| abstract |
PROBLEM TO BE SOLVED: To provide a factor VIII (FVIII) preparation which requires less frequent administration, that is, an FVIII preparation having a half-life longer than 1.5 to 2 times the half-life limit. The present invention comprises (i) a first polypeptide comprising FVIII fused to or a portion of a first immunoglobulin (Ig) constant region and (ii) a second Ig by an intermediate XTEN sequence. A chimeric protein comprising a D'domain of von Willebrand factor (VWF) fused to the constant region or a part thereof and a second polypeptide containing a VWF protein containing a D3 domain is provided, and the XTEN sequence is less than 288. It contains an amino acid residue and the first polypeptide is linked or associated with the second polypeptide. Certain embodiments include chimeric proteins as described herein, the XTEN sequence in the second polypeptide consisting of an amino acid sequence having a length between 12 and 287 amino acids. [Selection diagram] Fig. 1 |