Disclosed is a method of modifying a donor immunoglobulin for use in a target species, the method comprising the steps of: - identifying a donor immunoglobulin from a species other than the target species, wherein the donor immunoglobulin has binding specificity to a target epitope present in the target species, - determining an amino acid sequence of framework regions of heavy and/or light chain variable domains of the donor immunoglobulin, - comparing each amino acid residue of the amino acid sequence of the framework regions of the heavy and/or light chain variable domains of the donor immunoglobulin with an amino acid residue present at a corresponding position in an amino acid sequence of framework regions of a plurality of immunoglobulins derived from the target species to identify one or more amino acid residue within the amino acid sequence of the framework regions of the heavy and/or light chain variable domains of the donor immunoglobulin that is not present at the corresponding position in the amino acid sequence of the framework regions of at least one of the plurality of immunoglobulins derived from the target species, and - substituting the one or more identified amino acid residues present in the amino acid sequence of the framework regions of the heavy and/or light chain variable domains of the donor immunoglobulin, but not present at the corresponding position in the amino acid sequence of the framework regions of at least one of the plurality of immunoglobulins derived from the target species, with an amino acid residue which is present at the corresponding position in the amino acid sequence of the framework regions of at least one of the plurality of immunoglobulins derived from the target species - wherein the modified donor immunoglobulin does not contain any amino acid in any position within the framework regions of the heavy and/or light chain variable domains which would be foreign at that position in one or more immunoglobulins derived from
