FACTOR VIII, VILLEBRAND FACTOR OR THEIR COMPLEXES WITH EXTENDED SEMI-PERIOD OF EXISTENCE IN VIVO

摘要

1. Modified von Willebrand factor (VWF), including VWF, fused at the C-terminal portion of its primary translation product to the N-terminal portion of the half-life enhancing polypeptide (HLEP). ! 2. Modified VWF according to claim 1, where the modified VWF has an extended half-life of functional existence compared to a half-life of functional existence of VWF. ! 3. Modified VWF according to claim 2, where the modified VWF has a half-life of functional existence, increased by at least 25% compared with the half-life of the functional existence of VWF. ! 4. Modified VWF according to claim 1, where the modified VWF has an extended half-life as an antigen compared to a half-life as a VWF antigen. ! 5. Modified VWF according to claim 4, where the modified VWF has a half-life as an antigen, increased by at least 25% compared with a half-life as a VWF antigen. ! 6. Modified VWF according to claim 1, where the modified VWF has an increased ratio of actual maximum in vivo concentration to expected compared to the ratio of actual maximum in vivo concentration to expected for VWF. ! 7. Modified VWF according to claim 6, where the modified VWF has a ratio of the actual maximum in vivo concentration to the expected one, increased by at least 10% compared to the ratio of the actual maximum in vivo concentration to the expected one for VWF. ! 8. The modified VWF according to claim 1, wherein the VWF is fused to the N-terminal portion of the HLEP in the C-terminal amino acid of its primary translation product. ! 9. The modified VWF according to claim 1, where the VWF is fused at its C-terminal end