High-throughput genotyping has revolutionised the genome-wide search for
associations between genetic variants and disease. Professor Sir Edwin
Southern of the University of Oxford's Biochemistry Department invented
the highly cost-effective array-based method of analysing genetic
variation based on hybridisation between probes and samples on glass
slides or `chips'. The spin-out company Oxford Gene Technology (OGT)
founded by Southern in 1995 licenses the patent to manufacturers of
`single nucleotide polymorphism (SNP) chips', including Illumina and
Agilent, a global business exceeding $500M per year. Southern has
continued to refine and extend this technology to increase its speed,
efficiency and cost-effectiveness. This revolutionary technology has
widespread applications such as prediction of individual risk, development
of new drugs, provision of personalised treatments, and increased
cost-effectiveness of clinical trials. Licence revenues fund R&D
within OGT, and endow charitable trusts supporting primary school science
education in the UK and crop improvement in the developing world.
A first-in-class anticancer agent discovered in Thurston's laboratory at
the University of Portsmouth
in the 1990s has been commercially developed and clinically evaluated over
the last two decades.
SJG-136 was successful in Phase I clinical trials and is completing Phase
II clinical trials for the
treatment of ovarian cancer and leukaemia, where significant patient
benefit is observed.
Related molecules based on this parent compound are in drug programmes
being undertaken by
Seattle Genetics Inc. and Genentech Inc., leading to additional clinical
trials. A spin-out company,
Spirogen Ltd, was established in 2000 to commercialise the intellectual
property generated from
the underpinning research, and the company has recently been sold to
AstraZeneca for $200m.
This case study describes both economic and healthcare benefits that have
resulted from a new DNA (gene) sequencing technique known as SOLiD
sequencing. Through the 1990s until the present, Cosstick (University of
Liverpool since 1984) has both developed the synthesis and studied the
properties of chemically modified DNA in which a single oxygen atom is
replaced by sulfur; we have termed this a 3'-phosphorothiolate (3'-sp)
modification. Chemically prepared DNA containing the 3'-sp modification is
a key enabling component of the Applied Biosystems SOLiD DNA sequencing
instrument which is able to produce extremely rapid, cost-effective and
exceptionally accurate DNA sequence information. The impact of this very
powerful sequencing technology extends beyond economic benefits as it has
many healthcare applications which have impacted medical practice.
Through their study of DNA polymerases from organisms of the domain
archaea, researchers at Newcastle University and University College London
identified the mechanism by which these organisms avoid potentially
damaging mutations in their DNA. As a consequence of this work they
invented a novel genetically-engineered DNA polymerase. This enzyme has
been patented and is the world's only high-fidelity, proofreading DNA
polymerase that efficiently reads through uracil in the polymerase chain
reaction (PCR). PCR is a very widely used technique in biomedical
research. An international bioscience company [Text removed for
publication, EV d] signed a licensing agreement with Newcastle University
in 2008 to market the enzyme, and total sales since 2008 exceed [Text
removed for publication, EV d]. Further commercial exploitation has begun
through licensing agreements with other major companies.
The Ethics of Patenting DNA was a Nuffield Council on Bioethics Report by
a working party of which Thomas Baldwin was a member with responsibility
for providing the ethical framework for the report. The report was
published in 2002 and its initial impact occurred in the 2002-2005 period;
but it has had continuing impact during the current period on legal and
political debates concerning the granting of patents on DNA sequences to
pharmaceutical and biotechnology companies and to universities. More
generally it continues to have a significant impact on policy formation in
this much disputed area.
Impact on commerce: A patented technique for separating methylated
and non-methylated DNA has been licensed and a kit brought to market,
along with other commercial reagent licenses.
Impact on health and welfare: The demonstration that two
mechanisms of epigenetic gene regulation, DNA methylation and histone
acetylation, are linked, has led to trials of separate drugs known to
affect each mechanism as a combined treatment for high-risk patients with
myelodysplastic syndromes (MDS).
Beneficiaries: Companies have gained commercial benefit from
licensing UoE IP to market products. High-risk MDS patients will benefit
from improved treatment.
Significance and Reach: Commercial earnings across 4 companies
from international sales in the period estimated at over [text removed for
publication], mainly since 2010. Commercial significance includes the
first commercially-available technique for separating methylated and
The incidence of MDS is estimated at 3-4 cases diagnosed annually per
100,000 of the population in Europe (an estimated 26,000 individuals) and
up to 20,000 new diagnoses per year in the USA. Incidence increases with
age — up to 15 new cases annually per 100,000 in individuals aged over 70
years. MDS occurrence is increasing as the age of the population
increases, so the significance of new therapies is high.
Attribution: All research was led by Adrian Bird at UoE. Reik
(Babraham Institute) contributed to development of one of the licensed
Research by Professor Steve Jackson led to the discovery of synthetic
lethality as a means of selectively targeting cancer cells, and to Jackson
founding KuDOS Pharmaceuticals to translate this research into therapies.
This novel approach has changed the way pharmaceutical companies develop
cancer therapeutics and has led to several drugs reaching pre-clinical and
clinical development. The most advanced of these (olaparib, a PARP
inhibitor originally developed at KuDOS and acquired by Astra Zeneca) is
now entering Phase 3 trials and registration in Europe. In 2011, Jackson
founded MISSION Therapeutics Ltd, to extend the synthetic
lethality concept into targeting deubiquitylating enzymes to selectively
kill tumour cells.
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.
Impact: New business, technology, intellectual property and
employment resulting from the invention and exploitation of a micro-scale
laboratory device (ScreenTapeTM).
Significance: New business and technology commercialised resulting
in sales of novel products worldwide, acquisition by Agilent Technologies
Limited (Agilent) for £[text removed for publication] in 2011, product
sales of over £[text removed for publication] to August 2013, generation
of sustained employment for 50-160 people, major inward investment (£6M)
by local investors followed by a US multinational.
Beneficiaries: The economy, commerce, employment, research and
diagnostic laboratories, Agilent Technologies Inc. (Agilent).
Attribution: UoE Prof Peter Ghazal and Dr Douglas Roy inventors on
granted patent, establishment of multi-disciplinary research in biochip
medicine, collaborators with ex-Motorola engineers, co-founders of
spin-out company for commercialisation of intellectual property.
Reach: Worldwide, including employment and product sales. Inward
investment to UK.
This case study outlines the impact in generating investment in a
spin-out SME and in developing a technology for clinical diagnosis based
on chemistry research carried out in Bath. The research led to a spin-out
company, Atlas Genetics, which has raised over £18M funding in the REF
period specifically to develop the Atlas io™ platform, novel
technology for rapid (<30 minute) and robust detection of infectious
diseases suitable for point-of-care. The investment has created new jobs
for highly skilled workers at the cutting-edge of medical diagnostics,
with Atlas currently employing 36 staff. The io™ platform has
been fully developed and has undergone successful clinical tests on
multiple infections (based on bespoke Chemistry developed at Bath) prior
to clinical trialling and rollout in Europe and the United States.