Log in
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.
Proteins are fundamental to life and to many drugs, vaccines and new types of applied medicine with engineered cells. For this work, it is often essential to tag proteins to enable their identification and purification. The V5 tag, which was developed in St Andrews, is used very widely in this role and has some key advantages over alternatives.
Key impacts are:
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.
Professor Neil Barclay and Dr Nick Hutchings established Everest Biotech Ltd in 2000 in response to the increasing demand for high quality antibodies within the research community. This successful spin-out company has since become a major power in antibody research and production, a position reflected by its portfolio of more than 6,000 antibodies recognising human, mouse and rat proteins, and the generation of 60 new antibodies each month. With offices in the UK and Nepal, Everest Biotech Ltd also benefits one of the poorest communities in the world by providing additional income to hundreds of farmers in the Nepalese foothills.
A novel self-assembly process, developed at WestCHEM was shown to provide a step-change for stabilising proteins as dry powders. The spin-out company, XstalBio, was created in 2004 and licensed the patented technology with the aim of developing it for delivery and formulation of therapeutic biomolecules and vaccines. Over the period 2008-2012, eight leading international pharmaceutical and animal health companies paid XstalBio over £2.2M for access to its IP portfolio and to undertake evaluation studies with candidate biomedicines and vaccines. XstalBio employed 8 highly skilled research scientists over this period and 4 further patent families were generated. Boehringer Ingelheim licensed the technology for application to its therapeutic biomolecules and in collaboration with XstalBio built a dedicated €5M pilot plant for manufacture of inhalable dry powders.
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.
A novel conjugation technology has been developed to enable site-specific attachment of polyethylene glycol (PEG) to proteins to extend the in vivo half-life of biopharmaceuticals. The technology has been commercialised by an Imperial College spin-out company, PolyTherics Limited. In 2013, the merger of PolyTherics with Antitope Limited, enhanced the company's biopharmaceutical technology development offering. PolyTherics issued new shares to the value of £13.5 million to investors and Antitope shareholders in connection with the merger.
The company has enabled the development of novel forms of interferon 03b2 (for the treatment of multiple sclerosis) and blood factors VIIA, VIII and IX (for the treatment of haemophilia A and B) utilising original Imperial TheraPEG™ technology. This is achieved through licences granted by PolyTherics to Nuron Biotech and Celtic Pharma Holdings who are in early pre-clinical development. PolyTherics has further developed the conjugation technology (ThioBridge™) for its application in the creation of stable, homogeneous antibody-drug conjugates for the targeted cancer therapy.
Polytherics has impacted the UK economy generating intellectual capital, capital investment, new employment and novel compounds to treat disease.
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.
Bacillus species constitute an industrially-important group of bacteria that are used worldwide to produce carbohydrate and protein-digesting enzymes on a large scale. While the bacteria secrete native enzymes at an economically viable rate, generating strains of bacteria that could do the same for non-native enzymes has been an industry challenge. Researchers at Newcastle University have collaborated with industry since the early 1990s to study the mechanism of protein secretion in Bacillus. They discovered bottlenecks in the protein secretion pathway and used that knowledge to engineer more productive strains of bacteria. Since 2008, companies, including Novozymes (the world's largest manufacturer of industrial enzymes), have developed strains of bacteria, based on the Newcastle findings, for use in their manufacturing processes improving yields by more than four orders of magnitude in some cases.
Co-expression of multiple proteins within the same cell is critical for success in many areas of biomedicine and biotechnology. This can now be readily accomplished by using 2A co-expression technology, developed by the Ryan Laboratory in St Andrews University. This technology has been critical in strategies for human gene therapies targeting cancer, production of induced human pluripotent stem cells for regenerative medicine, creation of transgenic animals and plants with improved nutritional properties and the production of high-value proteins for the pharmaceutical industry. Over 400 patent applications in the REF period utilise 2A, and multiple companies market products based on the technology.