DK200200302A - Rekombinante polypeptider omfattende aminosyresekvensen af moden vævsfaktorinhibitor (TFI), polypeptidfragmenter deraf, ekspressionsvektorer der koder for disse, værtsceller transformeret dermed, og fremgangsmåde til fremstilling af et ........ - Google Patents

Rekombinante polypeptider omfattende aminosyresekvensen af moden vævsfaktorinhibitor (TFI), polypeptidfragmenter deraf, ekspressionsvektorer der koder for disse, værtsceller transformeret dermed, og fremgangsmåde til fremstilling af et ........ Download PDF

Info

Publication number: DK200200302A
Authority: DK; Denmark
Prior art keywords: asn; glu; cys; phe; gly
Prior art date: 1987-11-23

Application number

DK200200302A

Other languages

English (en)

Inventor

George John Broze Jr

Kretzmer Kuniko Kusano

Wun Tze-Chein

Original Assignee

Monsanto Co

Univ Washington

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1987-11-23

Filing date

2002-02-27

Publication date

2002-02-27

1987-11-23 Priority claimed from US07/123,753 external-priority patent/US4966852A/en

2000-10-27 Priority claimed from DK200001612A external-priority patent/DK174754B1/da

2002-02-27 Application filed by Monsanto Co, Univ Washington filed Critical Monsanto Co

2002-02-27 Priority to DK200200302A priority Critical patent/DK175430B1/da

2002-02-27 Publication of DK200200302A publication Critical patent/DK200200302A/da

2004-10-18 Application granted granted Critical

2004-10-18 Publication of DK175430B1 publication Critical patent/DK175430B1/da

Links

229920001184 polypeptide Polymers 0.000 title description 15
108090000765 processed proteins & peptides Proteins 0.000 title description 15
102000004196 processed proteins & peptides Human genes 0.000 title description 15
102000002262 Thromboplastin Human genes 0.000 title description 7
108010000499 Thromboplastin Proteins 0.000 title description 7
239000003112 inhibitor Substances 0.000 title description 7
239000013604 expression vector Substances 0.000 title description 5
238000004519 manufacturing process Methods 0.000 title description 2
125000003275 alpha amino acid group Chemical group 0.000 title 1
239000012634 fragment Substances 0.000 title 1
NUSWUSKZRCGFEX-FXQIFTODSA-N Glu-Glu-Cys Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CS)C(O)=O NUSWUSKZRCGFEX-FXQIFTODSA-N 0.000 description 16
108010012581 phenylalanylglutamate Proteins 0.000 description 16
HUZGPXBILPMCHM-IHRRRGAJSA-N Asn-Arg-Phe Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O HUZGPXBILPMCHM-IHRRRGAJSA-N 0.000 description 10
NVGWESORMHFISY-SRVKXCTJSA-N Asn-Asn-Phe Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O NVGWESORMHFISY-SRVKXCTJSA-N 0.000 description 10
XVAPVJNJGLWGCS-ACZMJKKPSA-N Asn-Glu-Asn Chemical compound C(CC(=O)O)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N XVAPVJNJGLWGCS-ACZMJKKPSA-N 0.000 description 10
JBCLFWXMTIKCCB-UHFFFAOYSA-N H-Gly-Phe-OH Natural products NCC(=O)NC(C(O)=O)CC1=CC=CC=C1 JBCLFWXMTIKCCB-UHFFFAOYSA-N 0.000 description 9
108010081551 glycylphenylalanine Proteins 0.000 description 9
HULHGJZIZXCPLD-FXQIFTODSA-N Arg-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N HULHGJZIZXCPLD-FXQIFTODSA-N 0.000 description 8
FVKHEKVYFTZWDX-GHCJXIJMSA-N Asn-Ile-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)N)N FVKHEKVYFTZWDX-GHCJXIJMSA-N 0.000 description 8
ZOLXQKZHYOHHMD-DLOVCJGASA-N Cys-Ala-Phe Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CS)N ZOLXQKZHYOHHMD-DLOVCJGASA-N 0.000 description 8
FIADUEYFRSCCIK-CIUDSAMLSA-N Cys-Glu-Arg Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FIADUEYFRSCCIK-CIUDSAMLSA-N 0.000 description 8
UDPSLLFHOLGXBY-FXQIFTODSA-N Cys-Glu-Glu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O UDPSLLFHOLGXBY-FXQIFTODSA-N 0.000 description 8
UHVIQGKBMXEVGN-WDSKDSINSA-N Glu-Gly-Asn Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O UHVIQGKBMXEVGN-WDSKDSINSA-N 0.000 description 8
YQAQQKPWFOBSMU-WDCWCFNPSA-N Glu-Thr-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O YQAQQKPWFOBSMU-WDCWCFNPSA-N 0.000 description 8
GQGAFTPXAPKSCF-WHFBIAKZSA-N Gly-Ala-Cys Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CS)C(=O)O GQGAFTPXAPKSCF-WHFBIAKZSA-N 0.000 description 8
KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 8
JQLQUPIYYJXZLJ-ZEWNOJEFSA-N Phe-Ile-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 JQLQUPIYYJXZLJ-ZEWNOJEFSA-N 0.000 description 8
150000001413 amino acids Chemical group 0.000 description 8
FSXRLASFHBWESK-UHFFFAOYSA-N dipeptide phenylalanyl-tyrosine Natural products C=1C=C(O)C=CC=1CC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FSXRLASFHBWESK-UHFFFAOYSA-N 0.000 description 8
108010065135 phenylalanyl-phenylalanyl-phenylalanine Proteins 0.000 description 8
108010072986 threonyl-seryl-lysine Proteins 0.000 description 8
108010017949 tyrosyl-glycyl-glycine Proteins 0.000 description 8
CEZSLNCYQUFOSL-BQBZGAKWSA-N Cys-Arg-Gly Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O CEZSLNCYQUFOSL-BQBZGAKWSA-N 0.000 description 7
IZUNQDRIAOLWCN-YUMQZZPRSA-N Cys-Leu-Gly Chemical compound CC(C)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CS)N IZUNQDRIAOLWCN-YUMQZZPRSA-N 0.000 description 7
RESAHOSBQHMOKH-KKUMJFAQSA-N Cys-Phe-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CS)N RESAHOSBQHMOKH-KKUMJFAQSA-N 0.000 description 7
RQNYYRHRKSVKAB-GUBZILKMSA-N Glu-Cys-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(O)=O RQNYYRHRKSVKAB-GUBZILKMSA-N 0.000 description 7
NKLRYVLERDYDBI-FXQIFTODSA-N Glu-Glu-Asp Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O NKLRYVLERDYDBI-FXQIFTODSA-N 0.000 description 7
IDEODOAVGCMUQV-GUBZILKMSA-N Glu-Ser-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O IDEODOAVGCMUQV-GUBZILKMSA-N 0.000 description 7
FEPSEIDIPBMIOS-QXEWZRGKSA-N Pro-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H]1CCCN1 FEPSEIDIPBMIOS-QXEWZRGKSA-N 0.000 description 7
HIINQLBHPIQYHN-JTQLQIEISA-N Tyr-Gly-Gly Chemical compound OC(=O)CNC(=O)CNC(=O)[C@@H](N)CC1=CC=C(O)C=C1 HIINQLBHPIQYHN-JTQLQIEISA-N 0.000 description 7
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 7
108010093581 aspartyl-proline Proteins 0.000 description 7
108010050848 glycylleucine Proteins 0.000 description 7
108010027338 isoleucylcysteine Proteins 0.000 description 7
OQCWXQJLCDPRHV-UWVGGRQHSA-N Arg-Gly-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O OQCWXQJLCDPRHV-UWVGGRQHSA-N 0.000 description 6
MNBHKGYCLBUIBC-UFYCRDLUSA-N Arg-Phe-Phe Chemical compound C([C@H](NC(=O)[C@H](CCCNC(N)=N)N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 MNBHKGYCLBUIBC-UFYCRDLUSA-N 0.000 description 6
UIUXXFIKWQVMEX-UFYCRDLUSA-N Arg-Phe-Tyr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O UIUXXFIKWQVMEX-UFYCRDLUSA-N 0.000 description 6
LFWOQHSQNCKXRU-UFYCRDLUSA-N Arg-Tyr-Phe Chemical compound C([C@H](NC(=O)[C@H](CCCN=C(N)N)N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=C(O)C=C1 LFWOQHSQNCKXRU-UFYCRDLUSA-N 0.000 description 6
SZQCDCKIGWQAQN-FXQIFTODSA-N Cys-Arg-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O SZQCDCKIGWQAQN-FXQIFTODSA-N 0.000 description 6
XZKJEOMFLDVXJG-KATARQTJSA-N Cys-Leu-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)N)O XZKJEOMFLDVXJG-KATARQTJSA-N 0.000 description 6
241000880493 Leptailurus serval Species 0.000 description 6
KIEPQOIQHFKQLK-PCBIJLKTSA-N Phe-Asn-Ile Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O KIEPQOIQHFKQLK-PCBIJLKTSA-N 0.000 description 6
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APKRGYLBSCWJJP-FXQIFTODSA-N Pro-Ala-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(O)=O APKRGYLBSCWJJP-FXQIFTODSA-N 0.000 description 6
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SCCKSNREWHMKOJ-SRVKXCTJSA-N Tyr-Asn-Ser Chemical compound N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O SCCKSNREWHMKOJ-SRVKXCTJSA-N 0.000 description 6
BXPOOVDVGWEXDU-WZLNRYEVSA-N Tyr-Ile-Thr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O BXPOOVDVGWEXDU-WZLNRYEVSA-N 0.000 description 6
UKEVLVBHRKWECS-LSJOCFKGSA-N Val-Ile-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](C(C)C)N UKEVLVBHRKWECS-LSJOCFKGSA-N 0.000 description 6
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108010087823 glycyltyrosine Proteins 0.000 description 6
108010003137 tyrosyltyrosine Proteins 0.000 description 6
WXERCAHAIKMTKX-ZLUOBGJFSA-N Ala-Asp-Asp Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O WXERCAHAIKMTKX-ZLUOBGJFSA-N 0.000 description 5
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FADYJNXDPBKVCA-UHFFFAOYSA-N L-Phenylalanyl-L-lysin Natural products NCCCCC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FADYJNXDPBKVCA-UHFFFAOYSA-N 0.000 description 5
ISHNZELVUVPCHY-ZETCQYMHSA-N Lys-Gly-Gly Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)NCC(O)=O ISHNZELVUVPCHY-ZETCQYMHSA-N 0.000 description 5
XROLYVMNVIKVEM-BQBZGAKWSA-N Pro-Asn-Gly Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O XROLYVMNVIKVEM-BQBZGAKWSA-N 0.000 description 5
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108010042598 glutamyl-aspartyl-glycine Proteins 0.000 description 5
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QSQXZZCGPXQBPP-BQBZGAKWSA-N Gly-Pro-Cys Chemical compound C1C[C@H](N(C1)C(=O)CN)C(=O)N[C@@H](CS)C(=O)O QSQXZZCGPXQBPP-BQBZGAKWSA-N 0.000 description 4
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HXOLCSYHGRNXJJ-IHRRRGAJSA-N Pro-Asp-Phe Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O HXOLCSYHGRNXJJ-IHRRRGAJSA-N 0.000 description 4
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108010047857 aspartylglycine Proteins 0.000 description 4
108010055341 glutamyl-glutamic acid Proteins 0.000 description 4
WOZDCBHUGJVJPL-AVGNSLFASA-N Arg-Val-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N WOZDCBHUGJVJPL-AVGNSLFASA-N 0.000 description 3
BKFXFUPYETWGGA-XVSYOHENSA-N Asn-Phe-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O BKFXFUPYETWGGA-XVSYOHENSA-N 0.000 description 3
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GFFRWIJAFFMQGM-NUMRIWBASA-N Asn-Glu-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GFFRWIJAFFMQGM-NUMRIWBASA-N 0.000 description 1
WZUZGDANRQPCDD-SRVKXCTJSA-N Asp-Phe-Cys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)O)N WZUZGDANRQPCDD-SRVKXCTJSA-N 0.000 description 1
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KOSRFJWDECSPRO-WDSKDSINSA-N Glu-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(O)=O KOSRFJWDECSPRO-WDSKDSINSA-N 0.000 description 1
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IDOGEHIWMJMAHT-BYPYZUCNSA-N Gly-Gly-Cys Chemical compound NCC(=O)NCC(=O)N[C@@H](CS)C(O)=O IDOGEHIWMJMAHT-BYPYZUCNSA-N 0.000 description 1
IBYOLNARKHMLBG-WHOFXGATSA-N Gly-Phe-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 IBYOLNARKHMLBG-WHOFXGATSA-N 0.000 description 1
FMEICTQWUKNAGC-YUMQZZPRSA-N Leu-Gly-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O FMEICTQWUKNAGC-YUMQZZPRSA-N 0.000 description 1
CAVRAQIDHUPECU-UVOCVTCTSA-N Lys-Thr-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CAVRAQIDHUPECU-UVOCVTCTSA-N 0.000 description 1
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LDEBVRIURYMKQS-WISUUJSJSA-N Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](N)CO LDEBVRIURYMKQS-WISUUJSJSA-N 0.000 description 1
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125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
JHKXZYLNVJRAAJ-UHFFFAOYSA-N methionyl-alanine Chemical group CSCCC(N)C(=O)NC(C)C(O)=O JHKXZYLNVJRAAJ-UHFFFAOYSA-N 0.000 description 1
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Preparation Of Compounds By Using Micro-Organisms (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Description

PATENTKRAV 1. Rekombinant polypeptid omfattende aminosyresekvensen af moden vævsfaktorinhibitor (TFI) som vist i Fig. 3. 2. Polypeptid ifølge krav 1 hvori den modne vævsfaktorinhibitor består af aminosyrerne 29-304 som vist i Fig. 3, 3. Polypeptid ifølge krav 1, som yderligere omfatter en forlænget ami-nosyresekvens umiddelbart forud for den modne vævsfaktorinhibitor. 4. Polypeptid bestående af moden vævsfaktorinhibitor (aminosyrerne 29-304) med en umiddelbart forudgående N-terminal methioninrest, alanin-rest eller methionin-alanin-dipeptid. 5. Renset og isoleret polypeptid omfattende en aminosyresekvens valgt blandt sekvenserne: (a) Cys Ala Phe Lys Ala Asp Asp Gly Pro Cys Lys Ala Ile Met Lys Arg Phe Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ile Tyr Gly Ala Cys Glu Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys; (b) Cys Phe Leu Glu Glu Asp Pro Gly Ile Cys Arg Gly Tyr Ile Thr Arg Tyr Phe Tyr Asn Asn Gin Thr Lys Gin Cys Glu Arg Phe Lys Tyr Gly Gly Cys Leu Gly Asn Met Asn Asn Phe Glu Thr Leu Glu Glu Cys Lys Asn Ile Cys; (c) Cys Leu Thr Pro Ala Asp Arg Gly Leu Cys Arg Ala Asn Glu Asn Arg Phe Tyr Tyr Asn Ser Val Ile Gly Lys Cys Arg Pro Phe Lys Tyr Ser Gly Cys Gly Gly Asn Glu Asn Asn Phe Thr Ser Lys Gin Glu Cys Leu Arg Ala Cys; (d) Leu Lys Leu Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly Pro Cys Lys Ala Ile Met Lys Arg Phe Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ile Tyr Gly Ala Cys Glu Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp Asn Ala Asn Arg Ile Ile Lys Thr Thr Leu; (e) Gin Gin Glu Lys Pro Asp Phe Cys Phe Leu Glu Glu Asp Pro Gly Ile Cys Arg Gly Tyr Ile Thr Arg Tyr Phe Tyr Asn Asn Gin Thr Lys Gin Cys Glu Arg Phe Lys Tyr Gly Gly Cys Leu Gly Asn Met Asn Asn Phe Glu Thr Leu Glu Glu Cys Lys Asn Ile Cys Glu Asp Gly Pro Asn Gly Phe Gin Val Asp Asn Tyr Gly; og (f) Glu Phe His Gly Pro Ser Trp Cys Leu Thr Pro Ala Asp Arg Gly Leu Cys Arg Ala Asn Glu Asn Arg Phe Tyr Tyr Asn Ser Val Ile Gly Lys Cys Arg Pro Phe Lys Tyr Ser Gly Cys Gly Gly Asn Glu Asn Asn Phe Thr Ser Lys Gin Glu Cys Leu Arg Ala Cys Lys Lys Gly Phe Ile Gin Arg Ile Ser Lys Gly Gly Leu. 6, Renset og isoleret polypeptid med en aminosyresekvens valgt blandt sekvenserne: (a) Cys Ala Phe Lys Ala Asp Asp Gly Pro Cys Lys Ala Ile Met Lys Arg Phe Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ile Tyr Gly Ala Cys Glu Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys; (b) Cys Phe Leu Glu Glu Asp Pro Gly Ile Cys Arg Gly Tyr Ile Thr Arg Tyr Phe Tyr Asn Asn Gin Thr Lys Gin Cys Glu Arg Phe Lys Tyr Gly Gly Cys Leu Gly Asn Met Asn Asn Phe Glu Thr Leu Glu Glu Cys Lys Asn Ile Cys; og (c) Cys Leu Thr Pro Ala Asp Arg Gly Leu Cys Arg Ala Asn Glu Asn Arg Phe Tyr Tyr Asn Ser Val Ile Gly Lys Cys Arg Pro Phe Lys Tyr Ser Gly Cys Gly Gly Asn Glu Asn Asn Phe Thr Ser Lys Gin Glu Cys Leu Arg Ala Cys. 7. Rekombinant polypeptid med aminosyresekvensen;

Asp Ser Glu Glu Asp Glu Glu His Thr Ile Ile Thr Asp Thr Glu Leu Pro Pro Leu Lys Leu Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly Pro Cys Lys Ala Ile Met Lys Arg Phe Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ile Tyr Gly Ala Cys Glu Gly Asn Gin Asn Arg Phe Glu Ser Ley Glu Glu Cys Lys Lys Met Cys Thr Arg Asp

Asn Ala Asn Arg Ile Ile Lys Thr Thr Leu Gin Gin Glu Lys Pro Asp Phe Cys Phe Leu Glu Giu Asp Pro Gly Ile Cys Arg Gly Tyr Ile Thr Arg Tyr Phe Tyr Asn Asn Gin Thr Lys Gin Cys Glu Arg Phe Lys Tyr Gly Gly Cys Leu Gly Asn Met Asn Asn Phe Glu Thr Leu Glu Glu Cys Lys Asn Ile Cys Glu Asp Gly Pro Asn Gly Phe Gin Val Asp Asn Tyr Gly Thr Gin Leu Asn Ala Val Asn Asn Ser Leu Thr Pro Gin Ser Thr Lys Val Pro Ser Leu Phe Glu Phe His Gly Pro Ser Trp Cys Leu Thr Pro Ala Asp Arg Gly Leu Cys Arg Ala Asn Glu Asn Arg Phe Tyr Tyr Asn Ser Val Ile Gly Lys Cys Arg Pro Phe Lys Tyr Ser Gly Cys Gly Gly Asn Glu Asn Asn Phe Thr Ser Lys Gin Glu Cys Leu Arg Ala Cys Lys Lys Gly Phe Ile Gin Arg Ile Ser Lys Gly Gly Leu Ile Lys Thr Lys Arg Lys Arg Lys Lys Gin Arg Val Lys Ile Ala Tyr Glu Glu Ile Phe Val Lys Asn Met. 8. Renset og isoleret polypeptid med aminosyresekvensen:

Asp Ser Glu Glu Asp Glu Glu His Thr Ile Ile Thr Asp Thr Glu Leu Pro Pro Leu Lys Leu Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly Pro Cys Lys Ala Ile Met Lys Arg Phe Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ile Tyr Gly Ala Cys Glu Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp Asn Ala Asn Arg Ile Ile Lys Thr Thr Leu Gin Glu Glu Lys Pro Asp Phe Cys Phe Leu Glu Glu Asp Pro Gly Ile Cys Arg Gly Tyr Ile Thr Arg Tyr Phe Tyr Asn Asn Gin Thr Lys Gin Cys Glu Arg Phe Lys Tyr Gly Gly Cys Leu Gly Asn Met Asn Asn Phe Glu Thr Leu Glu Glu Cys Lys Asn Ile Cys Glu Asp Gly Pro Asn Gly Phe Gin Val Asp Asn Tyr Gly Thr Gin Leu Asn Ala Val Asn Asn Ser Leu Thr Pro Gin Ser Thr Lys Val Pro Ser Leu Phe Glu Phe His Gly Pro Ser Trp Cys Leu Thr Pro Ala Asp Arg Gly Leu Cys Arg Ala Asn Glu Asn Arg Phe Tyr Tyr Asn Ser Val Ile Gly Lys Cys Arg Pro Phe Lys Tyr Ser Gly Cys Gly Gly Asn Glu Asn Asn Phe Thr Ser Lys Gin Glu Cys

Leu Arg Ala Cys Lys Lys Gly Phe Ile Gin Arg Ile Ser Lys Gly Gly Leu Ile Lys Thr Lys Arg Lys Arg Lys Lys Gin Arg Val Lys Ile Ala Tyr Glu Glu Ile Phe Val Lys Asn Met. 9. Ekspressionsvektor omfattende en renset og isoleret DNA, som koder for moden vævsfaktorinhibitor (TFI), som vist i Fig. 3. 10. Ekspressionsvektor omfattende en renset og isoleret DNA, som koder for et polypeptid valgt blandt: (a) Cys Ala Phe Lys Ala Asp Asp Gly Pro Cys Lys Ala Ile Met Lys Arg Phe Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ile Tyr Gly Ala Cys Glu Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys; (b) Cys Phe Leu Glu Glu Asp Pro Gly Ile Cys Arg Gly Tyr Ile Thr Arg Tyr Phe Tyr Asn Asn Gin Thr Lys Gin Cys Glu Arg Phe Lys Tyr Gly Gly Cys Leu Gly Asn Met Asn Asn Phe Glu Thr Leu Glu Glu Cys Lys Asn Ile Cys; (c) Cys Leu Thr Pro Ala Asp Arg Gly Leu Cys Arg Ala Asn Glu Asn Arg Phe Tyr Tyr Asn Ser Val Ile Gly Lys Cys Arg Pro Phe Lys Tyr Ser Gly Cys Gly Gly Asn Glu Asn Asn Phe Thr Ser Lys Gin Glu Cys Leu Arg Ala Cys; (d) Leu Lys Leu Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly Pro Cys Lys Ala Ile Met Lys Arg Phe Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ile Tyr Gly Ala Cys Glu Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp Asn Ala Asn Arg Ile Ile Lys Thr Thr Leu; (e) Gin Gin Glu Lys Pro Asp Phe Cys Phe Leu Glu Glu Asp Pro Gly Ile Cys Arg Gly Tyr Ile Thr Arg Tyr Phe Tyr Asn Asn Gin Thr Lys Gin Cys Glu Arg Phe Lys Tyr Gly Gly Cys Leu Gly Asn Met Asn Asn Phe Glu Thr Leu Glu Glu Cys Lys Asn Ile Cys Glu Asp Gly Pro Asn Gly Phe Gin Val Asp Asn Tyr Gly; og (f) Glu Phe His Gly Pro Ser Trp Cys Leu Thr Pro Ala Asp Arg Gly Leu Cys Arg Ala Asn Glu Asn Arg Phe Tyr Tyr Asn Ser Val Ile Gly Lys Cys Arg Pro Phe Lys Tyr Ser Gly Cys Gly Gly Asn Glu Asn Asn Phe Thr Ser Lys Gin Glu Cys Leu Arg Ala Cys Lys Lys Gly Phe Ile Gin Arg Ile Ser Lys Gly Gly Leu. 11. Ekspressionsvektor omfattende en renset og isoleret DNA, som koder for et polypeptid med sekvensen:

Asp Ser Glu Glu Asp Glu Glu His Thr Ile Ile Thr Asp Thr Glu Leu Pro Pro Leu Lys Leu Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Lys Pro Cys Lys Ala Ile Met Lys Arg Phe Phe Phe Asn Ile Phe THr Arg Gin Cys Glu Glu Phe Ile Tyr Gly Ala Cys Glu Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp Asn ALa Asn Arg Ile Ile Lys Thr Thr Leu Gin Gin Glu Lys Pro Asp Phe CYs Phe Leu Glu Glu Asp Pro Gly Ile Cys Arg Gly Ile Cys Arg Gly Tyr Ile Thr Arg Tyr Phe Tyr Asn Asn Glu Thr Lys Gin Cys Glu Arg Phe Lys Tyr Gly Gly Cys Leu Gly Asn Met Asn Asn Phe Glu Thr Leu Glu Glu Cys Lys Asn Ile Cys Glu Asp Gly Pro Asn Gly Phe Gin Val Asp Asn Tyr Gly Thr Gin Leu Asn Ala Val Asn Asn Ser Leu Thr Pro Gin Ser Thr Lys Val Pro Ser Leu Phe GLu Phe His Gly Pro Ser Trp Cys Leu Thr Pro ALa Asp Arg Gly Leu Cys Arg Ala Asn Glu Asn Arg Phe Tyr Tyr Asn Ser Val Ile GLy Lys Cys Arg Pro Phe Lys Tyr Ser GLy Cys Gly Gly Asn Glu Asn Asn Phe Thr Ser Lys Gin Glu Cys Leu Arg Ala Cys Lys Lys Gly Phe Ile Gin Arg Ile Ser Lys Gly Gly Leu Ile Lys Thr Lys Arg Lys Arg Lys Lys Gin ArG Val Lys Ile ALa Tyr Glu Glu Ile Phe Val Lys Asn Met. 12. Værtscelle transficeret eller transformeret med en ekspressionsvektor ifølge krav 9, 10 eller 11. 13. Fremgangsmåde til fremstilling af et vævsfaktorinhibitor-polypeptid, hvilken fremgangsmåde omfatter, at man: (a) dyrker en transficeret eller transformeret værtscelle ifølge krav 12 under egnede næringsbetingelser på en måde, som tillader ekspression af det nævnte polypeptid; og (b) isolerer det nævnte polypeptid.

DK200200302A 1987-11-23 2002-02-27 Rekombinante polypeptider omfattende aminosyresekvensen af moden vævsfaktorinhibitor (TFI), polypeptidfragmenter deraf, ekspressionsvektorer der koder for disse, værtsceller transformeret dermed, og fremgangsmåde til fremstilling af et ........ DK175430B1 (da)

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DK200200302A DK175430B1 (da)	1987-11-23	2002-02-27	Rekombinante polypeptider omfattende aminosyresekvensen af moden vævsfaktorinhibitor (TFI), polypeptidfragmenter deraf, ekspressionsvektorer der koder for disse, værtsceller transformeret dermed, og fremgangsmåde til fremstilling af et ........

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US07/123,753 US4966852A (en)	1987-07-23	1987-11-23	DNA clone of human tissue factor inhibitor
DK200001612A DK174754B1 (da)	1987-11-23	2000-10-27	Humane vævsfaktorinhibitor (TFI), antistof med bindingsspecificitet herfor, fremgangsmåde til anvendelse af en TFI-peptid-kolonne til at oprense et antistof og fremgangsmåder til detektion af TFI eller et polypeptid omfattende....
DK200200302A DK175430B1 (da)	1987-11-23	2002-02-27	Rekombinante polypeptider omfattende aminosyresekvensen af moden vævsfaktorinhibitor (TFI), polypeptidfragmenter deraf, ekspressionsvektorer der koder for disse, værtsceller transformeret dermed, og fremgangsmåde til fremstilling af et ........

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DK200200301A DK175431B1 (da)	1987-11-23	2002-02-27	Antistoffer som binder fragmenter af vævsfaktorinhibitor (TFI), sammensætninger omfattende disse antistoffer, og fremgangsmåde til anvendelse af en immunoaffinitetsmatrix omfattende et sådant antistof til at oprense et polypeptid fra et biologisk fluidum

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