DK1984503T4 - Modificeret koaguleringskator VIIa med forlænget halvliv - Google Patents
Modificeret koaguleringskator VIIa med forlænget halvliv Download PDFInfo
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- DK1984503T4 DK1984503T4 DK07703248.0T DK07703248T DK1984503T4 DK 1984503 T4 DK1984503 T4 DK 1984503T4 DK 07703248 T DK07703248 T DK 07703248T DK 1984503 T4 DK1984503 T4 DK 1984503T4
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- albumin
- factor
- polypeptide
- leu
- infused
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- C07K14/76—Albumins
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N15/62—DNA sequences coding for fusion proteins
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- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6437—Coagulation factor VIIa (3.4.21.21)
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/31—Fusion polypeptide fusions, other than Fc, for prolonged plasma life, e.g. albumin
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Claims (18)
1. Albuminfusioneret polypeptid omfattende mindst et Faktor VII- eller Faktor VIla-polypeptid fusioneret med albumin, hvori mindst et sådant Faktor VII- eller Faktor VIIa-polypeptid er placeret ved N-terminus af fusionsproteinet, og hvori fusionsproteinet har Faktor VII/VIIa biologisk aktivitet, og hvori en peptidbinding adskiller Faktor VII- eller Faktor Vlla-delen ved fusionsproteinets N-terminus fra albumindelen, hvilken binding omfatter mindst 25 aminosyrer og gentagelsesenheder omfattende glycin og serin.
2. Albuminfusioneret polypeptid ifølge krav 1, hvori fusionsproteinet har mindst 25% molspecifik Faktor VII/VIIa biologisk aktivitet sammenlignet med de respektive ufusionerede vildtype Faktor VII eller Faktor Vila.
3. Albuminfusioneret polypeptid omfattende Faktor VII- eller Faktor VIla- polypeptid ifølge krav 1 eller 2, hvori fusionsproteinet har øget funktionelt plas-mahalvliv in vivo sammenlignet med ikke-fusioneret Faktor FVII eller Faktor FVIIa.
4. Albuminfusioneret polypeptid omfattende Faktor VII- eller Faktor VIla- polypeptid ifølge krav 3, hvori fusionsproteinet har et funktionelt halvliv in vivo, som er øget med mindst 100% sammenlignet med den ikke-fusionerede Faktor FVII eller Faktor FVIIa.
5. Albuminfusioneret polypeptid ifølge krav 1 til 4, hvori bindingen indeholder et proteasespaltningssted.
6. Albuminfusioneret polypeptid ifølge krav 5, hvori spaltningsstedet kan spaltes med en koagulationsprotease valgt fra gruppen bestående af Faktor Ila, Faktor IXa, Faktor Xa, Faktor Xla, Faktor XIla, aktiveret protein C, elastase eller kal-likrein.
7. Albuminfusioneret polypeptid ifølge krav 1 til 6, hvori bindingen er modificeret ved indsætning af steder til posttranslationale modifikationer, og hvori den post-translationale modifikation omfatter et eller flere N-glykosyleringssteder med strukturen Asn-X-Ser/Thr, hvori X betegner enhver aminosyre undtagen prolin.
8. Albuminfusioneret polypeptid ifølge krav 1 til 7, hvori albuminfusionspolypepti-det er modificeret sådan, at modifikationen omfatter tilføjelse ved indsætning af mindst en del af aktiveringspeptidet af et andet K-vitaminafhængigt polypeptid eller tilføjelse ved indsætning af en analogi af aktiveringspeptidet af det andet K-vitaminafhængige polypeptid.
9. Albuminfusionerede polypeptider ifølge krav 1 til 8, hvori Faktor VII eller Faktor Vila polypeptiddelen har koaguleringsfremmende aktivitet.
10. Albuminfusioneret polypeptid ifølge krav 1 til 9 til anvendelse som medikament.
11. Farmaceutisk sammensætning, som omfatter en effektiv mængde af det albuminfusionerede polypeptid ifølge ethvert af krav 1 til 9 sammen med en farmaceutisk acceptabel bærer eller excipiens.
12. Farmaceutisk sammensætning ifølge krav 11 til brug ved behandling eller forebyggelse af blødningslidelser, hvori blødningslidelsen fortrinsvis er hæmofili A.
13. Farmaceutisk sammensætning ifølge krav 12, hvori det albuminfusionerede polypeptid gives intravenøst, subkutant, intramuskulært, intraperitonalt, intrace-rebralt, intrapulmonalt, intranasalt eller transdermalt.
14. Nukleinsyremolekyle, hvori nukleinsyremolekylet omfatter en polynu-kleotidsekvens, der koder albuminfusionspolypeptidet ifølge krav 1 til 9, hvori polynukleotidsekvensen er placeret ved 3’-enden af en nukleotidsekvens, der koder for et propeptid, der medierer gammakarboxylering af Faktor VII/VIIa-fusionsdelen.
15. Plasmid eller vektor, hvori plasmidet eller vektoren omfatter nukleinsyremolekylet ifølge krav 14.
16. Plasmid eller vektor ifølge krav 15, hvori plasmidet eller vektoren er i) en ekspressionsvektor eller ii) en transfervektor til anvendelse i menneskegenterapi.
17. Værtscelle, hvori værtscellen omfatter nukleinsyremolekylet ifølge krav 14 til 16.
18. Fremgangsmåde til fremstilling af et albuminfusionspolypeptid ifølge krav 1 til 9, hvori fremgangsmåden omfatter: a. tilvejebringelse af en nukleinsyre, der omfatter en nukleinsyresekvens, der koder albuminfusionspolypeptidet, som kan udtrykkes i en organisme; b. udtrykkelse af nukleinsyren i organismen for at danne et albuminfusionsprotein; og rensning af albuminfusionspolypeptidet.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP06002359A EP1816201A1 (en) | 2006-02-06 | 2006-02-06 | Modified coagulation factor VIIa with extended half-life |
PCT/EP2007/000937 WO2007090584A1 (en) | 2006-02-06 | 2007-02-03 | Modified coagulation factor vila with extended half-life |
Publications (2)
Publication Number | Publication Date |
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DK1984503T3 DK1984503T3 (da) | 2014-09-15 |
DK1984503T4 true DK1984503T4 (da) | 2018-12-03 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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DK07703248.0T DK1984503T4 (da) | 2006-02-06 | 2007-02-03 | Modificeret koaguleringskator VIIa med forlænget halvliv |
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EP (3) | EP1816201A1 (da) |
JP (2) | JP5726404B2 (da) |
KR (2) | KR101579083B1 (da) |
CN (1) | CN101379189B (da) |
AU (1) | AU2007214011B9 (da) |
BR (1) | BRPI0707513A2 (da) |
CA (1) | CA2636671C (da) |
DK (1) | DK1984503T4 (da) |
ES (2) | ES2793325T3 (da) |
HK (1) | HK1129421A1 (da) |
MX (1) | MX2008009893A (da) |
PL (1) | PL1984503T5 (da) |
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2006
- 2006-02-06 EP EP06002359A patent/EP1816201A1/en not_active Withdrawn
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2007
- 2007-02-03 EP EP10164043.1A patent/EP2233576B1/en active Active
- 2007-02-03 WO PCT/EP2007/000937 patent/WO2007090584A1/en active Application Filing
- 2007-02-03 MX MX2008009893A patent/MX2008009893A/es active IP Right Grant
- 2007-02-03 RU RU2008132760/10A patent/RU2466141C2/ru not_active IP Right Cessation
- 2007-02-03 KR KR1020147012098A patent/KR101579083B1/ko active IP Right Grant
- 2007-02-03 BR BRPI0707513-8A patent/BRPI0707513A2/pt not_active IP Right Cessation
- 2007-02-03 CN CN200780004623.4A patent/CN101379189B/zh not_active Expired - Fee Related
- 2007-02-03 KR KR1020087021858A patent/KR101439817B1/ko active IP Right Grant
- 2007-02-03 EP EP07703248.0A patent/EP1984503B2/en not_active Not-in-force
- 2007-02-03 DK DK07703248.0T patent/DK1984503T4/da active
- 2007-02-03 CA CA2636671A patent/CA2636671C/en not_active Expired - Fee Related
- 2007-02-03 US US12/223,616 patent/US8765915B2/en not_active Expired - Fee Related
- 2007-02-03 ES ES10164043T patent/ES2793325T3/es active Active
- 2007-02-03 AU AU2007214011A patent/AU2007214011B9/en not_active Ceased
- 2007-02-03 JP JP2008552755A patent/JP5726404B2/ja active Active
- 2007-02-03 PL PL07703248T patent/PL1984503T5/pl unknown
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2009
- 2009-09-23 HK HK09108088.7A patent/HK1129421A1/xx not_active IP Right Cessation
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2013
- 2013-06-26 JP JP2013133394A patent/JP2013188230A/ja active Pending
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- 2014-05-15 US US14/279,143 patent/US20140356346A1/en not_active Abandoned
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