Publications by authors named "Philipp Claar"
Article Synopsis
- Hemophilia B is an X-linked bleeding disorder caused by mutations in the FIX gene, necessitating continuous FIX replacement therapy, often through complex intravenous methods.
- This study focused on improving new rIX-FP variants, specifically R338L and R338L/E410K, to enhance their effectiveness and explore their potential for subcutaneous administration.
- Results showed that the R338L variant had 4-5 times greater specific activity and was effective in reducing bleeding, requiring significantly lower protein amounts compared to standard treatments.
Background: There is an emerging concept that in addition to circulating coagulation factor IX (FIX), extravascular FIX contributes to hemostasis.
Objective: Our objective was to evaluate the efficacy of extravascular FIX using animal models of tail clip bleeding and ferric chloride-induced thrombosis.
Methods: Mutant rFIX proteins with described enhanced (rFIX) or reduced (rFIX) binding to extracellular matrix were generated and characterized using aPTT, one-stage clotting, and modified FX assays.
Background: We have recently reported on a recombinant von Willebrand factor (VWF) D'D3 albumin fusion protein (rD'D3-FP) developed to extend the half-life of coagulation factor VIII (FVIII) for the treatment of hemophilia A. Based on predictive modelling presented in this study, we hypothesized that modifying rD'D3-FP to improve FVIII interaction would reduce exchange with endogenous VWF and provide additional FVIII half-life benefit.
Objectives: The aim of this study was to identify novel rD'D3-FP variants with enhanced therapeutic efficacy in extending FVIII half-life.
A novel mechanism for extending the circulatory half-life of coagulation factor VIII (FVIII) has been established and evaluated preclinically. The FVIII binding domain of von Willebrand factor (D'D3) fused to human albumin (rD'D3-FP) dose dependently improved pharmacokinetics parameters of coadministered FVIII in all animal species tested, from mouse to cynomolgus monkey, after IV injection. At higher doses, the half-life of recombinant FVIII (rVIII-SingleChain) was calculated to be increased 2.
View Article and Find Full Text PDFIntroduction: rVIII-SingleChain (CSL627), a novel recombinant coagulation factor VIII (FVIII), is under investigation in a phase I/III clinical programme (AFFINITY) for the treatment of haemophilia A. Non-clinical studies were conducted to investigate the pharmacokinetic/pharmacodynamic profile of rVIII-SingleChain in comparison with full-length recombinant FVIII.
Materials And Methods: Binding affinity of rVIII-SingleChain for von Willebrand factor was investigated by surface plasmon resonance analysis.