DE69132352T2 - Protein-antagonisten der blut-koagulation und ihre verwendung - Google Patents
Protein-antagonisten der blut-koagulation und ihre verwendungInfo
- Publication number
- DE69132352T2 DE69132352T2 DE69132352T DE69132352T DE69132352T2 DE 69132352 T2 DE69132352 T2 DE 69132352T2 DE 69132352 T DE69132352 T DE 69132352T DE 69132352 T DE69132352 T DE 69132352T DE 69132352 T2 DE69132352 T2 DE 69132352T2
- Authority
- DE
- Germany
- Prior art keywords
- factor
- viia
- human factor
- monoclonal antibody
- factor viia
- 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.)
- Expired - Fee Related
Links
- 229940076372 protein antagonist Drugs 0.000 title abstract 2
- 230000023555 blood coagulation Effects 0.000 title description 7
- 229940012414 factor viia Drugs 0.000 claims abstract description 101
- 108010054265 Factor VIIa Proteins 0.000 claims abstract description 97
- 102000002262 Thromboplastin Human genes 0.000 claims abstract description 74
- 108010000499 Thromboplastin Proteins 0.000 claims abstract description 74
- 238000004519 manufacturing process Methods 0.000 claims abstract description 9
- 229940012413 factor vii Drugs 0.000 claims description 62
- 102100023804 Coagulation factor VII Human genes 0.000 claims description 61
- 108010023321 Factor VII Proteins 0.000 claims description 61
- 210000004408 hybridoma Anatomy 0.000 claims description 32
- 239000012634 fragment Substances 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 27
- 208000007536 Thrombosis Diseases 0.000 claims description 25
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 22
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 17
- 238000002360 preparation method Methods 0.000 claims description 15
- 230000003053 immunization Effects 0.000 claims description 13
- 241001465754 Metazoa Species 0.000 claims description 12
- 206010040070 Septic Shock Diseases 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 12
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 11
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 11
- 239000005557 antagonist Substances 0.000 claims description 11
- 230000036303 septic shock Effects 0.000 claims description 11
- 229940099816 human factor vii Drugs 0.000 claims description 9
- 208000009190 disseminated intravascular coagulation Diseases 0.000 claims description 8
- 230000001154 acute effect Effects 0.000 claims description 6
- 150000001413 amino acids Chemical class 0.000 claims description 5
- 206010011091 Coronary artery thrombosis Diseases 0.000 claims description 4
- 206010047249 Venous thrombosis Diseases 0.000 claims description 4
- 208000002528 coronary thrombosis Diseases 0.000 claims description 4
- 206010051055 Deep vein thrombosis Diseases 0.000 claims description 3
- 230000002163 immunogen Effects 0.000 claims description 3
- 229920001184 polypeptide Polymers 0.000 claims description 3
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 claims description 2
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 claims description 2
- 206010052779 Transplant rejections Diseases 0.000 claims description 2
- 210000000056 organ Anatomy 0.000 claims description 2
- 230000003248 secreting effect Effects 0.000 claims description 2
- 230000003042 antagnostic effect Effects 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 230000015271 coagulation Effects 0.000 abstract description 33
- 238000005345 coagulation Methods 0.000 abstract description 33
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 9
- 201000010099 disease Diseases 0.000 abstract description 8
- 230000003472 neutralizing effect Effects 0.000 abstract description 8
- 238000011282 treatment Methods 0.000 abstract description 7
- 239000012472 biological sample Substances 0.000 abstract description 5
- 230000001732 thrombotic effect Effects 0.000 abstract description 5
- 230000002265 prevention Effects 0.000 abstract description 4
- 238000000746 purification Methods 0.000 abstract description 3
- 238000002955 isolation Methods 0.000 abstract description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 36
- 229960002897 heparin Drugs 0.000 description 36
- 229920000669 heparin Polymers 0.000 description 36
- 230000000694 effects Effects 0.000 description 33
- 230000004913 activation Effects 0.000 description 30
- 210000001772 blood platelet Anatomy 0.000 description 24
- 239000003146 anticoagulant agent Substances 0.000 description 23
- 210000004027 cell Anatomy 0.000 description 21
- 108090000190 Thrombin Proteins 0.000 description 20
- 108010014173 Factor X Proteins 0.000 description 19
- 239000000427 antigen Substances 0.000 description 19
- 108091007433 antigens Proteins 0.000 description 19
- 102000036639 antigens Human genes 0.000 description 19
- 238000003556 assay Methods 0.000 description 18
- 229960004072 thrombin Drugs 0.000 description 18
- 239000004365 Protease Substances 0.000 description 15
- 230000037361 pathway Effects 0.000 description 14
- 108010074860 Factor Xa Proteins 0.000 description 12
- 102000035195 Peptidases Human genes 0.000 description 12
- 108091005804 Peptidases Proteins 0.000 description 12
- 108010094028 Prothrombin Proteins 0.000 description 12
- 102100027378 Prothrombin Human genes 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 12
- 102000004169 proteins and genes Human genes 0.000 description 12
- 229940039716 prothrombin Drugs 0.000 description 12
- 102000009123 Fibrin Human genes 0.000 description 11
- 108010073385 Fibrin Proteins 0.000 description 11
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 11
- 229950003499 fibrin Drugs 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 11
- 238000012216 screening Methods 0.000 description 11
- 238000002560 therapeutic procedure Methods 0.000 description 11
- 229940127219 anticoagulant drug Drugs 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 9
- 239000003114 blood coagulation factor Substances 0.000 description 9
- 230000003197 catalytic effect Effects 0.000 description 9
- 238000002649 immunization Methods 0.000 description 9
- 102000004411 Antithrombin III Human genes 0.000 description 8
- 108090000935 Antithrombin III Proteins 0.000 description 8
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 8
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 8
- 208000032843 Hemorrhage Diseases 0.000 description 8
- 108010000487 High-Molecular-Weight Kininogen Proteins 0.000 description 8
- 102100035792 Kininogen-1 Human genes 0.000 description 8
- 229960005348 antithrombin iii Drugs 0.000 description 8
- 230000023597 hemostasis Effects 0.000 description 8
- 235000019419 proteases Nutrition 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 7
- 239000012228 culture supernatant Substances 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 230000007246 mechanism Effects 0.000 description 7
- 102000010911 Enzyme Precursors Human genes 0.000 description 6
- 108010062466 Enzyme Precursors Proteins 0.000 description 6
- 108010049003 Fibrinogen Proteins 0.000 description 6
- 102000008946 Fibrinogen Human genes 0.000 description 6
- 108090000113 Plasma Kallikrein Proteins 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 229940012952 fibrinogen Drugs 0.000 description 6
- 150000003904 phospholipids Chemical class 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 206010043554 thrombocytopenia Diseases 0.000 description 6
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 5
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 241000282577 Pan troglodytes Species 0.000 description 5
- 230000004927 fusion Effects 0.000 description 5
- 230000002439 hemostatic effect Effects 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 230000002947 procoagulating effect Effects 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 102100022641 Coagulation factor IX Human genes 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 4
- 108010076282 Factor IX Proteins 0.000 description 4
- 108010054218 Factor VIII Proteins 0.000 description 4
- 102000001690 Factor VIII Human genes 0.000 description 4
- 108090000526 Papain Proteins 0.000 description 4
- 101800004937 Protein C Proteins 0.000 description 4
- 102000017975 Protein C Human genes 0.000 description 4
- 101800001700 Saposin-D Proteins 0.000 description 4
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- 238000004220 aggregation Methods 0.000 description 4
- 208000034158 bleeding Diseases 0.000 description 4
- 231100000319 bleeding Toxicity 0.000 description 4
- 230000000740 bleeding effect Effects 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 230000001112 coagulating effect Effects 0.000 description 4
- 239000002158 endotoxin Substances 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 229960000301 factor viii Drugs 0.000 description 4
- 239000003527 fibrinolytic agent Substances 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 229940055729 papain Drugs 0.000 description 4
- 235000019834 papain Nutrition 0.000 description 4
- 229960000856 protein c Drugs 0.000 description 4
- 230000002797 proteolythic effect Effects 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 4
- 241001146702 Candidatus Entotheonella factor Species 0.000 description 3
- 206010053567 Coagulopathies Diseases 0.000 description 3
- 108010048049 Factor IXa Proteins 0.000 description 3
- 108010014172 Factor V Proteins 0.000 description 3
- 108010080865 Factor XII Proteins 0.000 description 3
- 102000000429 Factor XII Human genes 0.000 description 3
- 108010071241 Factor XIIa Proteins 0.000 description 3
- 102000001399 Kallikrein Human genes 0.000 description 3
- 108060005987 Kallikrein Proteins 0.000 description 3
- 241000282579 Pan Species 0.000 description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 description 3
- 102100034869 Plasma kallikrein Human genes 0.000 description 3
- 102000012479 Serine Proteases Human genes 0.000 description 3
- 108010022999 Serine Proteases Proteins 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000002785 anti-thrombosis Effects 0.000 description 3
- 230000010100 anticoagulation Effects 0.000 description 3
- 229940127218 antiplatelet drug Drugs 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000035602 clotting Effects 0.000 description 3
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 229960004222 factor ix Drugs 0.000 description 3
- 238000013467 fragmentation Methods 0.000 description 3
- 238000006062 fragmentation reaction Methods 0.000 description 3
- 210000004754 hybrid cell Anatomy 0.000 description 3
- 238000003018 immunoassay Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 230000001665 lethal effect Effects 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 201000000050 myeloid neoplasm Diseases 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 230000014508 negative regulation of coagulation Effects 0.000 description 3
- 229940127216 oral anticoagulant drug Drugs 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 210000004989 spleen cell Anatomy 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000001225 therapeutic 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
- VXIXUWQIVKSKSA-UHFFFAOYSA-N 4-hydroxycoumarin Chemical class C1=CC=CC2=C1OC(=O)C=C2O VXIXUWQIVKSKSA-UHFFFAOYSA-N 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 208000005189 Embolism Diseases 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 108010074864 Factor XI Proteins 0.000 description 2
- 108010071289 Factor XIII Proteins 0.000 description 2
- 206010018852 Haematoma Diseases 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 241000282520 Papio Species 0.000 description 2
- 241001504519 Papio ursinus Species 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 2
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000003024 amidolytic effect Effects 0.000 description 2
- 229960004676 antithrombotic agent Drugs 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000000601 blood cell Anatomy 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 235000011148 calcium chloride Nutrition 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000003593 chromogenic compound Substances 0.000 description 2
- 239000000701 coagulant Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 208000001780 epistaxis Diseases 0.000 description 2
- 230000006624 extrinsic pathway Effects 0.000 description 2
- 230000006251 gamma-carboxylation Effects 0.000 description 2
- 210000003630 histaminocyte Anatomy 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000006623 intrinsic pathway Effects 0.000 description 2
- 229960003299 ketamine Drugs 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 229960005202 streptokinase Drugs 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229960000103 thrombolytic agent Drugs 0.000 description 2
- 230000002537 thrombolytic effect Effects 0.000 description 2
- 229960000187 tissue plasminogen activator Drugs 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 229960005080 warfarin Drugs 0.000 description 2
- 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 2
- HMUBCRODSGHUNN-WKBBXPMVSA-N (3R,4R,5S,6R)-3-amino-6-(hydroxymethyl)oxane-2,4,5-triol (2S,3S,4S,5R)-2,3,4,5-tetrahydroxy-6-oxohexanoic acid Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O.O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O HMUBCRODSGHUNN-WKBBXPMVSA-N 0.000 description 1
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
- 206010000242 Abortion threatened Diseases 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 101001023095 Anemonia sulcata Delta-actitoxin-Avd1a Proteins 0.000 description 1
- 101710099705 Anti-lipopolysaccharide factor Proteins 0.000 description 1
- 101000641989 Araneus ventricosus Kunitz-type U1-aranetoxin-Av1a Proteins 0.000 description 1
- 200000000007 Arterial disease Diseases 0.000 description 1
- 206010003178 Arterial thrombosis Diseases 0.000 description 1
- 208000031729 Bacteremia Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 101001028691 Carybdea rastonii Toxin CrTX-A Proteins 0.000 description 1
- 101000685083 Centruroides infamatus Beta-toxin Cii1 Proteins 0.000 description 1
- 101000685085 Centruroides noxius Toxin Cn1 Proteins 0.000 description 1
- 241000283153 Cetacea Species 0.000 description 1
- 101001028688 Chironex fleckeri Toxin CfTX-1 Proteins 0.000 description 1
- 206010009192 Circulatory collapse Diseases 0.000 description 1
- UPUVZWMODCZKPJ-BAWLJGGUSA-N ClCC(=O)CCl.N[C@@H](CCCNC(N)=N)C(=O)O.N1[C@@H](CCC1)C(=O)O.N[C@H](CC1=CC=CC=C1)C(=O)O Chemical compound ClCC(=O)CCl.N[C@@H](CCCNC(N)=N)C(=O)O.N1[C@@H](CCC1)C(=O)O.N[C@H](CC1=CC=CC=C1)C(=O)O UPUVZWMODCZKPJ-BAWLJGGUSA-N 0.000 description 1
- 102100029117 Coagulation factor X Human genes 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 101000644407 Cyriopagopus schmidti U6-theraphotoxin-Hs1a Proteins 0.000 description 1
- 206010014080 Ecchymosis Diseases 0.000 description 1
- 206010014666 Endocarditis bacterial Diseases 0.000 description 1
- 208000037487 Endotoxemia Diseases 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 108010029144 Factor IIa Proteins 0.000 description 1
- 108010074105 Factor Va Proteins 0.000 description 1
- 108010000196 Factor XIIIa Proteins 0.000 description 1
- 108010080805 Factor XIa Proteins 0.000 description 1
- 208000012671 Gastrointestinal haemorrhages Diseases 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 108060003393 Granulin Proteins 0.000 description 1
- 108010054964 H-hexahydrotyrosyl-alanyl-arginine-4-nitroanilide Proteins 0.000 description 1
- 208000034507 Haematemesis Diseases 0.000 description 1
- 206010018985 Haemorrhage intracranial Diseases 0.000 description 1
- 206010061192 Haemorrhagic fever Diseases 0.000 description 1
- 208000031220 Hemophilia Diseases 0.000 description 1
- 208000009292 Hemophilia A Diseases 0.000 description 1
- 208000000616 Hemoptysis Diseases 0.000 description 1
- 229920002971 Heparan sulfate Polymers 0.000 description 1
- 101000635804 Homo sapiens Tissue factor Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 208000008574 Intracranial Hemorrhages Diseases 0.000 description 1
- 108010030317 Macrophage-1 Antigen Proteins 0.000 description 1
- 206010058858 Meningococcal bacteraemia Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 101000679608 Phaeosphaeria nodorum (strain SN15 / ATCC MYA-4574 / FGSC 10173) Cysteine rich necrotrophic effector Tox1 Proteins 0.000 description 1
- 102000013566 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- 108010077971 Plasminogen Inactivators Proteins 0.000 description 1
- 102000010752 Plasminogen Inactivators Human genes 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 229940096437 Protein S Drugs 0.000 description 1
- 102000029301 Protein S Human genes 0.000 description 1
- 108010066124 Protein S Proteins 0.000 description 1
- 208000010378 Pulmonary Embolism Diseases 0.000 description 1
- 206010037549 Purpura Diseases 0.000 description 1
- 241001672981 Purpura Species 0.000 description 1
- 229940122055 Serine protease inhibitor Drugs 0.000 description 1
- 101710102218 Serine protease inhibitor Proteins 0.000 description 1
- 208000006666 Shwartzman Phenomenon Diseases 0.000 description 1
- 231100000702 Shwartzman phenomenon Toxicity 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- 101000712605 Theromyzon tessulatum Theromin Proteins 0.000 description 1
- 208000005985 Threatened Abortion Diseases 0.000 description 1
- 229940122388 Thrombin inhibitor Drugs 0.000 description 1
- 208000001435 Thromboembolism Diseases 0.000 description 1
- 206010044248 Toxic shock syndrome Diseases 0.000 description 1
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 206010046788 Uterine haemorrhage Diseases 0.000 description 1
- 229930003448 Vitamin K Natural products 0.000 description 1
- 108091005605 Vitamin K-dependent proteins Proteins 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 208000036981 active tuberculosis Diseases 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000004931 aggregating effect Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 229960003896 aminopterin Drugs 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 230000000603 anti-haemophilic effect Effects 0.000 description 1
- 230000003106 anti-papain Effects 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 229940127090 anticoagulant agent Drugs 0.000 description 1
- 239000002506 anticoagulant protein Substances 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 208000028922 artery disease Diseases 0.000 description 1
- 208000009361 bacterial endocarditis Diseases 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 201000001531 bladder carcinoma Diseases 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000004856 capillary permeability Effects 0.000 description 1
- 108020001778 catalytic domains Proteins 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000007820 coagulation assay Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 238000005094 computer simulation Methods 0.000 description 1
- 150000004775 coumarins Chemical class 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 125000000600 disaccharide group Chemical group 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 229940012444 factor xiii Drugs 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- 230000003480 fibrinolytic effect Effects 0.000 description 1
- 210000000497 foam cell Anatomy 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 208000035861 hematochezia Diseases 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 208000006750 hematuria Diseases 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 230000008348 humoral response Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 201000007119 infective endocarditis Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000009593 lumbar puncture Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 210000001809 melena Anatomy 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 208000022089 meningococcemia Diseases 0.000 description 1
- 230000003458 metachromatic effect Effects 0.000 description 1
- 230000029052 metamorphosis Effects 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- QYSGYZVSCZSLHT-UHFFFAOYSA-N octafluoropropane Chemical compound FC(F)(F)C(F)(F)C(F)(F)F QYSGYZVSCZSLHT-UHFFFAOYSA-N 0.000 description 1
- 210000000287 oocyte Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 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
- 229940012957 plasmin Drugs 0.000 description 1
- 239000002797 plasminogen activator inhibitor Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 230000031915 positive regulation of coagulation Effects 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 108010014806 prothrombinase complex Proteins 0.000 description 1
- 210000001147 pulmonary artery Anatomy 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 108010013773 recombinant FVIIa Proteins 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 230000000405 serological effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 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 1
- KYITYFHKDODNCQ-UHFFFAOYSA-M sodium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [Na+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 KYITYFHKDODNCQ-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 239000003868 thrombin inhibitor Substances 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 239000003656 tris buffered saline Substances 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000005167 vascular cell Anatomy 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000009278 visceral effect 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
- 229960002647 warfarin sodium Drugs 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Diabetes (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US60145490A | 1990-10-22 | 1990-10-22 | |
| US07/759,443 US5506134A (en) | 1990-10-22 | 1991-09-13 | Hypridoma and monoclonal antibody which inhibits blood coagulation tissue factor/factor VIIa complex |
| PCT/US1991/007811 WO1992006711A1 (en) | 1990-10-22 | 1991-10-17 | Blood coagulation protein antagonists and uses therefor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69132352D1 DE69132352D1 (de) | 2000-09-07 |
| DE69132352T2 true DE69132352T2 (de) | 2001-03-15 |
Family
ID=27083860
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69132352T Expired - Fee Related DE69132352T2 (de) | 1990-10-22 | 1991-10-17 | Protein-antagonisten der blut-koagulation und ihre verwendung |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US5506134A (OSRAM) |
| EP (1) | EP0554383B1 (OSRAM) |
| JP (1) | JP2680192B2 (OSRAM) |
| AT (1) | ATE195149T1 (OSRAM) |
| AU (1) | AU654311B2 (OSRAM) |
| CA (1) | CA2094372A1 (OSRAM) |
| DE (1) | DE69132352T2 (OSRAM) |
| ES (1) | ES2151880T3 (OSRAM) |
| WO (1) | WO1992006711A1 (OSRAM) |
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5843442A (en) * | 1990-10-22 | 1998-12-01 | Corvas International, Inc. | Blood coagulation protein antagonists and uses therefor |
| EP0738156A1 (en) * | 1993-12-27 | 1996-10-23 | Hamilton Civic Hospitals Research Development, Inc. | Methods and compositions for inhibiting thrombogenesis |
| US5683899A (en) | 1994-02-03 | 1997-11-04 | University Of Hawaii | Methods and compositions for combinatorial-based discovery of new multimeric molecules |
| DE19802139C1 (de) * | 1998-01-22 | 1999-09-23 | Centeon Pharma Gmbh | Monoklonaler Antikörper spezifisch für aktivierten Gerinnungsfaktor VII und seine Verwendung |
| EP0987274A1 (en) | 1998-09-15 | 2000-03-22 | Hoechst Marion Roussel Deutschland GmbH | Factor VIIa Inhibitors |
| DE69906568T2 (de) * | 1998-11-20 | 2004-02-12 | Eli Lilly And Co., Indianapolis | Behandlung von hämorrhagischem virusfieber mit protein c |
| EP1059302A1 (en) | 1999-06-08 | 2000-12-13 | Aventis Pharma Deutschland GmbH | Factor VIIa inhibitors |
| EP1095933A1 (en) | 1999-10-30 | 2001-05-02 | Aventis Pharma Deutschland GmbH | Novel N-guanidinoalkylamides, their preparation, their use, and pharmaceutical preparations comprising them |
| US6677473B1 (en) | 1999-11-19 | 2004-01-13 | Corvas International Inc | Plasminogen activator inhibitor antagonists |
| EP1162194A1 (en) | 2000-06-06 | 2001-12-12 | Aventis Pharma Deutschland GmbH | Factor VIIa inhibitory (thio)urea derivatives, their preparation and their use |
| NZ526269A (en) | 2000-12-06 | 2004-11-26 | Aventis Pharma Gmbh | Guanidine and amidine derivatives as factor Xa inhibitors having antithrombotic effect |
| EP1348443A4 (en) * | 2000-12-08 | 2005-07-06 | Takeda Pharmaceutical | COMBINED MEDICINES |
| AU2002240000A1 (en) * | 2001-01-23 | 2002-08-06 | Saint Louis University | Factor ixa: factor viiia interaction and methods therefor |
| EP1260817A3 (en) | 2001-05-08 | 2002-12-18 | Warner-Lambert Company | Method for direct measurement of coagulation factor VIIa activity in plasma |
| EP1270551A1 (en) | 2001-06-26 | 2003-01-02 | Aventis Pharma Deutschland GmbH | Urea derivatives with antiproteolytic activity |
| WO2003004694A1 (en) * | 2001-07-03 | 2003-01-16 | Oklahoma Medical Research Foundation | ASSAY FOR MEASURING FACTOR VIIa-ANTITHROMBIN COMPLEXES |
| EA200400548A1 (ru) | 2001-10-15 | 2005-06-30 | Чирон Корпорейшн | Лечение тяжёлой пневмонии путём введения ингибитора пути тканевого фактора (tfpi) |
| EP1446150A1 (en) * | 2001-11-09 | 2004-08-18 | Novo Nordisk Health Care AG | Pharmaceutical composition comprising factor vii polypeptides and protein c inhibitors |
| EP1314733A1 (en) | 2001-11-22 | 2003-05-28 | Aventis Pharma Deutschland GmbH | Indole-2-carboxamides as factor Xa inhibitors |
| US20040126856A1 (en) * | 2002-01-23 | 2004-07-01 | Bajaj Paul S. | Factor ixa: factor Vllla interaction and methods therefor |
| US20050255111A1 (en) * | 2002-02-22 | 2005-11-17 | Olle Korsgren | Use of an inhibitor or antagonist against tissue factor |
| US6706068B2 (en) | 2002-04-23 | 2004-03-16 | Bret A. Ferree | Artificial disc replacements with natural kinematics |
| RS102404A (sr) * | 2002-05-01 | 2006-12-15 | Schering Aktiengesellschaft | Nova antitela koja ciljaju tkivni faktor kao antikoagulanti |
| US7579000B2 (en) | 2002-05-01 | 2009-08-25 | Bayer Schering Pharma Ag | Tissue factor targeted antibodies as anticoagulants |
| US20040110929A1 (en) * | 2002-07-12 | 2004-06-10 | Bjorn Soren E. | TF binding compound |
| US7358268B2 (en) | 2002-12-04 | 2008-04-15 | Sanofi-Aventis Deutschland Gmbh | Imidazole derivatives as factor Xa inhibitors |
| US7429581B2 (en) | 2002-12-23 | 2008-09-30 | Sanofi-Aventis Deutschland Gmbh | Pyrazole-derivatives as factor Xa inhibitors |
| US7425328B2 (en) * | 2003-04-22 | 2008-09-16 | Purdue Pharma L.P. | Tissue factor antibodies and uses thereof |
| US7223780B2 (en) | 2003-05-19 | 2007-05-29 | Sanofi-Aventis Deutschland Gmbh | Triazole-derivatives as blood clotting enzyme factor Xa inhibitors |
| EP1479677A1 (en) | 2003-05-19 | 2004-11-24 | Aventis Pharma Deutschland GmbH | New indole derivatives as factor xa inhibitors |
| US7317027B2 (en) | 2003-05-19 | 2008-01-08 | Sanofi-Aventis Deutschland Gmbh | Azaindole-derivatives as factor Xa inhibitors |
| US7741341B2 (en) | 2003-05-19 | 2010-06-22 | Sanofi-Aventis Deutschland Gmbh | Benzimidazole-derivatives as factor Xa inhibitors |
| EP1479675A1 (en) | 2003-05-19 | 2004-11-24 | Aventis Pharma Deutschland GmbH | Indazole-derivatives as factor Xa inhibitors |
| AU2004252568B2 (en) | 2003-06-27 | 2011-06-30 | Ethicon, Incorporated | Regeneration and repair of neural tissue using postpartum-derived cells |
| DE10333508A1 (de) * | 2003-07-18 | 2005-02-17 | Technische Universität Dresden | Gegen Prothrombin gerichtete Erkennungsmoleküle und die Verwendung dieser |
| EP1568698A1 (en) | 2004-02-27 | 2005-08-31 | Aventis Pharma Deutschland GmbH | Pyrrole-derivatives as factor Xa inhibitors |
| MXPA06011952A (es) * | 2004-04-16 | 2007-01-16 | Scripps Research Inst | Metodo para modulacion de vascularizacion. |
| PL1831356T3 (pl) | 2004-12-23 | 2017-07-31 | DePuy Synthes Products, Inc. | Komórki poporodowe pochodzące z tkanki pępowinowej i sposoby ich wytwarzania i stosowania |
| PL2297207T3 (pl) * | 2008-06-19 | 2019-03-29 | Prothix Bv | Zastosowanie przeciwciał przeciw czynnikowi XI do zapobiegania lub leczenia tworzenia skrzepliny |
| EP3281956A3 (en) | 2010-06-15 | 2018-04-18 | Genmab A/S | Human antibody drug conjugates against tissue factor |
| IL230564B2 (en) | 2011-07-22 | 2023-09-01 | Csl Ltd | Anticoagulant monoclonal antibodies anti–factor xii/fxiia, a method for their preparation, a pharmaceutical compound containing them and medical uses. |
| RS65556B1 (sr) | 2012-09-13 | 2024-06-28 | Bristol Myers Squibb Co | Proteini domena skele na bazi fibronektina koji vezuju miostatin |
| TWI841554B (zh) | 2018-03-21 | 2024-05-11 | 丹麥商珍美寶股份有限公司 | 以鉑為主之劑與抗組織因子抗體－藥物共軛物的組合治療癌症之方法 |
| CA3099547A1 (en) | 2018-05-07 | 2019-11-14 | Reshma Abdulla RANGWALA | Methods of treating cancer with a combination of an anti-pd-1 antibody and an anti-tissue factor antibody-drug conjugate |
| TWI844571B (zh) | 2018-10-30 | 2024-06-11 | 丹麥商珍美寶股份有限公司 | 使用抗血管內皮生長因子（ｖｅｇｆ）抗體與抗組織因子（ｔｆ）抗體－藥物共軛體之組合以治療癌症之方法 |
| CN113692415B (zh) | 2019-04-17 | 2025-01-07 | 诺和诺德股份有限公司 | 双特异性抗体 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4382083A (en) * | 1981-06-25 | 1983-05-03 | Baxter Travenol Laboratories, Inc. | Therapeutic method for treating blood-clotting defects with factor VIIa |
| GB2148299B (en) * | 1983-09-01 | 1988-01-06 | Hybritech Inc | Antibody compositions of therapeutic agents having an extended serum half-life |
| SE461315B (sv) * | 1988-06-16 | 1990-02-05 | Jan Niels Faergemann | Anvaendning av en komposition innehaallande aluminiumacetotartrat och en diol foer att minska hudirritationer orsakade av urin eller avfoering, samt bloeja impregnerad med kompositionen |
| US5190919A (en) * | 1989-11-13 | 1993-03-02 | Board Of Regents, The University Of Texas System | Antihemostatic factor vii peptides |
-
1991
- 1991-09-13 US US07/759,443 patent/US5506134A/en not_active Expired - Lifetime
- 1991-10-17 WO PCT/US1991/007811 patent/WO1992006711A1/en not_active Ceased
- 1991-10-17 DE DE69132352T patent/DE69132352T2/de not_active Expired - Fee Related
- 1991-10-17 JP JP3518610A patent/JP2680192B2/ja not_active Expired - Fee Related
- 1991-10-17 EP EP91920567A patent/EP0554383B1/en not_active Expired - Lifetime
- 1991-10-17 ES ES91920567T patent/ES2151880T3/es not_active Expired - Lifetime
- 1991-10-17 CA CA002094372A patent/CA2094372A1/en not_active Abandoned
- 1991-10-17 AT AT91920567T patent/ATE195149T1/de not_active IP Right Cessation
- 1991-10-17 AU AU90298/91A patent/AU654311B2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| AU9029891A (en) | 1992-05-20 |
| ATE195149T1 (de) | 2000-08-15 |
| US5506134A (en) | 1996-04-09 |
| CA2094372A1 (en) | 1992-04-23 |
| AU654311B2 (en) | 1994-11-03 |
| ES2151880T3 (es) | 2001-01-16 |
| JPH06502307A (ja) | 1994-03-17 |
| EP0554383A1 (en) | 1993-08-11 |
| JP2680192B2 (ja) | 1997-11-19 |
| EP0554383A4 (OSRAM) | 1994-04-27 |
| DE69132352D1 (de) | 2000-09-07 |
| WO1992006711A1 (en) | 1992-04-30 |
| EP0554383B1 (en) | 2000-08-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69132352T2 (de) | Protein-antagonisten der blut-koagulation und ihre verwendung | |
| US6221659B1 (en) | Blood coagulation protein antagonists and uses therefor | |
| US5990079A (en) | Agents affecting thrombosis and hemostasis | |
| DE69736197T2 (de) | Antikoagulierende humanisierte Antikörper gegen Faktor IX, zur Verwendung in der Behandlung von Thrombose | |
| DE69121272T2 (de) | Bispezifische monoklonale Antikörper, ihre Produktion und Verwendung | |
| DE69530316T2 (de) | Antithrombose mittel und gegen den von willebrand-faktor gerichtete monoklonale antikörper | |
| DE69229911T2 (de) | Monoklonale antikörper gegen rezeptor-induzierte bindungsstellen | |
| DE69632465T2 (de) | Cdr-transplantierte antikörper gegen "tissue factor" und verfahren zur deren verwendung | |
| DE68924773T2 (de) | Monoklonale antikörper gegen den bereich der leichten kette von menschlichem faktor xii sowie methoden zu deren herstellung und verwendung. | |
| JPWO1996017078A1 (ja) | 抗血栓剤及び抗フォンビルブランド因子モノクローナル抗体 | |
| DE60033814T2 (de) | Monoklonaler Antikörper der Faktor VIII selbst in molarem Überschuß nur teilweise inaktiviert und eine Methode zur Herstellung solch eines Antikörpers | |
| UA116531C2 (uk) | Виділена молекула антитіла, яка специфічно зв'язується з ділянкою екзосайта 1 тромбіну, та її застосування | |
| DE69411898T2 (de) | Neue antikoagulant-cofaktor aktivität | |
| DE69435072T2 (de) | Antikörper gegen menschliches lösliches fibrin, hybridome, die sie produzieren und immunmessverfahren | |
| DE69011531T2 (de) | Von faktor vii abgeleitete peptide mit antihämostatischer wirkung. | |
| KR20030034071A (ko) | 항혈전제 | |
| DE69229948T2 (de) | hGPIIb-FRAGMENTE UND IHRE VERWENDUNG IN IN-VITRO-VERFAHREN ZUR BESTIMMUNG VON IN VIVO STATTFINDENDEN THROMBOTISCHEN EREIGNISSEN | |
| DE3687542T2 (de) | Monoklonaler antikoerper gegen humanes protein c. | |
| EP0457532A1 (en) | Monoclonal antibody which inhibits the biological action of platelet factor 4 | |
| US20040072757A1 (en) | Agents affecting thrombosis and hemostasis | |
| Arnout et al. | Thrombosis: fundamental and clinical aspects | |
| Meyer | Monoclonal Antibodies to Human von Willebrand Factor Study of its Structure-Function Relationship | |
| MEYER | glycoprotein is present in plasma at about 5-10 ug per ml as a set |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8339 | Ceased/non-payment of the annual fee |