Factor VII requires the cleavage of an internal peptide bond and the association with tissue
factor (TF) to attain its fully active factor VIIa (FVIIa) conformation. The former event alone
leaves FVIIa in a zymogen-like state of relatively low specific activity. We have designed a
number of FVIIa mutants with the aim of mimicking the effect of TF, that is, creating molecules
with increased intrinsic (TF-independent) enzymatic activity. Based on a possible structural
difference between free and TF-bound FVIIa (Pike, ACW, Brzozowski, AM, Roberts, SM …