JP2593500C - - Google Patents
Info
- Publication number
- JP2593500C JP2593500C JP2593500C JP 2593500 C JP2593500 C JP 2593500C JP 2593500 C JP2593500 C JP 2593500C
- Authority
- JP
- Japan
- Prior art keywords
- fviii
- viii
- complex
- incubation
- buffer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 102100000368 F8 Human genes 0.000 claims description 40
- 101700070229 F8 Proteins 0.000 claims description 40
- 239000000203 mixture Substances 0.000 claims description 36
- 108010054218 Factor VIII Proteins 0.000 claims description 23
- 229960000301 Factor VIII Drugs 0.000 claims description 23
- 102000001690 Factor VIII Human genes 0.000 claims description 23
- 210000004898 N-terminal fragment Anatomy 0.000 claims description 5
- 150000002500 ions Chemical class 0.000 claims description 5
- 239000002184 metal Substances 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
- UIIMBOGNXHQVGW-UHFFFAOYSA-M buffer Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 29
- 239000000523 sample Substances 0.000 description 21
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- RAXXELZNTBOGNW-UHFFFAOYSA-N Imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
- 210000002381 Plasma Anatomy 0.000 description 10
- 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
- 239000000427 antigen Substances 0.000 description 6
- 102000038129 antigens Human genes 0.000 description 6
- 108091007172 antigens Proteins 0.000 description 6
- 230000015271 coagulation Effects 0.000 description 6
- 238000005345 coagulation Methods 0.000 description 6
- 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
- 229920002684 Sepharose Polymers 0.000 description 5
- 238000004166 bioassay Methods 0.000 description 5
- UXVMQQNJUSDDNG-UHFFFAOYSA-L cacl2 Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 5
- 229920003013 deoxyribonucleic acid Polymers 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- DGVVWUTYPXICAM-UHFFFAOYSA-N 2-mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 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
- 201000003542 factor VIII deficiency Diseases 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 2
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 2
- 206010018987 Haemorrhage Diseases 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- 102000017975 Protein C Human genes 0.000 description 2
- 229960000856 Protein C Drugs 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 102000004965 antibodies Human genes 0.000 description 2
- 108090001123 antibodies Proteins 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000740 bleeding Effects 0.000 description 2
- 231100000319 bleeding Toxicity 0.000 description 2
- 239000003114 blood coagulation factor Substances 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 210000004027 cells Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 230000000875 corresponding Effects 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 210000004748 cultured cells Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000005755 formation reaction Methods 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 108060005018 mobB Proteins 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- NKCXQMYPWXSLIZ-PSRDDEIFSA-N (2S)-2-[[(2S)-1-[(2S)-5-amino-2-[[2-[[(2S)-6-amino-2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-amino-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-hydroxybutanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]-3-m Chemical compound O=C([C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](N)[C@@H](C)O)[C@@H](C)O)C(C)C)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O NKCXQMYPWXSLIZ-PSRDDEIFSA-N 0.000 description 1
- VHJLVAABSRFDPM-UHFFFAOYSA-N 1,4-dimercaptobutane-2,3-diol Chemical compound SCC(O)C(O)CS VHJLVAABSRFDPM-UHFFFAOYSA-N 0.000 description 1
- 210000004369 Blood Anatomy 0.000 description 1
- 210000004899 C-terminal region Anatomy 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000283707 Capra Species 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
- 102000013831 Coagulation factor IX Human genes 0.000 description 1
- YVGGHNCTFXOJCH-UHFFFAOYSA-N DDT Chemical compound C1=CC(Cl)=CC=C1C(C(Cl)(Cl)Cl)C1=CC=C(Cl)C=C1 YVGGHNCTFXOJCH-UHFFFAOYSA-N 0.000 description 1
- 102100011228 F10 Human genes 0.000 description 1
- 102100015239 F2 Human genes 0.000 description 1
- 108010076282 Factor IX Proteins 0.000 description 1
- 108010014173 Factor X Proteins 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 229910017153 MnC Inorganic materials 0.000 description 1
- 210000004897 N-terminal region Anatomy 0.000 description 1
- 229940072417 Peroxidase Drugs 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 108090000437 Peroxidases Proteins 0.000 description 1
- 229940039716 Prothrombin Drugs 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 230000003213 activating 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
- 239000008280 blood Substances 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
- 230000000536 complexating Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000004059 degradation Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001419 dependent Effects 0.000 description 1
- 239000012470 diluted sample Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 230000002255 enzymatic Effects 0.000 description 1
- 229960004222 factor IX Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 101700025122 nac-1 Proteins 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000000770 propane-1,2-diol alginate Substances 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 239000002265 redox agent Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
Family
ID=
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