Turoctocog alfa (NovoEight®)--from design to clinical proof of concept.
Bottom Line: Viral inactivation is ensured by a detergent inactivation step as well as a 20-nm nano-filtration step.Tyr1680 was also fully sulphated in turoctocog alfa resulting in strong affinity (low nm Kd ) for binding to von Willebrand factor (VWF).The non-clinical data thus confirm the haemostatic effect of turoctocog alfa and, together with the comprehensive clinical evaluation, support the use as FVIII replacement therapy in patients with haemophilia A.
Affiliation: Novo Nordisk A/S, Maaloev, Denmark.Show MeSH
Related in: MedlinePlus
Mentions: The purity and homogeneity of turoctocog alfa allowed crystallisation of the protein. The resulting X-ray crystallographic structure of turoctocog alfa (Fig.4) confirms that the protein has a structure similar to those previously reported for other rFVIII molecules 27,28. The X-ray fluorescence wavelength scan of the turoctocog alfa crystals identified two significant peaks, indicating copper (Cu+) and zinc (Zn2+), respectively 29. The presence of both copper and zinc was supported by colorimetric data, indicating that the ion-binding site in the A1 domain is predominantly populated by zinc, while that in the A3 domain is predominantly populated by copper 29.