Prolonged In-Vivo Half-Life of FVIIa by Fusion to Albumin
| Autor: | Ulrich Kronthaler, Thomas Weimer, Uwe Liebing, Albrecht Groener, Stefan Schulte, Wilfried Wormsbaecher, Wiegand Lang |
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| Rok vydání: | 2007 |
| Předmět: | |
| Zdroj: | Blood. 110:3142-3142 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | For the treatment of hemophilia patients with inhibitors, recombinant Factor VIIa (rFVIIa) is available as a therapeutic option to control bleeding episodes with a good balance of safety and efficacy. The short in-vivo half-life of approximately 2.5 h requires multiple injections, which is inconvenient for treaters and patients. Here we describe the generation of a half-life extended recombinant FVIIa molecule based on genetic fusion of FVIIa to human albumin. In this fusion protein the design of the linker sequence is important to optimize the effect of the albumin moiety on FVII activity. The recombinant FVII-albumin fusion protein (rVII-FP) was expressed in mammalian cells and upon activation displayed a FVII activity comparable to wild type rFVIIa. Pharmacokinetic studies in rats and rabbits demonstrated that the half-life of the activated recombinant FVII albumin fusion protein (rVIIa-FP) was 6 to 9 fold extended compared to wild type rFVIIa. The in-vitro and in-vivo efficacy was evaluated and found comparable to commercially available rFVIIa (NovoSeven®). The results of this study demonstrate that it is feasible to improve the attributes of a rVIIa molecule by extending its half life, while retaining a molecule with very similar hemostatic properties to the wild type factor. |
| Databáze: | OpenAIRE |
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