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.  
     
     
         2 . The method of  claim 1  wherein said edema comprises cerebral edema.  
     
     
         3 . The method of  claim 1  wherein said mammal is a human further having a neoplastic disease.  
     
     
         4 . The method of  claim 3  wherein said neoplastic disease comprises a brain tumor.  
     
     
         5 . The method of  claim 4  wherein said hVEGF antagonist is administered to said mammal serially or in combination with chemotherapy or radiation therapy.  
     
     
         6 . The method of  claim 1  wherein said mammal is a human further having or having undergone a stroke.  
     
     
         7 . The method of  claim 1  wherein said hVEGF antagonist comprises an anti-hVEGF antibody.  
     
     
         8 . The method of  claim 7  wherein said anti-hVEGF antibody comprises a chimeric antibody.  
     
     
         9 . The method of  claim 7  wherein said anti-hVEGF antibody comprises a humanized antibody.  
     
     
         10 . The method of  claim 7  wherein said antibody comprises a monoclonal antibody.  
     
     
         11 . The method of  claim 1  wherein said hVEGF antagonist comprises a hVEGF receptor fusion protein.  
     
     
         12 . The method of  claim 11  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.  
     
     
         15 . The method of  claim 14  wherein said hVEGF antagonist comprises an anti-hVEGF antibody.  
     
     
         16 . The method of  claim 15  wherein said anti-hVEGF antibody comprises a chimeric antibody.  
     
     
         17 . The method of  claim 15  wherein said anti-hVEGF antibody comprises a humanized antibody.  
     
     
         18 . The method of  claim 15  wherein said antibody comprises a monoclonal antibody.  
     
     
         19 . The method of  claim 14  wherein said hVEGF antagonist comprises a hVEGF receptor fusion protein.  
     
     
         20 . The method of  claim 19  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 . A method of treating a mammal having cerebral edema comprising administering to said mammal an effective amount of hVEGF antagonist.  
     
     
         23 . The method of  claim 22  wherein said hVEGF antagonist comprises an anti-hVEGF antibody.  
     
     
         24 . The method of  claim 23  wherein said anti-hVEGF antibody comprises a chimeric antibody.  
     
     
         25 . The method of  claim 23  wherein said anti-hVEGF antibody comprises a humanized antibody.  
     
     
         26 . The method of  claim 23  wherein said antibody comprises a monoclonal antibody.  
     
     
         27 . The method of  claim 22  wherein said hVEGF antagonist comprises a hVEGF receptor fusion protein.  
     
     
         28 . The method of  claim 27  wherein said hVEGF receptor fusion protein comprises an extracellular domain sequence of a hVEGF receptor fused to an immunoglobulin.  
     
     
         29 . The method of  claim 28  wherein said hVEGF receptor fusion protein comprises a flt-IgG fusion protein.  
     
     
         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 a amount effective to reduce the volume of cerebral edema.  
     
     
         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 scleosis, cardiac arrest, birth asphyxia, glutamate toxicity, encephalopathy, hypoxia, ischemia, or renal dialysis.  
     
     
         32 . The method of  claim 31 , wherein the non-neoplastic condition comprises stroke.  
     
     
         33 . The method of  claim 32 , wherein stroke is ischemic stroke.  
     
     
         34 . The method of  claim 33 , wherein ischemic stroke is thrombotic stroke, embolic stroke, hemodynamic stroke, or lacunar stroke.  
     
     
         35 . The method of  claim 30 , wherein the non-neoplastic condition is head injury.  
     
     
         36 . The method of  claim 30 , wherein said hVEGF antagonist comprises a hVEGF receptor fusion protein.  
     
     
         37 . The method of  claim 36 , wherein said hVEGF receptor fusion protein comprises an extracellular domain sequence of a hVEGF receptor formed to an immunoglobulin.  
     
     
         38 . The method of  claim 37 , wherein the hVEGF receptor fusion protein comprises a flt-IgG fusion protein.