Impact case study database

In 2007, with support from OBU’s Research & Business Development Office and investment of approximately GBP375,000, OET was founded to exploit the new baculovirus technology developed by King and Possee through marketing a range of kits, and by providing specialist services to commercial and academic users worldwide (S1). The patents granted to OBU and NERC’s CEH were licenced to the new company in return for shares and a royalty income stream. Since 2007, OET’s ethos has been to invest in research & development (R&D) to ensure its platform technologies remain competitive and at the forefront of new expression vector development, through in-house and collaborative R&D with a range of UK and international commercial, and academic, partners (S1). Since 2013, OET has launched four improved versions of its core flashBAC^TM expression platform, including one that increases transduction of mammalian cells to enhance gene therapy applications, and has sub-licensed the core technology for use in both veterinary and clinical applications in biotech, diagnostic and vaccine companies including [text removed for publication]. Since 2015, OET has also been successful in gaining GBP2,421,953 Innovate UK contracts and grants and co-invested c.GBP750,000 own funds to enable it to capitalise on its own innovative platform technologies to develop diagnostics and vaccines for emerging viral diseases in a strategic partnership with PHE Porton Down and others. Between 2014 and 2020, OET has more than doubled its scientific staff from 7 to 16 with 50% at PhD level (S2), and increased annual turnover 4.5-fold to [text removed for publication] and profit by six-fold (S3), much of which has been reinvested in R&D and growing the company. Today OET is acknowledged as a world-renowned centre of excellence for baculovirus expression technologies, benefitting global academic and commercial end users for research, diagnostic and vaccine purposes (S1, S4).

The innovative technology ( flashBAC^TM) developed by King and Possee has resulted in a range of easy-to-use kits that enable users to make recombinant proteins in a rapid and convenient one-step process (S5). The benefits of the technology for end users relate partly to the simplification of the process, which enables a wide variety of academic and commercial laboratories to access the technology to make recombinant proteins without the need for a high level of virology-related skills. The simplified process is also quicker, thus saving several days’ time and resources in producing proteins at research scale through to bioreactors for commercial production. flashBAC^TM technology also has unique properties, which comprise: (1) its capacity for high-throughput production of multiple recombinant viruses, (2) improvements to the genetic backbone of the virus to generate higher yields of good-quality ‘difficult-to-express’ proteins and (3) avoidance of sequences that can lead to long-term genetic instability of the viral vector backbone.

While competitor baculovirus expression products exist (for example, Thermo Fisher’s BAC2BAC and BD Biosciences’ BACULOGOLD), the genetic backbones of these vectors have not been further developed since launching in the mid-1990s, and BAC2BAC retains bacterial sequences that can cause long-term genetic instability, often decreasing expression yields to almost zero over six or more passages of the virus and thus making it difficult to amplify virus for use at scale in bioreactors;. flashBAC^TM is the only baculovirus expression platform that has been genetically modified to improve the yield and quality of ‘difficult-to-express’ proteins (by deleting non-essential virus genes including chitinase, cathepsin and P10) and, at the same time, enabling high-throughput, simultaneous production of virus vectors in a simple one-step process. During the process of homologous recombination to insert foreign genes into the flashBAC^TM genome, bacterial artificial chromosome sequences (used to produce stocks of flashBAC^TM DNA) are deleted from the final vector sequences and hence recombinant flashBAC^TM vectors are genetically stable over the long-term, which ensures yields do not diminish during scale-up, for example, when providing a vaccine.

OET’s technology is now being used by multinational pharmaceutical (e.g. [text removed for publication]), biotech (e.g. [text removed for publication]), animal health companies (e.g. [text removed for publication]) and leading research institutions (e.g. PHE, the Francis Crick Institute and Universities of Oxford, Cambridge, Bristol, Manchester, Leicester, Reading, Gdansk, Aarhus, Wageningen, Harvard, Yale, Berlin, Tokyo, German Diabetes Centre, Animal & Plant Health Agency, APHA) worldwide to advance their drug discovery, biotherapeutic, diagnostic or vaccine development programmes. In addition, >100 companies and universities (many listed above) have also outsourced expression vector and protein production in insect cells to OET for ‘proteins to sell’ (e.g. [text removed for publication]) or incorporation into diagnostic assays or vaccines for veterinary (e.g. [text removed for publication]) and clinical purposes (e.g. [text removed for publication]); a number (>20) of larger academic research groups outsource construction of complex or challenging gene expression projects to OET’s experts, e.g. membrane proteins, virus-like particles and multiprotein complexes (e.g. Universities of [text removed for publication]).

Over the last few years, OET has completed increasing numbers of licence deals (>15) to enable companies to progress target vaccines or biotherapeutics through to clinical trials, or to commercialise products, (e.g. diagnostic assays) prepared using OET’s technology. For example, under a sub-licence agreement, OET produces many different proteins for [text removed for publication] for incorporation into its veterinary diagnostic assays for major avian (e.g. [text removed for publication]) and porcine (e.g. [[text removed for publication]) infectious diseases. In 2018, OET sub-licenced flashBAC^TM to [text removed for publication] for [text removed for publication] vaccine targets, two of which have successfully completed Phase 1 and 2 clinical trials for [text removed for publication]. In November 2020, [text removed for publication] vaccine for SARS-CoV-2 (the virus responsible for the Covid-19 global pandemic) (S6). The [text removed for publication] (S7). In August 2020, the UK Government [text removed for publication] (S8), and more recently [text removed for publication] (S9). In May 2020, OET agreed terms to licence its technology to Vaxine Pty, Australia for a vaccine for Covid-19, and in August 2020 Innovate UK provided GBP681,000 funding to OET to help Vaxine progress to a Phase 1 clinical trial.

The first commercial sales of flashBAC kits began in 2008 and the new technology has been widely adopted by the biotechnology sector (S4). Clients are both commercial and academic from across the globe, including all continents, either directly from OET’s Oxford base or through a number of international distributors (e.g. BioNovus for Australia, Cell Concepts for Germany, MirusBio for the US, Cosmo for Japan and Dakewe for Hong Kong and China) (S10), with non-UK kit sales comprising 80%. Approximately 43% of OET’s sales income ([text removed for publication]; 27% turnover, S3) over the assessment period derives from kit & product sales and, of this, approximately 40% through distributors and 60% direct sales. To access the American markets, the technology was licenced under Original Equipment Manufacturer agreements to [text removed for publication] and continues to be sold under the brand name [text removed for publication].

The flashBAC^TM technology is also used in-house by OET to produce recombinant proteins for customers unable to make them in their own laboratories and this accounts for approximately 43% [text removed for publication] of sales income (27% turnover). OET has thus established itself in the rapidly expanding market for ‘off-the-shelf’ research services that enable companies to avoid setting up their own dedicated facilities, enable them to outsource when in-house facilities are at capacity, or use OET’s expertise for complex or challenging projects. Since August 2014, OET has worked with >100 companies including [text removed for publication] plus government laboratories such as [text removed for publication] and many UK and global universities. We have enabled these companies and institutions to advance their drug discovery, diagnostic kit and/or vaccine development programmes by producing proteins more quickly and efficiently, and to increased yields and quality more than was possible previously. Companies utilizing OET technology are based in Europe, North and South America, South East Asia, Australia, the Middle East and China, as well as in the UK.

An increasing proportion of OET’s income comes from license deals to enable companies or organisations to use OET’s technology for commercial use including clinical trials for vaccine development (e.g. [text removed for publication]), Adeno-associated virus gene therapy vector production (e.g. [text removed for publication]) and multiple licences for commercial protein production (e.g. [text removed for publication]). A specific example of the licensed use of the technology has been in the development of vaccines for [text removed for publication], which have progressed to Phase 1, 2 and 3 clinical trials, respectively. Commercial protein production varies from simple preparation of proteins for sale to use of proteins in in vitro diagnostic assays (e.g. [text removed for publication]). Licence sales income accounted for 14% of OET’s sales income (8% of turnover; S4) in the designated period with individual licences ranging from [text removed for publication].