HRP20000826A2 - Human protein c polypeptide - Google Patents
Human protein c polypeptide Download PDFInfo
- Publication number
- HRP20000826A2 HRP20000826A2 HR20000826A HRP20000826A HRP20000826A2 HR P20000826 A2 HRP20000826 A2 HR P20000826A2 HR 20000826 A HR20000826 A HR 20000826A HR P20000826 A HRP20000826 A HR P20000826A HR P20000826 A2 HRP20000826 A2 HR P20000826A2
- Authority
- HR
- Croatia
- Prior art keywords
- protein
- polypeptide
- apc
- human protein
- heavy chain
- Prior art date
Links
- 101500025568 Homo sapiens Saposin-D Proteins 0.000 title claims description 35
- 101800004937 Protein C Proteins 0.000 claims description 34
- 101800001700 Saposin-D Proteins 0.000 claims description 33
- 208000007536 Thrombosis Diseases 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 15
- 229920001184 polypeptide Polymers 0.000 claims description 13
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 13
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 13
- 108020004414 DNA Proteins 0.000 claims description 10
- 102000053602 DNA Human genes 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 208000035475 disorder Diseases 0.000 claims description 5
- 230000002792 vascular Effects 0.000 claims description 4
- 108020004511 Recombinant DNA Proteins 0.000 claims description 3
- 201000005665 thrombophilia Diseases 0.000 claims description 3
- 239000013598 vector Substances 0.000 claims description 3
- 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 2
- 108020004707 nucleic acids Proteins 0.000 claims 2
- 102000039446 nucleic acids Human genes 0.000 claims 2
- 150000007523 nucleic acids Chemical class 0.000 claims 2
- 102400000827 Saposin-D Human genes 0.000 claims 1
- 102000017975 Protein C Human genes 0.000 description 31
- 229960000856 protein c Drugs 0.000 description 31
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 24
- 229940100689 human protein c Drugs 0.000 description 20
- 108090000190 Thrombin Proteins 0.000 description 19
- 229960004072 thrombin Drugs 0.000 description 19
- 239000007983 Tris buffer Substances 0.000 description 18
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 18
- 108090000623 proteins and genes Proteins 0.000 description 15
- 239000000243 solution Substances 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 12
- 235000018102 proteins Nutrition 0.000 description 12
- 102000004169 proteins and genes Human genes 0.000 description 12
- 239000011347 resin Substances 0.000 description 12
- 229920005989 resin Polymers 0.000 description 12
- 239000000523 sample Substances 0.000 description 12
- 239000011780 sodium chloride Substances 0.000 description 12
- 102000010911 Enzyme Precursors Human genes 0.000 description 8
- 108010062466 Enzyme Precursors Proteins 0.000 description 8
- 108091028043 Nucleic acid sequence Proteins 0.000 description 8
- 230000004913 activation Effects 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 239000013612 plasmid Substances 0.000 description 6
- 235000001014 amino acid Nutrition 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 5
- 206010053567 Coagulopathies Diseases 0.000 description 4
- 229920002684 Sepharose Polymers 0.000 description 4
- 206010040047 Sepsis Diseases 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 230000035602 clotting Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 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 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 3
- 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 3
- 241001465754 Metazoa Species 0.000 description 3
- 201000005660 Protein C Deficiency Diseases 0.000 description 3
- 108010000499 Thromboplastin Proteins 0.000 description 3
- 102000002262 Thromboplastin Human genes 0.000 description 3
- 206010047249 Venous thrombosis Diseases 0.000 description 3
- 230000003024 amidolytic effect Effects 0.000 description 3
- 239000003957 anion exchange resin Substances 0.000 description 3
- 239000003146 anticoagulant agent Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 239000001110 calcium chloride Substances 0.000 description 3
- 235000011148 calcium chloride Nutrition 0.000 description 3
- 229910001628 calcium chloride Inorganic materials 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 208000009190 disseminated intravascular coagulation Diseases 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 239000006167 equilibration buffer Substances 0.000 description 3
- 210000003527 eukaryotic cell Anatomy 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000014508 negative regulation of coagulation Effects 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000012488 sample solution Substances 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 101800001401 Activation peptide Proteins 0.000 description 2
- 102400000069 Activation peptide Human genes 0.000 description 2
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 2
- 206010051055 Deep vein thrombosis Diseases 0.000 description 2
- 108010016626 Dipeptides Proteins 0.000 description 2
- 208000032759 Hemolytic-Uremic Syndrome Diseases 0.000 description 2
- 206010062506 Heparin-induced thrombocytopenia Diseases 0.000 description 2
- 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 2
- 239000004743 Polypropylene Substances 0.000 description 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 2
- 108010022999 Serine Proteases Proteins 0.000 description 2
- 102000012479 Serine Proteases Human genes 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 208000002903 Thalassemia Diseases 0.000 description 2
- 201000007023 Thrombotic Thrombocytopenic Purpura Diseases 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 208000028227 Viral hemorrhagic fever Diseases 0.000 description 2
- 229930003448 Vitamin K Natural products 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 2
- 230000010100 anticoagulation Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 238000009739 binding Methods 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000013024 dilution buffer Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 230000023597 hemostasis Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 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 2
- -1 polypropylene Polymers 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 230000004481 post-translational protein modification Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 210000001236 prokaryotic cell Anatomy 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 201000005380 purpura fulminans Diseases 0.000 description 2
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 208000007056 sickle cell anemia Diseases 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 235000019168 vitamin K Nutrition 0.000 description 2
- 239000011712 vitamin K Substances 0.000 description 2
- 150000003721 vitamin K derivatives Chemical class 0.000 description 2
- 229940046010 vitamin k Drugs 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 229940123373 Adenovirus E1A gene Drugs 0.000 description 1
- 206010002388 Angina unstable Diseases 0.000 description 1
- 206010003178 Arterial thrombosis Diseases 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 206010058279 Factor V Leiden mutation Diseases 0.000 description 1
- 206010053172 Fatal outcomes Diseases 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000000447 Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Human genes 0.000 description 1
- 108010055817 Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Proteins 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 208000006011 Stroke Diseases 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
- 229930006000 Sucrose Natural products 0.000 description 1
- 102000012607 Thrombomodulin Human genes 0.000 description 1
- 108010079274 Thrombomodulin Proteins 0.000 description 1
- 208000007814 Unstable Angina Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 150000001450 anions Chemical group 0.000 description 1
- 229940127090 anticoagulant agent Drugs 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 229940019700 blood coagulation factors Drugs 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 230000021523 carboxylation Effects 0.000 description 1
- 238000006473 carboxylation reaction Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000012531 culture fluid Substances 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 230000000058 esterolytic effect Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 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
- 238000002523 gelfiltration Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- 208000013746 hereditary thrombophilia due to congenital protein C deficiency Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000001471 micro-filtration Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000008288 physiological mechanism Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000000019 pro-fibrinolytic effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 238000007631 vascular surgery Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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)
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Biotechnology (AREA)
- Diabetes (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Cardiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8758598P | 1998-06-01 | 1998-06-01 | |
| PCT/US1999/011969 WO1999063070A1 (en) | 1998-06-01 | 1999-06-01 | Human protein c polypeptide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20000826A2 true HRP20000826A2 (en) | 2001-10-31 |
Family
ID=22206075
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20000826A HRP20000826A2 (en) | 1998-06-01 | 2000-11-30 | Human protein c polypeptide |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US20040038288A1 (ja) |
| EP (1) | EP1084235A4 (ja) |
| JP (1) | JP2002517191A (ja) |
| KR (1) | KR20010043941A (ja) |
| CN (1) | CN1303428A (ja) |
| AR (1) | AR020082A1 (ja) |
| AU (1) | AU4409399A (ja) |
| BR (1) | BR9910858A (ja) |
| CA (1) | CA2330171A1 (ja) |
| CO (1) | CO5070672A1 (ja) |
| DZ (1) | DZ2803A1 (ja) |
| EA (1) | EA200001254A1 (ja) |
| HR (1) | HRP20000826A2 (ja) |
| HU (1) | HUP0102014A3 (ja) |
| ID (1) | ID27282A (ja) |
| IL (1) | IL139595A0 (ja) |
| NO (1) | NO20006091L (ja) |
| NZ (1) | NZ507982A (ja) |
| PE (1) | PE20000561A1 (ja) |
| PL (1) | PL344349A1 (ja) |
| SK (1) | SK17502000A3 (ja) |
| SV (1) | SV1999000067A (ja) |
| TR (1) | TR200003552T2 (ja) |
| WO (1) | WO1999063070A1 (ja) |
| ZA (1) | ZA200006647B (ja) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006025995A2 (en) * | 2004-07-27 | 2006-03-09 | The Regents Of The University Of California | Compositions and methods using md-2 mutants and chimeric proteins |
| CN108159399B (zh) * | 2017-12-29 | 2020-07-24 | 华中科技大学同济医学院附属同济医院 | 一种凝血蛋白酶aPC在防治糖尿病心肌病药物中的应用 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2728240B2 (ja) * | 1988-07-26 | 1998-03-18 | ヘキスト薬品工業株式会社 | ヒトプロテインｃ変異体及びその製造方法 |
| WO1991009960A1 (en) * | 1989-12-29 | 1991-07-11 | Zymogenetics, Inc. | Hybrid protein c |
| WO1991012320A1 (en) * | 1990-02-09 | 1991-08-22 | Zymogenetics, Inc. | Activated protein c with truncated light chain |
| JPH0564588A (ja) * | 1991-08-14 | 1993-03-19 | Teijin Ltd | 短い重鎖を有するヒトプロテインｃおよび活性化ヒトプロテインｃ |
-
1999
- 1999-05-28 SV SV1999000067A patent/SV1999000067A/es not_active Application Discontinuation
- 1999-05-31 AR ARP990102575A patent/AR020082A1/es not_active Application Discontinuation
- 1999-06-01 NZ NZ507982A patent/NZ507982A/en not_active Application Discontinuation
- 1999-06-01 EP EP99927111A patent/EP1084235A4/en not_active Withdrawn
- 1999-06-01 CO CO99034013A patent/CO5070672A1/es unknown
- 1999-06-01 AU AU44093/99A patent/AU4409399A/en not_active Abandoned
- 1999-06-01 KR KR1020007013511A patent/KR20010043941A/ko not_active Application Discontinuation
- 1999-06-01 CN CN99806859A patent/CN1303428A/zh active Pending
- 1999-06-01 PL PL99344349A patent/PL344349A1/xx not_active Application Discontinuation
- 1999-06-01 JP JP2000552266A patent/JP2002517191A/ja not_active Withdrawn
- 1999-06-01 DZ DZ990103A patent/DZ2803A1/xx active
- 1999-06-01 CA CA002330171A patent/CA2330171A1/en not_active Abandoned
- 1999-06-01 PE PE1999000461A patent/PE20000561A1/es not_active Application Discontinuation
- 1999-06-01 TR TR2000/03552T patent/TR200003552T2/xx unknown
- 1999-06-01 WO PCT/US1999/011969 patent/WO1999063070A1/en not_active Application Discontinuation
- 1999-06-01 BR BR9910858-5A patent/BR9910858A/pt not_active IP Right Cessation
- 1999-06-01 SK SK1750-2000A patent/SK17502000A3/sk unknown
- 1999-06-01 HU HU0102014A patent/HUP0102014A3/hu unknown
- 1999-06-01 EA EA200001254A patent/EA200001254A1/ru unknown
- 1999-06-01 ID IDW20002430A patent/ID27282A/id unknown
- 1999-06-01 IL IL13959599A patent/IL139595A0/xx unknown
-
2000
- 2000-11-15 ZA ZA200006647A patent/ZA200006647B/en unknown
- 2000-11-30 NO NO20006091A patent/NO20006091L/no not_active Application Discontinuation
- 2000-11-30 HR HR20000826A patent/HRP20000826A2/hr not_active Application Discontinuation
-
2003
- 2003-09-25 US US10/670,628 patent/US20040038288A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| NZ507982A (en) | 2004-01-30 |
| BR9910858A (pt) | 2001-03-06 |
| IL139595A0 (en) | 2002-02-10 |
| NO20006091D0 (no) | 2000-11-30 |
| PL344349A1 (en) | 2001-11-05 |
| EP1084235A1 (en) | 2001-03-21 |
| EA200001254A1 (ru) | 2001-06-25 |
| CA2330171A1 (en) | 1999-12-09 |
| HUP0102014A2 (hu) | 2001-10-28 |
| EP1084235A4 (en) | 2002-03-27 |
| JP2002517191A (ja) | 2002-06-18 |
| CO5070672A1 (es) | 2001-08-28 |
| ID27282A (id) | 2001-03-22 |
| HUP0102014A3 (en) | 2003-09-29 |
| CN1303428A (zh) | 2001-07-11 |
| AR020082A1 (es) | 2002-04-10 |
| WO1999063070A1 (en) | 1999-12-09 |
| NO20006091L (no) | 2001-01-31 |
| DZ2803A1 (fr) | 2003-12-01 |
| ZA200006647B (en) | 2001-11-15 |
| PE20000561A1 (es) | 2000-07-22 |
| SK17502000A3 (sk) | 2001-09-11 |
| US20040038288A1 (en) | 2004-02-26 |
| KR20010043941A (ko) | 2001-05-25 |
| AU4409399A (en) | 1999-12-20 |
| SV1999000067A (es) | 2000-07-06 |
| TR200003552T2 (tr) | 2001-05-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6162629A (en) | Methods for processing activated protein C | |
| US6037322A (en) | Methods for treating vascular disorders using activated protein C | |
| US20040028670A1 (en) | Activated protein C formulations | |
| CZ286016B6 (cs) | Derivát lidské bílkoviny C, způsob jeho přípravy a farmaceutický prostředek, který ho obsahuje | |
| JP3004375B2 (ja) | ヒトプロテインｃのグリコシル化突然変異体の発現のためのベクターおよび化合物 | |
| HRP20000826A2 (en) | Human protein c polypeptide | |
| RU2167936C2 (ru) | Способ минимизации деградации активированного протеина с (варианты), стабилизированная композиция активированного протеина с | |
| AU2003252774A1 (en) | Human Protein C Polypeptide | |
| MXPA00011807A (en) | Human protein c polypeptide | |
| AU769144B2 (en) | Improved methods for processing activated protein C | |
| EP1557463A1 (en) | Improved methods for processing activated protein C | |
| CZ20004422A3 (cs) | Polypeptid lidský protein C | |
| CZ373799A3 (cs) | Zlepšené způsoby zpracování aktivovaného proteinu C | |
| Swanson | Revisiting the antifibrinolytic effect of carboxypeptidase N: novel structure and regulation | |
| Smith | The molecular mechanism of factor IX activation by factor XIa | |
| EP1561469A1 (en) | Activated Protein C Formulations | |
| MXPA99008727A (en) | Methods for treating vascular disorders |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A1OB | Publication of a patent application | ||
| ARAI | Request for the grant of a patent on the basis of the submitted results of a substantive examination of a patent application | ||
| ODRP | Renewal fee for the maintenance of a patent |
Payment date: 20060608 Year of fee payment: 8 |
|
| OBST | Application withdrawn |