Introduction
Catalysis research has had a major positive impact on the UK economy. Evidence for this is provided by the over 60 impact case referencing catalysis or biocatalysis studies submitted to the 2014 REF exercise. Case studies involving catalysis and biocatalysis span Chemistry, Biology, Engineering, Agriculture, Pharmaceuticals, Built Environment, materials and Physics demonstrating wide ranging impact on industry since the involvement of the UK Catalysis Hub since 2013 in UK catalysis this impact will have grown. Highlights from the impact case studies from the 2008-2013 period are provided in this Appendix. More information can be found here
Catalysis and Biocatalysis Case Studies
Enabling the cost-effective and environmentally friendly production of Perspex
Summary
Advances in bisphosphine ligand synthesis carried out at Cardiff University have enabled industrial scale application of a cost-effective new process, the Alpha Process, for the production of methyl methacrylate (MMA) monomer a key commodity precursor to Perspex. The Alpha Process has had economic and environmental impacts.
Lucite International, the world’s leading MMA producer, has invested in major Alpha Process production facilities in Singapore and Saudi Arabia, benefitting from a production route which is more efficient, more reliable and cheaper than conventional routes.
The Alpha Process also brings environmental benefits, as it does not rely on the use of corrosive and toxic feedstocks, such as hydrogen cyanide, which are associated with conventional MMA processes.
Impact
The economic impact is demonstrated by investment of US$230 million by Lucite International, part of the Mitsubishi Group, in a new plant in Singapore which has been producing 120 kilotonnes of MMA per annum since 2008 [1]. Based on the success of the Singapore plant, Mitsubishi Group signed a Letter of Intent with Saudi Basic Industries Corporation, with the tender to issue in 2013, to build the largest MMA plant in the world, costing US$500 million and producing 250 kilotonnes annually (around 6% of global production) [2]
This process brings major environmental benefits compared to conventional manufacturing technologies, as it produces only environmentally benign waste products and does not rely on the use of toxic feedstocks, such as hydrogen cyanide and sulphuric acid, commonly used in alternative processes. For example, Alpha Process production at the Lucite Singapore plant produces annual savings of 19 kilotonnes of hydrogen cyanide and annual savings of 360 kilotonnes of spent acid, including sulfuric acid and ammonium sulphate, compared to the conventional ACH route. The atom-efficiency of the Alpha process also brings waste management benefits, as it means that there are no toxic wastes or by-products [1]. A purer MMA product also has knock-on benefits for downstream users and applications industries in minimising requirements for further purification as well as providing assurance of a dependable supply of higher quality plastics from readily available feedstocks.
More details can be found here
Industrial application of computational models and experimental techniques for catalyst development and optimisation
Summary
The development and application, by a UCL and Royal Institution (UCL/RI) team, of a powerful range of computational and experimental techniques has had a major impact on understanding of catalysis at the molecular level. The translation of these approaches to industry — achieved through fellowships, collaborations and employment of trained UCL/RI scientists — has had substantial impact on the development and optimisation of key catalytic systems used in energy, environmental, bulk and fine chemicals production. Computational modelling software has been commercialised by Accelrys. Products and processes at Johnson Matthey have been developed and enhanced over a shorter timescale, ultimately leading to good returns and a sustained market position. The approaches also provided evidence that platinum-containing vehicle emission catalysts are not a source of chloroplatinates in the environment and can therefore continue to be used.
Details of the impact
The translation to industry of QM/MM techniques has been realised through commercial software development. The Nanotechnology Consortium. in collaboration with the STFC, developed a QM/MM module (QMERA) for Accelrys’ Materials Studio® modelling and simulation environment software [A]. Materials Studio enables investigators to relate product performance with material properties and behaviour at the molecular, atomic, and meso scales.
At Johnson Matthey (JM), adoption of new techniques developed has shortened research projects, aided understanding and improved the company’s competitiveness [3]. Transfer of synchrotron radiation (SR)-based techniques to industry and the introduction of SR techniques at JM has been invaluable to the company’s catalytic technology and materials processing [3]. Furthermore, a range of in situ methodologies has been designed and developed for JM, which has helped make its analytical science and technology highly competitive with other similar chemical companies around the world [3].
Collaborative projects with JM — for example, have led to commercial benefits for the company [4,5]. Here, work has primarily focused on applying the techniques developed to the field of bulk industrial chemical production, particularly in the development of inorganic oxides. These are important industrial catalysts used in the annual worldwide production for example ammonia, hydrogen, nitric acid and methanol [6]. This work has contributed to novel materials design, cost-effective synthesis of catalysts and understanding of their application under aggressive chemical process conditions [6].
In 2011, in collaboration with JM and other international organisations, the application of XAS techniques [7] provided essential learning for members of the International Platinum Group Metals Association (IPA). The work was used in 2012 as part of the science case that demonstrated that the major industrial use of platinum in the catalysts was not a direct source of chloroplatinates. The global emission control catalyst market reached $6.7 billion in 2012 [3].
More details can be found here
Replacement of heavy metal catalysts in the plastics industry
Summary
Catalysis is a major UK industry strength and wealth generator for the UK economy. Research carried out at the University of Bath resulted in the development of titanium and zirconium alkoxide catalysts for use in three industrial polymerisation processes and patented by the UK companies ICI, Synetix and Johnson Matthey. Patents have also been acquired by the Indian multinational Dorf Ketal and filed by the Dutch multinational Corbion Purac. The research has resulted in the adoption of new catalysts in industry leading to increased turnover, onward dissemination and implementation of the Bath intellectual property. This work has focused on the use of more environmentally friendly metals such as titanium as replacements for heavy metals such as tin, antimony and mercury in areas such as catalysis. One such area has been the need to develop new Lewis acid catalysts to mediate industrial polymerisation processes such as PET and PU manufacture, as well as for the ring-opening polymerisation (ROP) of cyclic esters. The chemistry is motivated by a drive for the use of more sustainable metals in these high-volume manufacturing processes and also by the introduction of a new generation of commercially viable, sustainable degradable plastics available from renewable resources.
Details of the impact
Three classes of titanium and zirconium catalysts for plastics manufacture have been developed at Bath and patented, covering manufacturing processes for the important polymers poly(ethylene terephthalate) (PET), poly(urethane) (PU) (with plastics markets worth $23B and $33B, respectively, in 2010) and, more recently, towards use in improved processes for poly(lactic acid) (PLA).
A critical element of the Bath research is not only the specific catalysts developed in the published work but the fact that these innovations, and the sharing of the intellectual property with Johnson Matthey, through extensive collaboration
In March 2011 Dorf Ketal, an Indian Chemicals company who are one of the largest in the world, purchased PET and PU catalyst intellectual property from Johnson Matthey in a £4.6M transaction; this income can be directly attributable to the Bath research. These new Bath-developed catalysts have thus had impact through their adoption in manufacturing processes, as a replacement for undesirable heavy metal catalysts (notably antimony and more recently mercury). In addition to their adoption in manufacturing plants, aspects of these catalysts and associated processes have been sold on internationally, providing evidence that this chemistry is of ongoing value and impact.
More details can be found here:
Industrially relevant olefin polymerisation catalysis at UEA
Summary
Research at UEA over a 20 year period in the area of olefin polymerisation catalysis has had significant economic impact. A series of research programmes into the activation chemistry and mechanisms of single-site catalysts for olefin polymerisation, mainly metallocenes, has been undertaken alongside industrial partners and with industrial funding, thus maximising the opportunity for knowledge transfer to the manufacturing industry throughout the period.
Investigation of metallocenes as active species was followed by the development of activators that led to ultra-active catalysts. Studies on polymerisation kinetics, the solution dynamics and on aggregation phenomena led to the discovery of the “trityl effect”, which can increase the activity of metallocene catalysts by up to an order of magnitude. Research into the role of trimethylaluminium (TMA) in polymerisation catalysis includes the first identification of TMA association equilibria and their influence on catalyst activity in polymerisation catalysts. Using weakly coordinating anion chemistry, this research was able to provide a more energy-friendly alternative for butyl- rubber production.
Details of the impact
World polyolefin production has risen from 25.6M tonnes in 1983 to an estimated 150M tonnes in 2010, with a total market value of several billion US$, and single-site polymerisation catalysts market sector shows an annual growth rate of more than 10% p.a. A key route to economic impact has been through industry funded IPR protection. For example, within the butyl rubber polymerisation area, research has resulted in 5 world-wide `patent families’ each containing 5-7 filings. Statements from key industrial partners, DSM and Sabic, indicate quite clearly the importance of the UEA research.
DSM is a Dutch-based global life sciences and materials company with a wide range of product. In 2012 DSM had net sales figures of €9.13B. Sabic, one of the World’s top 10 petrochemical companies. In Europe, Sabic is a major producer of plastics and chemicals with approximately 6,300 employees. Sabic-Europe operates 13 petrochemical production sites, including a site at Geleen in The Netherlands which produces large volumes of polyethylene (940 ktpa), and polypropylene (620 ktpa). Geleen’s output is used in the automotive, luggage, and food packaging industries. The packaging market accounts for nearly a third of all Sabic-Europe’s polymer sales within Europe. For the production of food packaging materials, it is crucial that all polymers comply with EU Plastics Regulations, including the catalysts. This research has been important within such polymer production.
More details can be found here
Economical and beneficial environmental impact on industrial production of ethyl acetate
Summary
Studies into the deactivation and regeneration of heteropoly acid catalysts, which took place in Liverpool University, resulted in the large-scale industrial application of these catalysts in BP’s process for the synthesis of the widely used solvent ethyl acetate, thus making significant economic and environmental impact.
Catalysis by heteropoly acids (HPAs), also known as polyoxometalates, has attracted much interest both in fundamental and applied research because of its potential to generate significant economic and environmental benefits. This makes them promising solid acid catalysts for various reactions both in gas and liquid phases. However, the relatively low thermal stability of HPAs and difficulty of catalyst regeneration had always been obstacles to their commercialisation, rendering their use in heterogeneous acid catalysis rather limited. It was found that catalyst modification with platinum group metals, such as palladium, significantly reduced the temperature of catalyst regeneration without HPA degradation [9]. Particularly important was the finding that addition of polar molecules (n-donors) such as water etc. to the feed could greatly reduce coking of HPA catalysts thus improving catalyst life without the need for frequent regeneration [10].
The result of this collaborative research was the development of effective methods to improve the stability and lifetime of the HPA catalysts.
Details of the impact
This process, trademarked AVADA (for AdVanced Acetates by Direct Addition of acetic acid to ethylene), was launched in 2001 at Hull, UK, on a scale of 220,000 tonnes p.a., then the world’s largest ethyl acetate production plant. In October 2011, the AVADA process produced 56% of the ethyl acetate in Europe (245,000 tonnes p.a. production capacity and $340m p.a. factory gate value), being the second largest in the world after the Zhenjiang 270,000 tonnes p.a. ethyl acetate plant in China. Over the period 2008-2013, the AVADA process produced 1.2 million tonnes of ethyl acetate worth $1.7 billion. The AVADA process makes ethyl acetate with 100% atom efficiency, avoiding the use of ethanol as an intermediate. It beats conventional processes in environmental friendliness by reducing energy consumption by 20% and feedstock losses by 35%, thus removing more than 100,000 tonnes p.a. of wastewater stream. At the heart of the AVADA process is a highly efficient heteropoly acid catalyst that is responsible for its superior performance. Implementation of measures improving catalyst stability and resistance to coking, which originated from collaboration between Liverpool and BP Chemicals, prevented otherwise fast catalyst deactivation to create an economically viable process.
Regarding its environmental friendliness, the AVADA process is by far ahead of conventional ethyl acetate syntheses [11]. Traditional ethanol esterification units produce as much water as they do ethyl acetate and therefore require treatment and disposal of this waste stream. In the AVADA process, elimination of ethanol as intermediate eliminated the transport of some 60,000 tonnes of ethanol by road and removed more than 100,000 tonnes p.a. of wastewater stream. Compared to conventional processes, AVADA’s energy consumption is about 20% lower and feedstock losses are some 35% less than in conventional esterification with benefits to CO2 emissions [11]
In 2008, BP sold the ethyl acetate and related vinyl acetate monomer businesses to INEOS Enterprise, a Swiss headquartered petrochemical group, for an undisclosed amount. At that time each facility had 250,000 tonnes p.a. capacity and together employed around 40 people (www.knak.jp/big/ineos.htm).
According to a ICIS Chemical Business report (October 2011), the INEOS (former BP) plant at Hull (245,000 tonnes p.a. production capacity, $340m p.a. factory gate value) by far dominates ethyl acetate production in Europe (56% of the total 440,000 tonnes p.a.),
More details can be found here
Design and Application of a Tool for the Qualitative and Quantitative Analysis and Prediction of the Effect of Ligand Structure on the Catalytic Activity of Metal Complexes
Summary
The selection of ligand(s) for the transition metal complexes that are frequently employed as catalysts for the production of fine chemicals is a key activity ultimately governing the financial viability of the process. The development of a novel methodology for the qualitative and quantitative analysis and prediction of the effect of ligand structure on the catalytic activity of late-transition metals has been applied in process and discovery chemistry in pharmaceutical and agrochemical industries in the UK (and beyond). The analysis allows rapid, and therefore cost efficient, identification of ligands and catalysts with the potential to bypass intellectual property issues. Between 2006 and 2010 AstraZeneca provided £763k to fund this research in. In parallel, AstraZeneca invested £1m in the provision of a semi-automated catalyst testing facility at Avlon to service catalytic reactions in projects within the company that were proving unreliable or low-yielding for drug discovery or for scale-up for clinical trials. A second phase (“Phase 2”, 2010-2012) of underpinning research was supported by a Knowledge Transfer Partnership grant of £116k to develop the application of the Ligand Knowledge Base for amination reactions at AstraZeneca,
During the period of the Knowledge Transfer Partnership grant, and based on the extensive experience in catalyst development generated by collaboration with the Bristol based team “CatSci” was established in May 2011. This spin-out from AstraZeneca was established as a start-up company based in Cardiff which has led to a third phase (“Phase 3”, 2012-2014) of underpinning research being supported (£175k) by a Welsh Government “Research, Development and Innovation Grant” in collaboration with CatSci in a project to link calculated catalyst property descriptors with optimally designed catalyst screening data, and thus to develop novel catalysts. This project is allowing CatSci to more effectively apply its expertise in the development and optimisation of transition-metal catalysed reactions, and thus assist in the efficient evolution of this industrial spin-out activity.
Details of the impact
AstraZeneca
This company can now identify ligands for transition metal catalysis more efficiently. The Ligand Knowledge Base principal component analysis feeds into a Design of Experiment programme that defines the `chemical space’ within which ligands will be tested and how most efficiently to explore this space. AstraZeneca estimated at the end of Phase 2, that this advance led to about £250k cost saving and it anticipates on-going savings will be in the region of millions of pounds. The impact of these developments were recognised in the form of an AstraZeneca Science & Technical Award in October 2010.
CatSci Ltd
This company, which predominantly arose from activities under the auspices of the Ligand Knowledge Base programme. These techniques derive directly from this collaboration, Initial investment in facilities has been £0.52m in equipment staff, with £1.2m of business already secured (2013).
Phosphonics Ltd
Concepts arising during the initial phases of the research led to the design of unique `catalyst capture/release’ technology. This concept is now being made ready for the market by Phosphonics via a collaboration supported by the TSB/EPSRC through the Technology Strategy Board ” This £700k project (“Recyclable Catalyst Technology for Cross-Coupling Reactions at Manufacturing Scale“) draws together Phosphonics, CatSci, Syngenta, AstraZeneca, Albany Molecular Research and the University of Bristol. Initial applications towards the manufacture of pharmaceuticals & agrochemicals will be a demonstrable output during 2013-2015.
More details can be found here
Oxford Catalysts Group – a successful company built on the development and application of highly-active catalysts for the conversion of natural gas to liquid hydrocarbons
Summary
Research carried out at the University of Oxford led to the spin-out of Oxford Catalysts Ltd. A large part of the company’s technology is based on Green’s transition-metal catalysis research, which has enabled them to develop a highly efficient Fischer-Tropsch (FT) catalyst to convert natural gas to liquid hydrocarbons. In 2010, Oxford Catalysts Group (now Velocys) demonstrated the world’s first smaller-scale, modular gas-to-liquids and biomass-to-liquids FT plants which made use of the catalyst for the efficient conversion of low-value or waste gas to liquid hydrocarbon fuels.
The key technology behind the catalysts used by Oxford Catalysts was the development of a less expensive, non-precious metal, molybdenum and tungsten carbide catalysts [12-14]. A patented synthesis creates catalysts with superior activity and are less susceptible to deactivation over time and are effective for FT catalysis to converts syngas into hydrocarbons [15]. Moreover, they do not promote carbon deposition and are selective to form hydrocarbons with five or more carbon atoms. A high selectivity is required for an economic commercial process.
Details of the impact
After its spin-out from the University of Oxford in 2004, Oxford Catalysts Ltd. concentrated on the creation of highly active and efficient cobalt-based FT catalysts. Such was the perceived potential of this new technology that the company’s Initial Public Offering of 2006 raised £ 15M and was over-subscribed. In 2008, the company merged with Velocys, a US company specialising in microchannel chemical reactors Existing FT plants are huge, designed for production levels of around 30,000 barrels of liquid fuel per day (BPD), and cannot be scaled down economically. Gas located at remote locations, and Biomass resources that are often wasted because is not economically viable to pipe the gas to where it is needed. The technology developed by Oxford Catalysts Group makes it possible to take advantage of these `wasted resources’ to produce liquid fuels by using the biomass-to-liquids (BTL) or gas-to-liquids (GTL) processes. An added advantage is that the process creates synthetic clean fuels free from sulphur and aromatics (unlike those produced in conventional refinery processes), and can be tailored to produce high-value hydrocarbons[16]. Oxford Catalysts Group has established a partnership with offshore-facility developers MODEC and the global engineering firm Toyo Engineering to develop small-scale GTL facilities based on microchannel reactors and designed for use offshore [17].
The huge potential of the reactors has generated a high level of investment in the company. Between 2008 and the end of 2012, the group achieved revenue of £ 30M and received over £ 60M in investment. £ 30.6M of the investment was raised in January 2013, at which time Roman Abramovich invested £ 4.3M in the company,
In May 2012, Oxford Catalysts announced the sale and start-up of a commercial scale FT reactor at an integrated energy company facility [18]. The Group’s technology has been selected for 4 commercial-scale projects including:
- A 1,000 BPD commercial GTL plant for Calumet Specialty Product Partners, L.P., a major US-based producer of speciality petroleum products, [19].
- GreenSky London waste-biomass to jet fuel commercial plant, in partnership with BA. Like many airlines, [20] – reportedly 50,000 tonnes of jet fuel annually over 10 years equating to $ 500M at today’s prices.
- A 2,800 BPD GTL plant being developed by Pinto Energy in Ohio, USA, to convert low-cost natural gas into high value specialty products as well as ultra clean transportation fuels [21].
In November 2012, Oxford Catalysts Group was named as the preferred supplier of FT technology for Ventech Engineers LLC, a global leader in the design and construction of modular refineries. The deal raised £ 1.2M for the Group, and in April 2013, Ventech placed an order worth $ 8M for FT reactors for a plant of sufficient capacity to produce approximately 1,400 BPD. This gives an indication of the expected income from the projects listed above. Kevin Stanley, CEO of Ventech Engineers commented, `After an extensive search of available technologies we identified Oxford Catalysts’ FT product as the leading offering in the industry for modular GTL plants’ [22].
More details can be found here
Wills Catalysts: commercialised systems for enantioselective production of pharmaceutical intermediates
Summary
A process for the commercial production of a family of Warwick-invented organometallic catalysts has been developed and patented by Johnson Matthey (JM). The catalysts — which have been sold internationally to several fine chemical and pharmaceutical companies in kilogram quantities, capable of producing tonnes of product — are in widespread industrial use for synthesis and scale-up.
New Ru(II) tethered catalysts have been developed and their mechanisms and wider applications have been reported. Catalytic hydrogenation is a pivotal chemical transformation which underpins the synthesis of numerous high-value target molecules, materials and intermediates. Wills tethered catalysts — invented at Warwick and commercialized by collaborators and competitor businesses — have been shown to have significant commercial advantages over the existing systems.
The Wills catalyst was tested by Johnson Matthey Catalysis and Chiral Technologies (JM CCT) for a scalable synthetic route to the catalysts, which was later demonstrated on multi-100s gram scale and kg-scale at Alfa Aesar; a Johnson Matthey company [23]. A patent was filed in 2009 [24].
Details of the impact
Since 2009 JM CCT — through Alfa Aesar, SigmaAldrich and Strem — has sold four Wills tethered catalysts in the family, either individually or as a part of a `kit’ (catalogue prices £368-£560 per gram). JM CCT also uses the material in collaborative projects with client companies worldwide [23].
AstraZeneca (Sweden & UK), one of the largest pharmaceutical companies in the world, describes in a process patent the use of (S,S)-teth-TsDpen-RuCl (a JM CCT trade name for a Wills catalyst) in the catalytic asymmetric synthesis of a class of anti-asthmatic bronchodilator drugs [25].
Synthon BV (Netherlands) report the use of a Wills catalyst in the key chirality-inducing reduction step in their synthesis of the anti-asthmatic drug montelukast (singulair), a drug which in 2010 was the fourth most prescribed drug in the US (24.7 M). They conclude, “It has now been discovered that the use of [Wills catalyst] can provide a more suitable process for the asymmetric transfer hydrogenation reaction” [26].
Archimica GMBH (Germany) patented the use of a Wills tethered catalyst in the key chirality-generating step of their synthesis of the third generation antiepileptic drug Eslicarbazepine [27].
Boehringer Ingelheim (Germany), one of the largest pharmaceutical companies in the world, describe their route to certain chemokine inhibitors via the reduction of an early-stage intermediate using a Wills tethered catalyst [28].
Lek Pharmaceuticals (Slovenia), part of the Sandoz group, has reported an improved process for the preparation of intermediates on route to non-steroidal selective estrogen receptor modulators such as lasofoxifene using the Wills catalyst [29].
In collaboration with Eli Lilly (USA), one of the largest pharmaceutical companies in the world, JM CCT have developed an achiral version of the Wills tethered catalysts and have applied this to racemic reductions [23].
Additional examples from a rapidly growing list further demonstrate the international commercial reach of the Wills catalysts, in e.g. China (Hunan Fangsheng Pharma, patent CN102978253A), USA (Ambit Biosciences, patent US2012053193A1) and Italy (Zach Systems/Zambon Chemicals, patent WO2012120086).
JM CCT recognized the commercial need for the use of dihydrogen as the primary reducing agent and will develop this area with Wills through a TSB-funded collaborative grant Development of the future generation of catalysts for asymmetric reduction (TSB ref: 101330, Mar 2013, £216k plus £108K from JM CCT), extending the range of catalysts and their applications. In a further development, a new synthetic route to the Wills catalysts and novel variants is the subject of a patent application filed by Warwick (UK patent application 1219716.6, 02 Nov 2012; PCT/GB2013/05286901, 01 Nov 2013); licensing negotiations are ongoing.
More details can be found here
Catalytic Converter Research Leads to Major New Product for Motor Vehicles
Summary
Globally there are estimated to be 60 million cars produced each year. These all require catalysts emissions legislation. Catagen Ltd, a spin-out from Queen’s University has developed a product for testing motor vehicle catalysts that is 85% cheaper to operate than traditional methods and represents a 98% reduction in CO2 emission from testing and an 80% reduction in energy input. Major global customers including GM motors and Fiat have adopted this revolutionary patent protected technology and international sales growth has been recognised, winning an all- Ireland business award for BEST High Growth Company 2012. The development of the new dynamic Catalyst Ageing System for testing motor vehicle catalysts dates back to the formation of CenTACat in 2003 [30]. CenTACat undertakes multidisciplinary research involving chemists, physicists and engineers with a common interest in understanding the fundamental principles that underpin clean energy production and environmental protection. Within this facility Douglas supervised PhD student Andrew Woods (now CEO of Catagen) and together they filed a patent relating to the IP that their research had developed for testing of catalyst materials [31]
Details of the impact
Traditional methods for engine testing are not only expensive in terms of fuel consumption but have secondary negative impacts including CO2 emissions. The dynamic Catalyst Ageing System currently out performs all published ageing procedures in terms of the balance of overall cost. It was research into the ageing of catalysts within CenTACat that resulted in a QUB spinout company Catagen Ltd, which was formed in May 2011. The first system was manufactured by FAST Technologies Ltd in Derry City with product launch in January 2012. This brought much needed jobs to a region with the highest youth unemployment in N Ireland. Catagen will have their own Belfast-based manufacturing facility in 2013, with FAST involved as a component supplier. This low carbon technology also outputs 50 times less CO2. Catagen delivered the first machine to Fiat CRF, Italy in June 2012 and, at that time, quotations were sent to 6 automotive companies. Turnover for the year 2012 was £200k and the company is projecting sales of £1m for 2013, with a company valuation of about £5m at that time.
International success is now being demonstrated with global sales toFiat, General Motors Company and Mahle Powertrain, the second largest company in the world producing engine components. As well as bringing economic rewards to Catagen this has been acknowledged by the Best High Growth Company Award at InterTradeIreland’s 2012 all-island Seedcorn Business Competition.
More details can be found here
Power and fuel from renewable sources, waste and residues
Summary
The impacts of bioenergy research at Aston University, have been through influence and support for businesses. The EU, UK and local governments have developed policies with the Unit’s advice on the potential of bioenergy for power generation and waste reduction. Technical and business advice have been provided, a new company formed, investments made in new business directions by SMEs and large multinational companies. Pyrolysis reactors have been designed, modelled and built, at laboratory to pilot scale, for different biomass feedstocks and for the formation of specific products. Central to the research has been the evaluation of sources of biomass for the product required. Various high volume agricultural, domestic and industrial wastes and residues have been evaluated in collaboration with companies in these sectors, including paper mills (Aylesford Newsprint), brewery residues (Johnson Matthey with Molson Coors Brewery) and sewage sludge (Severn Trent Water). The research has shown that, through pyrolysis, biomass and residues can be used to produce power, fuels and chemicals but that careful control of feedstocks and process conditions is required to limit corrosion, minimise build-up of tar residues and to optimise physical and chemical properties of products [33]. A pilot-scale Pyroformer, installed by Aston on the Harper Adams University estate, demonstrated the use of agricultural, other bioresidues and waste products to generate heat and power cost-effectively during 2012, with residual char used for land improvement — a carbon negative process. The Pyroformer won “Best Technological Breakthrough” category at the national Climate Week Awards held at the House of Commons in March 2013.
Details of the impact
The Unit has achieved impacts internationally from the breadth of its bioenergy research through projects, demonstrations, advice and consultancy, for governments, companies, communities and charity work. The European Bioenergy Research Institute (EBRI) formed in 2008 resides in a self-sufficient building, completed at the end 2012, incorporates research laboratories and facilities for demonstration and pilot-scale trials by companies ( The expenditure of £16M) on.
Researchers contributed to “Sustainable biofuels: prospects and challenges”: an independent report for the Royal Society (2008) and provided expert advice to the Carbon Trust; in 2008 this led to the creation of the Pyrolysis Challenge with £20M funding supported by UK Government,
EBRI is used for promotion of bioenergy; including a visit by The Princess Royal (2012), MPs, MEPs, international Government representatives, the media, businesses and general public; there have been 41 press releases since its launch (2008-July2013) and 69 other media (international press — BBC, ITV, Sangat TV) and public briefings between January 2012 and July 2013.
From the start of the ERDF project in 2011 (to July 2013), more than 100 companies have benefitted from presentations and training. Companies include manufacturers with wastes and residues, waste contractors, land and estate developers, and pyrolysis equipment manufacturers. Of these, 85 partners (two thirds being SMEs) benefit by working actively with EBRI to develop their businesses. E.g. Brookside CIC secured funding (£15k) and support from UnLtd to follow up a feasibility study by EBRI that identified the viability of developing a `community-scale’ bioenergy plant, based on Aston research, to provide heat, power and cooling to a local Community Centre (July 2013). As part of Birmingham’s environmental planning to achieve CO2 reduction of 60% by 2026, a member of EBRI staff has been 50% funded by Birmingham City Council (UK’s most populous city after London). A small technical services company, C.A.R.E.Ltd, Belfast, has drawn knowledge since 2008 for customers worldwide [34], from Aston’s bioenergy research.
EBRI has impacted a Charity to support rural Indian communities, with consequential social and environmental benefits, and business opportunities for Industrial Boilers Ltd, Delhi. Working with the Indian Institute of Technology Ropar, through an RCUK Science Bridge project and more than £500k phased funding from Oglesby Charitable Trust [35] to provide reformers to rural communities providing energy and reducing pollution.
More details can be found here
Warwick Effect Polymers Ltd
Summary
Research at Warwick by Professor David Haddleton’s team led to the discovery of a new family of catalysts for living radical polymerisation. A spin-out company, Warwick Effect Polymers Ltd (WEP), was established to develop this research and received a total of £3.77M investment. Supplemented by income from contracts and operating in purpose-built laboratories on the Warwick Science Park, WEP employed 10-15 people and spent £3.0M developing a substantial patent portfolio. WEP’s commercial success and intellectual property in polymer therapeutics and nanomedicine led to its acquisition by PolyTherics Ltd in 2012.
A family of pyridine imine and diazabutadiene copper catalysts for living radical polymerization [36], Including methacrylate (as opposed to acrylate) monomers. The catalysis and polymerisation methodology allow new combinations of functional properties in the polymers, such as adhesion, pH sensitivity, thermal response and hydrophobicity/hydrophilicity [37]. Applications inflide pharmaceutical poly(ethylene glycol) with advantages over traditional architectures that have low tendency to crystallise, thus reducing damage to liver, spleen and brain [38, 39]. And expanded to the preparation of synthestic glycopolymers from functional initiators for bioconjugation [40].
Details of the impact
Polar polymers such as polyesters, polyamides, polycarbonates, acrylates and methacrylates are traditionally used in commodity applications such as in textiles and engineering. The spin-out company Warwick Effect Polymers Limited (WEP) was formed in 2001 with the initial purpose of exploiting the new Warwick living radical polymerization technology with end users. With a DTI SMART award, £5k from 1st prize at a Cambridge Enterprise Launch Pad event and investment from a US business angel the company started trading in 2002. In 2013 WEP is still based in its own laboratories on the University of Warwick Science Park employing 10-15 people on average]. The company has also funded over 20 students and research fellows.
The relevant Warwick/Haddleton IP was assigned to WEP, and a pipeline agreement (2002-12) facilitated collaborative work with several companies including Unilever, Courtaulds, ICI, BP, Geltex (Genzyme), Biocompatibles, Syngenta, Elf AtoChem in exploiting the underpinning research. With Unilever, for example, work on ABA triblocks led to patents relating to personal care products [12]. The focus of the WEP has been development polymers for therapeutics and nanomedicine. The pegylation and glycopolymer. WEP’s comb polymers (PolyPEGTM) have the advantage of “lower viscosity compared to conventional PEG polymer [that] is utilised to extend the in vivo half-life of protein therapeutics by reducing the clearance rate.” This advantage “has been demonstrated by WEP’s partners within the pharmaceutical industry”. To support its R&D programme, WEP received £3.77M since 2001 in venture capital funding (angel investors plus national, international and regional venture capital trusts) [41,42] and the company now holds three patent families [10]. Since 2008, WEP has supplemented its capital investment throuh a portfolio of more than 10 multi-contract projects with major companies. For example, with Unilever, a new technology in protein conjugation of polymers has been developed to protect human hair against damaging treatments [17]. New synthetic glycopolymer technologies, transferred to WEP under the pipeline agreement and developed as GlycoPolTM and ZenoPolTM (trademarked 2009 and 2011 respectively) are being tested by a global pharmaceuticals leader for gene delivery [43].
In 2012 WEP was acquired by PolyTherics Ltd in a substantial (undisclosed) share-for-share deal. In July 2013, following PolyTherics acquisition of WEP and Antitope Ltd, £13.5M further investment was raised from some of WEP’s funders (Mercia Fund Management and Advantage Enterprise & Innovation Fund) and Invesco Perpetual. The group now employs more than 80 staff. Revenues of the combined Polytherics businesses exceeded £8.5M
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Plaxica: Transformational Biopolymer Technology
Summary
Plaxica is a spin-out from, and based, at Imperial College London with economic, societal and environmental impacts. Launched in 2008, Plaxica is a process technology licensing business which is tackling the barriers that currently prevent a wider acceptance of bioplastics; specifically improving properties, decreasing cost and using non-food feedstocks to manufacture the biopolymer poly(lactic acid), PLA. Plaxica’s technology uses sustainable feedstocks to produce PLA using more energy-efficient processes, to produce a strong, high-quality polymer, the result of which is a low-cost, environmentally-friendly biopolymer for use in applications including textiles, packaging, and automobile parts. Aspects of this work have been performed in collaboration with a number of multinational chemical companies including BP and BASF.
Gibson and Marshall started to examine polymers from renewable resources and produced a number of academic publications and patents (e.g. [44-46], The properties of PLA could be improved by using catalysts to promote the formation of stereoregular PLA. With this advance, thermal stability, for example, could be increased to >100°C, greatly increasing the potential applications for PLA. Particular success was found with several families of aluminium catalysts, some of which led to PLA with melting points approaching 200°C [47,48]. These important and commercially-relevant findings in the mid-2000s spawned the idea of Plaxica.
Details of the impact
Plaxica was formed from academic research into catalysis for the production of PLA in 2008 [49]. The basis of Plaxica’s technology is fully-owned by the Company. Plaxica is a process technology licensing company. It develops, demonstrates and designs process plants for the production of the key intermediates, especially L- and D- lactic acids and lactides, for stereocomplex polylactic acid (PLA) — a high performance biopolymer made from non-food renewable materials, such as cellulosic based materials. Plaxica’s technology allows high performance PLA to replace traditional polymers produced from oil. Imperial Innovations funded the initial launch of the company in 2008. A project involving Plaxica, Imperial and Holloid Plastics Ltd won funding for the High Value Manufacturing Technology Strategy Board in September 2009 [50], leading to conditions for the successful injection moulding of stereocomplex PLA. In October 2009 Plaxica received £1m in equity funding from Imperial Innovations, the Carbon Trust Investments Ltd and the National Endowment for Science, Technology and the Arts (NESTA). In 2010 Plaxica announced that it raised a further £3 million in a Series A financing in which all existing institutional investors participated. The funds were used to accelerate development and scale up of the company’s next generation PLA technology [51]. The funding consists of £1.2m Imperial Innovations) and £1.8m from other existing shareholders [51]. In 2011 Plaxica completed a £5m round in Series B financing with investment from Imperial Innovations, Invesco Perpetual and NESTA Investment and continued to attract investment as demonstrated by the recent £8M Series C financing round [10/9/13 announcement, 52]. The construction of a pilot demonstration facility in Teesside demonstrates Plaxica’s commitment to creating jobs and revenue within the UK. Examples of the local press include:
“The global polymers market is worth more than $400 billion in annual sales and has grown at an average of 3.5% per year over the last two decades. The current biopolymers market is in excess of $2 billion per annum and is growing at more than 10% per year. PLA has 40% of this market, at some $800m, and this is forecast to grow to $1bn by 2012” [53].
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The Founding of Argenta Discovery and Pulmagen Therapeutics
Summary
The growth and performance of Biofocus Galapagos Argenta (BGA) and Pulmagen Therapeutics (PT) are underpinned by research from the Imperial-based TeknoMed project [54-57]. In collaboration with the University of Cambridge and Rhône-Poulenc Rorer [58,59], the TeknoMed Project, concerns drug-design using combinatorial chemistry (CC) and rapid parallel synthesis [60]. The new techniques embodied methods for purification-minimised parallel synthesis, which are crucial in the early stages of drug discovery. The most significant of these methods is the use of ring-opening metathesis polymerisation (ROMP) for the fabrication of polymer-supported reagents and catalysts: ROMPgels and ROMPspheres. These functional polymers are used in fundamentally important organic synthesis reactions such as alkene formation and nucleophilic displacement. In a related method, a polymer-supported transition metal catalyst which promotes the joining together of two alkenes to make a new, more complex alkene together. In a new methodology. This release-and-catch concept was termed `boomerang’ catalysis, and is significant in that it minimises transition metal contamination of the alkene products.
Details of the impact
BGA was formed in 2010 through the acquisition of Argenta Discovery (AD) by Biofocus Galapagos for €16.5 million and is one of the world’s largest drug discovery service organisations. PT was formed as a separate company to own the complete AD drug pipeline. It develops new medicines to treat asthma, cystic fibrosis and allergic diseases. In 2011 BGA signed agreements with PT for an initial £6million fee and with Genentech for £21.5million. Argenta Discovery was fully funded in 2000 with £7.2m of private investment. In 2007, Argenta signed the largest-ever pre-clinical deal worldwide with AstraZeneca for the co-development of new therapeutic agents for respiratory diseases. This collaboration with up-front and milestone payments is potentially worth in excess of $500M plus royalties.
Argenta patents, 2008—
WO 2010015818 (Feb 11 2010), WO 2009060209 (May 14 2009), WO 2009060203 (May 14 2009), WO 2009013444 (Jan 29 2009), WO 2008122784 (Oct 16 2008), WO 2008119917 (Oct 9 2008), WO 2008096094 (Aug 14 2008), WO 2008017824 (Feb 14 2008), WO 2008017827 (Feb 14 2008)
In addition, Argenta has entered into major collaborations with global pharmaceutical and biotechnology companies including Aventis, Lundbeck, GSK, Novartis, Genentech, Domantis, Pharmagene. In 2010, Argenta Discovery sold the contract business and company name for €16.5 million [61] in cash to Biofocus Galapagos to form Biofocus Galapagos Argenta. At the time, Argenta had 140 employees. The combined division is “one of the world’s largest drug discovery service organizations, with 390 employees, an estimated €70 million in annual turnover and significant profitability” [61]. The Group’s combined service division operations, which will operate under the BioFocus and Argenta brand names, were expected to achieve €70 million in 2010 revenues (including ~€11 million in service contracts by Galapagos) [61]. In 2011 Argenta signed an integrated service agreement with Pulmagen Therapeutics: Under the terms of the agreement, Argenta will be eligible to receive up to £6 million (€7 million) in fee-for-service payments over two years, with the possibility to extend” [62]. Also in 2011, Argenta and BioFocus announced a two-year extension of a drug discovery collaboration with Genetech: Total potential value of the contract extension is up to £21.5 million (€23.4 million). This is the third such extension since the agreement was announced in December 2005. [63]. Biofocus Galapagos Argenta continued to expand (2010 CRO turnover >€135M [61]).
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Improved drug discovery and development through use of novel iridium catalysts
Summary
Labelled compounds form an essential part of drug discovery and development within the pharmaceutical industry. Novel iridium catalysts, developed by Kerr at WestCHEM since 2008, have introduced a step-change in the ability to label pharmaceutical candidate compounds with radioactive (tritium) or non-radioactive (deuterium) isotopes. The catalysts are applicable to specific types of compounds that comprise approximately one-third of all drug candidates. Advantages of the catalysts include greater, greater speed (, and a significant decrease in radioactive waste compared with previous methods (environmental and safety benefits).
The design of drugs, with optimal potency and pharmacokinetic properties, as well as increased safety profile, poses a major challenge for pharmaceutical laboratories. Attrition, or high failure rate, has emerged as a central problem in modern drug development. This contributes to an average cost of $1.7 billion for developing a new chemical entity (NCE) into a marketable drug. Efforts to improve efficiency are of high interest to the pharma industry with gains of 10% in the study of the pharmacokinetics of candidate drugs resulting in savings of the order of $100M per drug [64]. Practical and convenient methods were developed for the preparation of novel iridium complexes, that show exceptional activity in hydrogen isotope exchange processes. Interaction with AstraZeneca led to further development and transfer of the technology between WestCHEM and Mölndal. By 2010, three novel air-stable complexes showed great promise, providing effective labelling in short times (hours rather than days) at low loading (usually 0.5 % catalyst loading) to an extended list of substituents with tolerance of a wider list of solvents than conventional methods.
Details of the impact
In drug candidate compounds that are susceptible to HIE reactions, 90% now use the Kerr catalysts while 10% still use the older Crabtree catalysts. Since these studies underpin the development of all of the AstraZeneca drug candidates, it is clear that the new catalysts have a pervasive and significant influence on the development of new medicines within this multinational company. An extension of the impact has been the adoption of the new catalysts as commercial products by Strem Chemicals. They have marketed and sold the catalysts since October 2012 and in the 9 months since launch.
The pharmaceutical industry is now applying the new technology directly to its pipeline of pharmaceutical candidates, with AstraZeneca in the lead, but with uptake gathering pace globally. At present, the principal impact is on operational efficiencies and cost reductions for the pharmaceutical companies, but the impact passes to the population at large through the provision of safer, more effective medicines at lower cost and with less environmental impact.
The application of the new catalysts within the pharmaceutical industry ultimately impacts on mankind, since we are dependent on the development of safe and effective medicines at reasonable cost and without detrimental effect on safety or the environment. Use of the Kerr catalysts is helping to speed up drug discovery and development, allowing a rapid understanding of the metabolism of candidate drugs, and discrimination between candidates that can be progressed and those that must be rejected.
More details can be found here
Improvements to biogas extraction
Summary
The anærobic production of gas from waste — or biogas — is an important renewable energy source and means to prevent the release of methane, which is a powerful greenhouse gas. Exploitation of biogas is hampered by traces of siloxanes and H2S, which damage engines through the formation of SiO2, SO2 and H2SO4 during combustion. Research at Sussex in collaboration with PpTek Ltd (engineers of purification technology) has expanded the scope of current purification technology, meaning that biogas systems can be installed in a range of new sites.
The strong relationship between Chen and Turner at Sussex and PpTek Ltd is based on research to underpin the development and deployment of the photocatalytic purification of biogas streams for renewable energy generation. Collaborative research between PpTek and Sussex has been focused on deploying an optimised photocatalytic system as the successor technology for PpTek’s current absorption process. Such an approach has many advantages, not least in the energy requirement for purification, which will be much lower than the current thermal-regeneration methods. The capture of solar energy by semiconductors, whereby hole-electron pairs are generated and can then be used, either as charge carriers for electricity generation or directly harnessed in chemical transformations, is well known.
Details of the impact
This collaborative research has led to a strong increase in the commercial activity of the company, with turnover increasing from £910,000 in 2008 to £1.95m in 2012-13 and half year figures suggest turnover of at least £3m 2013-14 with £4.3m predicted for 2014-15. As a result of Sussex research, a new process has been developed which allows expansion of PpTek’s commercial activity to biogas sources with more chemically difficult and variable gas compositions emitted from anærobic digesters and sewage treatment works. Previously, application of this technology in these chemical conditions was problematic and, in some cases, required the replacement of parts under a contractual obligation. One beneficial impact is that 81 additional biogas installations have been deployed on sites that generate on average 2-3 MW of green energy per year each, enabling the UK to better meet its target under the Climate Change Act of 2009 [see Section 5, C1]. Following analysis of biogas at Sussex, the company has been able to successfully deploy its technology into some highly contaminated landfill sites by filtering some components from the gas before the siloxanes removal system, thus avoiding media failure before end-of-life expectancy. As of June 2013, PpTek purification systems are now deployed in sites owned by CLP Envirogas (Bolton), Southern Water (Worthing), Wessex Water (Bath), Coxhoe Landfill (Durham), United Utilities (Manchester) and Severn Trent Water (Nottingham), amongst others. The collaborative research between PpTek and Sussex formed the technical core of negotiations with companies in 2012-13, the result of which was the award of contracts to PpTek with a value in excess of £1M during 2012-13, where four systems were sold in Chile and two systems to companies in Argentina. Importantly, these contracts are serviced in South America and constitute the first expansion of PpTek outside the UK and into South America.
More details can be found here
Ingenza Ltd; Technologies for new catalysts and products across the industrial biotechnology spectrum
Summary
2002 University of Edinburgh, (UoE) published in Angew. Chem. a new strategy of integrated chemo- and enzymatic catalysed routes to high-value chiral compounds that offered dramatic improvements over existing technologies (high yield and enantiomeric excesses often > 99.9%). They demonstrated the deracemisation of the amino acid DL-proline achieving a 94 % conversion of racemate to chiral amino acid after hydrolysis.[65] Previous dynamic kinetic resolutions have been hampered by the harsh conditions required to racemise amines. They extended this to a range of amino acids using commercially available oxidase enzymes.[66] Working in collaboration with GSK, the group optimised their biocatalysts using random mutagenesis and in vitro and in situ selection, and colorimetric solid phase screening, to generate new biocatalysts and commercially important targets (starting with chiral amines) of interest to pharmaceutical industry customers.[67]
Details of the impact
Ingenza is an industrial biotech company spun out from EaStCHEM research, which employs 34 people and had a turnover last year of £2.7M. [2012- 2013] and was set up to optimise and exploit the new robust, general, and scalable biocatalysis platform technology. These enabling technologies have helped establish Ingenza as the leading UK industrial biotechnology and synthetic biology company. As a direct result, Ingenza’s staff has grown 2-fold in the past 4 years and revenues have grown 5-fold. Ingenza’s revenue growth reflects the unique capabilities of the company’s technology in a challenging economic climate and its adaptability to other industries’ awareness and uptake of sustainable manufacturing practices. Total turnover for 2008-July 2013 = £7M. Enzyme expertise (engineering and catalysis optimisation by directed evolution) has been applied to the large-scale manufacture of pharmaceutical intermediates. The value of sales for 2008-July 2013 is £3M.
The enabling technologies developed in Section 2 are being used much more broadly by Ingenza for bioprocess optimisation and supply of improved production microbes, to provide large industries with new, sustainable manufacturing processes from renewable rather than petrochemical feedstocks. For example, multi-year partnerships have been established with leading global companies, such as Lucite International, the world’s leading manufacturer of poly-methylmethacrylate. Ingenza piloted one of its improved biofuel strains with another end-user in the US at full production scale of 2.4 million litres.
There is also strong R+D collaboration with EaStCHEM staff, with joint awards from TSB, SPARK, ERA-NET, and collaborative PhD students.
More details can be found here
Biocatalysis integrated with chemistry and engineering to speed development of green pharmaceutical processes (BiCE programme)
Summary
UCL research has been instrumental in creating critically needed new biocatalysts and bioprocess technologies for industrial biocatalytic process development. These have impact across the UK chemical and pharmaceutical sectors. The multi-disciplinary BiCE (Bioconversion — Chemistry — Engineering Interface) programme at UCL, conducted between 2004 and 2008, established a new integrated approach to development of biocatalysts and biocatalytic processes. This combined aspects of synthetic chemistry, molecular biology and process engineering to generate novel biocatalysts with increased productivity for application in the chemical and pharmaceutical industries. The programme also established a range of technologies to facilitate the rapid design and scale-up of green, more environmentally friendly, industrial biocatalytic processes. This new approach was shared with 13 industrial partners, enabling the early identification of all potential bottlenecks for efficient biocatalytic process development, from biocatalyst discovery through to process design and scale-up.
The underpinning research delivered a range of tools for synthetic biology, enzyme engineering and biocatalyst screening, as well as new enzyme variants and E. coli strains, enabling synthesis of important pharmaceutical intermediates (chiral ketodiols and aminodiols). Building on work from 2000 to 2003, which resulted in patents [68], the BiCE programme used this technology to engineer enzyme variants now used by the programme’s company partners. Automated, high-throughput methods for biocatalyst process evaluation were also developed, along with novel miniature stirred bioreactor technologies that help facilitate the rapid establishment of scalable biocatalytic and chemo-enzymatic synthetic routes.
Details of the impact
Since 2008, BiCE programme research has had wide-ranging impact, from the establishment of a successful spinout company to commercialisation of a miniature bioreactor technology. A number of pharmaceutical companies now using BiCE enzymes are benefiting from cost and time savings in their production process, along with reduced waste production. These impacts are summarised below and can be traced back directly to the original research outputs identified above. To capitalise on the knowledge generated in the BiCE programme, researchers at UCL set up the synthetic biology spin-out company, Synthace Ltd, in 2011. This aims to make high-value, bio-based chemical and biological products through the application of synthetic biology. Synthace has completed two rounds of investment funding as of 31 July 2013. These successful funding rounds have brought its total financing to £1.8m with TSB funding of £500,000 and a recent second stage finance of £1.3m from Sofinnova Partners’ Green Seed Fund and a syndicate of angel investors.
Impacts include
- Industrial adoption of high throughput bioprocess design methodologies. A number of BiCE programme industrial partners have now adopted UCL high-throughput and microscale technologies to help speed the design of new biocatalytic processes. These include Lonza, Merck & Co, Evonik and DSM. As an indication of the impact achieved the Executive Director of BioProcess Technology & Expression from Merck & Co has reported a 3-to-5-fold throughput improvement by the application of microscale-based techniques
- Economic benefits from screening and utilisation of BiCE enzyme libraries: Licensing of these libraries saves each company the time and costs involved in in-house library generation. For example, Almac has used it to identify transaminases that are able to catalyse amination of the substrates. The head of biocatalysis at Almac said: “The new enzyme process is one third of the cost of the chemical process and the yield of the process has increased from 10% to over 90%“. In a similar vein, Sigma-Aldrich has since 2006 used one of the BiCE TK variants for commercial preparation of D-xylulose-5-phosphate and a TAm variant to prepare pyridoxamine-5-phosphate.
- Environmental benefits arising from adoption of biocatalysis: Industrial adoption of BiCE enzyme variants for commercial production of chemicals and pharmaceutical intermediates, as described above, has major environmental benefits. For example, Almac’s head of biocatalysis noted: “Recent success using a BiCE transaminase enzyme has resulted in the removal of 8 steps of chemistry using a transaminase enzyme from the BiCE project. As you can imagine this has a major input into cost of goods by lowering reagent and energy usage and very importantly, waste production“.
More details can be found here
Improving green chemistry for the pharmaceutical industry using enzyme biocatalysts
Summary
Biocatalysts provide unique activities that facilitate chemical transformations that are simply not possible using abiotic methods. Northumbria University researchers with expertise in enzymes and biocatalysis have provided biocatalysis services to the pharmaceutical, fine chemical, food and biofuels industries through our business facing innovation unit Nzomics. This has generated significant contract research, collaboration and licence agreements to companies, including the pharmaceutical company GlaxoSmithKline and the services-led company Almac. Biocatalysts produced as a result of Northumbria University research and technology transfer are sold worldwide and benefit business through their use in research and development activities, such as the production of intermediates in drug synthesis.
Details of the impact
Through Nzomics, Northumbria researchers have now worked with over 20 clients (15 since 2008) providing a range of biocatalysis enzymes for processes in the pharmaceutical, fine chemical, food and biofuels sectors. Since 2008, Nzomics has offered fee-for-service contract research services totalling approximately £200,000 for a range of clients including GlaxoSmithKline and Almac Sciences, in the pharmaceutical sector; Glycoform, Prozomix, Hycagen, Protech Research, Sepagen and Micron Bio-systems, in the biotechnology sector; and Kraft Foods in the food sector. Additionally, Nzomics has entered into research and licence agreements with Almac (2009t), Prozomix (2009) and Megazyme International (2003): these companies sell enzymes developed by Nzomics to a worldwide market.
Carbonyl Reductase (CRED) Enzyme Screening Panel and the Nitrile Manipulator (NM) Enzyme Screening Panel have been developed by Nzominc with Almac. CRED and NM sales since 2009 are as follows: 27 CRED panels and the bulk purchase of 17 individual CREDs (corresponding to approx. £250,000 of sales) and 13 NM panels (corresponding to approx. £30,000 of sales). Development and sale of these panels has resulted in the significant expansion of Almac’s Biocatalysis team. In addition, Nzomics have provided services to GSK since 2009, supplying valued materials, such as enzyme panels and cloned genes.
In 2009, Nzomics also entered into a collaboration and licence agreement with Prozomix to provide recombinant DNA clones for the production of several research enzymes. So far this has resulted in approximately £20,000 of sales, to academia, biotechnology, fine chemical and pharmaceutical companies to 2013.
More details can be found here
Biocatalysists for Industrial and Medical Applications
Summary
Queen’s University Belfast has developed a number of biocatalytic processes for the production of pharmaceutical intermediates which have been applied commercially. The most significant involved Vernakalant, a new drug for treatment of the most common form of irregular heartbeat, now available in the EU, and currently awaiting approval in the USA and Canada. The research at Queen’s has led to an understanding of the remarkable potential of a range of biocatalysts which produce single enantiomer polyoxygenated products from aromatic substrates. (Figure 1).
Figure 1 Reaction scheme for the formation of cis-dihydrodiols from monosubstituted aromatics leading to the formation of Vernakalant
Importantly, the ability to translate the fundamental research into a commercial success, was due to the Queen’s group enabling the determination of structure, configuration and enantiopurity of these novel bioproducts (69,70). Through this knowledge, the scope and diversity of the bioproducts produced has been expanded significantly and the limitations of the substrates able to be biotransformed alleviated by the use of manipulation of the biocatalyst employed.
Details of the impact
Cardiome Pharma, a Canadian pharmaceutical company, recognised in 2003 that the team at QUB had the ability to deliver kilogram quantities, of a chiral intermediate required for an alternative chemoenzymatic route to their new drug candidate RSD1235 for a clinical trial for the treatment of atrial fibrillation by intravenous injection, investing more than CAN $1M. As a result of the clinical trials, in 2009 Merck signed a licensing agreement with Cardiome worth up to 600 million dollars to help rapidly get the drug to market [71] RSD 1235 has completed clinical trials, is now marketed as Vernakalant and in September 2010 was approved for use in over ten European countries and other areas under the trade name Brinavess (Cardiome/Merck). Vernakalant has undergone phase 3 clinical trials for FDA approval for use in the USA and is has being evaluated by the National Institute for Health and Clinical Excellence, NICE, as a prescription drug for NHS use in the UK [72]
Secondly, Almac Sciences have over the past five years developed an increasing biocatalytic capability within their business facilitated by the research undertaken in Queen’s. Many of the initial bioproducts marketed by Almac SelectAZyme, and new projects undertaken for external customers, were solely based on the biocatalytic pathways, enzymes, expertise and facilities developed in Queen’s which are utilized as precursors in synthetic routes to bioactive materials, such as the influenza drug Tamiflu [73]. This area is now growing into other markets significantly and the biocatalysis group in Almac now employ 30 staff including 15 PhD graduates from QUB. The biocatalysis group operates as a multi-million revenue provider for Almac providing solutions to customers through the application of enzymes.
More details can be found here
Therapeutic protein and vaccine stabilisation technology with global reach across the pharmaceutical industry
Summary
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. Medicines based on biomolecules, including vaccines, are currently the major engines of growth in the pharmaceutical industry, with sales predicted to increase from ~$130bn in 2012 to ~$280bn in 2022. The in vivo activity of biomolecules such as enzymes, monoclonal antibodies, and vaccines is determined by the tertiary structure, i.e., the three-dimensional conformation. This means that biologic drugs are much less stable and therefore harder to formulate and administer than traditional small molecule drugs. The pathway of transferring an enzyme from aqueous solution into non-aqueous media is found to be critical in maintaining catalytic activity and surprisingly, conventional protein drying methods such as lyophilisation give very poor results. This research identified a novel method for forming free-flowing dry powders by supercritical fluid carbon dioxide extraction of suspensions of PCMC in solvent. The formulations and process were patented (“Pharmaceutical Composition”, WO2004062560) in conjunction with an alternate continuous flow process for precipitating PCMC particles (“Process for Preparing Microcrystals”, WO2006010921). Other patents include “Precipitation Stabilising Compositions”, WO2008132439) and “Slow Release Compositions”, WO2009077732. These findings have led to the development of vaccines in which both antigens and toll-like receptor agonists are co-immobilised on slow-release particles, resulting in enhanced innate and adaptive immune responses. These are being exploited in temperature stable vaccines for treatment of helminths in livestock and in vivo trials are on-going in collaboration with the Moredun Research Institute. All of the patents filed have been licensed to XstalBio Ltd.
Details of the impact
XstalBio Ltd was formed as a spin-out company in 2004 to license, commercialise, and extend the intellectual property associated with the protein and vaccine stabilisation technology. XstalBio’s technology adds therapeutic value, accelerates the development, and extends the life-cycles of protein-based drugs as well as enabling new product opportunities. The company targets the $50bn currently spent per annum by the pharmaceutical industry on biopharmaceutical product development. XstalBio markets its expertise and technology to these pharma companies with the aim of enabling development of improved formulation and delivery methods for new candidate biologic drugs and vaccines.
In an internationally competitive market, XstalBio has succeeded in selling contracts for access to its Intellectual Property Portfolio for over 8 years and has continuously developed the patented technology to meet the new challenges facing the biopharmaceutical industry. These contracts, worth £2.2M over the period 2008-2012, are underpinned by option license agreements taken out on the WestCHEM owned patents. An early client was Boehringer Ingelheim who subsequently licensed the stabilisation technology from XstalBio, primarily for delivery of biologics by inhalation. As part of this license agreement the two companies co-developed and built a dedicated GMP compliant pilot plant for inhalation dry powders, which was commissioned in Biberach, Germany in 2008 at cost of €5M. The significant payments by international companies to XstalBio for access to its IP portfolio demonstrate that its biologic formulation and drug delivery technologies lie at the commercial cutting-edge.
The publication of the 6 filed and licensed patent families impacts on the overall knowledge base and direction of the pharmaceutical industry. This is evidenced by the presence of 11 patent filings from other companies, including BASF, Novo Nordisk, Boheringher Ingelheim, Lek, Taisho Pharmaceutical Co. Ltd and Dominó — Indústrias Cerâmicas that reference the technology and/or patents.
More details can be found here
References
[1] Confirmation of Lucite investment in Alpha process, together with environmental and other benefits, as part of a feature on the Alpha process as a finalist in the Royal Academy of Engineering MacRobert Award 2010,
Acrylics for the future, B. Harris, Ingenia, issue 45, December 2010, Royal Academy of Engineering, http://www.ingenia.org.uk/ingenia/issues/issue45/harris.pdf
[2] Confirmation of agreement between Sabic and Mitsubishi Rayon to build the largest MMA plant in the world in Saudi Arabia (capital expenditure of $500 million), using the Alpha process. http://www.2b1stconsulting.com/sabic-and-mitsubishi-to-tender-jubail-mma-pmma-epc- contract/.
[3] Supporting correspondence from Technology Manager, Johnson Matthey PLC — corroborates the contribution that Prof Sankar and the UCL/RI team have made to the programs of work at JM. Available on request.
[4] Combined experimental and computational modelling studies of the solubility of nickel in strontium titanate, A. M. Beale, M. Paul, G. Sankar, R. J. Oldman, C. R. A. Catlow, S. French and M. Fowles, J. Mater. Chem., 19, 4391-4400 (2009) doi.org/bz76g3 (In collaboration with Johnson Matthey)
[5] Computational modelling study of the solubility of cerium at LaCoO3 perovskite surfaces, S. Khan, R. J. Oldman, C. R. A. Catlow, S. A. French and S. A. Axon, J. Phys. Chem. C, 112(32), 12310-12320 (2008) doi.org/cvr8qb (In collaboration with Johnson Matthey)
[6] Supporting correspondence from Catalyst Research Associate, Johnson Matthey PLC — corroborates the contribution that the UCL team has made to the development of inorganic oxides and the impact that the UCL/RI team has had at JM. Available on request. [text removed for publication]
[7] X-ray absorption spectroscopic studies of platinum speciation in fresh and road aged light-duty diesel vehicle emission control catalysts, T. I. Hyde, P. W. Ash, D. A. Boyd, G. Randlshofer, K. Rothenbacher and G. Sankar Platinum Met. Rev., 55(4), 233-245 (2011) doi.org/d9h9gs (In collaboration with Johnson Matthey, International Platinum Group Metals Association and European Precious Metals Federation)
[8] Purchase of Intellectual Property by Dorf Ketal, 18 April 2011
http://www.reuters.com/article/2011/04/18/idUS125100+18-Apr-2011+PRN20110418
“Dorf Ketal Purchases VERTEC™ Patents and Intellectual Property”
[9] Coking and regeneration of palladium-doped H3PW12O40/SiO2 catalysts, M.R.H. Siddiqui, S. Holmes, H. He, W. Smith, E.N. Coker, M.P. Atkins & I.V. Kozhevnikov Catal. Lett. 66, 53-57 (2000) DOI https://doi.org/10.1023/A:1019083103395
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[12] Molybdenum and tungsten carbides as catalysts for the conversion of methane to synthesis gas using stoichiometric feedstocks. York, A. P. E.; Claridge, J. B.; Brungs, A. J.; Tsang, S. C.; Green, M. L. H. Chemical Communications 1, 39-40, 1997. DOI: 10.1039/A605693H
[13] New catalysts for the conversion of methane to synthesis gas: Molybdenum and tungsten carbide. Claridge, J. B.; York, A. P. E.; Brungs, A. J.; Marquez-Alvarez, C.; Sloan, J.; Tsang, S. C.; Green, M. L. H. Journal of Catalysis 180 (1), 85-100, 1998. DOI: 10.1006/jcat.1998.2260. Paper illustrates the underpinning expertise in carbide catalyst technology of the Oxford Research Group.
[14] Study on the mechanism of partial oxidation of methane to synthesis gas over molybdenum carbide catalyst. Xiao, T. C.; Hanif, A.; York, A. P. E.; Nishizaka, Y.; Green, M. L. H. Physical Chemistry Chemical Physics 4 (18), 4549-4554, 2002. DOI: 10.1039/b204347e. Underpinning expertise in carbide catalyst technology of the Oxford research group in combination with a microreactor.
[15] A supported cobalt-containing catalyst used in the partial oxidation of hydrocarbons or Fischer-Tropsch reaction. Green, M. L. H. and Xiao, T. C. Int. Appl. (2003), WO 2003002252. Assignee: Isis Innovation Limited, UK (a wholly-owned subsidiary of the University of Oxford, managing technology transfer). http://www.google.com/patents/WO2003002252A1?cl=en
[16]* A supported cobalt-containing catalyst used in the partial oxidation of hydrocarbons or Fischer-Tropsch reaction. Green, M. L. H. and Xiao, T. C. Int. Appl. (2003), WO 2003002252. Assignee: Isis Innovation Limited, UK (a wholly-owned subsidiary of the University of Oxford, managing technology transfer). http://www.google.com/patents/WO2003002252A1?cl=en
[17] http://www.velocys.com/our_business_partners.php
Oxford Catalyst Group (now Velocys) Partners webpage, corroborating details of the companies with whom the group has active partnerships.
[18] http://www.oxfordcatalysts.com/financial/fa/ocgfa20120524.php
May 2012 press release from Oxford Catalysts, confirming sale and successful start-up of a commercial scale FT Reactor with an anonymous integrated energy company.
[19] http://calumetspecialty.investorroom.com/2012-09-06-Calumet-Specialty-Products-Partners-L-P-Announces-Plan-to-Expand-its-Karns-City-PA-Specialty-Products-Facility
September 2012 press release from Calumet, confirming that it has commissioned Oxford Catalysts/Velocys to supply FT technology for 1,000 BPD commercial GTL plant for Calumet at its Karns City, Pennsylvania site.
[20] http://www.solenafuels.com/index.php/in-the-news/10-solena-makes-the-news-items/10-british-airways-pledges-10-year-offtake-agreement-as-greensky-project-with-solena-gathers-momentum-on-greenair-online
November 2012 press release from Solena, confirming the selection of Oxford Catalysts to provide FT technology to GreenSky London, Europe’s first commercial scale sustainable jet fuel facility, being developed in partnership with British Airways.
[21] http://pintogtl.com/partner/
Pinto Energy webpage confirming details of the joint project with Oxford Catalysts (Velocys).
[22] http://www2.ventech-eng.com/2012/11/oxford-catalysts-secures-1-3m-from-ventech/
November 2012 press release on the Ventech website confirming the Ventech/Oxford Catalysts collaboration and the fact that Ventech regards Oxford Catalysts’ FT technology as at the forefront of the GTL industry.
[23] Johnson Matthey, Catalysis and Chiral Technologies; statement 17 June 2013.
[24] Process patent WO2010106364A2 (Johnson Matthey, priority date 17 Mar 2009), web link.
[25] Process patent WO2012156693A1, Processes for the preparation of the compound of formula (II) and intermediate compounds for use in the processes (AstraZeneca Ab and AstraZeneca UK Ltd, priority date 13 May 2011), web link.
[26] Process patent WO2009130056A1, Process for making montelukast intermediates (Synthon BV., priority date Apr 25, 2008), web link.
[27] Process patent WO2011131315A1, Process for the asymmetric transfer hydrogenation of ketones (Archimica GMBH, priority date 23 Apr 2010), web link
[28] Patent US20130217728, New CCR2 Antagonists (Boehringer Ingelheim International GMBH, priority date 01 June 2010), web link.
[29] Patent EP2644603A1, Synthetic route for the preparation of substituted 2-phenyl-1,2,3,4-tetrahydronaphthalene-1-ols (LEK Pharmaceuticals d.d., priority date 30 Mar 2012), web link.
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[35] Copy of Funding proposal and agreement, Oglesby Charitable Trust
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[45] *E.L. Marshall, V.C. Gibson and H.S. Rzepa, “A computational analysis of the ring-opening polymerization of rac-lactide initiated by single-site beta-diketiminate metal complexes: defining the mechanistic pathway and the origin of stereocontrol”, J. Am. Chem. Soc., 127, 16, pp 6048-6051 (2005). DOI, 90 citations (as at 5/9/13)
[46] Patent WO2002038574 A1, “Diamido alkoxide complexes as polymerization initiators of lactides“, Inventors: AP Dove, VC Gibson, EL Marshall, Applicant: AP Dove, VC Gibson, EL Marshall, Imperial Innovations, Publication date: 16/5/02
[47] P. Hormnirun, E.L. Marshall, V.C. Gibson, R.I. Pugh and A.J.P. White, “Study of ligand substituent effects on the rate and stereoselectivity of lactide polymerization using aluminium salen-type initiators”, PNAS, 103, 42, pp 15343-15348 (2006). DOI, 58 citations (as at 5/9/13)
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