NO325358B1 - Fremgangsmate for fremstilling av en biologisk aktiv, rekombinant human blodkoaguleringsfaktor VIII i et celledyrkningsmedium som tillater ekspresjon og sekresjon av polypeptidet. - Google Patents
Fremgangsmate for fremstilling av en biologisk aktiv, rekombinant human blodkoaguleringsfaktor VIII i et celledyrkningsmedium som tillater ekspresjon og sekresjon av polypeptidet. Download PDFInfo
- Publication number
- NO325358B1 NO325358B1 NO19985297A NO985297A NO325358B1 NO 325358 B1 NO325358 B1 NO 325358B1 NO 19985297 A NO19985297 A NO 19985297A NO 985297 A NO985297 A NO 985297A NO 325358 B1 NO325358 B1 NO 325358B1
- Authority
- NO
- Norway
- Prior art keywords
- factor viii
- cell culture
- culture medium
- proteases
- cells
- Prior art date
Links
- 108010054218 Factor VIII Proteins 0.000 title claims abstract description 44
- 102000001690 Factor VIII Human genes 0.000 title claims abstract description 44
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 43
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 40
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 38
- 239000006143 cell culture medium Substances 0.000 title claims abstract description 37
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 22
- 230000028327 secretion Effects 0.000 title claims description 8
- 230000014509 gene expression Effects 0.000 title claims description 6
- 229960000301 factor viii Drugs 0.000 claims abstract description 37
- 239000003112 inhibitor Substances 0.000 claims abstract description 31
- 238000000034 method Methods 0.000 claims abstract description 31
- 230000008569 process Effects 0.000 claims abstract description 5
- 210000004027 cell Anatomy 0.000 claims description 39
- 230000000694 effects Effects 0.000 claims description 25
- YSOKXDUFQIWMQV-UHFFFAOYSA-N Chymostatin C Natural products CCCCC(NC(=O)CNC(=O)NC(Cc1ccccc1)C(=O)O)C(=O)NC(Cc2ccccc2)(C=O)C3CCNC(=N3)N YSOKXDUFQIWMQV-UHFFFAOYSA-N 0.000 claims description 10
- 108010025139 recombinant factor VIII SQ Proteins 0.000 claims description 8
- 210000004962 mammalian cell Anatomy 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- BEUQWPLRPXILQA-UHFFFAOYSA-N Chymostatin B Natural products CCCC(NC(=O)CNC(=O)NC(Cc1ccccc1)C(=O)O)C(=O)NC(Cc2ccccc2)(C=O)C3CCNC(=N3)N BEUQWPLRPXILQA-UHFFFAOYSA-N 0.000 claims description 4
- 241000238631 Hexapoda Species 0.000 claims description 4
- 241000699802 Cricetulus griseus Species 0.000 claims description 3
- 239000004471 Glycine Substances 0.000 claims description 3
- 230000015271 coagulation Effects 0.000 claims description 3
- 238000005345 coagulation Methods 0.000 claims description 3
- 229940105778 coagulation factor viii Drugs 0.000 claims description 3
- 210000004408 hybridoma Anatomy 0.000 claims description 3
- 210000001672 ovary Anatomy 0.000 claims description 3
- 239000012679 serum free medium Substances 0.000 claims description 3
- 241000699800 Cricetinae Species 0.000 claims description 2
- 230000001580 bacterial effect Effects 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 102000035195 Peptidases Human genes 0.000 abstract description 43
- 108091005804 Peptidases Proteins 0.000 abstract description 43
- 239000004365 Protease Substances 0.000 abstract description 39
- 229910052751 metal Inorganic materials 0.000 abstract description 31
- 239000002184 metal Substances 0.000 abstract description 31
- 230000001419 dependent effect Effects 0.000 abstract description 18
- 238000004113 cell culture Methods 0.000 abstract description 5
- 102100026735 Coagulation factor VIII Human genes 0.000 abstract description 4
- 201000003542 Factor VIII deficiency Diseases 0.000 abstract description 4
- 208000009292 Hemophilia A Diseases 0.000 abstract description 4
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 3
- 208000024891 symptom Diseases 0.000 abstract description 2
- 108090000144 Human Proteins Proteins 0.000 abstract 1
- 102000003839 Human Proteins Human genes 0.000 abstract 1
- 230000001627 detrimental effect Effects 0.000 abstract 1
- 230000003248 secreting effect Effects 0.000 abstract 1
- 102000004169 proteins and genes Human genes 0.000 description 20
- 108090000623 proteins and genes Proteins 0.000 description 20
- 235000018102 proteins Nutrition 0.000 description 19
- 102000004190 Enzymes Human genes 0.000 description 17
- 108090000790 Enzymes Proteins 0.000 description 17
- 229940088598 enzyme Drugs 0.000 description 17
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 17
- 108010006035 Metalloproteases Proteins 0.000 description 13
- 102000005741 Metalloproteases Human genes 0.000 description 13
- 108010022999 Serine Proteases Proteins 0.000 description 13
- 102000012479 Serine Proteases Human genes 0.000 description 13
- 239000002609 medium Substances 0.000 description 13
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 12
- 235000001014 amino acid Nutrition 0.000 description 9
- 150000001413 amino acids Chemical class 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- 102000005927 Cysteine Proteases Human genes 0.000 description 8
- 108010005843 Cysteine Proteases Proteins 0.000 description 8
- 150000002739 metals Chemical class 0.000 description 7
- 210000002381 plasma Anatomy 0.000 description 7
- ZPHBZEQOLSRPAK-UHFFFAOYSA-N Phosphoramidon Natural products C=1NC2=CC=CC=C2C=1CC(C(O)=O)NC(=O)C(CC(C)C)NP(O)(=O)OC1OC(C)C(O)C(O)C1O ZPHBZEQOLSRPAK-UHFFFAOYSA-N 0.000 description 6
- ZPHBZEQOLSRPAK-XLCYBJAPSA-N phosphoramidon Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)P(O)(=O)O[C@@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@H]1O ZPHBZEQOLSRPAK-XLCYBJAPSA-N 0.000 description 6
- 108010072906 phosphoramidon Proteins 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 5
- OLVPQBGMUGIKIW-UHFFFAOYSA-N Chymostatin Natural products C=1C=CC=CC=1CC(C=O)NC(=O)C(C(C)CC)NC(=O)C(C1NC(N)=NCC1)NC(=O)NC(C(O)=O)CC1=CC=CC=C1 OLVPQBGMUGIKIW-UHFFFAOYSA-N 0.000 description 5
- 108010059378 Endopeptidases Proteins 0.000 description 5
- 102000005593 Endopeptidases Human genes 0.000 description 5
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 5
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 5
- 238000012217 deletion Methods 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- 108090000317 Chymotrypsin Proteins 0.000 description 4
- -1 Cu<2>+ Chemical class 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 230000003833 cell viability Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 4
- 229960002376 chymotrypsin Drugs 0.000 description 4
- 229940066758 endopeptidases Drugs 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 125000001165 hydrophobic group Chemical group 0.000 description 4
- 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 4
- 150000008298 phosphoramidates Chemical class 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000002797 proteolythic effect Effects 0.000 description 4
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 4
- 239000011701 zinc Substances 0.000 description 4
- MRXDGVXSWIXTQL-HYHFHBMOSA-N (2s)-2-[[(1s)-1-(2-amino-1,4,5,6-tetrahydropyrimidin-6-yl)-2-[[(2s)-4-methyl-1-oxo-1-[[(2s)-1-oxo-3-phenylpropan-2-yl]amino]pentan-2-yl]amino]-2-oxoethyl]carbamoylamino]-3-phenylpropanoic acid Chemical compound C([C@H](NC(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C=O)C1NC(N)=NCC1)C(O)=O)C1=CC=CC=C1 MRXDGVXSWIXTQL-HYHFHBMOSA-N 0.000 description 3
- 108010039627 Aprotinin Proteins 0.000 description 3
- 108090000227 Chymases Proteins 0.000 description 3
- 102000003858 Chymases Human genes 0.000 description 3
- 108090001109 Thermolysin Proteins 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 102000004139 alpha-Amylases Human genes 0.000 description 3
- 108090000637 alpha-Amylases Proteins 0.000 description 3
- 229940024171 alpha-amylase Drugs 0.000 description 3
- 229960004405 aprotinin Drugs 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 108010086192 chymostatin Proteins 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 210000003527 eukaryotic cell Anatomy 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 3
- 229910021645 metal ion Inorganic materials 0.000 description 3
- 239000006225 natural substrate Substances 0.000 description 3
- 230000017854 proteolysis Effects 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229910052725 zinc Inorganic materials 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 102100022641 Coagulation factor IX Human genes 0.000 description 2
- 102100023804 Coagulation factor VII Human genes 0.000 description 2
- 108010076282 Factor IX Proteins 0.000 description 2
- 108010023321 Factor VII Proteins 0.000 description 2
- 108010074860 Factor Xa Proteins 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 108091006905 Human Serum Albumin Proteins 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 2
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 241000235347 Schizosaccharomyces pombe Species 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 108090000190 Thrombin Proteins 0.000 description 2
- 108090000901 Transferrin Proteins 0.000 description 2
- 102000004338 Transferrin Human genes 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 2
- 239000007640 basal medium Substances 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000003593 chromogenic compound Substances 0.000 description 2
- 230000001112 coagulating effect Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000000593 degrading effect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 229960004222 factor ix Drugs 0.000 description 2
- 229940012413 factor vii Drugs 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 102000028416 insulin-like growth factor binding Human genes 0.000 description 2
- 108091022911 insulin-like growth factor binding Proteins 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000004114 suspension culture Methods 0.000 description 2
- 229960004072 thrombin Drugs 0.000 description 2
- 239000012581 transferrin Substances 0.000 description 2
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 1
- OALHHIHQOFIMEF-UHFFFAOYSA-N 3',6'-dihydroxy-2',4',5',7'-tetraiodo-3h-spiro[2-benzofuran-1,9'-xanthene]-3-one Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=C(I)C=C21 OALHHIHQOFIMEF-UHFFFAOYSA-N 0.000 description 1
- 102000004411 Antithrombin III Human genes 0.000 description 1
- 108090000935 Antithrombin III Proteins 0.000 description 1
- 102000035101 Aspartic proteases Human genes 0.000 description 1
- 108091005502 Aspartic proteases Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 102100024746 Dihydrofolate reductase Human genes 0.000 description 1
- 108010014172 Factor V Proteins 0.000 description 1
- 102000003676 Glucocorticoid Receptors Human genes 0.000 description 1
- 108090000079 Glucocorticoid Receptors Proteins 0.000 description 1
- 102000018997 Growth Hormone Human genes 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 102000007625 Hirudins Human genes 0.000 description 1
- 108010007267 Hirudins Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 1
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 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
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 108010092277 Leptin Proteins 0.000 description 1
- 102000016267 Leptin Human genes 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- 102000007399 Nuclear hormone receptor Human genes 0.000 description 1
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 102000004067 Osteocalcin Human genes 0.000 description 1
- 108090000573 Osteocalcin Proteins 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 102000015433 Prostaglandin Receptors Human genes 0.000 description 1
- 108010050183 Prostaglandin Receptors Proteins 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 101000712605 Theromyzon tessulatum Theromin Proteins 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 229940122388 Thrombin inhibitor Drugs 0.000 description 1
- 102100033571 Tissue-type plasminogen activator Human genes 0.000 description 1
- 108050006955 Tissue-type plasminogen activator Proteins 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229960005348 antithrombin iii Drugs 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000157 blood function Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000012832 cell culture technique Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 238000004163 cytometry Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 108020001096 dihydrofolate reductase Proteins 0.000 description 1
- BVTBRVFYZUCAKH-UHFFFAOYSA-L disodium selenite Chemical compound [Na+].[Na+].[O-][Se]([O-])=O BVTBRVFYZUCAKH-UHFFFAOYSA-L 0.000 description 1
- 230000002900 effect on cell Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 229940031098 ethanolamine Drugs 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 230000003480 fibrinolytic effect Effects 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 description 1
- 229940006607 hirudin Drugs 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
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 108091008479 interferon binding proteins Proteins 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 1
- 229940039781 leptin Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 239000007758 minimum essential medium Substances 0.000 description 1
- 238000004264 monolayer culture Methods 0.000 description 1
- 230000014508 negative regulation of coagulation Effects 0.000 description 1
- 231100000989 no adverse effect Toxicity 0.000 description 1
- 108020004017 nuclear receptors Proteins 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
- 231100000719 pollutant Toxicity 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 229960001471 sodium selenite Drugs 0.000 description 1
- 235000015921 sodium selenite Nutrition 0.000 description 1
- 239000011781 sodium selenite Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000012622 synthetic inhibitor Substances 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 239000003868 thrombin inhibitor Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 108010047303 von Willebrand Factor Proteins 0.000 description 1
- 102100036537 von Willebrand factor Human genes 0.000 description 1
- 229960001134 von willebrand factor Drugs 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/745—Blood coagulation or fibrinolysis factors
- C07K14/755—Factors VIII, e.g. factor VIII C (AHF), factor VIII Ag (VWF)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- 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
- C12N15/67—General methods for enhancing the expression
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biophysics (AREA)
- Hematology (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Veterinary Medicine (AREA)
- Plant Pathology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Physics & Mathematics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Animal Behavior & Ethology (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9601855A SE9601855D0 (sv) | 1996-05-14 | 1996-05-14 | Process for producing a protein |
| US1887496P | 1996-05-29 | 1996-05-29 | |
| PCT/SE1997/000783 WO1997043436A1 (en) | 1996-05-14 | 1997-05-13 | A process for producing a recombinant polypeptide involving the addition of an inhibitor of metal-dependent proteases or chymotrypsins to the cell culture medium |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO985297D0 NO985297D0 (no) | 1998-11-13 |
| NO985297L NO985297L (no) | 1999-01-14 |
| NO325358B1 true NO325358B1 (no) | 2008-04-07 |
Family
ID=26662616
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19985297A NO325358B1 (no) | 1996-05-14 | 1998-11-13 | Fremgangsmate for fremstilling av en biologisk aktiv, rekombinant human blodkoaguleringsfaktor VIII i et celledyrkningsmedium som tillater ekspresjon og sekresjon av polypeptidet. |
| NO20065027A NO325633B1 (no) | 1996-05-14 | 2006-11-02 | Fremgangsmate for fremstilling av en biologisk aktiv, rekombinant, human, koaguleringsfaktor VIII i et celledyrkningsmedium som tillater ekspresjon og sekresjon av polypeptidet |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20065027A NO325633B1 (no) | 1996-05-14 | 2006-11-02 | Fremgangsmate for fremstilling av en biologisk aktiv, rekombinant, human, koaguleringsfaktor VIII i et celledyrkningsmedium som tillater ekspresjon og sekresjon av polypeptidet |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US5851800A (cg-RX-API-DMAC7.html) |
| EP (1) | EP0934424B1 (cg-RX-API-DMAC7.html) |
| JP (2) | JP2000509994A (cg-RX-API-DMAC7.html) |
| AT (2) | ATE321141T1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU716245B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2253287C (cg-RX-API-DMAC7.html) |
| DE (2) | DE69735510T2 (cg-RX-API-DMAC7.html) |
| DK (1) | DK0934424T3 (cg-RX-API-DMAC7.html) |
| ES (2) | ES2260524T3 (cg-RX-API-DMAC7.html) |
| NO (2) | NO325358B1 (cg-RX-API-DMAC7.html) |
| NZ (1) | NZ332751A (cg-RX-API-DMAC7.html) |
| PT (2) | PT1318198E (cg-RX-API-DMAC7.html) |
| WO (1) | WO1997043436A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6475725B1 (en) * | 1997-06-20 | 2002-11-05 | Baxter Aktiengesellschaft | Recombinant cell clones having increased stability and methods of making and using the same |
| CN100553678C (zh) | 1999-02-22 | 2009-10-28 | 巴克斯特国际有限公司 | 新的无白蛋白的因子ⅷ制剂 |
| AT409379B (de) | 1999-06-02 | 2002-07-25 | Baxter Ag | Medium zur protein- und serumfreien kultivierung von zellen |
| ATE330003T1 (de) * | 1999-08-05 | 2006-07-15 | Baxter Ag | Rekombinanter stabiler zellklon, seine herstellung und verwendung |
| WO2001052891A1 (fr) * | 2000-01-20 | 2001-07-26 | Nippon Organon K. K. | Inhibiteurs d'invasion plasmodiale dans des erythrocytes |
| CN100591759C (zh) * | 2002-07-09 | 2010-02-24 | 巴克斯特国际有限公司 | 用于细胞培养的无动物蛋白质培养基 |
| PL377731A1 (pl) * | 2002-12-23 | 2006-02-06 | Bristol-Myers Squibb Company | Sposoby hodowli komórek ssaczych do wytwarzania białka |
| PL377603A1 (pl) * | 2002-12-23 | 2006-02-06 | Bristol-Myers Squibb Company | Poprawa jakości produktu w hodowlach komórek ssaczych do wytwarzania białka |
| MXPA05011486A (es) * | 2003-04-25 | 2006-04-18 | Immunex Corp | Inductores de expresion de proteina recombinante. |
| US7255288B2 (en) * | 2004-03-08 | 2007-08-14 | Wan Shan Chan | Aroma therapy for fountain |
| US20060094104A1 (en) | 2004-10-29 | 2006-05-04 | Leopold Grillberger | Animal protein-free media for cultivation of cells |
| EP1707634A1 (en) * | 2005-03-29 | 2006-10-04 | Octapharma AG | Method for isolation of recombinantly produced proteins |
| DK2522717T3 (da) * | 2006-01-04 | 2014-04-22 | Baxter Int | Oligopeptid-frie cellekulturmedier |
| PT2126106T (pt) | 2007-02-23 | 2017-12-12 | Sk Chemicals Co Ltd | Proceso para produzir e purificar o fator viii e seus derivados |
| WO2008135498A2 (en) * | 2007-05-04 | 2008-11-13 | Novo Nordisk A/S | Prevention of protein degradation in mammalian cell cultures |
| EP1988101A1 (en) | 2007-05-04 | 2008-11-05 | Novo Nordisk A/S | Improvement of factor VIII polypeptide titers in cell cultures |
| CA2742328C (en) | 2008-11-07 | 2019-02-26 | Baxter International Inc. | Factor viii formulations |
| US9540426B2 (en) | 2009-10-06 | 2017-01-10 | Bristol-Myers Squibb Company | Mammalian cell culture processes for protein production |
| US10138290B2 (en) | 2010-10-05 | 2018-11-27 | Novo Nordisk Healthcare Ag | Process for protein production |
| CN104822826B (zh) | 2012-10-15 | 2019-04-30 | 百时美施贵宝公司 | 用于蛋白产生的哺乳动物细胞培养过程 |
| KR102668200B1 (ko) | 2015-10-28 | 2024-05-23 | 주식회사유한양행 | 지속형 fgf21 융합 단백질 및 이를 포함하는 약학적 조성물 |
| KR102670157B1 (ko) | 2015-10-28 | 2024-05-29 | 주식회사유한양행 | 이중 작용 단백질 및 이를 포함하는 약학적 조성물 |
| BR112019009581A2 (pt) | 2016-11-10 | 2019-10-08 | Yuhan Corp | composição farmacêutica para evitar ou tratar hepatite, fibrose hepática, e cirrose hepática que compreende proteínas de fusão |
| MX2019012331A (es) | 2017-04-21 | 2020-01-23 | Yuhan Corp | Metodo para producir proteinas de doble funcion y sus derivados. |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5149787A (en) * | 1984-05-22 | 1992-09-22 | The Blood Center Research Foundation | Method for maintaining intact, non-degraded factor VIII/von-Willebrand factor during blood processing |
| SE8501050D0 (sv) * | 1985-03-05 | 1985-03-05 | Kabivitrum Ab | Biologically active fragments of human antihemophilic factor and method for preparation thereof |
| US5279939A (en) * | 1986-08-18 | 1994-01-18 | Smithkline Beecham Corporation | Protein protease inhibitors from streptomyces |
| US4891356A (en) * | 1987-07-15 | 1990-01-02 | Brigham & Women's Hospital | Proteinase inhibitors for treatment of gastrointestinal ulcer disease |
| JPH0387173A (ja) * | 1987-09-10 | 1991-04-11 | Teijin Ltd | ヒト活性化天然型ファクター8cの製造方法及びそれに用いる形質転換体 |
| JP2769170B2 (ja) * | 1987-12-08 | 1998-06-25 | ザイモジェネティクス,インコーポレイティド | 真核細肪中での同時発現 |
| CA1340740C (en) * | 1987-12-08 | 1999-09-14 | Eileen R. Mulvihill | Co-expression in eukaryotic cells |
| DK457788D0 (da) * | 1988-08-16 | 1988-08-16 | Nordisk Gentofte | Fremgangsmaade til fremstilling af et oensket polypeptid |
| WO1990002175A1 (en) * | 1988-08-16 | 1990-03-08 | Novo Nordisk A/S | A method of producing polypeptides by culturing eukaryotic cells in the presence of protease inhibitors |
| GB8827305D0 (en) * | 1988-11-23 | 1988-12-29 | British Bio Technology | Compounds |
| DK105489D0 (da) * | 1989-03-03 | 1989-03-03 | Novo Nordisk As | Polypeptid |
| SE465222C5 (sv) * | 1989-12-15 | 1998-02-10 | Pharmacia & Upjohn Ab | Ett rekombinant, humant faktor VIII-derivat och förfarande för dess framställning |
| CA2076386C (en) * | 1990-02-26 | 2003-04-22 | David S. Hogness | Identification and expression of insect steroid receptor dna sequence |
| US5189178A (en) * | 1990-11-21 | 1993-02-23 | Galardy Richard E | Matrix metalloprotease inhibitors |
| US5304603A (en) * | 1991-06-18 | 1994-04-19 | The Population Council | Leydig cell stimulator |
| US5661034A (en) * | 1991-07-18 | 1997-08-26 | Fuji Yakuhin Kogyo Kabushiki Kaisha | Serum-free medium for tissue culture containing tissue inhibitor of metalloproteinases and method for growing cells using the medium |
| CA2116774C (en) * | 1991-09-19 | 2003-11-11 | Paul J. Carter | Expression in e. coli antibody fragments having at least a cysteine present as a free thiol. use for the production of bifunctional f(ab') 2 antibodies |
| CA2078721A1 (en) * | 1991-09-24 | 1993-03-25 | Hiroshi Yonemura | Process for preparing human coagulation factor viii protein complex |
| US5278289A (en) * | 1991-11-12 | 1994-01-11 | Johnson Alan J | Antihemophilic factor stabilization |
| US5296471A (en) * | 1992-12-22 | 1994-03-22 | Glycomed Incorporated | Method for controlling o-desulfation of heparin and compositions produced thereby |
| WO1995005477A1 (en) * | 1993-08-12 | 1995-02-23 | University Of Maryland | Thermostable alkaline metalloprotease produced by a hyphomonas, and preparation thereof |
| US5631159A (en) * | 1993-09-22 | 1997-05-20 | Creative Biomolecules, Inc. | Lipid-modified serum free media |
| US5543396A (en) * | 1994-04-28 | 1996-08-06 | Georgia Tech Research Corp. | Proline phosphonate derivatives |
-
1997
- 1997-05-07 US US08/852,783 patent/US5851800A/en not_active Expired - Lifetime
- 1997-05-13 DE DE69735510T patent/DE69735510T2/de not_active Expired - Lifetime
- 1997-05-13 PT PT03000391T patent/PT1318198E/pt unknown
- 1997-05-13 JP JP09540800A patent/JP2000509994A/ja active Pending
- 1997-05-13 NZ NZ332751A patent/NZ332751A/en not_active IP Right Cessation
- 1997-05-13 DE DE69736391T patent/DE69736391T2/de not_active Expired - Lifetime
- 1997-05-13 EP EP97923382A patent/EP0934424B1/en not_active Expired - Lifetime
- 1997-05-13 WO PCT/SE1997/000783 patent/WO1997043436A1/en not_active Ceased
- 1997-05-13 ES ES03000391T patent/ES2260524T3/es not_active Expired - Lifetime
- 1997-05-13 CA CA002253287A patent/CA2253287C/en not_active Expired - Fee Related
- 1997-05-13 PT PT97923382T patent/PT934424E/pt unknown
- 1997-05-13 ES ES97923382T patent/ES2270460T3/es not_active Expired - Lifetime
- 1997-05-13 AU AU29197/97A patent/AU716245B2/en not_active Ceased
- 1997-05-13 AT AT03000391T patent/ATE321141T1/de active
- 1997-05-13 AT AT97923382T patent/ATE334223T1/de active
- 1997-05-13 DK DK97923382T patent/DK0934424T3/da active
-
1998
- 1998-11-13 NO NO19985297A patent/NO325358B1/no not_active IP Right Cessation
-
2006
- 2006-11-02 NO NO20065027A patent/NO325633B1/no not_active IP Right Cessation
-
2009
- 2009-01-07 JP JP2009001597A patent/JP4896999B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| DE69736391T2 (de) | 2007-08-16 |
| EP0934424B1 (en) | 2006-07-26 |
| JP2009148271A (ja) | 2009-07-09 |
| NZ332751A (en) | 2000-06-23 |
| NO325633B1 (no) | 2008-06-30 |
| PT1318198E (pt) | 2006-08-31 |
| ATE334223T1 (de) | 2006-08-15 |
| ES2270460T3 (es) | 2007-04-01 |
| US5851800A (en) | 1998-12-22 |
| ES2260524T3 (es) | 2006-11-01 |
| CA2253287A1 (en) | 1997-11-20 |
| NO20065027L (no) | 1999-01-14 |
| NO985297D0 (no) | 1998-11-13 |
| DE69735510D1 (de) | 2006-05-11 |
| CA2253287C (en) | 2008-02-19 |
| DK0934424T3 (da) | 2006-11-20 |
| NO985297L (no) | 1999-01-14 |
| EP0934424A1 (en) | 1999-08-11 |
| ATE321141T1 (de) | 2006-04-15 |
| JP4896999B2 (ja) | 2012-03-14 |
| DE69736391D1 (de) | 2006-09-07 |
| PT934424E (pt) | 2006-12-29 |
| JP2000509994A (ja) | 2000-08-08 |
| AU2919797A (en) | 1997-12-05 |
| AU716245B2 (en) | 2000-02-24 |
| WO1997043436A1 (en) | 1997-11-20 |
| DE69735510T2 (de) | 2006-08-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4896999B2 (ja) | 細胞培養培地への金属依存性プロテアーゼ又はキモトリプシンの阻害物質の添加を含む組換えポリペプチドの製造法 | |
| EP2459702B1 (en) | Cell culture medium for adamts protein expression | |
| FI117831B (fi) | Menetelmiä trombiinin tuottamiseksi | |
| US5831026A (en) | Process for purifying factor VIII | |
| SG186936A1 (en) | METHOD OF PRODUCING RECOMBINANT HIGH MOLECULAR WEIGHT vWF IN CELL CULTURE | |
| IL124123A (en) | Preparation of recombinant factor VIII, recombinant factor VIII produced according to the method and substrate for cell culture for use in the method | |
| NO328022B1 (no) | Faktor XΔ-analog, rekombinant DNA som koder for denne, celler inneholdende slikt DNA samt preparat, anvendelse av preparatet og fremgangsmate for fremstilling av slike preparater inneholdende XΔ-analogene | |
| WO2001010896A2 (en) | Factor x analog with an improved ability to be activated | |
| EP1318198B1 (en) | Process for producing a recombinant polypeptide involving the addition of an inhibitor of chymotrypsins to the cell culture medium | |
| CN100362105C (zh) | 胰羧肽酶原b、其同工型和突变蛋白的制备及应用 | |
| US10947521B2 (en) | Process for producing recombinant trypsin | |
| AU2017261523B2 (en) | Cell culture medium for adamts protein expression | |
| US10301611B2 (en) | Process for refolding recombinant chymotrypsin | |
| Muranova et al. | Anti-adhesive property of the plasmin/plasminogen system: the use of plasmin (ogen) for cell detachment and disaggregation in cell culture technique | |
| CN114686519A (zh) | 一种制备丝氨酸蛋白酶的方法 | |
| EA041947B1 (ru) | Способ получения рекомбинантного высокомолекулярного vwf в культуре клеток | |
| MXPA01009979A (en) | Production of pancreatic procarboxy-peptidase b, isoforms and muteins thereof, and their use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |