Compositions and methods for modulating factor viii function

3:

• The FVIII variant of claim 1, wherein the B-domain is replaced with an amino acid sequence comprising SEQ ID NO:
• 18.

4:

• The FVIII variant of claim 1, wherein said B domain consists of amino acids 741-1648 of SEQ ID NO:
• 1.

5:

• The FVIII variant of claim 1, further comprising a substitution mutation of the Lys at position 659, the Asp at position 560, the Gln at position 561, the Asp at position 712, and/or the Lys at position 713.

6:

• A Factor VIII (FVIII) variant comprising a substitution mutation of the Lys at position 659, the Asp at position 560, the Gln at position 561, the Asp at position 712, and/or the Lys at position 713.

7:

• The FVIII variant of claim 6, wherein the Lys at position 659 is substituted with another amino acid.

9-11. (canceled)

12:

• The FVIII variant of claim 7, wherein the Asp at position 560 is substituted with Ala, Val, Ile, Leu, His, Arg, or Lys;
• or wherein the Asp at position 560 is substituted with Ile or His.

(canceled)

14:

• The FVIII variant of claim 7, wherein the Gln at position 561 is substituted with Asp or Glu;
• or wherein the Gln at position 561 is substituted with Asp.

(canceled)

16:

• The FVIII variant of claim 7, wherein the Asp at position 712 is substituted with Ala, Val, Ile, or Leu;
• or wherein the Asp at position 712 is substituted with Leu.

(canceled)

18:

• The FVIII variant of claim 7, wherein the Lys at position 713 is substituted with Arg, Met, Tyr, Asp, Cys, or Gly;
• or wherein the Lys at position 713 is substituted with Gly.

(canceled)

20:

• The FVIII variant of claim 1, wherein said FVIII comprises amino acids 1-740 and 1649-2332 of SEQ ID NO:
• 1.

21:

• A composition comprising at least one FVIII variant of claim 1 and at least one pharmaceutically acceptable carrier.

22:

• A method for treatment of a hemostasis related disorder in a patient in need thereof comprising administration of a therapeutically effective amount of the FVIII variant of claim 1 in a pharmaceutically acceptable carrier.

23:

• The method of claim 22, wherein said hemostasis related disorder is hemophilia A.

24:

• An isolated nucleic acid molecule encoding the FVIII variant of claim 1, optionally wherein said FVIII variant comprises a signal peptide.

(canceled)

26:

• An expression vector comprising the nucleic acid molecule of claim 24 operably linked to a regulatory sequence, optionally wherein the vector is selected from the group consisting of an adenoviral vector, an adenovirus-associated vector, a retroviral vector, a plasmid, and a lentiviral vector.

(canceled)

28:

• A host cell comprising the vector of claim 26, optionally wherein said host cells are human cells.

(canceled)

30:

• A method for treatment of a hemostasis related disorder in a patient in need thereof comprising administration of a therapeutically effective amount of the vector of claim 26 in a pharmaceutically acceptable carrier.

31:

• The activated form of the FVIII variant of claim 1.