Pharmacokinetics & Drug Delivery | Immunopharmacology & Hematologic Pharmacology | Molecular Pharmacology | Bleeding & Coagulation Disorders
Functional characterization of recombinant factor IX albumin fusion protein
Carsten Horn*, Burkhard Watzka, Hubert J Metzner, Thomas Weimer, Gerhard Dickneite, Stefan Schulte
*Corresponding author: Carsten Horn
CSL Behring GmbH, Marburg, Germany
F1000Posters 2012, 3: 372 (poster) [English]
Poster [672.95 KB]
56. Gesellschaft für Thrombose und Hämostaseforschung (German Society of Thrombosis and Haemostasis) 2012, 1 - 4 Feb 2012, P2-45
Improvement of the pharmacokinetic properties of factor IX (FIX) has the potential to increase convenience and compliance of the treatment of severe hemophilia B by reducing the dosing frequency. A concept for half-life increase of FIX was developed based on recombinant fusion protein technology linking recombinant coagulation factor IX and albumin (rIX-FP) via a cleavable linker.
The aim of this study was the functional characterization and comparison of rIX-FP to two commercially available FIX products – a recombinant ( r ) FIX (BeneFIX®) and a plasma-derived (pd) concentrate (Mononine®).
The ability of activated FIX (FIXa) to activate factor X (FX), as well as the inhibition of FIXa by antithrombin (AT), was investigated to assess structural functionality of FIXa. AT was able to inhibit FIXa activity completely in a concentration-dependent manner. The half-maximal inhibition was comparable for activated rIX-FP and FIX products, respectively. In a comparable, time-dependent manner, FXa was formed in presence of activated factor VIII (FVIIIa) by activated rIX-FP and pd or rFIX, respectively. Taken together, comparing activated rIX-FP and FIX products (BeneFIX® and Mononine®), a high degree of comparability was found in the assays applied.
All authors are employees of CSL Behring.
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