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The Abraham solvation parameter approach developed at UCL has become integral to the work carried out by drug discovery teams at [text removed for publication] and other major pharmaceutical companies, as well as research and development groups at international chemical companies including Syngenta and [text removed for publication]. It enables chemists to predict physicochemical and biochemical properties of chemicals, including drugs and agrochemicals, rapidly and efficiently, without the need to conduct time-consuming experiments. The method helps drug discovery teams to identify and optimise the most promising compounds, and often results in fewer compounds being made before a candidate is selected, saving time and resources. The approach has been integrated into software used for drug discovery [text removed for publication].
Development of the human cell GADD45a assay enabled accurate identification of carcinogens in vitro, with a low rate of misleading positives. Through the spin-out company Gentronix, this research is reducing costs to industry and decreasing the use of animals in research. Industrial collaboration has enabled commercial adoption of the technology in many sectors. With a 10-fold increase in orders in 2012 versus 2008, Gentronix is a profitable business employing 17 people and with an annual turnover of £1.88m. During 2008-12, Gentronix released a series of new products, established testing services, and signed a product license agreement with GlaxoSmithKline. More than 100 companies worldwide are using Gentronix kits, including pharmaceutical, agricultural and health and beauty companies, along with manufacturers of food flavourings and household goods. The Gentronix assay is currently being reviewed by the European Centre for the Validation of Alternative Methods.
As a result of our discoveries of a new splice variant (ASIC1b) and a new member (ASIC4) of the ASIC family, and elucidation of their roles in pain caused by tissue acidity, several pharmaceutical companies are now working on ASIC-targeted analgesics and one company has been set up specifically to focus on this work. ASIC-related therapies for a wide variety of conditions are now in clinical trials, with substantial patient involvement. Our work has allowed new therapeutic applications to be conceived for already existing prescribed compounds, and for naturally-occurring compounds, that act on ASICs. Thus, our research on ASICs has had clinical and commercial impact.
Haemophilia, an inherited bleeding disease, is treated by frequent and extremely expensive infusions of recombinant versions of the missing factors. Advances in gene therapy have now been achieved at UCL, with successful treatment of Haemophilia B in 10 severely affected patients. The novel factor IX expression cassette has been patented and licensed to an industrial partner (UniQure). Savings to the NHS in excess of £1.5m have already been made and increase every month. Pre-clinical advances have also been made in Haemophilia A, and the factor VIII expression cassette has been patented and licensed to an industrial partner (BioMarin).
Research into electrochemical biosensors conducted at the University of Cambridge between 1998 and 2002 led to the development of the WaveSense™ line of diabetes products by start-up, AgaMatrix. By 2012 AgaMatrix had sold 3M glucose meters & 3B biosensor test strips worldwide across 20,000+ retail locations including Boots UK, and since 2010 also globally in partnership with Sanofi. [text removed for publication] AgaMatrix UK continues to grow its business with compound annual growth rates for revenue in excess of 100%. Agamatrix UK now supplies over one million glucose test strips per month to the NHS. Agamatrix has developed >10 FDA-cleared products since 2008, including the first FDA approved smartphone linked diagnostic device.
Impact: EaStCHEM spin out Albachem (1994), subsequently incorporated into the Almac group, enabling the latter company to become a world leader in the provision of chemically synthesised proteins.
Significance: Chemical synthesis is competitive with recombinant methods for commercial production of the therapeutic polypeptides that represent ~50% of drugs in big pharma pipelines and have a market value in 2008 of over $13B. The value attributable to Ramage's methods for polypeptide syntheses over the REF period is estimated at approximately £6M.
Beneficiaries: Drug manufacturers, contract research organisations, patients, clinicians.
Research: Studies (1993-6) led by Ramage (at the University of Edinburgh) on new methods for high-yield total syntheses and purification of long polypeptides.
Reach: Almac's protein-manufacturing team remains in the UK with 24 staff members. The Almac Group, headquartered in N. Ireland, has 3300 employees globally (1300 outside UK) and sells to 600 companies worldwide.
The UCL Centre for Amyloidosis and Acute Phase Proteins has designed and developed new chemical entities targeting serum amyloid P component (SAP), C-reactive protein (CRP) and transthyretin, for novel therapeutic approaches to amyloidosis, Alzheimer's disease, cardiovascular and inflammatory diseases. The UCL spin out company, Pentraxin Therapeutics Ltd, founded by Sir Mark Pepys to hold his intellectual property (IP), has licensed two programmes to GlaxoSmithKline (GSK). These highly synergistic, collaborative multi-million pound developments, strikingly exemplify new working relationships between academia and the pharmaceutical industry.
Stem cells play an important role in drug discovery and development of therapeutic interventions. Differentiation (and maintenance) of stem cells into specialised cells is achieved by controlled application of specific, expensive growth factors.
Dr Hyvönen has developed an efficient method for producing highly purified, bioactive human growth factors from E.coli, reducing costs by up to 10-FOLD. tHE TECHNOLOGY HAS BEEN LICENSED TO A major international manufacturer of growth factors (PeproTech Inc.), and to a UK-based specialist stem cell company (CellGS Ltd), enabling them to implement new products and business strategies. Through a departmental facility, material is also being sold to external companies and Cambridge Stem Cell Consortium members. In addition, Dr Hyvönen has made his expertise available to biotech companies through consultancy.
Measurement of hormones is essential to the understanding and diagnosis of endocrine diseases. White and her research group have developed unique antibodies that are widely used in diagnostic assays for adrenocorticotrophic hormone (ACTH) and related peptides, including the first and only kit for measuring pro-opiomelanocortin (POMC), the precursor of ACTH. These assays are used worldwide for diagnosis, decisions on treatment, monitoring for recurrence of tumours and prognosis in a number of patient groups with life-threatening endocrine disorders. Global sales of the ACTH Elecsys tests by Roche exceeded 6 million kits since 2008. AstraZeneca has used the POMC and ACTH assays in its drug discovery programmes in the cardiovascular and metabolic diseases therapy area. The antibodies therefore have had health impact in relieving suffering and in improving patient care, as well as commercial impact in worldwide sales of assays and influencing drug development strategies.
Pioneering new immunoassays for inhibin A and B, developed by Professor Nigel Groome at Oxford Brookes University, have contributed to a significant improvement in the accuracy of pre- natal screening for Downs Syndrome. Use of inhibin A in the `Quad' and `integrated' tests, protected by international patents, is widespread in the US (c.3million screened annually) and was recommended by the NHS in 2010, leading to a significant increase in the use of the assays (c.120,000 annually) in the UK. They are also used in clinical diagnostic and monitoring applications for male and female infertility, abnormalities in sexual development in children and ovarian granulosa tumours. Commercialisation has led to royalty income to Brookes from sales which totalled approximately c.£5million in the period January 2008 to December 2012, indicative of the c.US$135million earned in worldwide sales in the same period.