Patent ID: 9145552
Filing Date: 2015-09-29
Classification: A61K,A61P,C12N

Abstract:
1. An isolated modified Factor X (FX) polypeptide, comprising amino acid replacements at positions corresponding to positions 196 and 332 in an unmodified FX polypeptide based on mature numbering with reference to amino acid positions set forth in SEQ ID NO:134, wherein: the amino acid replacement at position 196 is a serine (S) or threonine (T); the amino acid replacement at position 332 is selected from among amino acid replacement with alanine (A), aspartic acid (D), glutamic acid (E), serine (S) and glycine (G); the unmodified FX polypeptide has the sequence of amino acids set forth in SEQ ID NO:134, or is the zymogen, active or catalytically active form thereof or has at least 95% sequence identity with the polypeptide whose sequence is set forth in SEQ ID NO:134 or with the zymogen, active or catalytically active form of the polypeptide of SEQ ID NO:134; corresponding amino acid positions are identified by alignment of the unmodified FX polypeptide with the polypeptide set forth in SEQ ID NO:134; the modified FX polypeptide, when in active form, exhibits at least 50-fold increased factor Va (FVa) co-factor dependence, and increased resistance to anti-thrombin III (ATIII) compared to the active form of the unmodified FX polypeptide that is the same as the modified FX polypeptide, but does not contain the amino acid replacement(s); and co-factor dependence is assessed by comparing the ratio of FVa-dependent activity/FVa-independent activity of the modified FX polypeptide to that of the unmodified FX polypeptide not containing the modification(s).