TIE-2 ligands, methods of making and uses thereof

Abstract

The present invention provides for an isolated nucleic acid molecule encoding a human TIE-2 ligand. In addition, the invention provides for a receptor body which specifically binds a human TIE-2 ligand. The invention also provides an antibody which specifically binds a human TIE-2 ligand. The invention further provides for an antagonist of human TIE-2. The invention also provides for therapeutic compositions as well as a method of blocking blood vessel growth, a method of promoting neovascularization, a method of promoting the growth or differentiation of a cell expressing the TIE-2 receptor, a method of blocking the growth or differentiation of a cell expressing the TIE-2 receptor and a method of attenuating or preventing tumor growth in a human.

What is claimed is:  
     
         1 . An isolated and purified nucleic acid molecule comprising a nucleic acid sequence encoding a human TIE-2 ligand, wherein the nucleic acid sequence is selected from the group consisting of: 
 (a) the nucleic acid sequence comprising the coding region of the human TIE-2 ligand as set forth in FIG. 6;    (b) a nucleic acid sequence that hybridizes under moderately stringent conditions to the nucleic acid sequence of (a) and which encodes a TIE-2 ligand that binds TIE-2 receptor; and    (c) a nucleic acid sequence that is degenerate as a result of the genetic code to a nucleic acid sequence of (a) or (b), and which encodes a TIE-2 ligand that binds TIE-2 receptor.    
     
     
         2 . Isolated and purified human TIE-2 ligand encoded by the nucleic acid molecule of  claim 1 .  
     
     
         3 . A vector which comprises the isolated nucleic acid molecule of  claim 1 .  
     
     
         4 . An expression vector comprising a DNA molecule of  claim 1 , wherein the DNA molecule is operatively linked to an expression control sequence.  
     
     
         5 . A host-vector system for the production of a human TIE-2 ligand which comprises the vector of  claim 4 , in a suitable host cell.  
     
     
         6 . The host-vector system of  claim 5 , wherein the suitable host cell is a bacterial cell, yeast cell, insect cell, or mammalian cell.  
     
     
         7 . A method of producing a TIE-2 ligand which comprises growing cells of the host-vector system of  claim 5 , under conditions permitting production of the polypeptide and recovering the polypeptide so produced.  
     
     
         8 . A therapeutic composition comprising a ligand of  claim 2 , and a pharmaceutically acceptable carrier.  
     
     
         9 . A method of blocking blood vessel growth in a human comprising administering an effective amount of the therapeutic composition of  claim 8 .  
     
     
         10 . An antibody which specifically binds the ligand of  claim 2 .  
     
     
         11 . A monoclonal antibody of  claim 10 .  
     
     
         12 . A method of purifying human TIE-2 ligand comprising: 
 a) coupling at least one TIE-2 ligand binding substrate to a solid matrix;    b) incubating the substrate of a) with a cell lysate so that the substrate forms a complex with any human TIE-2 ligand in the cell lysate;    c) washing the solid matrix; and    d) eluting the human TIE-2 ligand from the coupled substrate.    
     
     
         13 . The method of  claim 12 , wherein the substrate is selected from the group consisting of anti-TIE-2 ligand antibody, TIE-2 receptor and TIE-2 receptorbody.  
     
     
         14 . A receptorbody which specifically binds the ligand of  claim 2 .  
     
     
         15 . A therapeutic composition comprising a receptorbody of  claim 14 , in a pharmaceutically acceptable vehicle.  
     
     
         16 . A method of blocking blood vessel growth in a human comprising administering an effective amount of the composition of  claim 15 .  
     
     
         17 . A method of inhibiting TIE-2 ligand activity in a mammal comprising administering to the mammal an effective amount of a TIE-2 antagonist.  
     
     
         18 . The method of  claim 17 , wherein the antagonist is an antibody capable of specifically binding TIE-2 ligand.  
     
     
         19 . The method of  claim 17 , wherein the antagonist is an antibody capable of specifically binding TIE-2 receptor.  
     
     
         20 . The method of  claim 17 , wherein the antagonist is a TIE-2 receptorbody.  
     
     
         21 . A method of inhibiting TIE-2 ligand activity in a mammal comprising administering to the mammal an effective amount of the ligand of  claim 2 .  
     
     
         22 . The method of  claim 17 , wherein the mammal is a human.  
     
     
         23 . The method of  claim 17 , used to attenuate or prevent tumor growth in a human.