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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.
Professors Zhelev (UoA5) and Bradley (UoA15) explored the scope and demonstrated the feasibility of using light-scattering methods for quantitative analysis of macromolecular associations and aggregation, including protein-protein and protein-DNA interactions. 16 years of design and development research was translated into a marketed product — the PAM™Zero — a novel hand-held, low-cost protein aggregation monitor capable of detecting macromolecule aggregation in microliter sample volumes. Manufactured and sold through a spinout company, Norton Scientific Inc. (established in 2010 and valued at $7M), this portable instrument is used in commercial Quality Control and academic research and has been sold to a range of stakeholders e.g. drug development companies, for food safety and water pollution monitoring.
Research in protein folding and technological development at the University of Leeds led to the creation of Optim1000, a high throughput microlitre protein stability analyser, through Leeds spin-off company Avacta. Used in the early stages of R&D in the biopharma industry, Optim1000 evaluates the stability and homogeneity of complex biological drugs, using just micrograms of protein sample. This screening reduces the costly development and late-stage failure of unsuitable candidate therapeutics. The platform has been sold to a wide range of global biopharma companies; it is reported to reduce drug stability screening by months. This provides economic impact through saving the industry millions of dollars in R&D costs, along with health impact by speeding up the emergence of new products. Avacta reported revenue of over £3 million in 2012 and employs 70 staff.
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.
Research undertaken at the University of Liverpool (UoL) has identified a new class of intestinal nutrient sensors that influence nutrient absorption properties of agricultural species. Specific sensor systems were stimulated by artificial sweeteners with positive effects on intestinal function and whole animal wellbeing. This work has provided the rational basis for the supplementation of animal feed with artificial sweeteners, which has led to their worldwide deployment in the diet of early-weaned piglets. This innovation has (i) improved health and survival rate of piglets by preventing post-weaning intestinal disorders, and (ii) created significant economic benefits for the animal production industry. A patent has been granted, there has been extensive collaboration with the animal feed company Pancosma, and industry is also actively investigating inclusion of sweeteners in feed for ruminants.
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.
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.
Essex research identified a novel bioprocessing matrix which has since been developed into commercial products and recently launched into external markets by Porvair Filtration Group Ltd. The discovery involved the chemical modification of sintered thermoplastic materials in order to attach biological molecules, so conferring highly specific functionalised properties to an otherwise inert base material. This enabled a new approach for protein immobilisation, having technical and practical advantages over existing processes. As a direct result, Porvair has adopted a new technology and invested £900k in R&D over eight years. Essex research has supported a change in business strategy, enabling entry into new markets, which has in turn both safeguarded and created jobs at Porvair.
Kinases, the enzymes that catalyse phosphorylation events, have been implicated in hundreds of different diseases, and hold rich promise for drug development. In 1998, The University of Dundee developed the first systematic assay to analyse the selectivity of protein kinase inhibitors, termed `kinase profiling'. This technology has been crucial for the development of new therapeutic drugs targeting protein kinases. In order to promote drug discovery in the area of kinases, the Division of Signal Transduction Therapy (DSTT) was formed and provides a unique collaboration between the University and six of the world's leading pharmaceutical companies.
The CATH classification of protein structure, developed at the Institute of Structural and Molecular Biology, UCL, by Janet Thornton and Christine Orengo, has been used widely across the pharmaceutical industry and academia to guide experiments on proteins. This has led to significant cost and time savings in drug discovery. The UCL-hosted online CATH database receives around 10,000 unique visitors per month, and is a partner in InterPro — the most frequently accessed protein function annotation server available.