Polymer von Willebrand factor-conjugates

摘要

The present invention relates to a proteinaceous construct (also designated as polymer-VWF-conjugate) comprising plasmatic and/or recombinant von Willebrand factor (VWF), said VWF being bound to at least one physiologically acceptable polymer molecule, as well as to a complex between said proteinaceous construct and at least one factor VIII (FVIII) protein. The physiologically acceptable polymer molecule can be, for instance, polyethylene glycol (PEG) or polysialic acid (PSA). Further the present invention relates to methods for prolonging the in vivo-half-life of VWF or FVIII in the blood of a mammal having a bleeding disorder associated with functional defects of or deficiencies of at least one of FVIII or VWF.

主权项

1. A proteinaceous molecule comprising:
(a) a VWF molecule selected from the group consisting of plasmatic von Willebrand factor (VWF), recombinant VWF, a precursor, subunit or fragment of VWF having a biological activity of VWF as determined in a ristocetin cofactor assay or a collagen binding assay, and dimers and multimers thereof; and (b) at least one physiologically acceptable polymer molecule bound to said VWF molecule;said proteinaceous molecule having the capability of binding at least one factor VIII (FVIII) molecule, wherein the in vivo half-life of said proteinaceous molecule is increased as compared to the in vivo half-life of a VWF molecule,and the in vivo half-life of said FVIII molecule bound to said proteinaceous molecule is increased as compared to the in vivo half-life of a FVIII molecule bound to VWF not linked to at least one physiologically acceptable polymer molecule.