetic patients by administering a pcsk9 inhibitor |
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| AU2012210480B2 (en) | 2011-01-28 | 2017-05-18 | Sanofi Biotechnology | Human antibodies to PCSK9 for use in methods of treating particular groups of subjects |
| AR087305A1 (en) | 2011-07-28 | 2014-03-12 | Regeneron Pharma | STABILIZED FORMULATIONS CONTAINING ANTI-PCSK9 ANTIBODIES, PREPARATION METHOD AND KIT |
| JP2018523684A (en) | 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． | Anti-PCSK9 inhibitory antibody for treating hyperlipidemic patients undergoing lipoprotein apheresis |
| CN113876956B (en) * | 2020-07-01 | 2023-07-04 | 陈敏 | Application of PCSK9 inhibitor in preparation of product for promoting skin pigmentation |
| CN114525258A (en) * | 2020-10-30 | 2022-05-24 | 未来智人再生医学研究院(广州)有限公司 | Pluripotent stem cell expressing PCSK9 blocker or derivative thereof and application |
| WO2023051822A1 (en) * | 2021-09-30 | 2023-04-06 | 北京安龙生物医药有限公司 | Targeting oligonucleotide for treating diseases associated with pcsk9 |
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| JO3672B1 (en) * | 2008-12-15 | 2020-08-27 | Regeneron Pharma | High Affinity Human Antibodies to PCSK9 |
| MX2017000628A (en) * | 2014-07-16 | 2017-04-27 | Sanofi Biotechnology | Methods for treating high cardiovascular risk patients with hypercholesterolemia. |
| RU2735521C2 (en) * | 2014-07-16 | 2020-11-03 | Санофи Байотекнолоджи | Methods of treating patients with heterozygous familial hypercholesterolemia (hefh) |
| JP2018523684A (en) * | 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． | Anti-PCSK9 inhibitory antibody for treating hyperlipidemic patients undergoing lipoprotein apheresis |
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