Method to screen phage display libraries with different ligands

Abstract

The present invention relates to methods for selecting repertoires of polypeptides using generic and target ligands. In particular, the invention relates to a library wherein the folded members have binding sites for both generic and target ligands.

1 . A library wherein the folded members have binding sites for both generic and target ligands.  
     
     
         2 . A library designed for selection with both generic and target ligands.  
     
     
         3 . The library according to  claim 1  or  claim 2  comprising a repertoire of polypeptides of the immunoglobulin superfamily.  
     
     
         4 . The library according to  claim 3  wherein the polypeptides are antibody or T-cell receptor polypeptides.  
     
     
         5 . The library according to  claim 4 , wherein the polypeptides are V H  or V β  domains.  
     
     
         6 . The library according to  claim 4 , wherein the polypeptides are V L  or V α  domains.  
     
     
         7 . The library wherein a repertoire of polypeptides according to  claim 5  and a repertoire of polypeptides according to  claim 6  are contacted with generic ligands and the subsets thereby obtained are then pooled.  
     
     
         8 . The library according to  claim 1 , wherein the polypeptides are varied at random positions.  
     
     
         9 . The library according to  claim 1 , wherein the polypeptides are varied at selected positions.  
     
     
         10 . The library according to  claim 9 , wherein the selected positions are those which form the binding site for the target ligand.  
     
     
         11 . The library according to  claim 10 , wherein the selected positions are a subset of those which form the binding site for the target ligand.  
     
     
         12 . The library wherein a repertoire of polypeptides according to  claim 11  is first contacted with a target ligand in order to isolate a subset of polypeptides specific for the target ligand, the subset of polypeptides then being varied at a further subset of residues in order to modify the function, specificity or affinity of target ligand interaction.  
     
     
         13 . The library according to any one of claims  9 - 12 , wherein the polypeptides are varied at selected positions by incorporating all 20 different amino acids at each position to be varied.  
     
     
         14 . The library according to any one of claims  9 - 12 , wherein the polypeptides are varied at selected positions by incorporating some but not all of the 20 different amino acids at each position to be varied.