| Title | Prolonged in-vivo half-life of factor VIIa by fusion to albumin. | | Author(s) | Weimer T, Wormsbächer W, Kronthaler U, Lang W, Liebing U, Schulte S | | Institution | CSL Behring GmbH, Emil-von-Behring-Strasse 76, 35041 Marburg, Germany. E-mail: stefan.schulte@cslbehring.com. | | Source | Thromb Haemost 2008 Apr; 99(4):659-67. | | 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 18392323 |
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