Factor VII or VIIa polypeptide variants with N-glycosylation

摘要

A factor VII or Factor VIIa polypeptide variant having an amino acid sequence comprising 3-15 amino acid modifications relative to human Factor VII or human Factor VIIa having the amino acid sequence shown in SEQ ID NO:2. The amino acid sequence of the variant comprises the amino acid substitutions P10Q and K32E and a sugar moiety is covalently attached to an introduced in vivo N-glycosylation site located outside the Gla domain and is introduced by at least one substitution selected from the group consisting of A51N, G58N, T106N, K109N, G124N, K143+N145T, A175T, I205T, V253N, T267N, T267N+S269T, S314N+K316S, S314N+K316T, R315N+V317S, R315N+V317T, K316N+G318S, K316N+G318T, G318N and D334N. Also described are nucleotide sequences encoding the factor VII or Factor VIIa polypeptide variants, expression vectors comprising the nucleotide sequences, host cells comprising the nucleotide sequences and use of the variants in a medicament for the treatment of a disease or disorder where clot formation is desirable.