Clotting Factor-Fc Chimeric Proteins to Treat Hemophilia

1 - 58 . (canceled)

59 . A chimeric protein comprising a first polypeptide and a second polypeptide, wherein the first polypeptide comprises (i) a clotting factor, which is Factor VIII, Factor VIIIa, Factor IX, Factor IXa, Factor VII, or Factor VIIa, and (ii) at least a portion of an immunoglobulin constant region fused to the clotting factor, which is a neonatal Fc Receptor (FcRn) binding partner, and

the second polypeptide comprises at least a portion of an immunoglobulin constant region, which is a FcRn binding partner, without the clotting factor of the first polypeptide and without an immunoglobulin variable domain, and

wherein the first polypeptide and the second polypeptide are linked.

60 . The chimeric protein of claim 59 , wherein the clotting factor is fused to the portion of an immunoglobulin constant region by a linker.

61 . The chimeric protein of claim 60 , wherein the linker comprises about 1 to about 20 amino acids.

62 . The chimeric protein of claim 60 , wherein the linker comprises the sequence (GlyGlySer)n or SEQ ID NO: 31, wherein n is an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10.

63 . The chimeric protein of claim 59 , wherein the portion of an immunoglobulin constant region of the first polypeptide is an Fc fragment.

64 . The chimeric protein of claim 63 , wherein the portion of an immunoglobulin constant region of the second polypeptide is an Fc fragment.

65 . The chimeric protein of claim 63 , wherein the Fc fragment comprises an amino acid sequence having at least 80% identity with the sequence set forth in SEQ ID NO: 3, wherein the amino acid sequence binds to FcRn.

66 . The chimeric protein of claim 64 , wherein the Fc fragment comprises an amino acid sequence having at least 80% identity with the sequence set forth in SEQ ID NO: 3, wherein the amino acid sequence binds to FcRn.

67 . The chimeric protein of claim 59 , wherein the portion of an immunoglobulin constant region of the first polypeptide and the portion of an immunoglobulin constant region of the second polypeptide are identical.

68 . The chimeric protein of claim 59 , wherein the first polypeptide and the second polypeptide are linked covalently or non-covalently.

69 . The chimeric protein of claim 59 , wherein the first polypeptide and the second polypeptide are linked via a disulfide bond.

70 . The chimeric protein of claim 59 , wherein the second polypeptide consists of at least a portion of an immunoglobulin constant region comprising a FcRn binding partner.

71 . The chimeric protein of claim 59 , wherein the clotting factor is full-length Factor VIII or B-domain deleted Factor VIII.

72 . The chimeric protein of claim 59 , wherein the clotting factor is Factor IX or Factor IXa.

73 . The chimeric protein of claim 59 , wherein the clotting factor is Factor VII or Factor VIIa.

74 . A pharmaceutical composition comprising the chimeric protein of claim 59 and a pharmaceutically acceptable carrier.

75 . The composition of claim 74 , which promotes hemostasis.

76 . The composition of claim 75 , which is formulated for administering intravenously, subcutaneously, intra-muscularly, orally, sublingually, buccally, nasally, rectally, vaginally or via a pulmonary route.

77 . The composition of claim 74 , further comprising at least one agent, which is capable of treating a disease or condition.

78 . The composition of claim 77 , wherein the at least one agent is a protein comprising a clotting factor.

79 . A nucleic acid molecule encoding a chimeric protein comprising a first polypeptide and a second polypeptide, the nucleic acid molecule comprising:

(i) a first nucleic acid sequence encoding the first polypeptide, which comprises a clotting factor and at least a portion of an immunoglobulin constant region, which is a neonatal Fc Receptor (FcRn) binding partner, wherein the clotting factor is Factor VIII, Factor VIIIa, Factor IX, Factor IXa, Factor VII, or Factor VIIa; and

(ii) a second nucleic acid sequence encoding the second polypeptide, which comprises at least a portion of an immunoglobulin constant region, which is a FcRn binding partner, wherein the second nucleic acid sequence does not encode the clotting factor.

80 . A vector comprising the nucleic acid molecule of claim 79 .

81 . A host cell comprising the vector of claim 80 .

82 . A method of making a chimeric protein having clotting activity comprising:

a) transfecting a cell comprising the nucleic acid molecule of claim 79 ; and

b) culturing the cell in media under conditions such that the chimeric protein is expressed.

83 . A method of treating a hemostatic disorder in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a chimeric protein, which comprises a first polypeptide and a second polypeptide, wherein the first polypeptide comprises (i) a clotting factor, which is Factor VIII, Factor VIIIa, Factor IX, Factor IXa, Factor VII, or Factor VIIa, and (ii) at least a portion of an immunoglobulin constant region fused to the clotting factor, which is a FcRn binding partner, and

the second polypeptide comprises at least a portion of an immunoglobulin constant region, which is a FcRn binding partner, without the clotting factor of the first polypeptide and without an immunoglobulin variable domain, and

wherein the first polypeptide and the second polypeptide are linked.

84 . The method of claim 83 , wherein the chimeric protein treats an acute bleeding episode in the subject.

85 . The method of claim 84 , wherein the chimeric protein is administered intravenously, subcutaneously, intra-muscularly, orally, sublingually, buccally, nasally, rectally, vaginally or via a pulmonary route.