BR112012002151B1 - método para expressar uma desintegrina e metaloproteinase com proteína de motivo trombospondina (adamts) - Google Patents
método para expressar uma desintegrina e metaloproteinase com proteína de motivo trombospondina (adamts) Download PDFInfo
- Publication number
- BR112012002151B1 BR112012002151B1 BR112012002151-6A BR112012002151A BR112012002151B1 BR 112012002151 B1 BR112012002151 B1 BR 112012002151B1 BR 112012002151 A BR112012002151 A BR 112012002151A BR 112012002151 B1 BR112012002151 B1 BR 112012002151B1
- Authority
- BR
- Brazil
- Prior art keywords
- protein
- culture medium
- culture
- adamts13
- cell
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 382
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 100
- 102000004169 proteins and genes Human genes 0.000 title claims abstract description 98
- 102000005741 Metalloproteases Human genes 0.000 title claims abstract description 51
- 108010006035 Metalloproteases Proteins 0.000 title claims abstract description 51
- 108060008245 Thrombospondin Proteins 0.000 title claims abstract description 46
- 102000002938 Thrombospondin Human genes 0.000 title claims abstract description 46
- 101800001224 Disintegrin Proteins 0.000 title claims abstract description 44
- 239000001963 growth medium Substances 0.000 claims abstract description 573
- 102000029750 ADAMTS Human genes 0.000 claims abstract description 314
- 108091022879 ADAMTS Proteins 0.000 claims abstract description 314
- 102000043853 ADAMTS13 Human genes 0.000 claims abstract description 174
- 108091005670 ADAMTS13 Proteins 0.000 claims abstract description 174
- 230000000694 effects Effects 0.000 claims abstract description 139
- 210000004027 cell Anatomy 0.000 claims description 368
- 239000011701 zinc Substances 0.000 claims description 357
- 229910052725 zinc Inorganic materials 0.000 claims description 352
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 351
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 273
- 239000011575 calcium Substances 0.000 claims description 273
- 229910052791 calcium Inorganic materials 0.000 claims description 273
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 233
- 150000007523 nucleic acids Chemical class 0.000 claims description 171
- 210000004962 mammalian cell Anatomy 0.000 claims description 170
- 108020004707 nucleic acids Proteins 0.000 claims description 168
- 102000039446 nucleic acids Human genes 0.000 claims description 168
- 238000012258 culturing Methods 0.000 claims description 145
- 229920000768 polyamine Polymers 0.000 claims description 123
- 238000004113 cell culture Methods 0.000 claims description 120
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical group NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 claims description 104
- 235000018102 proteins Nutrition 0.000 claims description 88
- 239000005700 Putrescine Substances 0.000 claims description 52
- 230000010412 perfusion Effects 0.000 claims description 52
- 235000021120 animal protein Nutrition 0.000 claims description 41
- 210000004978 chinese hamster ovary cell Anatomy 0.000 claims description 38
- 241000699800 Cricetinae Species 0.000 claims description 33
- 241001529936 Murinae Species 0.000 claims description 30
- 239000000725 suspension Substances 0.000 claims description 21
- 230000001464 adherent effect Effects 0.000 claims description 20
- 241000238631 Hexapoda Species 0.000 claims description 5
- 230000001580 bacterial effect Effects 0.000 claims description 4
- 210000005253 yeast cell Anatomy 0.000 claims description 4
- 241000271566 Aves Species 0.000 claims description 3
- 210000005260 human cell Anatomy 0.000 claims description 3
- 230000014509 gene expression Effects 0.000 abstract description 138
- 239000000203 mixture Substances 0.000 abstract description 85
- 238000000746 purification Methods 0.000 abstract description 17
- 239000002609 medium Substances 0.000 description 119
- 241001465754 Metazoa Species 0.000 description 108
- 108090000765 processed proteins & peptides Proteins 0.000 description 93
- 102000004196 processed proteins & peptides Human genes 0.000 description 90
- 229920001184 polypeptide Polymers 0.000 description 88
- 241000282414 Homo sapiens Species 0.000 description 48
- 239000000872 buffer Substances 0.000 description 47
- 238000004519 manufacturing process Methods 0.000 description 40
- 108010047303 von Willebrand Factor Proteins 0.000 description 37
- 102100036537 von Willebrand factor Human genes 0.000 description 34
- 229960001134 von willebrand factor Drugs 0.000 description 33
- 230000001965 increasing effect Effects 0.000 description 32
- 238000011026 diafiltration Methods 0.000 description 23
- 201000007023 Thrombotic Thrombocytopenic Purpura Diseases 0.000 description 20
- 230000012010 growth Effects 0.000 description 19
- 238000012365 batch cultivation Methods 0.000 description 18
- 239000006228 supernatant Substances 0.000 description 18
- 238000000108 ultra-filtration Methods 0.000 description 18
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 17
- 239000013589 supplement Substances 0.000 description 17
- 239000013598 vector Substances 0.000 description 17
- 206010043561 Thrombocytopenic purpura Diseases 0.000 description 15
- 150000003839 salts Chemical class 0.000 description 15
- 108010038807 Oligopeptides Proteins 0.000 description 14
- 102000015636 Oligopeptides Human genes 0.000 description 14
- 150000001413 amino acids Chemical group 0.000 description 14
- 239000011347 resin Substances 0.000 description 14
- 229920005989 resin Polymers 0.000 description 14
- 239000004017 serum-free culture medium Substances 0.000 description 14
- 210000004369 blood Anatomy 0.000 description 13
- 239000008280 blood Substances 0.000 description 13
- 239000012528 membrane Substances 0.000 description 13
- 230000003612 virological effect Effects 0.000 description 13
- 238000012832 cell culture technique Methods 0.000 description 12
- 239000012228 culture supernatant Substances 0.000 description 12
- 210000002966 serum Anatomy 0.000 description 12
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
- 238000001728 nano-filtration Methods 0.000 description 11
- 230000009469 supplementation Effects 0.000 description 11
- 235000001014 amino acid Nutrition 0.000 description 10
- 238000000502 dialysis Methods 0.000 description 10
- 229960003512 nicotinic acid Drugs 0.000 description 10
- 230000001502 supplementing effect Effects 0.000 description 10
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 9
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 9
- 241000700605 Viruses Species 0.000 description 9
- 238000011210 chromatographic step Methods 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 9
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 8
- 102000004877 Insulin Human genes 0.000 description 8
- 108090001061 Insulin Proteins 0.000 description 8
- 108010029485 Protein Isoforms Proteins 0.000 description 8
- 102000001708 Protein Isoforms Human genes 0.000 description 8
- 229930003537 Vitamin B3 Natural products 0.000 description 8
- 239000013604 expression vector Substances 0.000 description 8
- 229940125396 insulin Drugs 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- 235000019160 vitamin B3 Nutrition 0.000 description 8
- 239000011708 vitamin B3 Substances 0.000 description 8
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 7
- 238000010790 dilution Methods 0.000 description 7
- 239000012895 dilution Substances 0.000 description 7
- -1 for example Proteins 0.000 description 7
- 235000005152 nicotinamide Nutrition 0.000 description 7
- 239000011570 nicotinamide Substances 0.000 description 7
- 229960003966 nicotinamide Drugs 0.000 description 7
- 239000002773 nucleotide Substances 0.000 description 7
- 125000003729 nucleotide group Chemical group 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 241000196324 Embryophyta Species 0.000 description 6
- 235000010469 Glycine max Nutrition 0.000 description 6
- 239000008366 buffered solution Substances 0.000 description 6
- 210000002889 endothelial cell Anatomy 0.000 description 6
- 238000003306 harvesting Methods 0.000 description 6
- 230000002779 inactivation Effects 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 239000004365 Protease Substances 0.000 description 5
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 description 5
- 239000000427 antigen Substances 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- 206010003246 arthritis Diseases 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 239000012141 concentrate Substances 0.000 description 5
- 238000009295 crossflow filtration Methods 0.000 description 5
- 239000003599 detergent Substances 0.000 description 5
- 239000012538 diafiltration buffer Substances 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000002255 enzymatic effect Effects 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 210000003527 eukaryotic cell Anatomy 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 238000002523 gelfiltration Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 230000000670 limiting effect Effects 0.000 description 5
- 235000015097 nutrients Nutrition 0.000 description 5
- 229920001983 poloxamer Polymers 0.000 description 5
- 239000011148 porous material Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000012552 review Methods 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 102100027398 A disintegrin and metalloproteinase with thrombospondin motifs 1 Human genes 0.000 description 4
- 108091005660 ADAMTS1 Proteins 0.000 description 4
- 108010088751 Albumins Proteins 0.000 description 4
- 102000009027 Albumins Human genes 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 102000035195 Peptidases Human genes 0.000 description 4
- 108091005804 Peptidases Proteins 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 210000003292 kidney cell Anatomy 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000000717 retained effect Effects 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 description 4
- PFNFFQXMRSDOHW-UHFFFAOYSA-N spermine Chemical compound NCCCNCCCCNCCCN PFNFFQXMRSDOHW-UHFFFAOYSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 102100031765 3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase Human genes 0.000 description 3
- 102100027394 A disintegrin and metalloproteinase with thrombospondin motifs 20 Human genes 0.000 description 3
- 102100032638 A disintegrin and metalloproteinase with thrombospondin motifs 5 Human genes 0.000 description 3
- 102100032650 A disintegrin and metalloproteinase with thrombospondin motifs 9 Human genes 0.000 description 3
- 108091005663 ADAMTS5 Proteins 0.000 description 3
- 108091005669 ADAMTS9 Proteins 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 241000282693 Cercopithecidae Species 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 101000866618 Homo sapiens 3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase Proteins 0.000 description 3
- 101000798281 Homo sapiens A disintegrin and metalloproteinase with thrombospondin motifs 13 Proteins 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 208000007536 Thrombosis Diseases 0.000 description 3
- 238000001042 affinity chromatography Methods 0.000 description 3
- 210000004102 animal cell Anatomy 0.000 description 3
- 229910001622 calcium bromide Inorganic materials 0.000 description 3
- WGEFECGEFUFIQW-UHFFFAOYSA-L calcium dibromide Chemical compound [Ca+2].[Br-].[Br-] WGEFECGEFUFIQW-UHFFFAOYSA-L 0.000 description 3
- 159000000007 calcium salts Chemical class 0.000 description 3
- 229940041514 candida albicans extract Drugs 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 239000006143 cell culture medium Substances 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 239000000356 contaminant Substances 0.000 description 3
- 210000004748 cultured cell Anatomy 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 239000012894 fetal calf serum Substances 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 102000057210 human ADAMTS13 Human genes 0.000 description 3
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 3
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 238000004255 ion exchange chromatography Methods 0.000 description 3
- 239000002736 nonionic surfactant Substances 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 230000009465 prokaryotic expression Effects 0.000 description 3
- 239000003531 protein hydrolysate Substances 0.000 description 3
- 238000001742 protein purification Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 230000001603 reducing effect Effects 0.000 description 3
- 230000001177 retroviral effect Effects 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000004114 suspension culture Methods 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 239000013603 viral vector Substances 0.000 description 3
- 210000004269 weibel-palade body Anatomy 0.000 description 3
- 239000012138 yeast extract Substances 0.000 description 3
- 150000003751 zinc Chemical class 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 102100032295 A disintegrin and metalloproteinase with thrombospondin motifs 10 Human genes 0.000 description 2
- 102100032296 A disintegrin and metalloproteinase with thrombospondin motifs 12 Human genes 0.000 description 2
- 102100032310 A disintegrin and metalloproteinase with thrombospondin motifs 14 Human genes 0.000 description 2
- 102100032308 A disintegrin and metalloproteinase with thrombospondin motifs 19 Human genes 0.000 description 2
- 102100027399 A disintegrin and metalloproteinase with thrombospondin motifs 2 Human genes 0.000 description 2
- 102100027401 A disintegrin and metalloproteinase with thrombospondin motifs 3 Human genes 0.000 description 2
- 102100027400 A disintegrin and metalloproteinase with thrombospondin motifs 4 Human genes 0.000 description 2
- 102100032632 A disintegrin and metalloproteinase with thrombospondin motifs 6 Human genes 0.000 description 2
- 108091005668 ADAMTS10 Proteins 0.000 description 2
- 108091005671 ADAMTS12 Proteins 0.000 description 2
- 108091005673 ADAMTS14 Proteins 0.000 description 2
- 108091005570 ADAMTS19 Proteins 0.000 description 2
- 108091005662 ADAMTS2 Proteins 0.000 description 2
- 108091005569 ADAMTS20 Proteins 0.000 description 2
- 108091005661 ADAMTS3 Proteins 0.000 description 2
- 108091005664 ADAMTS4 Proteins 0.000 description 2
- 108091005665 ADAMTS6 Proteins 0.000 description 2
- 239000002028 Biomass Substances 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241000282465 Canis Species 0.000 description 2
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 208000022774 Congenital thrombotic thrombocytopenic purpura Diseases 0.000 description 2
- 241000702421 Dependoparvovirus Species 0.000 description 2
- 102100024746 Dihydrofolate reductase Human genes 0.000 description 2
- 101800000620 Disintegrin-like Proteins 0.000 description 2
- 108010054218 Factor VIII Proteins 0.000 description 2
- 102000001690 Factor VIII Human genes 0.000 description 2
- 208000002476 Falciparum Malaria Diseases 0.000 description 2
- 208000032759 Hemolytic-Uremic Syndrome Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 208000035888 Immune-mediated thrombotic thrombocytopenic purpura Diseases 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241000204031 Mycoplasma Species 0.000 description 2
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 2
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 2
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 2
- 201000011336 Plasmodium falciparum malaria Diseases 0.000 description 2
- 108010009736 Protein Hydrolysates Proteins 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 208000034841 Thrombotic Microangiopathies Diseases 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 235000011941 Tilia x europaea Nutrition 0.000 description 2
- 108700009124 Transcription Initiation Site Proteins 0.000 description 2
- 239000005862 Whey Substances 0.000 description 2
- 102000007544 Whey Proteins Human genes 0.000 description 2
- 108010046377 Whey Proteins Proteins 0.000 description 2
- MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 208000004886 acquired thrombotic thrombocytopenic purpura Diseases 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 238000005571 anion exchange chromatography Methods 0.000 description 2
- 239000003957 anion exchange resin Substances 0.000 description 2
- 230000003527 anti-angiogenesis Effects 0.000 description 2
- 239000007640 basal medium Substances 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- VHRGRCVQAFMJIZ-UHFFFAOYSA-N cadaverine Chemical compound NCCCCCN VHRGRCVQAFMJIZ-UHFFFAOYSA-N 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000005277 cation exchange chromatography Methods 0.000 description 2
- 239000003729 cation exchange resin Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 108020001096 dihydrofolate reductase Proteins 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000001493 electron microscopy Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 229960000301 factor viii Drugs 0.000 description 2
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000012737 fresh medium Substances 0.000 description 2
- 238000002825 functional assay Methods 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 210000003714 granulocyte Anatomy 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000011031 large-scale manufacturing process Methods 0.000 description 2
- 239000004571 lime Substances 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 210000005229 liver cell Anatomy 0.000 description 2
- 238000005374 membrane filtration Methods 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229960003104 ornithine Drugs 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000013600 plasmid vector Substances 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 235000019419 proteases Nutrition 0.000 description 2
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000001542 size-exclusion chromatography Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 229940063673 spermidine Drugs 0.000 description 2
- 229940063675 spermine Drugs 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 206010043554 thrombocytopenia Diseases 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 239000013621 viresolve pro solution Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 2
- 229910000368 zinc sulfate Inorganic materials 0.000 description 2
- 239000011686 zinc sulphate Substances 0.000 description 2
- 235000009529 zinc sulphate Nutrition 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- 102220526203 A disintegrin and metalloproteinase with thrombospondin motifs 13_R1095W_mutation Human genes 0.000 description 1
- 102220526220 A disintegrin and metalloproteinase with thrombospondin motifs 13_T1226I_mutation Human genes 0.000 description 1
- 102100032309 A disintegrin and metalloproteinase with thrombospondin motifs 15 Human genes 0.000 description 1
- 102100032291 A disintegrin and metalloproteinase with thrombospondin motifs 16 Human genes 0.000 description 1
- 102100032292 A disintegrin and metalloproteinase with thrombospondin motifs 17 Human genes 0.000 description 1
- 101710108762 A disintegrin and metalloproteinase with thrombospondin motifs 20 Proteins 0.000 description 1
- 102100032639 A disintegrin and metalloproteinase with thrombospondin motifs 7 Human genes 0.000 description 1
- 102100032635 A disintegrin and metalloproteinase with thrombospondin motifs 8 Human genes 0.000 description 1
- 239000013607 AAV vector Substances 0.000 description 1
- 102000029791 ADAM Human genes 0.000 description 1
- 108091022885 ADAM Proteins 0.000 description 1
- 108091005672 ADAMTS15 Proteins 0.000 description 1
- 108091005675 ADAMTS16 Proteins 0.000 description 1
- 108091005674 ADAMTS17 Proteins 0.000 description 1
- 108091005667 ADAMTS7 Proteins 0.000 description 1
- 108091005666 ADAMTS8 Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- ORILYTVJVMAKLC-UHFFFAOYSA-N Adamantane Natural products C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 1
- QYPPJABKJHAVHS-UHFFFAOYSA-N Agmatine Natural products NCCCCNC(N)=N QYPPJABKJHAVHS-UHFFFAOYSA-N 0.000 description 1
- 102100036826 Aldehyde oxidase Human genes 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- 101100437118 Arabidopsis thaliana AUG1 gene Proteins 0.000 description 1
- 206010003178 Arterial thrombosis Diseases 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 101100421200 Caenorhabditis elegans sep-1 gene Proteins 0.000 description 1
- 102000005701 Calcium-Binding Proteins Human genes 0.000 description 1
- 108010045403 Calcium-Binding Proteins Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 101150074155 DHFR gene Proteins 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 1
- 208000002197 Ehlers-Danlos syndrome Diseases 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 238000012366 Fed-batch cultivation Methods 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 101150094690 GAL1 gene Proteins 0.000 description 1
- 102100028501 Galanin peptides Human genes 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241000699694 Gerbillinae Species 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 101000928314 Homo sapiens Aldehyde oxidase Proteins 0.000 description 1
- 101100121078 Homo sapiens GAL gene Proteins 0.000 description 1
- 101000976075 Homo sapiens Insulin Proteins 0.000 description 1
- 101000782195 Homo sapiens von Willebrand factor Proteins 0.000 description 1
- 102000005561 Human Isophane Insulin Human genes 0.000 description 1
- 108010084048 Human Isophane Insulin Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010023421 Kidney fibrosis Diseases 0.000 description 1
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 1
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 101710141347 Major envelope glycoprotein Proteins 0.000 description 1
- 240000000233 Melia azedarach Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 108010021466 Mutant Proteins Proteins 0.000 description 1
- 102000008300 Mutant Proteins Human genes 0.000 description 1
- OVRNDRQMDRJTHS-RTRLPJTCSA-N N-acetyl-D-glucosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-RTRLPJTCSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- GKWTZACONBQTNK-IVIZKJKWSA-N N-benzyl-7H-purin-6-amine (1R,2R,5R,8R,9S,10R,12S)-12-hydroxy-11-methyl-6-methylidene-16-oxo-15-oxapentacyclo[9.3.2.15,8.01,10.02,8]heptadecane-9-carboxylic acid (1R,2R,5R,8R,9S,10R,12S)-12-hydroxy-11-methyl-6-methylidene-16-oxo-15-oxapentacyclo[9.3.2.15,8.01,10.02,8]heptadec-13-ene-9-carboxylic acid Chemical compound C(Nc1ncnc2nc[nH]c12)c1ccccc1.CC12[C@H]3[C@H](C(O)=O)[C@@]45C[C@@H](CC[C@H]4[C@@]3(CC[C@@H]1O)OC2=O)C(=C)C5.CC12[C@H]3[C@H](C(O)=O)[C@@]45C[C@@H](CC[C@H]4[C@]3(OC1=O)C=C[C@@H]2O)C(=C)C5 GKWTZACONBQTNK-IVIZKJKWSA-N 0.000 description 1
- 241001028048 Nicola Species 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 102100026459 POU domain, class 3, transcription factor 2 Human genes 0.000 description 1
- 101710133394 POU domain, class 3, transcription factor 2 Proteins 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 108010064851 Plant Proteins Proteins 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 101710176074 Protein A13 Proteins 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 108010026552 Proteome Proteins 0.000 description 1
- 101000774655 Protobothrops mucrosquamatus Snake venom metalloproteinase TM-1 Proteins 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 241000235070 Saccharomyces Species 0.000 description 1
- 241000235346 Schizosaccharomyces Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 208000000491 Tendinopathy Diseases 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 244000000188 Vaccinium ovalifolium Species 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 108700005077 Viral Genes Proteins 0.000 description 1
- 208000027276 Von Willebrand disease Diseases 0.000 description 1
- 101710151579 Zinc metalloproteinase Proteins 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 238000004115 adherent culture Methods 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- QYPPJABKJHAVHS-UHFFFAOYSA-P agmatinium(2+) Chemical compound NC(=[NH2+])NCCCC[NH3+] QYPPJABKJHAVHS-UHFFFAOYSA-P 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 238000004630 atomic force microscopy Methods 0.000 description 1
- 210000000270 basal cell Anatomy 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229960000182 blood factors Drugs 0.000 description 1
- 230000010072 bone remodeling Effects 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 102200146493 c.2944G>A Human genes 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 229940023913 cation exchange resins Drugs 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 239000012539 chromatography resin Substances 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 208000018631 connective tissue disease Diseases 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000005112 continuous flow technique Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 238000012364 cultivation method Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- AIUDWMLXCFRVDR-UHFFFAOYSA-N dimethyl 2-(3-ethyl-3-methylpentyl)propanedioate Chemical compound CCC(C)(CC)CCC(C(=O)OC)C(=O)OC AIUDWMLXCFRVDR-UHFFFAOYSA-N 0.000 description 1
- 229960003722 doxycycline Drugs 0.000 description 1
- XQTWDDCIUJNLTR-CVHRZJFOSA-N doxycycline monohydrate Chemical compound O.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@@H]1[C@H]2O XQTWDDCIUJNLTR-CVHRZJFOSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000002296 dynamic light scattering Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000009313 farming Methods 0.000 description 1
- 239000012526 feed medium Substances 0.000 description 1
- 239000012527 feed solution Substances 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 102000013361 fetuin Human genes 0.000 description 1
- 108060002885 fetuin Proteins 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 229910052587 fluorapatite Inorganic materials 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000000499 gel Substances 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
- 238000010353 genetic engineering Methods 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 239000012510 hollow fiber Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940034998 human von willebrand factor Drugs 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000002706 hydrostatic effect Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 1
- 239000004026 insulin derivative Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 238000012007 large scale cell culture Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 210000003593 megakaryocyte Anatomy 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 229940098815 novolin n Drugs 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 235000021118 plant-derived protein Nutrition 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001902 propagating effect Effects 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 239000013608 rAAV vector Substances 0.000 description 1
- 101150079601 recA gene Proteins 0.000 description 1
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 102200068289 rs121908467 Human genes 0.000 description 1
- 102200068293 rs121908470 Human genes 0.000 description 1
- 102200068136 rs121908471 Human genes 0.000 description 1
- 102200068906 rs121908472 Human genes 0.000 description 1
- 102200068909 rs121908474 Human genes 0.000 description 1
- 102200068182 rs121908475 Human genes 0.000 description 1
- 102200068110 rs121908477 Human genes 0.000 description 1
- 102200068114 rs121908478 Human genes 0.000 description 1
- 102200059216 rs1428029508 Human genes 0.000 description 1
- 102200068145 rs2301612 Human genes 0.000 description 1
- 102200068886 rs281875301 Human genes 0.000 description 1
- 102200068290 rs281875302 Human genes 0.000 description 1
- 102200068912 rs281875303 Human genes 0.000 description 1
- 102200068106 rs281875304 Human genes 0.000 description 1
- 102200068148 rs281875305 Human genes 0.000 description 1
- 102200068137 rs281875306 Human genes 0.000 description 1
- 102200068171 rs281875307 Human genes 0.000 description 1
- 102200068913 rs281875308 Human genes 0.000 description 1
- 102200068910 rs281875340 Human genes 0.000 description 1
- 102200068905 rs28503257 Human genes 0.000 description 1
- 102200068284 rs34024143 Human genes 0.000 description 1
- 102200068144 rs36220239 Human genes 0.000 description 1
- 102200068142 rs36220240 Human genes 0.000 description 1
- 102200008263 rs367643250 Human genes 0.000 description 1
- 102200068962 rs41314453 Human genes 0.000 description 1
- 102200024005 rs78678589 Human genes 0.000 description 1
- 102200068888 rs78977446 Human genes 0.000 description 1
- 102200041799 rs80338778 Human genes 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000000717 sertoli cell Anatomy 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000007669 thermal treatment Methods 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- STCOOQWBFONSKY-UHFFFAOYSA-N tributyl phosphate Chemical compound CCCCOP(=O)(OCCCC)OCCCC STCOOQWBFONSKY-UHFFFAOYSA-N 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 238000013060 ultrafiltration and diafiltration Methods 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 231100000216 vascular lesion Toxicity 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 208000012137 von Willebrand disease (hereditary or acquired) Diseases 0.000 description 1
- 230000004572 zinc-binding Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6489—Metalloendopeptidases (3.4.24)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0681—Cells of the genital tract; Non-germinal cells from gonads
- C12N5/0682—Cells of the female genital tract, e.g. endometrium; Non-germinal cells from ovaries, e.g. ovarian follicle cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0684—Cells of the urinary tract or kidneys
- C12N5/0686—Kidney cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/24—Metalloendopeptidases (3.4.24)
- C12Y304/24087—ADAMTS13 endopeptidase (3.4.24.87)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2500/00—Specific components of cell culture medium
- C12N2500/05—Inorganic components
- C12N2500/10—Metals; Metal chelators
- C12N2500/12—Light metals, i.e. alkali, alkaline earth, Be, Al, Mg
- C12N2500/14—Calcium; Ca chelators; Calcitonin
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2500/00—Specific components of cell culture medium
- C12N2500/05—Inorganic components
- C12N2500/10—Metals; Metal chelators
- C12N2500/20—Transition metals
- C12N2500/22—Zinc; Zn chelators
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2500/00—Specific components of cell culture medium
- C12N2500/30—Organic components
- C12N2500/38—Vitamins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2500/00—Specific components of cell culture medium
- C12N2500/90—Serum-free medium, which may still contain naturally-sourced components
- C12N2500/95—Protein-free medium and culture conditions
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2500/00—Specific components of cell culture medium
- C12N2500/99—Serum-free medium
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2510/00—Genetically modified cells
- C12N2510/02—Cells for production
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Cell Biology (AREA)
- Urology & Nephrology (AREA)
- Reproductive Health (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Enzymes And Modification Thereof (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| BR122021005965-9A BR122021005965B1 (pt) | 2009-07-31 | 2010-07-30 | Método para produzir uma composição de desintegrina e metaloproteinase com motivo trombospondina (adamts) |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23047709P | 2009-07-31 | 2009-07-31 | |
| US61/230,477 | 2009-07-31 | ||
| US61/230477 | 2009-07-31 | ||
| PCT/US2010/044020 WO2011014838A1 (en) | 2009-07-31 | 2010-07-30 | Cell culture medium for adamts protein expression |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| BR112012002151A2 BR112012002151A2 (pt) | 2020-03-03 |
| BR112012002151B1 true BR112012002151B1 (pt) | 2021-07-06 |
Family
ID=42668009
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR112012002151-6A BR112012002151B1 (pt) | 2009-07-31 | 2010-07-30 | método para expressar uma desintegrina e metaloproteinase com proteína de motivo trombospondina (adamts) |
| BR122021005965-9A BR122021005965B1 (pt) | 2009-07-31 | 2010-07-30 | Método para produzir uma composição de desintegrina e metaloproteinase com motivo trombospondina (adamts) |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR122021005965-9A BR122021005965B1 (pt) | 2009-07-31 | 2010-07-30 | Método para produzir uma composição de desintegrina e metaloproteinase com motivo trombospondina (adamts) |
Country Status (21)
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112012002151B1 (pt) * | 2009-07-31 | 2021-07-06 | Baxalta GmbH | método para expressar uma desintegrina e metaloproteinase com proteína de motivo trombospondina (adamts) |
| EA202090067A3 (ru) | 2010-07-08 | 2020-07-31 | Баксалта Инкорпорейтид | Способ получения рекомбинантного adamts13 в культуре клеток |
| LT2726600T (lt) | 2011-07-01 | 2017-05-25 | Amgen Inc. | Žinduolių ląstelių kultūra |
| ES2633960T3 (es) | 2012-10-15 | 2017-09-26 | Bristol-Myers Squibb Company | Procesos de cultivo de células de mamífero para la producción de proteínas |
| WO2014159831A1 (en) | 2013-03-13 | 2014-10-02 | Merck Sharp & Dohme Corp. | Adapted lepidopteran insect cells for the production of recombinant proteins |
| US9217168B2 (en) | 2013-03-14 | 2015-12-22 | Momenta Pharmaceuticals, Inc. | Methods of cell culture |
| AR095196A1 (es) | 2013-03-15 | 2015-09-30 | Regeneron Pharma | Medio de cultivo celular libre de suero |
| WO2015055324A1 (en) * | 2013-10-14 | 2015-04-23 | Ares Trading S.A | New medium for high performance mammalian fed-batch cultures |
| LT3926051T (lt) | 2014-06-04 | 2024-06-10 | Amgen Inc. | Žinduolių ląstelių kultūros surinkimo metodai |
| KR101867134B1 (ko) * | 2015-03-23 | 2018-06-12 | 한양대학교 산학협력단 | 포유류 세포를 이용하여 목적 물질을 고효율로 생산하기 위한 세포 배양 배지, 이를 이용한 세포 배양 방법 및 목적 물질의 생산 방법 |
| PT3298138T (pt) * | 2015-05-22 | 2022-11-02 | Dupont Nutrition Biosci Aps | Acetolactato descarboxilase |
| TWI870789B (zh) | 2015-08-04 | 2025-01-21 | 美商再生元醫藥公司 | 補充牛磺酸之細胞培養基及用法 |
| CA3031740A1 (en) | 2016-08-04 | 2018-02-08 | Baxalta Incorporated | Use of adamts13 for treating, ameliorating and/or preventing vaso-occlusive crisis in sickle cell disease, acute lung injury and/or acute respiratory distress syndrome |
| WO2018128688A1 (en) * | 2016-11-04 | 2018-07-12 | Baxalta Incorporated | Adeno-associated virus purification methods |
| MX2020000228A (es) * | 2017-07-06 | 2020-08-10 | Regeneron Pharma | Proceso de cultivo celular para producir una glicoproteina. |
| KR20250016476A (ko) * | 2018-03-16 | 2025-02-03 | 젠자임 코포레이션 | 생산용 생물 반응기에서의 세포 생존력을 개선하는 방법 |
| EP3807408A4 (en) * | 2018-06-18 | 2022-03-30 | Synthetic Biologics, Inc. | METHODS OF MAKING ALKALINE PHOSPHATASE AGENTS |
| EP4037704B1 (en) | 2019-10-04 | 2025-12-03 | The Children's Medical Center Corporation | Adamts13 treatment to enhance graft survival |
| US12297451B1 (en) | 2019-10-25 | 2025-05-13 | Regeneron Pharmaceuticals, Inc. | Cell culture medium |
| CA3159586A1 (en) | 2019-12-06 | 2021-06-10 | Regeneron Pharmaceuticals, Inc. | Anti-vegf protein compositions and methods for producing the same |
| CA3173709A1 (en) | 2020-04-02 | 2021-10-07 | Friedmund BACHMANN | Adamts13 variant, compositions, and uses thereof |
| JP2023525034A (ja) | 2020-05-08 | 2023-06-14 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | Ｖｅｇｆトラップおよびミニトラップならびに眼障害およびがんの治療方法 |
| JP2023526546A (ja) | 2020-05-22 | 2023-06-21 | 武田薬品工業株式会社 | コロナウイルス疾患の合併症の治療及び診断のための、ａｄａｍｔｓ１３組成物及び方法 |
| WO2021246557A1 (ko) * | 2020-06-05 | 2021-12-09 | 주식회사 프로앱텍 | 특정한 갯수의 알부민이 연결된 요산산화효소-알부민 복합체 및 이의 제조 방법 |
| CN111808822B (zh) * | 2020-07-02 | 2024-01-12 | 北京百普赛斯生物科技股份有限公司 | 细胞培养用补料液及提高重组hek293细胞蛋白表达量的方法 |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4797368A (en) | 1985-03-15 | 1989-01-10 | The United States Of America As Represented By The Department Of Health And Human Services | Adeno-associated virus as eukaryotic expression vector |
| US5139941A (en) | 1985-10-31 | 1992-08-18 | University Of Florida Research Foundation, Inc. | AAV transduction vectors |
| US5250421A (en) | 1986-01-03 | 1993-10-05 | Genetics Institute, Inc. | Method for producing factor VIII:C-type proteins |
| JPH0753104B2 (ja) * | 1989-02-28 | 1995-06-07 | 秀明 山田 | 細菌の培養法 |
| CZ280901B6 (cs) | 1988-10-06 | 1996-05-15 | Hideaki Yamada | Způsob kultivace bakterií |
| GB9022545D0 (en) | 1990-10-17 | 1990-11-28 | Wellcome Found | Culture medium |
| ATE542891T1 (de) | 1994-11-10 | 2012-02-15 | Baxter Healthcare Sa | Verfahren zur herstellung von biologischen produkten in protein-freier kultur |
| CA2211630A1 (en) | 1995-02-23 | 1996-08-29 | Quest International B.V. | Peptides for tissue and cell culture media |
| US6013516A (en) | 1995-10-06 | 2000-01-11 | The Salk Institute For Biological Studies | Vector and method of use for nucleic acid delivery to non-dividing cells |
| AU4330597A (en) | 1996-08-30 | 1998-03-19 | Life Technologies, Inc. | Serum-free mammalian cell culture medium, and uses thereof |
| IT1285158B1 (it) | 1996-09-17 | 1998-06-03 | Angeletti P Ist Richerche Bio | Polipeptidi solubili con l'attivita' di serino-proteasi di ns3 del virus dell'epatite c, e procedimento per la loro preparazione e il |
| KR100544044B1 (ko) | 1996-10-07 | 2006-01-23 | 솔루티아인코포레이티드 | 방향족 화합물 및 벤젠의 하이드록실화 방법 및 이를 위한 반응 혼합물 |
| JP4543402B2 (ja) | 1996-10-10 | 2010-09-15 | ライフ テクノロジーズ コーポレーション | 植物由来栄養素を含む動物細胞培養培地 |
| US5804420A (en) | 1997-04-18 | 1998-09-08 | Bayer Corporation | Preparation of recombinant Factor VIII in a protein free medium |
| US6475725B1 (en) | 1997-06-20 | 2002-11-05 | Baxter Aktiengesellschaft | Recombinant cell clones having increased stability and methods of making and using the same |
| AT407255B (de) | 1997-06-20 | 2001-02-26 | Immuno Ag | Rekombinanter zellklon mit erhöhter stabilität in serum- und proteinfreiem medium und verfahren zur gewinnung des stabilen zellklons |
| US5994136A (en) | 1997-12-12 | 1999-11-30 | Cell Genesys, Inc. | Method and means for producing high titer, safe, recombinant lentivirus vectors |
| US6406909B1 (en) | 1998-07-10 | 2002-06-18 | Chugai Seiyaku Kabushiki Kaisha | Serum-free medium for culturing animal cells |
| AT409379B (de) | 1999-06-02 | 2002-07-25 | Baxter Ag | Medium zur protein- und serumfreien kultivierung von zellen |
| US6926894B2 (en) | 2000-11-22 | 2005-08-09 | Baxter Aktiengesellschaft | Composition exhibiting a von willebrand factor (vWF) protease activity comprising a polypeptide chain with the amino acid sequence AAGGILHLELLV |
| WO2004056976A2 (en) | 2002-12-23 | 2004-07-08 | Fuji Photo Film B.V. | Process for coating cell-culture support |
| JP2007534675A (ja) * | 2004-04-16 | 2007-11-29 | ワイス | Ａｄａｍｔｓ−８タンパク質およびその使用 |
| US20060094104A1 (en) | 2004-10-29 | 2006-05-04 | Leopold Grillberger | Animal protein-free media for cultivation of cells |
| JP2007174948A (ja) * | 2005-12-27 | 2007-07-12 | Noritsu Koki Co Ltd | 酵素水製造装置 |
| JP4880997B2 (ja) * | 2005-12-28 | 2012-02-22 | アルフレッサファーマ株式会社 | Ａｄａｍｔｓ１３の安定化方法 |
| DK1974014T3 (en) | 2006-01-04 | 2017-06-19 | Baxalta Inc | OLIGOPEPTID-FREE CELL CULTURE MEDIA |
| CN101611268B (zh) * | 2006-12-22 | 2013-06-12 | 斯普灵格开利有限公司 | 用于空调单元的新鲜空气控制杆 |
| US20090067805A1 (en) | 2007-09-10 | 2009-03-12 | Victor Company Of Japan, Limited | Recording and reproducing device |
| NZ586250A (en) * | 2007-12-27 | 2012-11-30 | Baxter Int | Cell culture processes |
| BR112012002151B1 (pt) * | 2009-07-31 | 2021-07-06 | Baxalta GmbH | método para expressar uma desintegrina e metaloproteinase com proteína de motivo trombospondina (adamts) |
-
2010
- 2010-07-30 BR BR112012002151-6A patent/BR112012002151B1/pt active IP Right Grant
- 2010-07-30 AU AU2010278751A patent/AU2010278751B2/en active Active
- 2010-07-30 HR HRP20160783TT patent/HRP20160783T1/hr unknown
- 2010-07-30 ES ES10740810.6T patent/ES2583258T3/es active Active
- 2010-07-30 CA CA2769361A patent/CA2769361A1/en not_active Abandoned
- 2010-07-30 BR BR122021005965-9A patent/BR122021005965B1/pt active IP Right Grant
- 2010-07-30 EA EA201270224A patent/EA023193B1/ru not_active IP Right Cessation
- 2010-07-30 CN CN201080042028.1A patent/CN102549145B/zh active Active
- 2010-07-30 CN CN201510186244.8A patent/CN104962539B/zh active Active
- 2010-07-30 KR KR1020177018298A patent/KR101808496B1/ko active Active
- 2010-07-30 US US12/847,999 patent/US8313926B2/en active Active
- 2010-07-30 KR KR1020127005425A patent/KR101573972B1/ko active Active
- 2010-07-30 PL PL10740810.6T patent/PL2459702T3/pl unknown
- 2010-07-30 IN IN801DEN2012 patent/IN2012DN00801A/en unknown
- 2010-07-30 MX MX2012001261A patent/MX2012001261A/es active IP Right Grant
- 2010-07-30 EP EP10740810.6A patent/EP2459702B1/en active Active
- 2010-07-30 SG SG2012006839A patent/SG178194A1/en unknown
- 2010-07-30 WO PCT/US2010/044020 patent/WO2011014838A1/en not_active Ceased
- 2010-07-30 KR KR1020157009715A patent/KR101574056B1/ko active Active
- 2010-07-30 PT PT107408106T patent/PT2459702T/pt unknown
- 2010-07-30 KR KR1020177035177A patent/KR101912552B1/ko active Active
- 2010-07-30 JP JP2012523110A patent/JP5451884B2/ja active Active
- 2010-07-30 KR KR1020157033595A patent/KR101756354B1/ko active Active
- 2010-07-30 NZ NZ597727A patent/NZ597727A/xx unknown
- 2010-07-30 SI SI201031238A patent/SI2459702T1/sl unknown
- 2010-07-30 HU HUE10740810A patent/HUE029110T2/en unknown
-
2012
- 2012-01-27 MX MX2013009470A patent/MX344970B/es unknown
- 2012-02-27 CO CO12033821A patent/CO6501191A2/es unknown
- 2012-09-19 US US13/622,939 patent/US8759026B2/en active Active
-
2014
- 2014-05-13 US US14/276,819 patent/US9127265B2/en active Active
-
2015
- 2015-07-23 US US14/807,745 patent/US9441216B2/en active Active
-
2016
- 2016-05-06 JP JP2016093240A patent/JP6511007B2/ja active Active
- 2016-08-09 US US15/232,626 patent/US10072254B2/en active Active
-
2018
- 2018-01-26 JP JP2018011373A patent/JP6567707B2/ja active Active
- 2018-09-08 US US16/125,688 patent/US10724024B2/en active Active
-
2019
- 2019-07-31 JP JP2019141485A patent/JP6883071B2/ja active Active
-
2020
- 2020-06-16 US US16/903,185 patent/US11254921B2/en active Active
-
2021
- 2021-05-07 JP JP2021079239A patent/JP7083059B2/ja active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11254921B2 (en) | ADAMTS13 protein cell culture supernatant | |
| AU2017261523B2 (en) | Cell culture medium for adamts protein expression | |
| AU2019279943B2 (en) | Cell culture medium for adamts protein expression | |
| HK1171790B (en) | Cell culture medium for adamts protein expression |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B25A | Requested transfer of rights approved |
Owner name: BAXALTA GMBH (CH) ; BAXALTA INCORPORATED (US) |
|
| B06F | Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette] | ||
| B06U | Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette] | ||
| B07A | Application suspended after technical examination (opinion) [chapter 7.1 patent gazette] | ||
| B09A | Decision: intention to grant [chapter 9.1 patent gazette] | ||
| B16A | Patent or certificate of addition of invention granted [chapter 16.1 patent gazette] |
Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 30/07/2010, OBSERVADAS AS CONDICOES LEGAIS. PATENTE CONCEDIDA CONFORME ADI 5.529/DF, QUE DETERMINA A ALTERACAO DO PRAZO DE CONCESSAO. |
|
| B25A | Requested transfer of rights approved |
Owner name: TAKEDA PHARMACEUTICAL COMPANY LIMITED (JP) |
|
| B25L | Entry of change of name and/or headquarter and transfer of application, patent and certificate of addition of invention: publication cancelled |
Owner name: BAXALTA GMBH (CH) ; BAXALTA INCORPORATED (US) Free format text: ANULADA A PUBLICACAO CODIGO 25.1 NA RPI NO 2652 DE 03/11/2021 POR TER SIDO INDEVIDA. |
|
| B25A | Requested transfer of rights approved |
Owner name: TAKEDA PHARMACEUTICAL COMPANY LIMITED (JP) |