NO311299B1 - Protein C derivater, rekombinant DNA molekyl, kodende dette samt fremgangsmåte for fremstilling av proteinene - Google Patents
Protein C derivater, rekombinant DNA molekyl, kodende dette samt fremgangsmåte for fremstilling av proteinene Download PDFInfo
- Publication number
- NO311299B1 NO311299B1 NO19931840A NO931840A NO311299B1 NO 311299 B1 NO311299 B1 NO 311299B1 NO 19931840 A NO19931840 A NO 19931840A NO 931840 A NO931840 A NO 931840A NO 311299 B1 NO311299 B1 NO 311299B1
- Authority
- NO
- Norway
- Prior art keywords
- flin
- protein
- human protein
- derivative
- derivatives
- Prior art date
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- 101800004937 Protein C Proteins 0.000 title claims description 45
- 101800001700 Saposin-D Proteins 0.000 title claims description 43
- 229960000856 protein c Drugs 0.000 title claims description 43
- 238000000034 method Methods 0.000 title claims description 15
- 108020004511 Recombinant DNA Proteins 0.000 title claims description 11
- 102000053602 DNA Human genes 0.000 title claims description 6
- 102100036546 Salivary acidic proline-rich phosphoprotein 1/2 Human genes 0.000 title claims 4
- 108090000623 proteins and genes Proteins 0.000 title description 7
- 102000004169 proteins and genes Human genes 0.000 title description 5
- 101500025568 Homo sapiens Saposin-D Proteins 0.000 claims abstract description 70
- 229940100689 human protein c Drugs 0.000 claims abstract description 70
- 239000013598 vector Substances 0.000 claims abstract description 14
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 14
- 239000013612 plasmid Substances 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 239000003146 anticoagulant agent Substances 0.000 claims description 5
- 241000588724 Escherichia coli Species 0.000 claims description 4
- 241001646716 Escherichia coli K-12 Species 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 229960004676 antithrombotic agent Drugs 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 239000006228 supernatant Substances 0.000 claims description 2
- 230000001131 transforming effect Effects 0.000 claims description 2
- 238000012258 culturing Methods 0.000 claims 1
- 230000004913 activation Effects 0.000 abstract description 14
- 108090000190 Thrombin Proteins 0.000 abstract description 13
- 230000000694 effects Effects 0.000 abstract description 13
- 229960004072 thrombin Drugs 0.000 abstract description 13
- 150000001875 compounds Chemical class 0.000 abstract description 5
- 239000013604 expression vector Substances 0.000 abstract description 5
- 230000005714 functional activity Effects 0.000 abstract description 3
- 125000000837 carbohydrate group Chemical group 0.000 abstract description 2
- 102000017975 Protein C Human genes 0.000 description 41
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 16
- 108010062466 Enzyme Precursors Proteins 0.000 description 13
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 13
- 102000010911 Enzyme Precursors Human genes 0.000 description 12
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 9
- 108020004414 DNA Proteins 0.000 description 7
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 7
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 6
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 6
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 5
- 230000003024 amidolytic effect Effects 0.000 description 5
- 229940024606 amino acid Drugs 0.000 description 5
- 235000001014 amino acid Nutrition 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 235000009582 asparagine Nutrition 0.000 description 5
- 229960001230 asparagine Drugs 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 229920001184 polypeptide Polymers 0.000 description 5
- 101800001401 Activation peptide Proteins 0.000 description 4
- 102400000069 Activation peptide Human genes 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 102000012607 Thrombomodulin Human genes 0.000 description 4
- 108010079274 Thrombomodulin Proteins 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 230000015271 coagulation Effects 0.000 description 4
- 238000005345 coagulation Methods 0.000 description 4
- 239000003623 enhancer Substances 0.000 description 4
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 4
- 230000014508 negative regulation of coagulation Effects 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 241000701161 unidentified adenovirus Species 0.000 description 4
- 206010051055 Deep vein thrombosis Diseases 0.000 description 3
- 206010047249 Venous thrombosis Diseases 0.000 description 3
- 229940127219 anticoagulant drug Drugs 0.000 description 3
- 235000003704 aspartic acid Nutrition 0.000 description 3
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 3
- 230000035602 clotting Effects 0.000 description 3
- 230000001112 coagulating effect Effects 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 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 2
- 206010053567 Coagulopathies Diseases 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 241000206602 Eukaryota Species 0.000 description 2
- 101000763314 Homo sapiens Thrombomodulin Proteins 0.000 description 2
- 108700002232 Immediate-Early Genes Proteins 0.000 description 2
- 208000010378 Pulmonary Embolism Diseases 0.000 description 2
- 108010000499 Thromboplastin Proteins 0.000 description 2
- 102000002262 Thromboplastin Human genes 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 230000010100 anticoagulation Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 102000051206 human THBD Human genes 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 230000004481 post-translational protein modification Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 206010003178 Arterial thrombosis Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 241000271032 Daboia russelii Species 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 208000005189 Embolism Diseases 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
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 241000701109 Human adenovirus 2 Species 0.000 description 1
- 241000829111 Human polyomavirus 1 Species 0.000 description 1
- NPBGTPKLVJEOBE-IUCAKERBSA-N Lys-Arg Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=N NPBGTPKLVJEOBE-IUCAKERBSA-N 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 241000364057 Peoria Species 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 201000005660 Protein C Deficiency Diseases 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 206010043647 Thrombotic Stroke Diseases 0.000 description 1
- 208000007814 Unstable Angina Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 229930003448 Vitamin K Natural products 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 208000037919 acquired disease Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 206010000891 acute myocardial infarction Diseases 0.000 description 1
- 230000001365 aminolytic effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 208000015294 blood coagulation disease Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- 238000007820 coagulation assay Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 208000009190 disseminated intravascular coagulation Diseases 0.000 description 1
- 230000000058 esterolytic effect Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- UHBYWPGGCSDKFX-VKHMYHEASA-N gamma-carboxy-L-glutamic acid Chemical group OC(=O)[C@@H](N)CC(C(O)=O)C(O)=O UHBYWPGGCSDKFX-VKHMYHEASA-N 0.000 description 1
- 230000006251 gamma-carboxylation Effects 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical class 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 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 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000000019 pro-fibrinolytic effect Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 201000005380 purpura fulminans Diseases 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960003766 thrombin (human) Drugs 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000007631 vascular surgery Methods 0.000 description 1
- 239000002821 viper venom Substances 0.000 description 1
- 235000019168 vitamin K Nutrition 0.000 description 1
- 239000011712 vitamin K Substances 0.000 description 1
- 150000003721 vitamin K derivatives Chemical class 0.000 description 1
- 229940046010 vitamin k Drugs 0.000 description 1
- 230000003462 zymogenic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/745—Blood coagulation or fibrinolysis factors
-
- 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)
- C12N9/6464—Protein C (3.4.21.69)
-
- 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
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21069—Protein C activated (3.4.21.69)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Hematology (AREA)
- Microbiology (AREA)
- Public Health (AREA)
- Gastroenterology & Hepatology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Diabetes (AREA)
- Veterinary Medicine (AREA)
- Toxicology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US88719192A | 1992-05-21 | 1992-05-21 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO931840D0 NO931840D0 (no) | 1993-05-19 |
| NO931840L NO931840L (no) | 1993-11-22 |
| NO311299B1 true NO311299B1 (no) | 2001-11-12 |
Family
ID=25390640
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19931840A NO311299B1 (no) | 1992-05-21 | 1993-05-19 | Protein C derivater, rekombinant DNA molekyl, kodende dette samt fremgangsmåte for fremstilling av proteinene |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US5453373A (zh) |
| EP (1) | EP0575054B1 (zh) |
| JP (1) | JP3564150B2 (zh) |
| KR (1) | KR100291529B1 (zh) |
| CN (1) | CN1080658A (zh) |
| AT (1) | ATE286121T1 (zh) |
| AU (1) | AU661901B2 (zh) |
| BR (1) | BR9301944A (zh) |
| CA (1) | CA2096604C (zh) |
| CZ (1) | CZ286016B6 (zh) |
| DE (1) | DE69333727T2 (zh) |
| DK (1) | DK0575054T3 (zh) |
| ES (1) | ES2233925T3 (zh) |
| FI (1) | FI932282A (zh) |
| HU (1) | HU218408B (zh) |
| IL (1) | IL105757A0 (zh) |
| MX (1) | MX9302917A (zh) |
| MY (1) | MY110664A (zh) |
| NO (1) | NO311299B1 (zh) |
| NZ (1) | NZ247651A (zh) |
| PH (1) | PH29911A (zh) |
| PT (1) | PT575054E (zh) |
| RU (1) | RU2122004C1 (zh) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2067525C (en) * | 1991-05-09 | 1998-09-15 | Helmut G. Alt | Organometallic fluorenyl compounds, preparation and use |
| AT402262B (de) * | 1991-06-20 | 1997-03-25 | Immuno Ag | Arzneimittel enthaltend aktiviertes protein c |
| WO1993007491A1 (en) * | 1991-10-04 | 1993-04-15 | Board Of Regents Of The University Of Nebraska | A soluble thrombomodulin-based one-stage assay for vitamin k-dependent coagulation-inhibiting proteins |
| US5716795A (en) * | 1991-10-04 | 1998-02-10 | Matschiner; John T. | Thrombomodulin-based coagulometric assay of the protein C system |
| DE4320294A1 (de) * | 1993-06-18 | 1994-12-22 | Immuno Ag | Verwendung von humanem Protein C zur Verhinderung und Behandlung von Thrombozytenablagerungen |
| US6630137B1 (en) * | 1997-04-28 | 2003-10-07 | Eli Lilly And Company | Activated protein C formulations |
| KR100564189B1 (ko) | 1997-04-28 | 2006-03-27 | 일라이 릴리 앤드 캄파니 | 활성화 프로틴ｃ의 가공을 위한 개선된 방법 |
| JP2002502421A (ja) * | 1997-06-05 | 2002-01-22 | イーライ・リリー・アンド・カンパニー | 血栓障害の処置方法 |
| HUP0001237A3 (en) * | 1997-10-20 | 2002-01-28 | Lilly Co Eli | Methods for treating vascular disorders |
| WO2000006179A1 (en) * | 1998-07-31 | 2000-02-10 | Eli Lilly And Company | Cryogranulation of activated protein c |
| US6815533B1 (en) | 1998-07-31 | 2004-11-09 | Eli Lilly And Company | Cryogranulation of activated protein C |
| AU768075B2 (en) | 1998-10-22 | 2003-12-04 | Eli Lilly And Company | Methods for treating sepsis |
| BR9915317A (pt) | 1998-11-13 | 2001-08-07 | Lilly Co Eli | Método de tratar trombocitopenia induzida por heparina |
| ES2195655T3 (es) | 1998-11-20 | 2003-12-01 | Lilly Co Eli | Procedimiento para tratar fiebre hemorragica virica con proteina c. |
| AU1723200A (en) | 1998-11-23 | 2000-06-13 | Eli Lilly And Company | Method of treating sickle cell disease and thalassemia |
| US6998122B1 (en) * | 1999-04-30 | 2006-02-14 | Eli Lilly And Company | Protein C derivatives |
| JP2003514545A (ja) * | 1999-11-19 | 2003-04-22 | イーライ・リリー・アンド・カンパニー | プロテインｃ誘導体 |
| ES2234807T3 (es) * | 2000-02-02 | 2005-07-01 | Eli Lilly And Company | Derivados de proteina c. |
| JP2003521938A (ja) * | 2000-02-11 | 2003-07-22 | イーライ・リリー・アンド・カンパニー | プロテインｃ誘導体 |
| US7204981B2 (en) * | 2000-03-28 | 2007-04-17 | Eli Lilly And Company | Methods of treating diseases with activated protein C |
| EP1328622A2 (en) * | 2000-10-18 | 2003-07-23 | Maxygen Aps | Protein c or activated protein c-like molecules |
| BR0114771A (pt) * | 2000-10-18 | 2004-07-27 | Maxygen Aps | Moléculas de proteìna c ou semelhantes a proteìna c ativada |
| US6933367B2 (en) | 2000-10-18 | 2005-08-23 | Maxygen Aps | Protein C or activated protein C-like molecules |
| WO2002085117A1 (en) * | 2001-04-24 | 2002-10-31 | Eisai Co., Ltd. | Methods and compositions for preventing and treating septic shock and endotoxemia |
| JP2005528351A (ja) * | 2002-03-08 | 2005-09-22 | イーライ・リリー・アンド・カンパニー | 活性化プロテインｃ製剤 |
| AU2003232176A1 (en) * | 2002-06-14 | 2003-12-31 | Maxygen Aps | Protein c variants with altered properties |
| US20070142272A1 (en) * | 2003-01-24 | 2007-06-21 | Zlokovic Berislav V | Neuroprotective activity of activated protein c independent of its anticoagulant activity |
| WO2006014839A2 (en) * | 2004-07-23 | 2006-02-09 | The University Of Rochester | Activated protein c inhibits undesirable effects of plasminogen activator in the brain |
| CA2612859A1 (en) * | 2005-06-23 | 2006-12-28 | The University Of British Columbia | Coagulation factor iii polymorphisms associated with prediction of subject outcome and response to therapy |
| CA2654761A1 (en) * | 2006-06-09 | 2007-12-13 | The University Of British Columbia | Interferon gamma polymorphisms as indicators of subject outcome in critically ill subjects |
| EP2178556B1 (en) * | 2007-06-18 | 2011-08-17 | Oregon Health & Science University | Protein c for use in maintaining hemostasis |
| EP2242875A4 (en) * | 2008-01-15 | 2012-04-04 | Univ British Columbia | PROTEIN C RS2069915 AS A SURVIVOR RESPONSE PREDICTOR AND ADMINISTRATION OF PROTEIN C OR AN ACTIVE PROTEIN C COMPOUND |
| ES2629099T3 (es) | 2008-12-19 | 2017-08-07 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Derivados de serin proteasa y usos en la prevención o el tratamiento de y trastornos de la coagulación sanguinea |
| WO2012068519A2 (en) | 2010-11-19 | 2012-05-24 | Sirius Genomics Inc. | Markers associated with response to activated protein c administration, and uses thereof |
| WO2014005183A1 (en) | 2012-07-04 | 2014-01-09 | The University Of Sydney | Treatment of inflammatory skin disorders |
| EP3137102B1 (en) | 2014-04-16 | 2021-07-14 | ZZ Biotech LLC | Apc for use in the treatment of abnormal cutaneous scarring |
| WO2023119230A1 (en) | 2021-12-22 | 2023-06-29 | L'oreal | Coagulation pathway and nicotinamide-adenine dinucleotide pathway modulating compositions and methods of their use |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4775624A (en) * | 1985-02-08 | 1988-10-04 | Eli Lilly And Company | Vectors and compounds for expression of human protein C |
| US4992373A (en) * | 1987-12-04 | 1991-02-12 | Eli Lilly And Company | Vectors and compounds for direct expression of activated human protein C |
| ZA889497B (en) * | 1987-12-28 | 1990-08-29 | Lilly Co Eli | Vectors and compounds for expression of zymogen forms of human protein c |
| US4981952A (en) * | 1988-10-04 | 1991-01-01 | Eli Lilly And Company | Method for the purification of vitamin K-dependent proteins |
| IL97311A0 (en) * | 1990-02-23 | 1992-05-25 | Lilly Co Eli | Vectors and compounds for expression of glycosylation mutants of human protein c |
| US5270178A (en) * | 1990-02-23 | 1993-12-14 | Eli Lilly And Company | Vectors and compounds for expression of zymogen forms of human protein C |
-
1993
- 1993-05-18 MY MYPI93000913A patent/MY110664A/en unknown
- 1993-05-19 CA CA002096604A patent/CA2096604C/en not_active Expired - Fee Related
- 1993-05-19 MX MX9302917A patent/MX9302917A/es unknown
- 1993-05-19 NO NO19931840A patent/NO311299B1/no not_active IP Right Cessation
- 1993-05-19 EP EP93303894A patent/EP0575054B1/en not_active Expired - Lifetime
- 1993-05-19 DE DE69333727T patent/DE69333727T2/de not_active Expired - Fee Related
- 1993-05-19 KR KR1019930008613A patent/KR100291529B1/ko not_active IP Right Cessation
- 1993-05-19 RU RU93005089A patent/RU2122004C1/ru active
- 1993-05-19 HU HU9301461A patent/HU218408B/hu not_active IP Right Cessation
- 1993-05-19 AT AT93303894T patent/ATE286121T1/de not_active IP Right Cessation
- 1993-05-19 PT PT93303894T patent/PT575054E/pt unknown
- 1993-05-19 FI FI932282A patent/FI932282A/fi unknown
- 1993-05-19 ES ES93303894T patent/ES2233925T3/es not_active Expired - Lifetime
- 1993-05-19 NZ NZ247651A patent/NZ247651A/en unknown
- 1993-05-19 DK DK93303894T patent/DK0575054T3/da active
- 1993-05-19 CZ CZ93948A patent/CZ286016B6/cs not_active IP Right Cessation
- 1993-05-20 PH PH46212A patent/PH29911A/en unknown
- 1993-05-20 CN CN93106214A patent/CN1080658A/zh active Pending
- 1993-05-20 AU AU38699/93A patent/AU661901B2/en not_active Ceased
- 1993-05-20 JP JP11822393A patent/JP3564150B2/ja not_active Expired - Fee Related
- 1993-05-20 IL IL105757A patent/IL105757A0/xx unknown
- 1993-05-20 BR BR9301944A patent/BR9301944A/pt not_active Application Discontinuation
- 1993-07-09 US US08/089,215 patent/US5453373A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| HU218408B (hu) | 2000-08-28 |
| CA2096604C (en) | 2003-12-16 |
| EP0575054A2 (en) | 1993-12-22 |
| KR930023370A (ko) | 1993-12-18 |
| ATE286121T1 (de) | 2005-01-15 |
| DK0575054T3 (da) | 2005-04-25 |
| FI932282A (fi) | 1993-11-22 |
| AU3869993A (en) | 1993-11-25 |
| KR100291529B1 (ko) | 2001-06-01 |
| CN1080658A (zh) | 1994-01-12 |
| CZ286016B6 (cs) | 1999-12-15 |
| DE69333727T2 (de) | 2005-12-15 |
| DE69333727D1 (de) | 2005-02-03 |
| AU661901B2 (en) | 1995-08-10 |
| NZ247651A (en) | 1995-03-28 |
| CZ94893A3 (en) | 1994-01-19 |
| NO931840L (no) | 1993-11-22 |
| BR9301944A (pt) | 1993-11-30 |
| CA2096604A1 (en) | 1993-11-22 |
| JP3564150B2 (ja) | 2004-09-08 |
| MY110664A (en) | 1999-01-30 |
| MX9302917A (es) | 1993-11-01 |
| EP0575054B1 (en) | 2004-12-29 |
| JPH0680698A (ja) | 1994-03-22 |
| NO931840D0 (no) | 1993-05-19 |
| IL105757A0 (en) | 1993-09-22 |
| EP0575054A3 (en) | 1995-04-19 |
| HU9301461D0 (en) | 1993-09-28 |
| RU2122004C1 (ru) | 1998-11-20 |
| FI932282A0 (fi) | 1993-05-19 |
| PH29911A (en) | 1996-09-16 |
| PT575054E (pt) | 2005-03-31 |
| US5453373A (en) | 1995-09-26 |
| ES2233925T3 (es) | 2005-06-16 |
| HUT69615A (en) | 1995-09-28 |
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