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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.
In 2003, researchers at the University of Dundee identified the tumour suppressor LKB1 as a critical upstream activator of AMP-activated protein kinase (AMPK), which provided the first link between AMPK and cancer. Metformin, the front-line therapy for type-2 diabetes, was already known to exert its beneficial effects through AMPK. An interdisciplinary collaboration at the University examined the link between metformin and cancer, and reported in 2005 that diabetics taking metformin had a reduced incidence of cancer. The impact has been clinical trials worldwide testing the benefit of metformin for cancer treatment, and development of therapeutics by pharmaceutical companies targeting this pathway.
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.
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.
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.
Members of the Pharmacology Research Group identified hitherto unknown properties of G protein Coupled Receptors (GPCRs): that ligands can signal differentially through both G-protein-coupled and β-arrestin pathways. This led to the concept of GPCR `biased signalling' and development of fluorescent reporters to quantify β-arrestin signalling. These discoveries have been adopted widely by the pharmaceutical industry, attracting R&D investment and collaborative research funding, to drive discovery of new drugs operating through `biased signalling'. The commercial opportunity has also been exploited by screening reagent providers and contract screening organisations. These discoveries will ultimately produce better drugs to treat GPCR-based diseases to improve human health.
As sophisticated proteomics methodologies are increasingly embraced by both academics and industry across the globe, growth in this area is set to explode. The University of Dundee has a leadership position in quantitative proteomics technology, through the expertise of Professor Angus Lamond. Dundee Cell Products Ltd is a University of Dundee spin-out company that was created to commercialise life sciences technology and reagents, and to exploit technology and expertise in proteomics developed at the College of Life Sciences. As of 2013, DCP offers >5,000 research products and six contract research services, centred around quantitative proteomics.
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.
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.