Patent ID: 7211558
Filing Date: 2007-05-01
Classification: A61K,C07K

Abstract:
1. An isolated nucleic acid sequence which encodes a biologically active recombinant human factor VIII (FVIII) variant, wherein said FVIII variant comprises two segments connected by at least one PACE-furin cleavage site, wherein said segments are selected from the group consisting of: a) a first segment consisting of the sequence of amino acids 1 to 700 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1690 to 2332 of SEQ ID NO: 2; b) a first segment consisting of the sequence of amino acids 1 to 710 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1690 to 2332 of SEQ ID NO: 2; c) a first segment consisting of the sequence of amino acids 1 to 720 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1690 to 2332 of SEQ ID NO: 2; d) a first segment consisting of the sequence of amino acids 1 to 730 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1690 to 2332 of SEQ ID NO: 2; e) a first segment consisting of the sequence of amino acids 1 to 740 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1700 to 2332 of SEQ ID NO: 2; f) a first segment consisting of the sequence of amino acids 1 to 740 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1710 to 2332 of SEQ ID NO: 2; g) a first segment consisting of the sequence of amino acids 1 to 740 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1720 to 2332 of SEQ ID NO: 2; h) a first segment consisting of the sequence of amino acids 1 to 740 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1730 to 2332 of SEQ ID NO: 2; i) a first segment consisting of the sequence of amino acids 1 to 730 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1700 to 2332 of SEQ ID NO: 2; j) a first segment consisting of the sequence of amino acids 1 to 730 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1710 to 2332 of SEQ ID NO: 2; k) a first segment consisting of the sequence of amino acids 1 to 730 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1720 to 2332 of SEQ ID NO: 2; l) a first segment consisting of the sequence of amino acids 1 to 730 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1730 to 2332 of SEQ ID NO: 2; m) a first segment consisting of the sequence of amino acids 1 to 720 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1700 to 2332 of SEQ ID NO: 2; n) a first segment consisting of the sequence of amino acids 1 to 720 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1710 to 2332 of SEQ ID NO: 2; o) a first segment consisting of the sequence of amino acids 1 to 720 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1720 to 2332 of SEQ ID NO: 2; p) a first segment consisting of the sequence of amino acids 1 to720 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1730 to 2332 of SEQ ID NO: 2; q) a first segment consisting of the sequence of amino acids 1 to 710 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1700 to 2332 of SEQ ID NO: 2; r) a first segment consisting of the sequence of amino acids 1 to 710 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1710 to 2332 of SEQ ID NO: 2; s) a first segment consisting of the sequence of amino acids 1 to 710 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1720 to 2332 of SEQ ID NO: 2; t) a first segment consisting of the sequence of amino acids 1 to 710 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1730 to 2332 of SEQ ID NO: 2; u) a first segment consisting of the sequence of amino acids 1 to 700 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1700 to 2332 of SEQ ID NO: 2; v) a first segment consisting of the sequence of amino acids 1 to 700 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1710 to 2332 of SEQ ID NO: 2; w) a first segment consisting of the sequence of amino acids 1 to 700 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1720 to 2332 of SEQ ID NO: 2; and x) a first segment consisting of the sequence of amino acids 1 to 700 of SEQ ID NO: 2 and a second segment consisting of the sequence of amino acids 1730 to 2332 of SEQ ID NO: 2; wherein said FVIII variant lacks amino acids 1648 to 1689 of SEQ ID NO: 2 ; and wherein said variant has FVIII activity.