PREVENTION OF AGGREGATION OF IMMUNOGLOBULIN LIGHT OR HEAVY CHAINS

摘要

The present invention provides an inhibitor of the aggregation of immunoglobulin chains (or immunoglobulin VL or CHl domains). In preferred embodiments, the inhibitor comprises or consists of a polypeptide which comprises or consists of (a) an amino acid sequence corresponding to the amino acid sequence of the FRl region of an immunoglobulin light chain variable domain, or part thereof which includes amino acid residue 12, (b) an amino acid sequence corresponding to the amino acid sequence of the immunoglobulin-binding domain of bacterial superantigen Protein L, or part thereof, and/or (c) an amino acid sequence corresponding to the amino acid sequence of the immunoglobulin-binding domain of streptococcal protein G (SpG), or part thereof, or a variant, fusion or derivative thereof, or a fusion of a said variant or derivative thereof which retains the ability of the parent polypeptide to inhibit aggregation of immunoglobulin chains, or domains thereof. The invention further provides a non-naturally occurring antibody, or antigen-binding fragment, fusion or derivative thereof comprising a light chain variable domain, or a fusion of a said fragment or derivative, wherein the FRl region of the light chain variable domain is modified (e.g. mutated) so as to inhibit, at least in part, the ability of the antibody, fragment, fusion or derivative to form aggregates. Most preferably, the light chain variable domain is modified at position 12 of the FR1 region by replacing the naturally occurring amino acid (e.g. serine in ? light chains) with proline.