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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.
PKB (protein kinase B), also known as AKT, is an enzyme in the PI3 kinase/mTOR intracellular signalling pathway, which is deregulated in many cancers. Professor David Barford's team at the ICR solved the crystal structure of PKB03b2 using innovative protein engineering. The ICR has licensed six international pharmaceutical companies with reagents to enable them to begin PKB drug discovery programmes. The Barford team has also used their structural biology expertise to advance the ICR's own PKB inhibitor drug discovery programme. Two series of inhibitors were developed that were licensed to AstraZeneca and Astex and are now both in clinical trials.
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.
The protein kinase PKB (also known as Akt) is a key regulator of cell proliferation and survival that is commonly dysregulated in human cancers. Work at the University of Dundee in the late 1990s identified key components of this signaling pathway and established the mechanism by which PKB becomes activated through phosphorylation. Structural studies at the University provided important insights for the design of small molecules permitting targeted inhibition of this enzyme. PKB is a firmly established focus for pharmacological intervention and several clinical trials are underway testing the antineoplastic activity of PKB inhibitors in a variety of cancers.
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.
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.
Protein reagent production techniques developed at QUB, were transferred to UK-based biotechnology company, Fusion Antibodies Ltd, to increase their competitiveness in the production of diagnostic and therapeutic reagents. These techniques were commercialised by the company as the Fusion Expression TechnologyTM (FET) platform technology, to deliver contract research orders. The transfer of this technology allowed Fusion to accelerate its completion of orders and secure higher value projects. This increased competitiveness led to the tripling its technical workforce (at graduate and doctoral levels), securing new orders from over 15 countries and producing on average £300K per annum (from 2008 onwards) in revenue.
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.
Protein kinase B (PKB), also known as AKT, is an enzyme in the PI3 kinase/mTOR intracellular signalling pathway, which is found to be deregulated in many forms of cancer. Professor David Barford's team at the ICR solved the crystal structure of PKB03b2 using innovative protein engineering and licensed six international pharmaceutical companies with reagents to enable them to begin PKB drug discovery programmes. The ICR also initiated its own PKB drug discovery programme: two series of inhibitors were developed that were licensed to AstraZeneca and Astex and are now both in clinical trial. The ICR's work helped to establish PKB as a valid cancer therapeutic target. The ICR is involved in clinical research studies of multiple PI3 kinase and PKB inhibitors, and this research has led to the definition of useful clinical pharmacodynamic biomarkers.
The Fuller Longer™ (FL) food range was developed by Marks & Spencer (M&S) with expertise from the University of Aberdeen Rowett Institute of Nutrition and Health. Product development was based on Rowett research into the efficacy of high protein and mixed carbohydrate diets for sustained appetite control and weight loss. Obesity is a major public health challenge; therefore it is not surprising that FL has become an established brand for M&S's 20 million customers. This industry-academia partnership to develop a food range based on scientific input, was a first for M&S, and has led to one of the UK's most popular retail healthy-eating food ranges.
Therefore the claimed impact here includes benefits to health and welfare, on commerce, business performance and the economy.