WO2012109530A1 - Pcsk9 antagonists - Google Patents
Pcsk9 antagonists Download PDFInfo
- Publication number
- WO2012109530A1 WO2012109530A1 PCT/US2012/024633 US2012024633W WO2012109530A1 WO 2012109530 A1 WO2012109530 A1 WO 2012109530A1 US 2012024633 W US2012024633 W US 2012024633W WO 2012109530 A1 WO2012109530 A1 WO 2012109530A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- antibody
- seq
- pcsk9
- amino acid
- variable region
- Prior art date
Links
- 101150094724 PCSK9 gene Proteins 0.000 title claims description 45
- 239000005557 antagonist Substances 0.000 title abstract description 38
- 102100038955 Proprotein convertase subtilisin/kexin type 9 Human genes 0.000 claims abstract description 120
- 238000000034 method Methods 0.000 claims abstract description 59
- 101001098868 Homo sapiens Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 claims abstract description 14
- 101710180553 Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 claims description 120
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 105
- 150000007523 nucleic acids Chemical class 0.000 claims description 65
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 claims description 58
- 108010001831 LDL receptors Proteins 0.000 claims description 57
- 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 description 56
- 239000000203 mixture Substances 0.000 claims description 46
- 102000039446 nucleic acids Human genes 0.000 claims description 46
- 108020004707 nucleic acids Proteins 0.000 claims description 46
- 210000004602 germ cell Anatomy 0.000 claims description 45
- 239000003795 chemical substances by application Substances 0.000 claims description 36
- 239000003112 inhibitor Substances 0.000 claims description 34
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 29
- 108010028554 LDL Cholesterol Proteins 0.000 claims description 29
- 230000001404 mediated effect Effects 0.000 claims description 25
- 230000015556 catabolic process Effects 0.000 claims description 22
- 235000012000 cholesterol Nutrition 0.000 claims description 22
- 238000006731 degradation reaction Methods 0.000 claims description 22
- 230000002401 inhibitory effect Effects 0.000 claims description 21
- 230000000295 complement effect Effects 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 15
- 230000008685 targeting Effects 0.000 claims description 15
- 102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 claims description 14
- 108010038232 microsomal triglyceride transfer protein Proteins 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 13
- 102000053786 human PCSK9 Human genes 0.000 claims description 13
- 239000012634 fragment Substances 0.000 claims description 12
- 102000002148 Diacylglycerol O-acyltransferase Human genes 0.000 claims description 11
- 108010001348 Diacylglycerol O-acyltransferase Proteins 0.000 claims description 11
- 230000003993 interaction Effects 0.000 claims description 11
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 10
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 10
- 230000002829 reductive effect Effects 0.000 claims description 10
- 238000010494 dissociation reaction Methods 0.000 claims description 9
- 230000005593 dissociations Effects 0.000 claims description 9
- 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 description 7
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims description 7
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 7
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 7
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims description 7
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 7
- AJLFOPYRIVGYMJ-UHFFFAOYSA-N SJ000287055 Natural products C12C(OC(=O)C(C)CC)CCC=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 AJLFOPYRIVGYMJ-UHFFFAOYSA-N 0.000 claims description 7
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 claims description 7
- 229960005370 atorvastatin Drugs 0.000 claims description 7
- 229920000080 bile acid sequestrant Polymers 0.000 claims description 7
- 229960005110 cerivastatin Drugs 0.000 claims description 7
- SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 claims description 7
- 229940125753 fibrate Drugs 0.000 claims description 7
- 229960003765 fluvastatin Drugs 0.000 claims description 7
- 229960004844 lovastatin Drugs 0.000 claims description 7
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims description 7
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims description 7
- 229950009116 mevastatin Drugs 0.000 claims description 7
- AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 claims description 7
- BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 claims description 7
- 229960003512 nicotinic acid Drugs 0.000 claims description 7
- 235000001968 nicotinic acid Nutrition 0.000 claims description 7
- 239000011664 nicotinic acid Substances 0.000 claims description 7
- 229960002797 pitavastatin Drugs 0.000 claims description 7
- 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 description 7
- 229960002965 pravastatin Drugs 0.000 claims description 7
- 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 description 7
- 229960000672 rosuvastatin Drugs 0.000 claims description 7
- 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 description 7
- 229960002855 simvastatin Drugs 0.000 claims description 7
- 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 description 7
- 229940036555 thyroid hormone Drugs 0.000 claims description 7
- 239000005495 thyroid hormone Substances 0.000 claims description 7
- 229940096699 bile acid sequestrants Drugs 0.000 claims description 6
- 230000001906 cholesterol absorption Effects 0.000 claims description 6
- 208000000563 Hyperlipoproteinemia Type II Diseases 0.000 claims description 4
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 claims description 4
- 201000001386 familial hypercholesterolemia Diseases 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 102000014914 Carrier Proteins Human genes 0.000 claims description 2
- 108010078791 Carrier Proteins Proteins 0.000 claims description 2
- 206010064571 Gene mutation Diseases 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 102000000853 LDL receptors Human genes 0.000 claims 3
- FJLGEFLZQAZZCD-MCBHFWOFSA-N (3R,5S)-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-MCBHFWOFSA-N 0.000 claims 2
- 102000006437 Proprotein Convertases Human genes 0.000 abstract description 6
- 108010044159 Proprotein Convertases Proteins 0.000 abstract description 6
- 101710172072 Kexin Proteins 0.000 abstract description 4
- 108090000787 Subtilisin Proteins 0.000 abstract description 4
- 238000009739 binding Methods 0.000 description 154
- 230000027455 binding Effects 0.000 description 152
- 239000000427 antigen Substances 0.000 description 109
- 108091007433 antigens Proteins 0.000 description 107
- 102000036639 antigens Human genes 0.000 description 107
- AVIZABGQXBMRCJ-UHFFFAOYSA-N Mammea A/AB cyclo F Chemical compound C12=C(O)C(C(=O)C(C)CC)=C3OC(C(C)(C)O)CC3=C2OC(=O)C=C1C1=CC=CC=C1 AVIZABGQXBMRCJ-UHFFFAOYSA-N 0.000 description 86
- 210000004027 cell Anatomy 0.000 description 72
- 108090000623 proteins and genes Proteins 0.000 description 58
- 102000004169 proteins and genes Human genes 0.000 description 50
- 235000018102 proteins Nutrition 0.000 description 47
- AVIZABGQXBMRCJ-DYVFJYSZSA-N 1,2-Dihydro-5-hydroxy-2-(1-hydroxy-1-methylethyl)-4-(2-methylbutyryl)-6-phenylfurano[2,3-h][1]benzopyran-8-one Natural products O=C([C@@H](CC)C)c1c(O)c2C(c3ccccc3)=CC(=O)Oc2c2c1O[C@H](C(O)(C)C)C2 AVIZABGQXBMRCJ-DYVFJYSZSA-N 0.000 description 43
- 101100344898 Arabidopsis thaliana MED13 gene Proteins 0.000 description 43
- 101100075829 Caenorhabditis elegans mab-3 gene Proteins 0.000 description 43
- 239000002953 phosphate buffered saline Substances 0.000 description 41
- 235000001014 amino acid Nutrition 0.000 description 39
- 229940024606 amino acid Drugs 0.000 description 38
- 150000001413 amino acids Chemical class 0.000 description 38
- 108090000765 processed proteins & peptides Proteins 0.000 description 37
- 102000004196 processed proteins & peptides Human genes 0.000 description 32
- 241000699666 Mus <mouse, genus> Species 0.000 description 31
- 229920001184 polypeptide Polymers 0.000 description 26
- 102000040430 polynucleotide Human genes 0.000 description 24
- 108091033319 polynucleotide Proteins 0.000 description 24
- 239000002157 polynucleotide Substances 0.000 description 24
- 239000000872 buffer Substances 0.000 description 23
- 230000000694 effects Effects 0.000 description 22
- 238000003556 assay Methods 0.000 description 21
- 210000002381 plasma Anatomy 0.000 description 21
- 101100350216 Arabidopsis thaliana PDH2 gene Proteins 0.000 description 19
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 description 19
- 108010023302 HDL Cholesterol Proteins 0.000 description 19
- 241001529936 Murinae Species 0.000 description 19
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
- 101710117290 Aldo-keto reductase family 1 member C4 Proteins 0.000 description 16
- 241000124008 Mammalia Species 0.000 description 16
- 108091028043 Nucleic acid sequence Proteins 0.000 description 16
- 239000002831 pharmacologic agent Substances 0.000 description 16
- 208000035150 Hypercholesterolemia Diseases 0.000 description 15
- 238000011282 treatment Methods 0.000 description 15
- 238000002965 ELISA Methods 0.000 description 14
- 125000000539 amino acid group Chemical group 0.000 description 14
- 239000000523 sample Substances 0.000 description 14
- 238000005406 washing Methods 0.000 description 14
- 238000004422 calculation algorithm Methods 0.000 description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
- 210000004408 hybridoma Anatomy 0.000 description 13
- 230000001965 increasing effect Effects 0.000 description 13
- 230000035772 mutation Effects 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- YALRCXHVQYBSJC-UHFFFAOYSA-N Mammea A/AB Chemical compound C12=C(O)C(C(=O)C(C)CC)=C(O)C(CC=C(C)C)=C2OC(=O)C=C1C1=CC=CC=C1 YALRCXHVQYBSJC-UHFFFAOYSA-N 0.000 description 12
- 238000001514 detection method Methods 0.000 description 12
- -1 for example Proteins 0.000 description 12
- 239000002609 medium Substances 0.000 description 12
- 239000013598 vector Substances 0.000 description 12
- 108010007622 LDL Lipoproteins Proteins 0.000 description 11
- 102000007330 LDL Lipoproteins Human genes 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 11
- 238000011534 incubation Methods 0.000 description 11
- 108020004705 Codon Proteins 0.000 description 10
- 241000283973 Oryctolagus cuniculus Species 0.000 description 10
- 229920001213 Polysorbate 20 Polymers 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 10
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 10
- 238000007792 addition Methods 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 239000008194 pharmaceutical composition Substances 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 238000006467 substitution reaction Methods 0.000 description 9
- 241000283707 Capra Species 0.000 description 8
- 108060003951 Immunoglobulin Proteins 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 230000037396 body weight Effects 0.000 description 8
- 238000010790 dilution Methods 0.000 description 8
- 239000012895 dilution Substances 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 8
- 102000018358 immunoglobulin Human genes 0.000 description 8
- 238000001802 infusion Methods 0.000 description 8
- 239000006228 supernatant Substances 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 108010010234 HDL Lipoproteins Proteins 0.000 description 7
- 102000015779 HDL Lipoproteins Human genes 0.000 description 7
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 7
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 7
- 239000011230 binding agent Substances 0.000 description 7
- 230000005284 excitation Effects 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 230000036470 plasma concentration Effects 0.000 description 7
- 108010061846 Cholesterol Ester Transfer Proteins Proteins 0.000 description 6
- 102000012336 Cholesterol Ester Transfer Proteins Human genes 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 6
- 102000053602 DNA Human genes 0.000 description 6
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 6
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 239000000556 agonist Substances 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- 230000002998 immunogenetic effect Effects 0.000 description 6
- 239000002773 nucleotide Substances 0.000 description 6
- 125000003729 nucleotide group Chemical group 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].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 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 5
- 238000012286 ELISA Assay Methods 0.000 description 5
- 241000282567 Macaca fascicularis Species 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 239000007983 Tris buffer Substances 0.000 description 5
- 210000004899 c-terminal region Anatomy 0.000 description 5
- 230000001186 cumulative effect Effects 0.000 description 5
- 230000029087 digestion Effects 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 238000012216 screening Methods 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
- 201000001320 Atherosclerosis Diseases 0.000 description 4
- 102000009109 Fc receptors Human genes 0.000 description 4
- 108010087819 Fc receptors Proteins 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 108010093488 His-His-His-His-His-His Proteins 0.000 description 4
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 4
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 4
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical group CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 4
- 108091005461 Nucleic proteins Proteins 0.000 description 4
- 229930040373 Paraformaldehyde Natural products 0.000 description 4
- 239000004743 Polypropylene Substances 0.000 description 4
- 241000283984 Rodentia Species 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 230000009824 affinity maturation Effects 0.000 description 4
- 239000003524 antilipemic agent Substances 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 239000013604 expression vector Substances 0.000 description 4
- 230000004927 fusion Effects 0.000 description 4
- 238000003018 immunoassay Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 229930182817 methionine Chemical group 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 229920002866 paraformaldehyde Polymers 0.000 description 4
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 4
- 238000002823 phage display Methods 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 229920001155 polypropylene Polymers 0.000 description 4
- 230000000069 prophylactic effect Effects 0.000 description 4
- 238000000159 protein binding assay Methods 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 230000009870 specific binding Effects 0.000 description 4
- 229960001967 tacrolimus Drugs 0.000 description 4
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 4
- 238000004448 titration Methods 0.000 description 4
- 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 description 3
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 108700028369 Alleles Proteins 0.000 description 3
- AXRYRYVKAWYZBR-UHFFFAOYSA-N Atazanavir Natural products C=1C=C(C=2N=CC=CC=2)C=CC=1CN(NC(=O)C(NC(=O)OC)C(C)(C)C)CC(O)C(NC(=O)C(NC(=O)OC)C(C)(C)C)CC1=CC=CC=C1 AXRYRYVKAWYZBR-UHFFFAOYSA-N 0.000 description 3
- 108010019625 Atazanavir Sulfate Proteins 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- QAGYKUNXZHXKMR-UHFFFAOYSA-N CPD000469186 Natural products CC1=C(O)C=CC=C1C(=O)NC(C(O)CN1C(CC2CCCCC2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-UHFFFAOYSA-N 0.000 description 3
- 229920001268 Cholestyramine Polymers 0.000 description 3
- KPSRODZRAIWAKH-JTQLQIEISA-N Ciprofibrate Natural products C1=CC(OC(C)(C)C(O)=O)=CC=C1[C@H]1C(Cl)(Cl)C1 KPSRODZRAIWAKH-JTQLQIEISA-N 0.000 description 3
- 229920002911 Colestipol Polymers 0.000 description 3
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 3
- 101710088335 Diacylglycerol acyltransferase/mycolyltransferase Ag85A Proteins 0.000 description 3
- 101710088334 Diacylglycerol acyltransferase/mycolyltransferase Ag85B Proteins 0.000 description 3
- 101710088427 Diacylglycerol acyltransferase/mycolyltransferase Ag85C Proteins 0.000 description 3
- 241001050985 Disco Species 0.000 description 3
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 3
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 3
- KJHKTHWMRKYKJE-SUGCFTRWSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O KJHKTHWMRKYKJE-SUGCFTRWSA-N 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000315040 Omura Species 0.000 description 3
- 102000057297 Pepsin A Human genes 0.000 description 3
- 108090000284 Pepsin A Proteins 0.000 description 3
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 3
- 102000001494 Sterol O-Acyltransferase Human genes 0.000 description 3
- 108010054082 Sterol O-acyltransferase Proteins 0.000 description 3
- 108010090804 Streptavidin Proteins 0.000 description 3
- SUJUHGSWHZTSEU-UHFFFAOYSA-N Tipranavir Natural products C1C(O)=C(C(CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)C(=O)OC1(CCC)CCC1=CC=CC=C1 SUJUHGSWHZTSEU-UHFFFAOYSA-N 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 229960001830 amprenavir Drugs 0.000 description 3
- YMARZQAQMVYCKC-OEMFJLHTSA-N amprenavir Chemical compound C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 YMARZQAQMVYCKC-OEMFJLHTSA-N 0.000 description 3
- 239000012131 assay buffer Substances 0.000 description 3
- 229960003277 atazanavir Drugs 0.000 description 3
- AXRYRYVKAWYZBR-GASGPIRDSA-N atazanavir Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)[C@@H](O)CN(CC=1C=CC(=CC=1)C=1N=CC=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C1=CC=CC=C1 AXRYRYVKAWYZBR-GASGPIRDSA-N 0.000 description 3
- 229960000516 bezafibrate Drugs 0.000 description 3
- IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 3
- 239000003613 bile acid Substances 0.000 description 3
- 238000012575 bio-layer interferometry Methods 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 229960002174 ciprofibrate Drugs 0.000 description 3
- KPSRODZRAIWAKH-UHFFFAOYSA-N ciprofibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1C1C(Cl)(Cl)C1 KPSRODZRAIWAKH-UHFFFAOYSA-N 0.000 description 3
- 229960001214 clofibrate Drugs 0.000 description 3
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 229960002604 colestipol Drugs 0.000 description 3
- GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 208000029078 coronary artery disease Diseases 0.000 description 3
- 229960005107 darunavir Drugs 0.000 description 3
- CJBJHOAVZSMMDJ-HEXNFIEUSA-N darunavir Chemical compound C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1[C@@H]2CCO[C@@H]2OC1)C1=CC=CC=C1 CJBJHOAVZSMMDJ-HEXNFIEUSA-N 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 229910052805 deuterium Inorganic materials 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000007876 drug discovery Methods 0.000 description 3
- 230000009977 dual effect Effects 0.000 description 3
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 description 3
- 229960002297 fenofibrate Drugs 0.000 description 3
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 229960003142 fosamprenavir Drugs 0.000 description 3
- MLBVMOWEQCZNCC-OEMFJLHTSA-N fosamprenavir Chemical compound C([C@@H]([C@H](OP(O)(O)=O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 MLBVMOWEQCZNCC-OEMFJLHTSA-N 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 229960003627 gemfibrozil Drugs 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 229960001936 indinavir Drugs 0.000 description 3
- CBVCZFGXHXORBI-PXQQMZJSSA-N indinavir Chemical compound C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 CBVCZFGXHXORBI-PXQQMZJSSA-N 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 229960004525 lopinavir Drugs 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- FJQXCDYVZAHXNS-UHFFFAOYSA-N methadone hydrochloride Chemical compound Cl.C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 FJQXCDYVZAHXNS-UHFFFAOYSA-N 0.000 description 3
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 3
- 229960000884 nelfinavir Drugs 0.000 description 3
- QAGYKUNXZHXKMR-HKWSIXNMSA-N nelfinavir Chemical compound CC1=C(O)C=CC=C1C(=O)N[C@H]([C@H](O)CN1[C@@H](C[C@@H]2CCCC[C@@H]2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-HKWSIXNMSA-N 0.000 description 3
- 229940111202 pepsin Drugs 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 229960000311 ritonavir Drugs 0.000 description 3
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 3
- 229920002477 rna polymer Polymers 0.000 description 3
- 239000012898 sample dilution Substances 0.000 description 3
- 229960001852 saquinavir Drugs 0.000 description 3
- QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 description 3
- 230000003248 secreting effect Effects 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 238000013207 serial dilution Methods 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000012679 serum free medium Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000004885 tandem mass spectrometry Methods 0.000 description 3
- 229960000838 tipranavir Drugs 0.000 description 3
- SUJUHGSWHZTSEU-FYBSXPHGSA-N tipranavir Chemical compound C([C@@]1(CCC)OC(=O)C([C@H](CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)=C(O)C1)CC1=CC=CC=C1 SUJUHGSWHZTSEU-FYBSXPHGSA-N 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 230000032258 transport Effects 0.000 description 3
- 229940111527 trizivir Drugs 0.000 description 3
- 230000003442 weekly effect Effects 0.000 description 3
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 3
- 229960002555 zidovudine Drugs 0.000 description 3
- CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 241000282465 Canis Species 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 241000699800 Cricetinae Species 0.000 description 2
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 2
- 101100346152 Drosophila melanogaster modSP gene Proteins 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000283073 Equus caballus Species 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 241000282324 Felis Species 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 2
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical group CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- 101150013552 LDLR gene Proteins 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 101100135848 Mus musculus Pcsk9 gene Proteins 0.000 description 2
- 238000012408 PCR amplification Methods 0.000 description 2
- 229920002873 Polyethylenimine Polymers 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 101100135853 Rattus norvegicus Pcsk9 gene Proteins 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000007413 biotinylation Methods 0.000 description 2
- 230000006287 biotinylation Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 101150046240 bsd gene Proteins 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000011260 co-administration Methods 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 2
- 238000011033 desalting Methods 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 239000012893 effector ligand Substances 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000003306 harvesting Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000008676 import Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 238000005304 joining Methods 0.000 description 2
- 108010022197 lipoprotein cholesterol Proteins 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000000291 postprandial effect Effects 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 230000004797 therapeutic response Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 239000012096 transfection reagent Substances 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 238000011179 visual inspection Methods 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- DBGIVFWFUFKIQN-UHFFFAOYSA-N (+-)-Fenfluramine Chemical compound CCNC(C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-UHFFFAOYSA-N 0.000 description 1
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- VGONTNSXDCQUGY-RRKCRQDMSA-N 2'-deoxyinosine Chemical group C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC2=O)=C2N=C1 VGONTNSXDCQUGY-RRKCRQDMSA-N 0.000 description 1
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 235000002198 Annona diversifolia Nutrition 0.000 description 1
- 101150102415 Apob gene Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- CEUORZQYGODEFX-UHFFFAOYSA-N Aripirazole Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)CCC4=CC=3)CC2)=C1Cl CEUORZQYGODEFX-UHFFFAOYSA-N 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 108010037058 Bacterial Secretion Systems Proteins 0.000 description 1
- 241001589086 Bellapiscis medius Species 0.000 description 1
- 108050003866 Bifunctional ligase/repressor BirA Proteins 0.000 description 1
- 102100033743 Biotin-[acetyl-CoA-carboxylase] ligase Human genes 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282832 Camelidae Species 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 229940122502 Cholesterol absorption inhibitor Drugs 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- 102000010911 Enzyme Precursors Human genes 0.000 description 1
- 108010062466 Enzyme Precursors Proteins 0.000 description 1
- 229910052693 Europium Inorganic materials 0.000 description 1
- 238000004252 FT/ICR mass spectrometry Methods 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000690301 Homo sapiens Aldo-keto reductase family 1 member C4 Proteins 0.000 description 1
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 1
- 101001116548 Homo sapiens Protein CBFA2T1 Proteins 0.000 description 1
- 101000835093 Homo sapiens Transferrin receptor protein 1 Proteins 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
- 102000012745 Immunoglobulin Subunits Human genes 0.000 description 1
- 108010079585 Immunoglobulin Subunits Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 101150008942 J gene Proteins 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical group OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- QEFRNWWLZKMPFJ-ZXPFJRLXSA-N L-methionine (R)-S-oxide Chemical group C[S@@](=O)CC[C@H]([NH3+])C([O-])=O QEFRNWWLZKMPFJ-ZXPFJRLXSA-N 0.000 description 1
- QEFRNWWLZKMPFJ-UHFFFAOYSA-N L-methionine sulphoxide Chemical group CS(=O)CCC(N)C(O)=O QEFRNWWLZKMPFJ-UHFFFAOYSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 238000008214 LDL Cholesterol Methods 0.000 description 1
- 241000282838 Lama Species 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101100098973 Mus musculus Cct5 gene Proteins 0.000 description 1
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 108010021757 Polynucleotide 5'-Hydroxyl-Kinase Proteins 0.000 description 1
- 102000008422 Polynucleotide 5'-hydroxyl-kinase Human genes 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 238000010847 SEQUEST Methods 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 101710135785 Subtilisin-like protease Proteins 0.000 description 1
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 102100026144 Transferrin receptor protein 1 Human genes 0.000 description 1
- 101150117115 V gene Proteins 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 241001416177 Vicugna pacos Species 0.000 description 1
- 108010084455 Zeocin Proteins 0.000 description 1
- 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 Polymers 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 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000012436 analytical size exclusion chromatography Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 238000011091 antibody purification Methods 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960004372 aripiprazole Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 229940127236 atypical antipsychotics Drugs 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 238000010256 biochemical assay Methods 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- UHBYWPGGCSDKFX-UHFFFAOYSA-N carboxyglutamic acid Chemical compound OC(=O)C(N)CC(C(O)=O)C(O)=O UHBYWPGGCSDKFX-UHFFFAOYSA-N 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000009614 chemical analysis method Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000031154 cholesterol homeostasis Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 229960004170 clozapine Drugs 0.000 description 1
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 1
- 238000012761 co-transfection Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 210000003618 cortical neuron Anatomy 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 238000009295 crossflow filtration Methods 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- IJRJBQGVWNVZSA-UHFFFAOYSA-N dilC18(3)(1+) Chemical compound CC1(C)C2=CC=CC=C2N(CCCCCCCCCCCCCCCCCC)C1=CC=CC1=[N+](CCCCCCCCCCCCCCCCCC)C2=CC=CC=C2C1(C)C IJRJBQGVWNVZSA-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000001493 electron microscopy Methods 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000006862 enzymatic digestion Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 235000019534 high fructose corn syrup Nutrition 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 102000054751 human RUNX1T1 Human genes 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 150000002431 hydrogen Chemical group 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 238000011694 lewis rat Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000001785 maturational effect Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-O methylsulfide anion Chemical compound [SH2+]C LSDPWZHWYPCBBB-UHFFFAOYSA-O 0.000 description 1
- 108091070501 miRNA Proteins 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 229960005017 olanzapine Drugs 0.000 description 1
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000008196 pharmacological composition Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- CWCMIVBLVUHDHK-ZSNHEYEWSA-N phleomycin D1 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC[C@@H](N=1)C=1SC=C(N=1)C(=O)NCCCCNC(N)=N)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C CWCMIVBLVUHDHK-ZSNHEYEWSA-N 0.000 description 1
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 238000012514 protein characterization Methods 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 238000000455 protein structure prediction Methods 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 229960004431 quetiapine Drugs 0.000 description 1
- URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000002702 ribosome display Methods 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 229960001534 risperidone Drugs 0.000 description 1
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000013515 script Methods 0.000 description 1
- 230000000276 sedentary effect Effects 0.000 description 1
- 239000004017 serum-free culture medium Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 229960000607 ziprasidone Drugs 0.000 description 1
- MVWVFYHBGMAFLY-UHFFFAOYSA-N ziprasidone Chemical compound C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 MVWVFYHBGMAFLY-UHFFFAOYSA-N 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/44—Antibodies bound to carriers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
Claims
Priority Applications (10)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA2827091A CA2827091A1 (en) | 2011-02-11 | 2012-02-10 | Pcsk9 antagonists |
EA201391157A EA201391157A1 (en) | 2011-02-11 | 2012-02-10 | PCTA9 ANTAGONISTS |
JP2013553586A JP2014511378A (en) | 2011-02-11 | 2012-02-10 | PCSK9 antagonist |
BR112013020402A BR112013020402A2 (en) | 2011-02-11 | 2012-02-10 | pcsk9 antagonists |
EP12705564.8A EP2673302A1 (en) | 2011-02-11 | 2012-02-10 | Pcsk9 antagonists |
KR1020137023909A KR20140006022A (en) | 2011-02-11 | 2012-02-10 | Pcsk9 antagonists |
AU2012214251A AU2012214251A1 (en) | 2011-02-11 | 2012-02-10 | PCSK9 antagonists |
MX2013009258A MX2013009258A (en) | 2011-02-11 | 2012-02-10 | Pcsk9 antagonists. |
CN201280017658.2A CN103562227B (en) | 2011-02-11 | 2012-02-10 | PCSK9 antagonist |
US13/984,785 US20130315927A1 (en) | 2011-02-11 | 2012-02-10 | Pcsk9 antagonists |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201161442126P | 2011-02-11 | 2011-02-11 | |
US61/442,126 | 2011-02-11 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2012109530A1 true WO2012109530A1 (en) | 2012-08-16 |
Family
ID=45755544
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2012/024633 WO2012109530A1 (en) | 2011-02-11 | 2012-02-10 | Pcsk9 antagonists |
Country Status (11)
Country | Link |
---|---|
US (1) | US20130315927A1 (en) |
EP (1) | EP2673302A1 (en) |
JP (1) | JP2014511378A (en) |
KR (1) | KR20140006022A (en) |
CN (1) | CN103562227B (en) |
AU (2) | AU2012214251A1 (en) |
BR (1) | BR112013020402A2 (en) |
CA (1) | CA2827091A1 (en) |
EA (1) | EA201391157A1 (en) |
MX (1) | MX2013009258A (en) |
WO (1) | WO2012109530A1 (en) |
Cited By (114)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014081780A1 (en) | 2012-11-21 | 2014-05-30 | Amgen Inc. | Drug delivery device |
WO2014144080A2 (en) * | 2013-03-15 | 2014-09-18 | Amgen Inc. | Human antigen binding proteins that bind to proprotein convertase subtilisin kexin type 9 |
WO2014144096A1 (en) | 2013-03-15 | 2014-09-18 | Amgen Inc. | Drug cassette, autoinjector, and autoinjector system |
WO2014149357A1 (en) | 2013-03-22 | 2014-09-25 | Amgen Inc. | Injector and method of assembly |
WO2014152540A1 (en) * | 2013-03-15 | 2014-09-25 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
US8859741B2 (en) | 2007-08-23 | 2014-10-14 | Amgen Inc. | Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9) |
US8883157B1 (en) | 2013-12-17 | 2014-11-11 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
WO2014209384A1 (en) | 2013-06-28 | 2014-12-31 | Amgen Inc. | Methods for treating homozygous familial hypercholesterolema |
JP2015007622A (en) * | 2013-05-31 | 2015-01-15 | 株式会社ビー・エム・エル | Screening of pcsk9 relative agent or measurement method of pcsk9 to ascertain administration effect of agent |
US8945560B1 (en) | 2014-07-15 | 2015-02-03 | Kymab Limited | Method of treating rheumatoid arthritis using antibody to IL6R |
WO2015017791A1 (en) * | 2013-08-01 | 2015-02-05 | Atherotech, Inc. | Pcsk9 function assay |
US8980273B1 (en) | 2014-07-15 | 2015-03-17 | Kymab Limited | Method of treating atopic dermatitis or asthma using antibody to IL4RA |
US8986691B1 (en) | 2014-07-15 | 2015-03-24 | Kymab Limited | Method of treating atopic dermatitis or asthma using antibody to IL4RA |
US8986694B1 (en) | 2014-07-15 | 2015-03-24 | Kymab Limited | Targeting human nav1.7 variants for treatment of pain |
US8992927B1 (en) | 2014-07-15 | 2015-03-31 | Kymab Limited | Targeting human NAV1.7 variants for treatment of pain |
US8999341B1 (en) | 2014-07-15 | 2015-04-07 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
US9017678B1 (en) | 2014-07-15 | 2015-04-28 | Kymab Limited | Method of treating rheumatoid arthritis using antibody to IL6R |
WO2015061386A1 (en) | 2013-10-24 | 2015-04-30 | Amgen Inc. | Injector and method of assembly |
WO2015061389A1 (en) | 2013-10-24 | 2015-04-30 | Amgen Inc. | Drug delivery system with temperature-sensitive control |
US9034332B1 (en) | 2014-07-15 | 2015-05-19 | Kymab Limited | Precision medicine by targeting rare human PCSK9 variants for cholesterol treatment |
US9045545B1 (en) | 2014-07-15 | 2015-06-02 | Kymab Limited | Precision medicine by targeting PD-L1 variants for treatment of cancer |
US9045548B1 (en) | 2014-07-15 | 2015-06-02 | Kymab Limited | Precision Medicine by targeting rare human PCSK9 variants for cholesterol treatment |
US9051378B1 (en) | 2014-07-15 | 2015-06-09 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
US9062105B1 (en) | 2014-07-15 | 2015-06-23 | Kymab Limited | Precision Medicine by targeting VEGF-A variants for treatment of retinopathy |
US9067998B1 (en) | 2014-07-15 | 2015-06-30 | Kymab Limited | Targeting PD-1 variants for treatment of cancer |
WO2015119906A1 (en) | 2014-02-05 | 2015-08-13 | Amgen Inc. | Drug delivery system with electromagnetic field generator |
GB2523527A (en) * | 2013-04-05 | 2015-09-02 | Weiming Xu | Screen compounds for the modulation of proprotein convertase subtilisin/kexin type 9(PCSK9) |
US9139648B1 (en) | 2014-07-15 | 2015-09-22 | Kymab Limited | Precision medicine by targeting human NAV1.9 variants for treatment of pain |
US9150660B1 (en) | 2014-07-15 | 2015-10-06 | Kymab Limited | Precision Medicine by targeting human NAV1.8 variants for treatment of pain |
WO2015171777A1 (en) | 2014-05-07 | 2015-11-12 | Amgen Inc. | Autoinjector with shock reducing elements |
WO2015187797A1 (en) | 2014-06-03 | 2015-12-10 | Amgen Inc. | Controllable drug delivery system and method of use |
WO2016061220A2 (en) | 2014-10-14 | 2016-04-21 | Amgen Inc. | Drug injection device with visual and audio indicators |
WO2016100781A1 (en) | 2014-12-19 | 2016-06-23 | Amgen Inc. | Drug delivery device with proximity sensor |
WO2016100055A1 (en) | 2014-12-19 | 2016-06-23 | Amgen Inc. | Drug delivery device with live button or user interface field |
WO2016133947A1 (en) | 2015-02-17 | 2016-08-25 | Amgen Inc. | Drug delivery device with vacuum assisted securement and/or feedback |
WO2016138434A1 (en) | 2015-02-27 | 2016-09-01 | Amgen Inc. | Drug delivery device having a needle guard mechanism with a tunable threshold of resistance to needle guard movement |
US9540449B2 (en) | 2012-08-13 | 2017-01-10 | Regeneron Pharmaceuticals, Inc. | Anti-PCSK9 antibodies with pH-dependent binding characteristics |
US9550837B2 (en) | 2008-12-15 | 2017-01-24 | Regeneron Pharmaceuticals, Inc. | Therapeutic uses of anti-PCSK9 antibodies |
US9561155B2 (en) | 2011-01-28 | 2017-02-07 | Sanofi Biotechnology | Method of reducing cholesterol levels using a human anti-PCSK9 antibody |
WO2017039786A1 (en) | 2015-09-02 | 2017-03-09 | Amgen Inc. | Syringe assembly adapter for a syringe |
WO2017100501A1 (en) | 2015-12-09 | 2017-06-15 | Amgen Inc. | Auto-injector with signaling cap |
WO2017118307A1 (en) | 2016-01-05 | 2017-07-13 | 江苏恒瑞医药股份有限公司 | Pcsk9 antibody, antigen-binding fragment thereof, and medical uses thereof |
WO2017120178A1 (en) | 2016-01-06 | 2017-07-13 | Amgen Inc. | Auto-injector with signaling electronics |
US9724411B2 (en) | 2008-12-15 | 2017-08-08 | Regeneron Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia and reducing LDL-C using antibodies to PCSK9 |
WO2017160799A1 (en) | 2016-03-15 | 2017-09-21 | Amgen Inc. | Reducing probability of glass breakage in drug delivery devices |
WO2017189089A1 (en) | 2016-04-29 | 2017-11-02 | Amgen Inc. | Drug delivery device with messaging label |
WO2017192287A1 (en) | 2016-05-02 | 2017-11-09 | Amgen Inc. | Syringe adapter and guide for filling an on-body injector |
WO2017197222A1 (en) | 2016-05-13 | 2017-11-16 | Amgen Inc. | Vial sleeve assembly |
WO2017200989A1 (en) | 2016-05-16 | 2017-11-23 | Amgen Inc. | Data encryption in medical devices with limited computational capability |
WO2017209899A1 (en) | 2016-06-03 | 2017-12-07 | Amgen Inc. | Impact testing apparatuses and methods for drug delivery devices |
WO2018004842A1 (en) | 2016-07-01 | 2018-01-04 | Amgen Inc. | Drug delivery device having minimized risk of component fracture upon impact events |
WO2018034784A1 (en) | 2016-08-17 | 2018-02-22 | Amgen Inc. | Drug delivery device with placement detection |
WO2018081234A1 (en) | 2016-10-25 | 2018-05-03 | Amgen Inc. | On-body injector |
WO2018136398A1 (en) | 2017-01-17 | 2018-07-26 | Amgen Inc. | Injection devices and related methods of use and assembly |
WO2018151890A1 (en) | 2017-02-17 | 2018-08-23 | Amgen Inc. | Drug delivery device with sterile fluid flowpath and related method of assembly |
WO2018152073A1 (en) | 2017-02-17 | 2018-08-23 | Amgen Inc. | Insertion mechanism for drug delivery device |
WO2018165499A1 (en) | 2017-03-09 | 2018-09-13 | Amgen Inc. | Insertion mechanism for drug delivery device |
WO2018165143A1 (en) | 2017-03-06 | 2018-09-13 | Amgen Inc. | Drug delivery device with activation prevention feature |
WO2018164829A1 (en) | 2017-03-07 | 2018-09-13 | Amgen Inc. | Needle insertion by overpressure |
US10076571B2 (en) | 2011-09-16 | 2018-09-18 | Regeneron Pharmaceuticals, Inc. | Methods for reducing lipoprotein(a) levels by administering an inhibitor of proprotein convertase subtilisin kexin-9 (PCSK9) |
WO2018183039A1 (en) | 2017-03-28 | 2018-10-04 | Amgen Inc. | Plunger rod and syringe assembly system and method |
WO2018189705A1 (en) | 2017-04-13 | 2018-10-18 | Cadila Healthcare Limited | Novel peptide based pcsk9 vaccine |
US10111953B2 (en) | 2013-05-30 | 2018-10-30 | Regeneron Pharmaceuticals, Inc. | Methods for reducing remnant cholesterol and other lipoprotein fractions by administering an inhibitor of proprotein convertase subtilisin kexin-9 (PCSK9) |
WO2018226515A1 (en) | 2017-06-08 | 2018-12-13 | Amgen Inc. | Syringe assembly for a drug delivery device and method of assembly |
WO2018226565A1 (en) | 2017-06-08 | 2018-12-13 | Amgen Inc. | Torque driven drug delivery device |
WO2018236619A1 (en) | 2017-06-22 | 2018-12-27 | Amgen Inc. | Device activation impact/shock reduction |
WO2018237225A1 (en) | 2017-06-23 | 2018-12-27 | Amgen Inc. | Electronic drug delivery device comprising a cap activated by a switch assembly |
WO2019014014A1 (en) | 2017-07-14 | 2019-01-17 | Amgen Inc. | Needle insertion-retraction system having dual torsion spring system |
WO2019018169A1 (en) | 2017-07-21 | 2019-01-24 | Amgen Inc. | Gas permeable sealing member for drug container and methods of assembly |
WO2019022951A1 (en) | 2017-07-25 | 2019-01-31 | Amgen Inc. | Drug delivery device with gear module and related method of assembly |
WO2019022950A1 (en) | 2017-07-25 | 2019-01-31 | Amgen Inc. | Drug delivery device with container access system and related method of assembly |
WO2019032482A2 (en) | 2017-08-09 | 2019-02-14 | Amgen Inc. | Hydraulic-pneumatic pressurized chamber drug delivery system |
WO2019036181A1 (en) | 2017-08-18 | 2019-02-21 | Amgen Inc. | Wearable injector with sterile adhesive patch |
WO2019040548A1 (en) | 2017-08-22 | 2019-02-28 | Amgen Inc. | Needle insertion mechanism for drug delivery device |
WO2019070472A1 (en) | 2017-10-04 | 2019-04-11 | Amgen Inc. | Flow adapter for drug delivery device |
WO2019070552A1 (en) | 2017-10-06 | 2019-04-11 | Amgen Inc. | Drug delivery device with interlock assembly and related method of assembly |
WO2019074579A1 (en) | 2017-10-09 | 2019-04-18 | Amgen Inc. | Drug delivery device with drive assembly and related method of assembly |
WO2019090303A1 (en) | 2017-11-06 | 2019-05-09 | Amgen Inc. | Fill-finish assemblies and related methods |
WO2019090086A1 (en) | 2017-11-03 | 2019-05-09 | Amgen Inc. | Systems and approaches for sterilizing a drug delivery device |
WO2019089178A1 (en) | 2017-11-06 | 2019-05-09 | Amgen Inc. | Drug delivery device with placement and flow sensing |
WO2019094138A1 (en) | 2017-11-10 | 2019-05-16 | Amgen Inc. | Plungers for drug delivery devices |
WO2019099324A1 (en) | 2017-11-16 | 2019-05-23 | Amgen Inc. | Door latch mechanism for drug delivery device |
WO2019099322A1 (en) | 2017-11-16 | 2019-05-23 | Amgen Inc. | Autoinjector with stall and end point detection |
US10323076B2 (en) | 2013-10-03 | 2019-06-18 | Modernatx, Inc. | Polynucleotides encoding low density lipoprotein receptor |
US10428157B2 (en) | 2013-11-12 | 2019-10-01 | Sanofi Biotechnology | Dosing regimens for use with PCSK9 inhibitors |
US10472425B2 (en) | 2011-07-28 | 2019-11-12 | Regeneron Pharmaceuticals, Inc. | Stabilized formulations containing anti-PCSK9 antibodies |
US10494442B2 (en) | 2013-06-07 | 2019-12-03 | Sanofi Biotechnology | Methods for inhibiting atherosclerosis by administering an inhibitor of PCSK9 |
WO2019231618A1 (en) | 2018-06-01 | 2019-12-05 | Amgen Inc. | Modular fluid path assemblies for drug delivery devices |
WO2019231582A1 (en) | 2018-05-30 | 2019-12-05 | Amgen Inc. | Thermal spring release mechanism for a drug delivery device |
EP3593839A1 (en) | 2013-03-15 | 2020-01-15 | Amgen Inc. | Drug cassette |
US10544232B2 (en) | 2014-07-16 | 2020-01-28 | Sanofi Biotechnology | Methods for treating patients with heterozygous familial hypercholesterolemia (heFH) with an anti-PCSK9 antibody |
WO2020023451A1 (en) | 2018-07-24 | 2020-01-30 | Amgen Inc. | Delivery devices for administering drugs |
WO2020023220A1 (en) | 2018-07-24 | 2020-01-30 | Amgen Inc. | Hybrid drug delivery devices with tacky skin attachment portion and related method of preparation |
WO2020023336A1 (en) | 2018-07-24 | 2020-01-30 | Amgen Inc. | Hybrid drug delivery devices with grip portion |
WO2020023444A1 (en) | 2018-07-24 | 2020-01-30 | Amgen Inc. | Delivery devices for administering drugs |
WO2020028009A1 (en) | 2018-07-31 | 2020-02-06 | Amgen Inc. | Fluid path assembly for a drug delivery device |
WO2020068476A1 (en) | 2018-09-28 | 2020-04-02 | Amgen Inc. | Muscle wire escapement activation assembly for a drug delivery device |
WO2020068623A1 (en) | 2018-09-24 | 2020-04-02 | Amgen Inc. | Interventional dosing systems and methods |
WO2020072846A1 (en) | 2018-10-05 | 2020-04-09 | Amgen Inc. | Drug delivery device having dose indicator |
WO2020072577A1 (en) | 2018-10-02 | 2020-04-09 | Amgen Inc. | Injection systems for drug delivery with internal force transmission |
WO2020081479A1 (en) | 2018-10-15 | 2020-04-23 | Amgen Inc. | Drug delivery device having damping mechanism |
WO2020081480A1 (en) | 2018-10-15 | 2020-04-23 | Amgen Inc. | Platform assembly process for drug delivery device |
WO2020092056A1 (en) | 2018-11-01 | 2020-05-07 | Amgen Inc. | Drug delivery devices with partial needle retraction |
WO2020091981A1 (en) | 2018-11-01 | 2020-05-07 | Amgen Inc. | Drug delivery devices with partial drug delivery member retraction |
WO2020091956A1 (en) | 2018-11-01 | 2020-05-07 | Amgen Inc. | Drug delivery devices with partial drug delivery member retraction |
US10688119B2 (en) | 2015-03-20 | 2020-06-23 | Aarhus Universitet | Inhibitors of PCSK9 for treatment of lipoprotein metabolism disorders |
WO2020150473A2 (en) | 2019-01-18 | 2020-07-23 | Dogma Therapeutics, Inc. | Pcsk9 inhibitors and methods of use thereof |
US10772956B2 (en) | 2015-08-18 | 2020-09-15 | Regeneron Pharmaceuticals, Inc. | Methods for reducing or eliminating the need for lipoprotein apheresis in patients with hyperlipidemia by administering alirocumab |
US10793643B2 (en) | 2015-12-31 | 2020-10-06 | Jiangsu Hengrui Medicine Co., Ltd. | PCSK9 antibody, antigen-binding fragment thereof, and medical application thereof |
WO2020219482A1 (en) | 2019-04-24 | 2020-10-29 | Amgen Inc. | Syringe sterilization verification assemblies and methods |
WO2021041067A2 (en) | 2019-08-23 | 2021-03-04 | Amgen Inc. | Drug delivery device with configurable needle shield engagement components and related methods |
WO2022246055A1 (en) | 2021-05-21 | 2022-11-24 | Amgen Inc. | Method of optimizing a filling recipe for a drug container |
US11753479B2 (en) | 2014-03-04 | 2023-09-12 | Kymab Limited | Nucleic acids encoding anti-OX40L antibodies |
US11779604B2 (en) | 2016-11-03 | 2023-10-10 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses and methods |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9255154B2 (en) | 2012-05-08 | 2016-02-09 | Alderbio Holdings, Llc | Anti-PCSK9 antibodies and use thereof |
CN105085684B (en) * | 2014-05-14 | 2020-04-17 | 上海亨臻实业有限公司 | Design and application of PCSK9 targeted recombinant vaccine |
CN105801701B (en) * | 2016-03-31 | 2019-03-29 | 河北仁博科技有限公司 | The heavy chain and light chain variable region of a kind of PCSK9 antibody and its application |
JOP20190112A1 (en) | 2016-11-14 | 2019-05-14 | Amgen Inc | Combined therapies for atherosclerosis, including atherosclerotic cardiovascular disease |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
US5624821A (en) | 1987-03-18 | 1997-04-29 | Scotgen Biopharmaceuticals Incorporated | Antibodies with altered effector functions |
US20050255552A1 (en) | 2004-01-20 | 2005-11-17 | Kalobios, Inc. | Antibody specificity transfer using minimal essential binding determinants |
US20060134098A1 (en) | 2004-11-16 | 2006-06-22 | Kalobios, Inc. | Immunoglobulin variable region cassette exchange |
US20070020685A1 (en) | 2005-07-22 | 2007-01-25 | Kalobios Pharmaceuticals, Inc. | Secretion of antibodies without signal peptides from bacteria |
WO2009026558A1 (en) * | 2007-08-23 | 2009-02-26 | Amgen Inc. | Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (pcsk9) |
WO2009100297A1 (en) * | 2008-02-07 | 2009-08-13 | Merck & Co., Inc. | 1d05 pcsk9 antagonists |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050008625A1 (en) * | 2003-02-13 | 2005-01-13 | Kalobios, Inc. | Antibody affinity engineering by serial epitope-guided complementarity replacement |
AR066042A1 (en) * | 2007-04-13 | 2009-07-22 | Novartis Ag | MOLECULES AND METHODS TO MODULATE PROTEIN CONVERTASA-SUBTILISIN / QUEXIN TYPE 9 (PCSK9) |
WO2009055783A2 (en) * | 2007-10-26 | 2009-04-30 | Schering Corporation | Anti-pcsk9 and methods for treating lipid and cholesterol disorders |
-
2012
- 2012-02-10 CN CN201280017658.2A patent/CN103562227B/en not_active Expired - Fee Related
- 2012-02-10 EA EA201391157A patent/EA201391157A1/en unknown
- 2012-02-10 KR KR1020137023909A patent/KR20140006022A/en not_active Application Discontinuation
- 2012-02-10 WO PCT/US2012/024633 patent/WO2012109530A1/en active Application Filing
- 2012-02-10 BR BR112013020402A patent/BR112013020402A2/en not_active IP Right Cessation
- 2012-02-10 EP EP12705564.8A patent/EP2673302A1/en not_active Ceased
- 2012-02-10 CA CA2827091A patent/CA2827091A1/en not_active Abandoned
- 2012-02-10 MX MX2013009258A patent/MX2013009258A/en unknown
- 2012-02-10 AU AU2012214251A patent/AU2012214251A1/en not_active Abandoned
- 2012-02-10 US US13/984,785 patent/US20130315927A1/en not_active Abandoned
- 2012-02-10 JP JP2013553586A patent/JP2014511378A/en active Pending
-
2016
- 2016-05-09 AU AU2016202983A patent/AU2016202983A1/en not_active Abandoned
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US5624821A (en) | 1987-03-18 | 1997-04-29 | Scotgen Biopharmaceuticals Incorporated | Antibodies with altered effector functions |
US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
US20050255552A1 (en) | 2004-01-20 | 2005-11-17 | Kalobios, Inc. | Antibody specificity transfer using minimal essential binding determinants |
US20060134098A1 (en) | 2004-11-16 | 2006-06-22 | Kalobios, Inc. | Immunoglobulin variable region cassette exchange |
US20070020685A1 (en) | 2005-07-22 | 2007-01-25 | Kalobios Pharmaceuticals, Inc. | Secretion of antibodies without signal peptides from bacteria |
WO2009026558A1 (en) * | 2007-08-23 | 2009-02-26 | Amgen Inc. | Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (pcsk9) |
WO2009100297A1 (en) * | 2008-02-07 | 2009-08-13 | Merck & Co., Inc. | 1d05 pcsk9 antagonists |
Non-Patent Citations (90)
Title |
---|
"2009 Physicians' Desk Reference (PDR", 2008 |
"Goodman and Gilman 's The Pharmacological Basis of Therapeutics", 2006, MCGRAW-HILL |
"Martindale: The Complete Drug Reference", 2005, PHARMACEUTICAL PRESS. |
"Remington: The Science and Practice of Pharmacy", 2005, LIPPINCOTT WILLIAMS & WILKINS |
"Sustained and Controlled Release Drug Delivery Systems", 1978, MARCEL DEKKER, INC. |
ABIFADEL ET AL., HUM MUTAT, vol. 30, no. 4, 2009, pages 520 - 9 |
ABIFADEL ET AL., J MED GENET, vol. 45, no. 12, 2008, pages 780 - 6 |
AL-LAZIKANI ET AL., J.MOL.BIOL., vol. 273, 1997, pages 927 - 748 |
ALTSCHUL ET AL., J. MOL. BIOL., vol. 215, 1990, pages 403 - 410 |
ALTSCHUL ET AL., NUC. ACIDS RES., vol. 25, 1977, pages 3389 - 3402 |
AUSUBEL ET AL., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, 1995 |
BATZER ET AL., NUCLEIC ACID RES., vol. 19, 1991, pages 5081 |
BAXTER; WEBB, NATURE REVIEWS DRUG DISCOVERY, vol. 8, 2009, pages 308 - 320 |
BAYS; STEIN, EXPERT OPIN PHARMACOTHER, vol. 4, no. 11, 2003, pages 1901 - 38 |
BIRCH ET AL., J MED CHEM, vol. 52, no. 6, 2009, pages 1558 - 68 |
BIRCH ET AL., JMED CHEM, vol. 52, no. 6, 2009, pages 1558 - 68 |
BIRCH ET AL., JMED CLIEM, vol. 52, no. 6, 2009, pages 1558 - 68 |
BOND ET AL., J MOL BIOL., vol. 332, 2003, pages 643 - 55 |
BROOKS ET AL., CURR PSYCHIATRY REP, vol. 11, no. 1, 2009, pages 33 - 40 |
BURNETT; HOOPER, CLIN BIOCHEM REV, vol. 29, no. 1, 2008, pages 11 - 26 |
BURNETT; HOOPER, CLIN BIOCHEM REV., vol. 29, no. 1, 2008, pages 11 - 26 |
CHALMERS ET AL., ANAL CHEM, vol. 78, 2006, pages 1005 - 1014 |
CHANG ET AL., CURR OPIN DRUG DISCO DEVEL, vol. 5, no. 4, 2002, pages 562 - 70 |
CHOTHIA ET AL., J. MOL. BIOL., vol. 227, 1992, pages 799 - 817 |
CHOTHIA, NATURE, vol. 342, 1989, pages 877 - 883 |
CHOTHIA; LESK, J. MOL. BIOL., vol. 196, 1987, pages 901 - 917 |
COLE ET AL.: "Monoclonal Antibodies and Cancer Therapy", 1985, ALAN R. LISS, INC., pages: 77 - 96 |
CREIGHTON, PROTEINS, 1984 |
DUFF CHRISTOPHER J ET AL: "Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor", BIOCHEMICAL JOURNAL, THE BIOCHEMICAL SOCIETY, LONDON, GB, vol. 419, no. 3, 1 May 2009 (2009-05-01), pages 577 - 584, XP002619050, ISSN: 0264-6021 * |
DUMOULIN ET AL., NATURE STRUCT. BIOL., vol. 11, 2002, pages 500 - 515 |
EXP CLIN IMMUNOGENET., vol. 18, no. 4, 2001, pages 242 - 54 |
FASANO ET AL., ATHEROSCLEROSIS, vol. 203, no. 1, 2009, pages 166 - 71 |
GHAHROUDI ET AL., FEBS LETTERS, vol. 414, 1997, pages 521 - 526 |
GIUDICELLI ET AL., NUCLEIC ACIDS RES., vol. 33, 1 January 2005 (2005-01-01), pages D256 - 61 |
HAMPTON ET AL., PNAS, vol. 104, 2007, pages 14604 - 14609 |
HENDERSON, J CLIN PSYCHIATRY, vol. 69, no. 2, 2008, pages E04 |
HENIKOFF; HENIKOFF, PROC. NATL. ACAD. SCI. USA, vol. 89, 1989, pages 10915 |
HEZAREH ET AL., J VIROL, vol. 75, no. 24, pages 12161 - 8 |
JOHNSON ET AL., NUCLEIC ACIDS RES., vol. 29, 2001, pages 205 - 206 |
JONES ET AL., NATURE, vol. 321, 1986, pages 522 - 525 |
JOYCE C Y CHAN ET AL: "A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, NATIONAL ACADEMY OF SCIENCE, WASHINGTON, DC; US, vol. 106, no. 24, 16 June 2009 (2009-06-16), pages 9820 - 9825, XP002657619, ISSN: 0027-8424, [retrieved on 20090514], DOI: 10.1073/PNAS.0903849106 * |
KABAT ET AL.: "Sequences of Proteins of Immunological Interest", 1983, HEALTH AND HUMAN SERVICES |
KABAT ET AL.: "Sequences of Proteins of Immunological Interest", 1983, U.S. DEPT. HEALTH AND HUMAN SERVICES |
KARLIN; ALTSCHUL, PROC. NATL. ACAD. SCI. USA, vol. 90, 1993, pages 5873 - 5787 |
KASTELEIN, INT J CLIN PRACT SUPPL, March 2003 (2003-03-01), pages 45 - 50 |
KOHLER; MILSTEIN, NATURE, vol. 256, 1975, pages 495 - 497 |
KOSTELNY ET AL., J. IMMUNOL., vol. 148, 1992, pages 1547 - 1553 |
KOZBOR ET AL., IMMUNOLOGY TODAY, vol. 4, 1983, pages 72 |
KUBY: "Immunology", 2000, W.H. FREEMAN & CO. |
LE MAY ET AL., ARTERIOSCLER THROMB VASC BIOL, vol. 29, no. 5, 2009, pages 684 - 90 |
LEE ET AL., J MICROBIOL BIOTECHNOL, vol. 18, no. 11, 2008, pages 1785 - 8 |
LEFRANC, EXP CLIN IMMUNOGENET, vol. 18, no. 2, 2001, pages 100 - 16 |
LEFRANC, EXP CLIN IMMUNOGENET., vol. 18, no. 3, 2001, pages 161 - 74 |
LEFRANC, M.P., NUCLEIC ACIDS RES., vol. 29, 2001, pages 207 - 209 |
LI ET AL., RECENT PAT DNA GENE SEQ, 1 November 2009 (2009-11-01) |
MACCALLUM ET AL., J. MOL. BIOL., vol. 262, 1996, pages 732 - 745 |
MARKS ET AL., BIOTECHNOLOGY, vol. 10, 1992, pages 779 - 783 |
MARTIN ET AL., METHODS ENZYMOL., vol. 203, 1991, pages 121 - 153 |
MARTIN ET AL., PROC. NATL. ACAD. SCI. USA, vol. 86, 1989, pages 9268 - 9272 |
MARTINDALE: "Martindale: The Extra Pharmacopoeia", 1996, AMER PHARMACEUTICAL ASSN |
MCCAFFERTY ET AL., NATURE, vol. 348, 1990, pages 552 - 554 |
MORRISON ET AL., PROC. NCITL. ACAD. SCI. USA, vol. 81, 1984 |
MORRISON; OI, ADV. IMMUNOL., vol. 44, 1988, pages 65 - 92 |
NEEDLEMAN; WUNSCH, J. MOL. BIOL., vol. 48, 1970, pages 443 |
OH ET AL., ARCH PHARM RES, vol. 32, no. 1, 2009, pages 43 - 7 |
OHTSUKA ET AL., J. BIOL. CHEM., vol. 260, 1985, pages 2605 - 2608 |
PADLAN, MOLEC. IMMUN., vol. 28, 1991, pages 489 - 498 |
PADLAN, MOLEC. IMMUN., vol. 31, no. 3, 1994, pages 169 - 217 |
PAUL: "Fundamental Immunology", 1993 |
PEARSON; LIPMAN, PROC. NAT'L. ACAD. SCI. USA, vol. 85, 1988, pages 2444 |
PIEHLER ET AL., J IMMUNOL METHODS, vol. 201, 1997, pages 189 - 206 |
POIRIER ET AL., J BIOL CHEM, 2009 |
PRESTA, CURR. OP. STRUCT. BIOL., vol. 2, 1992, pages 593 - 596 |
RASHID S ET AL., PROC NCITL ACAD SCI, vol. 102, 2005, pages 5374 - 5379 |
REES ET AL.: "Protein Structure Prediction", 1996, OXFORD UNIVERSITY PRESS, pages: 141 - 172 |
RIECHMANN ET AL., NATURE, vol. 332, 1988, pages 323 - 327 |
ROSSOLINI ET AL., MOL. CELL. PROBES, vol. 8, 1994, pages 91 - 98 |
RUIZ ET AL., NUCLEIC ACIDS RES., vol. 28, 2000, pages 219 - 221 |
See also references of EP2673302A1 |
SEIDAH, EXPERT OPIN THER TARGETS, vol. 13, no. 1, 2009, pages 19 - 28 |
SMITH; WATERMAN, ADV. APPL. MATH., vol. 2, 1970, pages 482C |
SONGSIVILAI; LACHMANN, CLIN. EXP. IMMUNOL., vol. 79, 1990, pages 315 - 321 |
SUDHOP ET AL., DRUGS, vol. 62, no. 16, 2002, pages 2333 - 47 |
TENENBAUM ET AL., ADV CARDIOL, vol. 45, 2008, pages 127 - 53 |
TOMKIN, DIABETES CARE, vol. 31, no. 2, 2008, pages S241 - S248 |
TOMODA; OMURA, PHARMACOL THER, vol. 115, no. 3, 2007, pages 375 - 89 |
VAUGHAN; SOLLAZZO, COMB CHEM HIGH THROUGHPUT SCREEN, vol. 4, 2001, pages 417 - 30 |
VERHOEYEN ET AL., SCIENCE, vol. 239, 1988, pages 1534 - 1536 |
WOODLE ET AL., TRANSPLANTATION, vol. 68, no. 5, 1999, pages 608 - 616 |
XU ET AL., CELL IMMUNOL, vol. 200, no. 1, 2000, pages 16 - 26 |
Cited By (190)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8889834B2 (en) | 2007-08-23 | 2014-11-18 | Amgen Inc. | Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9) |
US9920134B2 (en) | 2007-08-23 | 2018-03-20 | Amgen Inc. | Monoclonal antibodies to proprotein convertase subtilisin kexin type 9 (PCSK9) |
US9056915B2 (en) | 2007-08-23 | 2015-06-16 | Amgen Inc. | Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9) |
US8981064B2 (en) | 2007-08-23 | 2015-03-17 | Amgen Inc. | Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9) |
US9045547B2 (en) | 2007-08-23 | 2015-06-02 | Amgen Inc. | Methods of using antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9) |
US8859741B2 (en) | 2007-08-23 | 2014-10-14 | Amgen Inc. | Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9) |
US8871914B2 (en) | 2007-08-23 | 2014-10-28 | Amgen, Inc. | Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9) |
US8871913B2 (en) | 2007-08-23 | 2014-10-28 | Amgen Inc. | Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9) |
US8883983B2 (en) | 2007-08-23 | 2014-11-11 | Amgen Inc. | Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9) |
US9493576B2 (en) | 2007-08-23 | 2016-11-15 | Amgen Inc. | Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9) |
US9724411B2 (en) | 2008-12-15 | 2017-08-08 | Regeneron Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia and reducing LDL-C using antibodies to PCSK9 |
US10941210B2 (en) | 2008-12-15 | 2021-03-09 | Regeneron Pharmaceuticals, Inc. | Anti-PCSK9 antibodies |
US9550837B2 (en) | 2008-12-15 | 2017-01-24 | Regeneron Pharmaceuticals, Inc. | Therapeutic uses of anti-PCSK9 antibodies |
US10023654B2 (en) | 2008-12-15 | 2018-07-17 | Regeneron Pharmaceuticals, Inc. | Anti-PCSK9 antibodies |
US9682013B2 (en) | 2011-01-28 | 2017-06-20 | Sanofi Biotechnology | Pharmaceutical compositions comprising human antibodies to PCSK9 |
US9561155B2 (en) | 2011-01-28 | 2017-02-07 | Sanofi Biotechnology | Method of reducing cholesterol levels using a human anti-PCSK9 antibody |
US11246925B2 (en) | 2011-01-28 | 2022-02-15 | Sanofi Biotechnology | Human antibodies to PCSK9 for use in methods of treating particular groups of subjects |
US11673967B2 (en) | 2011-07-28 | 2023-06-13 | Regeneron Pharmaceuticals, Inc. | Stabilized formulations containing anti-PCSK9 antibodies |
US10472425B2 (en) | 2011-07-28 | 2019-11-12 | Regeneron Pharmaceuticals, Inc. | Stabilized formulations containing anti-PCSK9 antibodies |
US10752701B2 (en) | 2011-07-28 | 2020-08-25 | Regeneron Pharmaceuticals, Inc. | Stabilized formulations containing anti-PCSK9 antibodies |
US10076571B2 (en) | 2011-09-16 | 2018-09-18 | Regeneron Pharmaceuticals, Inc. | Methods for reducing lipoprotein(a) levels by administering an inhibitor of proprotein convertase subtilisin kexin-9 (PCSK9) |
US11116839B2 (en) | 2011-09-16 | 2021-09-14 | Regeneron Pharmaceuticals, Inc. | Methods for reducing lipoprotein(a) levels by administering an inhibitor of proprotein convertase subtilisin kexin-9 (PCSK9) |
US9540449B2 (en) | 2012-08-13 | 2017-01-10 | Regeneron Pharmaceuticals, Inc. | Anti-PCSK9 antibodies with pH-dependent binding characteristics |
US11458247B2 (en) | 2012-11-21 | 2022-10-04 | Amgen Inc. | Drug delivery device |
US11439745B2 (en) | 2012-11-21 | 2022-09-13 | Amgen Inc. | Drug delivery device |
WO2014081780A1 (en) | 2012-11-21 | 2014-05-30 | Amgen Inc. | Drug delivery device |
EP3656426A1 (en) | 2012-11-21 | 2020-05-27 | Amgen, Inc | Drug delivery device |
US10682474B2 (en) | 2012-11-21 | 2020-06-16 | Amgen Inc. | Drug delivery device |
EP4234694A2 (en) | 2012-11-21 | 2023-08-30 | Amgen Inc. | Drug delivery device |
US11344681B2 (en) | 2012-11-21 | 2022-05-31 | Amgen Inc. | Drug delivery device |
EP3072548A1 (en) | 2012-11-21 | 2016-09-28 | Amgen, Inc | Drug delivery device |
EP3081249A1 (en) | 2012-11-21 | 2016-10-19 | Amgen, Inc | Drug delivery device |
US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
EP3593839A1 (en) | 2013-03-15 | 2020-01-15 | Amgen Inc. | Drug cassette |
WO2014144080A2 (en) * | 2013-03-15 | 2014-09-18 | Amgen Inc. | Human antigen binding proteins that bind to proprotein convertase subtilisin kexin type 9 |
WO2014144096A1 (en) | 2013-03-15 | 2014-09-18 | Amgen Inc. | Drug cassette, autoinjector, and autoinjector system |
WO2014152540A1 (en) * | 2013-03-15 | 2014-09-25 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
WO2014144080A3 (en) * | 2013-03-15 | 2014-12-18 | Amgen Inc. | Human antigen binding proteins that bind to proprotein convertase subtilisin kexin type 9 |
WO2014149357A1 (en) | 2013-03-22 | 2014-09-25 | Amgen Inc. | Injector and method of assembly |
EP3831427A1 (en) | 2013-03-22 | 2021-06-09 | Amgen Inc. | Injector and method of assembly |
GB2523527A (en) * | 2013-04-05 | 2015-09-02 | Weiming Xu | Screen compounds for the modulation of proprotein convertase subtilisin/kexin type 9(PCSK9) |
US10111953B2 (en) | 2013-05-30 | 2018-10-30 | Regeneron Pharmaceuticals, Inc. | Methods for reducing remnant cholesterol and other lipoprotein fractions by administering an inhibitor of proprotein convertase subtilisin kexin-9 (PCSK9) |
JP2015007622A (en) * | 2013-05-31 | 2015-01-15 | 株式会社ビー・エム・エル | Screening of pcsk9 relative agent or measurement method of pcsk9 to ascertain administration effect of agent |
US10995150B2 (en) | 2013-06-07 | 2021-05-04 | Regeneron Pharmaceuticals, Inc. | Methods for inhibiting atherosclerosis by administering an anti-PCSK9 antibody |
US10494442B2 (en) | 2013-06-07 | 2019-12-03 | Sanofi Biotechnology | Methods for inhibiting atherosclerosis by administering an inhibitor of PCSK9 |
AU2020201012C1 (en) * | 2013-06-28 | 2022-06-30 | Amgen Inc. | Methods for treating homozygous familial hypercholesterolemia |
AU2013396206B2 (en) * | 2013-06-28 | 2019-11-14 | Amgen Inc. | Methods for treating homozygous familial hypercholesterolemia |
AU2020201012B2 (en) * | 2013-06-28 | 2021-12-23 | Amgen Inc. | Methods for treating homozygous familial hypercholesterolemia |
WO2014209384A1 (en) | 2013-06-28 | 2014-12-31 | Amgen Inc. | Methods for treating homozygous familial hypercholesterolema |
WO2015017791A1 (en) * | 2013-08-01 | 2015-02-05 | Atherotech, Inc. | Pcsk9 function assay |
US10323076B2 (en) | 2013-10-03 | 2019-06-18 | Modernatx, Inc. | Polynucleotides encoding low density lipoprotein receptor |
WO2015061386A1 (en) | 2013-10-24 | 2015-04-30 | Amgen Inc. | Injector and method of assembly |
WO2015061389A1 (en) | 2013-10-24 | 2015-04-30 | Amgen Inc. | Drug delivery system with temperature-sensitive control |
EP3501575A1 (en) | 2013-10-24 | 2019-06-26 | Amgen, Inc | Drug delivery system with temperature-sensitive-control |
EP3789064A1 (en) | 2013-10-24 | 2021-03-10 | Amgen, Inc | Injector and method of assembly |
EP3421066A1 (en) | 2013-10-24 | 2019-01-02 | Amgen, Inc | Injector and method of assembly |
US10428157B2 (en) | 2013-11-12 | 2019-10-01 | Sanofi Biotechnology | Dosing regimens for use with PCSK9 inhibitors |
US10611849B2 (en) | 2013-12-17 | 2020-04-07 | Kymab Limited | Precision medicine by targeting rare human PCSK9 variants for cholesterol treatment |
US11434305B2 (en) | 2013-12-17 | 2022-09-06 | Kymab Limited | Precision medicine by targeting rare human PCSK9 variants for cholesterol treatment |
US10618971B2 (en) | 2013-12-17 | 2020-04-14 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
US8883157B1 (en) | 2013-12-17 | 2014-11-11 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
US9040052B1 (en) | 2013-12-17 | 2015-05-26 | Kymab Limited | Precision Medicine by targeting rare human PCSK9 variants for cholesterol treatment |
WO2015119906A1 (en) | 2014-02-05 | 2015-08-13 | Amgen Inc. | Drug delivery system with electromagnetic field generator |
US11753479B2 (en) | 2014-03-04 | 2023-09-12 | Kymab Limited | Nucleic acids encoding anti-OX40L antibodies |
US11773175B2 (en) | 2014-03-04 | 2023-10-03 | Kymab Limited | Antibodies, uses and methods |
WO2015171777A1 (en) | 2014-05-07 | 2015-11-12 | Amgen Inc. | Autoinjector with shock reducing elements |
EP3785749A1 (en) | 2014-05-07 | 2021-03-03 | Amgen Inc. | Autoinjector with shock reducing elements |
WO2015187793A1 (en) | 2014-06-03 | 2015-12-10 | Amgen Inc. | Drug delivery system and method of use |
US11738146B2 (en) | 2014-06-03 | 2023-08-29 | Amgen Inc. | Drug delivery system and method of use |
WO2015187797A1 (en) | 2014-06-03 | 2015-12-10 | Amgen Inc. | Controllable drug delivery system and method of use |
US11213624B2 (en) | 2014-06-03 | 2022-01-04 | Amgen Inc. | Controllable drug delivery system and method of use |
WO2015187799A1 (en) | 2014-06-03 | 2015-12-10 | Amgen Inc. | Systems and methods for remotely processing data collected by a drug delivery device |
EP4036924A1 (en) | 2014-06-03 | 2022-08-03 | Amgen, Inc | Devices and methods for assisting a user of a drug delivery device |
US8992927B1 (en) | 2014-07-15 | 2015-03-31 | Kymab Limited | Targeting human NAV1.7 variants for treatment of pain |
US9045545B1 (en) | 2014-07-15 | 2015-06-02 | Kymab Limited | Precision medicine by targeting PD-L1 variants for treatment of cancer |
US9394568B2 (en) | 2014-07-15 | 2016-07-19 | Kymab Limited | Methods of treating anaemia |
US8999341B1 (en) | 2014-07-15 | 2015-04-07 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
US9914769B2 (en) | 2014-07-15 | 2018-03-13 | Kymab Limited | Precision medicine for cholesterol treatment |
US9034331B1 (en) | 2014-07-15 | 2015-05-19 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
US9187562B1 (en) | 2014-07-15 | 2015-11-17 | Kymab Limited | Methods for treating anaemia |
US9023359B1 (en) | 2014-07-15 | 2015-05-05 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
US9109034B1 (en) | 2014-07-15 | 2015-08-18 | Kymab Limited | Precision medicine by targeting PD-L1 variants for treatment of cancer |
US11555066B2 (en) | 2014-07-15 | 2023-01-17 | Kymab Limited | Precision medicine for cholesterol treatment |
US9139648B1 (en) | 2014-07-15 | 2015-09-22 | Kymab Limited | Precision medicine by targeting human NAV1.9 variants for treatment of pain |
US8986694B1 (en) | 2014-07-15 | 2015-03-24 | Kymab Limited | Targeting human nav1.7 variants for treatment of pain |
US9067998B1 (en) | 2014-07-15 | 2015-06-30 | Kymab Limited | Targeting PD-1 variants for treatment of cancer |
US10711059B2 (en) | 2014-07-15 | 2020-07-14 | Kymab Limited | Methods for treating neurodegenerative diseases using anti-PD-L1 antibodies |
US9303089B2 (en) | 2014-07-15 | 2016-04-05 | Kymab Limited | Methods of treating anaemia |
US8986691B1 (en) | 2014-07-15 | 2015-03-24 | Kymab Limited | Method of treating atopic dermatitis or asthma using antibody to IL4RA |
US9150660B1 (en) | 2014-07-15 | 2015-10-06 | Kymab Limited | Precision Medicine by targeting human NAV1.8 variants for treatment of pain |
US9439963B2 (en) | 2014-07-15 | 2016-09-13 | Kymab Limited | Methods of treating anaemia |
US9017678B1 (en) | 2014-07-15 | 2015-04-28 | Kymab Limited | Method of treating rheumatoid arthritis using antibody to IL6R |
US9068012B1 (en) | 2014-07-15 | 2015-06-30 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
US9062105B1 (en) | 2014-07-15 | 2015-06-23 | Kymab Limited | Precision Medicine by targeting VEGF-A variants for treatment of retinopathy |
US9051378B1 (en) | 2014-07-15 | 2015-06-09 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
US8980273B1 (en) | 2014-07-15 | 2015-03-17 | Kymab Limited | Method of treating atopic dermatitis or asthma using antibody to IL4RA |
US9428578B2 (en) | 2014-07-15 | 2016-08-30 | Kymab Limited | Methods of treating anaemia |
US9045548B1 (en) | 2014-07-15 | 2015-06-02 | Kymab Limited | Precision Medicine by targeting rare human PCSK9 variants for cholesterol treatment |
US9034332B1 (en) | 2014-07-15 | 2015-05-19 | Kymab Limited | Precision medicine by targeting rare human PCSK9 variants for cholesterol treatment |
US8945560B1 (en) | 2014-07-15 | 2015-02-03 | Kymab Limited | Method of treating rheumatoid arthritis using antibody to IL6R |
US10618955B2 (en) | 2014-07-15 | 2020-04-14 | Kymab Limited | Methods for treating neurodegenerative disease using anti-PD-1 antibodies |
US11306155B2 (en) | 2014-07-16 | 2022-04-19 | Sanofi Biotechnology | Methods for treating patients with heterozygous familial hypercholesterolemia (heFH) with an anti-PCSK9 antibody |
US10544232B2 (en) | 2014-07-16 | 2020-01-28 | Sanofi Biotechnology | Methods for treating patients with heterozygous familial hypercholesterolemia (heFH) with an anti-PCSK9 antibody |
EP3943135A2 (en) | 2014-10-14 | 2022-01-26 | Amgen Inc. | Drug injection device with visual and audible indicators |
WO2016061220A2 (en) | 2014-10-14 | 2016-04-21 | Amgen Inc. | Drug injection device with visual and audio indicators |
US10799630B2 (en) | 2014-12-19 | 2020-10-13 | Amgen Inc. | Drug delivery device with proximity sensor |
EP3689394A1 (en) | 2014-12-19 | 2020-08-05 | Amgen Inc. | Drug delivery device with live button or user interface field |
US10765801B2 (en) | 2014-12-19 | 2020-09-08 | Amgen Inc. | Drug delivery device with proximity sensor |
EP3848072A1 (en) | 2014-12-19 | 2021-07-14 | Amgen Inc. | Drug delivery device with proximity sensor |
WO2016100055A1 (en) | 2014-12-19 | 2016-06-23 | Amgen Inc. | Drug delivery device with live button or user interface field |
US11357916B2 (en) | 2014-12-19 | 2022-06-14 | Amgen Inc. | Drug delivery device with live button or user interface field |
WO2016100781A1 (en) | 2014-12-19 | 2016-06-23 | Amgen Inc. | Drug delivery device with proximity sensor |
US11944794B2 (en) | 2014-12-19 | 2024-04-02 | Amgen Inc. | Drug delivery device with proximity sensor |
WO2016133947A1 (en) | 2015-02-17 | 2016-08-25 | Amgen Inc. | Drug delivery device with vacuum assisted securement and/or feedback |
EP3556411A1 (en) | 2015-02-17 | 2019-10-23 | Amgen Inc. | Drug delivery device with vacuum assisted securement and/or feedback |
EP3981450A1 (en) | 2015-02-27 | 2022-04-13 | Amgen, Inc | Drug delivery device having a needle guard mechanism with a tunable threshold of resistance to needle guard movement |
WO2016138434A1 (en) | 2015-02-27 | 2016-09-01 | Amgen Inc. | Drug delivery device having a needle guard mechanism with a tunable threshold of resistance to needle guard movement |
US10688119B2 (en) | 2015-03-20 | 2020-06-23 | Aarhus Universitet | Inhibitors of PCSK9 for treatment of lipoprotein metabolism disorders |
US11904017B2 (en) | 2015-08-18 | 2024-02-20 | Regeneron Pharmaceuticals, Inc. | Methods for reducing or eliminating the need for lipoprotein apheresis in patients with hyperlipidemia by administering alirocumab |
US10772956B2 (en) | 2015-08-18 | 2020-09-15 | Regeneron Pharmaceuticals, Inc. | Methods for reducing or eliminating the need for lipoprotein apheresis in patients with hyperlipidemia by administering alirocumab |
WO2017039786A1 (en) | 2015-09-02 | 2017-03-09 | Amgen Inc. | Syringe assembly adapter for a syringe |
WO2017100501A1 (en) | 2015-12-09 | 2017-06-15 | Amgen Inc. | Auto-injector with signaling cap |
US10793643B2 (en) | 2015-12-31 | 2020-10-06 | Jiangsu Hengrui Medicine Co., Ltd. | PCSK9 antibody, antigen-binding fragment thereof, and medical application thereof |
WO2017118307A1 (en) | 2016-01-05 | 2017-07-13 | 江苏恒瑞医药股份有限公司 | Pcsk9 antibody, antigen-binding fragment thereof, and medical uses thereof |
WO2017120178A1 (en) | 2016-01-06 | 2017-07-13 | Amgen Inc. | Auto-injector with signaling electronics |
WO2017160799A1 (en) | 2016-03-15 | 2017-09-21 | Amgen Inc. | Reducing probability of glass breakage in drug delivery devices |
EP4035711A1 (en) | 2016-03-15 | 2022-08-03 | Amgen Inc. | Reducing probability of glass breakage in drug delivery devices |
EP3721922A1 (en) | 2016-03-15 | 2020-10-14 | Amgen Inc. | Reducing probability of glass breakage in drug delivery devices |
WO2017189089A1 (en) | 2016-04-29 | 2017-11-02 | Amgen Inc. | Drug delivery device with messaging label |
WO2017192287A1 (en) | 2016-05-02 | 2017-11-09 | Amgen Inc. | Syringe adapter and guide for filling an on-body injector |
WO2017197222A1 (en) | 2016-05-13 | 2017-11-16 | Amgen Inc. | Vial sleeve assembly |
WO2017200989A1 (en) | 2016-05-16 | 2017-11-23 | Amgen Inc. | Data encryption in medical devices with limited computational capability |
WO2017209899A1 (en) | 2016-06-03 | 2017-12-07 | Amgen Inc. | Impact testing apparatuses and methods for drug delivery devices |
WO2018004842A1 (en) | 2016-07-01 | 2018-01-04 | Amgen Inc. | Drug delivery device having minimized risk of component fracture upon impact events |
WO2018034784A1 (en) | 2016-08-17 | 2018-02-22 | Amgen Inc. | Drug delivery device with placement detection |
WO2018081234A1 (en) | 2016-10-25 | 2018-05-03 | Amgen Inc. | On-body injector |
US11779604B2 (en) | 2016-11-03 | 2023-10-10 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses and methods |
WO2018136398A1 (en) | 2017-01-17 | 2018-07-26 | Amgen Inc. | Injection devices and related methods of use and assembly |
WO2018151890A1 (en) | 2017-02-17 | 2018-08-23 | Amgen Inc. | Drug delivery device with sterile fluid flowpath and related method of assembly |
WO2018152073A1 (en) | 2017-02-17 | 2018-08-23 | Amgen Inc. | Insertion mechanism for drug delivery device |
WO2018165143A1 (en) | 2017-03-06 | 2018-09-13 | Amgen Inc. | Drug delivery device with activation prevention feature |
WO2018164829A1 (en) | 2017-03-07 | 2018-09-13 | Amgen Inc. | Needle insertion by overpressure |
WO2018165499A1 (en) | 2017-03-09 | 2018-09-13 | Amgen Inc. | Insertion mechanism for drug delivery device |
EP4241807A2 (en) | 2017-03-28 | 2023-09-13 | Amgen Inc. | Plunger rod and syringe assembly system and method |
WO2018183039A1 (en) | 2017-03-28 | 2018-10-04 | Amgen Inc. | Plunger rod and syringe assembly system and method |
WO2018189705A1 (en) | 2017-04-13 | 2018-10-18 | Cadila Healthcare Limited | Novel peptide based pcsk9 vaccine |
WO2018226515A1 (en) | 2017-06-08 | 2018-12-13 | Amgen Inc. | Syringe assembly for a drug delivery device and method of assembly |
WO2018226565A1 (en) | 2017-06-08 | 2018-12-13 | Amgen Inc. | Torque driven drug delivery device |
WO2018236619A1 (en) | 2017-06-22 | 2018-12-27 | Amgen Inc. | Device activation impact/shock reduction |
WO2018237225A1 (en) | 2017-06-23 | 2018-12-27 | Amgen Inc. | Electronic drug delivery device comprising a cap activated by a switch assembly |
WO2019014014A1 (en) | 2017-07-14 | 2019-01-17 | Amgen Inc. | Needle insertion-retraction system having dual torsion spring system |
WO2019018169A1 (en) | 2017-07-21 | 2019-01-24 | Amgen Inc. | Gas permeable sealing member for drug container and methods of assembly |
EP4292576A2 (en) | 2017-07-21 | 2023-12-20 | Amgen Inc. | Gas permeable sealing member for drug container and methods of assembly |
WO2019022951A1 (en) | 2017-07-25 | 2019-01-31 | Amgen Inc. | Drug delivery device with gear module and related method of assembly |
EP4085942A1 (en) | 2017-07-25 | 2022-11-09 | Amgen Inc. | Drug delivery device with gear module and related method of assembly |
WO2019022950A1 (en) | 2017-07-25 | 2019-01-31 | Amgen Inc. | Drug delivery device with container access system and related method of assembly |
WO2019032482A2 (en) | 2017-08-09 | 2019-02-14 | Amgen Inc. | Hydraulic-pneumatic pressurized chamber drug delivery system |
WO2019036181A1 (en) | 2017-08-18 | 2019-02-21 | Amgen Inc. | Wearable injector with sterile adhesive patch |
WO2019040548A1 (en) | 2017-08-22 | 2019-02-28 | Amgen Inc. | Needle insertion mechanism for drug delivery device |
WO2019070472A1 (en) | 2017-10-04 | 2019-04-11 | Amgen Inc. | Flow adapter for drug delivery device |
EP4257164A2 (en) | 2017-10-06 | 2023-10-11 | Amgen Inc. | Drug delivery device with interlock assembly and related method of assembly |
WO2019070552A1 (en) | 2017-10-06 | 2019-04-11 | Amgen Inc. | Drug delivery device with interlock assembly and related method of assembly |
WO2019074579A1 (en) | 2017-10-09 | 2019-04-18 | Amgen Inc. | Drug delivery device with drive assembly and related method of assembly |
WO2019090086A1 (en) | 2017-11-03 | 2019-05-09 | Amgen Inc. | Systems and approaches for sterilizing a drug delivery device |
WO2019090079A1 (en) | 2017-11-03 | 2019-05-09 | Amgen Inc. | System and approaches for sterilizing a drug delivery device |
WO2019090303A1 (en) | 2017-11-06 | 2019-05-09 | Amgen Inc. | Fill-finish assemblies and related methods |
WO2019089178A1 (en) | 2017-11-06 | 2019-05-09 | Amgen Inc. | Drug delivery device with placement and flow sensing |
WO2019094138A1 (en) | 2017-11-10 | 2019-05-16 | Amgen Inc. | Plungers for drug delivery devices |
WO2019099324A1 (en) | 2017-11-16 | 2019-05-23 | Amgen Inc. | Door latch mechanism for drug delivery device |
WO2019099322A1 (en) | 2017-11-16 | 2019-05-23 | Amgen Inc. | Autoinjector with stall and end point detection |
WO2019231582A1 (en) | 2018-05-30 | 2019-12-05 | Amgen Inc. | Thermal spring release mechanism for a drug delivery device |
WO2019231618A1 (en) | 2018-06-01 | 2019-12-05 | Amgen Inc. | Modular fluid path assemblies for drug delivery devices |
WO2020023451A1 (en) | 2018-07-24 | 2020-01-30 | Amgen Inc. | Delivery devices for administering drugs |
WO2020023220A1 (en) | 2018-07-24 | 2020-01-30 | Amgen Inc. | Hybrid drug delivery devices with tacky skin attachment portion and related method of preparation |
WO2020023336A1 (en) | 2018-07-24 | 2020-01-30 | Amgen Inc. | Hybrid drug delivery devices with grip portion |
WO2020023444A1 (en) | 2018-07-24 | 2020-01-30 | Amgen Inc. | Delivery devices for administering drugs |
WO2020028009A1 (en) | 2018-07-31 | 2020-02-06 | Amgen Inc. | Fluid path assembly for a drug delivery device |
WO2020068623A1 (en) | 2018-09-24 | 2020-04-02 | Amgen Inc. | Interventional dosing systems and methods |
WO2020068476A1 (en) | 2018-09-28 | 2020-04-02 | Amgen Inc. | Muscle wire escapement activation assembly for a drug delivery device |
WO2020072577A1 (en) | 2018-10-02 | 2020-04-09 | Amgen Inc. | Injection systems for drug delivery with internal force transmission |
WO2020072846A1 (en) | 2018-10-05 | 2020-04-09 | Amgen Inc. | Drug delivery device having dose indicator |
WO2020081479A1 (en) | 2018-10-15 | 2020-04-23 | Amgen Inc. | Drug delivery device having damping mechanism |
WO2020081480A1 (en) | 2018-10-15 | 2020-04-23 | Amgen Inc. | Platform assembly process for drug delivery device |
WO2020092056A1 (en) | 2018-11-01 | 2020-05-07 | Amgen Inc. | Drug delivery devices with partial needle retraction |
WO2020091981A1 (en) | 2018-11-01 | 2020-05-07 | Amgen Inc. | Drug delivery devices with partial drug delivery member retraction |
WO2020091956A1 (en) | 2018-11-01 | 2020-05-07 | Amgen Inc. | Drug delivery devices with partial drug delivery member retraction |
WO2020150473A2 (en) | 2019-01-18 | 2020-07-23 | Dogma Therapeutics, Inc. | Pcsk9 inhibitors and methods of use thereof |
WO2020219482A1 (en) | 2019-04-24 | 2020-10-29 | Amgen Inc. | Syringe sterilization verification assemblies and methods |
WO2021041067A2 (en) | 2019-08-23 | 2021-03-04 | Amgen Inc. | Drug delivery device with configurable needle shield engagement components and related methods |
WO2022246055A1 (en) | 2021-05-21 | 2022-11-24 | Amgen Inc. | Method of optimizing a filling recipe for a drug container |
Also Published As
Publication number | Publication date |
---|---|
CN103562227A (en) | 2014-02-05 |
CA2827091A1 (en) | 2012-08-16 |
EP2673302A1 (en) | 2013-12-18 |
AU2016202983A1 (en) | 2016-05-26 |
JP2014511378A (en) | 2014-05-15 |
EA201391157A1 (en) | 2014-02-28 |
US20130315927A1 (en) | 2013-11-28 |
CN103562227B (en) | 2016-12-21 |
KR20140006022A (en) | 2014-01-15 |
BR112013020402A2 (en) | 2018-09-25 |
MX2013009258A (en) | 2013-10-17 |
AU2012214251A1 (en) | 2013-09-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20130315927A1 (en) | Pcsk9 antagonists | |
CA2781050C (en) | Pcsk9 antagonists | |
WO2012170607A2 (en) | Use of pcsk9 antagonists | |
AU2011208719C1 (en) | Anticoagulant antidotes | |
AU2011208719B2 (en) | Anticoagulant antidotes | |
WO2012168491A1 (en) | Pharmaceutical formulations of pcsk9 antagonists | |
JP2019516362A (en) | Anti-IL-33 antibodies, compositions, methods and uses thereof | |
AU2015384281B2 (en) | Novel antibody binding to TFPI and composition comprising the same | |
WO2014028748A1 (en) | Interleukin 2 antibodies and antibody complexes | |
JP2022540859A (en) | Novel BSSL antibody | |
JP7454106B2 (en) | Novel anti-A2AP antibodies and their uses | |
US20230242673A1 (en) | Anti-pcsk9 antibody and use thereof | |
KR20220116506A (en) | multi-specific antibody | |
CN115594762A (en) | Ferritin heavy chain antibody and application thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 12705564 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2013553586 Country of ref document: JP Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 13984785 Country of ref document: US Ref document number: MX/A/2013/009258 Country of ref document: MX |
|
ENP | Entry into the national phase |
Ref document number: 2827091 Country of ref document: CA |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
REEP | Request for entry into the european phase |
Ref document number: 2012705564 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2012705564 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 20137023909 Country of ref document: KR Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 201391157 Country of ref document: EA |
|
ENP | Entry into the national phase |
Ref document number: 2012214251 Country of ref document: AU Date of ref document: 20120210 Kind code of ref document: A |
|
REG | Reference to national code |
Ref country code: BR Ref legal event code: B01A Ref document number: 112013020402 Country of ref document: BR |
|
ENP | Entry into the national phase |
Ref document number: 112013020402 Country of ref document: BR Kind code of ref document: A2 Effective date: 20130809 |