Composite Human Antibodies 

Composite Human Antibody™ technology creates therapeutic antibodies comprising multiple segments of human variable region sequence from different human antibodies. Combinations of sequence segments are selected to avoid T cell epitopes in the final sequences. The technology is designed for the low-risk generation of therapeutic antibodies that are entirely human in origin. Antibodies are generated in an equivalent way to antibody humanization but without the requirement for third party humanization patents. These composite antibodies have been produced from reference monoclonal antibodies (MAb) with a wide range of specificities in which the sequence of the final antibody comprises a composite of many sequence segments, all of which are human in origin. Using Composite Human Antibody™ technology, the binding properties of the original mouse (or other species) reference MAb are preserved in the final antibody. A key step in the generation of Composite Human Antibodies™ involves a process of T cell epitope recognition in which human sequence segments are selected for incorporation into antibodies after filtering out potential T cell epitopes ("Epitope Avoidance") therby reducing the risk of immunogenicity.

Key steps (shown in the Figure below) in the generation of a composite human(ized) antibody are as follows;

1) Variable regions of a reference non-human antibody (if available) are modeled to determine antigen binding regions

2) Sequence segments are sourced from a database of unrelated human antibody variable regions

3) Composite human variable regions with similar binding properties to the reference antibody are created

4) Composite Human Antibody™ sequence segments are screened for the presence of potential T cell epitopes

5) Sequence segments containing T cell epitopes are discarded. Composite variable regions (minus T cell epitopes) are then constructed and tested for antibody binding and selection of lead candidates

6) Composite Human Antibodies with properties of the reference non-human antibody are created

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All lead Composite Human Antibodies™ are screened for immunogenicity using EpiScreen™ assays. Composite Human Antibody™ technology provides a unique hybrid between humanization and fully human antibody technologies where a therapeutic antibody is developed which retains the biological properties of a reference MAb but consists of only human sequences.

Composite Human Antibody™ technology provides antibodies suitable for therapeutic and in vivo diagnostic use with a low potential risk of immunogenicity in patients. In addition to whole antibodies, the technology has been used to generate forms of antibody including Fabs, single chain Fv's and antibody-protein fusions.