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.
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.
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.
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:
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.
Impact: EaStCHEM spin out Albachem (1994), subsequently incorporated into the Almac group, enabling the latter company to become a world leader in the provision of chemically synthesised proteins.
Significance: Chemical synthesis is competitive with recombinant methods for commercial production of the therapeutic polypeptides that represent ~50% of drugs in big pharma pipelines and have a market value in 2008 of over $13B. The value attributable to Ramage's methods for polypeptide syntheses over the REF period is estimated at approximately £6M.
Beneficiaries: Drug manufacturers, contract research organisations, patients, clinicians.
Research: Studies (1993-6) led by Ramage (at the University of Edinburgh) on new methods for high-yield total syntheses and purification of long polypeptides.
Reach: Almac's protein-manufacturing team remains in the UK with 24 staff members. The Almac Group, headquartered in N. Ireland, has 3300 employees globally (1300 outside UK) and sells to 600 companies worldwide.
Oxford Expression Technologies (OET) is a spin out company launched jointly by Oxford Brookes University (Brookes) and the Natural Environment Research Council (NERC) to exploit Intellectual Property (IP) in the field of protein expression using novel insect virus vectors. OET generates revenue through sale of kits, services & licences to a range of global customers including academia, research institutes, pharmaceutical and biotechnology companies. OET provides employment, invests in in-house Research and Development including funding collaborative PhD students, and generates royalty income streams for Brookes and NERC. Customers are able to produce multiple recombinant proteins to higher yields and quality than was otherwise possible and a number of companies are using the developments for the commercial production of vaccines and other uses.
This case study describes the impact of the discovery by Tuite and Freedman that elevating the levels of the enzyme protein disulphide isomerase (PDI) significantly increases the efficiency with which eukaryotic cells secrete disulphide-bonded proteins. This discovery led to the development of a patented, generic technology for improving both the yield and authenticity of high value, recombinant protein-based biopharmaceuticals. The patent has been used in the safe, animal free production of several FDA and EMEA approved biopharmaceuticals (e.g. recombinant human albumin; Recombumin®), generating multi-million dollar revenues. It has been sub-licensed to four major pharmaceutical companies (Novozymes, Pfizer, Glaxo, Repligen) to aid the safe production of biopharmaceuticals for a range of major human diseases (e.g. Type 2 diabetes).
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.
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.