BG65930B1 - Получаване на рекомбинантни фактори за съсирване на кръвта в човешки клетъчни линии - Google Patents
Получаване на рекомбинантни фактори за съсирване на кръвта в човешки клетъчни линии Download PDFInfo
- Publication number
- BG65930B1 BG65930B1 BG107152A BG10715202A BG65930B1 BG 65930 B1 BG65930 B1 BG 65930B1 BG 107152 A BG107152 A BG 107152A BG 10715202 A BG10715202 A BG 10715202A BG 65930 B1 BG65930 B1 BG 65930B1
- Authority
- BG
- Bulgaria
- Prior art keywords
- factor viii
- mutein
- factor
- vector
- amino acid
- Prior art date
Links
- 239000003114 blood coagulation factor Substances 0.000 title claims abstract description 41
- 210000005260 human cell Anatomy 0.000 title claims abstract description 24
- 238000004519 manufacturing process Methods 0.000 title abstract description 10
- 108010054218 Factor VIII Proteins 0.000 claims abstract description 95
- 102000001690 Factor VIII Human genes 0.000 claims abstract description 95
- 229960000301 factor viii Drugs 0.000 claims abstract description 92
- 239000013598 vector Substances 0.000 claims abstract description 69
- 210000004027 cell Anatomy 0.000 claims abstract description 53
- 238000000034 method Methods 0.000 claims abstract description 36
- 108091028043 Nucleic acid sequence Proteins 0.000 claims abstract description 30
- 230000003612 virological effect Effects 0.000 claims abstract description 29
- 208000009292 Hemophilia A Diseases 0.000 claims abstract description 16
- 238000011282 treatment Methods 0.000 claims abstract description 16
- 208000031220 Hemophilia Diseases 0.000 claims abstract description 14
- 238000002360 preparation method Methods 0.000 claims abstract description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 239000003814 drug Substances 0.000 claims abstract description 10
- 108090000623 proteins and genes Proteins 0.000 claims description 43
- 102000004169 proteins and genes Human genes 0.000 claims description 27
- 230000035772 mutation Effects 0.000 claims description 24
- 125000000539 amino acid group Chemical group 0.000 claims description 16
- 108010047303 von Willebrand Factor Proteins 0.000 claims description 15
- 102100036537 von Willebrand factor Human genes 0.000 claims description 15
- 229960001134 von willebrand factor Drugs 0.000 claims description 15
- 101710195626 Transcriptional activator protein Proteins 0.000 claims description 14
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 13
- 150000001413 amino acids Chemical class 0.000 claims description 12
- 230000002779 inactivation Effects 0.000 claims description 10
- 241000700605 Viruses Species 0.000 claims description 8
- 238000000746 purification Methods 0.000 claims description 8
- 108020004414 DNA Proteins 0.000 claims description 7
- 238000012546 transfer Methods 0.000 claims description 6
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 5
- 108010074506 Transfer Factor Proteins 0.000 claims description 5
- 210000004185 liver Anatomy 0.000 claims description 5
- 239000000427 antigen Substances 0.000 claims description 4
- 102000036639 antigens Human genes 0.000 claims description 4
- 108091007433 antigens Proteins 0.000 claims description 4
- 210000003292 kidney cell Anatomy 0.000 claims description 4
- 230000007935 neutral effect Effects 0.000 claims description 4
- 230000001105 regulatory effect Effects 0.000 claims description 4
- 238000012258 culturing Methods 0.000 claims description 3
- 238000002955 isolation Methods 0.000 claims description 2
- 210000004165 myocardium Anatomy 0.000 claims description 2
- 210000002460 smooth muscle Anatomy 0.000 claims description 2
- 210000003932 urinary bladder Anatomy 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 210000001035 gastrointestinal tract Anatomy 0.000 claims 1
- 210000003734 kidney Anatomy 0.000 claims 1
- 239000003550 marker Substances 0.000 claims 1
- 210000001672 ovary Anatomy 0.000 claims 1
- 102100022641 Coagulation factor IX Human genes 0.000 abstract description 32
- 108010076282 Factor IX Proteins 0.000 abstract description 31
- 229960004222 factor ix Drugs 0.000 abstract description 29
- 230000006490 viral transcription Effects 0.000 abstract description 4
- 108091006088 activator proteins Proteins 0.000 abstract description 3
- 235000018102 proteins Nutrition 0.000 description 22
- 239000012634 fragment Substances 0.000 description 19
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 14
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 14
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 12
- 210000002381 plasma Anatomy 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 102000004190 Enzymes Human genes 0.000 description 9
- 108090000790 Enzymes Proteins 0.000 description 9
- 229940088598 enzyme Drugs 0.000 description 9
- 238000001890 transfection Methods 0.000 description 9
- 238000002965 ELISA Methods 0.000 description 8
- 229930003448 Vitamin K Natural products 0.000 description 8
- 238000011534 incubation Methods 0.000 description 8
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 8
- 102000004196 processed proteins & peptides Human genes 0.000 description 8
- 235000019168 vitamin K Nutrition 0.000 description 8
- 239000011712 vitamin K Substances 0.000 description 8
- 150000003721 vitamin K derivatives Chemical class 0.000 description 8
- 229940046010 vitamin k Drugs 0.000 description 8
- 102100026735 Coagulation factor VIII Human genes 0.000 description 7
- 230000015271 coagulation Effects 0.000 description 7
- 238000005345 coagulation Methods 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 229920001184 polypeptide Polymers 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol group Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 5
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 238000010367 cloning Methods 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 102000057593 human F8 Human genes 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 229920000136 polysorbate Polymers 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 238000009631 Broth culture Methods 0.000 description 4
- 108020004638 Circular DNA Proteins 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 108700026244 Open Reading Frames Proteins 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 239000001506 calcium phosphate Substances 0.000 description 4
- 229960001714 calcium phosphate Drugs 0.000 description 4
- 229910000389 calcium phosphate Inorganic materials 0.000 description 4
- 235000011010 calcium phosphates Nutrition 0.000 description 4
- 230000029087 digestion Effects 0.000 description 4
- 239000013024 dilution buffer Substances 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 210000004962 mammalian cell Anatomy 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 4
- XMTQQYYKAHVGBJ-UHFFFAOYSA-N 3-(3,4-DICHLOROPHENYL)-1,1-DIMETHYLUREA Chemical compound CN(C)C(=O)NC1=CC=C(Cl)C(Cl)=C1 XMTQQYYKAHVGBJ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 102000003886 Glycoproteins Human genes 0.000 description 3
- 108090000288 Glycoproteins Proteins 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 229960000074 biopharmaceutical Drugs 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000023555 blood coagulation Effects 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 230000035602 clotting Effects 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 239000012678 infectious agent Substances 0.000 description 3
- 230000002458 infectious effect Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000017854 proteolysis Effects 0.000 description 3
- 230000002797 proteolythic effect Effects 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- CFWRDBDJAOHXSH-SECBINFHSA-N 2-azaniumylethyl [(2r)-2,3-diacetyloxypropyl] phosphate Chemical compound CC(=O)OC[C@@H](OC(C)=O)COP(O)(=O)OCCN CFWRDBDJAOHXSH-SECBINFHSA-N 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 102100023804 Coagulation factor VII Human genes 0.000 description 2
- 206010053567 Coagulopathies Diseases 0.000 description 2
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 2
- 108010023321 Factor VII Proteins 0.000 description 2
- 201000003542 Factor VIII deficiency Diseases 0.000 description 2
- 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 2
- GRRNUXAQVGOGFE-UHFFFAOYSA-N Hygromycin-B Natural products OC1C(NC)CC(N)C(O)C1OC1C2OC3(C(C(O)C(O)C(C(N)CO)O3)O)OC2C(O)C(CO)O1 GRRNUXAQVGOGFE-UHFFFAOYSA-N 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 108090000190 Thrombin Proteins 0.000 description 2
- 102000006601 Thymidine Kinase Human genes 0.000 description 2
- 108020004440 Thymidine kinase Proteins 0.000 description 2
- 108010067390 Viral Proteins Proteins 0.000 description 2
- 230000009102 absorption Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000005571 anion exchange chromatography Methods 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 230000001174 ascending effect Effects 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 229940082150 encore Drugs 0.000 description 2
- 229940012413 factor vii Drugs 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 208000009429 hemophilia B Diseases 0.000 description 2
- 208000031169 hemorrhagic disease Diseases 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 229960000027 human factor ix Drugs 0.000 description 2
- 229960000900 human factor viii Drugs 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- GRRNUXAQVGOGFE-NZSRVPFOSA-N hygromycin B Chemical compound O[C@@H]1[C@@H](NC)C[C@@H](N)[C@H](O)[C@H]1O[C@H]1[C@H]2O[C@@]3([C@@H]([C@@H](O)[C@@H](O)[C@@H](C(N)CO)O3)O)O[C@H]2[C@@H](O)[C@@H](CO)O1 GRRNUXAQVGOGFE-NZSRVPFOSA-N 0.000 description 2
- 229940097277 hygromycin b Drugs 0.000 description 2
- 238000010166 immunofluorescence Methods 0.000 description 2
- 230000000415 inactivating effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000012417 linear regression Methods 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 125000001483 monosaccharide substituent group Chemical group 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 229920001542 oligosaccharide Polymers 0.000 description 2
- 150000002482 oligosaccharides Chemical class 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 125000005629 sialic acid group Chemical group 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229960004072 thrombin Drugs 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)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)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 108010024878 Adenovirus E1A Proteins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 241000701822 Bovine papillomavirus Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 238000012286 ELISA Assay Methods 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
- 241000588724 Escherichia coli Species 0.000 description 1
- 101001091269 Escherichia coli Hygromycin-B 4-O-kinase Proteins 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 206010016077 Factor IX deficiency Diseases 0.000 description 1
- 108010048049 Factor IXa Proteins 0.000 description 1
- 108010014172 Factor V Proteins 0.000 description 1
- 108010014173 Factor X Proteins 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
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 101150066002 GFP gene Proteins 0.000 description 1
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins 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
- 230000004988 N-glycosylation Effects 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 229920002556 Polyethylene Glycol 300 Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- WDVSHHCDHLJJJR-UHFFFAOYSA-N Proflavine Chemical compound C1=CC(N)=CC2=NC3=CC(N)=CC=C3C=C21 WDVSHHCDHLJJJR-UHFFFAOYSA-N 0.000 description 1
- 101800004937 Protein C Proteins 0.000 description 1
- 102000017975 Protein C Human genes 0.000 description 1
- 108010019653 Pwo polymerase Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 101800001700 Saposin-D Proteins 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 101001091268 Streptomyces hygroscopicus Hygromycin-B 7''-O-kinase Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- 102000002262 Thromboplastin Human genes 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 208000027642 X-Linked Genetic disease Diseases 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000012223 aqueous fraction Substances 0.000 description 1
- OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 229960000182 blood factors Drugs 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 230000021523 carboxylation Effects 0.000 description 1
- 238000006473 carboxylation reaction Methods 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000000701 coagulant Substances 0.000 description 1
- 238000007820 coagulation assay Methods 0.000 description 1
- 229940105778 coagulation factor viii Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000014155 detection of activity Effects 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003337 fertilizer Substances 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000006662 intracellular pathway Effects 0.000 description 1
- 229940047434 kogenate Drugs 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000012528 membrane Substances 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
- 239000000203 mixture Substances 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 150000007523 nucleic acids Chemical group 0.000 description 1
- UZGLIIJVICEWHF-UHFFFAOYSA-N octogen Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)CN([N+]([O-])=O)C1 UZGLIIJVICEWHF-UHFFFAOYSA-N 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000151 polyglycol Polymers 0.000 description 1
- 239000010695 polyglycol Substances 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000003805 procoagulant Substances 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 229960000856 protein c Drugs 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 230000009145 protein modification Effects 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 229940047431 recombinate Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 102220033174 rs62642581 Human genes 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000018448 secretion by cell Effects 0.000 description 1
- 238000010187 selection method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000007669 thermal treatment Methods 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
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
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
-
- 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
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6437—Coagulation factor VIIa (3.4.21.21)
-
- 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
- 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
-
- 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)
-
- 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
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/644—Coagulation factor IXa (3.4.21.22)
-
- 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
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/647—Blood coagulation factors not provided for in a preceding group or according to more than one of the proceeding groups
-
- 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)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21021—Coagulation factor VIIa (3.4.21.21)
-
- 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)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21022—Coagulation factor IXa (3.4.21.22)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Hematology (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Diabetes (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00106225A EP1136553A1 (en) | 2000-03-22 | 2000-03-22 | Production of recombinant blood clotting factors in human cell lines |
| US20324900P | 2000-05-08 | 2000-05-08 | |
| PCT/EP2001/003220 WO2001070968A2 (en) | 2000-03-22 | 2001-03-21 | Production of recombinant blood clotting factors in human cell lines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| BG107152A BG107152A (bg) | 2003-06-30 |
| BG65930B1 true BG65930B1 (bg) | 2010-05-31 |
Family
ID=26070708
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BG107152A BG65930B1 (bg) | 2000-03-22 | 2002-09-26 | Получаване на рекомбинантни фактори за съсирване на кръвта в човешки клетъчни линии |
Country Status (28)
| Country | Link |
|---|---|
| US (1) | US7572619B2 (https=) |
| EP (2) | EP1266006B1 (https=) |
| JP (1) | JP3894795B2 (https=) |
| KR (1) | KR100581574B1 (https=) |
| CN (1) | CN1454257B (https=) |
| AT (1) | ATE312176T1 (https=) |
| AU (3) | AU2001254715B2 (https=) |
| BE (1) | BE2014C077I2 (https=) |
| BG (1) | BG65930B1 (https=) |
| BR (1) | BRPI0109494B8 (https=) |
| CA (1) | CA2404163C (https=) |
| CZ (1) | CZ303929B6 (https=) |
| DE (1) | DE60115613T2 (https=) |
| DK (1) | DK1266006T3 (https=) |
| EA (1) | EA004317B1 (https=) |
| EE (1) | EE200200538A (https=) |
| ES (1) | ES2254403T3 (https=) |
| FR (1) | FR15C0003I2 (https=) |
| HR (1) | HRP20020767B1 (https=) |
| HU (1) | HU228091B1 (https=) |
| IL (2) | IL151857A0 (https=) |
| MX (1) | MXPA02009221A (https=) |
| NO (1) | NO330910B1 (https=) |
| NZ (1) | NZ521732A (https=) |
| RS (1) | RS50743B (https=) |
| SI (1) | SI1266006T1 (https=) |
| SK (1) | SK287706B6 (https=) |
| WO (1) | WO2001070968A2 (https=) |
Families Citing this family (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EE200200538A (et) * | 2000-03-22 | 2004-04-15 | Octagene Gmbh | Rekombinantsete verehüübimisfaktorite produtseerimine inimese rakuliinides |
| PL206105B1 (pl) * | 2000-09-19 | 2010-07-30 | Emory Universityemory University | Zmodyfikowany ludzki czynnik VIII oraz sposób modyfikacji ludzkiego czynnika VIII ze zmniejszeniem reaktywności na przeciwciało hamujące i zachowaniem aktywności prokoagulacyjnej |
| EP1469064A1 (en) | 2003-04-15 | 2004-10-20 | DRK-Blutspendedienst Baden-Württemberg-Hessen gGmbH | Expression of proteins in endothelial cells derived from precursor cells from cord blood |
| EP1755652B1 (en) * | 2004-03-19 | 2010-11-24 | Baxter International Inc. | Factor ixa for the treatment of bleeding disorders |
| KR100624013B1 (ko) * | 2004-06-25 | 2006-09-19 | 주식회사 녹십자홀딩스 | 동결건조된 알부민 비함유 재조합 사람 혈액응고 제 8인자 제제 |
| WO2006036502A2 (en) | 2004-09-22 | 2006-04-06 | St. Jude Children's Research Hospital | Improved expression of factor ix in gene therapy vectors |
| US20060094104A1 (en) | 2004-10-29 | 2006-05-04 | Leopold Grillberger | Animal protein-free media for cultivation of cells |
| EP1851305B1 (en) * | 2005-02-11 | 2012-01-18 | Novo Nordisk Health Care AG | Production of a polypeptide in a serum-free cell culture liquid containing plant protein hydrolysate |
| EP1707634A1 (en) | 2005-03-29 | 2006-10-04 | Octapharma AG | Method for isolation of recombinantly produced proteins |
| EP1739179A1 (en) | 2005-06-30 | 2007-01-03 | Octapharma AG | Serum-free stable transfection and production of recombinant human proteins in human cell lines |
| EP3255141B1 (en) | 2006-07-13 | 2021-12-01 | Wyeth LLC | Production of antibodies with improved glycosylation pattern |
| JP6050927B2 (ja) * | 2007-04-26 | 2016-12-21 | シーエヌジェイ ホールディングス，インコーポレイテッド | 高シアル酸含量を有する組換えビタミンｋ依存性タンパク質およびその調製方法 |
| WO2009028575A1 (ja) * | 2007-08-27 | 2009-03-05 | National University Corporation Nagoya University | 血液凝固第vii因子プロモーターの活性化剤及びその利用 |
| MX2011001624A (es) | 2008-08-21 | 2011-03-28 | Octapharma Ag | Factor viii y ix humano producido en forma recombinante. |
| KR101722961B1 (ko) | 2009-02-11 | 2017-04-04 | 알부메딕스 에이/에스 | 알부민 변이체 및 접합체 |
| PT2482841T (pt) | 2009-10-02 | 2019-03-01 | Childrens Hospital Philadelphia | A presente invenção refere-se à utilização de lactonas macrocíclicas para o tratamento da demodicose, em particular em cães. |
| EP2493921B1 (en) | 2009-10-30 | 2018-09-26 | Albumedix Ltd | Albumin variants |
| EP2556087A1 (en) | 2010-04-09 | 2013-02-13 | Novozymes Biopharma DK A/S | Albumin derivatives and variants |
| BRPI1105317A2 (pt) * | 2011-01-24 | 2013-04-30 | Fundacco Hemoct De Ribeirco Preto | produÇço estÁvel e em larga escala de fviii humano em linhagem celular humana sk-hep-1 |
| MX352889B (es) | 2011-02-25 | 2017-12-13 | Chugai Pharmaceutical Co Ltd | Anticuerpo de fc especifico para fcyriib. |
| CN102199607B (zh) * | 2011-03-30 | 2012-11-14 | 山西大学 | 重组人凝血因子ix小基因及其ptc突变体稳定细胞株 |
| ES2970057T3 (es) | 2011-05-13 | 2024-05-24 | Octapharma Ag | Un procedimiento para aumentar la productividad de células eucarióticas en la producción de FVIII recombinante |
| TW201307563A (zh) * | 2011-05-19 | 2013-02-16 | Shire Human Genetic Therapies | 純化乙醯肝素－ｎ－硫酸酯酶之方法 |
| TWI687439B (zh) | 2011-06-30 | 2020-03-11 | 中外製藥股份有限公司 | 異源二聚化多胜肽 |
| CN102321668A (zh) * | 2011-07-06 | 2012-01-18 | 中国人民解放军军事医学科学院野战输血研究所 | 一种表达重组人凝血因子ⅶ的方法及其专用载体 |
| JP6322411B2 (ja) | 2011-09-30 | 2018-05-09 | 中外製薬株式会社 | 複数の生理活性を有する抗原の消失を促進する抗原結合分子 |
| KR20140084208A (ko) | 2011-10-18 | 2014-07-04 | 시에스엘 리미티드 | 정제된 인자 ｖｉｉｉ의 재구성 후의 안정성을 향상시키는 방법 |
| EP2780364A2 (en) | 2011-11-18 | 2014-09-24 | Eleven Biotherapeutics, Inc. | Proteins with improved half-life and other properties |
| KR20230143201A (ko) | 2011-11-30 | 2023-10-11 | 추가이 세이야쿠 가부시키가이샤 | 면역 복합체를 형성하는 세포내로의 운반체（캐리어）를 포함하는 의약 |
| DK2825556T3 (en) | 2012-03-16 | 2018-04-16 | Albumedix As | albumin Variants |
| CA2862516C (en) | 2012-03-27 | 2023-02-14 | Ngm Biopharmaceuticals, Inc. | Compositions and methods of use for treating metabolic disorders |
| GB201210357D0 (en) | 2012-06-12 | 2012-07-25 | Ucl Business Plc | Factor VIII sequences |
| US8986991B2 (en) * | 2012-07-03 | 2015-03-24 | Expression Therapeutics, Llc | High yield suspension cell line, system and method for making same |
| US10023628B2 (en) | 2012-07-06 | 2018-07-17 | Bioverativ Therapeutics Inc. | Cell line expressing single chain factor VIII polypeptides and uses thereof |
| MX2015005363A (es) | 2012-11-08 | 2015-11-06 | Novozymes Biopharma Dk As | Variantes de albumina. |
| CA2898975C (en) * | 2013-01-24 | 2021-06-15 | Portola Pharmaceuticals, Inc. | Inhibition of tissue factor pathway inhibitor with factor xa derivatives |
| CN105246914B (zh) | 2013-04-02 | 2021-08-27 | 中外制药株式会社 | Fc区变体 |
| EP2853538A1 (en) | 2013-09-27 | 2015-04-01 | Université Pierre et Marie Curie (Paris 6) | Analogues of temporin-SHa and uses thereof |
| AU2015296640B2 (en) * | 2014-07-30 | 2020-05-21 | Ngm Biopharmaceuticals, Inc. | Compositions and methods of use for treating metabolic disorders |
| EP3701969A1 (en) | 2014-10-31 | 2020-09-02 | NGM Biopharmaceuticals, Inc. | Compositions and methods of use for treating metabolic disorders |
| GB201420139D0 (en) | 2014-11-12 | 2014-12-24 | Ucl Business Plc | Factor IX gene therapy |
| KR101860280B1 (ko) | 2014-12-19 | 2018-05-21 | 추가이 세이야쿠 가부시키가이샤 | 항-마이오스타틴 항체, 변이체 Fc 영역을 함유하는 폴리펩타이드, 및 사용 방법 |
| KR102605798B1 (ko) | 2015-02-05 | 2023-11-23 | 추가이 세이야쿠 가부시키가이샤 | 이온 농도 의존적 항원 결합 도메인을 포함하는 항체, Fc 영역 개변체, IL-8에 결합하는 항체, 및 그들의 사용 |
| BR102015012334A2 (pt) | 2015-05-27 | 2016-11-29 | Fundação Hemoct De Ribeirão Preto Fundherp | processo de produção do fator vii de coagulação sanguínea e fator vii de coagulação sanguínea |
| WO2016198499A1 (en) | 2015-06-09 | 2016-12-15 | Glycotope Gmbh | IMPROVED METHOD FOR PRODUCTION OF γ-CARBOXYLATED POLYPEPTIDES |
| JP7007261B2 (ja) | 2015-08-20 | 2022-01-24 | アルブミディクス リミティド | アルブミン変異体及びコンジュゲート |
| CN105219739A (zh) * | 2015-09-21 | 2016-01-06 | 北京神源德生物科技有限公司 | 重组单纯疱疹病毒及它感染和制备它的宿主细胞以及它们的应用 |
| WO2017110981A1 (en) | 2015-12-25 | 2017-06-29 | Chugai Seiyaku Kabushiki Kaisha | Anti-myostatin antibodies and methods of use |
| MX2018012537A (es) | 2016-04-15 | 2019-02-25 | Univ Pennsylvania | Terapia de genes para tratar hemofilia a. |
| EP3494991A4 (en) | 2016-08-05 | 2020-07-29 | Chugai Seiyaku Kabushiki Kaisha | COMPOSITION FOR THE PROPHYLAXIS OR TREATMENT OF IL-8 RELATED DISEASES |
| WO2018210771A1 (en) | 2017-05-17 | 2018-11-22 | Octapharma Ag | Method for the production of a recombinant target protein |
| EP4640703A3 (en) | 2017-11-14 | 2026-04-08 | Chugai Seiyaku Kabushiki Kaisha | Anti-c1s antibodies and methods of use |
| WO2020020364A1 (zh) * | 2018-07-26 | 2020-01-30 | 正大天晴药业集团南京顺欣制药有限公司 | 一种制备重组人凝血因子ⅷ的方法 |
| KR102259473B1 (ko) | 2018-08-10 | 2021-06-02 | 추가이 세이야쿠 가부시키가이샤 | 항cd137 항원 결합 분자 및 그의 사용 |
| US10842885B2 (en) | 2018-08-20 | 2020-11-24 | Ucl Business Ltd | Factor IX encoding nucleotides |
| GB201813528D0 (en) | 2018-08-20 | 2018-10-03 | Ucl Business Plc | Factor IX encoding nucleotides |
| JP7672334B2 (ja) | 2018-10-23 | 2025-05-07 | ザ・チルドレンズ・ホスピタル・オブ・フィラデルフィア | 第ｖｉｉｉ因子機能を調節するための組成物および方法 |
| EP4696320A2 (en) | 2019-05-15 | 2026-02-18 | Chugai Seiyaku Kabushiki Kaisha | Anti-c1s antibody |
| JP2024521385A (ja) | 2021-06-11 | 2024-05-31 | ソルボンヌ・ユニヴェルシテ | 短鎖抗菌ペプチド |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0160457A1 (en) * | 1984-04-20 | 1985-11-06 | Genentech, Inc. | Human factor VIII, Compositions containing it, methods and materials for use in it production |
| WO1986001961A1 (fr) * | 1984-09-14 | 1986-03-27 | Sony Corporation | Dispositif de commande du courant de faisceau d'une camera de television |
| US4770999A (en) * | 1985-04-22 | 1988-09-13 | Genetics Institute, Inc. | High yield production of active Factor IX |
| US5521070A (en) * | 1988-11-09 | 1996-05-28 | Transgene S.A. | DNA sequence coding for human factor IX or a similar protein, expression vector, transformed cells, method for preparing factor IX and corresponding products obtained |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3785102T2 (de) * | 1986-01-03 | 1993-07-22 | Genetics Inst | Verfahren zur herstellung von faktor-viii:c-typ-proteinen. |
| US5422260A (en) | 1986-05-29 | 1995-06-06 | Genetics Institute, Inc. -Legal Affairs | Human factor VIII:c muteins |
| US5451521A (en) * | 1986-05-29 | 1995-09-19 | Genetics Institute, Inc. | Procoagulant proteins |
| US5024939A (en) * | 1987-07-09 | 1991-06-18 | Genentech, Inc. | Transient expression system for producing recombinant protein |
| KR960701899A (ko) * | 1989-11-17 | 1996-03-28 | 안네 제케르 | 인자 viii:c활성을 갖는 단백질 복합체 및 그의 제조 |
| SE465222C5 (sv) * | 1989-12-15 | 1998-02-10 | Pharmacia & Upjohn Ab | Ett rekombinant, humant faktor VIII-derivat och förfarande för dess framställning |
| DE69101634T4 (de) * | 1990-01-26 | 1994-12-01 | Immuno Ag | Rekombinant hergestellte blutfaktoren, verfahren zur exprimierung besagter blutfaktoren sowie in besagtem prozess verwendeter rekombinanter vaccina-virus. |
| US5445953A (en) * | 1991-08-26 | 1995-08-29 | Immuno Aktiengesellschaft | Direct molecular cloning of a modified poxvirus genome |
| EP0710288B1 (en) * | 1993-06-10 | 2006-04-05 | Genetic Therapy, Inc. | Adenoviral vectors for treatment of hemophilia |
| EP0951544A2 (en) * | 1996-07-03 | 1999-10-27 | Chiron Corporation | Methods for administration of recombinant gene delivery vehicles for treatment of human disease |
| US6114148C1 (en) * | 1996-09-20 | 2012-05-01 | Gen Hospital Corp | High level expression of proteins |
| EP1036177A1 (en) * | 1997-12-05 | 2000-09-20 | The Immune Response Corporation | Novel vectors and genes exhibiting increased expression |
| US6358703B1 (en) * | 1998-12-10 | 2002-03-19 | Bayer Corporation | Expression system for factor VIII |
| JP2002537311A (ja) * | 1999-02-19 | 2002-11-05 | オクタジーン・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | ホルモン−ホルモン受容体の複合体および核酸構築物、並びに遺伝子治療におけるそれらの使用 |
| AU6770200A (en) * | 1999-08-13 | 2001-03-13 | Fred Hutchinson Cancer Research Center | Crystal of a truncated protein construct containing a coagulation factor viii c2domain in the presence or absence of a bound ligand and methods of use thereof |
| EE200200538A (et) * | 2000-03-22 | 2004-04-15 | Octagene Gmbh | Rekombinantsete verehüübimisfaktorite produtseerimine inimese rakuliinides |
| WO2003009237A1 (en) * | 2001-07-18 | 2003-01-30 | Skaginn Hf. | A method and apparatus for relating information of a processed object to an operator |
-
2001
- 2001-03-21 EE EEP200200538A patent/EE200200538A/xx unknown
- 2001-03-21 AU AU2001254715A patent/AU2001254715B2/en not_active Expired
- 2001-03-21 DE DE60115613T patent/DE60115613T2/de not_active Expired - Lifetime
- 2001-03-21 AU AU5471501A patent/AU5471501A/xx active Pending
- 2001-03-21 SI SI200130501T patent/SI1266006T1/sl unknown
- 2001-03-21 WO PCT/EP2001/003220 patent/WO2001070968A2/en not_active Ceased
- 2001-03-21 KR KR1020027012443A patent/KR100581574B1/ko not_active Expired - Lifetime
- 2001-03-21 ES ES01927769T patent/ES2254403T3/es not_active Expired - Lifetime
- 2001-03-21 JP JP2001569351A patent/JP3894795B2/ja not_active Expired - Lifetime
- 2001-03-21 HU HU0300588A patent/HU228091B1/hu unknown
- 2001-03-21 EA EA200201008A patent/EA004317B1/ru active Protection Beyond IP Right Term
- 2001-03-21 DK DK01927769T patent/DK1266006T3/da active
- 2001-03-21 CZ CZ20023166A patent/CZ303929B6/cs not_active IP Right Cessation
- 2001-03-21 AT AT01927769T patent/ATE312176T1/de active
- 2001-03-21 CA CA002404163A patent/CA2404163C/en not_active Expired - Lifetime
- 2001-03-21 HR HR20020767A patent/HRP20020767B1/xx not_active IP Right Cessation
- 2001-03-21 EP EP01927769A patent/EP1266006B1/en not_active Expired - Lifetime
- 2001-03-21 EP EP04009279A patent/EP1460131A3/en not_active Withdrawn
- 2001-03-21 IL IL15185701A patent/IL151857A0/xx unknown
- 2001-03-21 MX MXPA02009221A patent/MXPA02009221A/es active IP Right Grant
- 2001-03-21 BR BRPI0109494A patent/BRPI0109494B8/pt not_active IP Right Cessation
- 2001-03-21 US US10/239,498 patent/US7572619B2/en not_active Expired - Lifetime
- 2001-03-21 RS YUP-710/02A patent/RS50743B/sr unknown
- 2001-03-21 SK SK1504-2002A patent/SK287706B6/sk not_active IP Right Cessation
- 2001-03-21 CN CN018097456A patent/CN1454257B/zh not_active Expired - Lifetime
- 2001-03-21 NZ NZ521732A patent/NZ521732A/en not_active IP Right Cessation
-
2002
- 2002-09-19 IL IL151857A patent/IL151857A/en active IP Right Grant
- 2002-09-19 NO NO20024475A patent/NO330910B1/no not_active IP Right Cessation
- 2002-09-26 BG BG107152A patent/BG65930B1/bg unknown
-
2006
- 2006-05-02 AU AU2006201848A patent/AU2006201848A1/en not_active Abandoned
-
2014
- 2014-12-29 BE BE2014C077C patent/BE2014C077I2/fr unknown
-
2015
- 2015-01-20 FR FR15C0003C patent/FR15C0003I2/fr active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0160457A1 (en) * | 1984-04-20 | 1985-11-06 | Genentech, Inc. | Human factor VIII, Compositions containing it, methods and materials for use in it production |
| WO1986001961A1 (fr) * | 1984-09-14 | 1986-03-27 | Sony Corporation | Dispositif de commande du courant de faisceau d'une camera de television |
| US4770999A (en) * | 1985-04-22 | 1988-09-13 | Genetics Institute, Inc. | High yield production of active Factor IX |
| US5521070A (en) * | 1988-11-09 | 1996-05-28 | Transgene S.A. | DNA sequence coding for human factor IX or a similar protein, expression vector, transformed cells, method for preparing factor IX and corresponding products obtained |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| BG65930B1 (bg) | Получаване на рекомбинантни фактори за съсирване на кръвта в човешки клетъчни линии | |
| AU2001254715A1 (en) | Production of recombinant blood clotting factors in human cell lines | |
| JP4361786B2 (ja) | 操作されたジスルフィド結合を有する安定化蛋白質 | |
| EP0506757B1 (en) | A recombinant human factor viii derivative | |
| US7122634B2 (en) | Modified factor VIII | |
| JP2022118129A (ja) | 第ｖｉｉｉ因子キメラタンパク質及びその使用 | |
| US20150352190A1 (en) | Modified Factor VIII | |
| KR20110114587A (ko) | 세린 프로테아제 유도체 및 혈액응고 장애의 치료 또는 예방의 용도 | |
| KR20010082521A (ko) | 변형된 인자 ⅷ | |
| JP2005511038A (ja) | 第ｖｉｉｉ因子ｃ２ドメインのバリアント | |
| Kaufman | Insight into the structure, function, and biosynthesis of factor VIII through recombinant DNA technology | |
| CZ140298A3 (cs) | Hybridní faktor VIII s modifikovanou aktivitou | |
| UA76102C2 (en) | Factor viii mutein and a method for obtaining thereof in human cells lines | |
| HK1009290B (en) | A recombinant human factor viii derivative |