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Genetic, biochemical and structural characterisation of drug targets in the human pathogen Streptococcus pneumoniae by Fisher and colleagues at St George's showed that antibacterial quinolones selectively target the enzymes gyrase, topoisomerase IV, or both, and led to the concept that `dual targeting' drugs minimise the emergence of drug resistance. They demonstrated the potency and the mechanism of action of besifloxacin, a fluoroquinolone developed by Bausch and Lomb which was subsequently approved by the FDA in 2009 for treatment of bacterial conjunctivitis. This has been shown to be a highly efficacious treatment with correspondingly increased usage and sales in the USA.
Professor James and colleagues developed a comprehensive, multi-strand strategy for control of healthcare-associated infections caused by life-threatening bacterial superbugs Clostridium difficile (C.diff) and methicillin-resistant Staphylococcus aureus (MRSA). Founded on research to understand the transmission, virulence and antibiotic resistance of these species, their approach resulted in: (i) increased public awareness of healthcare associated infections; (ii) changed behaviours of the public and healthcare professionals to reduce transmission; (iii) improved national healthcare policies to control infections; and (iv) development of new antibiotic methods to tackle the rapidly-evolving resistance. The outcome is a nationwide decline in reported cases of C.diff and MRSA infections in patients since 2008, with consequent economic benefits to the NHS, Government and employers.
Research by Smales has led to IP that protects novel technologies for mammalian recombinant cell line development. Based upon mass spectrometry and in silico modelling approaches, the technology has permitted the development of highly efficient cell lines for monoclonal antibody production in the commercial environment at Lonza Biologics. This IP has three important benefits to the pharmaceutical and biotechnology industries:
(a) It allows key biopharmaceuticals to be made using substantially less resource and with an overall higher efficiency.
(b) It reduces the time from transfection to production of cell banks.
(c) It accelerates bioreactor evaluation and the ability to predict cell line performance at the bioreactor scale early in cell line construction.
Impact: Economic. The EaStCHEM spin-out company Deliverics has commercialised biodegradable transfection reagents for both the "research tool" and the "RNAi therapeutics" markets (globally valued at £400M and £4 billion respectively). Beneficiaries are the pharmaceutical and biotechnology sectors, and clinicians. The turnover since 2010/11 is £330k and the company currently has five employees.
Significance: Deliveric's agents out-perfom existing materials in term of efficacy and reduced levels of toxicity. They are not hampered by the immunogenicity, manufacturing issues, and carcinogenicity previously seen for viral vectors used as delivery agents. This presents a wide ranging ability to deliver nucleic acids into cells and tissues for biological applications.
Research; date; attribution: EaStCHEM research (2008) led by Bradley reported a family of non-viral DNA delivery agents that offered a highly-efficient and non-toxic method of delivering siRNA/DNA into mammalian cells and tissues. Development and patenting of this technology led to the spin-out of Deliverics Ltd. in 2010.
Reach: International customer base (20 research groups and 10 companies) including specially appointed distributors in Spain (Albyn Medical), South Korea (CoreSciences), and US (Galen).
Cardiff University research in 1997-2008 resulted in the development of a family of novel far-red fluorescent dyes that stain the DNA of cells. The leading live cell dye DRAQ5™ is now utilised in a wide range of laboratory assays, transforming practice in clinical, commercial and research sectors. Smith co-founded the multi-award-winning start-up company Biostatus Ltd in 2001 to undertake product development. Commercial impact post-2008 has been the generation of over $3.2 million in sales revenue enabling job creation, direct funding of UK academic research positions and creation of new technology start-up companies. Used in over 3,500 research, pharmaceutical and clinical organisations, DRAQ™ technology has global reach.
Bacteria of the Clostridium genus are of pathogenic, medical and industrial importance. Development by University of Nottingham School of Life Science researchers of three patented methods for genetic manipulation of clostridial species has led to licensing agreements for commercial exploitation of the methodology to enhance strains for chemical commodity and biofuel production and for targeted cancer therapy. These methods are providing significant world-wide impact by facilitating commercial R&D investment and technology developments in fields ranging from healthcare, through chemicals manufacture, to the environment.
Psoriasis is a chronic inflammatory skin disorder affecting up to 2.5% of the world's population, approximately 30% of whom eventually develop psoriatic arthritis, which can lead to debilitating long-term health problems. Current therapies are limited owing to side effects or reductions in efficacy. Prof Miles Houslay, University of Glasgow has performed internationally recognised research on drug targets to alleviate the symptoms of inflammatory skin conditions. Working with Celgene, Houslay identified lead compounds and assays to screen promising early compounds for the treatment of psoriasis and psoriatic arthritis for clinical development. This identified the lead compound (apremilast), which was subsequently developed by Celgene. Between 2010 and 2013, phase III trials on apremilast have validated it as a safe, clinically effective oral drug, on the basis of which apremilast was submitted for regulatory approval of its use in patients with psoriatic arthritis to the health authorities of the USA and Canada in March 2013.
Many clinically-useful natural products fall into the class of polyketides. From 1993, research led by Professors Leadlay (Biochemistry) and Staunton (Chemistry) on polyketide biosynthesis pathways led to the foundation of the spin-out company Biotica Technology Ltd in 1996. Between 2008 and 2013 the company provided continuous employment for on average 15-20 highly-skilled scientists, and attracted additional investments of £4.43M. Its follow-on company Isomerase Therapeutics Ltd, founded by ex-Biotica researchers with Leadlay's support in 2013, has acquired compounds, strains and IP from Biotica. Using the methods developed in the University by Leadlay and Staunton, Biotica developed a HepC antiviral therapy, sold in 2013 to NeuroVive Pharmaceuticals AB and currently entering pre-clinical toxicology tests. Biotica have also licensed their technology to a number of companies globally, including GSK and Amyris.
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.
University of Huddersfield research in physical organic chemistry has delivered economic, industrial and societal benefits. It has led to process improvements in chemical manufacturing, most notably in the optimisation of the synthesis of antisense oligonucleotides and in the use of liquid ammonia as a solvent. It has also led to the development of new inhibitors of bacterial β-lactamases for use as antibacterials. The research team's expertise has been reflected in the success of IPOS (Innovative Physical Organic Solutions), a unit established in 2006 to carry out research in process and other areas of chemistry for the chemical industry. IPOS expanded significantly from 2009 to 2013 and has now collaborated with more than 150 companies, many of them based in Yorkshire/Humberside where regeneration is critically dependent on the success of new, non-traditional, high-technology firms and industries. Through these collaborative projects, IPOS has contributed to the growth and prosperity of both regional and national industry.