KR101623602B1 - 변형된 제ⅶ 인자 폴리펩티드 및 그의 용도 - Google Patents
변형된 제ⅶ 인자 폴리펩티드 및 그의 용도 Download PDFInfo
- Publication number
- KR101623602B1 KR101623602B1 KR1020107025264A KR20107025264A KR101623602B1 KR 101623602 B1 KR101623602 B1 KR 101623602B1 KR 1020107025264 A KR1020107025264 A KR 1020107025264A KR 20107025264 A KR20107025264 A KR 20107025264A KR 101623602 B1 KR101623602 B1 KR 101623602B1
- Authority
- KR
- South Korea
- Prior art keywords
- delete delete
- polypeptide
- fvii
- amino acid
- modified
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 430
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 427
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 426
- 229940012413 factor vii Drugs 0.000 title claims abstract description 99
- 230000000694 effects Effects 0.000 claims abstract description 113
- 102100023804 Coagulation factor VII Human genes 0.000 claims abstract description 100
- 108010023321 Factor VII Proteins 0.000 claims abstract description 99
- 230000001965 increasing effect Effects 0.000 claims abstract description 54
- 229940024606 amino acid Drugs 0.000 claims description 103
- 150000001413 amino acids Chemical class 0.000 claims description 102
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 86
- 230000015271 coagulation Effects 0.000 claims description 80
- 238000005345 coagulation Methods 0.000 claims description 80
- 150000007523 nucleic acids Chemical class 0.000 claims description 76
- 102000039446 nucleic acids Human genes 0.000 claims description 75
- 108020004707 nucleic acids Proteins 0.000 claims description 75
- 210000004027 cell Anatomy 0.000 claims description 60
- 238000000034 method Methods 0.000 claims description 49
- 108090000190 Thrombin Proteins 0.000 claims description 48
- 229960004072 thrombin Drugs 0.000 claims description 48
- 230000004048 modification Effects 0.000 claims description 46
- 238000012986 modification Methods 0.000 claims description 46
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 40
- 102100022641 Coagulation factor IX Human genes 0.000 claims description 35
- 238000006467 substitution reaction Methods 0.000 claims description 34
- 102000010911 Enzyme Precursors Human genes 0.000 claims description 32
- 108010062466 Enzyme Precursors Proteins 0.000 claims description 32
- 208000009292 Hemophilia A Diseases 0.000 claims description 29
- 201000010099 disease Diseases 0.000 claims description 29
- 208000031220 Hemophilia Diseases 0.000 claims description 21
- 208000014674 injury Diseases 0.000 claims description 21
- 102220604090 Homeobox protein SIX3_S52A_mutation Human genes 0.000 claims description 20
- 230000023555 blood coagulation Effects 0.000 claims description 20
- 238000011282 treatment Methods 0.000 claims description 20
- 239000013598 vector Substances 0.000 claims description 20
- 208000032843 Hemorrhage Diseases 0.000 claims description 18
- 208000031169 hemorrhagic disease Diseases 0.000 claims description 18
- 208000034158 bleeding Diseases 0.000 claims description 17
- 230000000740 bleeding effect Effects 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 206010053567 Coagulopathies Diseases 0.000 claims description 16
- 239000002773 nucleotide Substances 0.000 claims description 16
- 125000003729 nucleotide group Chemical group 0.000 claims description 16
- 238000003780 insertion Methods 0.000 claims description 15
- 230000037431 insertion Effects 0.000 claims description 15
- 208000024891 symptom Diseases 0.000 claims description 14
- 230000007812 deficiency Effects 0.000 claims description 13
- 208000035475 disorder Diseases 0.000 claims description 11
- 206010010356 Congenital anomaly Diseases 0.000 claims description 9
- 102220504523 Organic solute transporter subunit alpha_M19K_mutation Human genes 0.000 claims description 9
- 102100026735 Coagulation factor VIII Human genes 0.000 claims description 8
- 201000003542 Factor VIII deficiency Diseases 0.000 claims description 8
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 claims description 8
- 102200159067 c.130T>A Human genes 0.000 claims description 8
- 102220412822 c.160C>T Human genes 0.000 claims description 8
- 208000009429 hemophilia B Diseases 0.000 claims description 8
- 102200058924 rs121909542 Human genes 0.000 claims description 7
- 230000008733 trauma Effects 0.000 claims description 7
- 238000001356 surgical procedure Methods 0.000 claims description 6
- 239000013603 viral vector Substances 0.000 claims description 6
- 210000004962 mammalian cell Anatomy 0.000 claims description 5
- 102220020898 rs1800062 Human genes 0.000 claims description 5
- 102220523133 Eukaryotic translation initiation factor 4E-binding protein 2_T37E_mutation Human genes 0.000 claims description 4
- 102220550001 T-cell immunoreceptor with Ig and ITIM domains_I42A_mutation Human genes 0.000 claims description 4
- 208000011664 congenital factor XI deficiency Diseases 0.000 claims description 4
- 210000003527 eukaryotic cell Anatomy 0.000 claims description 4
- 230000001747 exhibiting effect Effects 0.000 claims description 4
- 201000007219 factor XI deficiency Diseases 0.000 claims description 4
- 102200153433 rs104894817 Human genes 0.000 claims description 4
- 102220071724 rs794728408 Human genes 0.000 claims description 4
- 102220279183 rs876660634 Human genes 0.000 claims description 4
- 241000699800 Cricetinae Species 0.000 claims description 3
- 102220603445 Homeobox protein SIX3_K32T_mutation Human genes 0.000 claims description 3
- 102220467432 Protein Jade-1_K38S_mutation Human genes 0.000 claims description 3
- 229960000310 isoleucine Drugs 0.000 claims description 3
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 3
- 102220024780 rs199473488 Human genes 0.000 claims description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 3
- 102220556665 Acetylcholinesterase_G97S_mutation Human genes 0.000 claims description 2
- 102220635301 Adenylate kinase isoenzyme 6_I42R_mutation Human genes 0.000 claims description 2
- 102220617593 B1 bradykinin receptor_K38R_mutation Human genes 0.000 claims description 2
- 102220615916 C-C chemokine receptor type 5_K62R_mutation Human genes 0.000 claims description 2
- 102220610985 Coagulation factor VII_G345S_mutation Human genes 0.000 claims description 2
- 102220496805 DNA dC->dU-editing enzyme APOBEC-3A_R28E_mutation Human genes 0.000 claims description 2
- 102220516207 Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial_K38T_mutation Human genes 0.000 claims description 2
- 102220471770 Fructose-bisphosphate aldolase A_E82Q_mutation Human genes 0.000 claims description 2
- 102220603449 Homeobox protein SIX3_A34S_mutation Human genes 0.000 claims description 2
- 102220520254 Phospholipase A2 group XV_D46C_mutation Human genes 0.000 claims description 2
- 102220547369 Protein APCDD1_L65S_mutation Human genes 0.000 claims description 2
- 102220626843 Protein phosphatase 1 regulatory subunit 35_S45D_mutation Human genes 0.000 claims description 2
- 102220631868 Regulator of G-protein signaling 2_W41D_mutation Human genes 0.000 claims description 2
- 102220494687 Small vasohibin-binding protein_R36E_mutation Human genes 0.000 claims description 2
- 102220586119 Tubulin polymerization-promoting protein_S45E_mutation Human genes 0.000 claims description 2
- 102220414499 c.131A>G Human genes 0.000 claims description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 claims description 2
- 239000003623 enhancer Substances 0.000 claims description 2
- 210000003292 kidney cell Anatomy 0.000 claims description 2
- 102220033735 rs104886489 Human genes 0.000 claims description 2
- 102220234446 rs1064795967 Human genes 0.000 claims description 2
- 102220004442 rs121918685 Human genes 0.000 claims description 2
- 102220276595 rs1553131446 Human genes 0.000 claims description 2
- 102220321823 rs1554812271 Human genes 0.000 claims description 2
- 102220249828 rs267606858 Human genes 0.000 claims description 2
- 102200118254 rs33995148 Human genes 0.000 claims description 2
- 102220005309 rs33995148 Human genes 0.000 claims description 2
- 102200118250 rs34446260 Human genes 0.000 claims description 2
- 102200082816 rs34868397 Human genes 0.000 claims description 2
- 102220114727 rs372166877 Human genes 0.000 claims description 2
- 102220297938 rs375722926 Human genes 0.000 claims description 2
- 102220005421 rs41381645 Human genes 0.000 claims description 2
- 102220037197 rs587780270 Human genes 0.000 claims description 2
- 102200020878 rs73015965 Human genes 0.000 claims description 2
- 102220217756 rs777095030 Human genes 0.000 claims description 2
- 102220064446 rs786205841 Human genes 0.000 claims description 2
- 102220272417 rs80357066 Human genes 0.000 claims description 2
- 102200057185 rs863225150 Human genes 0.000 claims description 2
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims description 2
- 102220486651 Mannose-1-phosphate guanyltransferase beta_S60A_mutation Human genes 0.000 claims 7
- 239000004475 Arginine Substances 0.000 claims 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims 4
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims 4
- 102220493749 Paired box protein Pax-6_I42S_mutation Human genes 0.000 claims 2
- CXLUIRPQSBYREP-WDSKDSINSA-N (3s)-3-[[(2s)-2-amino-4,4-dicarboxybutanoyl]amino]propane-1,1,3-tricarboxylic acid Chemical compound OC(=O)C(C(O)=O)C[C@H](N)C(=O)N[C@@H](CC(C(O)=O)C(O)=O)C(O)=O CXLUIRPQSBYREP-WDSKDSINSA-N 0.000 claims 1
- 102220531551 39S ribosomal protein L4, mitochondrial_S12A_mutation Human genes 0.000 claims 1
- 208000019838 Blood disease Diseases 0.000 claims 1
- 102220536010 Dynamin-1-like protein_K38A_mutation Human genes 0.000 claims 1
- 102220580969 Induced myeloid leukemia cell differentiation protein Mcl-1_Y46Y_mutation Human genes 0.000 claims 1
- 102220513482 Rab-interacting lysosomal protein_D33S_mutation Human genes 0.000 claims 1
- 239000012190 activator Substances 0.000 claims 1
- 102200102393 c.194T>A Human genes 0.000 claims 1
- 238000004113 cell culture Methods 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 201000007386 factor VII deficiency Diseases 0.000 claims 1
- 108010004609 gamma-carboxyglutamyl-gamma-carboxyglutamic acid Proteins 0.000 claims 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims 1
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 claims 1
- 208000014951 hematologic disease Diseases 0.000 claims 1
- 208000018706 hematopoietic system disease Diseases 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
- 102200145342 rs104894410 Human genes 0.000 claims 1
- 102220243326 rs1183892581 Human genes 0.000 claims 1
- 102220240214 rs1310676971 Human genes 0.000 claims 1
- 102220249718 rs1553408194 Human genes 0.000 claims 1
- 102220242717 rs1553780837 Human genes 0.000 claims 1
- 102220008235 rs199476326 Human genes 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 12
- 229940124597 therapeutic agent Drugs 0.000 abstract description 9
- 108010054265 Factor VIIa Proteins 0.000 abstract description 5
- 229940012414 factor viia Drugs 0.000 abstract description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 192
- 235000001014 amino acid Nutrition 0.000 description 142
- 108090000623 proteins and genes Proteins 0.000 description 110
- 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 103
- 102000004169 proteins and genes Human genes 0.000 description 96
- 230000027455 binding Effects 0.000 description 92
- 235000018102 proteins Nutrition 0.000 description 92
- 238000009739 binding Methods 0.000 description 91
- 102000002262 Thromboplastin Human genes 0.000 description 83
- 108010000499 Thromboplastin Proteins 0.000 description 83
- 210000001772 blood platelet Anatomy 0.000 description 83
- 102000035195 Peptidases Human genes 0.000 description 62
- 108091005804 Peptidases Proteins 0.000 description 62
- 239000004365 Protease Substances 0.000 description 50
- 238000001994 activation Methods 0.000 description 45
- 230000000875 corresponding effect Effects 0.000 description 45
- 230000004913 activation Effects 0.000 description 43
- 235000019419 proteases Nutrition 0.000 description 41
- 125000000539 amino acid group Chemical group 0.000 description 38
- 238000003776 cleavage reaction Methods 0.000 description 35
- 230000007017 scission Effects 0.000 description 35
- 108020004414 DNA Proteins 0.000 description 33
- 150000003904 phospholipids Chemical class 0.000 description 33
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 32
- 108010073385 Fibrin Proteins 0.000 description 31
- 102000009123 Fibrin Human genes 0.000 description 31
- 229950003499 fibrin Drugs 0.000 description 31
- 230000037361 pathway Effects 0.000 description 31
- 108010014173 Factor X Proteins 0.000 description 30
- 229940012426 factor x Drugs 0.000 description 29
- 102000004411 Antithrombin III Human genes 0.000 description 27
- 108090000935 Antithrombin III Proteins 0.000 description 27
- 108010076282 Factor IX Proteins 0.000 description 27
- 229960005348 antithrombin iii Drugs 0.000 description 27
- 229960004222 factor ix Drugs 0.000 description 26
- 239000002243 precursor Substances 0.000 description 26
- 239000000203 mixture Substances 0.000 description 25
- 230000015572 biosynthetic process Effects 0.000 description 24
- 230000002797 proteolythic effect Effects 0.000 description 24
- 108010022999 Serine Proteases Proteins 0.000 description 23
- 102000012479 Serine Proteases Human genes 0.000 description 23
- 230000035602 clotting Effects 0.000 description 23
- 230000003197 catalytic effect Effects 0.000 description 21
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 20
- 108090000317 Chymotrypsin Proteins 0.000 description 20
- 241000282414 Homo sapiens Species 0.000 description 20
- 102000007562 Serum Albumin Human genes 0.000 description 20
- 108010071390 Serum Albumin Proteins 0.000 description 20
- 229960002376 chymotrypsin Drugs 0.000 description 20
- 239000003112 inhibitor Substances 0.000 description 20
- 108010044426 integrins Proteins 0.000 description 20
- 102000006495 integrins Human genes 0.000 description 20
- 239000003114 blood coagulation factor Substances 0.000 description 19
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 18
- 230000013595 glycosylation Effects 0.000 description 18
- 238000006206 glycosylation reaction Methods 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- 239000011701 zinc Substances 0.000 description 18
- 150000001875 compounds Chemical class 0.000 description 17
- 230000001225 therapeutic effect Effects 0.000 description 17
- 108090000790 Enzymes Proteins 0.000 description 16
- 102000004190 Enzymes Human genes 0.000 description 16
- 230000006378 damage Effects 0.000 description 16
- 229940088598 enzyme Drugs 0.000 description 16
- 230000014509 gene expression Effects 0.000 description 16
- 230000003993 interaction Effects 0.000 description 15
- 230000008569 process Effects 0.000 description 15
- 208000027418 Wounds and injury Diseases 0.000 description 14
- 230000008859 change Effects 0.000 description 14
- 230000001419 dependent effect Effects 0.000 description 14
- 230000006870 function Effects 0.000 description 14
- 238000001727 in vivo Methods 0.000 description 14
- 241000894007 species Species 0.000 description 14
- 239000000758 substrate Substances 0.000 description 14
- 102000001690 Factor VIII Human genes 0.000 description 13
- 108010054218 Factor VIII Proteins 0.000 description 13
- 108010029485 Protein Isoforms Proteins 0.000 description 13
- 102000001708 Protein Isoforms Human genes 0.000 description 13
- 238000003556 assay Methods 0.000 description 13
- 229960000301 factor viii Drugs 0.000 description 13
- 230000023597 hemostasis Effects 0.000 description 13
- 238000004519 manufacturing process Methods 0.000 description 13
- 239000012528 membrane Substances 0.000 description 13
- 210000004379 membrane Anatomy 0.000 description 13
- -1 Arg (R) Chemical class 0.000 description 12
- 102220520852 Dynein light chain Tctex-type 3_S60A_mutation Human genes 0.000 description 12
- 108010076504 Protein Sorting Signals Proteins 0.000 description 12
- 238000000338 in vitro Methods 0.000 description 12
- 210000002381 plasma Anatomy 0.000 description 12
- 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 description 11
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 239000012634 fragment Substances 0.000 description 11
- 230000002401 inhibitory effect Effects 0.000 description 11
- 230000006337 proteolytic cleavage Effects 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 108010047303 von Willebrand Factor Proteins 0.000 description 11
- 102100036537 von Willebrand factor Human genes 0.000 description 11
- 108010049003 Fibrinogen Proteins 0.000 description 10
- 102000008946 Fibrinogen Human genes 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 10
- 102100027378 Prothrombin Human genes 0.000 description 10
- 108010094028 Prothrombin Proteins 0.000 description 10
- 230000002776 aggregation Effects 0.000 description 10
- 229940012952 fibrinogen Drugs 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 229940039716 prothrombin Drugs 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- 229960001134 von willebrand factor Drugs 0.000 description 10
- 238000004220 aggregation Methods 0.000 description 9
- 230000004071 biological effect Effects 0.000 description 9
- 238000012217 deletion Methods 0.000 description 9
- 230000037430 deletion Effects 0.000 description 9
- 230000002209 hydrophobic effect Effects 0.000 description 9
- 230000007246 mechanism Effects 0.000 description 9
- 230000035772 mutation Effects 0.000 description 9
- 102000040430 polynucleotide Human genes 0.000 description 9
- 108091033319 polynucleotide Proteins 0.000 description 9
- 239000002157 polynucleotide Substances 0.000 description 9
- 230000008023 solidification Effects 0.000 description 9
- 238000007711 solidification Methods 0.000 description 9
- 150000003721 vitamin K derivatives Chemical class 0.000 description 9
- 101800004937 Protein C Proteins 0.000 description 8
- 102000017975 Protein C Human genes 0.000 description 8
- 101800001700 Saposin-D Proteins 0.000 description 8
- 229930003448 Vitamin K Natural products 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 8
- 108020001507 fusion proteins Proteins 0.000 description 8
- 102000037865 fusion proteins Human genes 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
- 230000010118 platelet activation Effects 0.000 description 8
- 229960000856 protein c Drugs 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
- 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 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
- 108010088842 Fibrinolysin Proteins 0.000 description 7
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 7
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 7
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 7
- 230000003321 amplification Effects 0.000 description 7
- 230000021523 carboxylation Effects 0.000 description 7
- 238000006473 carboxylation reaction Methods 0.000 description 7
- 210000002889 endothelial cell Anatomy 0.000 description 7
- 238000003199 nucleic acid amplification method Methods 0.000 description 7
- 229940012957 plasmin Drugs 0.000 description 7
- 238000012545 processing Methods 0.000 description 7
- 230000001737 promoting effect Effects 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 235000004400 serine Nutrition 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 6
- 241000283690 Bos taurus Species 0.000 description 6
- 241000282472 Canis lupus familiaris Species 0.000 description 6
- 102000003886 Glycoproteins Human genes 0.000 description 6
- 108090000288 Glycoproteins Proteins 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 6
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 6
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 6
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 6
- 239000004473 Threonine Substances 0.000 description 6
- 108091005605 Vitamin K-dependent proteins Proteins 0.000 description 6
- 230000001413 cellular effect Effects 0.000 description 6
- 238000001415 gene therapy Methods 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 235000008521 threonine Nutrition 0.000 description 6
- 241000287828 Gallus gallus Species 0.000 description 5
- 241000282575 Gorilla Species 0.000 description 5
- 230000004988 N-glycosylation Effects 0.000 description 5
- 230000004989 O-glycosylation Effects 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 241000282898 Sus scrofa Species 0.000 description 5
- 208000007536 Thrombosis Diseases 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 230000017531 blood circulation Effects 0.000 description 5
- 210000004204 blood vessel Anatomy 0.000 description 5
- 239000011575 calcium Substances 0.000 description 5
- 210000003038 endothelium Anatomy 0.000 description 5
- 230000020764 fibrinolysis Effects 0.000 description 5
- 230000033444 hydroxylation Effects 0.000 description 5
- 238000005805 hydroxylation reaction Methods 0.000 description 5
- 230000000977 initiatory effect Effects 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 230000004481 post-translational protein modification Effects 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 108010013773 recombinant FVIIa Proteins 0.000 description 5
- 230000028327 secretion Effects 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 230000014616 translation Effects 0.000 description 5
- 238000013519 translation Methods 0.000 description 5
- 108700028369 Alleles Proteins 0.000 description 4
- 102000004506 Blood Proteins Human genes 0.000 description 4
- 108010017384 Blood Proteins Proteins 0.000 description 4
- 108090001126 Furin Proteins 0.000 description 4
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 4
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 4
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 241000282576 Pan paniscus Species 0.000 description 4
- 241000282405 Pongo abelii Species 0.000 description 4
- 229940096437 Protein S Drugs 0.000 description 4
- 108010066124 Protein S Proteins 0.000 description 4
- 102000029301 Protein S Human genes 0.000 description 4
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 4
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 4
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 4
- 208000024248 Vascular System injury Diseases 0.000 description 4
- 208000012339 Vascular injury Diseases 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 235000004279 alanine Nutrition 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 4
- 150000001720 carbohydrates Chemical group 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000000701 coagulant Substances 0.000 description 4
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 4
- 235000018417 cysteine Nutrition 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 239000013604 expression vector Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 4
- 230000002439 hemostatic effect Effects 0.000 description 4
- 239000004179 indigotine Substances 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 235000019833 protease Nutrition 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 229940068953 recombinant fviia Drugs 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 239000003001 serine protease inhibitor Substances 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
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 4
- 208000037816 tissue injury Diseases 0.000 description 4
- 229960000187 tissue plasminogen activator Drugs 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 230000002792 vascular Effects 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 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 3
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 3
- 102220500235 Coagulation factor VII_K197E_mutation Human genes 0.000 description 3
- 241000252212 Danio rerio Species 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
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 101000880344 Homo sapiens Elongation factor G, mitochondrial Proteins 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
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- 102220507071 Mothers against decapentaplegic homolog 1_I42S_mutation Human genes 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 102000004067 Osteocalcin Human genes 0.000 description 3
- 108090000573 Osteocalcin Proteins 0.000 description 3
- 241000282577 Pan troglodytes Species 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
- 108090000631 Trypsin Proteins 0.000 description 3
- 102000004142 Trypsin Human genes 0.000 description 3
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 3
- 208000013633 acquired hemophilia Diseases 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 239000003146 anticoagulant agent Substances 0.000 description 3
- 229940127219 anticoagulant drug Drugs 0.000 description 3
- 238000000149 argon plasma sintering Methods 0.000 description 3
- 235000009582 asparagine Nutrition 0.000 description 3
- 229960001230 asparagine Drugs 0.000 description 3
- 238000004422 calculation algorithm Methods 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 239000012707 chemical precursor Substances 0.000 description 3
- 230000000536 complexating effect Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 210000002744 extracellular matrix Anatomy 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 description 3
- 238000009396 hybridization Methods 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 102000043253 matrix Gla protein Human genes 0.000 description 3
- 108010057546 matrix Gla protein Proteins 0.000 description 3
- 239000005022 packaging material Substances 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 229940127126 plasminogen activator Drugs 0.000 description 3
- 230000017854 proteolysis Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 3
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000000725 suspension Substances 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
- 108010016054 tissue-factor-pathway inhibitor 2 Proteins 0.000 description 3
- 102000055046 tissue-factor-pathway inhibitor 2 Human genes 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- 239000012588 trypsin Substances 0.000 description 3
- 229960001322 trypsin Drugs 0.000 description 3
- 102220491410 ADP-ribosylation factor-like protein 16_T37N_mutation Human genes 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
- 102000000844 Cell Surface Receptors Human genes 0.000 description 2
- 108010001857 Cell Surface Receptors Proteins 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen 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
- 102000053602 DNA Human genes 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 108010048049 Factor IXa Proteins 0.000 description 2
- 108010071241 Factor XIIa Proteins 0.000 description 2
- 108010074860 Factor Xa Proteins 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 101800003778 Fibrinopeptide B Proteins 0.000 description 2
- 102400001063 Fibrinopeptide B Human genes 0.000 description 2
- 101150022345 GAS6 gene Proteins 0.000 description 2
- 102100025305 Integrin alpha-2 Human genes 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 241000282553 Macaca Species 0.000 description 2
- 241000282560 Macaca mulatta Species 0.000 description 2
- 241000147123 Moorella group Species 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- 102000013566 Plasminogen Human genes 0.000 description 2
- 108010051456 Plasminogen Proteins 0.000 description 2
- 102000015795 Platelet Membrane Glycoproteins Human genes 0.000 description 2
- 108010010336 Platelet Membrane Glycoproteins Proteins 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 108010047066 R 396 Proteins 0.000 description 2
- 241000700157 Rattus norvegicus Species 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
- 102000008847 Serpin Human genes 0.000 description 2
- 108050000761 Serpin Proteins 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-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
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 2
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- 241001441722 Takifugu rubripes Species 0.000 description 2
- 108010079274 Thrombomodulin Proteins 0.000 description 2
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 2
- 206010047139 Vasoconstriction Diseases 0.000 description 2
- 230000002378 acidificating effect Effects 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
- 230000004075 alteration Effects 0.000 description 2
- 230000001668 ameliorated effect Effects 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 238000000137 annealing Methods 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 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 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 229910001424 calcium ion Inorganic materials 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000002843 carboxylic acid group Chemical group 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 238000005094 computer simulation Methods 0.000 description 2
- 238000004132 cross linking Methods 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
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 208000037765 diseases and disorders Diseases 0.000 description 2
- 230000003511 endothelial effect Effects 0.000 description 2
- 230000008472 epithelial growth Effects 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
- 239000012530 fluid Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 230000004660 morphological change Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 244000144977 poultry Species 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 210000003370 receptor cell Anatomy 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 230000002885 thrombogenetic effect Effects 0.000 description 2
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 2
- 238000012384 transportation and delivery Methods 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 229960005356 urokinase Drugs 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- 210000003556 vascular endothelial cell Anatomy 0.000 description 2
- 210000004509 vascular smooth muscle cell Anatomy 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
- 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
- 102220623570 2-(3-amino-3-carboxypropyl)histidine synthase subunit 1_L65Q_mutation Human genes 0.000 description 1
- 102220511125 APC membrane recruitment protein 1_Y58S_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
- 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
- 108010007730 Apyrase Proteins 0.000 description 1
- 102000007347 Apyrase Human genes 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 101100540159 Candida albicans (strain SC5314 / ATCC MYA-2876) TFP1 gene Proteins 0.000 description 1
- 101000898643 Candida albicans Vacuolar aspartic protease Proteins 0.000 description 1
- 101000898783 Candida tropicalis Candidapepsin Proteins 0.000 description 1
- 108090000201 Carboxypeptidase B2 Proteins 0.000 description 1
- 102100035023 Carboxypeptidase B2 Human genes 0.000 description 1
- 101710082751 Carboxypeptidase S1 homolog A Proteins 0.000 description 1
- 102220493935 Casein kinase I isoform gamma-1_K38A_mutation Human genes 0.000 description 1
- 206010072043 Central nervous system haemorrhage Diseases 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 241000282994 Cervidae Species 0.000 description 1
- 108020004638 Circular DNA Proteins 0.000 description 1
- 102100029117 Coagulation factor X Human genes 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 208000027205 Congenital disease Diseases 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 101000898784 Cryphonectria parasitica Endothiapepsin Proteins 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
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 102100029722 Ectonucleoside triphosphate diphosphohydrolase 1 Human genes 0.000 description 1
- 108010059378 Endopeptidases Proteins 0.000 description 1
- 102000005593 Endopeptidases Human genes 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 108010080865 Factor XII Proteins 0.000 description 1
- 102000000429 Factor XII Human genes 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
- 208000012671 Gastrointestinal haemorrhages Diseases 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
- 239000004471 Glycine Substances 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
- 206010018852 Haematoma Diseases 0.000 description 1
- 229920002971 Heparan sulfate Polymers 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 102220570133 Histone PARylation factor 1_K32Q_mutation Human genes 0.000 description 1
- 102000006947 Histones Human genes 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 102220603448 Homeobox protein SIX3_A34R_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
- 206010020710 Hyperphagia Diseases 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
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 108010017642 Integrin alpha2beta1 Proteins 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- 125000000769 L-threonyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])[C@](O[H])(C([H])([H])[H])[H] 0.000 description 1
- 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 1
- 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 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
- 241000713666 Lentivirus Species 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- UGTZHPSKYRIGRJ-YUMQZZPRSA-N Lys-Glu Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCC(O)=O UGTZHPSKYRIGRJ-YUMQZZPRSA-N 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
- 208000024556 Mendelian disease Diseases 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 108091061960 Naked DNA Proteins 0.000 description 1
- 102220642831 Neuronal acetylcholine receptor subunit alpha-9_L141D_mutation Human genes 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
- 241000282579 Pan Species 0.000 description 1
- 102000005877 Peptide Initiation Factors Human genes 0.000 description 1
- 108010044843 Peptide Initiation Factors 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
- 102000004179 Plasminogen Activator Inhibitor 2 Human genes 0.000 description 1
- 108090000614 Plasminogen Activator Inhibitor 2 Proteins 0.000 description 1
- 108010077971 Plasminogen Inactivators Proteins 0.000 description 1
- 102000010752 Plasminogen Inactivators Human genes 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 241000485664 Protortonia cacti Species 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
- 108020005091 Replication Origin Proteins 0.000 description 1
- 101000933133 Rhizopus niveus Rhizopuspepsin-1 Proteins 0.000 description 1
- 101000910082 Rhizopus niveus Rhizopuspepsin-2 Proteins 0.000 description 1
- 101000910079 Rhizopus niveus Rhizopuspepsin-3 Proteins 0.000 description 1
- 101000910086 Rhizopus niveus Rhizopuspepsin-4 Proteins 0.000 description 1
- 101000910088 Rhizopus niveus Rhizopuspepsin-5 Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 241000282849 Ruminantia Species 0.000 description 1
- 102000044437 S1 domains Human genes 0.000 description 1
- 108700036684 S1 domains Proteins 0.000 description 1
- 102220610180 SR-related and CTD-associated factor 4_L141E_mutation Human genes 0.000 description 1
- 101000898773 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Saccharopepsin Proteins 0.000 description 1
- 101100316793 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) VMA1 gene Proteins 0.000 description 1
- 108091058545 Secretory proteins Proteins 0.000 description 1
- 102000040739 Secretory proteins Human genes 0.000 description 1
- 108090000083 Serine Endopeptidases Proteins 0.000 description 1
- 102000003667 Serine Endopeptidases Human genes 0.000 description 1
- 108090000787 Subtilisin Proteins 0.000 description 1
- 241001441724 Tetraodontidae 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
- 102100026966 Thrombomodulin Human genes 0.000 description 1
- 102000002938 Thrombospondin Human genes 0.000 description 1
- 108060008245 Thrombospondin Proteins 0.000 description 1
- 102100030951 Tissue factor pathway inhibitor Human genes 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 102220552168 Tricarboxylate transport protein, mitochondrial_I40N_mutation Human genes 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 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
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 238000012084 abdominal surgery Methods 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 208000037919 acquired disease Diseases 0.000 description 1
- 201000004208 acquired thrombocytopenia Diseases 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 238000007792 addition Methods 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
- 239000002671 adjuvant Substances 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000008841 allosteric interaction Effects 0.000 description 1
- 150000001408 amides Chemical group 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000004410 anthocyanin Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- 229940030225 antihemorrhagics Drugs 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
- 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
- 230000009286 beneficial effect 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
- 208000015294 blood coagulation disease Diseases 0.000 description 1
- 239000003130 blood coagulation factor inhibitor Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 102220360474 c.158G>A Human genes 0.000 description 1
- 102220411562 c.175G>A Human genes 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000004303 calcium sorbate 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
- 238000007675 cardiac surgery Methods 0.000 description 1
- 238000010523 cascade reaction Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 238000012412 chemical coupling Methods 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229940043292 chymotrypsin / trypsin Drugs 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 229940105774 coagulation factor ix Drugs 0.000 description 1
- 229940105772 coagulation factor vii Drugs 0.000 description 1
- 229940105756 coagulation factor x Drugs 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
- 238000010668 complexation reaction Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 230000001143 conditioned effect 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
- 230000002596 correlated effect Effects 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
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229940125808 covalent inhibitor Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 229940127089 cytotoxic agent Drugs 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
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 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
- 125000002228 disulfide group Chemical group 0.000 description 1
- 230000002183 duodenal effect Effects 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
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 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 1
- 229960001123 epoprostenol Drugs 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 230000003090 exacerbative effect Effects 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000006624 extrinsic pathway Effects 0.000 description 1
- 102000013373 fibrillar collagen Human genes 0.000 description 1
- 108060002894 fibrillar collagen Proteins 0.000 description 1
- 108010073651 fibrinmonomer Proteins 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 208000030304 gastrointestinal bleeding Diseases 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
- 102000035122 glycosylated proteins Human genes 0.000 description 1
- 108091005608 glycosylated proteins Proteins 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 208000002085 hemarthrosis Diseases 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 208000006750 hematuria Diseases 0.000 description 1
- 208000031209 hemophilic arthropathy Diseases 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 239000002874 hemostatic agent Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000002962 histologic effect Effects 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940027941 immunoglobulin g Drugs 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 230000006623 intrinsic pathway Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 230000004576 lipid-binding Effects 0.000 description 1
- 108010013555 lipoprotein-associated coagulation inhibitor Proteins 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 108010009298 lysylglutamic acid Proteins 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 210000000723 mammalian artificial chromosome Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 230000009149 molecular binding Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 230000001002 morphogenetic effect Effects 0.000 description 1
- 230000008450 motivation Effects 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 230000014508 negative regulation of coagulation Effects 0.000 description 1
- 230000008284 neuronal mechanism Effects 0.000 description 1
- 229960003753 nitric oxide Drugs 0.000 description 1
- 229940112216 novoseven Drugs 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 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
- 102000042648 peptidase S1 family Human genes 0.000 description 1
- 108091075463 peptidase S1 family Proteins 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 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
- 210000002826 placenta Anatomy 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
- 230000000379 polymerizing effect Effects 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 108010071808 prepro-factor VII Proteins 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 239000003805 procoagulant Substances 0.000 description 1
- 230000002947 procoagulating effect Effects 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000009465 prokaryotic expression Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 108010014806 prothrombinase complex Proteins 0.000 description 1
- 210000001243 pseudopodia Anatomy 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 230000004648 relaxation of smooth muscle Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 102220095974 rs149101834 Human genes 0.000 description 1
- 102220253478 rs1553261891 Human genes 0.000 description 1
- 102220288148 rs1554893773 Human genes 0.000 description 1
- 102220005499 rs33938574 Human genes 0.000 description 1
- 102200042755 rs34392760 Human genes 0.000 description 1
- 102200066497 rs35629723 Human genes 0.000 description 1
- 102220323551 rs771587118 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
- 230000007781 signaling event Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 230000019635 sulfation Effects 0.000 description 1
- 238000005670 sulfation reaction Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 230000007838 tissue remodeling Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 108010087967 type I signal peptidase Proteins 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 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 1
- 239000004474 valine Substances 0.000 description 1
- 230000007556 vascular defect Effects 0.000 description 1
- 238000007631 vascular surgery Methods 0.000 description 1
- 230000003639 vasoconstrictive effect Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 208000016794 vitamin K deficiency hemorrhagic disease Diseases 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 229960005080 warfarin Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6437—Coagulation factor VIIa (3.4.21.21)
-
- 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
- C12N15/62—DNA sequences coding for fusion proteins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21021—Coagulation factor VIIa (3.4.21.21)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12402108P | 2008-04-11 | 2008-04-11 | |
| US61/124,021 | 2008-04-11 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20110008084A KR20110008084A (ko) | 2011-01-25 |
| KR101623602B1 true KR101623602B1 (ko) | 2016-06-07 |
Family
ID=40872757
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020107025264A Active KR101623602B1 (ko) | 2008-04-11 | 2009-04-10 | 변형된 제ⅶ 인자 폴리펩티드 및 그의 용도 |
Country Status (23)
| Country | Link |
|---|---|
| US (4) | US8519103B2 (enExample) |
| EP (4) | EP3064580A1 (enExample) |
| JP (3) | JP2011517942A (enExample) |
| KR (1) | KR101623602B1 (enExample) |
| CN (2) | CN102083971B (enExample) |
| AU (1) | AU2009234390B2 (enExample) |
| BR (1) | BRPI0911060B1 (enExample) |
| CA (1) | CA2721038C (enExample) |
| CO (1) | CO6331368A2 (enExample) |
| DK (2) | DK2687596T3 (enExample) |
| EA (2) | EA020818B1 (enExample) |
| ES (3) | ES2556596T3 (enExample) |
| HU (1) | HUE026937T2 (enExample) |
| IL (2) | IL208373A (enExample) |
| MX (2) | MX2010011170A (enExample) |
| MY (1) | MY161581A (enExample) |
| NZ (1) | NZ588322A (enExample) |
| PL (1) | PL2281037T3 (enExample) |
| PT (1) | PT2281037E (enExample) |
| SG (2) | SG190560A1 (enExample) |
| SI (1) | SI2281037T1 (enExample) |
| TW (2) | TWI465247B (enExample) |
| WO (1) | WO2009126307A2 (enExample) |
Families Citing this family (66)
| 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 |
| TWI353991B (en) | 2003-05-06 | 2011-12-11 | Syntonix Pharmaceuticals Inc | Immunoglobulin chimeric monomer-dimer hybrids |
| WO2005110453A2 (en) | 2004-04-12 | 2005-11-24 | Catalyst Biosciences, Inc. | Cleavage of vegf and vegf receptor by wildtype and mutant mt-sp1 |
| JP5690047B2 (ja) | 2005-09-14 | 2015-03-25 | 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 |
| ES2611608T3 (es) * | 2005-10-21 | 2017-05-09 | Catalyst Biosciences, Inc. | Proteasas modificadas que inhiben la activación del complemento |
| US8383388B2 (en) * | 2006-06-19 | 2013-02-26 | Catalyst Biosciences, Inc. | Modified coagulation factor IX polypeptides and use thereof for treatment |
| TWI369402B (en) | 2006-07-05 | 2012-08-01 | Catalyst Biosciences Inc | Protease screening methods and proteases identified thereby |
| BRPI0810172A2 (pt) * | 2007-04-13 | 2014-10-14 | Catalyst Biosciences Inc | Polipeptídeos de fator vii modificado e seus usos |
| TWI465247B (zh) | 2008-04-11 | 2014-12-21 | Catalyst Biosciences Inc | 經修飾的因子ｖｉｉ多肽和其用途 |
| WO2010151736A1 (en) | 2009-06-25 | 2010-12-29 | The University Of North Carolina At Chapel Hill | Chimeric factor vii molecules |
| AU2011274423B2 (en) * | 2010-07-09 | 2016-02-11 | Bioverativ Therapeutics Inc. | Chimeric clotting factors |
| WO2012048276A2 (en) | 2010-10-08 | 2012-04-12 | Caridianbct, Inc. | Customizable 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 |
| WO2012142317A1 (en) * | 2011-04-15 | 2012-10-18 | Gamma Therapeutics, Inc | Fast-clotting wound dressings |
| 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 |
| PT2717898T (pt) | 2011-06-10 | 2019-05-20 | Bioverativ Therapeutics Inc | Compostos pró-coagulantes e processos para a sua utilização |
| EP2554161A1 (en) | 2011-08-02 | 2013-02-06 | LFB Biotechnologies | Pharmaceutical composition comprising factor VII encapsulated in micelles |
| KR102310704B1 (ko) * | 2012-02-14 | 2021-10-08 | 옵코 바이오로직스 리미티드 | 장기 작용 응고 인자들 및 이를 생산하는 방법들 |
| EA033469B1 (ru) | 2012-04-16 | 2019-10-31 | Cantab Biopharmaceuticals Patents Ltd | Подкожное введение конъюгатов факторов крови с полиэтиленгликолем |
| WO2014018120A1 (en) | 2012-07-25 | 2014-01-30 | Catalyst Biosciences, Inc. | Modified factor x polypeptides and uses thereof |
| JP2015532307A (ja) | 2012-10-15 | 2015-11-09 | ノヴォ・ノルディスク・ヘルス・ケア・アーゲー | 凝固因子ｖｉｉポリペプチド |
| CN104661685A (zh) | 2012-10-15 | 2015-05-27 | 诺和诺德保健Ag（股份有限公司） | 因子vii缀合物 |
| WO2014105784A1 (en) | 2012-12-24 | 2014-07-03 | Bayer Healthcare Llc | Short-acting factor vii polypeptides |
| WO2014144549A1 (en) | 2013-03-15 | 2014-09-18 | Biogen Idec Ma Inc. | Factor ix polypeptide formulations |
| 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 |
| BR112016008039A2 (pt) | 2013-10-15 | 2017-10-17 | Novo Nordisk Healthcare Ag | polipeptídeos do fator vii da coagulação |
| US10584147B2 (en) | 2013-11-08 | 2020-03-10 | Biovertiv Therapeutics Inc. | Procoagulant fusion compound |
| CN105992816B (zh) | 2013-11-16 | 2018-04-17 | 泰尔茂比司特公司 | 生物反应器中的细胞扩增 |
| AR099328A1 (es) * | 2014-02-12 | 2016-07-13 | Novo Nordisk As | Conjugados de factor vii |
| CN106232800B (zh) | 2014-03-25 | 2020-07-03 | 泰尔茂比司特公司 | 介质的被动替代 |
| SI3149163T1 (sl) | 2014-05-26 | 2020-10-30 | Academisch Ziekenhuis Leiden | Prohemostatski proteini za zdravljenje krvavitve |
| WO2016049421A1 (en) | 2014-09-26 | 2016-03-31 | Terumo Bct, Inc. | Scheduled feed |
| AU2015373910B2 (en) | 2015-01-02 | 2021-11-18 | Takeda Pharmaceutical Company Limited | Bispecific antibodies against plasma kallikrein and factor XII |
| WO2017004592A1 (en) | 2015-07-02 | 2017-01-05 | Terumo Bct, Inc. | Cell growth with mechanical stimuli |
| US10913802B2 (en) | 2015-07-21 | 2021-02-09 | Dyax Corp. | Monoclonal antibody inhibitor of factor XIIA |
| MA45328A (fr) | 2016-04-01 | 2019-02-06 | Avidity Biosciences Llc | Compositions acide nucléique-polypeptide et utilisations de celles-ci |
| WO2017181145A1 (en) * | 2016-04-14 | 2017-10-19 | Iconic Therapeutics, Inc. | Compositions and methods for treating disorders associated with νeοvascularization |
| CN109415696A (zh) | 2016-05-25 | 2019-03-01 | 泰尔茂比司特公司 | 细胞扩增 |
| 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 |
| US20200317749A1 (en) * | 2016-07-01 | 2020-10-08 | Denali Therapeutics Inc. | Albumin variants for enhanced serum half-life |
| CN110494163A (zh) * | 2017-02-06 | 2019-11-22 | 应用干细胞有限公司 | 凝血因子viii模拟蛋白及其用途 |
| US11624046B2 (en) | 2017-03-31 | 2023-04-11 | Terumo Bct, Inc. | Cell expansion |
| EP3656841A1 (en) | 2017-03-31 | 2020-05-27 | Terumo BCT, Inc. | Cell expansion |
| US12234441B2 (en) | 2017-03-31 | 2025-02-25 | Terumo Bct, Inc. | Cell expansion |
| AU2018328223A1 (en) * | 2017-09-05 | 2020-03-12 | GLAdiator Biosciences, Inc. | Delivery of payloads to stem cells |
| WO2019067766A1 (en) | 2017-09-27 | 2019-04-04 | Sigilon Therapeutics, Inc. | METHODS, COMPOSITIONS AND IMPLANTABLE ELEMENTS COMPRISING ACTIVE CELLS |
| AU2018346507B2 (en) | 2017-10-04 | 2025-03-13 | Avidity Biosciences, Inc. | Nucleic acid-polypeptide compositions and uses thereof |
| MA51583A (fr) * | 2018-01-04 | 2020-11-11 | Avidity Biosciences Inc | Molécules d'acide nucléique hétéroduplex et leurs utilisations |
| WO2019195056A1 (en) | 2018-04-04 | 2019-10-10 | Sigilon Therapeutics, Inc. | Methods, compositions, and implantable elements comprising stem cells |
| UY38160A (es) | 2018-04-04 | 2019-11-29 | Sigilon Therapeutics Inc | Partículas implantables y métodos relacionados |
| WO2020010189A1 (en) * | 2018-07-06 | 2020-01-09 | Children's Medical Center Corporation | Methods and compositions for analyzing platelets by mass cytometry |
| UY38389A (es) | 2018-09-27 | 2020-04-30 | Sigilon Therapeutics Inc | Dispositivos implantables para terapia celular y métodos relacionados |
| CA3142337A1 (en) | 2019-06-06 | 2020-12-10 | Avidity Biosciences, Inc. | Una amidites and uses thereof |
| US11578090B2 (en) | 2019-06-06 | 2023-02-14 | Avidity Biosciences, Inc. | Nucleic acid-polypeptide compositions and uses thereof |
| EP3833381B1 (en) * | 2019-08-15 | 2022-08-03 | Catalyst Biosciences, Inc. | Modified factor vii polypeptides for subcutaneous administration |
| US20230083751A1 (en) * | 2019-12-30 | 2023-03-16 | Nanjing GenScript Biotech Co., Ltd. | Method For Constructing Gene Mutation Library |
| JP7759719B2 (ja) * | 2020-02-27 | 2025-10-24 | オムロン株式会社 | 流量測定装置 |
| 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 |
| CN120659872A (zh) | 2022-10-11 | 2025-09-16 | 西吉隆医疗股份有限公司 | 用于治疗疾病的经工程化的细胞和可植入元件 |
| EP4602155A1 (en) | 2022-10-11 | 2025-08-20 | Sigilon Therapeutics, Inc. | Engineered cells and implantable elements for treatment of disease |
| US12385818B2 (en) | 2023-02-14 | 2025-08-12 | Saudi Arabian Oil Company | Modeling gas desorption in a subsurface reservoir |
| CN118126161B (zh) * | 2024-03-26 | 2025-10-24 | 福州大学 | 一种凝血因子FXIa的多肽抑制剂及其在抗凝治疗方面的应用 |
| CN119372186B (zh) * | 2024-12-30 | 2025-04-15 | 深圳市卫光生物制品股份有限公司 | 一种重组人凝血因子vii的纯化方法和应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007031559A2 (en) | 2005-09-14 | 2007-03-22 | Novo Nordisk Health Care Ag | Human coagulation factor vii polypeptides |
| US20070117756A1 (en) | 2003-06-19 | 2007-05-24 | Maxygen Holdings, Ltd. | FVII or FVIIa Gla domain variants |
Family Cites Families (131)
| 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 |
| US5033252A (en) * | 1987-12-23 | 1991-07-23 | Entravision, Inc. | Method of packaging and sterilizing a pharmaceutical product |
| US5033352A (en) | 1989-01-19 | 1991-07-23 | Yamaha Corporation | Electronic musical instrument with frequency modulation |
| US5304482A (en) | 1989-03-06 | 1994-04-19 | The Board Of Regents Of The University Of Texas System | Serine protease mutants of the chymotrypsin superfamily resistant to inhibition by their cognate inhibitors |
| US5580560A (en) | 1989-11-13 | 1996-12-03 | Novo Nordisk A/S | Modified factor VII/VIIa |
| JP3330932B2 (ja) * | 1990-01-29 | 2002-10-07 | 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 | 抗凝固剤タンパク質 |
| US5583107A (en) | 1990-09-04 | 1996-12-10 | Cor Therapeutics, Inc. | Agents affecting thrombosis and hemostasis |
| US5788965A (en) * | 1991-02-28 | 1998-08-04 | Novo Nordisk A/S | Modified factor VII |
| US20040087498A1 (en) * | 1991-02-28 | 2004-05-06 | Novo Nordisk Health Care Ag | Modified factor VII |
| US5861374A (en) * | 1991-02-28 | 1999-01-19 | Novo Nordisk A/S | Modified Factor VII |
| US5997864A (en) * | 1995-06-07 | 1999-12-07 | Novo Nordisk A/S | Modified factor VII |
| US5817788A (en) * | 1991-02-28 | 1998-10-06 | Zymogenetics, Inc. | Modified factor VII |
| US5323907A (en) * | 1992-06-23 | 1994-06-28 | Multi-Comp, Inc. | Child resistant package assembly for dispensing pharmaceutical medications |
| CA2280700A1 (en) * | 1997-02-14 | 1998-08-20 | American Red Cross | Expression of active human factor ix in mammary tissue of transgenic animals |
| US20050032690A1 (en) * | 1997-09-10 | 2005-02-10 | Rojkjaer Lisa Payne | Factor VII polypeptides for preventing formation of inhibitors in subjects with haemophilia |
| 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 |
| US6017882A (en) * | 1997-10-23 | 2000-01-25 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| 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 |
| US20050287153A1 (en) | 2002-06-28 | 2005-12-29 | Genentech, Inc. | Serum albumin binding peptides for tumor targeting |
| US6797504B1 (en) | 2000-09-08 | 2004-09-28 | Dendreon San Diego Llc | Inhibitors of serine protease activity of matriptase or MTSP1 |
| US7700341B2 (en) * | 2000-02-03 | 2010-04-20 | Dendreon Corporation | Nucleic acid molecules encoding transmembrane serine proteases, the encoded proteins and methods based thereon |
| PL206148B1 (pl) | 2000-02-11 | 2010-07-30 | Bayer HealthCare LLCBayer HealthCare LLC | Koniugat polipeptydowy, polipeptyd, sekwencja nukleotydowa, wektor ekspresyjny, komórka gospodarz, sposób wytwarzania koniugatu polipeptydowego, środek farmaceutyczny i zastosowanie koniugatu polipeptydowego |
| US7220837B1 (en) | 2000-04-28 | 2007-05-22 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| US6905683B2 (en) * | 2000-05-03 | 2005-06-14 | Novo Nordisk Healthcare A/G | Human coagulation factor VII variants |
| AU2001256148A1 (en) | 2000-05-03 | 2001-11-12 | Novo-Nordisk A/S | Subcutaneous administration of coagulation factor vii |
| WO2001083725A1 (en) | 2000-05-03 | 2001-11-08 | Novo Nordisk A/S | Human coagulation factor vii variants |
| EP1282438B1 (en) | 2000-05-10 | 2005-08-03 | Novo Nordisk Health Care AG | Use of pharmaceutical composition comprising a factor viia and a factor xiii |
| US20030211094A1 (en) | 2001-06-26 | 2003-11-13 | Nelsestuen Gary L. | High molecular weight derivatives of vitamin k-dependent polypeptides |
| JP4361728B2 (ja) | 2000-09-13 | 2009-11-11 | 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 | ヒト凝固因子ｖｉｉ変異型 |
| CN100475959C (zh) * | 2000-09-13 | 2009-04-08 | 诺沃挪第克健康护理股份公司 | 人凝血因子vii变体 |
| IL154879A0 (en) | 2000-10-02 | 2003-10-31 | Novo Nordisk As | Factor vii glycoforms |
| US7173000B2 (en) * | 2000-11-09 | 2007-02-06 | The Scripps Research Institute | Modified factor VIIa |
| DE60225118T2 (de) | 2001-02-05 | 2009-03-05 | Novo Nordisk Health Care Ag | Kombinierte verwendung von faktor vii polypeptiden und faktor viii polypeptiden |
| CA2440582A1 (en) * | 2001-03-09 | 2002-10-03 | Dyax Corp. | Serum albumin binding moieties |
| 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 |
| WO2002072786A2 (en) | 2001-03-13 | 2002-09-19 | Corvas International, Inc. | Nucleic acid molecules encoding a transmembrane serine protease 7, the encoded polypeptides and methods based thereon |
| AU2002249096B2 (en) | 2001-03-22 | 2007-06-28 | Novo Nordisk Health Care Ag | Coagulation factor VII derivatives |
| JP2004535166A (ja) | 2001-03-22 | 2004-11-25 | デンドレオン・サンディエゴ・リミテッド・ライアビリティ・カンパニー | セリンプロテアーゼｃｖｓｐ１４をコードする核酸分子、コードされるポリペプチドおよびそれに基づく方法 |
| US7235638B2 (en) * | 2001-03-22 | 2007-06-26 | Novo Nordisk Healthcare A/G | Coagulation factor VII derivatives |
| US7105333B2 (en) | 2001-03-27 | 2006-09-12 | Deadreon Corporation | Nucleic acid molecules encoding a transmembrane serine protease 9, the encoded polypeptides and methods based thereon |
| KR20040080940A (ko) | 2001-05-14 | 2004-09-20 | 덴드레온 코포레이션 | 트랜스막 세린 프로테아제 10을 암호화하는 핵산 분자,암호화된 폴리펩티드 및 이에 근거한 방법 |
| WO2002095007A2 (en) | 2001-05-23 | 2002-11-28 | Dendreon San Diego Llc | Conjugates activated by cell surface proteases and therapeutic uses thereof |
| AU2002315525A1 (en) | 2001-07-03 | 2003-01-21 | Dendreon San Diego Llc | 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 |
| PL368619A1 (en) | 2001-09-27 | 2005-04-04 | Novo Nordisk Health Care Ag | Human coagulation factor vii polypeptides |
| US7052868B2 (en) * | 2001-09-27 | 2006-05-30 | Novo Nordisk Healthcare A/G | Human coagulation factor VII polypeptides |
| WO2003029442A1 (en) | 2001-10-02 | 2003-04-10 | 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 |
| AU2002336919A1 (en) | 2001-11-02 | 2003-05-12 | Novo Nordisk Health Care Ag | 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 |
| WO2003044179A2 (en) | 2001-11-20 | 2003-05-30 | Dendreon San Diego Llc | Nucleic acid molecules encoding serine protease 17, the encoded polypeptides and methods based thereon |
| CN1607958A (zh) | 2001-12-21 | 2005-04-20 | 诺和诺德医疗保健公司 | 因子ⅶ多肽的液体组合物 |
| EP1458407A1 (en) | 2001-12-21 | 2004-09-22 | Novo Nordisk A/S | Liquid composition of modified factor vii polypeptides |
| RU2004134726A (ru) | 2002-04-30 | 2005-06-10 | Максиджен Холдингз Лтд. (Ky) | Варианты полипептида фактора vii или viia |
| EP1361284A1 (en) | 2002-05-10 | 2003-11-12 | Direvo Biotech AG | Process for generating sequence-specific proteases by directed evolution and use thereof |
| WO2003104394A2 (en) | 2002-05-21 | 2003-12-18 | Dendreon San Diego Llc | Nucleic acid molecules encoding a transmembrane serine protease 12, the encoded polypeptides and methods based thereon |
| US20040001801A1 (en) * | 2002-05-23 | 2004-01-01 | Corvas International, Inc. | Conjugates activated by cell surface proteases and therapeutic uses thereof |
| JP2006507477A (ja) | 2002-06-14 | 2006-03-02 | ダイアックス、コープ | タンパク質分析 |
| ATE503498T1 (de) | 2002-06-21 | 2011-04-15 | Novo Nordisk Healthcare Ag | Pegylierte glykoformen von faktor vii |
| MXPA04012496A (es) | 2002-06-21 | 2005-09-12 | Novo Nordisk Healthcare Ag | Glicoformos del factor vii pegilados. |
| WO2004005471A2 (en) | 2002-07-02 | 2004-01-15 | Dendreon Corporation | Serine protease 16 |
| US6911323B2 (en) * | 2002-09-25 | 2005-06-28 | Novo Nordisk Healthcare A/G | Human coagulation factor VII polypeptides |
| ES2293088T3 (es) | 2002-09-25 | 2008-03-16 | Novo Nordisk Health Care Ag | Polipeptidos del factor vii de la coagulacion humana. |
| CA2840692A1 (en) | 2002-09-30 | 2004-04-08 | Bayer Healthcare Llc | Fvii or fviia variants having increased clotting activity |
| JP5376747B2 (ja) * | 2002-10-02 | 2013-12-25 | カタリスト バイオサイエンシーズ， インコーポレイテッド | 改変された特異性を有するプロテアーゼを作製する方法およびスクリーニングする方法 |
| US7939304B2 (en) * | 2002-10-02 | 2011-05-10 | Catalyst Biosciences, Inc. | Mutant MT-SP1 proteases with altered substrate specificity or activity |
| US20060024289A1 (en) * | 2002-10-02 | 2006-02-02 | Ruggles Sandra W | Cleavage of VEGF and VEGF receptor by wild-type and mutant proteases |
| RU2364626C2 (ru) | 2003-03-18 | 2009-08-20 | Ново Нордиск Хелт Кэр Аг | Способ получения, способ очистки и способ стабилизации полипептидов фактора vii, ix и x |
| CA2519873C (en) | 2003-03-20 | 2012-12-18 | Maxygen Holdings Ltd. | Fvii or fviia variants |
| CA2528239A1 (en) | 2003-06-05 | 2004-12-16 | Canadian Blood Services | Mutants of the factor vii epidermal growth factor domain |
| EP1646398A2 (en) | 2003-06-13 | 2006-04-19 | Novo Nordisk Health Care AG | Formulations comprising factor viia and a factor vii related polypeptide |
| US20060116324A1 (en) * | 2003-06-13 | 2006-06-01 | Novo Nordisk Healthcare A/G | Novel formulations |
| ATE526399T1 (de) | 2003-06-18 | 2011-10-15 | Bayer Pharma AG | Neue biologische einheiten und deren verwendung |
| EP1633866A1 (en) | 2003-06-18 | 2006-03-15 | Direvo Biotech AG | New biological entities and the pharmaceutical or diagnostic use thereof |
| WO2005023308A1 (en) | 2003-09-05 | 2005-03-17 | Maxygen Holdings Ltd. | Formulations of vitamin k-dependent polypeptides and sulfoalkyl ether cycloextrins |
| EP1664291B1 (en) | 2003-09-09 | 2012-02-29 | Novo Nordisk Health Care AG | Coagulation factor vii polypeptides |
| ES2381110T3 (es) * | 2003-09-09 | 2012-05-23 | Novo Nordisk Health Care Ag | Polipéptidos de factor VII de coagulación |
| WO2005032581A2 (en) | 2003-10-07 | 2005-04-14 | Novo Nordisk Health Care Ag | Hybrid molecules having factor vii/viia activity |
| US20080193441A1 (en) | 2003-11-18 | 2008-08-14 | Iconic Therapeutics, Inc. | Homogeneous Preparations of Chimeric Protein |
| WO2005068620A1 (en) | 2004-01-07 | 2005-07-28 | Novo Nordisk Health Care Ag | Method for the production of recombinant proteins |
| WO2005075635A2 (en) | 2004-02-03 | 2005-08-18 | Novo Nordisk Health Care Ag | Coagulation factor vii/viia variants lacking a functional lipid membrane binding domain |
| WO2005100556A2 (en) | 2004-04-12 | 2005-10-27 | Catalyst Biosciences | Cleavage of vegf and vegf receptor by wild-type and mutant proteases |
| WO2005110453A2 (en) | 2004-04-12 | 2005-11-24 | Catalyst Biosciences, Inc. | Cleavage of vegf and vegf receptor by wildtype and mutant mt-sp1 |
| MXPA06012676A (es) | 2004-05-04 | 2007-04-02 | Novo Nordisk Healthcare Ag | Glucoformas o-enlazadas de polipeptidos y metodos de fabricacion de los mismos. |
| WO2005123119A2 (en) | 2004-06-10 | 2005-12-29 | Catalyst Biosciences, Inc. | Administration of neutral endopeptidase to treat inflammatory bowel disease |
| AU2005253749A1 (en) | 2004-06-21 | 2005-12-29 | Novo Nordisk Health Care Ag | Use of factor VIIa or factor VIIa equivalents for preventing or attenuating haemorrhage growth, and/or oedema generation following intracerebral haemorrhage (ICH) |
| EP1761630A2 (en) * | 2004-06-21 | 2007-03-14 | Novo Nordisk Health Care AG | Glycosylation-disrupted factor vii variants |
| WO2006014253A2 (en) | 2004-07-02 | 2006-02-09 | Genentech, Inc. | Factor viia variants |
| WO2006008267A2 (en) | 2004-07-16 | 2006-01-26 | Novo Nordisk Health Care Ag | Methods for optimizing forming viiia-based hemostatic treatment |
| WO2006013202A2 (en) | 2004-08-02 | 2006-02-09 | Novo Nordisk Health Care Ag | Conjugation of fvii |
| MX2007001294A (es) | 2004-08-17 | 2008-03-04 | Zlb Behring Gmbh | Polipeptidos modificados que dependen de vitamina k. |
| WO2006035057A1 (en) | 2004-09-29 | 2006-04-06 | Novo Nordisk Health Care Ag | Modified proteins |
| WO2006067198A2 (en) | 2004-12-22 | 2006-06-29 | Direvo Biotech Ag | Targeted use of engineered enzymes |
| EP2360171A1 (en) | 2004-12-23 | 2011-08-24 | Novo Nordisk Health Care AG | Reduction of the content of protein contaminants in compositions comprising a vitamin K-dependent protein of interest |
| WO2006114105A2 (en) | 2005-04-26 | 2006-11-02 | Maxygen Holdings Ltd. | Use of modified factor vii for treating bleeding |
| EP1877037A2 (en) | 2005-04-28 | 2008-01-16 | Novo Nordisk Health Care AG | A closed container comprising an activated factor vii polypeptide, processes for the preparation of the same, and a kit and a method for use of the kit |
| EP1726643A1 (en) | 2005-05-27 | 2006-11-29 | Direvo Biotech AG | Method for the provision, identification and selection of proteases with altered sensitivity to activity-modulating substances |
| EP2360170A3 (en) | 2005-06-17 | 2012-03-28 | Novo Nordisk Health Care AG | Selective reduction and derivatization of engineered proteins comprinsing at least one non-native cysteine |
| EP1893631B1 (en) | 2005-06-17 | 2013-08-14 | Novo Nordisk Health Care AG | Dimeric and multimeric fviia compounds |
| CN102719508A (zh) * | 2005-08-19 | 2012-10-10 | 诺和诺德公司 | 糖基聚乙二醇化的因子vii和因子viia |
| US20090017007A1 (en) | 2005-08-26 | 2009-01-15 | Maxygen Holdings Ltd. | Liquid factor vii composition |
| EP1924688A1 (en) | 2005-09-01 | 2008-05-28 | Novo Nordisk Health Care AG | Purification of coagulation factor vii polypeptides |
| US20090011992A1 (en) | 2005-09-21 | 2009-01-08 | Novo Nordisk Healthcare A/G | Human Coagulation Factor VII Polypeptides |
| WO2007044874A2 (en) | 2005-10-07 | 2007-04-19 | Novo Nordisk A/S | Use of factor vii polypeptides for neuroprotection |
| ES2611608T3 (es) * | 2005-10-21 | 2017-05-09 | Catalyst Biosciences, Inc. | Proteasas modificadas que inhiben la activación del complemento |
| US8383388B2 (en) * | 2006-06-19 | 2013-02-26 | Catalyst Biosciences, Inc. | Modified coagulation factor IX polypeptides and use thereof for treatment |
| TWI369402B (en) | 2006-07-05 | 2012-08-01 | Catalyst Biosciences Inc | Protease screening methods and proteases identified thereby |
| EP2046371A2 (en) | 2006-07-17 | 2009-04-15 | Novo Nordisk Health Care AG | Factor viia analogues with increased activity for treating thrombocytopenia |
| JP2010513462A (ja) | 2006-12-20 | 2010-04-30 | バイエル・ヘルスケア・エルエルシー | 第ＶＩＩおよび第ＶＩＩａ因子組成物 |
| EP1952822A1 (en) * | 2007-01-26 | 2008-08-06 | Novo Nordisk A/S | Factor VII polypeptides with increased affinity to platelets |
| BRPI0810172A2 (pt) * | 2007-04-13 | 2014-10-14 | Catalyst Biosciences Inc | Polipeptídeos de fator vii modificado e seus usos |
| US9102962B2 (en) | 2007-10-16 | 2015-08-11 | Shiu Nan Chen | Production method for solid cultured active mushroom mycelium and fruit-body metabolites (AMFM) products thereof |
| GB0800938D0 (en) * | 2008-01-18 | 2008-02-27 | Ge Healthcare Uk Ltd | Multiplex cell signalling assay |
| TWI465247B (zh) | 2008-04-11 | 2014-12-21 | Catalyst Biosciences Inc | 經修飾的因子ｖｉｉ多肽和其用途 |
| US8266208B2 (en) | 2008-11-06 | 2012-09-11 | Joseph Mahon | Method and system for sharing documents among members of an online community |
| WO2010151736A1 (en) * | 2009-06-25 | 2010-12-29 | The University Of North Carolina At Chapel Hill | Chimeric factor vii molecules |
| CN201753815U (zh) | 2010-07-27 | 2011-03-02 | 江森自控空调冷冻设备(无锡)有限公司 | 三通结构 |
| 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 |
| WO2014018120A1 (en) | 2012-07-25 | 2014-01-30 | Catalyst Biosciences, Inc. | Modified factor x polypeptides and uses thereof |
| JP2015532307A (ja) | 2012-10-15 | 2015-11-09 | ノヴォ・ノルディスク・ヘルス・ケア・アーゲー | 凝固因子ｖｉｉポリペプチド |
| EP3833381B1 (en) | 2019-08-15 | 2022-08-03 | Catalyst Biosciences, Inc. | Modified factor vii polypeptides for subcutaneous administration |
-
2009
- 2009-04-09 TW TW098111791A patent/TWI465247B/zh not_active IP Right Cessation
- 2009-04-09 TW TW103116777A patent/TWI538916B/zh not_active IP Right Cessation
- 2009-04-10 SI SI200931368T patent/SI2281037T1/sl unknown
- 2009-04-10 ES ES09730852.2T patent/ES2556596T3/es active Active
- 2009-04-10 JP JP2011504007A patent/JP2011517942A/ja active Pending
- 2009-04-10 EP EP16159675.4A patent/EP3064580A1/en not_active Withdrawn
- 2009-04-10 HU HUE09730852A patent/HUE026937T2/en unknown
- 2009-04-10 ES ES13162174.0T patent/ES2577055T3/es active Active
- 2009-04-10 PT PT97308522T patent/PT2281037E/pt unknown
- 2009-04-10 MX MX2010011170A patent/MX2010011170A/es active IP Right Grant
- 2009-04-10 DK DK13162166.6T patent/DK2687596T3/da active
- 2009-04-10 US US12/384,915 patent/US8519103B2/en active Active
- 2009-04-10 MX MX2012012083A patent/MX344220B/es unknown
- 2009-04-10 MY MYPI2010004758A patent/MY161581A/en unknown
- 2009-04-10 SG SG2013027644A patent/SG190560A1/en unknown
- 2009-04-10 CA CA2721038A patent/CA2721038C/en active Active
- 2009-04-10 EP EP13162174.0A patent/EP2679678B1/en active Active
- 2009-04-10 AU AU2009234390A patent/AU2009234390B2/en not_active Ceased
- 2009-04-10 CN CN200980121895.1A patent/CN102083971B/zh active Active
- 2009-04-10 EA EA201001628A patent/EA020818B1/ru not_active IP Right Cessation
- 2009-04-10 CN CN201510387292.3A patent/CN105039291A/zh active Pending
- 2009-04-10 EP EP13162166.6A patent/EP2687596B1/en active Active
- 2009-04-10 WO PCT/US2009/002248 patent/WO2009126307A2/en not_active Ceased
- 2009-04-10 ES ES13162166.6T patent/ES2560236T3/es active Active
- 2009-04-10 EP EP09730852.2A patent/EP2281037B1/en active Active
- 2009-04-10 BR BRPI0911060-7A patent/BRPI0911060B1/pt not_active IP Right Cessation
- 2009-04-10 KR KR1020107025264A patent/KR101623602B1/ko active Active
- 2009-04-10 NZ NZ588322A patent/NZ588322A/en unknown
- 2009-04-10 EA EA201301350A patent/EA024760B1/ru not_active IP Right Cessation
- 2009-04-10 SG SG2013057724A patent/SG193779A1/en unknown
- 2009-04-10 PL PL09730852T patent/PL2281037T3/pl unknown
- 2009-04-10 DK DK09730852.2T patent/DK2281037T3/en active
-
2010
- 2010-10-03 IL IL208373A patent/IL208373A/en active IP Right Grant
- 2010-10-13 CO CO10127271A patent/CO6331368A2/es not_active Application Discontinuation
-
2013
- 2013-04-14 IL IL225740A patent/IL225740A/en active IP Right Grant
- 2013-07-30 US US13/987,492 patent/US9476037B2/en active Active
-
2014
- 2014-01-09 JP JP2014002379A patent/JP5976021B2/ja not_active Expired - Fee Related
- 2014-07-31 JP JP2014155757A patent/JP5659312B1/ja not_active Expired - Fee Related
-
2016
- 2016-09-07 US US15/258,908 patent/US10160961B2/en active Active
-
2018
- 2018-11-02 US US16/179,642 patent/US11203749B2/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070117756A1 (en) | 2003-06-19 | 2007-05-24 | Maxygen Holdings, Ltd. | FVII or FVIIa Gla domain variants |
| WO2007031559A2 (en) | 2005-09-14 | 2007-03-22 | Novo Nordisk Health Care Ag | Human coagulation factor vii polypeptides |
Non-Patent Citations (2)
| Title |
|---|
| Craig D. Dickinson 등. PNAS. Vol. 93, No. 1, 페이지 14379-14384 (1996.) |
| Jais R. Bjelke 등. FEBS Letters. Vol. 581, No. 1, 페이지 71-76 (2007.) |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101623602B1 (ko) | 변형된 제ⅶ 인자 폴리펩티드 및 그의 용도 | |
| JP5761782B2 (ja) | 改変第ｖｉｉ因子ポリペプチド及びその使用 | |
| AU2013203608B2 (en) | Factor vii polypeptides that are modified and uses thereof | |
| AU2015224596A1 (en) | Factor vii polypeptides that are modified and uses thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20101110 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20130903 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20150629 Patent event code: PE09021S01D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20160225 |
|
| GRNT | Written decision to grant | ||
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20160517 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 20160517 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration | ||
| FPAY | Annual fee payment |
Payment date: 20190425 Year of fee payment: 4 |
|
| PR1001 | Payment of annual fee |
Payment date: 20190425 Start annual number: 4 End annual number: 4 |
|
| PR1001 | Payment of annual fee |
Payment date: 20200507 Start annual number: 5 End annual number: 5 |
|
| PR1001 | Payment of annual fee |
Payment date: 20210506 Start annual number: 6 End annual number: 6 |
|
| PR1001 | Payment of annual fee |
Payment date: 20240327 Start annual number: 9 End annual number: 9 |