PHARMACEUTICAL PREPARATION CONTAINING ONE OR SEVERAL FACTOR VIII-DERIVED PEPTIDES HAVING EFFECT OF IMPROVING BLOOD CLOTTING DISORDER BECAUSE PEPTIDES ARE INFUSED WITH OR CHEMICALLY BOUND TO MORE LARGER PLASMA PROTEINS HAVING ENHANCED PLASMA HALF LIFE, PREFERABLY ALBUMIN

摘要

PURPOSE: A pharmaceutical preparation containing one or several factor VIII-derived peptides which increase the plasma half life of factor VIII is provided. The peptides are infused with or chemically bound to larger plasma proteins having enhanced plasma half life, preferably albumin, thereby improving a blood clotting disorder. Also are provided the peptides, their DNA-sequences, their recombinant expression as albumin fusion proteins and vectors containing the DNA-sequences as well as host cells for the recombinant expression vectors and the use of such DNA-sequences in a transfer vector for gene therapy. CONSTITUTION: The pharmaceutical preparation for the improved treatment of blood-clotting disorders contains: peptides including one or several binding sites for low-density lipoprotein receptor-related protein(LRP) of heparan sulfate proteoglycans(HSPG) and/or human factor VIII sequence; and wild-type factor VIII and mutants of factor VIII coagulation activity. The peptide contains amino acid 558 and/or 484 to 509 of A2 subunit of human factor VIII. The albumin-infused proteins contain a thrombin cleavage site between human albumin amino acid sequence and human factor VIII sequence.