Vascular endothelial growth factor 2

Abstract

Disclosed are human VEGF-2 antibodies, antibody fragments, or variants thereof. Also provided are processes for producing such antibodies. The present invention relates to methods and compositions for preventing, treating or ameliorating a disease or disorder comprising administering to an animal, preferably a human, an effective amount of one or more VEGF-2 antibodies or fragments or variants thereof.

1 - 133 . (canceled) 
     
     
         134 . A method of treating corneal neovascularization in a human subject, comprising administering to the eye of the human subject an effective amount of an isolated antibody or antigen binding fragment thereof that specifically binds to a human VEGF-2 polypeptide. 
     
     
         135 . The method of  claim 134 , wherein the administering results in inhibition of the formation of new blood vessels in the human subject. 
     
     
         136 . The method of  claim 134 , wherein the corneal neovascularization is associated with a corneal infection, an immunological process, alkali burns, trauma, inflammation, toxic states, nutritional deficiency states, or a complication of wearing contact lenses. 
     
     
         137 . The method of  claim 136 , wherein the corneal infection is trachoma, herpes simplex keratitis, leishmaniasis, or onchocerciasis. 
     
     
         138 . The method of  claim 136 , wherein the immunological process is corneal graft rejection or Stevens-Johnson's syndrome. 
     
     
         139 . The method of  claim 134 , wherein the isolated antibody or antigen binding fragment thereof is administered at a dosage of 0.1 mg/kg to 100 mg/kg of the human's body weight. 
     
     
         140 . The method of  claim 134 , wherein the isolated antibody or antigen binding fragment thereof is administered at a dosage of 0.1 mg/kg to 20 mg/kg of the human's body weight. 
     
     
         141 . The method of  claim 134 , wherein the isolated antibody or antigen binding fragment thereof is administered at a dosage of 0.1 mg/kg to 10 mg/kg of the human's body weight. 
     
     
         142 . The method of  claim 134 , wherein the isolated antibody is a monoclonal antibody. 
     
     
         143 . The method of  claim 134 , wherein the isolated antibody is a human antibody or humanized antibody. 
     
     
         144 . The method of  claim 134 , wherein the antigen binding fragment is Fab, Fab′, F(ab′) 2 , Fv, single-chain Fv, or disulfide-linked Fv. 
     
     
         145 . The method of  claim 134 , wherein the isolated antibody or antigen binding fragment thereof binds to a VEGF-2 polypeptide selected from the group consisting of:
 (a) a VEGF-2 polypeptide comprising amino acids 1-419 of SEQ ID NO:18;   (b) a VEGF-2 polypeptide comprising amino acids 32-419 of SEQ ID NO:18;   (c) a VEGF-2 polypeptide comprising amino acids 103-227 of SEQ ID NO:18;   (d) a VEGF-2 polypeptide comprising amino acids 112-227 of SEQ ID NO:18;   (e) a dimeric VEGF-2 polypeptide consisting of two polypeptides each consisting of amino acids 103-227 of SEQ ID NO:18;   (f) a dimeric VEGF-2 polypeptide consisting of two polypeptides each consisting of amino acids 112-227 of SEQ ID NO:18;   (g) the amino acid sequence of the full-length VEGF-2 polypeptide encoded by cDNA contained in ATCC Deposit Number 97149;   (h) the amino acid sequence of the pro-protein VEGF-2 polypeptide encoded by cDNA contained in ATCC Deposit Number 97149;   (i) the amino acid sequence of the secreted VEGF-2 polypeptide encoded by cDNA contained in ATCC Deposit Number 97149;   (j) the amino acid sequence of the full-length VEGF-2 polypeptide encoded by cDNA contained in ATCC Deposit Number 75698;   (k) the amino acid sequence of the pro-protein VEGF-2 polypeptide encoded by cDNA contained in ATCC Deposit Number 75698;   (l) the amino acid sequence of the secreted VEGF-2 polypeptide encoded by cDNA contained in ATCC Deposit Number 75698; and   (m) the amino acid sequence of the secreted form of the VEGF-2 polypeptide of SEQ ID NO:18.   
     
     
         146 . The method of  claim 134 , wherein the isolated antibody or antigen binding fragment thereof is administered to the cornea of the human subject. 
     
     
         147 . The method of  claim 134 , wherein the isolated antibody or antigen binding fragment thereof is administered in a composition comprising saline. 
     
     
         148 . The method of  claim 134 , wherein the isolated antibody or antigen binding fragment thereof is administered topically to the eye of the human subject. 
     
     
         149 . The method of  claim 134 , wherein the isolated antibody or antigen binding fragment thereof is administered to the eye of the human subject by injection. 
     
     
         150 . The method of  claim 134 , wherein the isolated antibody or antigen binding fragment thereof is administered to the eye of the human subject by injection into the corneal stroma. 
     
     
         151 . The method of  claim 134 , wherein the isolated antibody or antigen binding fragment thereof is administered to the eye of the human subject by perilimbic corneal injection. 
     
     
         152 . The method of  claim 134 , wherein the isolated antibody or antigen binding fragment thereof is administered to the eye of the human subject by a sustained-release form injection. 
     
     
         153 . The method of  claim 134 , wherein the isolated antibody or antigen binding fragment thereof is administered to the eye of the human subject in eye drop form. 
     
     
         154 . The method of  claim 134 , wherein the isolated antibody or antigen binding fragment thereof is administered to the eye of the human subject in a composition comprising a muco-adhesive polymer which binds to cornea. 
     
     
         155 . The method of  claim 134 , wherein the isolated antibody or antigen binding fragment thereof is administered to the eye of the human subject between the region of abnormal neovascularization of the eye and the cornea. 
     
     
         156 . The method of  claim 134 , wherein the isolated antibody or antigen binding fragment thereof is administered with a steroid.