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

Thomas Weimer; Wilfried Wormsbächer; Ulrich Kronthaler; Wiegand Lang; Uwe Liebing; Stefan Schulte

doi:10.1160/TH07-08-0525

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2008; 99(04): 659-667
DOI: 10.1160/TH07-08-0525

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

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

Thomas Weimer

¹CSL Behring GmbH, Marburg, Germany

,

Wilfried Wormsbächer

¹CSL Behring GmbH, Marburg, Germany

,

Ulrich Kronthaler

¹CSL Behring GmbH, Marburg, Germany

,

Wiegand Lang

¹CSL Behring GmbH, Marburg, Germany

,

Uwe Liebing

¹CSL Behring GmbH, Marburg, Germany

,

Stefan Schulte

¹CSL Behring GmbH, Marburg, Germany

› Institutsangaben

Abstract

Summary

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 sevenfold 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^®). 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.

Keywords

FVIIa - albumin fusion - rVIIa-FP - coagulation

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Referenzen

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