CA2351470A1 - Method of treating viral hemorrhagic fever - Google Patents
Method of treating viral hemorrhagic fever Download PDFInfo
- Publication number
- CA2351470A1 CA2351470A1 CA002351470A CA2351470A CA2351470A1 CA 2351470 A1 CA2351470 A1 CA 2351470A1 CA 002351470 A CA002351470 A CA 002351470A CA 2351470 A CA2351470 A CA 2351470A CA 2351470 A1 CA2351470 A1 CA 2351470A1
- Authority
- CA
- Canada
- Prior art keywords
- protein
- hemorrhagic fever
- activated protein
- administered
- viral hemorrhagic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 208000028227 Viral hemorrhagic fever Diseases 0.000 title claims abstract description 29
- 238000000034 method Methods 0.000 title claims abstract description 21
- 101800004937 Protein C Proteins 0.000 claims abstract description 82
- 101800001700 Saposin-D Proteins 0.000 claims abstract description 80
- 229960000856 protein c Drugs 0.000 claims abstract description 80
- 102000017975 Protein C Human genes 0.000 claims description 81
- 101500025568 Homo sapiens Saposin-D Proteins 0.000 claims description 16
- 229940100689 human protein c Drugs 0.000 claims description 16
- 238000001802 infusion Methods 0.000 claims description 10
- 102000010911 Enzyme Precursors Human genes 0.000 claims description 7
- 108010062466 Enzyme Precursors Proteins 0.000 claims description 7
- 238000002347 injection Methods 0.000 claims description 6
- 239000007924 injection Substances 0.000 claims description 6
- 230000036470 plasma concentration Effects 0.000 claims description 3
- 239000003146 anticoagulant agent Substances 0.000 abstract description 8
- 230000000694 effects Effects 0.000 abstract description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
- 238000002560 therapeutic procedure Methods 0.000 abstract description 4
- 206010062713 Haemorrhagic diathesis Diseases 0.000 abstract description 2
- 229940127090 anticoagulant agent Drugs 0.000 abstract description 2
- 208000035475 disorder Diseases 0.000 abstract description 2
- 208000031169 hemorrhagic disease Diseases 0.000 abstract description 2
- 230000001988 toxicity Effects 0.000 abstract description 2
- 231100000419 toxicity Toxicity 0.000 abstract description 2
- 102100036546 Salivary acidic proline-rich phosphoprotein 1/2 Human genes 0.000 abstract 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 32
- 239000011780 sodium chloride Substances 0.000 description 16
- 239000007983 Tris buffer Substances 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 12
- 108090000190 Thrombin Proteins 0.000 description 10
- 108090000623 proteins and genes Proteins 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 229960004072 thrombin Drugs 0.000 description 10
- 102000004169 proteins and genes Human genes 0.000 description 9
- 239000000872 buffer Substances 0.000 description 7
- 241000700605 Viruses Species 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 229940127219 anticoagulant drug Drugs 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 230000000019 pro-fibrinolytic effect Effects 0.000 description 6
- 239000011347 resin Substances 0.000 description 6
- 229920005989 resin Polymers 0.000 description 6
- 206010053567 Coagulopathies Diseases 0.000 description 5
- 208000032843 Hemorrhage Diseases 0.000 description 5
- 230000003110 anti-inflammatory effect Effects 0.000 description 5
- 239000000463 material 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
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 4
- 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 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 230000003024 amidolytic effect Effects 0.000 description 4
- 239000004067 bulking agent Substances 0.000 description 4
- 239000001110 calcium chloride Substances 0.000 description 4
- 235000011148 calcium chloride Nutrition 0.000 description 4
- 229910001628 calcium chloride Inorganic materials 0.000 description 4
- 230000035602 clotting Effects 0.000 description 4
- 208000009190 disseminated intravascular coagulation Diseases 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 208000000307 Crimean Hemorrhagic Fever Diseases 0.000 description 3
- 201000003075 Crimean-Congo hemorrhagic fever Diseases 0.000 description 3
- 206010012310 Dengue fever Diseases 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
- 201000011001 Ebola Hemorrhagic Fever Diseases 0.000 description 3
- 206010061192 Haemorrhagic fever Diseases 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 208000000705 Rift Valley Fever Diseases 0.000 description 3
- 208000003152 Yellow Fever Diseases 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
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000006167 equilibration buffer Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 239000012931 lyophilized formulation Substances 0.000 description 3
- 230000014508 negative regulation of coagulation Effects 0.000 description 3
- 239000000902 placebo Substances 0.000 description 3
- 229940068196 placebo Drugs 0.000 description 3
- 239000001509 sodium citrate Substances 0.000 description 3
- 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 3
- 230000003319 supportive effect Effects 0.000 description 3
- 206010043554 thrombocytopenia Diseases 0.000 description 3
- 230000003612 virological effect Effects 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
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 241000712892 Arenaviridae Species 0.000 description 2
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 2
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 208000001490 Dengue Diseases 0.000 description 2
- 241000711950 Filoviridae Species 0.000 description 2
- 241000710781 Flaviviridae Species 0.000 description 2
- 208000032982 Hemorrhagic Fever with Renal Syndrome Diseases 0.000 description 2
- 208000003140 Kyasanur forest disease Diseases 0.000 description 2
- 206010023927 Lassa fever Diseases 0.000 description 2
- 208000011448 Omsk hemorrhagic fever Diseases 0.000 description 2
- 241000150350 Peribunyaviridae Species 0.000 description 2
- 201000005660 Protein C Deficiency 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
- 108010000499 Thromboplastin Proteins 0.000 description 2
- 102000002262 Thromboplastin Human genes 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000010100 anticoagulation Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003114 blood coagulation factor Substances 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000015271 coagulation Effects 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 208000025729 dengue disease Diseases 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000013024 dilution buffer Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 230000003511 endothelial effect Effects 0.000 description 2
- 244000309457 enveloped RNA virus Species 0.000 description 2
- 230000000058 esterolytic effect Effects 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 230000023597 hemostasis Effects 0.000 description 2
- 208000013746 hereditary thrombophilia due to congenital protein C deficiency Diseases 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 201000005665 thrombophilia Diseases 0.000 description 2
- 230000008728 vascular permeability Effects 0.000 description 2
- 238000005406 washing Methods 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
- 241000283690 Bos taurus Species 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 208000030820 Ebola disease Diseases 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 208000000932 Marburg Virus Disease Diseases 0.000 description 1
- 201000011013 Marburg hemorrhagic fever Diseases 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 241000699673 Mesocricetus auratus Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 208000009714 Severe Dengue Diseases 0.000 description 1
- 102000012607 Thrombomodulin Human genes 0.000 description 1
- 108010079274 Thrombomodulin Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 229930003448 Vitamin K Natural products 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 150000001450 anions Chemical group 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 208000015294 blood coagulation disease Diseases 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 208000035850 clinical syndrome Diseases 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000012531 culture fluid Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 201000002950 dengue hemorrhagic fever Diseases 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 208000027700 hepatic dysfunction Diseases 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000005210 lymphoid organ Anatomy 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000007726 management method 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
- 230000017074 necrotic cell death Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 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
- 230000008288 physiological mechanism Effects 0.000 description 1
- 230000031915 positive regulation of coagulation Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 230000009076 regulation of hemostasis Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 239000004017 serum-free culture medium Substances 0.000 description 1
- -1 sodium chloride Chemical class 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 208000014173 thrombophilia due to thrombin defect Diseases 0.000 description 1
- 230000035921 thrombopoiesis Effects 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 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
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 229940046010 vitamin k Drugs 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P31/12—Antivirals
-
- 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
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Virology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10915398P | 1998-11-20 | 1998-11-20 | |
| US60/109,153 | 1998-11-20 | ||
| PCT/US1999/027074 WO2000030677A1 (en) | 1998-11-20 | 1999-11-15 | Method of treating viral hemorrhagic fever |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2351470A1 true CA2351470A1 (en) | 2000-06-02 |
Family
ID=22326085
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002351470A Abandoned CA2351470A1 (en) | 1998-11-20 | 1999-11-15 | Method of treating viral hemorrhagic fever |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US6270764B1 (https=) |
| EP (1) | EP1131091B1 (https=) |
| JP (1) | JP2002530353A (https=) |
| CN (1) | CN1326356A (https=) |
| AT (1) | ATE235915T1 (https=) |
| AU (1) | AU2149800A (https=) |
| BR (1) | BR9915460A (https=) |
| CA (1) | CA2351470A1 (https=) |
| DE (1) | DE69906568T2 (https=) |
| ES (1) | ES2195655T3 (https=) |
| IL (1) | IL142220A0 (https=) |
| WO (1) | WO2000030677A1 (https=) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2351470A1 (en) * | 1998-11-20 | 2000-06-02 | Charles Jack Fisher | Method of treating viral hemorrhagic fever |
| 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 |
| EA200400548A1 (ru) | 2001-10-15 | 2005-06-30 | Чирон Корпорейшн | Лечение тяжёлой пневмонии путём введения ингибитора пути тканевого фактора (tfpi) |
| US7132398B2 (en) | 2003-05-06 | 2006-11-07 | Dendreon Corporation | Method of treatment of hemorrhagic disease using a factor VIIa/tissue factor inhibitor |
| EP1729791A2 (en) * | 2004-03-17 | 2006-12-13 | Chiron Corporation | Treatment of severe community-acquired pneumonia by admistration of tissue factor pathway inhibitor (tfpi) |
| WO2007092607A2 (en) * | 2006-02-09 | 2007-08-16 | Genetech, Inc. | Treatment of hemorrhagic viral infections using a tissue factor inhibitor |
| RU2379034C1 (ru) * | 2008-11-17 | 2010-01-20 | Государственное образовательное учреждение высшего профессионального образования "Мордовский государственный университет им. Н.П. Огарева" | Способ лечения геморрагической лихорадки с почечным синдромом |
| EP3551198B1 (en) * | 2016-12-08 | 2022-02-02 | Cellphire Inc. | Compositions and methods for treatment of loss of fluids leading to hypotension and/or hypovolemia |
| CA3121200A1 (en) | 2018-11-30 | 2020-06-04 | Cellphire, Inc. | Platelets as delivery agents |
| WO2020112963A1 (en) | 2018-11-30 | 2020-06-04 | Cellphire, Inc. | Platelets as delivery agents |
| IL322149A (en) | 2019-05-03 | 2025-09-01 | Cellphire Inc | Materials and methods for manufacturing blood products |
| CN114450066A (zh) | 2019-08-16 | 2022-05-06 | 塞尔菲乐有限公司 | 作为抗血小板剂逆转剂的血栓小体 |
| CA3170196A1 (en) | 2020-02-04 | 2021-08-12 | Cellphire, Inc. | Anti-fibrinolytic loaded platelets |
| TW202245814A (zh) | 2021-02-17 | 2022-12-01 | 美商賽菲爾公司 | 用於治療抗血小板誘導的凝血病之凍乾血小板衍生物組成物 |
Family Cites Families (13)
| 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 |
| US5550036A (en) | 1986-04-09 | 1996-08-27 | Eli Lilly And Company | Method for co-amplification of human protein C genes in human cells |
| US4992373A (en) | 1987-12-04 | 1991-02-12 | Eli Lilly And Company | Vectors and compounds for direct expression of activated human protein C |
| US4981952A (en) | 1988-10-04 | 1991-01-01 | Eli Lilly And Company | Method for the purification of vitamin K-dependent proteins |
| 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 |
| US5506134A (en) * | 1990-10-22 | 1996-04-09 | Corvas International, Inc. | Hypridoma and monoclonal antibody which inhibits blood coagulation tissue factor/factor VIIa complex |
| 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 |
| WO1997020043A1 (en) | 1995-11-30 | 1997-06-05 | Zymogenetics, Inc. | Protein c production in transgenic animals |
| CZ298429B6 (cs) * | 1997-04-28 | 2007-10-03 | Eli Lilly And Company | Stabilní lyofilizovaný prostredek |
| CA2351470A1 (en) * | 1998-11-20 | 2000-06-02 | Charles Jack Fisher | Method of treating viral hemorrhagic fever |
| EP1090130A1 (en) * | 1999-04-30 | 2001-04-11 | Eli Lilly And Company | Protein c derivatives |
-
1999
- 1999-11-15 CA CA002351470A patent/CA2351470A1/en not_active Abandoned
- 1999-11-15 ES ES99965808T patent/ES2195655T3/es not_active Expired - Lifetime
- 1999-11-15 WO PCT/US1999/027074 patent/WO2000030677A1/en not_active Ceased
- 1999-11-15 BR BR9915460-9A patent/BR9915460A/pt not_active Application Discontinuation
- 1999-11-15 CN CN99813313A patent/CN1326356A/zh active Pending
- 1999-11-15 AU AU21498/00A patent/AU2149800A/en not_active Abandoned
- 1999-11-15 AT AT99965808T patent/ATE235915T1/de not_active IP Right Cessation
- 1999-11-15 DE DE69906568T patent/DE69906568T2/de not_active Expired - Lifetime
- 1999-11-15 JP JP2000583560A patent/JP2002530353A/ja active Pending
- 1999-11-15 IL IL14222099A patent/IL142220A0/xx unknown
- 1999-11-15 EP EP99965808A patent/EP1131091B1/en not_active Expired - Lifetime
- 1999-11-19 US US09/444,479 patent/US6270764B1/en not_active Expired - Fee Related
-
2001
- 2001-04-25 US US09/842,337 patent/US6767539B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1326356A (zh) | 2001-12-12 |
| US20010028880A1 (en) | 2001-10-11 |
| US6270764B1 (en) | 2001-08-07 |
| ES2195655T3 (es) | 2003-12-01 |
| US6767539B2 (en) | 2004-07-27 |
| EP1131091A1 (en) | 2001-09-12 |
| DE69906568T2 (de) | 2004-02-12 |
| AU2149800A (en) | 2000-06-13 |
| DE69906568D1 (de) | 2003-05-08 |
| EP1131091B1 (en) | 2003-04-02 |
| ATE235915T1 (de) | 2003-04-15 |
| WO2000030677A1 (en) | 2000-06-02 |
| JP2002530353A (ja) | 2002-09-17 |
| BR9915460A (pt) | 2001-07-17 |
| IL142220A0 (en) | 2002-03-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU741983B2 (en) | Methods for treating thrombotic disorders | |
| WO1999020293A1 (en) | Methods for treating hypercoagulable states or acquired protein c deficiency | |
| WO1998048818A1 (en) | Activated protein c formulations | |
| US6270764B1 (en) | Method of treating viral hemorrhagic fever with activated protein C | |
| EP1133314B1 (en) | Protein c for the treatment of sickle cell disease and thalassemia | |
| EP1128842B1 (en) | Use of human protein c for the manufacture of a medicament for treating heparin-induced thrombocytopenia | |
| US20050143283A1 (en) | Activated protein c formulations | |
| EP1137432B1 (en) | Use of protein c for the treatment of thrombocytopenic purpura and hemolytic uremic syndrome | |
| MXPA01005038A (en) | Method of treating viral hemorrhagic fever | |
| MXPA01005124A (en) | Method of treating sickle cell disease and thalassemia | |
| MXPA01005689A (en) | Method of treating thrombocytopenic purpura and hemolytic uremic syndrome | |
| HK1020529B (en) | Use of activated protein c for the treatment of hypercoagulable states associated with sepsis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |