C4BP join activity is insufficient, but the protein S deficiency mutant which possesses APC assistant factor activity, the constituent and cure

摘要

The present invention relates to various functional variants of recombinant protein S (PS) that do not significantly bind C4b binding protein (C4BP) and uses of the variants as a therapeutic reagent. In particular the invention is directed at deletion mutants of protein S, having cofactor activity toward APC and lacking at least the two postulated C4BP binding domains of the SHBG-like domain of the corresponding mature wild type protein S. Such a deletion mutant in particular lacks at least amino acid residues 401-457 and 583-635 of the corresponding mature wild type human protein S.