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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.
Researchers at Newcastle University discovered interactions in vitro between the widely prescribed cholesterol-lowering drug rosuvastatin and cyclosporine, and between rosuvastatin and gemfibrozil, at the liver transporter protein OATP1B1. Subsequent clinical trials showed that the interactions occurred in patients and slowed clearance of rosuvastatin from the body. The research findings not only had direct implications for the safe prescribing of rosuvastatin when it came to be marketed but also more far-reaching impact. US Food and Drug Administration and European Medicines Agency guidelines published in 2012 stipulate that pharmaceutical companies must investigate potential drug-drug interactions in the pre-clinical development phase of all candidates that bind that transporter.
Alzheimer's disease (AD) affects one in seven of the population over 60 years of age, and represents an increasing burden on worldwide medical and care resources. Treatments currently available are symptomatic. Despite pharmaceutical industry efforts there has been little indication of a marketable product for long-term treatment.
To address this problem, a joint venture was established in 2001 between the University of Aberdeen and TauRx Pharmaceuticals. A team was created of chemists, biologists, animal behaviourists, working together with a clinical trial team. A drug effective against the progress of AD based on the compound methylene blue was synthesised and scaled up within the Chemistry Department (led by Professor John Storey), with a quality that was proved acceptable through successful phase two clinical trials (2006-8), and is now used in phase three clinical trials which are due to complete in 2015. Several other drug candidates have also been developed and evaluated in pre-clinical and phase one clinical studies that show promise. Collaborations with commercial pharmaceutical companies have as a result led to the manufacture of significant quantities of drug medicines for TauRx Pharmaceuticals based on IP generated within the Chemistry Department and these drugs have been used in clinical trials and for named patient supply (c. 60 patients). This has resulted in increased commercial revenue for these companies and the creation of new employment.
ProTide technology, discovered by the McGuigan team at Cardiff University, is a pro-drug strategy with proven capacity to generate new drug candidates for nucleoside-based antiviral and anti- cancer indications. In the assessment period the McGuigan team has attracted more than £2 million direct research funding through sustained collaborations on ProTide technology with global pharmaceutical companies and smaller biotech firms in the USA and Europe. In the same period, either through working directly with Cardiff or by independent adoption of McGuigan's research, eight ProTide entities have progressed to clinical trials as cancer, HIV and hepatitis C treatments. The technology is demonstrating significant commercial impact for companies with ProTide-based drug candidates.
Hagan Bayley's research on nanopore sensing for DNA sequencing at the University of Oxford led to the formation of the spin-out company Oxford Nanopore Technologies Ltd (ONT) in 2005. Since 2008, ONT has raised £ 97.8M to support research and product development. This level of investment arises as a direct result of the pioneering technology ONT has developed, based on research in the UOA, which has the potential to revolutionise DNA sequencing and other single molecule analyses. ONT currently employs 145 people, nearly six times as many as in 2008, and was recently valued at $ 2 billion. Evidence from ONT was used in a 2009 House of Lords report on genomic medicine, demonstrating ONT's position at the forefront of this new technology.
Leeds researchers discovered a novel class of tissue penetrating, light-activated dyes that were selectively and rapidly taken up by bacteria. Based on the dyes' promising antimicrobial activity, the University of Leeds span-out Photopharmica Ltd. Further research at Leeds has progressed the development of a targeted antimicrobial for chronic wound infections. Photopharmica has raised £11.5M in external investment, around £6.0M of which has been deployed since 2009 to support a 57 patient phase IIb clinical trial. The results, which showed substantially reduced loads of all bacterial species, led to a further £250K investment in 2012 to support Photopharmica's strategy to bring an antimicrobial drug to the market.
Since 2008, pioneering contributions to the field of computational chemistry for drug discovery have been made by InhibOx Ltd., a spin-out company based on the research of Graham Richards and co-workers at the University of Oxford. InhibOx launched Scopius, the world's largest searchable virtual database of small-molecules (>112 million compounds) and pioneered the use of cloud computing for large-scale molecular modelling. The key impact for customers of InhibOx has been the reduced costs in identifying molecular leads for new drugs. InhibOx's work has helped to open up early stages of drug development to smaller companies; 75% of InhibOx's clients are SMEs. Since 2008, InhibOx has received £ 2.8M in income and investment.
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.
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.
Labelled compounds form an essential part of drug discovery and development within the pharmaceutical industry. Novel iridium catalysts, developed by Kerr at WestCHEM since 2008, have introduced a step-change in the ability to label pharmaceutical candidate compounds with radioactive (tritium) or non-radioactive (deuterium) isotopes.
The catalysts are applicable to specific types of compounds that comprise approximately one-third of all drug candidates. Advantages of the catalysts include greater efficacy (less catalyst needed and higher yield of labelled product, giving cost savings), greater speed (efficiency savings), and a significant decrease in radioactive waste compared with previous methods (environmental and safety benefits).
Even since 2008, their adoption within the pharmaceutical industry has been extremely rapid; e.g., the multinational pharmaceutical company AstraZeneca now applies the Kerr methodology to 90% of their relevant candidate compounds. Additional impact has been achieved by Strem Chemicals who have been manufacturing and marketing the catalysts worldwide since October 2012. Even in that very short period, multiple sales have been made on three continents providing economic benefit to the company.