KR20010031370A - 변형된 비타민 ｋ-의존성 폴리펩티드 - Google Patents
변형된 비타민 ｋ-의존성 폴리펩티드 Download PDFInfo
- Publication number
- KR20010031370A KR20010031370A KR1020007004378A KR20007004378A KR20010031370A KR 20010031370 A KR20010031370 A KR 20010031370A KR 1020007004378 A KR1020007004378 A KR 1020007004378A KR 20007004378 A KR20007004378 A KR 20007004378A KR 20010031370 A KR20010031370 A KR 20010031370A
- Authority
- KR
- South Korea
- Prior art keywords
- amino acid
- vitamin
- protein
- polypeptide
- factor
- 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.)
- Ceased
Links
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 142
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 142
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 141
- 230000001419 dependent effect Effects 0.000 title claims abstract description 111
- 229940046010 vitamin k Drugs 0.000 title claims abstract description 109
- 239000012528 membrane Substances 0.000 claims abstract description 111
- 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 claims abstract description 109
- 229930003448 Vitamin K Natural products 0.000 claims abstract description 108
- 239000011712 vitamin K Substances 0.000 claims abstract description 108
- 235000019168 vitamin K Nutrition 0.000 claims abstract description 108
- 150000003721 vitamin K derivatives Chemical class 0.000 claims abstract description 108
- 238000000034 method Methods 0.000 claims abstract description 48
- 241000124008 Mammalia Species 0.000 claims abstract description 24
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 24
- 208000007536 Thrombosis Diseases 0.000 claims abstract description 18
- 235000001014 amino acid Nutrition 0.000 claims description 156
- 150000001413 amino acids Chemical group 0.000 claims description 125
- 229960000856 protein c Drugs 0.000 claims description 76
- 101800004937 Protein C Proteins 0.000 claims description 68
- 101800001700 Saposin-D Proteins 0.000 claims description 68
- 108010023321 Factor VII Proteins 0.000 claims description 63
- 229940012414 factor viia Drugs 0.000 claims description 63
- 102100023804 Coagulation factor VII Human genes 0.000 claims description 62
- 108010054265 Factor VIIa Proteins 0.000 claims description 62
- 229940012413 factor vii Drugs 0.000 claims description 62
- 238000006467 substitution reaction Methods 0.000 claims description 60
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 claims description 26
- 102100022641 Coagulation factor IX Human genes 0.000 claims description 20
- 108010076282 Factor IX Proteins 0.000 claims description 17
- 239000011575 calcium Substances 0.000 claims description 17
- 229960004222 factor ix Drugs 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 16
- 229910052791 calcium Inorganic materials 0.000 claims description 16
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 claims description 15
- 108010048049 Factor IXa Proteins 0.000 claims description 12
- CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical group N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 11
- 239000013598 vector Substances 0.000 claims description 9
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 108020004707 nucleic acids Proteins 0.000 claims description 6
- 102000039446 nucleic acids Human genes 0.000 claims description 6
- 150000007523 nucleic acids Chemical class 0.000 claims description 6
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 5
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 5
- 125000002091 cationic group Chemical group 0.000 claims description 4
- 235000013922 glutamic acid Nutrition 0.000 claims description 4
- 239000004220 glutamic acid Substances 0.000 claims description 4
- 239000004471 Glycine Substances 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 102400000827 Saposin-D Human genes 0.000 claims 2
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 229940088594 vitamin Drugs 0.000 claims 1
- 229930003231 vitamin Natural products 0.000 claims 1
- 235000013343 vitamin Nutrition 0.000 claims 1
- 239000011782 vitamin Substances 0.000 claims 1
- 150000003722 vitamin derivatives Chemical class 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 description 82
- 102000004169 proteins and genes Human genes 0.000 description 80
- 235000018102 proteins Nutrition 0.000 description 79
- UHBYWPGGCSDKFX-VKHMYHEASA-N gamma-carboxy-L-glutamic acid Chemical group OC(=O)[C@@H](N)CC(C(O)=O)C(O)=O UHBYWPGGCSDKFX-VKHMYHEASA-N 0.000 description 68
- 102000017975 Protein C Human genes 0.000 description 67
- 241000283690 Bos taurus Species 0.000 description 58
- 230000000694 effects Effects 0.000 description 57
- 101500025568 Homo sapiens Saposin-D Proteins 0.000 description 48
- 229940100689 human protein c Drugs 0.000 description 47
- 230000002776 aggregation Effects 0.000 description 43
- 238000004220 aggregation Methods 0.000 description 41
- 125000003275 alpha amino acid group Chemical group 0.000 description 39
- 101500025565 Bos taurus Saposin-D Proteins 0.000 description 38
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 33
- 239000002299 complementary DNA Substances 0.000 description 33
- 150000003904 phospholipids Chemical class 0.000 description 31
- 230000035772 mutation Effects 0.000 description 30
- 108010014173 Factor X Proteins 0.000 description 29
- 229940012426 factor x Drugs 0.000 description 29
- 108010000499 Thromboplastin Proteins 0.000 description 24
- 102000002262 Thromboplastin Human genes 0.000 description 24
- 239000012634 fragment Substances 0.000 description 22
- 230000004913 activation Effects 0.000 description 19
- 239000000872 buffer Substances 0.000 description 18
- 239000000203 mixture Substances 0.000 description 18
- 239000011780 sodium chloride Substances 0.000 description 17
- 108090000790 Enzymes Proteins 0.000 description 15
- 102000004190 Enzymes Human genes 0.000 description 15
- 229940088598 enzyme Drugs 0.000 description 15
- 238000003556 assay Methods 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 13
- 108010025221 plasma protein Z Proteins 0.000 description 13
- 101000651448 Bos taurus Prothrombin Proteins 0.000 description 12
- 101000924577 Homo sapiens Adenomatous polyposis coli protein Proteins 0.000 description 12
- 230000015271 coagulation Effects 0.000 description 12
- 238000005345 coagulation Methods 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- 238000009472 formulation Methods 0.000 description 11
- 230000004048 modification Effects 0.000 description 11
- 238000012986 modification Methods 0.000 description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 11
- 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 10
- 241000282412 Homo Species 0.000 description 10
- 125000000539 amino acid group Chemical group 0.000 description 10
- 230000003993 interaction Effects 0.000 description 10
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 9
- 102100034540 Adenomatous polyposis coli protein Human genes 0.000 description 9
- 108010054218 Factor VIII Proteins 0.000 description 9
- 102000001690 Factor VIII Human genes 0.000 description 9
- 108010074860 Factor Xa Proteins 0.000 description 9
- 208000009292 Hemophilia A Diseases 0.000 description 9
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 9
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 9
- 108010094028 Prothrombin Proteins 0.000 description 9
- 108090000190 Thrombin Proteins 0.000 description 9
- 230000035602 clotting Effects 0.000 description 9
- 238000010494 dissociation reaction Methods 0.000 description 9
- 230000005593 dissociations Effects 0.000 description 9
- 229960000301 factor viii Drugs 0.000 description 9
- 229940039716 prothrombin Drugs 0.000 description 9
- 229960004072 thrombin Drugs 0.000 description 9
- 108020004414 DNA Proteins 0.000 description 8
- 108010074105 Factor Va Proteins 0.000 description 8
- 108090000144 Human Proteins Proteins 0.000 description 8
- 102000003839 Human Proteins Human genes 0.000 description 8
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 8
- 102100027378 Prothrombin Human genes 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 7
- 239000007983 Tris buffer Substances 0.000 description 7
- 108091005605 Vitamin K-dependent proteins Proteins 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 230000023555 blood coagulation Effects 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 7
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 6
- 208000031220 Hemophilia Diseases 0.000 description 6
- 108010066124 Protein S Proteins 0.000 description 6
- 229940096437 Protein S Drugs 0.000 description 6
- 102000029301 Protein S Human genes 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 230000002779 inactivation Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 238000001890 transfection Methods 0.000 description 6
- NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical group OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 229930182816 L-glutamine Natural products 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 102000055691 human APC Human genes 0.000 description 5
- 102000035118 modified proteins Human genes 0.000 description 5
- 108091005573 modified proteins Proteins 0.000 description 5
- 239000002773 nucleotide Substances 0.000 description 5
- 125000003729 nucleotide group Chemical group 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 4
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 4
- 108010021466 Mutant Proteins Proteins 0.000 description 4
- 102000008300 Mutant Proteins Human genes 0.000 description 4
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 4
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 238000000149 argon plasma sintering Methods 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 239000001110 calcium chloride Substances 0.000 description 4
- 229910001628 calcium chloride Inorganic materials 0.000 description 4
- 229910001424 calcium ion Inorganic materials 0.000 description 4
- 230000002950 deficient Effects 0.000 description 4
- 229940047127 fiore Drugs 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 230000014508 negative regulation of coagulation Effects 0.000 description 4
- 102220022330 rs193922746 Human genes 0.000 description 4
- 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 3
- 102100026735 Coagulation factor VIII Human genes 0.000 description 3
- 201000003542 Factor VIII deficiency Diseases 0.000 description 3
- 108010061932 Factor VIIIa Proteins 0.000 description 3
- 101800000342 Glycoprotein C Proteins 0.000 description 3
- 102000003886 Glycoproteins Human genes 0.000 description 3
- 108090000288 Glycoproteins Proteins 0.000 description 3
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 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
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 3
- 239000003146 anticoagulant agent Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
- 238000007820 coagulation assay Methods 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 208000009429 hemophilia B Diseases 0.000 description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 3
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 229960000485 methotrexate Drugs 0.000 description 3
- 239000011772 phylloquinone Substances 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 230000012846 protein folding Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 238000002741 site-directed mutagenesis Methods 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- 229960005322 streptomycin Drugs 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 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 2
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 2
- 101710112282 Adenomatous polyposis coli protein Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 206010053567 Coagulopathies Diseases 0.000 description 2
- 108020004635 Complementary DNA Proteins 0.000 description 2
- 238000001712 DNA sequencing Methods 0.000 description 2
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 2
- 108010007979 Glycocholic Acid Proteins 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 101000651439 Homo sapiens Prothrombin Proteins 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 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 2
- 239000008351 acetate buffer Substances 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000011543 agarose gel Substances 0.000 description 2
- 238000005054 agglomeration Methods 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 229940127219 anticoagulant drug Drugs 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- XTKDAFGWCDAMPY-UHFFFAOYSA-N azaperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCN(C=2N=CC=CC=2)CC1 XTKDAFGWCDAMPY-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 150000007942 carboxylates Chemical class 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000004925 denaturation Methods 0.000 description 2
- 230000036425 denaturation Effects 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 108010030074 endodeoxyribonuclease MluI Proteins 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
- RFDAIACWWDREDC-FRVQLJSFSA-N glycocholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 RFDAIACWWDREDC-FRVQLJSFSA-N 0.000 description 2
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 2
- 230000023597 hemostasis Effects 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 229940099816 human factor vii Drugs 0.000 description 2
- 229940039715 human prothrombin Drugs 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 210000003292 kidney cell Anatomy 0.000 description 2
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 239000007923 nasal drop Substances 0.000 description 2
- 229940100662 nasal drops Drugs 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 2
- MBWXNTAXLNYFJB-LKUDQCMESA-N phylloquinone Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CCCC(C)CCCC(C)CCCC(C)C)=C(C)C(=O)C2=C1 MBWXNTAXLNYFJB-LKUDQCMESA-N 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 102220074242 rs34116584 Human genes 0.000 description 2
- 102220048271 rs587784390 Human genes 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 238000012289 standard assay Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 239000002691 unilamellar liposome Substances 0.000 description 2
- KWPACVJPAFGBEQ-IKGGRYGDSA-N (2s)-1-[(2r)-2-amino-3-phenylpropanoyl]-n-[(3s)-1-chloro-6-(diaminomethylideneamino)-2-oxohexan-3-yl]pyrrolidine-2-carboxamide Chemical compound C([C@@H](N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)CCl)C1=CC=CC=C1 KWPACVJPAFGBEQ-IKGGRYGDSA-N 0.000 description 1
- 241000238876 Acari Species 0.000 description 1
- 101000689231 Aeromonas salmonicida S-layer protein Proteins 0.000 description 1
- 208000002109 Argyria Diseases 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 101000946068 Caenorhabditis elegans Ceramide glucosyltransferase 3 Proteins 0.000 description 1
- 101100512078 Caenorhabditis elegans lys-1 gene Proteins 0.000 description 1
- 102000005701 Calcium-Binding Proteins Human genes 0.000 description 1
- 108010045403 Calcium-Binding Proteins Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 102000010911 Enzyme Precursors Human genes 0.000 description 1
- 108010062466 Enzyme Precursors Proteins 0.000 description 1
- 108010014172 Factor V Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 101000577630 Homo sapiens Vitamin K-dependent protein S Proteins 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 101710172804 K protein Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- ABSPRNADVQNDOU-UHFFFAOYSA-N Menaquinone 1 Natural products C1=CC=C2C(=O)C(CC=C(C)C)=C(C)C(=O)C2=C1 ABSPRNADVQNDOU-UHFFFAOYSA-N 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102100029796 Protein S100-A10 Human genes 0.000 description 1
- 101710089165 Protein white Proteins 0.000 description 1
- 108010019653 Pwo polymerase Proteins 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 108010073771 Soybean Proteins Proteins 0.000 description 1
- 101000748795 Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8) Cytochrome c oxidase polypeptide I+III Proteins 0.000 description 1
- 102100026966 Thrombomodulin Human genes 0.000 description 1
- 108010079274 Thrombomodulin Proteins 0.000 description 1
- 229940127508 Vitamin K Inhibitors Drugs 0.000 description 1
- FJWGYAHXMCUOOM-QHOUIDNNSA-N [(2s,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6s)-4,5-dinitrooxy-2-(nitrooxymethyl)-6-[(2r,3r,4s,5r,6s)-4,5,6-trinitrooxy-2-(nitrooxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-3,5-dinitrooxy-6-(nitrooxymethyl)oxan-4-yl] nitrate Chemical compound O([C@@H]1O[C@@H]([C@H]([C@H](O[N+]([O-])=O)[C@H]1O[N+]([O-])=O)O[C@H]1[C@@H]([C@@H](O[N+]([O-])=O)[C@H](O[N+]([O-])=O)[C@@H](CO[N+]([O-])=O)O1)O[N+]([O-])=O)CO[N+](=O)[O-])[C@@H]1[C@@H](CO[N+]([O-])=O)O[C@@H](O[N+]([O-])=O)[C@H](O[N+]([O-])=O)[C@H]1O[N+]([O-])=O FJWGYAHXMCUOOM-QHOUIDNNSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- LZCZIHQBSCVGRD-UHFFFAOYSA-N benzenecarboximidamide;hydron;chloride Chemical compound [Cl-].NC(=[NH2+])C1=CC=CC=C1 LZCZIHQBSCVGRD-UHFFFAOYSA-N 0.000 description 1
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N benzo-alpha-pyrone Natural products C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000006696 biosynthetic metabolic pathway Effects 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 102220363778 c.97C>G Human genes 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- UHBYWPGGCSDKFX-UHFFFAOYSA-N carboxyglutamic acid Chemical compound OC(=O)C(N)CC(C(O)=O)C(O)=O UHBYWPGGCSDKFX-UHFFFAOYSA-N 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 235000001671 coumarin Nutrition 0.000 description 1
- 150000004775 coumarins Chemical class 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
- 239000013078 crystal Substances 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229940009976 deoxycholate Drugs 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- 239000005549 deoxyribonucleoside Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 230000001614 effect on membrane Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 201000007386 factor VII deficiency Diseases 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003630 growth substance Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 102000052932 human PROS1 Human genes 0.000 description 1
- 229940099815 human protein s Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 125000003010 ionic group Chemical group 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000001471 micro-filtration Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000002790 naphthalenes Chemical class 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229940127216 oral anticoagulant drug Drugs 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 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
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 235000019175 phylloquinone Nutrition 0.000 description 1
- MBWXNTAXLNYFJB-NKFFZRIASA-N phylloquinone Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CCC[C@H](C)CCC[C@H](C)CCCC(C)C)=C(C)C(=O)C2=C1 MBWXNTAXLNYFJB-NKFFZRIASA-N 0.000 description 1
- 229960001898 phytomenadione Drugs 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003805 procoagulant Substances 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
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000003946 protein process Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 108010013773 recombinant FVIIa Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229940001941 soy protein Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229910052712 strontium Inorganic materials 0.000 description 1
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 1
- 229910001427 strontium ion Inorganic materials 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960003766 thrombin (human) Drugs 0.000 description 1
- 230000008791 toxic response Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- 125000002264 triphosphate group Chemical class [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 238000002525 ultrasonication Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 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 1
- 229960005080 warfarin Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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
- 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
- C12N15/52—Genes encoding for enzymes or proenzymes
-
- 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
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- 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)
- C12N9/644—Coagulation factor IXa (3.4.21.22)
-
- 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)
- C12N9/6464—Protein C (3.4.21.69)
-
- 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)
- C12N9/647—Blood coagulation factors not provided for in a preceding group or according to more than one of the proceeding groups
-
- 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)
-
- 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)
- C12Y304/21022—Coagulation factor IXa (3.4.21.22)
-
- 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)
- C12Y304/21069—Protein C activated (3.4.21.69)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Hematology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Diabetes (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8/955,636 | 1997-10-23 | ||
| US08/955,636 US6017882A (en) | 1997-10-23 | 1997-10-23 | Modified vitamin K-dependent polypeptides |
| PCT/US1998/022152 WO1999020767A1 (en) | 1997-10-23 | 1998-10-20 | Modified vitamin k-dependent polypeptides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20010031370A true KR20010031370A (ko) | 2001-04-16 |
Family
ID=25497114
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020007004378A Ceased KR20010031370A (ko) | 1997-10-23 | 1998-10-20 | 변형된 비타민 ｋ-의존성 폴리펩티드 |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US6017882A (https=) |
| EP (2) | EP1676919B1 (https=) |
| JP (1) | JP4276379B2 (https=) |
| KR (1) | KR20010031370A (https=) |
| CN (1) | CN1246462C (https=) |
| AP (1) | AP2000001811A0 (https=) |
| AR (2) | AR020048A1 (https=) |
| AT (1) | ATE390486T1 (https=) |
| AU (1) | AU749279C (https=) |
| BR (1) | BR9814611A (https=) |
| CA (1) | CA2307175C (https=) |
| DE (1) | DE69839313T2 (https=) |
| DK (1) | DK1090128T3 (https=) |
| EA (1) | EA200000449A1 (https=) |
| ES (2) | ES2303362T3 (https=) |
| HR (1) | HRP20000234A2 (https=) |
| HU (1) | HU225993B1 (https=) |
| ID (1) | ID26330A (https=) |
| IL (1) | IL135603A0 (https=) |
| IS (1) | IS5449A (https=) |
| MY (1) | MY136336A (https=) |
| NO (1) | NO20002025L (https=) |
| NZ (1) | NZ504114A (https=) |
| PL (1) | PL194194B1 (https=) |
| PT (1) | PT1090128E (https=) |
| SG (1) | SG105547A1 (https=) |
| TR (1) | TR200001105T2 (https=) |
| TW (1) | TW587081B (https=) |
| WO (1) | WO1999020767A1 (https=) |
| ZA (1) | ZA989597B (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100755967B1 (ko) * | 2003-10-23 | 2007-09-06 | 한국타이어 주식회사 | 타이어의 비드와 휠의 갭 측정장치 |
Families Citing this family (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6747003B1 (en) * | 1997-10-23 | 2004-06-08 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| US6693075B1 (en) * | 1997-10-23 | 2004-02-17 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| US7247708B2 (en) * | 1997-10-23 | 2007-07-24 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| US6998122B1 (en) | 1999-04-30 | 2006-02-14 | Eli Lilly And Company | Protein C derivatives |
| CA2391651A1 (en) * | 1999-11-19 | 2001-05-25 | Eli Lilly And Company | Protein c derivatives |
| WO2001057193A2 (en) | 2000-02-02 | 2001-08-09 | Eli Lilly And Company | Protein c derivatives |
| DE60138364D1 (de) * | 2000-02-11 | 2009-05-28 | Bayer Healthcare Llc | Gerinnungsfaktor vii oder viia konjugate |
| CA2400187A1 (en) | 2000-02-11 | 2001-08-16 | Eli Lilly And Company | Protein c derivatives |
| US7220837B1 (en) | 2000-04-28 | 2007-05-22 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| US7812132B2 (en) | 2000-04-28 | 2010-10-12 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| US6423826B1 (en) | 2000-06-30 | 2002-07-23 | Regents Of The University Of Minnesota | High molecular weight derivatives of vitamin K-dependent polypeptides |
| US20030211094A1 (en) * | 2001-06-26 | 2003-11-13 | Nelsestuen Gary L. | High molecular weight derivatives of vitamin k-dependent polypeptides |
| US7160540B2 (en) * | 2000-06-30 | 2007-01-09 | Regents Of The University Of Minnesota | Methods for detecting activity of clottings factors |
| US6828306B2 (en) * | 2000-07-31 | 2004-12-07 | Ottawa Heart Institute Research Corporation | Charged lipid compositions and methods for their use |
| US6933367B2 (en) | 2000-10-18 | 2005-08-23 | Maxygen Aps | Protein C or activated protein C-like molecules |
| JP2004527239A (ja) * | 2001-03-02 | 2004-09-09 | テイ・エイ・シー・スロムボシス・アンド・コアグラシヨン・エイ・ビー | プロテインｃ変異体 |
| WO2003073980A2 (en) * | 2002-03-01 | 2003-09-12 | T.A.C. Thrombosis And Coagulation Aktiebolag | Recombinant protein c variants |
| US20030186862A1 (en) * | 2002-04-02 | 2003-10-02 | Nelsestuen Gary L. | Factor VIIa compositions |
| SI1499719T1 (sl) * | 2002-04-30 | 2011-03-31 | Bayer Healthcare Llc | Polipeptidne variante faktorja VII ali VIIa |
| US20030232075A1 (en) * | 2002-05-06 | 2003-12-18 | University Of Minnesota, A Minnesota Corporation | Compositions for producing factor Xa |
| PT1517698E (pt) | 2002-06-21 | 2014-11-19 | Novo Nordisk Healthcare Ag | Composições sólidas estabilizadas de polipéptidos do fator viia |
| US20040176704A1 (en) * | 2003-03-04 | 2004-09-09 | Stevens Timothy A | Collection device adapted to accept cartridge for point of care system |
| 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 |
| DK1608745T3 (da) | 2003-03-20 | 2009-06-15 | Bayer Healthcare Llc | FVII eller FVIIa-Varianter |
| NZ573412A (en) * | 2003-06-19 | 2010-09-30 | Maxygen Holdings Ltd | Factor VII or VIIa Gla domain variants |
| ES2381110T3 (es) | 2003-09-09 | 2012-05-23 | Novo Nordisk Health Care Ag | Polipéptidos de factor VII de coagulación |
| EP1711513B1 (en) | 2003-12-01 | 2014-07-02 | Novo Nordisk Health Care AG | Nanofiltration of factor vii solutions to remove virus |
| RU2373953C2 (ru) | 2003-12-19 | 2009-11-27 | Ново Нордиск Хелс Кеа Аг | Стабилизированная композиция, содержащая полипептид фактора vii |
| EP2033662B1 (en) | 2004-01-21 | 2012-10-17 | Novo Nordisk Health Care AG | Transglutaminase mediated conjugation of peptides |
| ES2395544T3 (es) | 2004-12-23 | 2013-02-13 | Novo Nordisk Health Care Ag | Reducción del contenido de contaminantes proteínicos en composiciones que comprenden una proteína dependiente de la vitamina K de interés |
| US8206750B2 (en) | 2005-03-24 | 2012-06-26 | Cerenis Therapeutics Holding S.A. | Charged lipoprotein complexes and their uses |
| EP1893230A2 (en) * | 2005-04-26 | 2008-03-05 | Maxygen Holdings Ltd. | Use of modified factor vii for treating bleeding |
| EP1893632B1 (en) | 2005-06-17 | 2015-08-12 | Novo Nordisk Health Care AG | Selective reduction and derivatization of engineered factor vii proteins comprising at least one non-native cysteine |
| ES2397851T3 (es) | 2005-07-13 | 2013-03-11 | Novo Nordisk Health Care Ag | Células de inactivación proteínica de la célula huésped para la producción de proteínas terapéuticas |
| JP5894722B2 (ja) | 2005-09-01 | 2016-03-30 | ノボ ノルディスク ヘルス ケア アーゲー | 第ｖｉｉ因子ポリペプチドの疎水性相互作用クロマトグラフィ精製 |
| 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 |
| WO2008025856A2 (en) | 2006-09-01 | 2008-03-06 | Novo Nordisk Health Care Ag | Modified glycoproteins |
| WO2008078189A2 (en) * | 2006-12-20 | 2008-07-03 | Bayer Healthcare Llc | Factor vii and viia compositions |
| BRPI0810172A2 (pt) | 2007-04-13 | 2014-10-14 | Catalyst Biosciences Inc | Polipeptídeos de fator vii modificado e seus usos |
| US20080305157A1 (en) * | 2007-06-08 | 2008-12-11 | University Of Maryland Office Of Technology Commercialization | Encapsulation and separation of charged organic solutes inside catanionic vesicles |
| PL2235197T3 (pl) | 2007-12-27 | 2018-01-31 | Baxalta GmbH | Sposoby hodowli komórek |
| TWI465247B (zh) | 2008-04-11 | 2014-12-21 | Catalyst Biosciences Inc | 經修飾的因子ｖｉｉ多肽和其用途 |
| KR102170375B1 (ko) | 2009-06-09 | 2020-10-27 | 프로롱 파마슈티컬스, 엘엘씨 | 헤모글로빈 조성물 |
| WO2011074578A1 (ja) * | 2009-12-14 | 2011-06-23 | 国立大学法人北海道大学 | 脂質膜構造体に細胞透過能を付与および／または脂質膜構造体の細胞透過能を増強するペプチド、ならびにそれらペプチドと結合した脂質を構成脂質として含む、細胞透過能を有するまたは細胞透過能が増強された脂質膜構造体 |
| 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 |
| MX365612B (es) | 2012-07-25 | 2019-06-07 | Catalyst Biosciences Inc | Polipeptidos de factor x modificados y usos de los mismos. |
| US11491212B1 (en) | 2017-09-27 | 2022-11-08 | Catalyst Biosciences, Inc. | Subcutaneous administration of modified factor IX polypeptides and treatment of hemophilia B |
| WO2021030787A1 (en) | 2019-08-15 | 2021-02-18 | Catalyst Biosciences, Inc. | Modified factor vii polypeptides for subcutaneous administration and on-demand treatment |
| WO2021154414A2 (en) | 2020-01-29 | 2021-08-05 | Catalyst Biosciences, Inc. | Gene therapy for hemophilia b with a chimeric aav capsid vector encoding modified factor ix polypeptides |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI882746L (fi) * | 1987-06-12 | 1988-12-13 | Hoechst Japan | Hybridprotein c och foerfarande foer dess framstaellning. |
| JPH0246296A (ja) * | 1988-08-09 | 1990-02-15 | Hoechst Japan Ltd | 雑種プロテインｃ及びその製造方法 |
| 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 |
| US5504064A (en) * | 1991-04-10 | 1996-04-02 | Oklahoma Medical Research Foundation | Treatment of bleeding with modified tissue factor in combination with an activator of FVII |
-
1997
- 1997-10-23 US US08/955,636 patent/US6017882A/en not_active Expired - Lifetime
-
1998
- 1998-10-20 EP EP05026205.4A patent/EP1676919B1/en not_active Expired - Lifetime
- 1998-10-20 DK DK98967009T patent/DK1090128T3/da active
- 1998-10-20 BR BR9814611-4A patent/BR9814611A/pt active Search and Examination
- 1998-10-20 TW TW087117304A patent/TW587081B/zh active
- 1998-10-20 KR KR1020007004378A patent/KR20010031370A/ko not_active Ceased
- 1998-10-20 WO PCT/US1998/022152 patent/WO1999020767A1/en not_active Ceased
- 1998-10-20 AU AU27024/99A patent/AU749279C/en not_active Ceased
- 1998-10-20 EA EA200000449A patent/EA200000449A1/ru unknown
- 1998-10-20 NZ NZ504114A patent/NZ504114A/xx unknown
- 1998-10-20 DE DE69839313T patent/DE69839313T2/de not_active Expired - Lifetime
- 1998-10-20 CN CNB988125811A patent/CN1246462C/zh not_active Expired - Fee Related
- 1998-10-20 AP APAP/P/2000/001811A patent/AP2000001811A0/en unknown
- 1998-10-20 SG SG200203078A patent/SG105547A1/en unknown
- 1998-10-20 ID IDW20000983A patent/ID26330A/id unknown
- 1998-10-20 HU HU0102257A patent/HU225993B1/hu not_active IP Right Cessation
- 1998-10-20 IL IL13560398A patent/IL135603A0/xx unknown
- 1998-10-20 JP JP2000517087A patent/JP4276379B2/ja not_active Expired - Fee Related
- 1998-10-20 PT PT98967009T patent/PT1090128E/pt unknown
- 1998-10-20 ES ES98967009T patent/ES2303362T3/es not_active Expired - Lifetime
- 1998-10-20 ES ES05026205.4T patent/ES2496104T3/es not_active Expired - Lifetime
- 1998-10-20 HR HR20000234A patent/HRP20000234A2/hr not_active Application Discontinuation
- 1998-10-20 PL PL98340284A patent/PL194194B1/pl unknown
- 1998-10-20 TR TR2000/01105T patent/TR200001105T2/xx unknown
- 1998-10-20 CA CA002307175A patent/CA2307175C/en not_active Expired - Fee Related
- 1998-10-20 AT AT98967009T patent/ATE390486T1/de active
- 1998-10-20 EP EP98967009A patent/EP1090128B1/en not_active Expired - Lifetime
- 1998-10-21 ZA ZA989597A patent/ZA989597B/xx unknown
- 1998-10-22 MY MYPI98004808A patent/MY136336A/en unknown
- 1998-10-22 AR ARP980105278A patent/AR020048A1/es unknown
-
2000
- 2000-04-14 IS IS5449A patent/IS5449A/is unknown
- 2000-04-18 NO NO20002025A patent/NO20002025L/no not_active Application Discontinuation
-
2002
- 2002-03-20 AR ARP020101003A patent/AR035786A2/es active IP Right Grant
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100755967B1 (ko) * | 2003-10-23 | 2007-09-06 | 한국타이어 주식회사 | 타이어의 비드와 휠의 갭 측정장치 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR20010031370A (ko) | 변형된 비타민 ｋ-의존성 폴리펩티드 | |
| ES2327811T3 (es) | Polipeptidos de factor viia modificados. | |
| US9266931B2 (en) | Modified vitamin K-dependent polypeptides | |
| US8415457B2 (en) | Modified vitamin K-dependent polypeptides | |
| US9493757B2 (en) | Modified factor VII or factor VIIa polypeptides | |
| MXPA00003916A (en) | Modified vitamin k-dependent polypeptides |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20000422 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: 20031007 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: 20050825 Patent event code: PE09021S01D |
|
| E601 | Decision to refuse application | ||
| PE0601 | Decision on rejection of patent |
Patent event date: 20051031 Comment text: Decision to Refuse Application Patent event code: PE06012S01D Patent event date: 20050825 Comment text: Notification of reason for refusal Patent event code: PE06011S01I |