RU2571931C2 - Полипептиды на основе модифицированного фактора vii и их применение - Google Patents
Полипептиды на основе модифицированного фактора vii и их применение Download PDFInfo
- Publication number
- RU2571931C2 RU2571931C2 RU2009141510/10A RU2009141510A RU2571931C2 RU 2571931 C2 RU2571931 C2 RU 2571931C2 RU 2009141510/10 A RU2009141510/10 A RU 2009141510/10A RU 2009141510 A RU2009141510 A RU 2009141510A RU 2571931 C2 RU2571931 C2 RU 2571931C2
- Authority
- RU
- Russia
- Prior art keywords
- fvii
- polypeptide
- fvii polypeptide
- amino acid
- modified
- Prior art date
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 467
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 464
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 463
- 229940012413 factor vii Drugs 0.000 title claims description 50
- 150000001413 amino acids Chemical class 0.000 claims abstract description 173
- 230000000694 effects Effects 0.000 claims abstract description 131
- 230000004048 modification Effects 0.000 claims abstract description 100
- 238000012986 modification Methods 0.000 claims abstract description 100
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 76
- 230000001965 increasing effect Effects 0.000 claims abstract description 60
- 238000006467 substitution reaction Methods 0.000 claims abstract description 41
- 239000003112 inhibitor Substances 0.000 claims abstract description 37
- 239000002243 precursor Substances 0.000 claims abstract description 33
- 125000000539 amino acid group Chemical class 0.000 claims abstract description 32
- 239000000701 coagulant Substances 0.000 claims abstract description 17
- 239000003814 drug Substances 0.000 claims abstract description 14
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims abstract description 4
- 229940024606 amino acid Drugs 0.000 claims description 142
- 210000004027 cell Anatomy 0.000 claims description 82
- 150000007523 nucleic acids Chemical class 0.000 claims description 76
- 102000039446 nucleic acids Human genes 0.000 claims description 74
- 108020004707 nucleic acids Proteins 0.000 claims description 74
- 102100022641 Coagulation factor IX Human genes 0.000 claims description 55
- 102100023804 Coagulation factor VII Human genes 0.000 claims description 54
- 102100030951 Tissue factor pathway inhibitor Human genes 0.000 claims description 53
- 108010013555 lipoprotein-associated coagulation inhibitor Proteins 0.000 claims description 53
- 238000000034 method Methods 0.000 claims description 53
- 108010023321 Factor VII Proteins 0.000 claims description 52
- 108010076282 Factor IX Proteins 0.000 claims description 44
- 229960004222 factor ix Drugs 0.000 claims description 43
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 40
- 208000032843 Hemorrhage Diseases 0.000 claims description 39
- 208000034158 bleeding Diseases 0.000 claims description 39
- 230000000740 bleeding effect Effects 0.000 claims description 39
- 208000009292 Hemophilia A Diseases 0.000 claims description 38
- 239000013598 vector Substances 0.000 claims description 32
- 201000010099 disease Diseases 0.000 claims description 29
- 238000011282 treatment Methods 0.000 claims description 29
- 208000031220 Hemophilia Diseases 0.000 claims description 27
- 230000006378 damage Effects 0.000 claims description 24
- 230000014509 gene expression Effects 0.000 claims description 22
- 102000001690 Factor VIII Human genes 0.000 claims description 20
- 108010054218 Factor VIII Proteins 0.000 claims description 20
- 238000001356 surgical procedure Methods 0.000 claims description 20
- 241000282414 Homo sapiens Species 0.000 claims description 19
- 229960000301 factor viii Drugs 0.000 claims description 19
- 208000014674 injury Diseases 0.000 claims description 19
- 239000012634 fragment Substances 0.000 claims description 18
- 102100026735 Coagulation factor VIII Human genes 0.000 claims description 13
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 claims description 13
- 206010010356 Congenital anomaly Diseases 0.000 claims description 12
- 201000003542 Factor VIII deficiency Diseases 0.000 claims description 11
- 208000009429 hemophilia B Diseases 0.000 claims description 11
- 208000031169 hemorrhagic disease Diseases 0.000 claims description 11
- 208000027418 Wounds and injury Diseases 0.000 claims description 10
- 230000004481 post-translational protein modification Effects 0.000 claims description 9
- 230000008733 trauma Effects 0.000 claims description 9
- 206010053567 Coagulopathies Diseases 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 7
- 208000015294 blood coagulation disease Diseases 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 239000013603 viral vector Substances 0.000 claims description 6
- 230000001154 acute effect Effects 0.000 claims description 5
- 239000013604 expression vector Substances 0.000 claims description 5
- 210000004185 liver Anatomy 0.000 claims description 5
- 230000003462 zymogenic effect Effects 0.000 claims description 5
- 241000699800 Cricetinae Species 0.000 claims description 4
- 210000003527 eukaryotic cell Anatomy 0.000 claims description 4
- 201000007386 factor VII deficiency Diseases 0.000 claims description 4
- 208000014951 hematologic disease Diseases 0.000 claims description 4
- 229960000310 isoleucine Drugs 0.000 claims description 4
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 4
- 210000004962 mammalian cell Anatomy 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 238000002054 transplantation Methods 0.000 claims description 4
- 241000701161 unidentified adenovirus Species 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 238000002399 angioplasty Methods 0.000 claims description 3
- 230000009852 coagulant defect Effects 0.000 claims description 3
- 208000011664 congenital factor XI deficiency Diseases 0.000 claims description 3
- 201000007219 factor XI deficiency Diseases 0.000 claims description 3
- 210000002216 heart Anatomy 0.000 claims description 3
- 239000001630 malic acid Substances 0.000 claims description 3
- 210000000056 organ Anatomy 0.000 claims description 3
- 230000002685 pulmonary effect Effects 0.000 claims description 3
- 206010008111 Cerebral haemorrhage Diseases 0.000 claims description 2
- 241000701022 Cytomegalovirus Species 0.000 claims description 2
- 208000012671 Gastrointestinal haemorrhages Diseases 0.000 claims description 2
- 206010018852 Haematoma Diseases 0.000 claims description 2
- 238000012084 abdominal surgery Methods 0.000 claims description 2
- 210000001185 bone marrow Anatomy 0.000 claims description 2
- 210000003169 central nervous system Anatomy 0.000 claims description 2
- 238000007385 chemical modification Methods 0.000 claims description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 claims description 2
- 230000001684 chronic effect Effects 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims description 2
- 208000030304 gastrointestinal bleeding Diseases 0.000 claims description 2
- 208000002085 hemarthrosis Diseases 0.000 claims description 2
- 208000006750 hematuria Diseases 0.000 claims description 2
- 208000031209 hemophilic arthropathy Diseases 0.000 claims description 2
- 238000002955 isolation Methods 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 210000004072 lung Anatomy 0.000 claims description 2
- 210000000496 pancreas Anatomy 0.000 claims description 2
- 241001529453 unidentified herpesvirus Species 0.000 claims description 2
- 238000007631 vascular surgery Methods 0.000 claims description 2
- 210000005253 yeast cell Anatomy 0.000 claims description 2
- 239000004475 Arginine Substances 0.000 claims 1
- 241000235058 Komagataella pastoris Species 0.000 claims 1
- 241000713666 Lentivirus Species 0.000 claims 1
- 241000235061 Pichia sp. Species 0.000 claims 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 125000003827 glycol group Chemical group 0.000 claims 1
- 210000005260 human cell Anatomy 0.000 claims 1
- 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 claims 1
- 210000001161 mammalian embryo Anatomy 0.000 claims 1
- 241001430294 unidentified retrovirus Species 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 13
- 235000001014 amino acid Nutrition 0.000 description 162
- 102000002262 Thromboplastin Human genes 0.000 description 132
- 108010000499 Thromboplastin Proteins 0.000 description 132
- 108090000623 proteins and genes Proteins 0.000 description 116
- 102000004169 proteins and genes Human genes 0.000 description 103
- 235000018102 proteins Nutrition 0.000 description 97
- 210000001772 blood platelet Anatomy 0.000 description 84
- 101150108358 GLAA gene Proteins 0.000 description 78
- 101150014526 Gla gene Proteins 0.000 description 78
- 230000015271 coagulation Effects 0.000 description 78
- 238000005345 coagulation Methods 0.000 description 78
- UHBYWPGGCSDKFX-VKHMYHEASA-N gamma-carboxy-L-glutamic acid Chemical compound OC(=O)[C@@H](N)CC(C(O)=O)C(O)=O UHBYWPGGCSDKFX-VKHMYHEASA-N 0.000 description 76
- 230000027455 binding Effects 0.000 description 70
- 108090000190 Thrombin Proteins 0.000 description 65
- 229960004072 thrombin Drugs 0.000 description 65
- 102000035195 Peptidases Human genes 0.000 description 63
- 108091005804 Peptidases Proteins 0.000 description 63
- 230000015572 biosynthetic process Effects 0.000 description 54
- 238000001994 activation Methods 0.000 description 53
- 239000004365 Protease Substances 0.000 description 52
- 229940012426 factor x Drugs 0.000 description 49
- 108010014173 Factor X Proteins 0.000 description 48
- 230000004913 activation Effects 0.000 description 47
- 150000003904 phospholipids Chemical class 0.000 description 45
- 235000019419 proteases Nutrition 0.000 description 39
- 108010073385 Fibrin Proteins 0.000 description 37
- 102000009123 Fibrin Human genes 0.000 description 37
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 37
- 230000000875 corresponding effect Effects 0.000 description 37
- 229950003499 fibrin Drugs 0.000 description 37
- 108090000935 Antithrombin III Proteins 0.000 description 35
- 102000004411 Antithrombin III Human genes 0.000 description 35
- 102000010911 Enzyme Precursors Human genes 0.000 description 35
- 108010062466 Enzyme Precursors Proteins 0.000 description 35
- 229960005348 antithrombin iii Drugs 0.000 description 35
- 238000003776 cleavage reaction Methods 0.000 description 34
- 230000007017 scission Effects 0.000 description 34
- 108020004414 DNA Proteins 0.000 description 31
- 230000037361 pathway Effects 0.000 description 29
- 230000002797 proteolythic effect Effects 0.000 description 29
- 239000000203 mixture Substances 0.000 description 26
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 25
- 230000003197 catalytic effect Effects 0.000 description 25
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 23
- 108010022999 Serine Proteases Proteins 0.000 description 23
- 102000012479 Serine Proteases Human genes 0.000 description 23
- 239000003114 blood coagulation factor Substances 0.000 description 23
- 241000894007 species Species 0.000 description 22
- 210000004369 blood Anatomy 0.000 description 21
- 239000008280 blood Substances 0.000 description 21
- 230000023597 hemostasis Effects 0.000 description 20
- 230000003993 interaction Effects 0.000 description 20
- 230000008569 process Effects 0.000 description 20
- 239000000047 product Substances 0.000 description 20
- 108090000317 Chymotrypsin Proteins 0.000 description 19
- 229960002376 chymotrypsin Drugs 0.000 description 19
- 230000007246 mechanism Effects 0.000 description 18
- 230000001225 therapeutic effect Effects 0.000 description 18
- 150000001875 compounds Chemical class 0.000 description 17
- 230000006870 function Effects 0.000 description 17
- 108010013773 recombinant FVIIa Proteins 0.000 description 17
- 239000008194 pharmaceutical composition Substances 0.000 description 16
- 108090000790 Enzymes Proteins 0.000 description 15
- 102000004190 Enzymes Human genes 0.000 description 15
- 230000008859 change Effects 0.000 description 15
- 229940088598 enzyme Drugs 0.000 description 15
- 210000002381 plasma Anatomy 0.000 description 15
- 108010049003 Fibrinogen Proteins 0.000 description 14
- 102000008946 Fibrinogen Human genes 0.000 description 14
- 108010094028 Prothrombin Proteins 0.000 description 14
- 229940012952 fibrinogen Drugs 0.000 description 14
- 229940068953 recombinant fviia Drugs 0.000 description 14
- 239000000758 substrate Substances 0.000 description 14
- 102100027378 Prothrombin Human genes 0.000 description 13
- 230000001419 dependent effect Effects 0.000 description 13
- -1 for example Proteins 0.000 description 13
- 238000001727 in vivo Methods 0.000 description 13
- 239000002773 nucleotide Substances 0.000 description 13
- 229940039716 prothrombin Drugs 0.000 description 13
- 102000005962 receptors Human genes 0.000 description 13
- 108020003175 receptors Proteins 0.000 description 13
- 208000024891 symptom Diseases 0.000 description 13
- 101800004937 Protein C Proteins 0.000 description 12
- 102000017975 Protein C Human genes 0.000 description 12
- 108010029485 Protein Isoforms Proteins 0.000 description 12
- 102000001708 Protein Isoforms Human genes 0.000 description 12
- 108010076504 Protein Sorting Signals Proteins 0.000 description 12
- 125000003729 nucleotide group Chemical group 0.000 description 12
- 230000006337 proteolytic cleavage Effects 0.000 description 12
- 108010047303 von Willebrand Factor Proteins 0.000 description 12
- 102100036537 von Willebrand factor Human genes 0.000 description 12
- 241000282412 Homo Species 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 11
- 101800001700 Saposin-D Proteins 0.000 description 11
- 230000007812 deficiency Effects 0.000 description 11
- 208000035475 disorder Diseases 0.000 description 11
- 210000002889 endothelial cell Anatomy 0.000 description 11
- 239000012528 membrane Substances 0.000 description 11
- 210000004379 membrane Anatomy 0.000 description 11
- 229960000856 protein c Drugs 0.000 description 11
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 11
- 229960001134 von willebrand factor Drugs 0.000 description 11
- 102000012545 EGF-like domains Human genes 0.000 description 10
- 108050002150 EGF-like domains Proteins 0.000 description 10
- 101800003838 Epidermal growth factor Proteins 0.000 description 10
- 102100033237 Pro-epidermal growth factor Human genes 0.000 description 10
- 230000004071 biological effect Effects 0.000 description 10
- 230000023555 blood coagulation Effects 0.000 description 10
- 239000011575 calcium Substances 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 229940116977 epidermal growth factor Drugs 0.000 description 10
- 238000000338 in vitro Methods 0.000 description 10
- 238000003780 insertion Methods 0.000 description 10
- 230000037431 insertion Effects 0.000 description 10
- 230000001404 mediated effect Effects 0.000 description 10
- 238000002560 therapeutic procedure Methods 0.000 description 10
- 241000283690 Bos taurus Species 0.000 description 9
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 9
- 208000007536 Thrombosis Diseases 0.000 description 9
- 238000012217 deletion Methods 0.000 description 9
- 230000037430 deletion Effects 0.000 description 9
- 230000013595 glycosylation Effects 0.000 description 9
- 238000006206 glycosylation reaction Methods 0.000 description 9
- 230000002209 hydrophobic effect Effects 0.000 description 9
- 239000003805 procoagulant Substances 0.000 description 9
- 230000002947 procoagulating effect Effects 0.000 description 9
- 150000003721 vitamin K derivatives Chemical class 0.000 description 9
- 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 8
- 108010088842 Fibrinolysin Proteins 0.000 description 8
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- 229930003448 Vitamin K Natural products 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 230000035602 clotting Effects 0.000 description 8
- 230000000977 initiatory effect Effects 0.000 description 8
- 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 8
- 229940012957 plasmin Drugs 0.000 description 8
- 102000040430 polynucleotide Human genes 0.000 description 8
- 108091033319 polynucleotide Proteins 0.000 description 8
- 239000002157 polynucleotide Substances 0.000 description 8
- 108010016054 tissue-factor-pathway inhibitor 2 Proteins 0.000 description 8
- 102000055046 tissue-factor-pathway inhibitor 2 Human genes 0.000 description 8
- 239000011712 vitamin K Substances 0.000 description 8
- 235000019168 vitamin K Nutrition 0.000 description 8
- 229940046010 vitamin k Drugs 0.000 description 8
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 7
- 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 7
- 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 7
- 108090001126 Furin Proteins 0.000 description 7
- 241000282575 Gorilla Species 0.000 description 7
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 7
- 230000002776 aggregation Effects 0.000 description 7
- 238000004220 aggregation Methods 0.000 description 7
- 210000004204 blood vessel Anatomy 0.000 description 7
- 230000021523 carboxylation Effects 0.000 description 7
- 238000006473 carboxylation reaction Methods 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 230000010118 platelet activation Effects 0.000 description 7
- 238000012545 processing Methods 0.000 description 7
- 230000028327 secretion Effects 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 6
- 241000282472 Canis lupus familiaris Species 0.000 description 6
- 108010059378 Endopeptidases Proteins 0.000 description 6
- 102000005593 Endopeptidases Human genes 0.000 description 6
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 description 6
- 241000283973 Oryctolagus cuniculus Species 0.000 description 6
- 229940096437 Protein S Drugs 0.000 description 6
- 108010066124 Protein S Proteins 0.000 description 6
- 102000029301 Protein S Human genes 0.000 description 6
- 108091005605 Vitamin K-dependent proteins Proteins 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 230000033228 biological regulation Effects 0.000 description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
- 210000003038 endothelium Anatomy 0.000 description 6
- 230000020764 fibrinolysis Effects 0.000 description 6
- 238000001415 gene therapy Methods 0.000 description 6
- 230000002439 hemostatic effect Effects 0.000 description 6
- 230000005847 immunogenicity Effects 0.000 description 6
- 230000001976 improved effect Effects 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 230000014616 translation Effects 0.000 description 6
- 102000008186 Collagen Human genes 0.000 description 5
- 108010035532 Collagen Proteins 0.000 description 5
- 241000252212 Danio rerio Species 0.000 description 5
- 108010074860 Factor Xa Proteins 0.000 description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
- 102000003886 Glycoproteins Human genes 0.000 description 5
- 108090000288 Glycoproteins Proteins 0.000 description 5
- 241000282576 Pan paniscus Species 0.000 description 5
- 241000282405 Pongo abelii Species 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 235000004279 alanine Nutrition 0.000 description 5
- 230000003321 amplification Effects 0.000 description 5
- 210000000170 cell membrane Anatomy 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 229920001436 collagen Polymers 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 230000007547 defect Effects 0.000 description 5
- 235000013922 glutamic acid Nutrition 0.000 description 5
- 239000004220 glutamic acid Substances 0.000 description 5
- 230000033444 hydroxylation Effects 0.000 description 5
- 238000005805 hydroxylation reaction Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 238000003199 nucleic acid amplification method Methods 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 238000012546 transfer Methods 0.000 description 5
- 230000001960 triggered effect Effects 0.000 description 5
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 4
- 102000004506 Blood Proteins Human genes 0.000 description 4
- 108010017384 Blood Proteins Proteins 0.000 description 4
- 108050006018 Coagulation factor VII Proteins 0.000 description 4
- 108010071241 Factor XIIa Proteins 0.000 description 4
- 102100035233 Furin Human genes 0.000 description 4
- 241000287828 Gallus gallus Species 0.000 description 4
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
- 241000282898 Sus scrofa Species 0.000 description 4
- 102000004142 Trypsin Human genes 0.000 description 4
- 230000003213 activating effect Effects 0.000 description 4
- 239000003146 anticoagulant agent Substances 0.000 description 4
- 229940127219 anticoagulant drug Drugs 0.000 description 4
- 235000003704 aspartic acid Nutrition 0.000 description 4
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 4
- 238000004422 calculation algorithm Methods 0.000 description 4
- 235000013330 chicken meat Nutrition 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 102220024780 rs199473488 Human genes 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 230000000451 tissue damage Effects 0.000 description 4
- 231100000827 tissue damage Toxicity 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- 239000012588 trypsin Substances 0.000 description 4
- 101000984722 Bos taurus Pancreatic trypsin inhibitor Proteins 0.000 description 3
- 102100037642 Elongation factor G, mitochondrial Human genes 0.000 description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
- 108010048049 Factor IXa Proteins 0.000 description 3
- 108010054265 Factor VIIa Proteins 0.000 description 3
- 102000004961 Furin Human genes 0.000 description 3
- 101150022345 GAS6 gene Proteins 0.000 description 3
- 101000880344 Homo sapiens Elongation factor G, mitochondrial Proteins 0.000 description 3
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 241000282560 Macaca mulatta Species 0.000 description 3
- 102220507071 Mothers against decapentaplegic homolog 1_I42S_mutation Human genes 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 108091061960 Naked DNA Proteins 0.000 description 3
- 108090000573 Osteocalcin Proteins 0.000 description 3
- 102000004067 Osteocalcin Human genes 0.000 description 3
- 108010051456 Plasminogen Proteins 0.000 description 3
- 102000013566 Plasminogen Human genes 0.000 description 3
- 102000001938 Plasminogen Activators Human genes 0.000 description 3
- 108010001014 Plasminogen Activators Proteins 0.000 description 3
- 241000288906 Primates Species 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- 241000282887 Suidae Species 0.000 description 3
- 241001441724 Tetraodontidae Species 0.000 description 3
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 3
- 239000004473 Threonine Substances 0.000 description 3
- 108010079274 Thrombomodulin Proteins 0.000 description 3
- 108090000631 Trypsin Proteins 0.000 description 3
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 3
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 3
- 229910001424 calcium ion Inorganic materials 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 125000003636 chemical group Chemical group 0.000 description 3
- 239000012707 chemical precursor Substances 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 238000005094 computer simulation Methods 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 208000037765 diseases and disorders Diseases 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 3
- 210000002744 extracellular matrix Anatomy 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 210000002288 golgi apparatus Anatomy 0.000 description 3
- 238000009396 hybridization Methods 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 229930182817 methionine Natural products 0.000 description 3
- 238000002703 mutagenesis Methods 0.000 description 3
- 231100000350 mutagenesis Toxicity 0.000 description 3
- 229940112216 novoseven Drugs 0.000 description 3
- 230000008520 organization Effects 0.000 description 3
- 239000005022 packaging material Substances 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 235000019833 protease Nutrition 0.000 description 3
- 238000010188 recombinant method Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 102220020898 rs1800062 Human genes 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000003001 serine protease inhibitor Substances 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000006641 stabilisation Effects 0.000 description 3
- 238000011105 stabilization Methods 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- 102220491410 ADP-ribosylation factor-like protein 16_T37N_mutation Human genes 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 241000271566 Aves Species 0.000 description 2
- 102220617593 B1 bradykinin receptor_K38R_mutation Human genes 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 2
- 102000005701 Calcium-Binding Proteins Human genes 0.000 description 2
- 108010045403 Calcium-Binding Proteins Proteins 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 108010048623 Collagen Receptors Proteins 0.000 description 2
- 102000016511 Cyclic GMP-Dependent Protein Kinase Type I Human genes 0.000 description 2
- 108010067530 Cyclic GMP-Dependent Protein Kinase Type I Proteins 0.000 description 2
- 102220636170 Cystatin-A_I42A_mutation Human genes 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- 102220516207 Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial_K38T_mutation Human genes 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 102220523133 Eukaryotic translation initiation factor 4E-binding protein 2_T37E_mutation Human genes 0.000 description 2
- 108091060211 Expressed sequence tag Proteins 0.000 description 2
- 108010080865 Factor XII Proteins 0.000 description 2
- 102000000429 Factor XII Human genes 0.000 description 2
- 108010000196 Factor XIIIa Proteins 0.000 description 2
- 101800003778 Fibrinopeptide B Proteins 0.000 description 2
- 102400001063 Fibrinopeptide B Human genes 0.000 description 2
- 102000006395 Globulins Human genes 0.000 description 2
- 108010044091 Globulins Proteins 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 102220603445 Homeobox protein SIX3_K32T_mutation Human genes 0.000 description 2
- 208000026350 Inborn Genetic disease Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 102100025305 Integrin alpha-2 Human genes 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 208000024556 Mendelian disease Diseases 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 230000004989 O-glycosylation Effects 0.000 description 2
- 241000282579 Pan Species 0.000 description 2
- 241000282577 Pan troglodytes Species 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- 102220467432 Protein Jade-1_K38S_mutation Human genes 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 238000012300 Sequence Analysis Methods 0.000 description 2
- 229940122055 Serine protease inhibitor Drugs 0.000 description 2
- 101710102218 Serine protease inhibitor Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 102000007637 Soluble Guanylyl Cyclase Human genes 0.000 description 2
- 108010007205 Soluble Guanylyl Cyclase Proteins 0.000 description 2
- 101100226845 Strongylocentrotus purpuratus EGF2 gene Proteins 0.000 description 2
- 241001441722 Takifugu rubripes Species 0.000 description 2
- 102100026966 Thrombomodulin Human genes 0.000 description 2
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 2
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 2
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 208000037919 acquired disease Diseases 0.000 description 2
- 208000013633 acquired hemophilia Diseases 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 230000003281 allosteric effect Effects 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 238000000137 annealing Methods 0.000 description 2
- 238000000149 argon plasma sintering Methods 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 239000003130 blood coagulation factor inhibitor Substances 0.000 description 2
- 229940019700 blood coagulation factors Drugs 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 102200159067 c.130T>A Human genes 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- ZOOGRGPOEVQQDX-KHLHZJAASA-N cyclic guanosine monophosphate Chemical compound C([C@H]1O2)O[P@](O)(=O)O[C@@H]1[C@H](O)[C@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-KHLHZJAASA-N 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 2
- 229960001123 epoprostenol Drugs 0.000 description 2
- 239000003527 fibrinolytic agent Substances 0.000 description 2
- 230000003480 fibrinolytic effect Effects 0.000 description 2
- MYRIFIVQGRMHRF-OECXYHNASA-N fibrinopeptide b Chemical compound N([C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(=O)CNC(=O)[C@@H]1CCC(=O)N1 MYRIFIVQGRMHRF-OECXYHNASA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 description 2
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000002008 hemorrhagic effect Effects 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 150000008106 phosphatidylserines Chemical class 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 229940127126 plasminogen activator Drugs 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 238000001243 protein synthesis Methods 0.000 description 2
- 108010014806 prothrombinase complex Proteins 0.000 description 2
- 230000003331 prothrombotic effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000015139 regulation of coagulation Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 102200153433 rs104894817 Human genes 0.000 description 2
- 102220071724 rs794728408 Human genes 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 2
- 229960005356 urokinase Drugs 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- 229910052720 vanadium Inorganic materials 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 230000003966 vascular damage Effects 0.000 description 2
- 230000025033 vasoconstriction Effects 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
- 238000005406 washing Methods 0.000 description 2
- IWLNMFOBCLVBRQ-NFJMKROFSA-N (2s)-2-amino-4-carbamoylpentanedioic acid Chemical group OC(=O)[C@@H](N)CC(C(N)=O)C(O)=O IWLNMFOBCLVBRQ-NFJMKROFSA-N 0.000 description 1
- OIXLLKLZKCBCPS-RZVRUWJTSA-N (2s)-2-azanyl-5-[bis(azanyl)methylideneamino]pentanoic acid Chemical compound OC(=O)[C@@H](N)CCCNC(N)=N.OC(=O)[C@@H](N)CCCNC(N)=N OIXLLKLZKCBCPS-RZVRUWJTSA-N 0.000 description 1
- YYLQUHNPNCGKJQ-NHYDCYSISA-N (3R)-3-hydroxy-L-aspartic acid Chemical compound OC(=O)[C@@H](N)[C@@H](O)C(O)=O YYLQUHNPNCGKJQ-NHYDCYSISA-N 0.000 description 1
- JWICNZAGYSIBAR-LEEGLKINSA-N (4s)-4-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-2-aminopropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-5-[[2-[[(2s)-3-carboxy-1-[[(2s)-1-[[1-[[(2s)-1-[[(2s)-4-carboxy-1-[[2-[[2-[[2-[[(2s)-1-[[(1s)-1-carboxy-4-(diaminomethylideneamino Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)C(CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)N)CC1=CC=CC=C1 JWICNZAGYSIBAR-LEEGLKINSA-N 0.000 description 1
- YVOOPGWEIRIUOX-UHFFFAOYSA-N 2-azanyl-3-sulfanyl-propanoic acid Chemical compound SCC(N)C(O)=O.SCC(N)C(O)=O YVOOPGWEIRIUOX-UHFFFAOYSA-N 0.000 description 1
- 102220556665 Acetylcholinesterase_G97S_mutation Human genes 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 description 1
- 102220635301 Adenylate kinase isoenzyme 6_I42R_mutation Human genes 0.000 description 1
- 102220479262 Anaphase-promoting complex subunit 4_D33K_mutation Human genes 0.000 description 1
- 102000004149 Annexin A2 Human genes 0.000 description 1
- 108090000668 Annexin A2 Proteins 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 102000035101 Aspartic proteases Human genes 0.000 description 1
- 108091005502 Aspartic proteases Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000019838 Blood disease Diseases 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 108090000201 Carboxypeptidase B2 Proteins 0.000 description 1
- 102100035023 Carboxypeptidase B2 Human genes 0.000 description 1
- 102220493935 Casein kinase I isoform gamma-1_K38A_mutation Human genes 0.000 description 1
- 241000282994 Cervidae Species 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 102000005927 Cysteine Proteases Human genes 0.000 description 1
- 108010005843 Cysteine Proteases Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102220496805 DNA dC->dU-editing enzyme APOBEC-3A_R28E_mutation Human genes 0.000 description 1
- 102220597860 DNA endonuclease RBBP8_K62R_mutation Human genes 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 102100029722 Ectonucleoside triphosphate diphosphohydrolase 1 Human genes 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 102220516902 Estrogen-related receptor gamma_S45D_mutation Human genes 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 229940117942 Factor IX inhibitor Drugs 0.000 description 1
- 229940124135 Factor VIII inhibitor Drugs 0.000 description 1
- 108010074105 Factor Va Proteins 0.000 description 1
- 108010074864 Factor XI Proteins 0.000 description 1
- 108010071289 Factor XIII Proteins 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 101800000974 Fibrinopeptide A Proteins 0.000 description 1
- 102400000525 Fibrinopeptide A Human genes 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 1
- 241000699694 Gerbillinae Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108060003393 Granulin Proteins 0.000 description 1
- 108010054964 H-hexahydrotyrosyl-alanyl-arginine-4-nitroanilide Proteins 0.000 description 1
- 102220594400 HLA class I histocompatibility antigen, C alpha chain_D33F_mutation Human genes 0.000 description 1
- 102220594399 HLA class I histocompatibility antigen, C alpha chain_D33S_mutation Human genes 0.000 description 1
- 229920002971 Heparan sulfate Polymers 0.000 description 1
- 108010000487 High-Molecular-Weight Kininogen Proteins 0.000 description 1
- 102220570133 Histone PARylation factor 1_K32Q_mutation Human genes 0.000 description 1
- 102220603448 Homeobox protein SIX3_A34R_mutation Human genes 0.000 description 1
- 102220603449 Homeobox protein SIX3_A34S_mutation Human genes 0.000 description 1
- 102220603453 Homeobox protein SIX3_A34W_mutation Human genes 0.000 description 1
- 102220603436 Homeobox protein SIX3_K32A_mutation Human genes 0.000 description 1
- 101001012447 Homo sapiens Ectonucleoside triphosphate diphosphohydrolase 1 Proteins 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
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 108010017642 Integrin alpha2beta1 Proteins 0.000 description 1
- 102000001399 Kallikrein Human genes 0.000 description 1
- 108060005987 Kallikrein Proteins 0.000 description 1
- 102100035792 Kininogen-1 Human genes 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 102220566643 Lipoprotein lipase_E82A_mutation Human genes 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- DINOPBPYOCMGGD-VEDJBHDQSA-N Man(a1-2)Man(a1-2)Man(a1-3)[Man(a1-2)Man(a1-3)[Man(a1-2)Man(a1-6)]Man(a1-6)]Man(b1-4)GlcNAc(b1-4)GlcNAc Chemical compound O[C@@H]1[C@@H](NC(=O)C)C(O)O[C@H](CO)[C@H]1O[C@H]1[C@H](NC(C)=O)[C@@H](O)[C@H](O[C@H]2[C@H]([C@@H](O[C@@H]3[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O[C@@H]3[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O[C@@H]3[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)[C@H](O)[C@@H](CO[C@@H]3[C@H]([C@@H](O[C@@H]4[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O[C@@H]4[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)[C@H](O)[C@@H](CO[C@@H]4[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O[C@@H]4[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)O3)O)O2)O)[C@@H](CO)O1 DINOPBPYOCMGGD-VEDJBHDQSA-N 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 102220540445 Ovarian cancer-related protein 1_Y44S_mutation Human genes 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108090000279 Peptidyltransferases Proteins 0.000 description 1
- 102220469874 Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN_A34D_mutation Human genes 0.000 description 1
- 102220520254 Phospholipase A2 group XV_D46C_mutation Human genes 0.000 description 1
- 102000012335 Plasminogen Activator Inhibitor 1 Human genes 0.000 description 1
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 1
- 102000004179 Plasminogen Activator Inhibitor 2 Human genes 0.000 description 1
- 108090000614 Plasminogen Activator Inhibitor 2 Proteins 0.000 description 1
- 102000010752 Plasminogen Inactivators Human genes 0.000 description 1
- 108010077971 Plasminogen Inactivators Proteins 0.000 description 1
- 206010073391 Platelet dysfunction Diseases 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102220547369 Protein APCDD1_L65S_mutation Human genes 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 241000282849 Ruminantia Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 108090000083 Serine Endopeptidases Proteins 0.000 description 1
- 102000003667 Serine Endopeptidases Human genes 0.000 description 1
- 102000008847 Serpin Human genes 0.000 description 1
- 108050000761 Serpin Proteins 0.000 description 1
- 102220494687 Small vasohibin-binding protein_R36E_mutation Human genes 0.000 description 1
- 241000718541 Tetragastris balsamifera Species 0.000 description 1
- 102000035100 Threonine proteases Human genes 0.000 description 1
- 108091005501 Threonine proteases Proteins 0.000 description 1
- 102000003790 Thrombin receptors Human genes 0.000 description 1
- 108090000166 Thrombin receptors Proteins 0.000 description 1
- 102000002938 Thrombospondin Human genes 0.000 description 1
- 108060008245 Thrombospondin Proteins 0.000 description 1
- 108060008539 Transglutaminase Proteins 0.000 description 1
- 101710162629 Trypsin inhibitor Proteins 0.000 description 1
- 102220586119 Tubulin polymerization-promoting protein_S45E_mutation Human genes 0.000 description 1
- 206010046306 Upper respiratory tract infection Diseases 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 201000000839 Vitamin K Deficiency Bleeding Diseases 0.000 description 1
- 206010047634 Vitamin K deficiency Diseases 0.000 description 1
- 208000027276 Von Willebrand disease Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 201000004208 acquired thrombocytopenia Diseases 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical class N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000008841 allosteric interaction Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000004410 anthocyanin Substances 0.000 description 1
- 230000000603 anti-haemophilic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- 229940030225 antihemorrhagics Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000004019 antithrombin Substances 0.000 description 1
- 239000013011 aqueous formulation Substances 0.000 description 1
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 108010083526 asialo-von Willebrand Factor Proteins 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical group N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000003851 biochemical process Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 102220411562 c.175G>A Human genes 0.000 description 1
- 102200102393 c.194T>A Human genes 0.000 description 1
- 239000004303 calcium sorbate Substances 0.000 description 1
- 108090001015 cancer procoagulant Proteins 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- UHBYWPGGCSDKFX-UHFFFAOYSA-N carboxyglutamic acid Chemical compound OC(=O)C(N)CC(C(O)=O)C(O)=O UHBYWPGGCSDKFX-UHFFFAOYSA-N 0.000 description 1
- 238000010523 cascade reaction Methods 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- 229940043292 chymotrypsin / trypsin Drugs 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 229940105772 coagulation factor vii Drugs 0.000 description 1
- 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 1
- 102000021124 collagen binding proteins Human genes 0.000 description 1
- 108091011142 collagen binding proteins Proteins 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 230000009073 conformational modification Effects 0.000 description 1
- 230000008876 conformational transition Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 229940072645 coumadin Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 102220500037 eIF5-mimic protein 2_K32G_mutation Human genes 0.000 description 1
- 230000008753 endothelial function Effects 0.000 description 1
- 230000009843 endothelial lesion Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 229940012414 factor viia Drugs 0.000 description 1
- 229940012444 factor xiii Drugs 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
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 108010013113 glutamyl carboxylase Proteins 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000002874 hemostatic agent Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940027941 immunoglobulin g Drugs 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 210000000723 mammalian artificial chromosome Anatomy 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 230000009149 molecular binding Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 230000014508 negative regulation of coagulation Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000008288 physiological mechanism Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 108010025221 plasma protein Z Proteins 0.000 description 1
- 239000002797 plasminogen activator inhibitor Substances 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 235000015277 pork Nutrition 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000008742 procoagulation Effects 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000009465 prokaryotic expression Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 210000001243 pseudopodia Anatomy 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 229940124553 radioprotectant Drugs 0.000 description 1
- 230000003439 radiotherapeutic effect Effects 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 208000020029 respiratory tract infectious disease Diseases 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 102220033735 rs104886489 Human genes 0.000 description 1
- 102220234446 rs1064795967 Human genes 0.000 description 1
- 102220004442 rs121918685 Human genes 0.000 description 1
- 102220095974 rs149101834 Human genes 0.000 description 1
- 102220276595 rs1553131446 Human genes 0.000 description 1
- 102220253478 rs1553261891 Human genes 0.000 description 1
- 102220249718 rs1553408194 Human genes 0.000 description 1
- 102220321823 rs1554812271 Human genes 0.000 description 1
- 102220288148 rs1554893773 Human genes 0.000 description 1
- 102220071725 rs199473488 Human genes 0.000 description 1
- 102220008235 rs199476326 Human genes 0.000 description 1
- 102220249828 rs267606858 Human genes 0.000 description 1
- 102220005499 rs33938574 Human genes 0.000 description 1
- 102200118254 rs33995148 Human genes 0.000 description 1
- 102220005309 rs33995148 Human genes 0.000 description 1
- 102200118250 rs34446260 Human genes 0.000 description 1
- 102200082816 rs34868397 Human genes 0.000 description 1
- 102200066497 rs35629723 Human genes 0.000 description 1
- 102220114727 rs372166877 Human genes 0.000 description 1
- 102220297938 rs375722926 Human genes 0.000 description 1
- 102220005421 rs41381645 Human genes 0.000 description 1
- 102220037197 rs587780270 Human genes 0.000 description 1
- 102200020878 rs73015965 Human genes 0.000 description 1
- 102220323551 rs771587118 Human genes 0.000 description 1
- 102220217756 rs777095030 Human genes 0.000 description 1
- 102220064446 rs786205841 Human genes 0.000 description 1
- 102220272417 rs80357066 Human genes 0.000 description 1
- 102200057185 rs863225150 Human genes 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 230000002311 subsequent effect Effects 0.000 description 1
- 238000006277 sulfonation reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 230000002885 thrombogenetic effect Effects 0.000 description 1
- 229960000187 tissue plasminogen activator Drugs 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 230000007838 tissue remodeling Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 102000003601 transglutaminase Human genes 0.000 description 1
- 238000012384 transportation and delivery Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 229960001322 trypsin Drugs 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 108010087967 type I signal peptidase Proteins 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000007556 vascular defect Effects 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 230000003639 vasoconstrictive effect Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 208000016794 vitamin K deficiency hemorrhagic disease Diseases 0.000 description 1
- 208000012137 von Willebrand disease (hereditary or acquired) Diseases 0.000 description 1
- 229960005080 warfarin Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/745—Blood coagulation or fibrinolysis factors
-
- 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/36—Blood coagulation or fibrinolysis factors
-
- 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/36—Blood coagulation or fibrinolysis factors
- A61K38/37—Factors VIII
-
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
-
- 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)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Zoology (AREA)
- Hematology (AREA)
- Genetics & Genomics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Toxicology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Diabetes (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Neurology (AREA)
- Urology & Nephrology (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US92351207P | 2007-04-13 | 2007-04-13 | |
| US60/923,512 | 2007-04-13 | ||
| PCT/US2008/004795 WO2008127702A2 (en) | 2007-04-13 | 2008-04-11 | Modified factor vii polypetides and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2009141510A RU2009141510A (ru) | 2011-05-20 |
| RU2571931C2 true RU2571931C2 (ru) | 2015-12-27 |
Family
ID=39689319
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2009141510/10A RU2571931C2 (ru) | 2007-04-13 | 2008-04-11 | Полипептиды на основе модифицированного фактора vii и их применение |
Country Status (29)
| Country | Link |
|---|---|
| US (1) | US20100166729A9 (enExample) |
| EP (2) | EP2147096B1 (enExample) |
| JP (3) | JP5761782B2 (enExample) |
| KR (2) | KR20100016462A (enExample) |
| CN (2) | CN101743309B (enExample) |
| AU (1) | AU2008239586B2 (enExample) |
| BR (1) | BRPI0810172A2 (enExample) |
| CA (1) | CA2683443A1 (enExample) |
| CO (1) | CO6231052A2 (enExample) |
| CR (1) | CR11058A (enExample) |
| DK (1) | DK2147096T3 (enExample) |
| EC (1) | ECSP099735A (enExample) |
| ES (1) | ES2537328T3 (enExample) |
| GT (1) | GT200900268A (enExample) |
| HN (1) | HN2009002098A (enExample) |
| IL (2) | IL201173A0 (enExample) |
| MX (1) | MX2009010997A (enExample) |
| NI (1) | NI200900187A (enExample) |
| NZ (2) | NZ593611A (enExample) |
| PH (1) | PH12014501960A1 (enExample) |
| PL (1) | PL2147096T3 (enExample) |
| PT (1) | PT2147096E (enExample) |
| RU (1) | RU2571931C2 (enExample) |
| SG (1) | SG174077A1 (enExample) |
| SI (1) | SI2147096T1 (enExample) |
| SV (1) | SV2009003393A (enExample) |
| UA (1) | UA101155C2 (enExample) |
| WO (1) | WO2008127702A2 (enExample) |
| ZA (2) | ZA200906854B (enExample) |
Families Citing this family (60)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7700341B2 (en) * | 2000-02-03 | 2010-04-20 | Dendreon Corporation | Nucleic acid molecules encoding transmembrane serine proteases, the encoded proteins and methods based thereon |
| WO2004031733A2 (en) * | 2002-10-02 | 2004-04-15 | Catalyst Biosciences | Methods of generating and screenign for porteases with altered specificity |
| US7939304B2 (en) * | 2002-10-02 | 2011-05-10 | Catalyst Biosciences, Inc. | Mutant MT-SP1 proteases with altered substrate specificity or activity |
| WO2005110453A2 (en) * | 2004-04-12 | 2005-11-24 | Catalyst Biosciences, Inc. | Cleavage of vegf and vegf receptor by wildtype and mutant mt-sp1 |
| KR101126423B1 (ko) | 2005-10-21 | 2012-07-11 | 카탈리스트 바이오사이언시즈, 인코포레이티드 | 보체 활성화를 억제하는 변형된 프로테아제 |
| EP2423307A1 (en) * | 2006-06-19 | 2012-02-29 | Catalyst Biosciences, Inc. | Modified coagulation factor IV polypeptides and use thereof for treatment |
| ES2372709T3 (es) | 2006-07-05 | 2012-01-25 | Catalyst Biosciences, Inc. | Procedimientos de cribado de proteasas y proteasas identificadas por los mismos. |
| RU2571931C2 (ru) * | 2007-04-13 | 2015-12-27 | Каталист Биосайенсис, Инк. | Полипептиды на основе модифицированного фактора vii и их применение |
| TWI465247B (zh) | 2008-04-11 | 2014-12-21 | Catalyst Biosciences Inc | 經修飾的因子ｖｉｉ多肽和其用途 |
| EP2177624A1 (en) * | 2008-10-02 | 2010-04-21 | Siemens Healthcare Diagnostics Products GmbH | Blood coagulation assays |
| AU2010266065B2 (en) | 2009-06-25 | 2016-01-14 | The University Of North Carolina At Chapel Hill | Chimeric Factor VII molecules |
| GB0916578D0 (en) * | 2009-09-22 | 2009-10-28 | Malmsten Nils M | Polypeptides and uses thereof |
| GB201007356D0 (en) | 2010-04-30 | 2010-06-16 | Leverton Licence Holdings Ltd | Conjugated factor VIIa |
| DK2624859T3 (en) | 2010-10-06 | 2017-06-06 | Medimmune Ltd | FACTOR II ALONE OR IN COMBINATION WITH OTHER FACTORS FOR TREATMENT OF REDUCED HEMOSTASE IN CONNECTION WITH DILUTION COAGULOPATHY |
| US8663624B2 (en) | 2010-10-06 | 2014-03-04 | The Regents Of The University Of California | Adeno-associated virus virions with variant capsid and methods of use thereof |
| US9725689B2 (en) | 2010-10-08 | 2017-08-08 | Terumo Bct, Inc. | Configurable methods and systems of growing and harvesting cells in a hollow fiber bioreactor system |
| TWI595004B (zh) | 2010-11-03 | 2017-08-11 | 介控生化科技公司 | 經修飾之第九因子多胜肽及其用途 |
| DK3693025T3 (da) | 2011-04-22 | 2022-01-10 | Univ California | Adenoassocierede virus-virioner med variant capsid og fremgangsmåder til anvendelse heraf |
| WO2012149463A1 (en) * | 2011-04-29 | 2012-11-01 | The University Of North Carolina At Chapel Hill | Chimeric factor vii molecules with enhanced half life and methods of use |
| EP2554161A1 (en) | 2011-08-02 | 2013-02-06 | LFB Biotechnologies | Pharmaceutical composition comprising factor VII encapsulated in micelles |
| HRP20191920T1 (hr) * | 2012-01-12 | 2020-01-10 | Bioverativ Therapeutics Inc. | Kimerni polipeptidi faktora viii i njihova uporaba |
| HK1200695A1 (en) | 2012-04-16 | 2015-08-14 | Cantab Biopharmaceuticals Patents Limited | Optimised subcutaneous therapeutic agents |
| WO2013177584A2 (en) * | 2012-05-25 | 2013-11-28 | The Children's Hospital Of Philadelphia | FVIIa VARIANTS EXHIBITING ALTERED INTERACTION WITH ENDOTHELIAL PROTEIN C RECEPTOR (EPCR) AND METHODS OF USE THEREOF FOR MODULATING HEMOSTASIS |
| WO2014008172A2 (en) * | 2012-07-03 | 2014-01-09 | Expression Therapeutics, Llc | High yield suspension cell line, system and method for making same |
| KR102049900B1 (ko) | 2012-07-25 | 2019-11-28 | 카탈리스트 바이오사이언시즈, 인코포레이티드 | 변형 인자 x 폴리펩티드 및 이의 용도 |
| JP2015533152A (ja) | 2012-10-15 | 2015-11-19 | ノヴォ・ノルディスク・ヘルス・ケア・アーゲー | 第ｖｉｉ因子コンジュゲート |
| PT3524618T (pt) | 2013-03-15 | 2023-06-06 | Gladiator Biosciences Inc | Domínios gla como agentes de marcação |
| US11136557B2 (en) | 2013-05-31 | 2021-10-05 | The Regents Of The University Of California | Adeno-associated virus variants and methods of use thereof |
| CN104774269B (zh) * | 2013-08-16 | 2016-02-24 | 安源生物科技(上海)有限公司 | 改良型人凝血因子FVII-Fc融合蛋白及其制备方法与用途 |
| CA2927756A1 (en) | 2013-10-15 | 2015-04-23 | Novo Nordisk Health Care Ag | Coagulation factor vii polypeptides |
| EP3068867B1 (en) | 2013-11-16 | 2018-04-18 | Terumo BCT, Inc. | Expanding cells in a bioreactor |
| EA201691111A1 (ru) | 2014-01-10 | 2017-01-30 | Байоджен Ма Инк. | Химерные белки фактора viii и их применение |
| ES2822551T3 (es) | 2014-03-17 | 2021-05-04 | Adverum Biotechnologies Inc | Composiciones y métodos para la expresión génica mejorada en células de los conos |
| US11008547B2 (en) | 2014-03-25 | 2021-05-18 | Terumo Bct, Inc. | Passive replacement of media |
| NZ727444A (en) * | 2014-05-26 | 2021-12-24 | Academisch Ziekenhuis Leiden | Prohemostatic proteins for the treatment of bleeding |
| EP3198006B1 (en) | 2014-09-26 | 2021-03-24 | Terumo BCT, Inc. | Scheduled feed |
| FI3265178T3 (fi) | 2015-03-02 | 2026-08-03 | Adverum Biotechnologies Inc | Koostumuksia ja menetelmiä polynukleotidien viemiseksi intravitreaalisesti retinaalisiin tappisoluihin |
| JP6836999B2 (ja) | 2015-03-24 | 2021-03-03 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニアＴｈｅ Ｒｅｇｅｎｔｓ Ｏｆ Ｔｈｅ Ｕｎｉｖｅｒｓｉｔｙ Ｏｆ Ｃａｌｉｆｏｒｎｉａ | アデノ随伴ウイルス変異体及びその使用方法 |
| WO2017004592A1 (en) | 2015-07-02 | 2017-01-05 | Terumo Bct, Inc. | Cell growth with mechanical stimuli |
| WO2017205667A1 (en) | 2016-05-25 | 2017-11-30 | Terumo Bct, Inc. | Cell expansion |
| US11104874B2 (en) | 2016-06-07 | 2021-08-31 | Terumo Bct, Inc. | Coating a bioreactor |
| US11685883B2 (en) | 2016-06-07 | 2023-06-27 | Terumo Bct, Inc. | Methods and systems for coating a cell growth surface |
| CN109640949B (zh) | 2016-07-29 | 2022-11-25 | 加利福尼亚大学董事会 | 具有变异衣壳的腺相关病毒病毒体和其使用方法 |
| AU2017345470B2 (en) | 2016-10-19 | 2023-08-03 | Adverum Biotechnologies, Inc. | Modified AAV capsids and uses thereof |
| KR20190090827A (ko) | 2016-12-02 | 2019-08-02 | 바이오버라티브 테라퓨틱스 인크. | 키메라 응고 인자를 사용해 혈우병성 관절증을 치료하는 방법 |
| JP7393945B2 (ja) | 2017-03-31 | 2023-12-07 | テルモ ビーシーティー、インコーポレーテッド | 細胞増殖 |
| US12234441B2 (en) | 2017-03-31 | 2025-02-25 | Terumo Bct, Inc. | Cell expansion |
| US11624046B2 (en) | 2017-03-31 | 2023-04-11 | Terumo Bct, Inc. | Cell expansion |
| JP2020519272A (ja) * | 2017-05-09 | 2020-07-02 | エモリー ユニバーシティー | 凝固因子変異体及びその使用 |
| WO2018222503A1 (en) * | 2017-05-31 | 2018-12-06 | The Regents Of The University Of California | Adeno-associated virus with variant capsid and methods of use thereof |
| KR20250023600A (ko) | 2017-06-30 | 2025-02-18 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | 변이체 캡시드를 보유한 아데노-부속 바이러스 비리온 및 이의 사용 방법 |
| MX2020001997A (es) | 2017-08-28 | 2020-07-20 | Univ California | Variantes de capside de virus adenoasociado y metodos de uso de estas. |
| JP2020533976A (ja) | 2017-09-05 | 2020-11-26 | グラディエーター バイオサイエンシーズ インコーポレイテッド | エキソソームを標的化する方法 |
| KR102914074B1 (ko) | 2018-05-18 | 2026-01-16 | 바이오버라티브 테라퓨틱스 인크. | A형 혈우병의 치료 방법 |
| US11560556B2 (en) | 2018-08-03 | 2023-01-24 | Duke University | Protein C-factor VII chimeras |
| EP3833381B1 (en) * | 2019-08-15 | 2022-08-03 | Catalyst Biosciences, Inc. | Modified factor vii polypeptides for subcutaneous administration |
| EP4314244B1 (en) | 2021-03-23 | 2025-07-23 | Terumo BCT, Inc. | Cell capture and expansion |
| US12152699B2 (en) | 2022-02-28 | 2024-11-26 | Terumo Bct, Inc. | Multiple-tube pinch valve assembly |
| USD1099116S1 (en) | 2022-09-01 | 2025-10-21 | Terumo Bct, Inc. | Display screen or portion thereof with a graphical user interface for displaying cell culture process steps and measurements of an associated bioreactor device |
| EP4704876A2 (en) * | 2023-05-04 | 2026-03-11 | The Cleveland Clinic Foundation | Human factor vii deletion constructs for treating cancer |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004083361A2 (en) * | 2003-03-20 | 2004-09-30 | Maxygen Holdings Ltd. | FVII OR FVIIa VARIANTS |
| RU2278123C2 (ru) * | 2000-02-11 | 2006-06-20 | Максиджен Холдингз Лтд. | Молекулы, подобные фактору vii или viia |
| WO2006114105A2 (en) * | 2005-04-26 | 2006-11-02 | Maxygen Holdings Ltd. | Use of modified factor vii for treating bleeding |
| WO2007031559A2 (en) * | 2005-09-14 | 2007-03-22 | Novo Nordisk Health Care Ag | Human coagulation factor vii polypeptides |
Family Cites Families (88)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| US4952496A (en) | 1984-03-30 | 1990-08-28 | Associated Universities, Inc. | Cloning and expression of the gene for bacteriophage T7 RNA polymerase |
| GR860984B (en) * | 1985-04-17 | 1986-08-18 | Zymogenetics Inc | Expression of factor vii and ix activities in mammalian cells |
| DK323587D0 (da) | 1987-06-25 | 1987-06-25 | Novo Industri As | Protein |
| US5283187A (en) | 1987-11-17 | 1994-02-01 | Brown University Research Foundation | Cell culture-containing tubular capsule produced by co-extrusion |
| US4892538A (en) | 1987-11-17 | 1990-01-09 | Brown University Research Foundation | In vivo delivery of neurotransmitters by implanted, encapsulated cells |
| US5052558A (en) | 1987-12-23 | 1991-10-01 | Entravision, Inc. | Packaged pharmaceutical product |
| DE68927933T2 (de) | 1988-09-02 | 1997-08-14 | Dyax Corp | Herstellung und auswahl von rekombinantproteinen mit verschiedenen bindestellen |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| US5033352A (en) | 1989-01-19 | 1991-07-23 | Yamaha Corporation | Electronic musical instrument with frequency modulation |
| US5580560A (en) | 1989-11-13 | 1996-12-03 | Novo Nordisk A/S | Modified factor VII/VIIa |
| ATE180834T1 (de) * | 1990-01-29 | 1999-06-15 | Zymogenetics Inc | Antikoagulierende proteine |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| ES2139598T3 (es) | 1990-07-10 | 2000-02-16 | Medical Res Council | Procedimientos para la produccion de miembros de parejas de union especifica. |
| DE69129154T2 (de) | 1990-12-03 | 1998-08-20 | Genentech, Inc., South San Francisco, Calif. | Verfahren zur anreicherung von proteinvarianten mit geänderten bindungseigenschaften |
| US5817788A (en) * | 1991-02-28 | 1998-10-06 | Zymogenetics, Inc. | Modified factor VII |
| US5861374A (en) * | 1991-02-28 | 1999-01-19 | Novo Nordisk A/S | Modified Factor VII |
| US20040087498A1 (en) * | 1991-02-28 | 2004-05-06 | Novo Nordisk Health Care Ag | Modified factor VII |
| US5788965A (en) * | 1991-02-28 | 1998-08-04 | Novo Nordisk A/S | Modified factor VII |
| DE69233697T2 (de) | 1991-03-01 | 2008-01-24 | Dyax Corp., Cambridge | Verfahren zur Entwicklung von bindenden Mikroproteinen |
| PT100379B (pt) | 1991-04-10 | 1999-01-29 | Scripps Research Inst | Bibliotecas de receptores heterodimericos usando fagomideos |
| DE4122599C2 (de) | 1991-07-08 | 1993-11-11 | Deutsches Krebsforsch | Phagemid zum Screenen von Antikörpern |
| US5323907A (en) | 1992-06-23 | 1994-06-28 | Multi-Comp, Inc. | Child resistant package assembly for dispensing pharmaceutical medications |
| DE69841459D1 (en) | 1997-02-14 | 2010-03-11 | American Nat Red Cross | Expression des active human factor ix im brustdrüsengewebe transgener tiere |
| US20050032690A1 (en) * | 1997-09-10 | 2005-02-10 | Rojkjaer Lisa Payne | Factor VII polypeptides for preventing formation of inhibitors in subjects with haemophilia |
| US6017882A (en) | 1997-10-23 | 2000-01-25 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| US6693075B1 (en) | 1997-10-23 | 2004-02-17 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| US7247708B2 (en) * | 1997-10-23 | 2007-07-24 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| EP1068356B8 (en) | 1998-04-03 | 2007-01-03 | Adnexus Therapeutics, Inc. | Addressable protein arrays |
| DE19937219A1 (de) | 1999-08-06 | 2001-02-08 | Aventis Behring Gmbh | Verfahren zur Reindarstellung der den Blutgerinnungsfaktor VII aktivierenden Protease, ihres Proenzyms oder eines Gemisches beider Proteine mittels Ionenaustauscherchromatographie |
| WO2001032711A2 (en) | 1999-10-21 | 2001-05-10 | Board Of Trustees Of The University Of Arkansas | Adeno-associated virus aav rep78 major regulatory protein, mutants thereof and uses thereof |
| GB9928787D0 (en) | 1999-12-03 | 2000-02-02 | Medical Res Council | Direct screening method |
| US6905683B2 (en) * | 2000-05-03 | 2005-06-14 | Novo Nordisk Healthcare A/G | Human coagulation factor VII variants |
| WO2001083725A1 (en) | 2000-05-03 | 2001-11-08 | Novo Nordisk A/S | Human coagulation factor vii variants |
| DK1282438T3 (da) * | 2000-05-10 | 2005-11-14 | Novo Nordisk Healthcare Ag | Farmaceutisk sammensætning omfattende en faktor VIIa og en faktor XIII |
| EP2226385B1 (en) | 2000-09-13 | 2013-07-10 | Novo Nordisk Health Care AG | Human Coagulation Factor VII Variants |
| RU2326126C2 (ru) * | 2000-09-13 | 2008-06-10 | Ново Нордиск Хелт Кэр Аг | Полипептид фактора vii свертывания крови, его получение и применение |
| AU2001291653A1 (en) * | 2000-10-02 | 2002-04-15 | Novo-Nordisk A/S | Industrial-scale serum-free production of recombinant factor vii in mammalian cells |
| WO2002038162A1 (en) | 2000-11-09 | 2002-05-16 | The Scripps Research Institute | MODIFIED FACTOR VIIa |
| US6800453B2 (en) | 2001-01-23 | 2004-10-05 | President And Fellows Of Harvard College | Nucleic-acid programmable protein arrays |
| US20040133930A1 (en) | 2002-03-11 | 2004-07-08 | Cooper Julian D. | Production of high levels of transgenic factor ix without gene rescue, and its therapeutic uses |
| US7235638B2 (en) * | 2001-03-22 | 2007-06-26 | Novo Nordisk Healthcare A/G | Coagulation factor VII derivatives |
| ES2432967T3 (es) | 2001-03-22 | 2013-12-05 | Novo Nordisk Health Care Ag | Derivados del Factor VII de coagulación |
| US20030134298A1 (en) * | 2001-07-03 | 2003-07-17 | Madison Edwin L. | Nucleic acid molecules encoding a transmembrane serine protease 20, the encoded polypeptides and methods based thereon |
| US7419949B2 (en) * | 2001-07-16 | 2008-09-02 | Novo Noridsk Healthcare A/G | Single-dose administration of factor VIIa |
| US6882883B2 (en) * | 2001-08-31 | 2005-04-19 | Medtronic, Inc. | Implantable medical device (IMD) system configurable to subject a patient to a stress test and to detect myocardial ischemia within the patient |
| US7052868B2 (en) * | 2001-09-27 | 2006-05-30 | Novo Nordisk Healthcare A/G | Human coagulation factor VII polypeptides |
| HUP0500060A3 (en) | 2001-09-27 | 2010-01-28 | Novo Nordisk Healthcare Ag | Human coagulation factor vii polypeptides |
| EP1434857B1 (en) * | 2001-10-02 | 2007-08-01 | Novo Nordisk Health Care AG | Method for production of recombinant proteins in eukaryote cells |
| US20030143219A1 (en) * | 2001-10-09 | 2003-07-31 | Madison Edwin L | Nucleic acid molecules encoding a transmembrane serine protease 25, the encoded polypeptides and methods based thereon |
| JP3862996B2 (ja) | 2001-10-31 | 2006-12-27 | 帝人ファイバー株式会社 | ポリトリメチレンテレフタレートフィラメント糸およびその製造方法 |
| US6960657B2 (en) * | 2001-11-02 | 2005-11-01 | Novo Nordisk Healthcare A/G | Human coagulation factor VII polypeptides |
| US7291587B2 (en) * | 2001-11-09 | 2007-11-06 | Novo Nordisk Healthcare A/G | Pharmaceutical composition comprising factor VII polypeptides and TAFI polypeptides |
| US20030134794A1 (en) * | 2001-11-20 | 2003-07-17 | Madison Edwin L. | Nucleic acid molecules encoding serine protease 17, the encoded polypeptides and methods based thereon |
| KR20040065278A (ko) * | 2001-12-21 | 2004-07-21 | 노보 노르디스크 에이/에스 | 변경된 인자 ⅶ 폴리펩티드의 액체 조성물 |
| PL370656A1 (en) * | 2001-12-21 | 2005-05-30 | Novo Nordisk A/S | Liquid composition of modified factor vii polypeptides |
| DE60334983D1 (de) * | 2002-04-30 | 2010-12-30 | Bayer Healthcare Llc | Faktor vii oder faktor viia polypeptidvarianten |
| US20040009918A1 (en) * | 2002-05-03 | 2004-01-15 | Hanne Nedergaard | Stabilised solid compositions of modified factor VII |
| US20040001801A1 (en) * | 2002-05-23 | 2004-01-01 | Corvas International, Inc. | Conjugates activated by cell surface proteases and therapeutic uses thereof |
| DE60336555D1 (de) * | 2002-06-21 | 2011-05-12 | Novo Nordisk Healthcare Ag | Pegylierte glykoformen von faktor vii |
| WO2004005471A2 (en) * | 2002-07-02 | 2004-01-15 | Dendreon Corporation | Serine protease 16 |
| ATE370968T1 (de) | 2002-09-25 | 2007-09-15 | Novo Nordisk Healthcare Ag | Varianten des menschliche koagulationsfaktors vii |
| US6911323B2 (en) * | 2002-09-25 | 2005-06-28 | Novo Nordisk Healthcare A/G | Human coagulation factor VII polypeptides |
| JP4472526B2 (ja) | 2002-09-30 | 2010-06-02 | バイエル ヘルスケア エルエルシー | 凝血活性が増加した第ＶＩＩ因子または第ＶＩＩａ因子変種 |
| WO2004031733A2 (en) | 2002-10-02 | 2004-04-15 | Catalyst Biosciences | Methods of generating and screenign for porteases with altered specificity |
| FI20030413L (fi) | 2003-03-20 | 2004-09-21 | Suomen Intech Oy | Kaasulaakerointi |
| US7897734B2 (en) * | 2003-03-26 | 2011-03-01 | Novo Nordisk Healthcare Ag | Method for the production of proteins |
| WO2004087933A2 (en) | 2003-03-28 | 2004-10-14 | The Regents Of The University Of California | A novel encoding method for 'one-bead one-compound' combinatorial libraries |
| WO2004108763A2 (en) | 2003-06-05 | 2004-12-16 | Canadian Blood Services | Mutants of the factor vii epidermal growth factor domain |
| US20060116324A1 (en) * | 2003-06-13 | 2006-06-01 | Novo Nordisk Healthcare A/G | Novel formulations |
| JP4915918B2 (ja) * | 2003-06-19 | 2012-04-11 | バイエル ヘルスケア エルエルシー | 第ＶＩＩ因子または第ＶＩＩａ因子のＧｌａドメイン変種 |
| CN101870729A (zh) * | 2003-09-09 | 2010-10-27 | 诺和诺德医疗保健公司 | 凝固因子ⅶ多肽 |
| EP1673453A2 (en) * | 2003-10-07 | 2006-06-28 | Novo Nordisk Health Care AG | Hybrid molecules having factor vii/viia activity |
| US20070072271A1 (en) * | 2004-01-07 | 2007-03-29 | Novo Nordisk Healthcare A/G | Method for the production of recombinant proteins |
| EP1713906A2 (en) | 2004-02-03 | 2006-10-25 | Novo Nordisk Health Care AG | Coagulation factor vii/viia variants lacking functional lipid membrane binding domain |
| WO2005110453A2 (en) * | 2004-04-12 | 2005-11-24 | Catalyst Biosciences, Inc. | Cleavage of vegf and vegf receptor by wildtype and mutant mt-sp1 |
| JP2008503541A (ja) | 2004-06-21 | 2008-02-07 | ノボ ノルディスク ヘルス ケア アクチェンゲゼルシャフト | グリコシル化分裂型因子ｖｉｉ変異体 |
| US20060019893A1 (en) * | 2004-07-02 | 2006-01-26 | Genentech, Inc. | Factor VIIa variants |
| JP2009508510A (ja) * | 2005-09-21 | 2009-03-05 | ノボ ノルディスク ヘルス ケア アーゲー | ヒト凝固第ｖｉｉ因子ポリペプチド |
| KR101126423B1 (ko) * | 2005-10-21 | 2012-07-11 | 카탈리스트 바이오사이언시즈, 인코포레이티드 | 보체 활성화를 억제하는 변형된 프로테아제 |
| EP2423307A1 (en) * | 2006-06-19 | 2012-02-29 | Catalyst Biosciences, Inc. | Modified coagulation factor IV polypeptides and use thereof for treatment |
| ES2372709T3 (es) * | 2006-07-05 | 2012-01-25 | Catalyst Biosciences, Inc. | Procedimientos de cribado de proteasas y proteasas identificadas por los mismos. |
| RU2571931C2 (ru) * | 2007-04-13 | 2015-12-27 | Каталист Биосайенсис, Инк. | Полипептиды на основе модифицированного фактора vii и их применение |
| TWI465247B (zh) * | 2008-04-11 | 2014-12-21 | Catalyst Biosciences Inc | 經修飾的因子ｖｉｉ多肽和其用途 |
| AU2010266065B2 (en) * | 2009-06-25 | 2016-01-14 | The University Of North Carolina At Chapel Hill | Chimeric Factor VII molecules |
| TWI595004B (zh) * | 2010-11-03 | 2017-08-11 | 介控生化科技公司 | 經修飾之第九因子多胜肽及其用途 |
| KR102049900B1 (ko) * | 2012-07-25 | 2019-11-28 | 카탈리스트 바이오사이언시즈, 인코포레이티드 | 변형 인자 x 폴리펩티드 및 이의 용도 |
-
2008
- 2008-04-11 RU RU2009141510/10A patent/RU2571931C2/ru not_active IP Right Cessation
- 2008-04-11 MX MX2009010997A patent/MX2009010997A/es active IP Right Grant
- 2008-04-11 BR BRPI0810172-8A2A patent/BRPI0810172A2/pt active Search and Examination
- 2008-04-11 US US12/082,662 patent/US20100166729A9/en not_active Abandoned
- 2008-04-11 JP JP2010503081A patent/JP5761782B2/ja not_active Expired - Fee Related
- 2008-04-11 UA UAA200911564A patent/UA101155C2/ru unknown
- 2008-04-11 DK DK08742852.0T patent/DK2147096T3/da active
- 2008-04-11 NZ NZ593611A patent/NZ593611A/en unknown
- 2008-04-11 EP EP08742852.0A patent/EP2147096B1/en active Active
- 2008-04-11 AU AU2008239586A patent/AU2008239586B2/en not_active Ceased
- 2008-04-11 EP EP12156573A patent/EP2481797A1/en not_active Withdrawn
- 2008-04-11 KR KR1020097023568A patent/KR20100016462A/ko not_active Abandoned
- 2008-04-11 PT PT87428520T patent/PT2147096E/pt unknown
- 2008-04-11 SG SG2011058658A patent/SG174077A1/en unknown
- 2008-04-11 CA CA002683443A patent/CA2683443A1/en not_active Abandoned
- 2008-04-11 PL PL08742852T patent/PL2147096T3/pl unknown
- 2008-04-11 WO PCT/US2008/004795 patent/WO2008127702A2/en not_active Ceased
- 2008-04-11 NZ NZ579985A patent/NZ579985A/en unknown
- 2008-04-11 CN CN200880016982.6A patent/CN101743309B/zh not_active Expired - Fee Related
- 2008-04-11 KR KR1020157014839A patent/KR20150067772A/ko not_active Ceased
- 2008-04-11 ES ES08742852.0T patent/ES2537328T3/es active Active
- 2008-04-11 CN CN201310367450XA patent/CN103451172A/zh active Pending
- 2008-04-11 SI SI200831442T patent/SI2147096T1/sl unknown
-
2009
- 2009-09-24 IL IL201173A patent/IL201173A0/en unknown
- 2009-10-01 ZA ZA2009/06854A patent/ZA200906854B/en unknown
- 2009-10-08 CO CO09111636A patent/CO6231052A2/es unknown
- 2009-10-09 HN HN2009002098A patent/HN2009002098A/es unknown
- 2009-10-09 CR CR11058A patent/CR11058A/es not_active Application Discontinuation
- 2009-10-12 NI NI200900187A patent/NI200900187A/es unknown
- 2009-10-13 GT GT200900268A patent/GT200900268A/es unknown
- 2009-10-13 SV SV2009003393A patent/SV2009003393A/es unknown
- 2009-11-13 EC EC2009009735A patent/ECSP099735A/es unknown
-
2011
- 2011-12-13 ZA ZA2011/09181A patent/ZA201109181B/en unknown
-
2012
- 2012-03-22 IL IL218776A patent/IL218776A0/en unknown
-
2013
- 2013-10-23 JP JP2013220232A patent/JP2014042523A/ja not_active Withdrawn
-
2014
- 2014-09-01 PH PH12014501960A patent/PH12014501960A1/en unknown
-
2016
- 2016-03-17 JP JP2016054083A patent/JP2016155836A/ja active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2278123C2 (ru) * | 2000-02-11 | 2006-06-20 | Максиджен Холдингз Лтд. | Молекулы, подобные фактору vii или viia |
| WO2004083361A2 (en) * | 2003-03-20 | 2004-09-30 | Maxygen Holdings Ltd. | FVII OR FVIIa VARIANTS |
| WO2006114105A2 (en) * | 2005-04-26 | 2006-11-02 | Maxygen Holdings Ltd. | Use of modified factor vii for treating bleeding |
| WO2007031559A2 (en) * | 2005-09-14 | 2007-03-22 | Novo Nordisk Health Care Ag | Human coagulation factor vii polypeptides |
Non-Patent Citations (1)
| Title |
|---|
| GENG J. P. ET AL., Properties of a recombinant chimeric protein in which the gamma-carboxyglutamic acid and helical stack domains of human anticoagulant protein C are replaced by those of human coagulation factor VII, THROMBOSIS AND HAEMOSTASIS, 1997, v. 77, n. 5, p.926-933. SHAH A. ET AL., Manipulation of the membrane binding site of vitamin K-dependent proteins: enhanced biological function of human factor VII, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, 1998, v. 95, n. 8, p. 4229-4234. * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5761782B2 (ja) | 改変第ｖｉｉ因子ポリペプチド及びその使用 | |
| US11203749B2 (en) | Factor VII polypeptides that are modified and uses thereof | |
| AU2013204377B2 (en) | Modified factor vii polypeptides and uses thereof | |
| HK1134520B (en) | Modified factor vii polypeptides and uses thereof | |
| HK1174059A (en) | Modified factor vii polypeptides and uses thereof | |
| HK1227434A (en) | Factor vii polypeptides that are modified and uses thereof | |
| HK1227434A1 (en) | Factor vii polypeptides that are modified and uses thereof | |
| HK1194096B (en) | Factor vii polypeptides that are modified and uses thereof | |
| HK1192905B (en) | Factor vii polypeptides that are modified and uses thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | The patent is invalid due to non-payment of fees |
Effective date: 20170412 |