Factor viii compositions and methods
AssigneeUniversity of Maryland, Baltimore
InventorsEvgueni L. SAENKO, Andrey G. Sarafanov, Natalya M. Ananyeva
Life of this patent
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Abstract
The present invention provides methods of increasing the half-life and/or specific activity of factor VIII. More specifically, the invention provides methods of increasing the half-life and/or specific activity of factor VIII by substituting one or more amino acids in the A2 domain. It further provides methods for producing such factor VIII mutants. The invention also provides polynucleotides encoding the mutant factor VIII, and methods of treating hemophilia using the polypeptides and polynucleotides of the invention.
Claims13
1-4. (canceled)
An isolated polynucleotide encoding a mutant factor VIII comprising the amino acid sequence of SEQ ID NO:5, further comprising an amino acid substitution at position Lys(466) and/or position Arg(471) and optionally at one or more positions selected from the group consisting of Lys(380), Arg(484), Tyr(487), Ser(488), Arg(489), Arg(490), His(497), His(499), Lys(523), and Lys(556).
6-10. (canceled)
An isolated polynucleotide encoding a mutant factor VIII comprising the amino acid sequence of SEQ ID NO:5, further comprising an amino acid substitution at position Lys(466) and/or position Arg(471) and optionally at one or more positions selected from the group consisting of Lys(380), Arg(484), Tyr(487), Ser(488), Arg(489), Arg(490), His(497), His(499), Lys(523), and Lys(556), further comprising an amino acid substitution at one or more additional positions in the A2 domain.
12-16. (canceled)
A polynucleotide encoding a mutant factor VIII comprising the amino acid sequence of SEQ ID NO:5, further comprising a substitution at one or more positions selected from the group consisting of Lys(377), His(378), and Lys(466), and optionally at one or more positions selected from the group consisting of Lys (380), Ser(488), Arg(489), Arg(490), Leu(491), Lys(493), Lys(496), His(497), His(499), Lys(512), Lys(523), and Lys(556).
18-22. (canceled)
A polynucleotide encoding a mutant factor VIII comprising the amino acid sequence of SEQ ID NO:5, further comprising a substitution at one or more positions selected from the group consisting of Lys(377), His(378), and Lys(466), and optionally at one or more positions selected from the group consisting of Lys(380), Ser(488), Arg(489), Arg(490), Leu(491), Lys(493), Lys(496), His(497), His(499), Lys(512), Lys(523), and Lys(556), further comprising the amino acid substitution at one or more additional positions in the A2 domain.
24-32. (canceled)
Dependencies are inferred from the claim text.