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Comparative Study
. 2008 Apr;99(4):659-67.
doi: 10.1160/TH07-08-0525.

Prolonged in-vivo half-life of factor VIIa by fusion to albumin

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Comparative Study

Prolonged in-vivo half-life of factor VIIa by fusion to albumin

Thomas Weimer et al. Thromb Haemost. 2008 Apr.

Abstract

For the treatment of haemophilia 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. However, the short in-vivo half-life of approximately 2.5 hours makes multiple injections necessary, which is inconvenient for both physicians and patients. Here we describe the generation of a recombinant FVIIa molecule with an extended half-life based on genetic fusion to human albumin. The recombinant FVII albumin fusion protein (rVII-FP) was expressed in mammalian cells and upon activation displayed a FVII activity close to that of wild type FVIIa. Pharmacokinetic studies in rats demonstrated that the half-life of the activated recombinant FVII albumin fusion protein (rVIIa-FP) was extended six- to seven-fold compared with wild type rFVIIa. The in-vitro and in-vivo efficacy was evaluated and was found to be comparable to a commercially available rFVIIa (NovoSeven((R))). The results of this study demonstrate that it is feasible to develop a half-life extended FVIIa molecule with haemostatic properties very similar to the wild-type factor.

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Comment in

  • Factor VIIa gets even bigger.
    Sheffield WP, Clarke BJ. Sheffield WP, et al. Thromb Haemost. 2008 Apr;99(4):653-4. doi: 10.1160/TH08-02-0120. Thromb Haemost. 2008. PMID: 18392320 No abstract available.

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