JP2593500C - - Google Patents

Info

Publication number: JP2593500C
Authority: JP; Japan
Prior art keywords: fviii; viii; complex; incubation; buffer
Prior art date: 1999-01-20
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Lifetime

Application number

Other languages

English (en)

Japanese (ja)

Original Assignee

ノボ・ノルディスク・エー／エス

Publication date

1999-01-20

Links

102100026735 Coagulation factor VIII Human genes 0.000 claims description 40
101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 claims description 40
239000000203 mixture Substances 0.000 claims description 36
239000012634 fragment Substances 0.000 claims description 25
108010054218 Factor VIII Proteins 0.000 claims description 23
102000001690 Factor VIII Human genes 0.000 claims description 23
229960000301 factor viii Drugs 0.000 claims description 23
238000000034 method Methods 0.000 claims description 16
229910021645 metal ion Inorganic materials 0.000 claims description 5
210000004898 n-terminal fragment Anatomy 0.000 claims description 5
210000004900 c-terminal fragment Anatomy 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
239000000126 substance Substances 0.000 claims description 4
150000001875 compounds Chemical class 0.000 claims 2
230000009257 reactivity Effects 0.000 claims 2
238000011534 incubation Methods 0.000 description 39
239000000872 buffer Substances 0.000 description 29
239000000523 sample Substances 0.000 description 21
238000012360 testing method Methods 0.000 description 21
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 18
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
238000002474 experimental method Methods 0.000 description 13
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
235000018102 proteins Nutrition 0.000 description 7
102000004169 proteins and genes Human genes 0.000 description 7
108090000623 proteins and genes Proteins 0.000 description 7
239000011780 sodium chloride Substances 0.000 description 7
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 6
239000000427 antigen Substances 0.000 description 6
102000036639 antigens Human genes 0.000 description 6
108091007433 antigens Proteins 0.000 description 6
230000015271 coagulation Effects 0.000 description 6
238000005345 coagulation Methods 0.000 description 6
229920002684 Sepharose Polymers 0.000 description 5
238000003556 assay Methods 0.000 description 5
230000000694 effects Effects 0.000 description 4
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
201000003542 Factor VIII deficiency Diseases 0.000 description 3
208000009292 Hemophilia A Diseases 0.000 description 3
108010094028 Prothrombin Proteins 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
230000035602 clotting Effects 0.000 description 3
238000000502 dialysis Methods 0.000 description 3
DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 3
239000003112 inhibitor Substances 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 3
102000015081 Blood Coagulation Factors Human genes 0.000 description 2
108010039209 Blood Coagulation Factors Proteins 0.000 description 2
208000032843 Hemorrhage Diseases 0.000 description 2
102000017975 Protein C Human genes 0.000 description 2
208000007536 Thrombosis Diseases 0.000 description 2
238000001042 affinity chromatography Methods 0.000 description 2
230000000740 bleeding effect Effects 0.000 description 2
239000003114 blood coagulation factor Substances 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
238000004113 cell culture Methods 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 2
239000012141 concentrate Substances 0.000 description 2
230000021615 conjugation Effects 0.000 description 2
239000012228 culture supernatant Substances 0.000 description 2
210000004748 cultured cell Anatomy 0.000 description 2
230000001900 immune effect Effects 0.000 description 2
238000003018 immunoassay Methods 0.000 description 2
238000011533 pre-incubation Methods 0.000 description 2
229960000856 protein c Drugs 0.000 description 2
238000011002 quantification Methods 0.000 description 2
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
101100459438 Caenorhabditis elegans nac-1 gene Proteins 0.000 description 1
241000282465 Canis Species 0.000 description 1
241000283707 Capra Species 0.000 description 1
102100022641 Coagulation factor IX Human genes 0.000 description 1
102100029117 Coagulation factor X Human genes 0.000 description 1
101001030665 Dictyostelium discoideum GDP-L-fucose synthase Proteins 0.000 description 1
108010076282 Factor IX Proteins 0.000 description 1
108010014173 Factor X Proteins 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
102000003992 Peroxidases Human genes 0.000 description 1
101800004937 Protein C Proteins 0.000 description 1
102100027378 Prothrombin Human genes 0.000 description 1
101800001700 Saposin-D Proteins 0.000 description 1
108090000190 Thrombin Proteins 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
230000004913 activation Effects 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
239000012062 aqueous buffer Substances 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
210000004899 c-terminal region Anatomy 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
230000015556 catabolic process Effects 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
229940105774 coagulation factor ix Drugs 0.000 description 1
229940105756 coagulation factor x Drugs 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
230000009918 complex formation Effects 0.000 description 1
230000000536 complexating effect Effects 0.000 description 1
239000002131 composite material Substances 0.000 description 1
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
235000018417 cysteine Nutrition 0.000 description 1
230000002950 deficient Effects 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
239000012470 diluted sample Substances 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
239000012149 elution buffer Substances 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
230000023597 hemostasis Effects 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
238000005259 measurement Methods 0.000 description 1
238000002156 mixing Methods 0.000 description 1
210000004897 n-terminal region Anatomy 0.000 description 1
108040007629 peroxidase activity proteins Proteins 0.000 description 1
150000003904 phospholipids Chemical class 0.000 description 1
239000013612 plasmid Substances 0.000 description 1
239000000047 product Substances 0.000 description 1
239000000770 propane-1,2-diol alginate Substances 0.000 description 1
229940039716 prothrombin Drugs 0.000 description 1
238000005215 recombination Methods 0.000 description 1
230000006798 recombination Effects 0.000 description 1
239000002265 redox agent Substances 0.000 description 1
238000011160 research Methods 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
229960004072 thrombin Drugs 0.000 description 1

Family

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