GTC Biotherapeutics (fka GTCB)

[DewDiligence]

Prolonged In-Vivo Half-Life of FVIIa by Fusion to Albumin

[This is an attempt to create a successor to NovoSeven with a longer half-life. The PR announcing this paper was posted in #msg-25188594.]

http://www.ncbi.nlm.nih.gov/pubmed/18392323

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Thromb Haemost. 2008 Apr;99(4):659-67.

Weimer T, Wormsbächer W, Kronthaler U, Lang W, Liebing U, Schulte S.

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

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®). 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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