NO319266B1 - Fremgangsmate ved fremstilling og utvinning av proteiner fra pro-proteiner i ett fremgangsmatetrinn samt anvendelse av fremgangsmaten til fremstilling av proteiner. - Google Patents
Fremgangsmate ved fremstilling og utvinning av proteiner fra pro-proteiner i ett fremgangsmatetrinn samt anvendelse av fremgangsmaten til fremstilling av proteiner. Download PDFInfo
- Publication number
- NO319266B1 NO319266B1 NO19964965A NO964965A NO319266B1 NO 319266 B1 NO319266 B1 NO 319266B1 NO 19964965 A NO19964965 A NO 19964965A NO 964965 A NO964965 A NO 964965A NO 319266 B1 NO319266 B1 NO 319266B1
- Authority
- NO
- Norway
- Prior art keywords
- protein
- pro
- factor
- stated
- protease
- Prior art date
Links
- 102000004169 proteins and genes Human genes 0.000 title claims abstract description 177
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 177
- 238000000034 method Methods 0.000 title claims abstract description 86
- 230000008569 process Effects 0.000 title claims abstract description 9
- 239000004365 Protease Substances 0.000 claims abstract description 64
- 108091005804 Peptidases Proteins 0.000 claims abstract description 63
- 239000007787 solid Substances 0.000 claims abstract description 24
- 238000004519 manufacturing process Methods 0.000 claims abstract description 21
- 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 claims abstract description 12
- 102000007625 Hirudins Human genes 0.000 claims abstract description 11
- 108010007267 Hirudins Proteins 0.000 claims abstract description 11
- 229940006607 hirudin Drugs 0.000 claims abstract description 11
- 238000001179 sorption measurement Methods 0.000 claims abstract description 7
- 239000007857 degradation product Substances 0.000 claims abstract description 6
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims abstract 11
- 108090000190 Thrombin Proteins 0.000 claims description 61
- 229960004072 thrombin Drugs 0.000 claims description 61
- 102000035195 Peptidases Human genes 0.000 claims description 52
- 108090000631 Trypsin Proteins 0.000 claims description 37
- 102000004142 Trypsin Human genes 0.000 claims description 37
- 239000012588 trypsin Substances 0.000 claims description 37
- 108010094028 Prothrombin Proteins 0.000 claims description 30
- 108010074860 Factor Xa Proteins 0.000 claims description 29
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 13
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 13
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 claims description 12
- 102000004190 Enzymes Human genes 0.000 claims description 10
- 108090000790 Enzymes Proteins 0.000 claims description 10
- 229940088598 enzyme Drugs 0.000 claims description 10
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 9
- 102100022641 Coagulation factor IX Human genes 0.000 claims description 7
- 108010062466 Enzyme Precursors Proteins 0.000 claims description 7
- 102000010911 Enzyme Precursors Human genes 0.000 claims description 7
- 108010076282 Factor IX Proteins 0.000 claims description 7
- 108010014173 Factor X Proteins 0.000 claims description 7
- 229960004222 factor ix Drugs 0.000 claims description 7
- 229940012426 factor x Drugs 0.000 claims description 7
- 101800004937 Protein C Proteins 0.000 claims description 6
- 102000017975 Protein C Human genes 0.000 claims description 6
- 101800001700 Saposin-D Proteins 0.000 claims description 6
- 229960000856 protein c Drugs 0.000 claims description 6
- 108010048049 Factor IXa Proteins 0.000 claims description 5
- 238000000605 extraction Methods 0.000 claims description 5
- 108010047303 von Willebrand Factor Proteins 0.000 claims description 5
- 102100036537 von Willebrand factor Human genes 0.000 claims description 5
- 229960001134 von willebrand factor Drugs 0.000 claims description 5
- 108010074105 Factor Va Proteins 0.000 claims description 4
- 238000003776 cleavage reaction Methods 0.000 claims description 4
- 230000007017 scission Effects 0.000 claims description 4
- 108090000317 Chymotrypsin Proteins 0.000 claims description 3
- 108010014172 Factor V Proteins 0.000 claims description 3
- 108010071289 Factor XIII Proteins 0.000 claims description 3
- 108010058683 Immobilized Proteins Proteins 0.000 claims description 3
- 102000012479 Serine Proteases Human genes 0.000 claims description 3
- 108010022999 Serine Proteases Proteins 0.000 claims description 3
- 229960002376 chymotrypsin Drugs 0.000 claims description 3
- 229940012444 factor xiii Drugs 0.000 claims description 3
- 239000002243 precursor Substances 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- 102100023804 Coagulation factor VII Human genes 0.000 claims description 2
- 108010023321 Factor VII Proteins 0.000 claims description 2
- 108010054218 Factor VIII Proteins 0.000 claims description 2
- 102000001690 Factor VIII Human genes 0.000 claims description 2
- 108010061932 Factor VIIIa Proteins 0.000 claims description 2
- 108010054265 Factor VIIa Proteins 0.000 claims description 2
- 108010088842 Fibrinolysin Proteins 0.000 claims 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 claims description 2
- 108090000787 Subtilisin Proteins 0.000 claims description 2
- 101710181748 Venom protease Proteins 0.000 claims description 2
- 238000004113 cell culture Methods 0.000 claims description 2
- 229940012413 factor vii Drugs 0.000 claims description 2
- 229960000301 factor viii Drugs 0.000 claims description 2
- 229960002897 heparin Drugs 0.000 claims description 2
- 229920000669 heparin Polymers 0.000 claims description 2
- 229940012957 plasmin Drugs 0.000 claims description 2
- 229920001184 polypeptide Polymers 0.000 claims description 2
- 108010039209 Blood Coagulation Factors Proteins 0.000 claims 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 claims 1
- 108010000196 Factor XIIIa Proteins 0.000 claims 1
- 238000010352 biotechnological method Methods 0.000 claims 1
- 239000003114 blood coagulation factor Substances 0.000 claims 1
- 229940019700 blood coagulation factors Drugs 0.000 claims 1
- 230000015271 coagulation Effects 0.000 claims 1
- 238000005345 coagulation Methods 0.000 claims 1
- 239000012460 protein solution Substances 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 69
- 230000004913 activation Effects 0.000 description 45
- 235000019419 proteases Nutrition 0.000 description 45
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 44
- 229920002684 Sepharose Polymers 0.000 description 30
- 239000007979 citrate buffer Substances 0.000 description 27
- 239000000243 solution Substances 0.000 description 23
- 239000000872 buffer Substances 0.000 description 22
- 239000011780 sodium chloride Substances 0.000 description 22
- 102100027378 Prothrombin Human genes 0.000 description 20
- 239000007983 Tris buffer Substances 0.000 description 20
- 229940039716 prothrombin Drugs 0.000 description 20
- 238000011084 recovery Methods 0.000 description 20
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 20
- 239000011521 glass Substances 0.000 description 19
- 238000001042 affinity chromatography Methods 0.000 description 18
- 239000007788 liquid Substances 0.000 description 17
- 238000001962 electrophoresis Methods 0.000 description 16
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 15
- 239000011543 agarose gel Substances 0.000 description 12
- 239000003550 marker Substances 0.000 description 11
- 238000010828 elution Methods 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 239000007858 starting material Substances 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000000499 gel Substances 0.000 description 8
- 230000015556 catabolic process Effects 0.000 description 7
- 239000000758 substrate Substances 0.000 description 6
- 239000000969 carrier Substances 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 230000009471 action Effects 0.000 description 4
- 230000029087 digestion Effects 0.000 description 4
- 108010088751 Albumins Proteins 0.000 description 3
- 102000009027 Albumins Human genes 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000003599 detergent Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000017854 proteolysis Effects 0.000 description 3
- 231100000611 venom Toxicity 0.000 description 3
- 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 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 108060005987 Kallikrein Proteins 0.000 description 2
- 102000001399 Kallikrein Human genes 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 230000008033 biological extinction Effects 0.000 description 2
- 230000023555 blood coagulation Effects 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 230000003196 chaotropic effect Effects 0.000 description 2
- 239000003593 chromogenic compound Substances 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 108010007093 dispase Proteins 0.000 description 2
- 230000007071 enzymatic hydrolysis Effects 0.000 description 2
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 230000006337 proteolytic cleavage Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 239000002435 venom Substances 0.000 description 2
- 210000001048 venom Anatomy 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 1
- 229920000936 Agarose Polymers 0.000 description 1
- 241000238421 Arthropoda Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 238000009010 Bradford assay Methods 0.000 description 1
- 108010065152 Coagulase Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000122860 Echis carinatus Species 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- 108010079356 FIIa Proteins 0.000 description 1
- 108010029144 Factor IIa Proteins 0.000 description 1
- 108010051815 Glutamyl endopeptidase Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 101000651439 Homo sapiens Prothrombin Proteins 0.000 description 1
- 101500025568 Homo sapiens Saposin-D Proteins 0.000 description 1
- 102100027612 Kallikrein-11 Human genes 0.000 description 1
- 101001018085 Lysobacter enzymogenes Lysyl endopeptidase Proteins 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 241000272112 Oxyuranus scutellatus Species 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108010030544 Peptidyl-Lys metalloendopeptidase Proteins 0.000 description 1
- 108010059712 Pronase Proteins 0.000 description 1
- 101710111620 Protein C activator Proteins 0.000 description 1
- 241000270295 Serpentes Species 0.000 description 1
- 101000759013 Streptomyces griseus Trypsin Proteins 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 101710152431 Trypsin-like protease Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229940057326 agkistrodon contortrix venom Drugs 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000004019 antithrombin Substances 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 230000006790 cellular biosynthetic process Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 108010003914 endoproteinase Asp-N Proteins 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229940100689 human protein c Drugs 0.000 description 1
- 229940039715 human prothrombin Drugs 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 108010014806 prothrombinase complex Proteins 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 108010059339 submandibular proteinase A Proteins 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000003396 thiol group Chemical class [H]S* 0.000 description 1
- 239000002821 viper venom Substances 0.000 description 1
- 244000000009 viral human pathogen Species 0.000 description 1
- 108010088109 von Willebrand factor propolypeptide Proteins 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
- 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)
- C12N9/6429—Thrombin (3.4.21.5)
-
- 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
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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)
-
- 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
-
- 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)
- C12N9/6432—Coagulation factor Xa (3.4.21.6)
-
- 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
- C12P21/06—Preparation of peptides or proteins produced by the hydrolysis of a peptide bond, e.g. hydrolysate products
-
- 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)
- C12Y304/21005—Thrombin (3.4.21.5)
-
- 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)
- C12Y304/21006—Coagulation factor Xa (3.4.21.6)
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AT0192795A AT404597B (de) | 1995-11-24 | 1995-11-24 | Verfahren zur herstellung von proteinen |
Publications (3)
Publication Number | Publication Date |
---|---|
NO964965D0 NO964965D0 (no) | 1996-11-22 |
NO964965L NO964965L (no) | 1997-05-26 |
NO319266B1 true NO319266B1 (no) | 2005-07-11 |
Family
ID=3524033
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19964965A NO319266B1 (no) | 1995-11-24 | 1996-11-22 | Fremgangsmate ved fremstilling og utvinning av proteiner fra pro-proteiner i ett fremgangsmatetrinn samt anvendelse av fremgangsmaten til fremstilling av proteiner. |
Country Status (7)
Country | Link |
---|---|
US (1) | US6010844A (ja) |
EP (1) | EP0776969B1 (ja) |
JP (1) | JP4180671B2 (ja) |
AT (2) | AT404597B (ja) |
CA (1) | CA2190802C (ja) |
DE (1) | DE59611093D1 (ja) |
NO (1) | NO319266B1 (ja) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATA159597A (de) * | 1997-09-19 | 2000-09-15 | Immuno Ag | Präparat zur behandlung von blutgerinnungsstörungen |
US7560622B2 (en) * | 2000-10-06 | 2009-07-14 | Pioneer Hi-Bred International, Inc. | Methods and compositions relating to the generation of partially transgenic organisms |
US6830917B2 (en) | 2001-12-10 | 2004-12-14 | Baxter Healthcare S.A. | Method of isolation and purification of trypsin from pronase protease and use thereof |
US7235655B2 (en) * | 2002-03-22 | 2007-06-26 | Pharmacia & Upjohn Company | Processes to prepare eplerenone |
CA2558811A1 (en) | 2004-03-08 | 2005-09-22 | Zymogenetics, Inc. | Dimeric fusion proteins and materials and methods for producing them |
JP2012050386A (ja) * | 2010-09-01 | 2012-03-15 | Kaneka Corp | 2種類以上の多孔質充填剤を充填するカラム |
JP2012050387A (ja) * | 2010-09-01 | 2012-03-15 | Kaneka Corp | 2種類以上の分子を多孔質担体に固定化する方法 |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2000887A1 (en) * | 1988-11-01 | 1990-05-01 | Cecilia S.L. Ku | Thromboresistant materials and methods for making same |
US5053453A (en) * | 1988-11-01 | 1991-10-01 | Baxter International Inc. | Thromboresistant materials and methods for making same |
DE3843126C3 (de) * | 1988-12-22 | 1994-10-06 | Octapharma Ag | Verfahren zur Herstellung eines hochreinen Thrombinkonzentrates |
CA2024598A1 (en) * | 1989-09-05 | 1991-03-06 | Sau-Chi B. Yan | Method for activating protein c |
US5296352A (en) * | 1990-10-02 | 1994-03-22 | Ciba-Geigy Corporation | Monoclonal antibodies directed against complexes formed by thrombin and hirudin |
AT398079B (de) | 1991-11-04 | 1994-09-26 | Immuno Ag | Präparation mit thrombinaktivität sowie verfahren zu ihrer herstellung |
AT396937B (de) * | 1992-04-06 | 1993-12-27 | Immuno Ag | Verfahren zur aktivierung von blutgerinnungsfaktoren |
AT397390B (de) * | 1992-04-06 | 1994-03-25 | Immuno Ag | Verfahren zur spaltung von proteinen |
-
1995
- 1995-11-24 AT AT0192795A patent/AT404597B/de not_active IP Right Cessation
-
1996
- 1996-11-19 AT AT96890172T patent/ATE277169T1/de active
- 1996-11-19 EP EP96890172A patent/EP0776969B1/de not_active Expired - Lifetime
- 1996-11-19 DE DE59611093T patent/DE59611093D1/de not_active Expired - Lifetime
- 1996-11-20 CA CA002190802A patent/CA2190802C/en not_active Expired - Fee Related
- 1996-11-20 US US08/752,892 patent/US6010844A/en not_active Expired - Lifetime
- 1996-11-22 NO NO19964965A patent/NO319266B1/no not_active IP Right Cessation
- 1996-11-25 JP JP33027896A patent/JP4180671B2/ja not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
US6010844A (en) | 2000-01-04 |
DE59611093D1 (de) | 2004-10-28 |
NO964965D0 (no) | 1996-11-22 |
JP4180671B2 (ja) | 2008-11-12 |
NO964965L (no) | 1997-05-26 |
CA2190802C (en) | 2008-02-12 |
EP0776969A3 (de) | 1999-06-02 |
EP0776969B1 (de) | 2004-09-22 |
ATA192795A (de) | 1998-05-15 |
JPH09183794A (ja) | 1997-07-15 |
CA2190802A1 (en) | 1997-05-25 |
EP0776969A2 (de) | 1997-06-04 |
AT404597B (de) | 1998-12-28 |
ATE277169T1 (de) | 2004-10-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Radcliffe et al. | Activation and control of factor VII by activated factor X and thrombin. Isolation and characterization of a single chain form of factor VII | |
Jesty et al. | The mechanism of activation of factor X: kinetic control of alternative pathways leading to the formation of activated factor X | |
Mann | [13] Prothrombin | |
US5304372A (en) | Process for preparing a human thrombin concentrate intended for therapeutic use | |
DK176090B1 (da) | Fremgangsmåde til oprensning af proteiner | |
AU677309B2 (en) | Purification of factor VII | |
Zhang et al. | Role of the hexapeptide disulfide loop present in the. gamma.-carboxyglutamic acid domain of human protein C in its activation properties and in the in vitro anticoagulant activity of activated protein C | |
Bortoleto et al. | Purification, characterization and crystallization of Jararacussin-I, a fibrinogen-clotting enzyme isolated from the venom of Bothrops jararacussu | |
NO319266B1 (no) | Fremgangsmate ved fremstilling og utvinning av proteiner fra pro-proteiner i ett fremgangsmatetrinn samt anvendelse av fremgangsmaten til fremstilling av proteiner. | |
Kawabata et al. | A microsomal endopeptidase from liver with substrate specificity for processing proproteins such as the vitamin K-dependent proteins of plasma. | |
DK147408B (da) | Fremgangsmaade til udvinding af thrombinagtige enzymer fra slangegifte eller slangegiftfraktioner | |
JP2832129B2 (ja) | 酵素的分解によるタンパク質の切断方法およびその利用方法 | |
JP2723445B2 (ja) | 血液凝固因子を活性化する方法 | |
Leonardi et al. | Two coagulation factor X activators from Vipera a. ammodytes venom with potential to treat patients with dysfunctional factors IXa or VIIa | |
Iwasaki et al. | Purification and Characterization of a Coagulant Enzyme, Okinaxobin I, from the Venom of Trimeresums okinavensis (Himehabu Snake) Which Releases Fibrinopeptide B | |
IE903212A1 (en) | Method for activating protein c | |
Samel et al. | Metalloproteinase with factor X activating and fibrinogenolytic activities from Vipera berus berus venom | |
Rabiet et al. | Activation of prothrombin Barcelona evidence for active high molecular weight intermediates | |
Taby et al. | Inhibition of activated protein C by aprotinin and the use of the insolubilized inhibitor for its purification | |
Kumar et al. | Specific molecular interaction sites on factor VII involved in factor X activation | |
Sakai et al. | Blood clotting factor IX Kashihara: amino acid substitution of valine-182 by phenylalanine | |
Nakagaki et al. | Isolation and characterization of a protein C activator from tropical moccasin venom | |
Dode et al. | Characterization of a proteolytically modified form of human prothrombin | |
AU4311893A (en) | Purification of kringle containing proteins, and especially t-pa | |
Mollerup et al. | The use of RP‐HPLC for measuring activation and cleavage of rFVIIA during purification |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
CHAD | Change of the owner's name or address (par. 44 patent law, par. patentforskriften) |
Owner name: BAXALTA INCORPORATED, CH |
|
MK1K | Patent expired |