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DICHROWEB is a comprehensive, user-friendly server that provides access to computational tools for the determination of protein secondary structure from data obtained through circular dichroism (CD) and synchrotron radiation (SRCD) spectroscopy. The Protein Circular Dichroism Data Bank (PCDDB) is a database of spectra obtained using these techniques and allied data. Both resources are widely and increasingly used in many countries and are proving useful in industrial research (for example, in drug discovery) as well as academia and advanced teaching. DICHROWEB currently has over 3,600 registered users and over 375,000 DICHROWEB analyses have been run. Since the launch of PCDDB in 2009, the database has had over 175,000 unique hits from 41 different countries, and 89,890 downloads.
Novel rapid methods for predicting protein structure, particularly functional loop structures, have been developed by researchers at the University of Oxford. These have been made accessible to a large audience through a suite of computational tools. The methods have had general impact through download and online access and specific impact through extensive use within UCB Pharma. The tools are much faster than other methods, creating equal or better predictions in approximately a thousandth of the time. Commonly exploited by UCB Pharma in their drug discovery pipeline, they have cut computational cost, but, more importantly, they have greatly reduced the time for process improvements. UCB Pharma estimate that the tool pyFREAD alone saves over £5 million in the discovery costs for a single drug molecule. FREAD (a version of pyFREAD coded in C) is also being used more widely, for example by Crysalin Ltd and InhibOx.
Research carried out at Birkbeck's Department of Computer Science and Information Systems since 2000 has produced techniques for the management and integration of complex, heterogeneous life sciences data not previously possible with large-scale life sciences data repositories. The research has involved members of the department and researchers from the European Bioinformatics Institute (EBI) and University College London (UCL) and has led to the creation of several resources providing information about genes and proteins. These resources include the BioMap data warehouse, which integrated the CATH database — holding a classification of proteins into families according to their structure, the Gene3D database — holding information about protein sequences, and other related information on protein families, structures and the functions of proteins such as enzymes. These resources are heavily utilised by companies worldwide to explore relationships between protein structure and protein function and to aid in drug design.
Serum amyloid P, or pentraxin-2, is a pentameric calcium-binding protein that binds to amyloid fibrils. It has been implicated in the protection of those fibrils from proteolytic digestion and in the immune response to tissue damage. The structure of pentraxin-2 was first solved by Steve Wood and his co-workers in Tom Blundell's lab at Birkbeck in the 1990s. Wood has continued his work on the pentraxins at UCL, and the company Pentraxin Therapeutics Ltd was spun out of UCL to design and develop pentraxin-binding ligands (based on its structure) as potential treatments for Alzheimer's disease and amyloidosis. Promedior Inc. in the US is developing recombinant forms of pentraxin to control fibrosis. Several of these molecules are now in clinical trials.
Research at the University of Oxford's Glycobiology Institute (OGBI) has led to the development of `state-of-the-art' platform technologies for the analysis of oligosaccharides (sugars) that are linked to proteins and lipids. These enabling technologies have had major impacts worldwide on drug discovery programmes, have enabled robust procedures to be developed for the quality control of biopharmaceutical production, and have been widely adopted by the pharmaceutical industry.
Combinatorial Domain Hunting (CDH) technology is a technique for producing fragments of proteins that are soluble and tractable for biophysical analysis. It was developed between 1999 and 2008 at Birkbeck College, in the laboratory of Dr Renos Savva. This technology was patented in 2001 and the biotech company Domainex Ltd was then formed to commercialise it. In 2007, Domainex merged with a UCL spinout company, NCE Discovery Ltd. The company has attracted over £3m in investment and employs about 31 people. In addition to its contract research programme, it has developed an in-house drug discovery programme utilising CDH. Early in 2012 a patent was filed on a series of inhibitors of the protein kinases IKK03b5 and TBK1, which are validated drug targets for cancer and inflammation, and the first of these are expected to begin clinical trials in 2014.
Protein modification represents a highly significant and growing source of new products for the biopharmaceuticals market. This case study outlines the development of PolyTherics, a highly successful spin-out company from the UCL School of Pharmacy, and the impact that their enabling technology has had on the pharmaceutical and biotechnology industries. The company was developed as a direct result of new conjugate technology developed by Professor Steve Brocchini and coworkers at the School. The company moved to independent premises in 2006 and now manages a portfolio of over 100 granted and pending patents. Several licensing agreements are in place, including with Celtic Pharma Holdings for haemophilia treatments and Nuron for a multiple sclerosis treatment based on PEGylation conjugation technology. Revenue is expected to be £8m in 2013. The impact of Polytherics is therefore as a significant and effective technology provider to the pharmaceutical and biotechnology industries.
New computational analysis methods have been developed to make drug discovery and toxicological analysis much more efficient. These methods have been patented (UK, EU, US) and are employed in e-Therapeutics Plc, a computational drug discovery spin-off company of the University. The company, introduced to the Alternative Investment Market of the London Stock Exchange in 2007, is now the eighth largest company (by market capitalisation - £92.7M (26/6/2013)) in the pharma/biotech sector. The underlying technologies derive from network analysis and workflow research at the University. The company has an anti-cancer drug (ETS2101) in phase I clinical trials in the UK and the US, and an anti-depression drug (ETS6103) planned to enter phase IIb clinical trial shortly. The beneficiaries of this research are e- Therapeutics directly, other drug companies, and ultimately patients.
The Institute of Cancer Research (ICR) founded the spin out company Domainex in 2002 in collaboration with UCL and Birkbeck. The company was set up on the basis of novel research into the expression of soluble protein domains to provide services to a range of bioscience-based companies. Within the period 2008-2013, Domainex has established profitability and positioned itself as a successful company employing over 30 scientists at its laboratories in Cambridge. It has established programmes and contracts with over 20 international clients in medicinal chemistry, drug discovery, monoclonal antibody development and agrochemical science, making a major commercial impact in all these fields.
Breakthrough structural and mechanistic work at Oxford University investigating how enzymes catalyse oxidising reactions has had major impacts in biomedicinal fields, including how humans adapt to changes in oxygen availability. Impacts arising from the work since 2008 include the identification of new drug targets for major diseases ranging from anaemia to cancer that are being clinically pursued by pharmaceutical companies (including GSK, Bayer, Astellas, Akebia) and smaller companies (including the Oxford spin out ReOx), and the sale of products including small-molecule probes (e.g. by Tocris, Millipore, Selleck Chem) that are of use in biomedicinal/pharmaceutical research, especially in the emerging field of epigenetics.