NO301374B1 - Fremgangsmåte for fremstilling av et <alfa>2-antiplasmin monoklonalt antistoff - Google Patents
Fremgangsmåte for fremstilling av et <alfa>2-antiplasmin monoklonalt antistoff Download PDFInfo
- Publication number
- NO301374B1 NO301374B1 NO904294A NO904294A NO301374B1 NO 301374 B1 NO301374 B1 NO 301374B1 NO 904294 A NO904294 A NO 904294A NO 904294 A NO904294 A NO 904294A NO 301374 B1 NO301374 B1 NO 301374B1
- Authority
- NO
- Norway
- Prior art keywords
- antiplasmin
- antibody
- clot
- fibrin
- plasmin
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 229940012957 plasmin Drugs 0.000 claims abstract description 27
- 230000005764 inhibitory process Effects 0.000 claims abstract description 18
- 108090000183 alpha-2-Antiplasmin Proteins 0.000 claims abstract description 8
- 102000003801 alpha-2-Antiplasmin Human genes 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 16
- 210000004754 hybrid cell Anatomy 0.000 claims description 6
- 210000004027 cell Anatomy 0.000 claims description 3
- 238000010367 cloning Methods 0.000 claims description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 2
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 2
- 210000004989 spleen cell Anatomy 0.000 claims description 2
- 230000009089 cytolysis Effects 0.000 abstract description 44
- 239000003527 fibrinolytic agent Substances 0.000 abstract description 37
- 229960000103 thrombolytic agent Drugs 0.000 abstract description 37
- 108010049003 Fibrinogen Proteins 0.000 abstract description 14
- 102000008946 Fibrinogen Human genes 0.000 abstract description 14
- 229940012952 fibrinogen Drugs 0.000 abstract description 14
- 206010038563 Reocclusion Diseases 0.000 abstract description 13
- 208000007536 Thrombosis Diseases 0.000 abstract description 13
- 208000010125 myocardial infarction Diseases 0.000 abstract description 13
- 230000015572 biosynthetic process Effects 0.000 abstract description 11
- 238000002560 therapeutic procedure Methods 0.000 abstract description 10
- 230000001965 increasing effect Effects 0.000 abstract description 7
- 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 abstract description 4
- 230000015556 catabolic process Effects 0.000 abstract description 4
- 210000004351 coronary vessel Anatomy 0.000 abstract description 4
- 229960002897 heparin Drugs 0.000 abstract description 4
- 229920000669 heparin Polymers 0.000 abstract description 4
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 52
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 52
- 229960000187 tissue plasminogen activator Drugs 0.000 description 44
- 108010088842 Fibrinolysin Proteins 0.000 description 23
- 102000009123 Fibrin Human genes 0.000 description 22
- 108010073385 Fibrin Proteins 0.000 description 22
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 22
- 229950003499 fibrin Drugs 0.000 description 22
- 239000003795 chemical substances by application Substances 0.000 description 15
- 238000011282 treatment Methods 0.000 description 12
- 238000001802 infusion Methods 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 210000004204 blood vessel Anatomy 0.000 description 9
- 239000012634 fragment Substances 0.000 description 9
- 239000002806 plasmin inhibitor Substances 0.000 description 8
- 208000032843 Hemorrhage Diseases 0.000 description 7
- 208000034158 bleeding Diseases 0.000 description 7
- 230000000740 bleeding effect Effects 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 230000004087 circulation Effects 0.000 description 7
- 230000035602 clotting Effects 0.000 description 7
- 102100035991 Alpha-2-antiplasmin Human genes 0.000 description 6
- 208000031481 Pathologic Constriction Diseases 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 230000036262 stenosis Effects 0.000 description 6
- 208000037804 stenosis Diseases 0.000 description 6
- 229940122791 Plasmin inhibitor Drugs 0.000 description 5
- 108010023197 Streptokinase Proteins 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 210000004408 hybridoma Anatomy 0.000 description 5
- 229960005202 streptokinase Drugs 0.000 description 5
- 241001529936 Murinae Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 4
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000002195 synergetic effect Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 229960005356 urokinase Drugs 0.000 description 4
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 3
- 101710149643 Integrin alpha-IIb Proteins 0.000 description 3
- 102100032999 Integrin beta-3 Human genes 0.000 description 3
- 108010020950 Integrin beta3 Proteins 0.000 description 3
- 241000276498 Pollachius virens Species 0.000 description 3
- 108090000190 Thrombin Proteins 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 239000003146 anticoagulant agent Substances 0.000 description 3
- 230000017531 blood circulation Effects 0.000 description 3
- 230000002779 inactivation Effects 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 239000003094 microcapsule Substances 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000010410 reperfusion Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 230000002537 thrombolytic effect Effects 0.000 description 3
- 206010003445 Ascites Diseases 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
- 201000000057 Coronary Stenosis Diseases 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 206010061216 Infarction Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 206010028851 Necrosis Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 102000013566 Plasminogen Human genes 0.000 description 2
- 108010051456 Plasminogen Proteins 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 230000008901 benefit 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
- 230000008859 change Effects 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 229960005156 digoxin Drugs 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000007574 infarction Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229940099990 ogen Drugs 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 229920001308 poly(aminoacid) Polymers 0.000 description 2
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 2
- 229920000728 polyester Polymers 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 108010073863 saruplase Proteins 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 229960004072 thrombin Drugs 0.000 description 2
- FJQZXCPWAGYPSD-UHFFFAOYSA-N 1,3,4,6-tetrachloro-3a,6a-diphenylimidazo[4,5-d]imidazole-2,5-dione Chemical compound ClN1C(=O)N(Cl)C2(C=3C=CC=CC=3)N(Cl)C(=O)N(Cl)C12C1=CC=CC=C1 FJQZXCPWAGYPSD-UHFFFAOYSA-N 0.000 description 1
- 238000013296 A/J mouse Methods 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 102100033312 Alpha-2-macroglobulin Human genes 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 206010008088 Cerebral artery embolism Diseases 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 206010053261 Coronary artery reocclusion Diseases 0.000 description 1
- 206010011091 Coronary artery thrombosis Diseases 0.000 description 1
- 206010051055 Deep vein thrombosis Diseases 0.000 description 1
- 108010012088 Fibrinogen Receptors Proteins 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 101000783712 Homo sapiens Alpha-2-antiplasmin Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 238000012695 Interfacial polymerization Methods 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 239000004907 Macro-emulsion Substances 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000609499 Palicourea Species 0.000 description 1
- 241000282320 Panthera leo Species 0.000 description 1
- 206010072564 Peripheral artery thrombosis Diseases 0.000 description 1
- 108010015078 Pregnancy-Associated alpha 2-Macroglobulins Proteins 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 208000010378 Pulmonary Embolism Diseases 0.000 description 1
- 206010038548 Renal vein thrombosis Diseases 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 206010000891 acute myocardial infarction Diseases 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000011360 adjunctive therapy Methods 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 1
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000003302 anti-idiotype Effects 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000002820 assay format Methods 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 208000002528 coronary thrombosis Diseases 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 238000005189 flocculation Methods 0.000 description 1
- 230000016615 flocculation Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)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)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 201000010849 intracranial embolism Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229950008679 protamine sulfate Drugs 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000002796 renal vein Anatomy 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000013595 supernatant sample Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000003656 tris buffered saline Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229960001134 von willebrand factor 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)
-
- 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
- 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)
- A61K38/49—Urokinase; Tissue plasminogen activator
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/38—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against protease inhibitors of peptide structure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Mycology (AREA)
- Vascular Medicine (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Microbiology (AREA)
- Diabetes (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Surgical Instruments (AREA)
- External Artificial Organs (AREA)
- Compositions Of Macromolecular Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17722288A | 1988-04-04 | 1988-04-04 | |
| PCT/US1989/001065 WO1989009817A1 (en) | 1988-04-04 | 1989-03-15 | Composition and method for acceleration of clot lysis |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO904294D0 NO904294D0 (no) | 1990-10-03 |
| NO904294L NO904294L (no) | 1990-12-04 |
| NO301374B1 true NO301374B1 (no) | 1997-10-20 |
Family
ID=22647707
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO904294A NO301374B1 (no) | 1988-04-04 | 1990-10-03 | Fremgangsmåte for fremstilling av et <alfa>2-antiplasmin monoklonalt antistoff |
Country Status (15)
| Country | Link |
|---|---|
| EP (1) | EP0336693B1 (de) |
| JP (1) | JP2871775B2 (de) |
| KR (1) | KR100194113B1 (de) |
| AT (1) | ATE114480T1 (de) |
| AU (1) | AU628041B2 (de) |
| CA (1) | CA1341377C (de) |
| DE (1) | DE68919504T2 (de) |
| DK (1) | DK174062B1 (de) |
| ES (1) | ES2064435T3 (de) |
| FI (1) | FI102812B (de) |
| GR (1) | GR3015182T3 (de) |
| HU (1) | HU207349B (de) |
| NO (1) | NO301374B1 (de) |
| WO (1) | WO1989009817A1 (de) |
| ZA (1) | ZA892464B (de) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5357042A (en) * | 1984-04-23 | 1994-10-18 | The General Hospital Corporation | Synthetic peptides capable of eliciting fibrin-specific monoclonal antibodies lacking fibrinogen-cross-reactivity |
| US5453269A (en) * | 1986-04-14 | 1995-09-26 | The General Hospital Corporation | Heterobifunctional antibodies having dual specificity for fibrin and thrombolylic agents and methods of use |
| US5372812A (en) * | 1988-04-04 | 1994-12-13 | The General Hospital Corporation | Composition and method for acceleration of clot lysis |
| US5582862A (en) | 1988-04-04 | 1996-12-10 | General Hospital Corporation | Antibodies that bind to α2-antiplasmin crosslinked to fibrin which do not inhibit plasma α2-antiplasmin |
| US5609869A (en) * | 1988-08-19 | 1997-03-11 | The General Hospital Corporation | Hybrid immunoglobulin-thrombolytic enzyme molecules which specifically bind a thrombus, and methods of their production and use |
| US5811265A (en) * | 1988-08-19 | 1998-09-22 | The General Hospital Corporation | Hybrid immunoglobulin-thrombolytic enzyme molecules which specifically bind a thrombus, and methods of their production and use |
| JPH02268694A (ja) * | 1989-04-07 | 1990-11-02 | Teijin Ltd | 血栓溶解剤 |
| CA2266339A1 (en) * | 1996-09-20 | 1998-03-26 | The General Hospital Corporation | Chimeric, humanized and single chain antibodies to alpha-2-antiplasmin |
| US6524675B1 (en) | 1999-05-13 | 2003-02-25 | 3M Innovative Properties Company | Adhesive-back articles |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0735340B2 (ja) * | 1985-05-23 | 1995-04-19 | 帝人株式会社 | 血栓溶解促進剤 |
| ATE142502T1 (de) * | 1986-05-15 | 1996-09-15 | Univ Emory | Injizierbares arzneimittel zum schutz vor gewebebeschädigung durch ischemie |
-
1989
- 1989-03-15 WO PCT/US1989/001065 patent/WO1989009817A1/en active IP Right Grant
- 1989-03-15 AU AU32845/89A patent/AU628041B2/en not_active Ceased
- 1989-03-15 JP JP1503381A patent/JP2871775B2/ja not_active Expired - Fee Related
- 1989-03-15 HU HU892304A patent/HU207349B/hu not_active IP Right Cessation
- 1989-03-15 KR KR1019890702259A patent/KR100194113B1/ko not_active IP Right Cessation
- 1989-03-29 CA CA000594988A patent/CA1341377C/en not_active Expired - Fee Related
- 1989-04-04 AT AT89303293T patent/ATE114480T1/de not_active IP Right Cessation
- 1989-04-04 EP EP89303293A patent/EP0336693B1/de not_active Expired - Lifetime
- 1989-04-04 ES ES89303293T patent/ES2064435T3/es not_active Expired - Lifetime
- 1989-04-04 ZA ZA892464A patent/ZA892464B/xx unknown
- 1989-04-04 DE DE68919504T patent/DE68919504T2/de not_active Expired - Fee Related
-
1990
- 1990-10-03 FI FI904867A patent/FI102812B/fi not_active IP Right Cessation
- 1990-10-03 NO NO904294A patent/NO301374B1/no not_active IP Right Cessation
- 1990-10-04 DK DK199002401A patent/DK174062B1/da not_active IP Right Cessation
-
1995
- 1995-02-27 GR GR940403885T patent/GR3015182T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DK240190D0 (da) | 1990-10-04 |
| EP0336693A2 (de) | 1989-10-11 |
| GR3015182T3 (en) | 1995-05-31 |
| DE68919504T2 (de) | 1995-06-29 |
| KR900700129A (ko) | 1990-08-11 |
| DK240190A (da) | 1990-10-04 |
| EP0336693B1 (de) | 1994-11-30 |
| AU3284589A (en) | 1989-11-03 |
| ES2064435T3 (es) | 1995-02-01 |
| EP0336693A3 (en) | 1990-03-21 |
| NO904294D0 (no) | 1990-10-03 |
| CA1341377C (en) | 2002-07-16 |
| ATE114480T1 (de) | 1994-12-15 |
| JP2871775B2 (ja) | 1999-03-17 |
| HUT56394A (en) | 1991-08-28 |
| JPH03504717A (ja) | 1991-10-17 |
| FI102812B1 (fi) | 1999-02-26 |
| HU207349B (en) | 1993-03-29 |
| AU628041B2 (en) | 1992-09-10 |
| WO1989009817A1 (en) | 1989-10-19 |
| ZA892464B (en) | 1989-12-27 |
| KR100194113B1 (ko) | 1999-06-15 |
| HU892304D0 (en) | 1991-07-29 |
| DK174062B1 (da) | 2002-05-13 |
| DE68919504D1 (de) | 1995-01-12 |
| FI102812B (fi) | 1999-02-26 |
| NO904294L (no) | 1990-12-04 |
| FI904867A0 (fi) | 1990-10-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2297207B1 (de) | Verwendung von antikörpern gegen gerinnungsfaktor xi zur vorbeugung oder behandlung von thrombosen | |
| US20030082636A1 (en) | Antibodies for inhibiting blood coagulation and methods of use thereof | |
| US20070224198A1 (en) | Antithrombotic agents | |
| US6280730B1 (en) | Antibodies that bind to α2-antiplasmin crosslinked to fibrin which do not inhibit plasma α2-antiplasmin | |
| NO301374B1 (no) | Fremgangsmåte for fremstilling av et <alfa>2-antiplasmin monoklonalt antistoff | |
| US20090010934A1 (en) | Cell lines, ligands and antibody fragments for use in pharmaceutical compositions for preventing and treating haemostasis disorders | |
| EP1825864A2 (de) | Anthithrombose Agenzien | |
| Jiang et al. | Safety and efficacy of an anti–human APC antibody for prophylaxis of congenital factor deficiencies in preclinical models | |
| US20020136725A1 (en) | Antithrombotic agents | |
| US5275812A (en) | Method of treatment for myocardial infarction | |
| US11066482B2 (en) | Specific plasmin inactivation by anticatalytic antibody | |
| US5372812A (en) | Composition and method for acceleration of clot lysis | |
| EP0339505A2 (de) | Monoklonale Antikörper gegen Gewebe-Plasminogen-Aktivator (t-PA), die sein funktionales Halbleben verlängern | |
| US20070190059A1 (en) | Antithrombotic agents | |
| US20090311267A1 (en) | Inhibition of VWF - GPIb/V/IX interaction and platelet-collagen interaction for prevention and treatment of cerebral attacks | |
| Chesebro | Direct thrombin inhibitor therapy in the cardiovascular patient | |
| Jacquemin et al. | The use of antibodies to coagulation factors for anticoagulant therapy | |
| JPH02268694A (ja) | 血栓溶解剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |