UA72194C2 - Method of treatment for patients with acquired hypercoagulable state or acquired protein c deficiency - Google Patents
Method of treatment for patients with acquired hypercoagulable state or acquired protein c deficiency Download PDFInfo
- Publication number
- UA72194C2 UA72194C2 UA2000042259A UA2000042259A UA72194C2 UA 72194 C2 UA72194 C2 UA 72194C2 UA 2000042259 A UA2000042259 A UA 2000042259A UA 2000042259 A UA2000042259 A UA 2000042259A UA 72194 C2 UA72194 C2 UA 72194C2
- Authority
- UA
- Ukraine
- Prior art keywords
- protein
- hours
- deficiency
- acquired
- dose
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 37
- 201000005665 thrombophilia Diseases 0.000 title claims abstract description 29
- 238000011282 treatment Methods 0.000 title claims abstract description 28
- 208000014171 autosomal dominant thrombophilia due to protein C deficiency Diseases 0.000 title claims abstract description 16
- 206010040047 Sepsis Diseases 0.000 claims abstract description 32
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims abstract description 13
- 208000014674 injury Diseases 0.000 claims abstract description 12
- 230000035935 pregnancy Effects 0.000 claims abstract description 11
- 238000001356 surgical procedure Methods 0.000 claims abstract description 11
- 230000008733 trauma Effects 0.000 claims abstract description 10
- 238000002054 transplantation Methods 0.000 claims abstract description 7
- 210000001185 bone marrow Anatomy 0.000 claims abstract description 5
- 229960000856 protein c Drugs 0.000 claims description 75
- 101800004937 Protein C Proteins 0.000 claims description 70
- 101800001700 Saposin-D Proteins 0.000 claims description 67
- 238000001802 infusion Methods 0.000 claims description 17
- 101500025568 Homo sapiens Saposin-D Proteins 0.000 claims description 16
- 229940100689 human protein c Drugs 0.000 claims description 16
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 12
- 238000002347 injection Methods 0.000 claims description 12
- 239000007924 injection Substances 0.000 claims description 12
- 210000000056 organ Anatomy 0.000 claims description 12
- 206010020608 Hypercoagulation Diseases 0.000 claims description 10
- 230000003027 hypercoagulation Effects 0.000 claims description 10
- 201000005660 Protein C Deficiency Diseases 0.000 claims description 9
- 208000013746 hereditary thrombophilia due to congenital protein C deficiency Diseases 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- 206010037549 Purpura Diseases 0.000 claims description 7
- 241001672981 Purpura Species 0.000 claims description 7
- 230000009424 thromboembolic effect Effects 0.000 claims description 7
- 206010058858 Meningococcal bacteraemia Diseases 0.000 claims description 5
- 208000022089 meningococcemia Diseases 0.000 claims description 5
- 230000036470 plasma concentration Effects 0.000 claims description 4
- 102100036546 Salivary acidic proline-rich phosphoprotein 1/2 Human genes 0.000 claims 9
- 201000005380 purpura fulminans Diseases 0.000 abstract description 5
- 206010027280 Meningococcal sepsis Diseases 0.000 abstract 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 abstract 1
- 102000017975 Protein C Human genes 0.000 description 61
- 208000009190 disseminated intravascular coagulation Diseases 0.000 description 22
- 239000007983 Tris buffer Substances 0.000 description 17
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 17
- 102000010911 Enzyme Precursors Human genes 0.000 description 14
- 108010062466 Enzyme Precursors Proteins 0.000 description 14
- 230000004913 activation Effects 0.000 description 14
- 230000035939 shock Effects 0.000 description 14
- 108090000623 proteins and genes Proteins 0.000 description 13
- 108090000190 Thrombin Proteins 0.000 description 12
- 239000000902 placebo Substances 0.000 description 12
- 229940068196 placebo Drugs 0.000 description 12
- 235000018102 proteins Nutrition 0.000 description 12
- 102000004169 proteins and genes Human genes 0.000 description 12
- 229960004072 thrombin Drugs 0.000 description 12
- 230000015271 coagulation Effects 0.000 description 10
- 238000005345 coagulation Methods 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 9
- 102000004506 Blood Proteins Human genes 0.000 description 8
- 108010017384 Blood Proteins Proteins 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 230000034994 death Effects 0.000 description 8
- 231100000517 death Toxicity 0.000 description 8
- 230000003247 decreasing effect Effects 0.000 description 8
- 239000002552 dosage form Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000003146 anticoagulant agent Substances 0.000 description 7
- 229940127219 anticoagulant drug Drugs 0.000 description 7
- 230000023555 blood coagulation Effects 0.000 description 7
- 238000010322 bone marrow transplantation Methods 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 201000011461 pre-eclampsia Diseases 0.000 description 7
- 206010053567 Coagulopathies Diseases 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- 230000003024 amidolytic effect Effects 0.000 description 6
- 208000015294 blood coagulation disease Diseases 0.000 description 6
- 239000011347 resin Substances 0.000 description 6
- 229920005989 resin Polymers 0.000 description 6
- 102000009123 Fibrin Human genes 0.000 description 5
- 108010073385 Fibrin Proteins 0.000 description 5
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 5
- 208000007536 Thrombosis Diseases 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 229950003499 fibrin Drugs 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 230000009261 transgenic effect Effects 0.000 description 5
- 208000008425 Protein deficiency Diseases 0.000 description 4
- 206010040070 Septic Shock Diseases 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 230000036303 septic shock Effects 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 208000011580 syndromic disease Diseases 0.000 description 4
- 230000002792 vascular Effects 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 description 3
- 208000007257 Budd-Chiari syndrome Diseases 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 208000005189 Embolism Diseases 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 206010019713 Hepatic vein thrombosis Diseases 0.000 description 3
- 108010022999 Serine Proteases Proteins 0.000 description 3
- 102000012479 Serine Proteases Human genes 0.000 description 3
- 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 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 239000003957 anion exchange resin Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 239000003527 fibrinolytic agent Substances 0.000 description 3
- 238000010253 intravenous injection Methods 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- 230000018341 negative regulation of fibrinolysis Effects 0.000 description 3
- KJONHKAYOJNZEC-UHFFFAOYSA-N nitrazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1 KJONHKAYOJNZEC-UHFFFAOYSA-N 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- 230000004768 organ dysfunction Effects 0.000 description 3
- 230000031915 positive regulation of coagulation Effects 0.000 description 3
- 230000004481 post-translational protein modification Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 238000011477 surgical intervention Methods 0.000 description 3
- 208000004043 venous thromboembolism Diseases 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 class 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
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- 235000006491 Acacia senegal Nutrition 0.000 description 2
- 208000035143 Bacterial infection Diseases 0.000 description 2
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 206010018910 Haemolysis Diseases 0.000 description 2
- 241000282520 Papio Species 0.000 description 2
- 208000010362 Protozoan Infections Diseases 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 229940127218 antiplatelet drug Drugs 0.000 description 2
- 229910052785 arsenic Inorganic materials 0.000 description 2
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 208000022362 bacterial infectious disease Diseases 0.000 description 2
- 201000005008 bacterial sepsis Diseases 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008033 biological extinction Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 230000035606 childbirth Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 239000006167 equilibration buffer Substances 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 230000020764 fibrinolysis Effects 0.000 description 2
- 230000003480 fibrinolytic effect Effects 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 210000003292 kidney cell Anatomy 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 229920006008 lipopolysaccharide Polymers 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000014508 negative regulation of coagulation Effects 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000000019 pro-fibrinolytic effect Effects 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000003612 virological effect Effects 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
- 208000009206 Abruptio Placentae Diseases 0.000 description 1
- 208000031729 Bacteremia Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 206010063094 Cerebral malaria Diseases 0.000 description 1
- 241000507614 Chama Species 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
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 208000028399 Critical Illness Diseases 0.000 description 1
- 241000072967 Cyathea ars Species 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 206010013453 Disseminated tuberculosis Diseases 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
- 206010014080 Ecchymosis Diseases 0.000 description 1
- 206010014522 Embolism venous Diseases 0.000 description 1
- 108010074860 Factor Xa Proteins 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- 108010007267 Hirudins Proteins 0.000 description 1
- 102000007625 Hirudins Human genes 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 206010022822 Intravascular haemolysis Diseases 0.000 description 1
- 208000007764 Legionnaires' Disease Diseases 0.000 description 1
- 206010024238 Leptospirosis Diseases 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 201000006836 Miliary Tuberculosis Diseases 0.000 description 1
- 101150027985 NAA35 gene Proteins 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 206010053159 Organ failure Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010033546 Pallor Diseases 0.000 description 1
- 241001504519 Papio ursinus Species 0.000 description 1
- 206010035148 Plague Diseases 0.000 description 1
- 206010035718 Pneumonia legionella Diseases 0.000 description 1
- 241000288906 Primates Species 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
- 208000010378 Pulmonary Embolism Diseases 0.000 description 1
- 206010037423 Pulmonary oedema Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 206010039207 Rocky Mountain Spotted Fever Diseases 0.000 description 1
- 244000082951 Senecio elegans Species 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 241000718541 Tetragastris balsamifera Species 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 208000037386 Typhoid Diseases 0.000 description 1
- 208000024248 Vascular System injury Diseases 0.000 description 1
- 208000012339 Vascular injury Diseases 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 229930003448 Vitamin K Natural products 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 206010000269 abscess Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 206010069351 acute lung injury Diseases 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 230000001567 anti-fibrinolytic effect Effects 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 101150046576 arsC gene Proteins 0.000 description 1
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- OIRCOABEOLEUMC-GEJPAHFPSA-N bivalirudin 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(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 OIRCOABEOLEUMC-GEJPAHFPSA-N 0.000 description 1
- 108010055460 bivalirudin Proteins 0.000 description 1
- 229960001500 bivalirudin Drugs 0.000 description 1
- 239000003130 blood coagulation factor inhibitor Substances 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 201000006824 bubonic plague Diseases 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 230000021523 carboxylation Effects 0.000 description 1
- 238000006473 carboxylation reaction Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 230000009852 coagulant defect Effects 0.000 description 1
- 230000001447 compensatory effect Effects 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000013024 dilution buffer Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 208000002296 eclampsia Diseases 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 208000028104 epidemic louse-borne typhus Diseases 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 238000004108 freeze drying Methods 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
- 230000008588 hemolysis Effects 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 210000002989 hepatic vein Anatomy 0.000 description 1
- WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 description 1
- 229940006607 hirudin Drugs 0.000 description 1
- 230000009215 host defense mechanism Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 208000018875 hypoxemia Diseases 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000003434 inspiratory effect Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000005976 liver dysfunction Effects 0.000 description 1
- 208000007903 liver failure Diseases 0.000 description 1
- 231100000835 liver failure Toxicity 0.000 description 1
- 229940127215 low-molecular weight heparin Drugs 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000012792 lyophilization process Methods 0.000 description 1
- 239000008176 lyophilized powder Substances 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
- 238000005399 mechanical ventilation Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 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
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 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
- 210000002826 placenta Anatomy 0.000 description 1
- 201000008532 placental abruption Diseases 0.000 description 1
- 230000003169 placental effect Effects 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 231100001271 preclinical toxicology Toxicity 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000009117 preventive therapy Methods 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 108010042388 protease C Proteins 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 208000005333 pulmonary edema Diseases 0.000 description 1
- 238000012207 quantitative assay Methods 0.000 description 1
- 238000011555 rabbit model Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000009076 regulation of hemostasis Effects 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 201000005608 severe pre-eclampsia Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000002764 solid phase assay Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000008718 systemic inflammatory response Effects 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
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 208000014173 thrombophilia due to thrombin defect Diseases 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 1
- 201000008297 typhoid fever Diseases 0.000 description 1
- 206010061393 typhus Diseases 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000003966 vascular damage Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 201000002282 venous insufficiency Diseases 0.000 description 1
- 210000000264 venule Anatomy 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
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
- 229960005080 warfarin Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4866—Protein C (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
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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)
- 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)
-
- 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)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6254997P | 1997-10-20 | 1997-10-20 | |
| US6476597P | 1997-11-07 | 1997-11-07 | |
| PCT/US1998/021723 WO1999020293A1 (en) | 1997-10-20 | 1998-10-14 | Methods for treating hypercoagulable states or acquired protein c deficiency |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA72194C2 true UA72194C2 (en) | 2005-02-15 |
Family
ID=26742406
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA2000042259A UA72194C2 (en) | 1997-10-20 | 1998-10-14 | Method of treatment for patients with acquired hypercoagulable state or acquired protein c deficiency |
Country Status (28)
| Country | Link |
|---|---|
| US (7) | US6037322A (da) |
| EP (2) | EP0913156B1 (da) |
| JP (2) | JP3805981B2 (da) |
| KR (1) | KR100798174B1 (da) |
| CN (1) | CN1276726A (da) |
| AT (1) | ATE292979T1 (da) |
| AU (1) | AU748417B2 (da) |
| BR (1) | BR9812965A (da) |
| CA (1) | CA2306983A1 (da) |
| DE (1) | DE69829721T2 (da) |
| DK (1) | DK0913156T3 (da) |
| EA (1) | EA002496B1 (da) |
| ES (1) | ES2239382T3 (da) |
| HK (1) | HK1020529A1 (da) |
| HU (2) | HUP0001237A3 (da) |
| ID (1) | ID24901A (da) |
| IL (2) | IL135712A0 (da) |
| MY (1) | MY117655A (da) |
| NO (1) | NO20002005L (da) |
| NZ (1) | NZ504026A (da) |
| PL (1) | PL200515B1 (da) |
| PT (1) | PT913156E (da) |
| SI (1) | SI0913156T1 (da) |
| TR (1) | TR200001059T2 (da) |
| TW (1) | TWI225404B (da) |
| UA (1) | UA72194C2 (da) |
| WO (1) | WO1999020293A1 (da) |
| ZA (1) | ZA989385B (da) |
Families Citing this family (72)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6630137B1 (en) | 1997-04-28 | 2003-10-07 | Eli Lilly And Company | Activated protein C formulations |
| HU224826B1 (en) | 1997-04-28 | 2006-02-28 | Lilly Co Eli | Activated protein c formulations |
| HUP0001237A3 (en) * | 1997-10-20 | 2002-01-28 | Lilly Co Eli | Methods for treating vascular disorders |
| US6844315B2 (en) * | 1998-05-20 | 2005-01-18 | Erasmus Universiteit Rotterdam | Immunoregulator |
| US6921751B1 (en) * | 1998-05-20 | 2005-07-26 | Erasmus Universiteit Rotterdam | Immunoregulator |
| US20040202645A1 (en) * | 2003-04-08 | 2004-10-14 | Khan Nisar Ahmed | Administration of gene-regulatory peptides |
| US20030220258A1 (en) * | 2001-12-21 | 2003-11-27 | Robbert Benner | Treatment of ischemic events |
| US7175679B2 (en) * | 2001-03-29 | 2007-02-13 | Biotempt B.V. | Oligopeptide treatment of NF-κB mediated inflammation |
| EP1138692A1 (en) | 2000-03-29 | 2001-10-04 | Erasmus Universiteit Rotterdam | Fragments of human chorionic gonadotropin (hcg) as immunoregulator |
| US20050227925A1 (en) * | 2004-04-08 | 2005-10-13 | Robbert Benner | Compositions capable of reducing elevated blood urea concentration |
| US8680059B2 (en) | 1998-05-20 | 2014-03-25 | Biotempt B.V. | Oligopeptide acetate and formulations thereof |
| US6287516B1 (en) | 1998-07-10 | 2001-09-11 | Immunocept, L.L.C. | Hemofiltration systems, methods, and devices used to treat inflammatory mediator related disease |
| US20040199099A1 (en) * | 1998-07-10 | 2004-10-07 | Matson James R | Hemofiltration systems, methods and devices used to treat inflammatory mediator related disease |
| CN1324244A (zh) | 1998-10-22 | 2001-11-28 | 伊莱利利公司 | 治疗脓毒症的方法 |
| CA2351067A1 (en) * | 1998-11-13 | 2000-05-25 | Eli Lilly And Company | Method of treating heparin-induced thrombocytopenia |
| BR9915572A (pt) * | 1998-11-23 | 2001-08-14 | Lilly Co Eli | Processo de tratamento de doença de célula falciforme e talassemia |
| WO2001056532A2 (en) * | 2000-02-04 | 2001-08-09 | The Scripps Research Institute | Neuroprotective, antithrombotic and anti-inflammatory uses of activated protein c (apc) |
| US6736972B1 (en) | 2000-03-24 | 2004-05-18 | Immunocept, L.L.C. | Method and system for providing therapeutic agents with hemofiltration for reducing inflammatory mediator related diseases |
| US8535258B2 (en) * | 2000-03-24 | 2013-09-17 | Immunocept, L.L.C. | Hemofiltration methods for treatment of diseases in a mammal |
| US7291122B2 (en) * | 2000-03-24 | 2007-11-06 | Immunocept, L.L.C. | Hemofiltration methods for treatment of diseases in a mammal |
| US7204981B2 (en) * | 2000-03-28 | 2007-04-17 | Eli Lilly And Company | Methods of treating diseases with activated protein C |
| DE60111620T2 (de) * | 2000-03-28 | 2006-05-18 | Eli Lilly And Co., Indianapolis | Aktiviertes protein c zur behandlung von pankreatitis |
| USRE43279E1 (en) | 2000-03-29 | 2012-03-27 | Biotemp B.V. | Compositions capable of reducing elevated blood urea concentration |
| US7576174B2 (en) * | 2000-03-29 | 2009-08-18 | Biotempt B.V. | Compositions capable of reducing elevated blood urea concentration |
| US7358330B2 (en) | 2001-03-29 | 2008-04-15 | Biotempt B.V. | Immunoregulatory compositions |
| US20050037430A1 (en) * | 2000-03-29 | 2005-02-17 | Biotempt B.V. | Methods and uses for protein breakdown products |
| EP1300418A1 (en) | 2001-10-04 | 2003-04-09 | Erasmus Universiteit Rotterdam | Gene regulation by oligopeptides |
| US6787040B2 (en) * | 2000-05-16 | 2004-09-07 | Immunocept, L.L.C. | Method and system for colloid exchange therapy |
| US8597516B2 (en) * | 2000-05-16 | 2013-12-03 | Immunocept, L.L.C. | Methods and systems for colloid exchange therapy |
| US7087578B2 (en) * | 2000-05-24 | 2006-08-08 | Eli Lilly And Company | Formulations and methods for treating hypercoagulable states |
| WO2002024215A2 (en) * | 2000-09-18 | 2002-03-28 | Eli Lilly And Company | Method for using activated protein c for the treatment of coagulation-associated disorders |
| CN100404673C (zh) | 2001-02-19 | 2008-07-23 | 默克专利有限公司 | 鉴定t细胞表位的方法及制备具有降低的免疫原性的分子的用途 |
| US20040198652A1 (en) * | 2001-04-24 | 2004-10-07 | Carter J. Paul | Methods and compositions for preventing and treating septic shock and endotoxemia |
| WO2002100445A1 (en) * | 2001-06-13 | 2002-12-19 | The University Of Sydney | Treatment and composition for wound healing |
| US20030055003A1 (en) * | 2001-07-19 | 2003-03-20 | David Bar-Or | Use of copper chelators to inhibit the inactivation of protein C |
| US20030220259A1 (en) * | 2001-12-21 | 2003-11-27 | Robbert Benner | Treatment of neurological disorders |
| PL372138A1 (en) | 2001-10-15 | 2005-07-11 | Chiron Corporation | Treatment of sepsis by low dose administration of tissue factor pathway inhibitor (tfpi) |
| US20030224995A1 (en) * | 2001-12-21 | 2003-12-04 | Khan Nisar Ahmed | Treatment of burns |
| US20040013661A1 (en) * | 2001-12-21 | 2004-01-22 | Gert Wensvoort | Stratification |
| US20030220257A1 (en) * | 2001-12-21 | 2003-11-27 | Robbert Benner | Treatment of trauma |
| US20030220261A1 (en) * | 2001-12-21 | 2003-11-27 | Khan Nisar Ahmed | Treatment of iatrogenic disease |
| US7501391B2 (en) * | 2001-12-21 | 2009-03-10 | Biotempt B.V. | Treatment of transplant survival |
| US7786084B2 (en) | 2001-12-21 | 2010-08-31 | Biotempt B.V. | Treatment of burns |
| US20080318871A1 (en) * | 2001-12-21 | 2008-12-25 | Khan Nisar A | Treatment of neurological disorders |
| US7560433B2 (en) * | 2001-12-21 | 2009-07-14 | Biotempt B.V. | Treatment of multiple sclerosis (MS) |
| US20030220260A1 (en) * | 2001-12-21 | 2003-11-27 | Khan Nisar Ahmed | Peptide compositions |
| AU2003213146A1 (en) * | 2002-03-08 | 2003-09-22 | Eli Lilly And Company | Activated protein c formulations |
| TW200407335A (en) * | 2002-07-22 | 2004-05-16 | Chugai Pharmaceutical Co Ltd | Non-neutralizing antibody to inhibit the inactivation of activated protein C |
| WO2004014315A2 (en) * | 2002-08-13 | 2004-02-19 | Arbios Systems, Inc. | Selective plasma exchange therapy |
| WO2004056309A2 (en) | 2002-12-05 | 2004-07-08 | Socratech L.L.C. | Neuroprotective activity of activated protein c is independent of its anticoagulant activity |
| WO2004065418A1 (ja) * | 2003-01-20 | 2004-08-05 | Chugai Seiyaku Kabushiki Kaisha | 抗pci中和抗体 |
| US20070142272A1 (en) * | 2003-01-24 | 2007-06-21 | Zlokovic Berislav V | Neuroprotective activity of activated protein c independent of its anticoagulant activity |
| US7517529B2 (en) * | 2003-04-08 | 2009-04-14 | Biotempt B.V. | Treatment of type I diabetes |
| AU2004241069B2 (en) | 2003-05-15 | 2010-09-09 | Genentech, Inc. | Methods and compositions for the prevention and treatment of sepsis |
| US9192657B2 (en) * | 2003-07-08 | 2015-11-24 | The Scripps Research Institute | Activated protein C variants with normal cytoprotective activity but reduced anticoagulant activity |
| KR101284884B1 (ko) | 2003-07-08 | 2013-07-10 | 더 스크립스 리서치 인스티튜트 | 정상의 세포보호 활성 및 저하된 항응고 활성을 지닌활성화 단백질 ｃ 변이체 |
| US20090227669A1 (en) * | 2004-01-23 | 2009-09-10 | The University Of Toledo | Compositions and Methods for Perioperative Bladder Instillation |
| RU2006136267A (ru) * | 2004-03-17 | 2008-04-27 | Чирон Корпорейшн (Us) | Лечение тяжелой внебольничной пневмонии путем введения ингибитора пути тканевого фактора (tfpi) |
| EP1745145A4 (en) * | 2004-05-11 | 2008-03-26 | Heptest Lab Inc | COMPOSITIONS, KIT AND METHOD IN ONE STEP FOR MONITORING COMPOUNDS HAVING XA AND / OR ANTIFACTOR IIA ANTIFACTOR ACTIVITIES |
| WO2006014839A2 (en) * | 2004-07-23 | 2006-02-09 | The University Of Rochester | Activated protein c inhibits undesirable effects of plasminogen activator in the brain |
| WO2006124770A2 (en) * | 2005-05-13 | 2006-11-23 | The Feinstein Institute For Medical Research | Treatment of sepsis and inflammation with alpha2a adrenergic antagonists |
| CN101262879B (zh) * | 2005-06-24 | 2013-04-10 | 德拉格雷丘尔公司 | 在影响呼吸道的炎症病状中气道施用活化的蛋白c |
| JP4846799B2 (ja) | 2005-07-05 | 2011-12-28 | バイオテンプト ベー．フェー． | 腫瘍の治療 |
| EP1864692A1 (en) | 2006-06-07 | 2007-12-12 | Biotempt B.V. | Use of peptides for the control of radiation injury |
| US7785857B2 (en) * | 2006-08-31 | 2010-08-31 | Saint Louis University | Protein C variant |
| GR1005700B (el) * | 2006-09-01 | 2007-10-22 | (40%) ����� �������� | Τροπος αντιμετωπισης της 1ης φασης του εγκαυματοσσε μη σηπτικους ασθενεις με συνεχη ενδοφλεβια χορηγηση ενεργοποιημενης πρωτεινης-c για 48 ωρες με στοχο τη μειωση της τελικης εγκαυματικης βλαβης καιαυξηση της ταχυτητας επουλωσης κατα τα πρωτα επτα μετεγκαυματικα 24ωρα |
| US20100284997A1 (en) * | 2006-10-31 | 2010-11-11 | Griffin John H | Dosing regimen of activated protein c and variants having reduced anticoagulant activity |
| RU2445365C1 (ru) * | 2010-11-03 | 2012-03-20 | Общество с ограниченной ответственностью "Инновационный Центр "Новые Технологии и Материалы" (ООО "ИЦ Новтехмат") | Штамм гибридных культивируемых клеток mus musculus - продуцент моноклональных антител, специфичных к протеину с человека (варианты) |
| RU2490722C1 (ru) * | 2012-04-24 | 2013-08-20 | Федеральное государственное бюджетное учреждение науки Институт химической биологии и фундаментальной медицины Сибирского отделения Российской академии наук (ИХБФМ СО РАН) | Способ восстановления кровотока в регионе тромбированной вены в эксперименте |
| US20150150954A1 (en) | 2012-07-04 | 2015-06-04 | The University Of Sydney | Treatment of inflammatory skin disorders |
| DK3137102T3 (da) | 2014-04-16 | 2021-10-11 | Zz Biotech Llc | Apc til anvendelse til behandling af unormal kutan ardannelse |
| EP3807427A1 (en) | 2018-06-15 | 2021-04-21 | AB Sandvik Materials Technology | A duplex stainless steel strip and method for producing thereof |
Family Cites Families (17)
| 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 |
| US5516650A (en) * | 1985-06-27 | 1996-05-14 | Zymogenetics, Inc. | Production of activated protein C |
| US5084274A (en) * | 1987-11-17 | 1992-01-28 | Scripps Clinic And Research Foundation | Inhibition of arterial thrombotic occlusion or thromboembolism |
| US4992373A (en) * | 1987-12-04 | 1991-02-12 | Eli Lilly And Company | Vectors and compounds for direct expression of activated human protein C |
| US5009889A (en) * | 1987-12-31 | 1991-04-23 | Oklahoma Medical Research Foundation | Treatment of dysfunctional vascular endothelium using activated protein C |
| GB8819607D0 (en) * | 1988-08-17 | 1988-09-21 | Wellcome Found | Novel combination |
| US4981952A (en) * | 1988-10-04 | 1991-01-01 | Eli Lilly And Company | Method for the purification of vitamin K-dependent proteins |
| US5254532A (en) * | 1989-06-26 | 1993-10-19 | Immuno Aktiengesellschaft Fur Chemisch-Medizinische Produkte | Preparation for treating and preventing thromboses and thromboembolic complications, use of such a preparation and a method of producing the same |
| IL97312A (en) * | 1990-02-23 | 1999-01-26 | Lilly Co Eli | A method of generating a polypeptide in an eukaryotic vector AND recombinant surrogate cell containing an enhanced transcriptional control unit based on the primary late adenovirus coefficient |
| AT402262B (de) * | 1991-06-20 | 1997-03-25 | Immuno Ag | Arzneimittel enthaltend aktiviertes protein c |
| MY110664A (en) * | 1992-05-21 | 1999-01-30 | Lilly Co Eli | Protein c derivatives |
| JP3434326B2 (ja) * | 1992-08-25 | 2003-08-04 | 財団法人化学及血清療法研究所 | 成人呼吸窮迫症候群（ａｒｄｓ）予防、治療剤 |
| JP2825739B2 (ja) * | 1993-09-20 | 1998-11-18 | 帝人株式会社 | 急性肝不全治療剤 |
| JP3802104B2 (ja) * | 1995-05-31 | 2006-07-26 | 財団法人化学及血清療法研究所 | 脊髄損傷に伴う神経障害の予防・治療剤 |
| WO1997020043A1 (en) * | 1995-11-30 | 1997-06-05 | Zymogenetics, Inc. | Protein c production in transgenic animals |
| HU224826B1 (en) * | 1997-04-28 | 2006-02-28 | Lilly Co Eli | Activated protein c formulations |
| HUP0001237A3 (en) * | 1997-10-20 | 2002-01-28 | Lilly Co Eli | Methods for treating vascular disorders |
-
1998
- 1998-03-24 HU HU0001237A patent/HUP0001237A3/hu unknown
- 1998-09-28 US US09/161,900 patent/US6037322A/en not_active Expired - Lifetime
- 1998-10-14 CA CA002306983A patent/CA2306983A1/en not_active Abandoned
- 1998-10-14 TW TW087117061A patent/TWI225404B/zh not_active IP Right Cessation
- 1998-10-14 KR KR1020007004170A patent/KR100798174B1/ko not_active IP Right Cessation
- 1998-10-14 HU HU0100025A patent/HU224901B1/hu not_active IP Right Cessation
- 1998-10-14 CN CN98810307A patent/CN1276726A/zh active Pending
- 1998-10-14 UA UA2000042259A patent/UA72194C2/uk unknown
- 1998-10-14 ID IDW20000683A patent/ID24901A/id unknown
- 1998-10-14 JP JP2000516690A patent/JP3805981B2/ja not_active Expired - Fee Related
- 1998-10-14 EA EA200000445A patent/EA002496B1/ru not_active IP Right Cessation
- 1998-10-14 WO PCT/US1998/021723 patent/WO1999020293A1/en not_active Application Discontinuation
- 1998-10-14 IL IL13571298A patent/IL135712A0/xx unknown
- 1998-10-14 AU AU98040/98A patent/AU748417B2/en not_active Ceased
- 1998-10-14 TR TR2000/01059T patent/TR200001059T2/xx unknown
- 1998-10-14 ZA ZA9809385A patent/ZA989385B/xx unknown
- 1998-10-14 BR BR9812965-1A patent/BR9812965A/pt not_active Application Discontinuation
- 1998-10-14 NZ NZ504026A patent/NZ504026A/xx not_active IP Right Cessation
- 1998-10-14 PL PL340096A patent/PL200515B1/pl not_active IP Right Cessation
- 1998-10-15 EP EP98308413A patent/EP0913156B1/en not_active Expired - Lifetime
- 1998-10-15 EP EP04005955A patent/EP1449537A3/en not_active Withdrawn
- 1998-10-15 PT PT98308413T patent/PT913156E/pt unknown
- 1998-10-15 DE DE69829721T patent/DE69829721T2/de not_active Expired - Lifetime
- 1998-10-15 ES ES98308413T patent/ES2239382T3/es not_active Expired - Lifetime
- 1998-10-15 MY MYPI98004703A patent/MY117655A/en unknown
- 1998-10-15 DK DK98308413T patent/DK0913156T3/da active
- 1998-10-15 AT AT98308413T patent/ATE292979T1/de active
- 1998-10-15 SI SI9830773T patent/SI0913156T1/xx unknown
- 1998-10-16 US US09/174,507 patent/US6008199A/en not_active Expired - Lifetime
-
1999
- 1999-10-08 US US09/415,761 patent/US6268344B1/en not_active Expired - Fee Related
- 1999-10-08 US US09/415,876 patent/US6156734A/en not_active Expired - Lifetime
- 1999-11-02 HK HK99104976A patent/HK1020529A1/xx not_active IP Right Cessation
- 1999-12-16 US US09/465,076 patent/US6268337B1/en not_active Expired - Fee Related
-
2000
- 2000-04-17 NO NO20002005A patent/NO20002005L/no not_active Application Discontinuation
- 2000-04-17 IL IL135712A patent/IL135712A/en not_active IP Right Cessation
- 2000-05-10 US US09/568,146 patent/US6489296B1/en not_active Expired - Fee Related
-
2001
- 2001-06-08 US US09/877,759 patent/US6426071B2/en not_active Expired - Fee Related
-
2004
- 2004-11-11 JP JP2004327938A patent/JP2005097313A/ja active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| UA72194C2 (en) | Method of treatment for patients with acquired hypercoagulable state or acquired protein c deficiency | |
| US20010006806A1 (en) | Methods for treating sepsis | |
| US7087578B2 (en) | Formulations and methods for treating hypercoagulable states | |
| EP0872245B1 (en) | Methods for treating vascular disorders with activated Protein C | |
| US6743426B2 (en) | Method of treating heparin-induced thrombocytopenia | |
| AU1723200A (en) | Method of treating sickle cell disease and thalassemia | |
| EP1137432B1 (en) | Use of protein c for the treatment of thrombocytopenic purpura and hemolytic uremic syndrome | |
| CZ20001392A3 (cs) | kané nedostatečnosti proteinu C | |
| MXPA00003805A (en) | Methods for treating hypercoagulable states or acquired protein c deficiency |