2 min readNew Antibody Discovery Technology Developed

Hinxton, UK – Kymab, a monoclonal antibody biopharmaceutical company founded on research from the Wellcome Trust Sanger Institute, has announced the publication in Nature Biotechnology of a paper describing its new therapeutic antibody discovery technology, Kymouse.

Scientists at Kymab have engineered a mouse with the full set of genes encoding the human antibody repertoire, calling this new technology Kymouse. They have demonstrated that these mice develop an enormous range of human antibodies which can be developed as potent drugs to treat a variety of human diseases such as cancer, autoimmune and infectious diseases.

“This is a remarkable achievement in our journey towards delivering therapeutic antibodies and to facilitate vaccine development,” says Professor Allan Bradley, Founder and Chief Scientific Officer of Kymab. “Kymab scientists have completed the most ambitious humanization project of the mouse genome ever undertaken, with 5.4 million bases of human DNA, representing 0.1% of the human genome into the appropriate place in the mouse genome.”

Antibodies are one of the best-selling classes of drugs today; five of the top ten best-selling drugs are antibodies. This is because antibodies are natural products with exquisite specificity and potency, and generally have superior safety profiles. The challenge has been to capture the full human antibody repertoire and to recapitulate all its attributes.

Mice with portions of the human antibody repertoire have been developed previously. However, the technology used at the time proved unsuitable for moving the very large stretches of DNA from the human genome into the mouse. As a result, their antibody gene repertoires were both incomplete and in the wrong location in the genome. Kymab scientists took a different approach and moved these vast stretches of DNA into the mouse genome in a series of steps each with a smaller segment of DNA, carefully re-joining them and thereby re-constructing the complete human repertoire in the correct place in the mouse genome.

 “Antibodies discovered using Kymouse strains are essentially ready to be developed as drugs,” says Dr. Christian Grøndahl, Chief Executive Officer of Kymab. “We are building a rich pipeline of first-in-class therapeutics in five areas: haematology, oncology, auto-immunity, pain and cardiovascular disease. This technology offers great potential to advance patient care in diseases with significant unmet medical need.”

By using the Kymouse technology, Kymab can pursue the targeting of the most challenging drug targets ranging from complicated ion channels and GPCRs to deeply hidden epitopes in heavily glycosylated virus proteins.

Dr. David Chiswell, former CEO of Cambridge Antibody Technology and Chairman of Kymab’s Board of Directors says: “Kymab’s highly innovative and technically advanced Kymouse platform has overcome the problems which limited previous generations of human antibody generating mice and is a strong foundation on which we can build a global biotechnology company.”

To make these sophisticated resources widely available, Kymab has created Kymab Access, a programme that enables academic researchers to pursue the discovery and development of novel human monoclonal antibody therapeutics by partnering with Kymab and its world leading Kymouse antibody technology.

Publication: Complete humanization of the mouse immunoglobulin loci enables efficient therapeutic antibody discovery. Lee E-C et al. Nature Biotechnology (2014): http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.2825.html

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