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

A nucleic acid molecule encoding a stabilized 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 in the chimera one or more of the residues present at identified framework positions in the acceptor are replaced by those present at corresponding positions in the donor so that the chimera has increased stability as compared to a chimera wherein the identified framework positions are not replaced, 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, and wherein said chimera is able to bind to said antigen.