Domain structure of recombinant fVIII constructs.

Amino acid numbering refers to mature, full-length human fVIII. The A3, C1, and C2 domains are defined as amino acids 1690-2019, 2020-2172, and 2173-2332, respectively.36 The light chain activation peptide, ap, corresponds to amino acids 1649-1689. The constructs lack the B domain, which is defined as amino acids 741-1648. Stippled regions indicate areas of porcine substitution. Boundaries are defined by amino acids in which porcine and human fVIII differ. Porcine A2, ap, A3, and C2 substitutions correspond to amino acids 484-508, 1649-1687, 1694-2019, and 2181-2321, respectively.