Method for engineering immunoglobulins

Abstract

The present invention relates to a method for engineering an immunoglobulin comprising a variable domain and at least one modification in at least two structural loops of said immunoglobulin and determining the binding of said immunoglobulin to an epitope of an antigen, wherein the unmodified immunoglobulin does not significantly bind to said epitope, comprising the steps of: providing a nucleic acid encoding an immunoglobulin comprising at least two structural loops, modifying at least one nucleotide residue of each of said structural loops, transferring said modified nucleic acid in an expression System, expressing said modified immunoglobulin, contacting the expressed modified immunoglobulin with an epitope, and determining whether said modified immunoglobulin binds to said epitope, immunoglobulins produced by such a method and libraries of immunoglobulins.

What is claimed is: 
     
         1 . A polypeptide scaffold comprising an immunoglobulin fold of a human antibody Constant domain, wherein the structural loops of said human antibody constant domain are connected by beta strands, wherein at least two of said structural loops (i) comprise at least one amino acid selected from the group consisting of tryptophan, tyrosine, phenylalanine, histidine, isoleucine, serine, methionine, alanine and asparagine, and (ii) form a solvent accessible surface.