Vascular endothelial growth factor 2

Abstract

Disclosed are human VEGF-2 polypeptides, biologically active, diagnostically or therapeutically useful fragments, analogs, or derivatives thereof, and DNA(RNA) encoding such VEGF-2 polypeptides. Also provided are procedures for producing such polypeptides by recombinant techniques and antibodies and antagonists against such polypeptides. Such polypeptides and polynucleotides may be used therapeutically for stimulating wound healing and for vascular tissue repair. Also provided are methods of using the antibodies and antagonists to inhibit tumor angiogenesis and thus tumor growth, inflammation, diabetic retinopathy, rheumatoid arthritis, and psoriasis.

What is claimed is:  
     
         1 . An isolated polynucleotide comprising a nucleic acid sequence at least 95% identical to a polynucleotide which encodes a polypeptide selected from the group consisting of: 
 (a) a N-terminal deletion fragment described by the general formula m−396 of SEQ ID NO:2;    (b) a C-terminal deletion fragment described by the general formula −23−n of SEQ ID NO:2;    (c) a N-terminal and C-terminal deletion fragment described by the general formula m−n of SEQ ID NO:2; and    (d) a C-terminal deletion fragment described by the general formula +9−n of SEQ ID NO:2.    
     
     
         2 . The isolated polynucleotide of  claim 1 , wherein said polypeptide comprises amino acid residues S-205 to S-396 of SEQ ID NO:2 and/or amino acid residues F-9 to R-203 of SEQ ID NO:2.  
     
     
         3 . A composition comprising the isolated polynucleotide of  claim 1 .  
     
     
         4 . The isolated polynucleotide of  claim 1 , wherein the polynucleotide encodes a biologically active fragment of VEGF-2.  
     
     
         5 . The isolated polynucleotide of  claim 1 , wherein the polynucleotide encodes a polypeptide which binds an antibody for VEGF-2.  
     
     
         6 . The polynucleotide of  claim 1  further comprising a polynucleotide which encodes a heterologous polypeptide.  
     
     
         7 . A vector comprising the polynucleotide of  claim 1 .  
     
     
         8 . The vector of  claim 7 , wherein said polynucleotide is operatively associated with a heterologous regulatory sequence.  
     
     
         9 . A host cell comprising the vector of  claim 7  or the polynucleotide of  claim 1 .  
     
     
         10 . A method for producing a VEGF-2 polypeptide, comprising: 
 (a) culturing the host cell of  claim 9  under conditions suitable to produce the polypeptide; and    (b) recovering the polypeptide from the cell culture.    
     
     
         11 . The polypeptide produced by the method of  claim 10 .  
     
     
         12 . An isolated polypeptide comprising polypeptide at least 95% identical to an amino acid sequence selected from the group consisting of: 
 (a) a N-terminal deletion fragment described by the general formula m−396 of SEQ ID NO:2;    (b) a C-terminal deletion fragment described by the general formula −23−n of SEQ ID NO:2;    (c) a N-terminal and C-terminal deletion fragment described by the general formula m−n of SEQ ID NO:2; and    (d) a C-terminal deletion fragment described by the general formula +9−n of SEQ ID NO:2.    
     
     
         13 . The isolated polypeptide of  claim 12 , wherein said polypeptide comprises amino acid residues S-205 to S-396 of SEQ ID NO:2 and/or amino acid residues F-9 to R-203 of SEQ ID NO:2.  
     
     
         14 . A composition comprising the isolated polypeptide of  claim 1 .  
     
     
         15 . A composition comprising a first polypeptide fragment comprising amino acids residues S-205 to S-396 of SEQ ID NO:2 and a second polypeptide fragment comprising amino acid residues F-9 to R-203 of SEQ ID NO:2.  
     
     
         16 . The isolated polypeptide of  claim 12 , wherein the polypeptide is a biologically active fragment.  
     
     
         17 . The isolated polypeptide of  claim 12 , wherein the polypeptide is antigenic.  
     
     
         18 . The isolated polypeptide of  claim 12 , further comprising a heterologous polypeptide.  
     
     
         19 . An antibody to the polypeptide of  claim 12 .  
     
     
         20 . A compound which activates the polypeptide of  claim 12 .  
     
     
         21 . A compound which inhibits the polypeptide of  claim 12 .  
     
     
         22 . A method for preventing, treating, or ameliorating a medical condition which comprises administering to a mammalian subject a therapeutically effective amount of the polypeptide of claims  12 - 13 , the composition of claims  3 ,  14 - 15 , or of the polynucleotide of claim  1 - 2 .  
     
     
         23 . A method of diagnosing a pathological condition or a susceptibility to a pathological condition in a subject related to expression or activity of a secreted protein comprising: 
 (a) determining the presence or absence of a mutation in the polynucleotide of  claim 1;     (b) diagnosing a pathological condition or a susceptibility to a pathological condition based on the presence or absence of said mutation.    
     
     
         24 . A method of diagnosing a pathological condition or a susceptibility to a pathological condition in a subject related to expression or activity of a secreted protein comprising: 
 (a) determining the presence or amount of expression of the polypeptide of  claim 12  in a biological sample;    (b) diagnosing a pathological condition or a susceptibility to a pathological condition based on the presence or amount of expression of the polypeptide.    
     
     
         25 . A method for identifying binding partner to the polypeptide of  claim 10  comprising: 
 (a) contacting the polypeptide of  claim 12  with a binding partner; and  
 (b) determining whether the binding partner effects an activity of the polypeptide.  
 
     
     
         26 . A method of identifying an activity in a biological assay, wherein the method comprises: 
 (a) expressing the polypeptide of  claim 12  in a cell;    (b) isolating the supernatant;    (c) detecting an activity in a biological assay; and    (d) identifying the protein in the supernatant having the activity.