The invention relates to artificial modified proteins, preferably fusion
proteins, having a reduced immunogenicity compared to the parent
non-modified molecule when exposed to a species in vivo. The invention
relates, above all, to novel immunoglobulin fusion proteins which
essentially consist of an immunoglobulin molecule or a fragment thereof
covalently fused via its C-terminus to the N-terminus of a biologically
active non-immunoglobulin molecule, preferably a polypeptide or protein
or a biologically active fragment thereof. In a specific embodiment, the
invention relates to fusion proteins consisting of an Fc portion of an
antibody which is fused as mentioned to the non-immunological target
molecule which elicits biological or pharmacological efficacy. The
molecules of the invention have amino acid sequences which are altered in
one or more amino acid residue positions but have in principal the same
biological activity as compared with the non-altered molecules. The
changes are made in regions of the molecules which are identified as
T-cell epitopes, which contribute to an immune reaction in a living host.
Thus, the invention also relates to a novel method of making such fusion
proteins by identifying said epitopes comprising calculation of T-cell
epitope values for MHC Class II molecule binding sites in a peptide by
computer-aided methods.