Abstract: The present invention relates to an improved method for the production of recombinant human blood clotting factors, in particular of factor VIII and factor IX. An immortalized human cell line can be used to stably express viral transcription activator proteins and carrying a vector having a promoter functionally linked to a DNA sequence coding for a blood coagulating factor, provided that said promoter is not a viral promoter which is stimulated by said viral transcription activator proteins. The invention further relates to an immortalized human cell line carrying said vector, factor VIII muteins particularly suitable for the above production method; pharmaceutical compositions comprising such factor VIII muteins, and the use of such factor VIII muteins for preparing a medicament for treating hemophilia.