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Thromb Haemost. 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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1
CSL Behring GmbH, Emil-von-Behring-Strasse 76, 35041 Marburg, Germany.

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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PMID:
18392323
DOI:
10.1160/TH07-08-0525
[Indexed for MEDLINE]

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