BRPI0819780B1 - Polinucleotídeo e método para produzir um ou mais polipeptídeos de plasmina recombinante - Google Patents
Polinucleotídeo e método para produzir um ou mais polipeptídeos de plasmina recombinante Download PDFInfo
- Publication number
- BRPI0819780B1 BRPI0819780B1 BRPI0819780-6A BRPI0819780A BRPI0819780B1 BR PI0819780 B1 BRPI0819780 B1 BR PI0819780B1 BR PI0819780 A BRPI0819780 A BR PI0819780A BR PI0819780 B1 BRPI0819780 B1 BR PI0819780B1
- Authority
- BR
- Brazil
- Prior art keywords
- polypeptide
- plasminogen
- tal6003
- amino acid
- plasmin
- Prior art date
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 132
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 124
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 124
- 229940012957 plasmin Drugs 0.000 title claims abstract description 86
- 108091033319 polynucleotide Proteins 0.000 title claims abstract description 43
- 102000040430 polynucleotide Human genes 0.000 title claims abstract description 43
- 239000002157 polynucleotide Substances 0.000 title claims abstract description 43
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 13
- 230000027455 binding Effects 0.000 claims abstract description 38
- 230000004913 activation Effects 0.000 claims abstract description 34
- 101000605403 Homo sapiens Plasminogen Proteins 0.000 claims abstract description 33
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims abstract description 25
- 239000004472 Lysine Substances 0.000 claims abstract description 24
- 108010088842 Fibrinolysin Proteins 0.000 claims description 80
- 238000000034 method Methods 0.000 claims description 51
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 40
- 239000002773 nucleotide Substances 0.000 claims description 29
- 125000003729 nucleotide group Chemical group 0.000 claims description 29
- 108010022999 Serine Proteases Proteins 0.000 claims description 27
- 102000012479 Serine Proteases Human genes 0.000 claims description 27
- 102000009123 Fibrin Human genes 0.000 claims description 24
- 108010073385 Fibrin Proteins 0.000 claims description 24
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 claims description 24
- 229950003499 fibrin Drugs 0.000 claims description 24
- 125000000539 amino acid group Chemical group 0.000 claims description 17
- 108010015052 miniplasmin Proteins 0.000 claims description 15
- 241000588724 Escherichia coli Species 0.000 claims description 13
- 210000004899 c-terminal region Anatomy 0.000 claims description 10
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 8
- 230000005847 immunogenicity Effects 0.000 claims description 8
- 108010049003 Fibrinogen Proteins 0.000 claims description 5
- 102000008946 Fibrinogen Human genes 0.000 claims description 5
- 229940012952 fibrinogen Drugs 0.000 claims description 5
- 239000004365 Protease Substances 0.000 claims description 4
- 108091005804 Peptidases Proteins 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 1
- 102000013566 Plasminogen Human genes 0.000 abstract description 103
- 108010051456 Plasminogen Proteins 0.000 abstract description 103
- 239000013598 vector Substances 0.000 abstract description 41
- 108090000790 Enzymes Proteins 0.000 abstract description 3
- 102000004190 Enzymes Human genes 0.000 abstract description 3
- 230000002255 enzymatic effect Effects 0.000 abstract description 3
- 229940088598 enzyme Drugs 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 61
- 108090000623 proteins and genes Proteins 0.000 description 44
- 235000018102 proteins Nutrition 0.000 description 37
- 102000004169 proteins and genes Human genes 0.000 description 37
- 235000001014 amino acid Nutrition 0.000 description 23
- 150000007523 nucleic acids Chemical class 0.000 description 22
- 238000006467 substitution reaction Methods 0.000 description 22
- 230000014509 gene expression Effects 0.000 description 20
- 102000039446 nucleic acids Human genes 0.000 description 19
- 108020004707 nucleic acids Proteins 0.000 description 19
- 239000000243 solution Substances 0.000 description 15
- 229940024606 amino acid Drugs 0.000 description 14
- 230000005764 inhibitory process Effects 0.000 description 13
- 229920002684 Sepharose Polymers 0.000 description 11
- 150000001413 amino acids Chemical group 0.000 description 11
- 238000012217 deletion Methods 0.000 description 11
- 230000037430 deletion Effects 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 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 10
- 230000000694 effects Effects 0.000 description 10
- 108020004414 DNA Proteins 0.000 description 9
- 108010023197 Streptokinase Proteins 0.000 description 9
- 102000003801 alpha-2-Antiplasmin Human genes 0.000 description 9
- 108090000183 alpha-2-Antiplasmin Proteins 0.000 description 9
- 230000001580 bacterial effect Effects 0.000 description 9
- 229960005202 streptokinase Drugs 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 238000007792 addition Methods 0.000 description 8
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 8
- 239000013604 expression vector Substances 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 229940099990 ogen Drugs 0.000 description 7
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 6
- 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
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 6
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 6
- -1 aliphatic amino acid Chemical class 0.000 description 6
- 229960002684 aminocaproic acid Drugs 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 239000003623 enhancer Substances 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 102000037865 fusion proteins Human genes 0.000 description 6
- 108020001507 fusion proteins Proteins 0.000 description 6
- 108010068982 microplasmin Proteins 0.000 description 6
- 230000003472 neutralizing effect Effects 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 5
- 238000002835 absorbance Methods 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 230000009089 cytolysis Effects 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 230000013595 glycosylation Effects 0.000 description 5
- 238000006206 glycosylation reaction Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 230000002537 thrombolytic effect Effects 0.000 description 5
- JJMDCOVWQOJGCB-UHFFFAOYSA-N 5-aminopentanoic acid Chemical compound [NH3+]CCCCC([O-])=O JJMDCOVWQOJGCB-UHFFFAOYSA-N 0.000 description 4
- 239000004475 Arginine Substances 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 238000012258 culturing Methods 0.000 description 4
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000003480 fibrinolytic effect Effects 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 108010049112 miniplasminogen Proteins 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- 230000001177 retroviral effect Effects 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 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 3
- 229920000936 Agarose Polymers 0.000 description 3
- 102000010911 Enzyme Precursors Human genes 0.000 description 3
- 108010062466 Enzyme Precursors Proteins 0.000 description 3
- 241000238631 Hexapoda Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 208000007536 Thrombosis Diseases 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000003146 anticoagulant agent Substances 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 239000001506 calcium phosphate Substances 0.000 description 3
- 229910000389 calcium phosphate Inorganic materials 0.000 description 3
- 235000011010 calcium phosphates Nutrition 0.000 description 3
- 238000004520 electroporation Methods 0.000 description 3
- 230000020764 fibrinolysis Effects 0.000 description 3
- 210000003000 inclusion body Anatomy 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000006337 proteolytic cleavage Effects 0.000 description 3
- 238000010188 recombinant method Methods 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 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 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- CAJXYXPLLJDEOB-SLFFLAALSA-N (2s)-6-amino-2-[[(2s)-2-[[(2r)-2-amino-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-n-(4-nitrophenyl)hexanamide Chemical compound CC(C)[C@@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)NC1=CC=C([N+]([O-])=O)C=C1 CAJXYXPLLJDEOB-SLFFLAALSA-N 0.000 description 2
- XDOLZJYETYVRKV-UHFFFAOYSA-N 7-Aminoheptanoic acid Chemical compound NCCCCCCC(O)=O XDOLZJYETYVRKV-UHFFFAOYSA-N 0.000 description 2
- 244000105975 Antidesma platyphyllum Species 0.000 description 2
- 102100040214 Apolipoprotein(a) Human genes 0.000 description 2
- 108010012927 Apoprotein(a) Proteins 0.000 description 2
- DAQIJMOLTMGJLO-YUMQZZPRSA-N Arg-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H](N)CCCNC(N)=N DAQIJMOLTMGJLO-YUMQZZPRSA-N 0.000 description 2
- 101100230428 Caenorhabditis elegans hil-5 gene Proteins 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 241000701959 Escherichia virus Lambda Species 0.000 description 2
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 102000003839 Human Proteins Human genes 0.000 description 2
- 108090000144 Human Proteins Proteins 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 229940122791 Plasmin inhibitor Drugs 0.000 description 2
- 108010001014 Plasminogen Activators Proteins 0.000 description 2
- 102000001938 Plasminogen Activators Human genes 0.000 description 2
- 108020005091 Replication Origin Proteins 0.000 description 2
- 241000714474 Rous sarcoma virus Species 0.000 description 2
- GYDJEQRTZSCIOI-UHFFFAOYSA-N Tranexamic acid Chemical compound NCC1CCC(C(O)=O)CC1 GYDJEQRTZSCIOI-UHFFFAOYSA-N 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 239000013504 Triton X-100 Substances 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 230000021736 acetylation Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 2
- 108010036533 arginylvaline Proteins 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 2
- 208000034158 bleeding Diseases 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 230000003139 buffering effect Effects 0.000 description 2
- 125000000837 carbohydrate group Chemical group 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000012501 chromatography medium Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 239000003527 fibrinolytic agent Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 2
- 235000009424 haa Nutrition 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 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 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000002806 plasmin inhibitor Substances 0.000 description 2
- 230000033885 plasminogen activation Effects 0.000 description 2
- 229940127126 plasminogen activator Drugs 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 235000019419 proteases Nutrition 0.000 description 2
- 101150079601 recA gene Proteins 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 239000003656 tris buffered saline Substances 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 241001515965 unidentified phage Species 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 210000005253 yeast cell Anatomy 0.000 description 2
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 1
- PKSBDZOBYIKNGY-UHFFFAOYSA-N (4-nitrophenyl) 4-(diaminomethylideneamino)benzoate;hydrochloride Chemical compound Cl.C1=CC(N=C(N)N)=CC=C1C(=O)OC1=CC=C([N+]([O-])=O)C=C1 PKSBDZOBYIKNGY-UHFFFAOYSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 108090000317 Chymotrypsin Proteins 0.000 description 1
- 108091062157 Cis-regulatory element Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 238000012270 DNA recombination Methods 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 108010051815 Glutamyl endopeptidase Proteins 0.000 description 1
- 108010053070 Glutathione Disulfide Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 108090000157 Metallothionein Proteins 0.000 description 1
- 102000003792 Metallothionein Human genes 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 101000969137 Mus musculus Metallothionein-1 Proteins 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 241000256248 Spodoptera Species 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 241000701093 Suid alphaherpesvirus 1 Species 0.000 description 1
- 108020005038 Terminator Codon Proteins 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 108020004566 Transfer RNA Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- YJQCOFNZVFGCAF-UHFFFAOYSA-N Tunicamycin II Natural products O1C(CC(O)C2C(C(O)C(O2)N2C(NC(=O)C=C2)=O)O)C(O)C(O)C(NC(=O)C=CCCCCCCCCC(C)C)C1OC1OC(CO)C(O)C(O)C1NC(C)=O YJQCOFNZVFGCAF-UHFFFAOYSA-N 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 239000007801 affinity label Substances 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 238000012867 alanine scanning Methods 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 230000003024 amidolytic effect Effects 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 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 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 210000004900 c-terminal fragment Anatomy 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 230000002759 chromosomal effect Effects 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
- 238000012411 cloning technique Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 208000010932 epithelial neoplasm Diseases 0.000 description 1
- 239000006167 equilibration buffer Substances 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000011536 extraction buffer Substances 0.000 description 1
- 239000013020 final formulation Substances 0.000 description 1
- 230000022244 formylation Effects 0.000 description 1
- 238000006170 formylation reaction Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- YPZRWBKMTBYPTK-BJDJZHNGSA-N glutathione disulfide Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@H](C(=O)NCC(O)=O)CSSC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O YPZRWBKMTBYPTK-BJDJZHNGSA-N 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229960004198 guanidine Drugs 0.000 description 1
- 238000012188 high-throughput screening assay Methods 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 210000001822 immobilized cell Anatomy 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 101150066555 lacZ gene Proteins 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 125000001909 leucine group Chemical class [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 230000006911 nucleation Effects 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 101150093139 ompT gene Proteins 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 210000001322 periplasm Anatomy 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 238000005222 photoaffinity labeling Methods 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 108010016700 plasminogen kringle 5 Proteins 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 210000004896 polypeptide structure Anatomy 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000007281 self degradation Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 229960001322 trypsin Drugs 0.000 description 1
- 230000001810 trypsinlike Effects 0.000 description 1
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- ZHSGGJXRNHWHRS-VIDYELAYSA-N tunicamycin Chemical compound O([C@H]1[C@@H]([C@H]([C@@H](O)[C@@H](CC(O)[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C(NC(=O)C=C2)=O)O)O1)O)NC(=O)/C=C/CC(C)C)[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1NC(C)=O ZHSGGJXRNHWHRS-VIDYELAYSA-N 0.000 description 1
- MEYZYGMYMLNUHJ-UHFFFAOYSA-N tunicamycin Natural products CC(C)CCCCCCCCCC=CC(=O)NC1C(O)C(O)C(CC(O)C2OC(C(O)C2O)N3C=CC(=O)NC3=O)OC1OC4OC(CO)C(O)C(O)C4NC(=O)C MEYZYGMYMLNUHJ-UHFFFAOYSA-N 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000001018 virulence Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6435—Plasmin (3.4.21.7), i.e. fibrinolysin
-
- 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
-
- 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
- C12N11/00—Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
- C12N11/02—Enzymes or microbial cells immobilised on or in an organic carrier
- C12N11/04—Enzymes or microbial cells immobilised on or in an organic carrier entrapped within the carrier, e.g. gel or hollow fibres
-
- 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)
- C12Y304/21007—Plasmin (3.4.21.7), i.e. fibrinolysin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Dispersion Chemistry (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Enzymes And Modification Thereof (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US99114807P | 2007-11-29 | 2007-11-29 | |
| US60/991,148 | 2007-11-29 | ||
| PCT/US2008/084645 WO2009073471A1 (en) | 2007-11-29 | 2008-11-25 | Recombinantly modified plasmin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| BRPI0819780A2 BRPI0819780A2 (pt) | 2015-08-11 |
| BRPI0819780B1 true BRPI0819780B1 (pt) | 2023-01-24 |
Family
ID=40379999
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0819780-6A BRPI0819780B1 (pt) | 2007-11-29 | 2008-11-25 | Polinucleotídeo e método para produzir um ou mais polipeptídeos de plasmina recombinante |
Country Status (17)
| Country | Link |
|---|---|
| US (3) | US8101394B2 (https=) |
| EP (1) | EP2220221B1 (https=) |
| JP (1) | JP5539896B2 (https=) |
| KR (1) | KR101529743B1 (https=) |
| CN (1) | CN101918548B (https=) |
| AU (1) | AU2008331545B2 (https=) |
| BR (1) | BRPI0819780B1 (https=) |
| CA (1) | CA2707266C (https=) |
| ES (1) | ES2534040T3 (https=) |
| HU (1) | HUE024916T2 (https=) |
| IL (1) | IL205936A (https=) |
| MX (1) | MX2010005947A (https=) |
| NZ (2) | NZ593837A (https=) |
| PL (1) | PL2220221T3 (https=) |
| PT (1) | PT2220221E (https=) |
| WO (1) | WO2009073471A1 (https=) |
| ZA (1) | ZA201003730B (https=) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102660564B (zh) | 2004-04-22 | 2013-05-08 | 泰勒克里斯生物治疗学公司 | 重组修饰的纤溶酶 |
| PL2220221T3 (pl) | 2007-11-29 | 2015-07-31 | Grifols Therapeutics Inc | Rekombinacyjnie zmodyfikowana plazmina |
| MX2010013282A (es) | 2008-06-04 | 2010-12-21 | Talecris Biotherapeutics Inc | Composicion, metodo y kit para la preparacion de plasmina. |
| HUE025670T2 (en) * | 2009-03-03 | 2016-04-28 | Grifols Therapeutics Inc | A method for producing plasminogen |
| WO2011004011A1 (en) | 2009-07-10 | 2011-01-13 | Thrombogenics Nv | Variants of plasminogen and plasmin |
| ES2534911T3 (es) | 2009-08-28 | 2015-04-30 | Thrombogenics N.V. | Uso de plasmina para el tratamiento de fallo de filtración después de trabeculectomía |
| CN102121023B (zh) * | 2010-12-22 | 2012-07-04 | 中山大学 | 突变型人纤溶酶原kringle5及其制备方法及应用 |
| JP6085568B2 (ja) | 2011-01-05 | 2017-02-22 | スロンボジェニックス・ナムローゼ・フェンノートシャップＴｈｒｏｍｂｏＧｅｎｉｃｓ ＮＶ | プラスミノーゲンおよびプラスミンの変異体 |
| US9644196B2 (en) | 2011-08-12 | 2017-05-09 | Thrombogenics Nv | Plasminogen and plasmin variants |
| CN103205410B (zh) * | 2012-01-13 | 2018-03-06 | 蔺莹莹 | 重组微纤维蛋白溶酶及其制备方法和应用 |
| SG11201506886TA (en) | 2013-03-14 | 2015-09-29 | Bayer Healthcare Llc | Monoclonal antibodies against antithrombin beta complexed with heparin |
| DE102014112212A1 (de) * | 2014-08-26 | 2016-03-03 | Akesion Gmbh | Rekombinante Fusionsproteine zur Vorbeugung oder Behandlung von Adhäsionen bei Geweben oder Organen |
| FR3035120B1 (fr) * | 2015-04-15 | 2020-02-07 | Arcadophta | Composition de plasminogenase immobilisee, procede de preparation, utilisation et dispositif comprenant une telle composition |
| WO2017101870A1 (zh) | 2015-12-18 | 2017-06-22 | 深圳瑞健生命科学研究院有限公司 | 一种预防或治疗糖尿病性视网膜病变的方法 |
| TWI725092B (zh) | 2015-12-18 | 2021-04-21 | 大陸商深圳瑞健生命科學硏究院有限公司 | 纖溶酶原在製備預防或治療糖尿病腎病或其相關病症之藥劑上的用途 |
| TWI624268B (zh) | 2015-12-18 | 2018-05-21 | Talengen Institute Of Life Sciences Co Ltd | 纖溶酶原在製備藥劑上的用途及包括纖溶酶原之藥劑 |
| WO2017101867A1 (zh) | 2015-12-18 | 2017-06-22 | 深圳瑞健生命科学研究院有限公司 | 一种预防或治疗糖尿病性神经损伤及其相关病症的方法 |
| CN108210897A (zh) * | 2016-12-15 | 2018-06-29 | 深圳瑞健生命科学研究院有限公司 | 预防和治疗肺纤维化的药物及其用途 |
| WO2018107707A1 (zh) | 2016-12-15 | 2018-06-21 | 深圳瑞健生命科学研究院有限公司 | 一种改善心脏病变的方法 |
| JP7175270B2 (ja) * | 2016-12-15 | 2022-11-18 | タレンゲン インターナショナル リミテッド | グルカゴン、インスリンを正常なバランスに戻らせる方法 |
| US11207387B2 (en) | 2016-12-15 | 2021-12-28 | Talengen International Limited | Method and drug for preventing and treating obesity |
| WO2018107688A1 (zh) * | 2016-12-15 | 2018-06-21 | 深圳瑞健生命科学研究院有限公司 | 一种预防和治疗脂肪肝的方法 |
| US11154595B2 (en) | 2016-12-15 | 2021-10-26 | Talengen International Limited | Method for preventing and treating pulmonary fibrosis |
| CA3067890A1 (en) | 2017-06-19 | 2018-12-27 | Talengen International Limited | Method for regulating and controling glp-1/glp-1r and drug |
| US11140020B1 (en) | 2018-03-01 | 2021-10-05 | Amazon Technologies, Inc. | Availability-enhancing gateways for network traffic in virtualized computing environments |
| WO2020152713A1 (en) * | 2019-01-25 | 2020-07-30 | Council Of Scientific & Industrial Research | Fibrinolytic composition and method of its preparation |
| CN115697385A (zh) * | 2020-05-11 | 2023-02-03 | 泰伦基国际有限公司 | 一种治疗脊髓性肌萎缩症的方法和药物 |
| CN118308334B (zh) * | 2024-06-06 | 2024-10-08 | 深圳市卫光生物制品股份有限公司 | 一种重组人纤溶酶原及其制备方法和应用 |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4652639A (en) | 1982-05-06 | 1987-03-24 | Amgen | Manufacture and expression of structural genes |
| US4631211A (en) | 1985-03-25 | 1986-12-23 | Scripps Clinic & Research Foundation | Means for sequential solid phase organic synthesis and methods using the same |
| US4774087A (en) | 1987-08-14 | 1988-09-27 | Northwestern University | Micro-size fibrinolytic plasmin |
| US7253264B1 (en) | 1990-06-28 | 2007-08-07 | Sanofi-Arentideutschland GmbH | Immunoglobulin fusion proteins, their production and use |
| US6312893B1 (en) | 1996-01-23 | 2001-11-06 | Qiagen Genomics, Inc. | Methods and compositions for determining the sequence of nucleic acid molecules |
| DE69739304D1 (de) | 1996-01-23 | 2009-04-23 | Operon Biotechnologies Inc | Verfahren und Zusammensetzungen zur Bestimmung von Sequenzen von Nukleinsäure-Molekülen |
| US6613508B1 (en) | 1996-01-23 | 2003-09-02 | Qiagen Genomics, Inc. | Methods and compositions for analyzing nucleic acid molecules utilizing sizing techniques |
| JPH10158300A (ja) | 1996-11-28 | 1998-06-16 | Suzuki Motor Corp | 血管新生抑制効果を有するタンパク質とその製造方法及びアンギオスタチンの製造方法 |
| JP2001511362A (ja) | 1997-07-22 | 2001-08-14 | ラピジーン，インコーポレイテッド | Ｍｓにより配列決定データを相関させるコンピュータ方法およびシステム |
| AU751283B2 (en) | 1998-07-14 | 2002-08-08 | Bristol-Myers Squibb Company | Lysine binding fragments of angiostatin |
| ATE349226T1 (de) | 1998-09-29 | 2007-01-15 | Leuven Res & Dev Vzw | Verwendung von verbindungen die alpha2- antiplasmin in vivo reduzieren zur herstellung einer zusammensetzung zur behandlung ischämischer schlaganfälle |
| US6355243B1 (en) | 1999-11-13 | 2002-03-12 | Bayer Corporation | Method of thrombolysis by local delivery of active plasmin |
| US6969515B2 (en) | 1999-11-13 | 2005-11-29 | Talecris Biotherapeutics, Inc. | Method of thrombolysis by local delivery of reversibly inactivated acidified plasmin |
| US6964764B2 (en) | 1999-11-13 | 2005-11-15 | Talecris Biotherapeutics, Inc. | Method of thrombolysis by local delivery of reversibly inactivated acidified plasmin |
| AU2001275091A1 (en) | 2000-06-02 | 2001-12-17 | Blue Heron Biotechnology, Inc. | Methods for improving the sequence fidelity of synthetic double-stranded oligonucleotides |
| JP4047170B2 (ja) | 2000-12-21 | 2008-02-13 | トロム−イクス・ナムローゼ・フエンノートシャップ | 酵母発現ベクターおよび酵母細胞における発現による組換えタンパク質の製造方法 |
| WO2003054232A2 (en) | 2001-12-13 | 2003-07-03 | Blue Heron Biotechnology, Inc. | Methods for removal of double-stranded oligonucleotides containing sequence errors using mismatch recognition proteins |
| US7776026B2 (en) | 2002-02-06 | 2010-08-17 | Nuvue Technologies, Inc. | Method for vitreous liquefaction |
| DE10390418D2 (de) | 2002-02-06 | 2005-01-13 | N Zyme Biotec Gmbh | Verfahren zur Herstellung von rekombinanten Proteinen in Mikroorganismen |
| GB0228409D0 (en) * | 2002-12-06 | 2003-01-08 | Thromb X Nv | Pharmacological vitreolysis |
| CN102660564B (zh) * | 2004-04-22 | 2013-05-08 | 泰勒克里斯生物治疗学公司 | 重组修饰的纤溶酶 |
| WO2007047874A2 (en) * | 2005-10-20 | 2007-04-26 | Talecris Biotherapeutics, Inc. | Recombinantly modified plasmin |
| PL2220221T3 (pl) | 2007-11-29 | 2015-07-31 | Grifols Therapeutics Inc | Rekombinacyjnie zmodyfikowana plazmina |
-
2008
- 2008-11-25 PL PL08857923T patent/PL2220221T3/pl unknown
- 2008-11-25 WO PCT/US2008/084645 patent/WO2009073471A1/en not_active Ceased
- 2008-11-25 PT PT88579230T patent/PT2220221E/pt unknown
- 2008-11-25 JP JP2010536117A patent/JP5539896B2/ja active Active
- 2008-11-25 CN CN2008801232704A patent/CN101918548B/zh active Active
- 2008-11-25 US US12/744,376 patent/US8101394B2/en active Active
- 2008-11-25 KR KR1020107014243A patent/KR101529743B1/ko not_active Expired - Fee Related
- 2008-11-25 EP EP08857923.0A patent/EP2220221B1/en active Active
- 2008-11-25 AU AU2008331545A patent/AU2008331545B2/en active Active
- 2008-11-25 NZ NZ593837A patent/NZ593837A/xx not_active IP Right Cessation
- 2008-11-25 MX MX2010005947A patent/MX2010005947A/es active IP Right Grant
- 2008-11-25 CA CA2707266A patent/CA2707266C/en active Active
- 2008-11-25 HU HUE08857923A patent/HUE024916T2/en unknown
- 2008-11-25 BR BRPI0819780-6A patent/BRPI0819780B1/pt not_active IP Right Cessation
- 2008-11-25 NZ NZ585715A patent/NZ585715A/en not_active IP Right Cessation
- 2008-11-25 ES ES08857923.0T patent/ES2534040T3/es active Active
-
2010
- 2010-05-24 IL IL205936A patent/IL205936A/en active IP Right Grant
- 2010-05-25 ZA ZA2010/03730A patent/ZA201003730B/en unknown
-
2011
- 2011-11-22 US US13/302,322 patent/US8182808B2/en active Active
-
2012
- 2012-05-03 US US13/463,437 patent/US8512980B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| KR20100102135A (ko) | 2010-09-20 |
| HK1146089A1 (en) | 2011-05-13 |
| IL205936A0 (en) | 2010-11-30 |
| US8512980B2 (en) | 2013-08-20 |
| ES2534040T3 (es) | 2015-04-16 |
| MX2010005947A (es) | 2010-09-10 |
| CN101918548A (zh) | 2010-12-15 |
| NZ585715A (en) | 2011-11-25 |
| IL205936A (en) | 2015-04-30 |
| CN101918548B (zh) | 2013-10-16 |
| EP2220221A1 (en) | 2010-08-25 |
| US20120276611A1 (en) | 2012-11-01 |
| CA2707266C (en) | 2013-12-31 |
| US8182808B2 (en) | 2012-05-22 |
| BRPI0819780A2 (pt) | 2015-08-11 |
| JP2011505140A (ja) | 2011-02-24 |
| EP2220221B1 (en) | 2014-12-31 |
| AU2008331545B2 (en) | 2014-01-16 |
| HUE024916T2 (en) | 2016-02-29 |
| WO2009073471A1 (en) | 2009-06-11 |
| AU2008331545A1 (en) | 2009-06-11 |
| KR101529743B1 (ko) | 2015-06-17 |
| US8101394B2 (en) | 2012-01-24 |
| US20120093799A1 (en) | 2012-04-19 |
| CA2707266A1 (en) | 2009-06-11 |
| US20110003332A1 (en) | 2011-01-06 |
| PT2220221E (pt) | 2015-04-16 |
| ZA201003730B (en) | 2012-11-28 |
| JP5539896B2 (ja) | 2014-07-02 |
| PL2220221T3 (pl) | 2015-07-31 |
| NZ593837A (en) | 2013-01-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| BRPI0819780B1 (pt) | Polinucleotídeo e método para produzir um ou mais polipeptídeos de plasmina recombinante | |
| US8420079B2 (en) | Recombinantly modified plasmin | |
| HK1146089B (en) | Recombinantly modified plasmin | |
| HK1099341B (en) | Recombinantly modified plasmin | |
| HK1150242B (en) | Recombinantly modified plasmin | |
| HK1175812B (en) | Recombinantly modified plasmin |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B25D | Requested change of name of applicant approved |
Owner name: GRIFOLS THERAPEUTICS INC. (US) |
|
| B06F | Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette] | ||
| B07D | Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette] | ||
| B07E | Notification of approval relating to section 229 industrial property law [chapter 7.5 patent gazette] | ||
| B07A | Application suspended after technical examination (opinion) [chapter 7.1 patent gazette] | ||
| B09B | Patent application refused [chapter 9.2 patent gazette] | ||
| B12B | Appeal against refusal [chapter 12.2 patent gazette] | ||
| B16A | Patent or certificate of addition of invention granted [chapter 16.1 patent gazette] |
Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 25/11/2008, OBSERVADAS AS CONDICOES LEGAIS. PATENTE CONCEDIDA CONFORME ADI 5.529/DF, QUE DETERMINA A ALTERACAO DO PRAZO DE CONCESSAO. |
|
| B21F | Lapse acc. art. 78, item iv - on non-payment of the annual fees in time |
Free format text: REFERENTE A 16A ANUIDADE. |
|
| B24J | Lapse because of non-payment of annual fees (definitively: art 78 iv lpi, resolution 113/2013 art. 12) |
Free format text: EM VIRTUDE DA EXTINCAO PUBLICADA NA RPI 2802 DE 17-09-2024 E CONSIDERANDO AUSENCIA DE MANIFESTACAO DENTRO DOS PRAZOS LEGAIS, INFORMO QUE CABE SER MANTIDA A EXTINCAO DA PATENTE E SEUS CERTIFICADOS, CONFORME O DISPOSTO NO ARTIGO 12, DA RESOLUCAO 113/2013. |