NO310778B1 - Fremgangsmåte for fremstilling av vevsplasminogen-aktivator med zymogeniske eller fibrinspesifikke egenskaper - Google Patents
Fremgangsmåte for fremstilling av vevsplasminogen-aktivator med zymogeniske eller fibrinspesifikke egenskaper Download PDFInfo
- Publication number
- NO310778B1 NO310778B1 NO19910811A NO910811A NO310778B1 NO 310778 B1 NO310778 B1 NO 310778B1 NO 19910811 A NO19910811 A NO 19910811A NO 910811 A NO910811 A NO 910811A NO 310778 B1 NO310778 B1 NO 310778B1
- Authority
- NO
- Norway
- Prior art keywords
- amino acid
- type
- variant
- wild
- host cell
- Prior art date
Links
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 title claims abstract description 503
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 title claims abstract description 502
- 229960000187 tissue plasminogen activator Drugs 0.000 title claims abstract description 501
- 102000009123 Fibrin Human genes 0.000 title claims abstract description 61
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 title claims abstract description 61
- 229950003499 fibrin Drugs 0.000 title claims abstract description 61
- 108010073385 Fibrin Proteins 0.000 title claims abstract description 60
- 238000000034 method Methods 0.000 title claims description 82
- 230000008569 process Effects 0.000 title claims description 6
- 230000003462 zymogenic effect Effects 0.000 title abstract description 23
- 238000002360 preparation method Methods 0.000 title description 9
- 150000001413 amino acids Chemical class 0.000 claims abstract description 94
- 108010049003 Fibrinogen Proteins 0.000 claims abstract description 25
- 102000008946 Fibrinogen Human genes 0.000 claims abstract description 24
- 108091005804 Peptidases Proteins 0.000 claims abstract description 24
- 239000004365 Protease Substances 0.000 claims abstract description 24
- 229940012952 fibrinogen Drugs 0.000 claims abstract description 24
- 108091028043 Nucleic acid sequence Proteins 0.000 claims abstract description 21
- 239000013604 expression vector Substances 0.000 claims abstract description 16
- 235000001014 amino acid Nutrition 0.000 claims description 107
- 210000004027 cell Anatomy 0.000 claims description 97
- 229940024606 amino acid Drugs 0.000 claims description 84
- 230000000694 effects Effects 0.000 claims description 65
- 108020004414 DNA Proteins 0.000 claims description 55
- 238000003556 assay Methods 0.000 claims description 46
- 239000013598 vector Substances 0.000 claims description 43
- 238000006467 substitution reaction Methods 0.000 claims description 37
- 108090000623 proteins and genes Proteins 0.000 claims description 36
- 102000035195 Peptidases Human genes 0.000 claims description 23
- 108010031891 KHRR 296-299 AAAA T103N Proteins 0.000 claims description 21
- 238000012217 deletion Methods 0.000 claims description 20
- 230000037430 deletion Effects 0.000 claims description 20
- 238000004519 manufacturing process Methods 0.000 claims description 19
- 235000004279 alanine Nutrition 0.000 claims description 16
- 229960003767 alanine Drugs 0.000 claims description 16
- 230000001419 dependent effect Effects 0.000 claims description 15
- 238000003780 insertion Methods 0.000 claims description 14
- 230000037431 insertion Effects 0.000 claims description 14
- 241000588724 Escherichia coli Species 0.000 claims description 13
- 238000004458 analytical method Methods 0.000 claims description 13
- 102000053602 DNA Human genes 0.000 claims description 11
- 239000003102 growth factor Substances 0.000 claims description 11
- 150000007523 nucleic acids Chemical class 0.000 claims description 11
- 239000004475 Arginine Substances 0.000 claims description 10
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 10
- 229960003121 arginine Drugs 0.000 claims description 10
- 235000009697 arginine Nutrition 0.000 claims description 10
- 230000035772 mutation Effects 0.000 claims description 10
- 102000039446 nucleic acids Human genes 0.000 claims description 10
- 108020004707 nucleic acids Proteins 0.000 claims description 10
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 9
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 9
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 9
- 108010001014 Plasminogen Activators Proteins 0.000 claims description 9
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 claims description 9
- 235000009582 asparagine Nutrition 0.000 claims description 9
- 229960001230 asparagine Drugs 0.000 claims description 9
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 9
- 235000008729 phenylalanine Nutrition 0.000 claims description 9
- 229960005190 phenylalanine Drugs 0.000 claims description 9
- COLNVLDHVKWLRT-QMMMGPOBSA-N phenylalanine group Chemical group N[C@@H](CC1=CC=CC=C1)C(=O)O COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 9
- 229940127126 plasminogen activator Drugs 0.000 claims description 9
- 235000002374 tyrosine Nutrition 0.000 claims description 9
- 229960004441 tyrosine Drugs 0.000 claims description 9
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 9
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 8
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 8
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 8
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims description 8
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 8
- 102000001938 Plasminogen Activators Human genes 0.000 claims description 8
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 8
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 8
- 235000004554 glutamine Nutrition 0.000 claims description 8
- 229960002743 glutamine Drugs 0.000 claims description 8
- 235000004400 serine Nutrition 0.000 claims description 8
- 229960001153 serine Drugs 0.000 claims description 8
- 101000801481 Homo sapiens Tissue-type plasminogen activator Proteins 0.000 claims description 7
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 7
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 7
- 239000004473 Threonine Substances 0.000 claims description 7
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 7
- 229960002885 histidine Drugs 0.000 claims description 7
- 235000014304 histidine Nutrition 0.000 claims description 7
- 102000047823 human PLAT Human genes 0.000 claims description 7
- 235000008521 threonine Nutrition 0.000 claims description 7
- 229960002898 threonine Drugs 0.000 claims description 7
- 239000004472 Lysine Substances 0.000 claims description 6
- 230000004071 biological effect Effects 0.000 claims description 6
- 230000002255 enzymatic effect Effects 0.000 claims description 6
- 235000018977 lysine Nutrition 0.000 claims description 6
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 5
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 5
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 5
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 5
- 229960003646 lysine Drugs 0.000 claims description 5
- 235000014393 valine Nutrition 0.000 claims description 5
- 229960004295 valine Drugs 0.000 claims description 5
- 239000004474 valine Substances 0.000 claims description 5
- 102220566256 Acid-sensing ion channel 3_Y67N_mutation Human genes 0.000 claims description 4
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 4
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 4
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 4
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 4
- 238000012258 culturing Methods 0.000 claims description 4
- 235000014705 isoleucine Nutrition 0.000 claims description 4
- 229960000310 isoleucine Drugs 0.000 claims description 4
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 4
- 235000005772 leucine Nutrition 0.000 claims description 4
- 229960003136 leucine Drugs 0.000 claims description 4
- 210000004962 mammalian cell Anatomy 0.000 claims description 4
- 230000001131 transforming effect Effects 0.000 claims description 4
- 238000005345 coagulation Methods 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 238000003259 recombinant expression Methods 0.000 claims description 3
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 claims description 2
- 210000003527 eukaryotic cell Anatomy 0.000 claims description 2
- 239000001878 Bakers yeast glycan Substances 0.000 claims 1
- 125000000837 carbohydrate group Chemical group 0.000 claims 1
- 230000007935 neutral effect Effects 0.000 claims 1
- 210000005253 yeast cell Anatomy 0.000 claims 1
- 102000010911 Enzyme Precursors Human genes 0.000 abstract description 26
- 108010062466 Enzyme Precursors Proteins 0.000 abstract description 26
- 230000015572 biosynthetic process Effects 0.000 abstract description 14
- 230000008021 deposition Effects 0.000 abstract description 5
- 230000004075 alteration Effects 0.000 abstract description 3
- 208000019553 vascular disease Diseases 0.000 abstract description 2
- 241000124008 Mammalia Species 0.000 abstract 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 abstract 1
- 239000000825 pharmaceutical preparation Substances 0.000 abstract 1
- 239000012634 fragment Substances 0.000 description 53
- 239000013612 plasmid Substances 0.000 description 43
- 102000013566 Plasminogen Human genes 0.000 description 29
- 239000000203 mixture Substances 0.000 description 28
- 108010051456 Plasminogen Proteins 0.000 description 27
- 230000007017 scission Effects 0.000 description 26
- 238000003776 cleavage reaction Methods 0.000 description 25
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 24
- 229940012957 plasmin Drugs 0.000 description 22
- 108010088842 Fibrinolysin Proteins 0.000 description 21
- 125000003275 alpha amino acid group Chemical group 0.000 description 20
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 18
- 108010022394 Threonine synthase Proteins 0.000 description 17
- 102000004419 dihydrofolate reductase Human genes 0.000 description 17
- 108090000790 Enzymes Proteins 0.000 description 16
- 102000004190 Enzymes Human genes 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- 229940088598 enzyme Drugs 0.000 description 16
- 235000018102 proteins Nutrition 0.000 description 16
- 102000004169 proteins and genes Human genes 0.000 description 16
- 230000027455 binding Effects 0.000 description 15
- 239000002299 complementary DNA Substances 0.000 description 15
- 239000000499 gel Substances 0.000 description 15
- 108091008146 restriction endonucleases Proteins 0.000 description 15
- 238000002835 absorbance Methods 0.000 description 14
- 230000004048 modification Effects 0.000 description 14
- 238000012986 modification Methods 0.000 description 14
- 239000000523 sample Substances 0.000 description 14
- 108091034117 Oligonucleotide Proteins 0.000 description 13
- 239000011780 sodium chloride Substances 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- 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 12
- 238000010276 construction Methods 0.000 description 12
- 229960000485 methotrexate Drugs 0.000 description 12
- 230000010076 replication Effects 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 239000002609 medium Substances 0.000 description 11
- 230000008488 polyadenylation Effects 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 108020005067 RNA Splice Sites Proteins 0.000 description 10
- 230000013595 glycosylation Effects 0.000 description 10
- 238000006206 glycosylation reaction Methods 0.000 description 10
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 10
- 229920000053 polysorbate 80 Polymers 0.000 description 10
- 238000002741 site-directed mutagenesis Methods 0.000 description 10
- 239000007983 Tris buffer Substances 0.000 description 9
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 9
- 239000003623 enhancer Substances 0.000 description 9
- 230000014509 gene expression Effects 0.000 description 9
- 238000011534 incubation Methods 0.000 description 9
- 239000002953 phosphate buffered saline Substances 0.000 description 9
- 239000000758 substrate Substances 0.000 description 9
- 238000001890 transfection Methods 0.000 description 9
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 9
- 229920002684 Sepharose Polymers 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 239000003550 marker Substances 0.000 description 8
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 7
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 7
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 7
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 7
- 229960000723 ampicillin Drugs 0.000 description 7
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 7
- 238000004113 cell culture Methods 0.000 description 7
- 230000008859 change Effects 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 229960005356 urokinase Drugs 0.000 description 7
- 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 6
- 102000004594 DNA Polymerase I Human genes 0.000 description 6
- 108010017826 DNA Polymerase I Proteins 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 230000009089 cytolysis Effects 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 230000009466 transformation Effects 0.000 description 6
- 241000701022 Cytomegalovirus Species 0.000 description 5
- 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 5
- 108010054218 Factor VIII Proteins 0.000 description 5
- 102000001690 Factor VIII Human genes 0.000 description 5
- 108010023197 Streptokinase Proteins 0.000 description 5
- 108090000190 Thrombin Proteins 0.000 description 5
- 238000012867 alanine scanning Methods 0.000 description 5
- 238000005119 centrifugation Methods 0.000 description 5
- 229960000301 factor viii Drugs 0.000 description 5
- 238000009396 hybridization Methods 0.000 description 5
- 244000005700 microbiome Species 0.000 description 5
- 238000002703 mutagenesis Methods 0.000 description 5
- 231100000350 mutagenesis Toxicity 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 235000012434 pretzels Nutrition 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 229960004072 thrombin Drugs 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 4
- 241000699802 Cricetulus griseus Species 0.000 description 4
- 102000012410 DNA Ligases Human genes 0.000 description 4
- 108010061982 DNA Ligases Proteins 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 241000276498 Pollachius virens Species 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
- 208000007536 Thrombosis Diseases 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 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 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 230000029087 digestion Effects 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 4
- 230000000813 microbial effect Effects 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 239000013600 plasmid vector Substances 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 230000003612 virological effect Effects 0.000 description 4
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 3
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 108091027305 Heteroduplex Proteins 0.000 description 3
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 3
- 108010067060 Immunoglobulin Variable Region 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
- 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 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- 108010022999 Serine Proteases Proteins 0.000 description 3
- 102000012479 Serine Proteases Human genes 0.000 description 3
- 108020004682 Single-Stranded DNA Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000007853 buffer solution Substances 0.000 description 3
- 239000006143 cell culture medium Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000012737 fresh medium Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 229920002401 polyacrylamide Polymers 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000012679 serum free medium Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 229960003766 thrombin (human) Drugs 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 230000005030 transcription termination Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- OSJPPGNTCRNQQC-UWTATZPHSA-N 3-phospho-D-glyceric acid Chemical compound OC(=O)[C@H](O)COP(O)(O)=O OSJPPGNTCRNQQC-UWTATZPHSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 238000001712 DNA sequencing Methods 0.000 description 2
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 2
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 2
- 206010051055 Deep vein thrombosis Diseases 0.000 description 2
- 241001646716 Escherichia coli K-12 Species 0.000 description 2
- 102000016359 Fibronectins Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- 102000005731 Glucose-6-phosphate isomerase Human genes 0.000 description 2
- 108010070600 Glucose-6-phosphate isomerase Proteins 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 2
- 108091006905 Human Serum Albumin Proteins 0.000 description 2
- 206010061216 Infarction Diseases 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 241001460678 Napo <wasp> Species 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 206010047249 Venous thrombosis Diseases 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 239000012223 aqueous fraction Substances 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 239000011324 bead Substances 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
- 210000004204 blood vessel Anatomy 0.000 description 2
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 229960003669 carbenicillin Drugs 0.000 description 2
- FPPNZSSZRUTDAP-UWFZAAFLSA-N carbenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(O)=O)C1=CC=CC=C1 FPPNZSSZRUTDAP-UWFZAAFLSA-N 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- RGWHQCVHVJXOKC-SHYZEUOFSA-J dCTP(4-) Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-J 0.000 description 2
- 239000005547 deoxyribonucleotide Substances 0.000 description 2
- 230000030609 dephosphorylation Effects 0.000 description 2
- 238000006209 dephosphorylation reaction Methods 0.000 description 2
- 239000010432 diamond Substances 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 2
- 229960005542 ethidium bromide Drugs 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- 229960002449 glycine Drugs 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 208000006454 hepatitis Diseases 0.000 description 2
- 231100000283 hepatitis Toxicity 0.000 description 2
- 125000000487 histidyl group Chemical class [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 2
- 229940106780 human fibrinogen Drugs 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 230000007574 infarction Effects 0.000 description 2
- -1 isocytochrome C Proteins 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 229940099990 ogen Drugs 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 150000004671 saturated fatty acids Chemical class 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 229960005202 streptokinase Drugs 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 230000010474 transient expression Effects 0.000 description 2
- 239000001226 triphosphate Substances 0.000 description 2
- 235000011178 triphosphate Nutrition 0.000 description 2
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- IJRKANNOPXMZSG-SSPAHAAFSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;(2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O.OC(=O)CC(O)(C(O)=O)CC(O)=O IJRKANNOPXMZSG-SSPAHAAFSA-N 0.000 description 1
- 102000013563 Acid Phosphatase Human genes 0.000 description 1
- 108010051457 Acid Phosphatase Proteins 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 101710187573 Alcohol dehydrogenase 2 Proteins 0.000 description 1
- 101710133776 Alcohol dehydrogenase class-3 Proteins 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 208000002109 Argyria Diseases 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 108010077805 Bacterial Proteins Proteins 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 108090000317 Chymotrypsin Proteins 0.000 description 1
- 101800004419 Cleaved form Proteins 0.000 description 1
- 101150074155 DHFR gene Proteins 0.000 description 1
- 230000008836 DNA modification Effects 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102000004533 Endonucleases Human genes 0.000 description 1
- 241000588921 Enterobacteriaceae Species 0.000 description 1
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 1
- 101100390711 Escherichia coli (strain K12) fhuA gene Proteins 0.000 description 1
- 241001522878 Escherichia coli B Species 0.000 description 1
- 241001302584 Escherichia coli str. K-12 substr. W3110 Species 0.000 description 1
- 241001524679 Escherichia virus M13 Species 0.000 description 1
- 108010058861 Fibrin Fibrinogen Degradation Products Proteins 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 1
- 102000030595 Glucokinase Human genes 0.000 description 1
- 108010021582 Glucokinase Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000005548 Hexokinase Human genes 0.000 description 1
- 108700040460 Hexokinases Proteins 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 241000701109 Human adenovirus 2 Species 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 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
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108020002230 Pancreatic Ribonuclease Proteins 0.000 description 1
- 102000005891 Pancreatic ribonuclease Human genes 0.000 description 1
- 108010087702 Penicillinase Proteins 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- 102000001105 Phosphofructokinases Human genes 0.000 description 1
- 108010069341 Phosphofructokinases Proteins 0.000 description 1
- 102000012288 Phosphopyruvate Hydratase Human genes 0.000 description 1
- 108010022181 Phosphopyruvate Hydratase Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 208000010378 Pulmonary Embolism Diseases 0.000 description 1
- 108010011939 Pyruvate Decarboxylase Proteins 0.000 description 1
- 102000013009 Pyruvate Kinase Human genes 0.000 description 1
- 108020005115 Pyruvate Kinase Proteins 0.000 description 1
- 108020005091 Replication Origin Proteins 0.000 description 1
- 241000235070 Saccharomyces Species 0.000 description 1
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
- 239000012506 Sephacryl® Substances 0.000 description 1
- 102000008847 Serpin Human genes 0.000 description 1
- 108050000761 Serpin Proteins 0.000 description 1
- 241000607720 Serratia Species 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 102000005924 Triose-Phosphate Isomerase Human genes 0.000 description 1
- 108700015934 Triose-phosphate isomerases Proteins 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 101710162629 Trypsin inhibitor Proteins 0.000 description 1
- 229940122618 Trypsin inhibitor Drugs 0.000 description 1
- 108091034131 VA RNA Proteins 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 229940045687 antimetabolites folic acid analogs Drugs 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 239000013011 aqueous formulation Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000010310 bacterial transformation Effects 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000010504 bond cleavage reaction Methods 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical group NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000015861 cell surface binding Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 229960002376 chymotrypsin Drugs 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000001143 conditioned effect Effects 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
- 239000012228 culture supernatant Substances 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- SUYVUBYJARFZHO-RRKCRQDMSA-N dATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-RRKCRQDMSA-N 0.000 description 1
- SUYVUBYJARFZHO-UHFFFAOYSA-N dATP Natural products C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-UHFFFAOYSA-N 0.000 description 1
- HAAZLUGHYHWQIW-KVQBGUIXSA-N dGTP Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 HAAZLUGHYHWQIW-KVQBGUIXSA-N 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 239000005549 deoxyribonucleoside Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000005546 dideoxynucleotide Substances 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000006334 disulfide bridging Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 108010052305 exodeoxyribonuclease III Proteins 0.000 description 1
- 239000000208 fibrin degradation product Substances 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 230000003480 fibrinolytic effect Effects 0.000 description 1
- 150000002224 folic acids Chemical class 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 230000002414 glycolytic effect Effects 0.000 description 1
- 239000011544 gradient gel Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 230000010005 growth-factor like effect Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000009629 microbiological culture Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 102000042567 non-coding RNA Human genes 0.000 description 1
- 229940124276 oligodeoxyribonucleotide Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229950009506 penicillinase Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 229960004838 phosphoric acid Drugs 0.000 description 1
- 238000013492 plasmid preparation Methods 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000000379 polymerizing effect Effects 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 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
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 101150108727 trpl gene Proteins 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 238000004879 turbidimetry Methods 0.000 description 1
- 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 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000002700 urine 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
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000012178 vegetable wax Substances 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
- 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
-
- 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)
- C12N9/6456—Plasminogen activators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Compounds Of Unknown Constitution (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US24085688A | 1988-09-02 | 1988-09-02 | |
| US07/384,608 US5108901A (en) | 1988-09-02 | 1989-07-24 | Tissue plasminogen activator having zymogenic or fibrin specific properties |
| PCT/US1989/003755 WO1990002798A1 (en) | 1988-09-02 | 1989-08-29 | Tissue plasminogen activator having zymogenic or fibrin specific properties |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO910811D0 NO910811D0 (no) | 1991-02-28 |
| NO910811L NO910811L (no) | 1991-02-28 |
| NO310778B1 true NO310778B1 (no) | 2001-08-27 |
Family
ID=26933781
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19910811A NO310778B1 (no) | 1988-09-02 | 1991-02-28 | Fremgangsmåte for fremstilling av vevsplasminogen-aktivator med zymogeniske eller fibrinspesifikke egenskaper |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US5108901A (da) |
| EP (1) | EP0457758B1 (da) |
| JP (1) | JP2794028B2 (da) |
| KR (1) | KR0148575B1 (da) |
| AT (1) | ATE124452T1 (da) |
| AU (1) | AU626323B2 (da) |
| CA (1) | CA1341484C (da) |
| DE (1) | DE68923298T2 (da) |
| DK (1) | DK175958B1 (da) |
| ES (1) | ES2018729A6 (da) |
| FI (1) | FI109359B (da) |
| HK (1) | HK1007334A1 (da) |
| HU (1) | HU213922B (da) |
| IE (1) | IE67508B1 (da) |
| IL (1) | IL91306A (da) |
| NO (1) | NO310778B1 (da) |
| NZ (1) | NZ230509A (da) |
| WO (1) | WO1990002798A1 (da) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5736134A (en) * | 1985-04-22 | 1998-04-07 | Genentech, In.C | Tissue plasminogen activator variants |
| US5756093A (en) * | 1985-04-22 | 1998-05-26 | Genentech, Inc. | Tissue plasminogen activator variants |
| GB8815135D0 (en) * | 1988-06-24 | 1988-08-03 | British Bio Technology | Proteins & nucleic acids |
| DK395288D0 (da) * | 1988-07-15 | 1988-07-15 | Novo Industri As | Proteiner |
| US5262170A (en) * | 1988-09-02 | 1993-11-16 | Genentech, Inc. | Tissue plasminogen activator having zymogenic or fibrin specific properties and substituted at amino acid positions 296-299, DNA molecules encoding them, vectors, and host cells |
| US5714145A (en) * | 1988-09-02 | 1998-02-03 | Genentech, Inc. | Tissue plasminogen activator having zymogenic or fibrin specific properties |
| US5156969A (en) * | 1988-09-02 | 1992-10-20 | Genentech Inc. | Tissue plasminogen activator variant with deletion of amino acids 466-470 having fibrin specific properties |
| ES2185529T3 (es) * | 1989-03-06 | 2003-05-01 | Univ Texas | T-pa resistente a la serpina; mutante; genes. |
| 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 |
| US5550042A (en) * | 1989-03-06 | 1996-08-27 | The Board Of Regents Of The University Of Texas System | Serine protease mutants of the chymotrypsin superfamily resistant to inhibition by their cognate inhibitors and genes encoding the same and serine protease inhibitor mutants and genes encoding the same |
| US5866413A (en) * | 1989-03-06 | 1999-02-02 | Board Of Regents Of The University Of Texas System | Pai-1 mutants |
| AU664469B2 (en) * | 1992-06-03 | 1995-11-16 | Genentech Inc. | Tissue plasminogen activator glycosylation variants with improved therapeutic properties |
| US5472692A (en) * | 1993-07-02 | 1995-12-05 | New England Deaconess Hospital Corporation | Pro-urokinase mutants |
| US5877016A (en) | 1994-03-18 | 1999-03-02 | Genentech, Inc. | Human trk receptors and neurotrophic factor inhibitors |
| US5656427A (en) * | 1994-08-29 | 1997-08-12 | Gen-Probe Incorporated | Nucleic acid hybridization assay probes, helper probes and amplification oligonucleotides targeted to Mycoplasma pneumoniae nucleic acid |
| US5759775A (en) * | 1994-10-27 | 1998-06-02 | Genetech, Inc. | Methods for detecting nucleic acids encoding AL--1 neurotrophic factor |
| ZA966663B (en) | 1995-08-17 | 1998-02-06 | Genentech Inc | Traf Inhibitors. |
| US6610296B2 (en) | 1995-10-26 | 2003-08-26 | Genentech, Inc. | Methods of enhancing cognitive function using an AL-1 neurotrophic factor immunoadhesin |
| US6706504B1 (en) | 1996-11-12 | 2004-03-16 | The Scripps Research Institute | Tissue type plasminogen activator (t-PA) variants: compositions and methods of use |
| WO1998021320A2 (en) * | 1996-11-12 | 1998-05-22 | The Scripps Research Institute | TISSUE TYPE PLASMINOGEN ACTIVATOR (t-PA) VARIANTS: COMPOSITIONS AND METHODS OF USE |
| US20030113271A1 (en) * | 1997-01-29 | 2003-06-19 | University Technology Corporation | Formulations for pulmonary delivery |
| EP0942992B1 (en) | 1997-01-31 | 2007-03-07 | Genentech, Inc. | O-fucosyltransferase |
| US20040241645A1 (en) * | 1997-01-31 | 2004-12-02 | Genentech, Inc. | O-fucosyltransferase |
| WO1999009184A1 (de) * | 1997-08-13 | 1999-02-25 | Roche Diagnostics Gmbh | Plasminogenaktivator mit verbesserter zymogenität und verminderter fibrinbindung |
| WO1999009185A1 (de) * | 1997-08-13 | 1999-02-25 | Roche Diagnostics Gmbh | Plasminogenaktivator mit verbesserter zymogenität |
| KR100408844B1 (ko) * | 2000-07-29 | 2003-12-06 | 한국산업기술평가원 | 동물세포 발현벡터 |
| WO2006023530A2 (en) * | 2004-08-16 | 2006-03-02 | Massachusetts Institute Of Technology | Compositions and methods for enhancing structural and functional nervous system reorganization and recovery |
| WO2007120847A2 (en) * | 2006-04-14 | 2007-10-25 | Massachusetts Institute Of Technology | Identifying and modulating molecular pathways that mediate nervous system plasticity |
| EP2056852A4 (en) * | 2006-07-27 | 2010-01-13 | Centocor Ortho Biotech Inc | BMP-7 VARIANTS COMPOSITIONS, METHODS AND USES |
| US10220008B2 (en) | 2013-08-14 | 2019-03-05 | Stc.Unm | Treatment and prevention of stroke and other neurological disorders |
| WO2016073514A2 (en) | 2014-11-03 | 2016-05-12 | Thrombolytic Science, Llc | Methods and compositions for safe and effective thrombolysis |
| WO2018232305A1 (en) | 2017-06-16 | 2018-12-20 | Thrombolytic Science, Llc | Methods and compositions for thrombolysis |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1984001960A1 (en) * | 1982-11-11 | 1984-05-24 | Beecham Group Plc | Pharmaceutically active compounds |
| EP0112122B1 (en) * | 1982-12-14 | 1991-08-28 | South African Inventions Development Corporation | Plasminogen activator |
| US4753879A (en) * | 1984-08-27 | 1988-06-28 | Biogen N.V. | Modified tissue plasminogen activators |
| EP0201153A3 (en) * | 1985-02-09 | 1987-10-07 | Beecham Group Plc | Modified enzyme and process for its preparation |
| IL78571A (en) * | 1985-04-22 | 1991-06-30 | Genentech Inc | Human tissue plasminogen activator mutants resistant to enzymatic cleavage resulting in two-chain form |
| GB8528321D0 (en) * | 1985-11-18 | 1985-12-24 | Ciba Geigy Ag | Modified fibrinolytic agents |
| AU605124B2 (en) * | 1985-12-23 | 1991-01-10 | Behringwerke Aktiengesellschaft | Novel peptide plasminogen activators |
| DK43387A (da) * | 1986-01-29 | 1987-07-30 | Beecham Group Plc | Fibrinolytisk enzym |
| WO1987004722A1 (en) * | 1986-01-31 | 1987-08-13 | Genetics Institute, Inc. | Novel thrombolytic proteins |
| IE81073B1 (en) * | 1986-03-18 | 2000-01-12 | Genentech Inc | Modified human tissue-type plasminogen activator and its preparation |
| PT84589B (en) * | 1986-04-02 | 1989-05-09 | Beecham Group Plc | Process for preparing a fibrinolytic enzyme |
| DK345087A (da) * | 1986-07-11 | 1988-01-12 | Novo Industri As | Modificeret vaevsplasminogenaktivator |
| WO1988005081A2 (en) * | 1986-12-30 | 1988-07-14 | Cetus Corporation | Novel plasminogen activator |
| GB8705377D0 (en) * | 1987-03-07 | 1987-04-08 | Beecham Group Plc | Compounds |
| DK275788A (da) * | 1987-05-22 | 1989-02-03 | Zymogenetics Inc | Fibrinolytiske proteiner |
| ES2058180T3 (es) * | 1987-06-04 | 1994-11-01 | Zymogenetics Inc | T-pa mutante con reemplazo de kringle. |
| DK302388A (da) * | 1987-06-04 | 1989-02-03 | Zymogenetics Inc | T-pa analoger med dodificeret vaekstfaktordomaene |
| SE8702562L (sv) * | 1987-06-18 | 1988-12-19 | Kabigen Ab | Nya fibrinolytiska enzymer |
| HUT51901A (en) * | 1987-06-22 | 1990-06-28 | Genetics Inst | Process for production of new trombolitic ensimes |
| JPH03500002A (ja) * | 1987-07-06 | 1991-01-10 | ジェネティックス・インスチチュート・インコーポレーテッド | 新規な血栓崩壊蛋白 |
| AU1893988A (en) * | 1987-07-13 | 1989-01-19 | Collaborative Research Inc. | Nonglycosylated plasminogen activator and method of preparation |
| DK395288D0 (da) * | 1988-07-15 | 1988-07-15 | Novo Industri As | Proteiner |
-
1989
- 1989-07-24 US US07/384,608 patent/US5108901A/en not_active Expired - Lifetime
- 1989-08-14 IL IL9130689A patent/IL91306A/xx active IP Right Grant
- 1989-08-17 IE IE265089A patent/IE67508B1/en not_active IP Right Cessation
- 1989-08-29 KR KR1019900700927A patent/KR0148575B1/ko not_active IP Right Cessation
- 1989-08-29 DE DE68923298T patent/DE68923298T2/de not_active Expired - Lifetime
- 1989-08-29 AU AU41946/89A patent/AU626323B2/en not_active Expired
- 1989-08-29 WO PCT/US1989/003755 patent/WO1990002798A1/en active IP Right Grant
- 1989-08-29 HU HU896005A patent/HU213922B/hu unknown
- 1989-08-29 AT AT89909997T patent/ATE124452T1/de not_active IP Right Cessation
- 1989-08-29 JP JP1509288A patent/JP2794028B2/ja not_active Expired - Lifetime
- 1989-08-29 EP EP89909997A patent/EP0457758B1/en not_active Expired - Lifetime
- 1989-08-31 NZ NZ230509A patent/NZ230509A/en unknown
- 1989-09-01 CA CA000610241A patent/CA1341484C/en not_active Expired - Lifetime
- 1989-09-01 ES ES8903004A patent/ES2018729A6/es not_active Expired - Fee Related
-
1991
- 1991-02-28 NO NO19910811A patent/NO310778B1/no not_active IP Right Cessation
- 1991-03-01 DK DK199100369A patent/DK175958B1/da not_active IP Right Cessation
- 1991-03-01 FI FI911049A patent/FI109359B/fi active
-
1998
- 1998-06-25 HK HK98106560A patent/HK1007334A1/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| NZ230509A (en) | 1991-06-25 |
| JP2794028B2 (ja) | 1998-09-03 |
| KR0148575B1 (ko) | 1998-10-15 |
| IE67508B1 (en) | 1996-04-03 |
| NO910811D0 (no) | 1991-02-28 |
| HU896005D0 (en) | 1991-07-29 |
| IL91306A0 (en) | 1990-03-19 |
| EP0457758A1 (en) | 1991-11-27 |
| DK36991D0 (da) | 1991-03-01 |
| DK36991A (da) | 1991-05-02 |
| ATE124452T1 (de) | 1995-07-15 |
| EP0457758B1 (en) | 1995-06-28 |
| JPH04500157A (ja) | 1992-01-16 |
| DE68923298T2 (de) | 1996-01-11 |
| CA1341484C (en) | 2005-05-24 |
| FI911049A0 (fi) | 1991-03-01 |
| IL91306A (en) | 1997-08-14 |
| ES2018729A6 (es) | 1991-05-01 |
| FI109359B (fi) | 2002-07-15 |
| DK175958B1 (da) | 2005-08-29 |
| AU626323B2 (en) | 1992-07-30 |
| DE68923298D1 (de) | 1995-08-03 |
| NO910811L (no) | 1991-02-28 |
| US5108901A (en) | 1992-04-28 |
| HK1007334A1 (en) | 1999-04-09 |
| HU213922B (en) | 1997-11-28 |
| WO1990002798A1 (en) | 1990-03-22 |
| KR900702019A (ko) | 1990-12-05 |
| HUT58812A (en) | 1992-03-30 |
| IE892650L (en) | 1990-03-02 |
| AU4194689A (en) | 1990-04-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO310778B1 (no) | Fremgangsmåte for fremstilling av vevsplasminogen-aktivator med zymogeniske eller fibrinspesifikke egenskaper | |
| US5770426A (en) | Tissue plasminogen activator having zymogenic or fibrin specific properties | |
| DK174236B1 (da) | Fremgangsmåde til fremstilling af et protein som har human vævsplasminogenaktivatorfunktion, fremgangsmåde til fremstilling af et farmaceutisk præparat indeholdende proteinet, DNA-isolat, som koder for proteinet, rekombinante klonings- og ...... | |
| IL89500A (en) | Human tissue plasminogen activator variants methods for their production and pharmaceutical compositions and preparations containing them | |
| US5246850A (en) | DNA molecules encoding human tissue plasminogen activator variants with decreased clearance, vectors, and host cells | |
| DK175938B1 (da) | Plasminogenaktivator-varianter, DNA-sekvenser, vektorer, celler og cellekulturer, der omfatter DNA-sekvenser, der koder for sådanne varianter, samt sammensætninger til behandling af karsygdom eller -tilstand, der omfatter en sådan variant | |
| US5258180A (en) | Tissue plasminogen activator having fibrin specific properties and deletion of amino acids 466-970, compositions and methods of treatment | |
| US5714145A (en) | Tissue plasminogen activator having zymogenic or fibrin specific properties | |
| EP0517756B1 (en) | Tissue plaminogen activator having fibrin specific properties | |
| EP0542869B1 (en) | Tissue plasminogen activator variants with decreased clearance | |
| JP3696617B2 (ja) | フィブリン特異性が改善されたｔ‐ＰＡ置換変異体 | |
| EP0563280B1 (en) | Tissue plasminogen activator substitution variant | |
| HU210541A9 (hu) | Zimogén- vagy fibrin-specifikus tulajdonságú, a 296-299 aminosav-tartományban helyettesített szöveti plazminogén aktivátor, ezt kódoló DNS-molekulák, vektorok és gazdasejtek | |
| HU210529A9 (hu) | Zimogén vagy fibrinspecifikus tulajdonságokkal rendelkező szöveti plazminogén aktivátor Az átmeneti oltalom az 1-7. igénypontra vonatkozik. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1K | Patent expired |