Method for the stabilization of chimeric immunoglobulins or immunoglobulin fragments, and stabilized anti-EGP-2 scFv fragment

A method for stabilizing a chimeric immunoglobulin or immunoglobulin fragment (chimera) that comprises

• i) VH domain antigen-binding loops from a donor immunoglobulin or immunoglobulin fragment (donor) which is able to bind to an antigen, and
• ii) VH domain framework regions from an acceptor immunoglobulin or immunoglobulin fragment (acceptor),
• wherein the VH domains of said donor and of said acceptor belong to different framework structure subgroups,
• and wherein said method comprises the step of
• replacing in the chimera one or more of the residues present at identified framework positions in the acceptor by those present at corresponding positions in the donor,
• wherein different amino acid residues present in said acceptor and said donor at one or more of said identified framework positions lead to the formation of different framework structure subgroups,
• wherein said identified framework positions are selected from the group consisting of H6, H7, H8, H9, H10, H18, H20, H38, H63, H67, H82 and H109 in said VH domains,
• wherein a stabilized antigen-binding immunoglobulin or immunoglobulin fragment is established, and wherein said chimera is able to bind to said antigen.