CLOTTING FACTOR-FC CHIMERIC PROTEINS TO TREAT HEMOPHILIA
The invention relates to a chimeric protein comprising at least one clotting factor and at least a portion of an immunoglobulin constant region. The invention relates to a method of treating a hemostatic disorder comprising administering a therapeutically effective amount of a chimeric protein wherein the chimeric protein comprises at least one clotting factor and at least a portion of an immunoglobulin constant region.
1 . A chimeric protein comprising at least a portion of an immunoglobulin constant region, at least one clotting factor, and optionally at least one linker.
2 . The chimeric protein of claim 1 , wherein the portion of an immunoglobulin constant region is a portion of an IgG.
3 . (canceled)
4 . The chimeric protein of claim 2 , wherein the portion of an immunoglobulin constant region is an FcRn binding partner.
5 - 8 . (cancel)
9 . A pharmaceutical composition comprising the chimeric protein of claim, and pharmaceutically acceptable excipient.
10 . The chimeric protein of claim 1 , wherein said chimeric protein is a dimer.
11 - 12 . (cancel)
13 . The chimeric protein of claim 1 , comprising the formula:
X-L-F
wherein F is an Fc fragment of an immunoglobulin, L is a linker or a direct bond, and X is the at least one clotting factor.
14 - 21 . (cancel)
22 . A method of treating a hemostatic disorder comprising administering a therapeutically effective amount of at least one chimeric protein having clotting activity to a subject, wherein said chimeric protein comprises at least a portion of an immunoglobulin and a clotting factor, and allowing the chimeric protein to treat the hemostatic disorder.
23 . The method of claim 22 , wherein the hemostatic disorder is hemophilia A or hemophilia B.
24 - 25 . (cancel)
26 . The method of claim 22 , wherein said portion of an immunoglobulin constant region is an FcRn binding partner.
27 . The method of claim 22 , wherein the chimeric protein is administered intravenously, subcutaneously, intra-muscularly, or via a mucosal surface.
28 - 32 . (cancel)
33 . A method of making a chimeric protein having clotting activity comprising at least a portion of an immunoglobulin constant region and a clotting factor, said method comprising:
a) transfecting a cell with a DNA construct comprising a first DNA sequence encoding at least a portion of an immunoglobulin constant region operatively linked to a second DNA sequence encoding a clotting factor and optionally a third DNA sequence encoding an endoprotease;
b) culturing said cell under conditions such that the chimeric protein is expressed; and
c) isolating said chimeric protein from said cell.
34 - 35 . (cancel)
36 . The method of claim 33 , wherein the cell is a eukaryotie cell.
37 - 40 . (cancel)
41 . The method of claim 33 or 38 , wherein said portion of an immunoglobulin constant region is FcRn binding partner.
42 . (canceled)
43 . A nucleic acid molecule comprising a nucleic acid sequence encoding at least one clotting factor and at least a portion of an immunoglobulin constant region.
44 . A vector comprising the nucleic acid molecule of claim 43 .
45 . (canceled)
46 . The nucleic acid molecule of claim 43 , wherein said portion of an immunoglobulin constant region is an FcRn binding partner.
47 . The nucleic acid molecule of claim 43 , wherein said portion of an immunoglobulin constant region is a portion of an IgG.
48 . (canceled)
49 . A host cell comprising the vector of claim 44 .
50 - 54 . (cancel)
55 . A method of treating a hemostatic disorder comprising administering to a subject a therapeutically effective amount of a first agent to treat a hemostatic disorder, wherein said first agent comprises at least one chimeric protein having clotting activity, and wherein said chimeric protein comprises at least a portion of an immunoglobulin and a clotting factor, in combination with a second agent, wherein said second agent is any agent known to have clotting factor activity and allowing the first and second agent to treat the hemostatic disorder.
56 . (canceled)
57 . The chimeric protein of claim 10 , wherein the chimeric protein is a dimer comprising a first chain and a second chain, wherein said first chain comprises an Fc fragment of an immunoglobulin and Factor VIII, and said second chain comprises an Fc fragment of an immunoglobulin without Factor VIII.
58 . The chimeric protein of claim 10 , wherein the chimeric protein is a dimer comprising a first chain and a second chain, wherein said first chain comprises an Fc fragment of an immunoglobulin and Factor IX, and said second chain comprises an Fc fragment of an immunoglobulin without Factor IX.