The present invention relates to modified nucleic acid sequences coding for coagulation factors preferably coagulation factor VIII and their derivatives, recombinant expression vectors containing such nucleic acid sequences, host cells transformed with such recombinant expression vectors, recombinant polypeptides and derivatives coded for by said nucleic acid sequences which recombinant polypeptides and derivatives do have biological activities and prolonged in vivo half-life compared to the unmodified wild-type protein. The invention also relates to corresponding sequences that result in improved in vitro stability. The present invention further relates to processes for the manufacture of such recombinant proteins and their derivatives are covered. The invention also relates to a transfer vector for use in human gene therapy, which comprises such modified nucleic acid sequences.
