Protein complexes having factor VIII:C activity and production thereof

A DNA composition for transforming a eukaryotic host cell to obtain expression of a recombinant protein complex having human Factor VIII:C activity, wherein said DNA composition comprises:

• a first expression cassette, said first expression cassette comprising a first polynucleotide encoding a first signal sequence capable of directing secretion and a first polypeptide comprising a first region having an amino acid sequence homologous to the A domain of human Factor VIII:C;
• and
• a second expression cassette, said second expression cassette comprising a second polynucleotide encoding a second signal sequence capable of directing secretion and a second polypeptide having an amino acid sequence homologous to the C domain of human Factor VIII:C.

A polypeptide having human Factor VIII:C activity when combined with a polypeptide homologous to human Factor VIII:C Mr 80 K protein, wherein said polypeptide comprises from N-terminal to C-terminal:

• a first region having an amino acid sequence homologous to the A domain of human Factor VIII:C, and
• a second region comprising the N-terminal sequence of the B domain of human Factor VIII:C, a polypeptide spacer of about 3 to 40 peptides which has fewer than 5 sites of N-linked glycosylation, and the C-terminal sequence of the B domain of human Factor VIII:C.