ABSTRACT
Coagulation factor IX (FIX) is a zymogen of a vitamin K-dependent serine protease that plays a critical role in the intrinsic blood-clotting pathway. The protease zymogen undergoes extensive post-translational modifications after synthesis, which is required for the normal biological activity of its enzymatic form, activated FIX. Deficiencies of FIX result in a severe bleeding disorder called hemophilia B. The activation peptide of FIX is separated from the epidermal growth factor 2 domain by a short linker residue of unknown function. The hydrophobic signal sequence is removed following translocation of the nascent FIX polypeptide to the lumen of the Endoplasmic reticulum. The distribution of mutations according to the FIX protein domain structure, infers that mutations have been detected in all of the FIX protein domains. A lyophilized form of recombinant FIX has been formulated that is reconstituted easily in sterile water for injection and which exhibits a high degree of stability.
