COMPOSITIONS AND METHODS FOR ENHANCING COAGULATION FACTOR VIII FUNCTION
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Abstract
Factor VIII variants and methods of use thereof are disclosed.
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25 Claims
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1-12. -12. (canceled)
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13. An isolated recombinant nucleic acid encoding a FVIII variant having a modified PACE/furinsleavage site and a B domain deletion (BDD) for modulating hemostasis, said human PACE/furin cleavage site consisting of amino acids RHQR, said FVIII variant being a human variant selected from the group consisting essentially of:
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i) a FVIII variant with said BDD and wherein R is substituted with an H in the PACE/furin cleavage site; ii) a FVIII variant with said BDD and wherein S is substituted with an H in the PACE/furin cleavage site; iii) a FVIII variant with said BDD and wherein one amino acid at said PACE/furin cleavage site is deleted; iv) a FVIII variant with said BDD and wherein R at said cleavage site is substituted with an amino acid selected from the group consisting of a serine, lysine, methionine, cysteine, proline and tyrosine; and v) a FVIII variant wherein one or more amino acids at said PACE/furin cleavage site and a B domain are deleted, each of i), ii), iii), iv) and v) exhibiting increased specific activity and stability relative to human FVIII-BDD lacking said substitution and deletions. - View Dependent Claims (14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25)
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Specification