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High-throughput genotyping has revolutionised the genome-wide search for associations between genetic variants and disease. Professor Sir Edwin Southern of the University of Oxford's Biochemistry Department invented the highly cost-effective array-based method of analysing genetic variation based on hybridisation between probes and samples on glass slides or `chips'. The spin-out company Oxford Gene Technology (OGT) founded by Southern in 1995 licenses the patent to manufacturers of `single nucleotide polymorphism (SNP) chips', including Illumina and Agilent, a global business exceeding $500M per year. Southern has continued to refine and extend this technology to increase its speed, efficiency and cost-effectiveness. This revolutionary technology has widespread applications such as prediction of individual risk, development of new drugs, provision of personalised treatments, and increased cost-effectiveness of clinical trials. Licence revenues fund R&D within OGT, and endow charitable trusts supporting primary school science education in the UK and crop improvement in the developing world.
A first-in-class anticancer agent discovered in Thurston's laboratory at the University of Portsmouth in the 1990s has been commercially developed and clinically evaluated over the last two decades. SJG-136 was successful in Phase I clinical trials and is completing Phase II clinical trials for the treatment of ovarian cancer and leukaemia, where significant patient benefit is observed. Related molecules based on this parent compound are in drug programmes being undertaken by Seattle Genetics Inc. and Genentech Inc., leading to additional clinical trials. A spin-out company, Spirogen Ltd, was established in 2000 to commercialise the intellectual property generated from the underpinning research, and the company has recently been sold to AstraZeneca for $200m.
This case study describes both economic and healthcare benefits that have resulted from a new DNA (gene) sequencing technique known as SOLiD sequencing. Through the 1990s until the present, Cosstick (University of Liverpool since 1984) has both developed the synthesis and studied the properties of chemically modified DNA in which a single oxygen atom is replaced by sulfur; we have termed this a 3'-phosphorothiolate (3'-sp) modification. Chemically prepared DNA containing the 3'-sp modification is a key enabling component of the Applied Biosystems SOLiD DNA sequencing instrument which is able to produce extremely rapid, cost-effective and exceptionally accurate DNA sequence information. The impact of this very powerful sequencing technology extends beyond economic benefits as it has many healthcare applications which have impacted medical practice.
Through their study of DNA polymerases from organisms of the domain archaea, researchers at Newcastle University and University College London identified the mechanism by which these organisms avoid potentially damaging mutations in their DNA. As a consequence of this work they invented a novel genetically-engineered DNA polymerase. This enzyme has been patented and is the world's only high-fidelity, proofreading DNA polymerase that efficiently reads through uracil in the polymerase chain reaction (PCR). PCR is a very widely used technique in biomedical research. An international bioscience company [Text removed for publication, EV d] signed a licensing agreement with Newcastle University in 2008 to market the enzyme, and total sales since 2008 exceed [Text removed for publication, EV d]. Further commercial exploitation has begun through licensing agreements with other major companies.
The Ethics of Patenting DNA was a Nuffield Council on Bioethics Report by a working party of which Thomas Baldwin was a member with responsibility for providing the ethical framework for the report. The report was published in 2002 and its initial impact occurred in the 2002-2005 period; but it has had continuing impact during the current period on legal and political debates concerning the granting of patents on DNA sequences to pharmaceutical and biotechnology companies and to universities. More generally it continues to have a significant impact on policy formation in this much disputed area.
Impact on commerce: A patented technique for separating methylated and non-methylated DNA has been licensed and a kit brought to market, along with other commercial reagent licenses.
Impact on health and welfare: The demonstration that two mechanisms of epigenetic gene regulation, DNA methylation and histone acetylation, are linked, has led to trials of separate drugs known to affect each mechanism as a combined treatment for high-risk patients with myelodysplastic syndromes (MDS).
Beneficiaries: Companies have gained commercial benefit from licensing UoE IP to market products. High-risk MDS patients will benefit from improved treatment.
Significance and Reach: Commercial earnings across 4 companies from international sales in the period estimated at over [text removed for publication], mainly since 2010. Commercial significance includes the first commercially-available technique for separating methylated and non-methylated DNA.
The incidence of MDS is estimated at 3-4 cases diagnosed annually per 100,000 of the population in Europe (an estimated 26,000 individuals) and up to 20,000 new diagnoses per year in the USA. Incidence increases with age — up to 15 new cases annually per 100,000 in individuals aged over 70 years. MDS occurrence is increasing as the age of the population increases, so the significance of new therapies is high.
Attribution: All research was led by Adrian Bird at UoE. Reik (Babraham Institute) contributed to development of one of the licensed antibodies.
Research by Professor Steve Jackson led to the discovery of synthetic lethality as a means of selectively targeting cancer cells, and to Jackson founding KuDOS Pharmaceuticals to translate this research into therapies. This novel approach has changed the way pharmaceutical companies develop cancer therapeutics and has led to several drugs reaching pre-clinical and clinical development. The most advanced of these (olaparib, a PARP inhibitor originally developed at KuDOS and acquired by Astra Zeneca) is now entering Phase 3 trials and registration in Europe. In 2011, Jackson founded MISSION Therapeutics Ltd, to extend the synthetic lethality concept into targeting deubiquitylating enzymes to selectively kill tumour cells.
Genetic, biochemical and structural characterisation of drug targets in the human pathogen Streptococcus pneumoniae by Fisher and colleagues at St George's showed that antibacterial quinolones selectively target the enzymes gyrase, topoisomerase IV, or both, and led to the concept that `dual targeting' drugs minimise the emergence of drug resistance. They demonstrated the potency and the mechanism of action of besifloxacin, a fluoroquinolone developed by Bausch and Lomb which was subsequently approved by the FDA in 2009 for treatment of bacterial conjunctivitis. This has been shown to be a highly efficacious treatment with correspondingly increased usage and sales in the USA.
Impact: New business, technology, intellectual property and employment resulting from the invention and exploitation of a micro-scale laboratory device (ScreenTapeTM).
Significance: New business and technology commercialised resulting in sales of novel products worldwide, acquisition by Agilent Technologies Limited (Agilent) for £[text removed for publication] in 2011, product sales of over £[text removed for publication] to August 2013, generation of sustained employment for 50-160 people, major inward investment (£6M) by local investors followed by a US multinational.
Beneficiaries: The economy, commerce, employment, research and diagnostic laboratories, Agilent Technologies Inc. (Agilent).
Attribution: UoE Prof Peter Ghazal and Dr Douglas Roy inventors on granted patent, establishment of multi-disciplinary research in biochip medicine, collaborators with ex-Motorola engineers, co-founders of spin-out company for commercialisation of intellectual property.
Reach: Worldwide, including employment and product sales. Inward investment to UK.
This case study outlines the impact in generating investment in a spin-out SME and in developing a technology for clinical diagnosis based on chemistry research carried out in Bath. The research led to a spin-out company, Atlas Genetics, which has raised over £18M funding in the REF period specifically to develop the Atlas io™ platform, novel technology for rapid (<30 minute) and robust detection of infectious diseases suitable for point-of-care. The investment has created new jobs for highly skilled workers at the cutting-edge of medical diagnostics, with Atlas currently employing 36 staff. The io™ platform has been fully developed and has undergone successful clinical tests on multiple infections (based on bespoke Chemistry developed at Bath) prior to clinical trialling and rollout in Europe and the United States.