Vascular endothelial cell growth factor antagonists and uses thereof

Abstract

The present invention provides vascular endothelial cell growth factor (VEGF) antagonists and methods of using VEGF antagonists. VEGF antagonists contemplated by the invention include VEGF antibodies and VEGF receptor fusion proteins. Methods of treating edema and stroke using VEGF antagonists are also provided.

1 . A method of treating a mammal having edema comprising administering to said mammal an effective amount of hVEGF antagonist, wherein said hVEGF antagonist comprises an hVEGF receptor fusion protein. 
     
     
         2 . The method of  claim 1  wherein said edema comprises cerebral edema. 
     
     
         3 .- 11 . (canceled) 
     
     
         12 . The method of  claim 1  wherein said hVEGF receptor fusion protein comprises an extracellular domain sequence of a hVEGF receptor fused to an immunoglobulin. 
     
     
         13 . The method of  claim 12  wherein said hVEGF receptor fusion protein comprises a flt-IgG fusion protein. 
     
     
         14 . A method of treating a mammal having or having undergone a stroke, comprising administering to said mammal an effective amount of hVEGF antagonist, wherein said hVEGF antagonist comprises an hVEGF receptor fusion protein. 
     
     
         15 .- 19 . (canceled) 
     
     
         20 . The method of  claim 14  wherein said hVEGF receptor fusion protein comprises an extracellular domain sequence of a hVEGF receptor fused to an immunoglobulin. 
     
     
         21 . The method of  claim 20  wherein said hVEGF receptor fusion protein comprises a flt-IgG fusion protein. 
     
     
         22 .- 29 . (canceled) 
     
     
         30 . A method of reducing cerebral edema due to a non-neoplastic condition in a mammal, comprising administering to said mammal a hVEGF antagonist in an amount effective to reduce the volume of cerebral edema, wherein said hVEGF antagonist comprises an hVEGF receptor fusion protein. 
     
     
         31 . The method of  claim 30 , wherein the non-neoplastic condition comprises head injury, spinal cord injury, acute hypertension, meningitis, encephalitis, abscess, hemorrhage, viral infection, cerebral malaria, radiation, multiple sclerosis, cardiac arrest, birth asphyxia, glutamate toxicity, encephalopathy, hypoxia, ischemia, or renal dialysis. 
     
     
         32 .- 36 . (canceled) 
     
     
         37 . The method of  claim 30 , wherein said hVEGF receptor fusion protein comprises an extracellular domain sequence of a hVEGF receptor fused to an immunoglobulin. 
     
     
         38 . The method of  claim 37 , wherein the hVEGF receptor fusion protein comprises a flt-IgG fusion protein. 
     
     
         39 . The method of  claim 1  wherein the hVEGF receptor fusion protein comprises a truncated form of an hVEGF receptor. 
     
     
         40 . The method of  claim 39  wherein the transmembrane and the cytoplasmic domains of a hVEGF receptor are not present in the truncated form of the hVEGF receptor. 
     
     
         41 . The method of  claim 1  wherein the hVEGF receptor fusion protein comprises a hVEGF receptor or fragment thereof conjugated to a non-hVEGF receptor polymer or polypeptide. 
     
     
         42 . The method of  claim 41  wherein non-hVEGF receptor polymer or polypeptide is an immunoglobulin or fragment thereof. 
     
     
         43 . The method of  claim 42  wherein the fragment of the immunoglobulin comprises an Fv domain, a CH1 domain, a CH2 domain, or a hinge region between the CH1 and CH2 domains. 
     
     
         44 . The method of  claim 43  wherein the Fv domain is located in an extracellular domain of the hVEGF fusion protein. 
     
     
         45 . The method of  claim 43  wherein the N-terminus of the CH1 domain, CH2 domain, or hinge region between the CH1 and CH2 domains is covalently joined to the C-terminus of an extracellular domain of the VEGF receptor fusion protein.