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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.
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.
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.
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.
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.
A computer technology has been invented to accelerate drug discovery. It predicts locations in disease-associated biomolecules where drug molecules could bind, induce shape changes, and thereby bring the activity of the biomolecule under control. A U.S. drug discovery company, Serometrix, has exclusively licensed this technology and incorporated it within their core discovery process. The impact upon them has been:
Research at the University of Oxford's Glycobiology Institute (OGBI) has led to the development of `state-of-the-art' platform technologies for the analysis of oligosaccharides (sugars) that are linked to proteins and lipids. These enabling technologies have had major impacts worldwide on drug discovery programmes, have enabled robust procedures to be developed for the quality control of biopharmaceutical production, and have been widely adopted by the pharmaceutical industry.
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.
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.
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).