Modified Chimeric Polypeptides with Improved Pharmacokinetic Properties
Modified chimeric polypeptides with improved pharmacokinetics are disclosed. Specifically, modified chimeric Flt1 receptor polypeptides that have been modified in such a way as to improve their pharmacokinetic profile are disclosed. Also disclosed are methods of making and using the modified polypeptides including but not limited to using the modified polypeptides to decrease or inhibit plasma leakage and/or vascular permeability in a mammal.
1 - 51 . (canceled)
52 . A chimeric polypeptide consisting essentially of the amino acid sequence of Ig-like domain 2 of an extracellular domain of a first VEGF receptor and the amino acid sequence of Ig-like domain 3 of an extracellular domain of a second VEGF receptor operably linked to an immunoglobulin domain.
53 . The chimeric polypeptide of claim 52 , wherein one Ig-like domain is from flt-1 and one Ig-like domain is from KDR.
54 . The chimeric polypeptide of claim 52 , wherein the Ig-like domain 2 is from flt-1.
55 . The chimeric polypeptide of claim 53 , wherein the Ig-like domain 2 is from flt-1.
56 . The chimeric polypeptide of claim 52 , wherein the Ig-like domain 3 is from KDR.
57 . The chimeric polypeptide of claim 53 , wherein the Ig-like domain 3 is from KDR.
58 . The chimeric polypeptide of claim 52 , wherein the Ig-like domain 2 is from flt-1 and the Ig-like domain 3 is from KDR.
59 . The chimeric polypeptide of claim 52 , wherein the immunoglobulin domain is a heavy chain of IgG.
60 . The chimeric polypeptide of claim 53 , wherein the immunoglobulin domain is a heavy chain of IgG.
61 . The chimeric polypeptide of claim 54 , wherein the immunoglobulin domain is a heavy chain of IgG.
62 . The chimeric polypeptide of claim 55 , wherein the immunoglobulin domain is a heavy chain of IgG.
63 . The chimeric polypeptide of claim 56 , wherein the immunoglobulin domain is a heavy chain of IgG.
64 . The chimeric polypeptide of claim 57 , wherein the immunoglobulin domain is a heavy chain of IgG.
65 . The chimeric polypeptide of claim 58 , wherein the immunoglobulin domain is a heavy chain of IgG.
66 . The chimeric polypeptide of claim 52 , wherein the immunoglobulin domain is the Fc domain of IgG.
67 . The chimeric polypeptide of claim 53 , wherein the immunoglobulin domain is the Fc domain of IgG.
68 . The chimeric polypeptide of claim 54 , wherein the immunoglobulin domain is the Fc domain of IgG.
69 . The chimeric polypeptide of claim 55 , wherein the immunoglobulin domain is the Fc domain of IgG.
70 . The chimeric polypeptide of claim 56 , wherein the immunoglobulin domain is the Fc domain of IgG.
71 . The chimeric polypeptide of claim 57 , wherein the immunoglobulin domain is the Fc domain of IgG.
72 . The chimeric polypeptide of claim 58 , wherein the immunoglobulin domain is the Fc domain of IgG.