A method of designing an immunoglobulin library for optimisation of a biological property of a first lead immunoglobulin, the method comprising: a) identifying one or more related immunoglobulins of common lineage with and that bind the same target antigen as the first lead immunoglobulin, said one or more related immunoglobulins being related to the first lead immunoglobulin, each immunoglobulin having been raised against a target antigen by immunisation of a transgenic non-human mammal comprising human immunoglobulin genes with the target antigen and said one or more related immunoglobulins being derived from the same germline sequence by somatic hypermutation of a germline sequence in the transgenic non-human mammal; b) comparing amino acid sequences of the first lead immunoglobulin and the one or more related immunoglobulins; c) identifying, based on the sequence comparison, one or more sites at which there are variant amino acid residues between: (i) the first lead immunoglobulin and the one or more related immunoglobulins, and/or (ii) where the one or more related immunoglobulins is a plurality of immunoglobulins, between the plurality of immunoglobulins, wherein the one or more sites at which there are variant amino acid residues comprise somatic hypermutation hot spots targeted during the immune response that are potential sites for modification of the first lead immunoglobulin; d) selecting one or more sites for modification to replace an amino acid of the first lead immunoglobulin with the corresponding variant amino acid of one or more of the related immunoglobulins, based on the sequence comparison; and e) generating immunoglobulin sequences for the library based on the sequence of the first lead immunoglobulin, modified at one or more of the selected sites for modification. a) identifying one or more related immunoglobulins of common lineage with and that bind the same target antigen as the first lead immunoglobulin, said one or more related immunoglobulins being related to the first lead immunoglobulin, each immunoglobulin having been raised against a target antigen by immunisation of a transgenic non-human mammal comprising human immunoglobulin genes with the target antigen and said one or more related immunoglobulins being derived from the same germline sequence by somatic hypermutation of a germline sequence in the transgenic non-human mammal; b) comparing amino acid sequences of the first lead immunoglobulin and the one or more related immunoglobulins; c) identifying, based on the sequence comparison, one or more sites at which there are variant amino acid residues between: (i) the first lead immunoglobulin and the one or more related immunoglobulins, and/or (ii) where the one or more related immunoglobulins is a plurality of immunoglobulins, between the plurality of immunoglobulins, wherein the one or more sites at which there are variant amino acid residues comprise somatic hypermutation hot spots targeted during the immune response that are potential sites for modification of the first lead immunoglobulin; (i) the first lead immunoglobulin and the one or more related immunoglobulins, and/or (ii) where the one or more related immunoglobulins is a plurality of immunoglobulins, between the plurality of immunoglobulins, d) selecting one or more sites for modification to replace an amino acid of the first lead immunoglobulin with the corresponding variant amino acid of one or more of the related immunoglobulins, based on the sequence comparison; and e) generating immunoglobulin sequences for the library based on the sequence of the first lead immunoglobulin, modified at one or more of the selected sites for modification.