Antibodies, variable domains & chains tailored for human use

A method for producing an antibody heavy chain, VH domain or an antibody specific to a target antigen, wherein the heavy chain, VH domain or antibody comprises an HCDR3 that is at least 20 amino acids in length and is derived from the recombination of human JH6*02 with a human VH gene segment and a human D gene segment, the method comprising

• expressing the heavy chain, VH domain or antibody from a cell, wherein the cell comprises nucleic acid encoding the heavy chain, VH domain or antibody,
• wherein the heavy chain, VH domain or antibody is of a transgenic non-human vertebrate contacted with the target antigen, the non-human vertebrate being a mouse or a rat,
• wherein the non-human vertebrate has a genome comprising an immunoglobulin heavy chain locus comprising unrearranged human gene segment JH6*02, one or more human VH gene segments and a plurality of human D gene segments upstream of a constant region,
• wherein the plurality of human D gene segments includes a human D gene segment selected from the group consisting of D3-9, D3-10, D6-19, D4-17, D6-13, D3-22 and D1-26,
• wherein the gene segments in the heavy chain locus are operably linked to the constant region thereof so that the vertebrate is capable of producing an antibody heavy chain produced by recombination of the human JH6*02 with a human D segment and a human VH segment,
• wherein the JH6*02 gene segment comprises the following nucleotide sequence:
• ATTACTA CTACTACTAC GGTATGGACG TCTGGGGCCA AGGGACCACG GTCACCGTCT CCTCAG, and
• wherein the vertebrate produces an antibody heavy chain specific for the target antigen wherein the variable domain of the heavy chain is the product of recombination between a human VH, D and JH6*02 and wherein the HCDR3 length is at least 20 amino acids.