HUE024916T2 - Recombinantly modified plasmin - Google Patents

Info

Publication number

HUE024916T2

HUE024916T2 HUE08857923A HUE08857923A HUE024916T2 HU E024916 T2 HUE024916 T2 HU E024916T2 HU E08857923 A HUE08857923 A HU E08857923A HU E08857923 A HUE08857923 A HU E08857923A HU E024916 T2 HUE024916 T2 HU E024916T2

Authority

HU

Hungary

Prior art keywords

pro

gly

thr

ser

polypeptide

Prior art date

2007-11-29

Links

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• 229940012957 plasmin Drugs 0.000 title claims description 75
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 125
• 229920001184 polypeptide Polymers 0.000 claims description 120
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 120
• 108010088842 Fibrinolysin Proteins 0.000 claims description 43
• 230000027455 binding Effects 0.000 claims description 34
• 238000009739 binding Methods 0.000 claims description 34
• 230000004913 activation Effects 0.000 claims description 33
• 108091033319 polynucleotide Proteins 0.000 claims description 33
• 102000040430 polynucleotide Human genes 0.000 claims description 33
• 239000002157 polynucleotide Substances 0.000 claims description 33
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 31
• 102000013566 Plasminogen Human genes 0.000 claims description 29
• 108010051456 Plasminogen Proteins 0.000 claims description 29
• 101000605403 Homo sapiens Plasminogen Proteins 0.000 claims description 26
• 108010022999 Serine Proteases Proteins 0.000 claims description 26
• 102000012479 Serine Proteases Human genes 0.000 claims description 26
• 125000003275 alpha amino acid group Chemical group 0.000 claims description 26
• 108010073385 Fibrin Proteins 0.000 claims description 25
• 102000009123 Fibrin Human genes 0.000 claims description 25
• BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 claims description 25
• 229950003499 fibrin Drugs 0.000 claims description 25
• 238000000034 method Methods 0.000 claims description 24
• 230000014509 gene expression Effects 0.000 claims description 21
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 20
• 239000004472 Lysine Substances 0.000 claims description 17
• 241000588724 Escherichia coli Species 0.000 claims description 15
• 108010015052 miniplasmin Proteins 0.000 claims description 14
• 230000002829 reductive effect Effects 0.000 claims description 14
• 239000002773 nucleotide Substances 0.000 claims description 13
• 125000003729 nucleotide group Chemical group 0.000 claims description 13
• 230000005764 inhibitory process Effects 0.000 claims description 12
• 125000000539 amino acid group Chemical group 0.000 claims description 10
• 238000004519 manufacturing process Methods 0.000 claims description 10
• 238000006467 substitution reaction Methods 0.000 claims description 10
• 108010049003 Fibrinogen Proteins 0.000 claims description 9
• 102000008946 Fibrinogen Human genes 0.000 claims description 9
• 210000004899 c-terminal region Anatomy 0.000 claims description 9
• 239000013604 expression vector Substances 0.000 claims description 9
• 229940012952 fibrinogen Drugs 0.000 claims description 9
• 230000005847 immunogenicity Effects 0.000 claims description 8
• 230000003480 fibrinolytic effect Effects 0.000 claims description 6
• 239000004475 Arginine Substances 0.000 claims description 4
• 108091005804 Peptidases Proteins 0.000 claims description 4
• 239000004365 Protease Substances 0.000 claims description 4
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 4
• 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims description 3
• 210000004748 cultured cell Anatomy 0.000 claims description 3
• 108091028043 Nucleic acid sequence Proteins 0.000 claims description 2
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims 3
• 235000006679 Mentha X verticillata Nutrition 0.000 claims 2
• 235000002899 Mentha suaveolens Nutrition 0.000 claims 2
• 235000001636 Mentha x rotundifolia Nutrition 0.000 claims 2
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 2
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
• 235000014820 Galium aparine Nutrition 0.000 claims 1
• 240000005702 Galium aparine Species 0.000 claims 1
• 210000004027 cell Anatomy 0.000 description 46
• 108090000623 proteins and genes Proteins 0.000 description 37
• 239000013598 vector Substances 0.000 description 33
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• 235000018102 proteins Nutrition 0.000 description 30
• 108010026333 seryl-proline Proteins 0.000 description 20
• ZJICFHQSPWFBKP-AVGNSLFASA-N Glu-Asn-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ZJICFHQSPWFBKP-AVGNSLFASA-N 0.000 description 16
• 241000282414 Homo sapiens Species 0.000 description 16
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• 108010050848 glycylleucine Proteins 0.000 description 15
• 239000000243 solution Substances 0.000 description 15
• PRVVCRZLTJNPCS-FXQIFTODSA-N Cys-Arg-Asn Chemical compound C(C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CS)N)CN=C(N)N PRVVCRZLTJNPCS-FXQIFTODSA-N 0.000 description 14
• 150000007523 nucleic acids Chemical class 0.000 description 14
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• 108020004707 nucleic acids Proteins 0.000 description 12
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• KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 11
• 238000012217 deletion Methods 0.000 description 11
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• YRTOMUMWSTUQAX-FXQIFTODSA-N Asn-Pro-Asp Chemical compound NC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O YRTOMUMWSTUQAX-FXQIFTODSA-N 0.000 description 10
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• AHFOKDZWPPGJAZ-SRVKXCTJSA-N Lys-Lys-Cys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)O)N AHFOKDZWPPGJAZ-SRVKXCTJSA-N 0.000 description 10
• JXKMXEBNZCKSDY-JIOCBJNQSA-N Thr-Asp-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N)O JXKMXEBNZCKSDY-JIOCBJNQSA-N 0.000 description 10
• KLGFILUOTCBNLJ-IHRRRGAJSA-N Tyr-Cys-Arg Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N)O KLGFILUOTCBNLJ-IHRRRGAJSA-N 0.000 description 10
• 108010070944 alanylhistidine Proteins 0.000 description 10
• 235000001014 amino acid Nutrition 0.000 description 10
• 108010060035 arginylproline Proteins 0.000 description 10
• 230000001580 bacterial effect Effects 0.000 description 10
• GHNDBBVSWOWYII-LPEHRKFASA-N Arg-Asn-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O GHNDBBVSWOWYII-LPEHRKFASA-N 0.000 description 9
• ISSDODCYBOWWIP-GJZGRUSLSA-N Gly-Pro-Trp Chemical compound [H]NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O ISSDODCYBOWWIP-GJZGRUSLSA-N 0.000 description 9
• OGUUKPXUTHOIAV-SDDRHHMPSA-N Leu-Glu-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N OGUUKPXUTHOIAV-SDDRHHMPSA-N 0.000 description 9
• GVKINWYYLOLEFQ-XIRDDKMYSA-N Lys-Trp-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CO)C(O)=O GVKINWYYLOLEFQ-XIRDDKMYSA-N 0.000 description 9
• MTHRMUXESFIAMS-DCAQKATOSA-N Pro-Asn-Lys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O MTHRMUXESFIAMS-DCAQKATOSA-N 0.000 description 9
• LCUOTSLIVGSGAU-AVGNSLFASA-N Pro-His-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O LCUOTSLIVGSGAU-AVGNSLFASA-N 0.000 description 9
• 108010023197 Streptokinase Proteins 0.000 description 9
• 108010084758 arginyl-tyrosyl-aspartic acid Proteins 0.000 description 9
• 108010093581 aspartyl-proline Proteins 0.000 description 9
• 108010047857 aspartylglycine Proteins 0.000 description 9
• 108010055341 glutamyl-glutamic acid Proteins 0.000 description 9
• 108010049041 glutamylalanine Proteins 0.000 description 9
• 229960005202 streptokinase Drugs 0.000 description 9
• 239000000126 substance Substances 0.000 description 9
• YNQMEIJEWSHOEO-SRVKXCTJSA-N Asn-Tyr-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)N)N)O YNQMEIJEWSHOEO-SRVKXCTJSA-N 0.000 description 8
• UGVQELHRNUDMAA-BYPYZUCNSA-N Gly-Ala-Gly Chemical compound [NH3+]CC(=O)N[C@@H](C)C(=O)NCC([O-])=O UGVQELHRNUDMAA-BYPYZUCNSA-N 0.000 description 8
• LLWQVJNHMYBLLK-CDMKHQONSA-N Gly-Thr-Phe Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O LLWQVJNHMYBLLK-CDMKHQONSA-N 0.000 description 8
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• 108010065920 Insulin Lispro Proteins 0.000 description 8
• IIKJNQWOQIWWMR-CIUDSAMLSA-N Leu-Cys-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)N IIKJNQWOQIWWMR-CIUDSAMLSA-N 0.000 description 8
• PXHCFKXNSBJSTQ-KKUMJFAQSA-N Lys-Asn-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCCN)N)O PXHCFKXNSBJSTQ-KKUMJFAQSA-N 0.000 description 8
• KKKVOZNCLALMPV-XKBZYTNZSA-N Ser-Thr-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O KKKVOZNCLALMPV-XKBZYTNZSA-N 0.000 description 8
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