Edition 43 - Isis Innovation

News
Reviewing the latest innovations, collaborations
and technology transfer from Isis Innovation Limited
Edition 43 Winter 2004
Network
nerves
Contents: News and Events 3 Oxford Innovation Society Talk 4
Technologies 7 Spin-out Updates 13 Isis Angels Network 14 OIS Meetings 20

Editorial
Tim Cook
Lawyers, Links and Investigations
The themes of several of the
articles in this Newsletter are
pathways and linkages.
Professor Steve New’s paper,
Supply Chain Innovation,
which he gave at the
September meeting of the
Oxford Innovation Society,
Dr Tim Cook, Managing
describes the management
Director, Isis Innovation.
and morphologies of the
supply chain. Although Steve’s subject was primarily
focussed on the supply chain in a commercial context there
is some interesting analysis to be done applying the concepts
he describes to other activities, not least the transfer of technologies
from universities!
Professor Steve Davies’ latest spin-out VASTox, (which name
originated from Value Added Screening Technologies
Oxford), works in chemical genomics and floated on AIM in
October at a valuation of £45 million. The company
describes Chemical Genomics, as “Chemistry probing
Biology” and using Oxford’s combined world-class expertise
in both these disciplines, and as well as a very large workforce
of fruit flies and zebrafish they will screen drug candidate
molecules for the pharmaceutical industry. The company is
already running a programme in Duchenne Muscular
Dystrophy and has recently licensed in some Isis technology
in this area.
A recent International Patent Litigation Conference in
London identified major opportunities for the Oxford Expert
Witness Programme, operated from Isis Innovation, which is
described on page 3.
Contents
News and events 3
Supply chain innovation 4
Dr Steve New
Research Patents – 6
don’t forget your colleagues!
By Hamish Bennett, Darbys
Oxford simulation apparatus 7
for flexible endoscopy
Isis Project 1422
Innovations in biological nanostructures 8
Isis Project 2113
VASTox plc 9
Spin-out
Diagnostic for Myasthenia Gravis 10
Licence deal signed with Athena Diagnostics Inc
Vaccines which pack a double punch 11
Isis Project 1444
Therapeutic Applications of a 12
CC Chemokine Binding Protein
Isis Project 1325
Spin-outs – growths and change 13
Rounding up spin-out news
Isis Angels Network 14
By James Mallinson
Echocardiographic image analysis 15
Isis Projects 1283, 676, 874 and 1095
Brain connectivity mapping 18
Isis Project 1341
Oxford Innovation Society Meetings 20
2

News and events
The latest developments in Oxford and the world of Technology Transfer
The views of two Vice-Chancellors
Lawyers seek Oxford experts for patent litigation cases
One of the reasons Isis Innovation has developed so rapidly
has been the support we have received from the top over
recent years. On 5 th October, in the oration marking his
retirement as Vice Chancellor of the University, Professor
Colin Lucas, said:
Legal professionals are increasingly turning to Oxford
University when they need independent, authoritative
advice and expertise. This was one message from the recent
13 th International Patent Litigation Conference held in
Bloomsbury, London.
“We have grown Isis innovation into an arm of technology
transfer that has been publicly recognised as exemplary.”
This reflects the changes that occurred in Isis during Colin
Lucas’ Vice-Chancellorship, a growth in patents to one a
week and the creation of forty new spin-out companies.
This would not have been possible without University
support at the highest level, both financial and non-financial.
At the same occasion in his address as incoming Vice
Chancellor, Dr John Hood said:
“Isis Innovation is an acknowledged leader in the management
and commercialisation of intellectual property. It is
therefore imperative that we continue to engage in the
evolution of public policy, to be creative and innovative in
our strategic responses, and to develop our resources so
that we build strongly on our past successes.”
So I believe we can expect no diminution in either the
support we can expect, or the demands, from the University
and I am sure Isis Innovation will continue to lead the field.
Tim Cook
Oxford University Consulting (OUC), part of Isis Innovation,
attended the September meeting in order to promote the
Oxford Expert Witness business to around 80 intellectual
property managers, including patent agents and attorneys
from around the world.
Dr Rick Inwood, from OUC, commented, “As a direct result
of this meeting we have had requests for Oxford experts
from IP lawyers litigating patent violation cases in Australia,
Israel and the USA.”
OUC sources renowned experts from the University of
Oxford for clients who value a professional service that is
accredited to ISO 9001 standards of quality assurance.
Clients who contact OUC are assigned a project manager
whose role it is to identify the expert in the University most
suitable to meet the client’s specific needs. OUC produces
all the necessary documentation and manages administration
and financial considerations on behalf of the expert and the
University. Monitoring the progress of the contract to
completion, the OUC project manager acts as a link
between client and expert to ensure a continued flow of
communication.
JP Morgan sponsors Oxford Innovation Society meeting
The September meeting of the OIS was sponsored by JP
Morgan and Julian Oakley, Managing Director of JP
Morgan Partners Europe Limited, presented a fascinating
account of some of the deals in capital structure of early
stage companies, providing a uniquely informed insight into
the critical importance of strategic financial management in
technology based businesses.
As well as the provision of expert witnesses to the legal
profession, OUC is also actively engaged in the areas of due
diligence, management consultancy, process optimisation,
data analysis, and specialist scientific testing services.
We hope to publish an account of his presentation in future
issues of Oxford Innovation News.
3

Supply chain innovation
OIS meeting at the Saïd Business School
from the interaction between the chain members.
Innovation becomes a distributed, shared activity – a pattern
seen in many industries, including automotive and
pharmaceuticals.
The question then arises: in what sense does a) affect b)
To understand this, we need to consider the two major
developments in supply chain thinking that have arisen
over the past twenty years or so.
By adopting a long-term,
trusting relationship, firms can
lower what economists call the
intrinsic ‘transaction costs’
within the chain
The partnership idea
Dr Steve New.
Introduction
The term ‘supply chain innovation’ can be taken in two
ways: a) innovations in the way firms manage their supply
chain relationships, and b) the way technological innovations
emerge in the context of the supply chain. The first of these
has become a major area of interest in both practice and
research; to focus merely on the internal management of
organisations is not sensible. Firms operate in webs of complex
interdependency with customers and suppliers, and –
although the metaphor needs careful handling – the
competitive unit can often be conceived as the ‘chain’,
rather than the individual firm. Marketing, operations and
financing become issues best addressed by seeking some
kind of coordination with other members of the chain. The
second interpretation of ‘supply chain innovation’ follows
from this idea: new technologies do not tend to emerge
fully formed from within a single organisation, but arise
The first could be labelled ‘the Partnership Revolution’: the
substitution of traditional, adversarial buyer-supplier
relationships with longer-term, cooperative arrangements.
Instead of being enemies who try to outwit one another in
the rough and tumble of commercial negotiation, buying
and selling organisations become ‘partners’ who seek
mutual, rather than local, advantage. This manifests itself in
the integration of the firms’ operations, as in the Just-In-
Time system, or in efforts to reduce the waste and cost of
unnecessary friction between the parties. By adopting a
long-term, trusting relationship, firms can lower what
economists call the intrinsic ‘transaction costs’ within the
chain.
This approach has significant implications for the management
of technological innovation. Rather as in theories of
employee empowerment (‘with every pair of hands, you get
a free brain’), the partnership idea means that buyers can,
for example, delegate technological expertise to the point in
the chain to which it best belongs. Under adversarial
relationships, powerful firms usually cling to all the technical
knowledge themselves – finding negotiating power in
concentrating technological ownership. This can be seen in
4

the way traditional car manufacturers clung to the design
of the whole car – using suppliers as mere sub-contractors
to make the parts to a provided specification. In contrast,
the partnership model allows skills and expertise to be
distributed more optimally, with knowledge about design
and manufacture held by those best placed to apply it.
Furthermore, the partnership model encourages firms to
delegate particularly risky technological projects to smaller
firms, who may be culturally and structurally more
equipped for high-speed, high-uncertainty innovation.
Firms working in relatively stable, long-term relationships
may also develop inter-firm technology transfer so new
ideas about products and processes can rapidly disseminate
between organisations. The emergence of paradigmbusting
industrial practices in the Japanese automotive and
electronics industry in the 1970s was reinforced by the
remarkable speed with which suppliers adopted the new
approaches. Under this model, it becomes in the firms’
interest to share their technology with supply chain partners
as effectively as possible.
The B2B approach, with its
focus on simple price
competition, fails to address
the way innovation really
works
The B2B frenzy
The second ‘revolution’ emerged in the dot.com bubble of
the late 1990s, only to burst early in the new decade.
When the promise of B2C (business-to-consumer) on-line
businesses became a little jaded, an excitable group of
consultants, merchant banks and pundits began predicting
that the Internet would transform B2B (business-tobusiness)
trading relations.
In particular, B2B Internet sites (‘hubs’ or ‘exchanges’)
would emerge to intermediate the relationship between
buyers and sellers; buyers would post their needs, and
suppliers (globally, and in real time) would bid for the work.
The hubs would be commercial matchmakers, making
redundant traditional sales forces and purchasing
departments. The market for all the stuff that organisations
buy from and sell to one another would become more like
those ‘pure’ and efficient markets about which economists
fantasise, and in consequence prices would rapidly fall. The
hubs, taking a tiny turn on the trillions of dollars of trade,
would fulfil the dot.com dream of being low-capital, instant
businesses that only needed to stake their claim in a
particular sector to generate enormous profits.
Thousands of such hubs were founded – only for the sector
to collapse when people realised that the model rested on a
number of flawed hypotheses about inter-organisational
trade. This can be largely explained by the way these
underlying assumptions failed to account for the nature of
innovation.
The B2B model rests on the notion that markets can become
increasing standardised and commodified. But most industrial
products are not commodities: their specification depends
on constant dialogue between customer and supplier.
In fact, the B2B model constrains innovation by limiting the
intellectual traffic between trading parties. Furthermore, the
buyers and suppliers are suspicious of interaction mediated
by a third party. Additionally, much innovation is about
product differentiation on non-price criteria (such as product
specification, quality and so on). The B2B approach, with its
focus on simple price competition, fails to address the way
innovation really works.
In conclusion, the Partnership model seems to win over the
B2B model in regard to promoting technology innovation.
But the B2B approach – in as much as it still exists in practice
– can exhibit some potential advantages. For example, in
some cases, it has allowed firms to expand the range of
firms on whose expertise they can draw.
In some sectors, such as automotive, B2B initiatives have led
to industry-wide rationalisation of data formats, enabling the
more efficient exchange of technical data. For innovative
firms, however, the key opportunities lie in finding those
long-term relationships with particular customers and
suppliers in which collaborative technology transfer leads to
mutual, and sustained, advantage.
Steve New teaches at the Saïd Business School. His new
book Understanding Supply Chains: Concepts, Critiques
and Futures (co-edited with Roy Westbrook) has just been
published by Oxford University Press.
W www.sbs.ox.ac.uk
5

Research Patents – don’t forget your colleagues!
By Hamish Bennett, Darbys’ Corporate, Technology & Finance Team
Inventions which are novel,
inventive and capable of
industrial application are
patentable in the UK provided
that they do not fall within
certain exclusions.
Scientific knowledge concerning
Hamish Bennett, Solicitor, natural phenomena is excluded,
Darbys’ Corporate, Technology
as are those inventions whose
& Finance Team.
commercial exploitation is
considered contrary to the values of society. However, when
a university academic applies for a patent which falls
squarely between discovery and invention, tensions may
arise over exactly who are the inventors and beneficiaries of
the patentable invention.
If granted, a patent will confer monopoly rights within the
scope of its claim, but does this monopoly provide just
reward for the endeavour of the inventor or create an
unnecessary barrier to further academic work The statutory
exemption from patent infringement for non-profit-making
academic research often throws up more questions than it
answers, so how then to reward our academic for their
inspiration without biting the hand that feeds them
there are statutory entitlements for the employees to
receive a share of the royalties. When the university own
the patent rights, which is the case in Oxford, it may reserve
the right for its staff to continue to use the patent for their
own internal purposes. This principle will apply should the
university licence the patent straight into the market place,
or ‘spin out’ a company to exploit it. Furthermore, any
subsequent assignment of intellectual property rights to a
spin out company may be made conditional upon a licence
back to the university for research or other commercial
purposes.
Such steps will help to create certainty without reducing
the value of the patent or limiting the inventor’s potential
for significant financial return. It is true that a spin-out
company with the unfettered right to exploit a patented
invention may be more attractive at first glace to venture
capital, but any potential investor should be reassured of
the wisdom in granting such a licence at an uncertain stage
in the company’s development.
A patent owner is under no legal duty to license their
patent, but in some circumstances they may find themselves
the subject of legal sanctions should they refuse to exploit it
or otherwise abuse their monopoly. They should therefore
grasp the opportunity to negotiate a limited licence on their
own terms at an early stage. With patent granted and
academic community placated, our patent owner may
concentrate on exploiting their invention and earning the
plaudits that their genius deserves.
First of all, an applicant may specify in their claim the
commercial use to which they intend to put their invention;
reserving for themselves the right to improve or adapt it, but
clearly setting out the circumstances in which they would
not consider their patent infringed.
Should a patent holder be an employee of a company or a
university the way the benefits are shared between
employer and employee will depend on the employee’s
terms of employment. These vary from institution to
institution, in Oxford and most UK universities the
institution owns the rights and pays the patent costs but
Contact
Hamish Bennett
Solicitor, Darbys’ Corporate, Technology & Finance Team
DT 01865 811733
DF 01865 811766
T 01865 811700
E hbennett@darbys.co.uk
W www.darbys.co.uk
6

Oxford simulation apparatus for flexible endoscopy
OxSAFE: Isis Project 1422
Research undertaken within the Nuffield Department of
Anaesthetics has resulted in an invention known as the
Oxford Simulation Apparatus for Flexible Endoscopy
(OxSAFE). This low-cost system enables clinicians to
perform endoscopic procedures in a realistic, virtual reality
environment.
Background
Endoscopy is an important technical skill for many medical
disciplines. This is especially the case for anaesthetists, who
use an endoscope (the intubating fibreoptic bronchoscope) to
visualise and negotiate a patient’s airway past obstacles, such
as tumours or anatomical deformities, in order to correctly
place a breathing tube. Failure to thus ‘secure’ the airway of
a patient undergoing surgery or otherwise unable to breathe
for themselves, can result in a life-threatening loss of oxygen
supply. Managing the ‘difficult airway’ is therefore considered
the anaesthetist’s specialist skill. However, the incidence of
patients presenting with ‘difficult airways’ is low (1 in 3000
general population), making it difficult to acquire and
maintain this crucial skill.
Physicians and surgeons undertaking other important, but
less time-critical, endoscopic procedures, such as
gastroscopy, colonoscopy, ureteroscopy and diagnostic
bronchoscopy face similar issues as the anaesthetists.
Snapshot of initial OxSAFE model.
system may be the cornerstone of a new generation of
endoscope simulators.
The Oxford Invention
Commercialisation opportunity
OxSAFE is a novel device that exploits recent advances in
computer vision, 3D computer graphics and simulation.
OxSAFE isolates the three basic flexible endoscope
movements and then uses computer vision to responsively
measure them. These basic movement parameters are then
fed into a 3D computer graphics engine, where training
scenarios are simulated. The result is an endoscopic simulator
that is simple and inexpensive, yet elegant and responsive.
OxSAFE is also more versatile than current high-fidelity
simulators, as the same device can be configured to receive
endoscopes of all sizes and be oriented either vertically or
horizontally. The inherent advantages of OxSAFE may be
further enhanced by an internet library of virtual-reality
models, constructed de novo or reconstructed from video
samples of real-life cases. The inventors believe that this
Isis Innovation Limited is in a position to offer this technology
exclusively to a commercial licensee. This technology is the
subject of a UK Patent Application.
Contact
Mrs Gill Rowe
BIC Project Manager
T 01865 280825
E gill.rowe@isis.ox.ac.uk
W www.isis-innovation.com
7

Innovations in biological nanostructures
Isis Project 2113
“When we start being able to build micro- and nano-scale
components with imprinted information to self-assemble
with themselves and into hierarchical structures, a whole
new area of engineering will evolve”
Prof. Whitesides, Harvard University
a Strand 1 Strand 2 Strand 3 Strand 4
+ + +
b
Nanobiotechnology is an emerging field of research with
several attractive applications including biological computing
and self-assembling nanorobots. DNA is commonly used as
a biomaterial in the development of nanostructures due to
its chemical characteristics and ability to form large uniform
and/or patterned structures with variable reactivity. DNA
lattices, tiling and nanowires are all currently in development
for scaffolds, membranes and bio-computing, respectively.
Enantiomer 1
17bp (5.8nm)
Or
Enantiomer 2
Digestion
We have developed a simple, one step technique for the
self-assembly of a three dimensional DNA tetrahedron.
While existing methods for generating such structures often
rely on enzymatic treatments as well as laborious purification
steps, the basic synthesis of our structure can be
accomplished in minutes.
By themselves, DNA tetrahedra have a number of potential
applications in drug delivery, gene therapy, and vaccine
delivery. As the structure is three-dimensional, it possesses a
cavity that could host a number of different biomolecules.
Current research at Oxford, for example, is examining the
potential for the tetrahedra to carry biologically significant
proteins and enzymes, which would allow us to modulate
the molecule’s function and activity in vitro and in vivo. One
application being explored is the ability of the structures to
act as taste masking cages.
Another exciting application of these structures is the
assembly of arbitrary shapes and structures on the
nanometre scale. Tetrahedra are natural geometric building
blocks for the construction of other objects, and we are
currently exploring a number of ways of joining tetrahedra
together into custom-designed 3D structures. Once successful,
we may be able to generate extended structures with
nanometre scale precision. This would open up applications
in molecular computing with nanometre scale circuits.
Should we prove successful in generating periodic structures
in three dimensions, the ability to host other biomolecules
Equivalent for
A, B, C, or D digest
could allow the tetrahedral to act as scaffolds for protein
crystallisation. This in turn could facilitate the artificial
crystallisation of proteins, which have failed to generate
crystals using conventional techniques.
This is exciting new technology with many potential applications
and the team is seeking commercial input and
support to develop specific products in the various areas of
interest. We would welcome any interest from commercial
partners with expertise and vision to develop products in the
above areas of drug delivery, biocomputing and protein
crystallisation fields. The inventors are dedicated to enhancing
the value of the technology by understanding and refining
the method of production. If you are interested and would
like further information on this technology or wish to meet
or discuss the invention with the inventors, please do not
hesitate to contact Isis Innovation Ltd.
Contact
Dr Goslik Schepers
Life Sciences Project Manager
T 01865 280844
Equivalent for
E or F digest
E goslik.schepers@isis.ox.ac.uk
W www.isis-innovation.com
8

VASTox plc
Spin-out
At present there is no cure for either Duchenne or Becker
muscular dystrophy. To date treatment consists of extreme
physical therapy, to avoid tightening of the muscles, and
spinal surgery to treat resulting scoliosis. Steroids can be
used in an attempt to slow the disease progression.
Also gene therapy approaches to this problem have been
investigated but to date they have not been successful.
VASTox PLC, a spin-out from the Department of Chemistry,
listed recently on the AIM market of the London Stock
Exchange. VASTox, an acronym for Value Added Screening
Technologies Oxford, is a chemical genomics business that
offers unique drug discovery and toxicology services to the
pharmaceutical industry as well as developing a new
strategy for drug discovery. Based on the work of Professor
Steve Davies and Dr Andy Mulvaney, the company utilises
zebrafish embryonic cells and fruit flies to assess the
suitability of chemical compounds to be developed as
drugs.
Traditionally, pharmaceutical companies have used a ‘Geneto-Screen’
approach, whereby genomics technologies are
employed to find new targets for drugs to treat human
disease. Once the targets are located, vast numbers of
chemical compounds are screened to identify drug prototypes
that modulate the disease target. However, this
approach has been proven largely ineffective except for a
handful of new drug launches.
VASTox’s ‘Screen-to-Gene’ approach reverses this process.
Rather than starting with the disease, clients’ chemical
libraries are probed in phenotypic screens, which allows the
rapid and simultaneous identification of both the molecular
targets for human disease as well as a suitable drug prototype.
The Oxford researchers have
identified a promoter of the
production of utrophin,
which is both highly
regulated and expressed in a
wide range of tissues
Exciting new research in Professor Kay Davies’ lab has
focused on the possibility of compensating for the loss of
functional dystrophin by up-regulating a related protein
named utrophin. The Oxford researchers have identified a
promoter of the production of utrophin, which is both highly
regulated and expressed in a wide range of tissues, and
Professor Kay Davies working together with Professor Steve
Davies has shown that this biological target of the utrophin
promoter is druggable. That is, they have identified classes
of small molecules (chemicals) that significantly up-regulate
the utrophin gene and these ‘hits’ have been externally
validated by a third party. With this work in the background,
VASTox will now seek to find chemicals that can be used as
pharmaceutical agents to increase the expression of
utrophin in people suffering from the disease.
Additionally, VASTox has licensed technology from Isis which
will enable it to continue the research programme begun in
the MRC funded laboratory of Professor Kay Davies at the
University of Oxford. This programme is aimed at finding a
treatment for the muscle wasting disorders of Duchenne
Muscular Dystrophy and the milder form of Becker Muscular
Dystrophy both of which are caused by a mutation in the
dystrophin gene.
Contact
Dr Richard Middleton and Dr James Hamilton
Life Science Project Managers
T 01865 280847 and 280843
E richard.middleton@isis.ox.ac.uk and
james.hamilton@isis.ox.ac.uk
W www.isis-innovation.com
9

Diagnostic for Myasthenia Gravis
Licence deal signed with Athena Diagnostics Inc.
Myasthenia Gravis is a disease which causes muscle weakness
and fatigue without general tiredness. It is described as an
autoimmune disease in that the immune system (or defence
mechanism) of the body has started to treat a normal part
of the body as being foreign – in this case the nerve-muscle
junction.
MuSK
Acetylcholine
receptors
Most people who suffer from this disease have formed an
immune response against a particular molecule on the
surface of the muscle called the Acetyl Choline Receptor
(see diagram). The body’s autoimmune response leads to
loss of this molecule leading to the symptoms of muscle weakness
and fatigue. It can even cause death if the breathing and
swallowing muscles are badly affected.
Nerve
Dr McConville and Professor
Vincent were able to develop a
quick and accurate blood test
that could help the doctors
Muscle
In mysathenia gravis, the patient’s immune response attacks the muscle
surface where acetylcholine receptors and MuSK are situated.
identify these patients and
treat them effectively
Professor Angela Vincent of the Weatherall Institute for
Molecular Medicine at Oxford University and Dr Werner
Hoch of the Max Planck Institute in Tuebingen, Germany,
studied those patients who had the symptoms of
Myasthenia Gravis and yet were not producing an immune
response to the Acetyl Choline Receptor. They found that in
these cases the immune response was to a different
molecule at the nerve-muscle junction called MuSK. With Dr
McConville, a Wellcome Trust supported clinical training
fellow, Professor Vincent was able to develop a quick and
accurate blood test that could help the doctors identify
these patients and treat them effectively. Isis recently signed
a royalty-bearing licence agreement with the Worcester,
Massachusetts company Athena Diagnostics, Inc. to market
and carry out the test. Athena is the leading provider of
advanced neurological diagnostic assays in the United
States of America and Isis is pleased to have entered into
this partnership with them.
Contact
Dr Richard Middleton
Life Sciences Project Manager
T 01865 280847
E richard.middleton@isis.ox.ac.uk
W www.isis-innovation.com
10

Vaccines which pack a double punch
Isis Project 1444
A vaccination regime that powerfully activates both arms of
the immune system has been developed in the Nuffield
Department of Clinical Medicine in the University of Oxford.
The production of potent cellular, as well as antibody
responses to a single vaccination regime, has long been
sought by immunologists.
In order to combat diseases more effectively, it is desirable
to induce stronger immune responses by vaccination.
However, vaccination methods that generate high level
antibody responses can differ significantly from those that
engender strong cell-mediated or T cell responses. For
example, alum is a useful adjuvant for inducing antibodies
but generates weak or negligible CD8 + T cell responses. In
contrast, heterologous prime-boost immunisation methods
have induced strong T cell responses in humans, but only
minimal antibody responses; whereas immune protection
against many diseases can be mediated by either T cells or
antibodies at sufficient levels, and optimal protection may
be achieved by inducing strong responses of both types.
Unfortunately, no vaccination approach currently exists that
allows strong responses of each type to be generated.
Researchers at the University of Oxford, funded by the
Wellcome Trust, have developed a vaccination regime
whereby a virus is mixed with a material (antigen) that is
intended to induce an antibody response. The virus both stimulates
a cellular response and also enhances (adjuvants) the
antibody response to the co-administered antigen. This result
is in itself surprising, but it has also been found that the type
of virus used affects the type of antibody response obtained.
A strong cellular and antibody response to the same
vaccination regime should provide clinicians with much
more effective vaccines for a number of diseases.
Additionally, many standard vaccines are designed to raise
an antibody response against the surface structures of
infectious agents. Some infectious agents, such as the
influenza virus, have highly variable and rapidly changing
surface components and so new vaccines may be frequently
required – in the case of influenza, on an annual basis. The
cellular immune response can be raised against internal
structures of infectious agents, and these are usually much
less variable. A longer lasting effect complementary to the
antibody effect may be achieved with this new approach.
Some infectious agents, such as
the influenza virus, have highly
variable and rapidly changing
surface components and so new
vaccines may be frequently
required
Another application would be in malaria or HIV vaccine
development where it is likely that very effective vaccines will
need to induce strongly both arms of the immune system. In
addition, combinations of vaccines to different diseases
could also be envisaged as a result of this method. This
would obviously have an impact on the cost of immunisation,
and possibly also compliance. Isis has filed a patent on
this method and would like to talk any parties who would be
interested in developing the technology further into the
clinical setting.
Contact
Dr Richard Middleton
Life Sciences Project Manager
T 01865 280847
E richard.middleton@isis.ox.ac.uk
W www.isis-innovation.com
11

Therapeutic Applications of a CC Chemokine
Binding Protein
Isis Project 1325
Researchers at the Department of Cardiovascular Medicine
and the Sir William Dunn School of Pathology have identified
a novel way to reduce local and systemic inflammation
following adenovirus gene transfer. The technology exploits
a protein encoded by the vaccinia virus that binds to CC
chemokines, an important class of inflammatory mediators.
Recent experiments have shown that this approach can
significantly reduce atherosclerosis, which is the underlying
cause of heart attacks and strokes. This technology may find
application in the treatment of other inflammatory diseases
including rheumatoid arthritis, inflammatory bowel disease,
asthma and psoriasis.
Chronic inflammatory diseases are characterised by the
continued recruitment of white blood cells called T cells and
macrophages, which can cause tissue damage.
Macrophages secrete signalling molecules called
chemokines that act to recruit more macrophages and T
cells into the site of inflammation. The continued presence
of T cells and macrophages drives the inflammatory disease
process eventually causing joint erosion (in arthritis) and
blocking of major arteries (in atherosclerosis).
Chemokines are an important class of signalling molecule
that are responsible for continued T cell and macrophage
recruitment in inflammatory disease.
There are over 40 identified human chemokines that
mediate their effects on cells by binding to specific cell
surface receptors. These signalling proteins play an important
role in normal host defence by attracting T cells and
macrophages to sites of infection. Several DNA viruses have
evolved mechanisms to limit the action of these signalling
Treatment with the chemokine binding protein (Ad35K) dramatically
reduces the number of macrophages (stained red) in atherosclerotic
plaques. There was no effect on macrophage recruitment in control
experiments (PBS and AdGFP). For more details see Bursill et al. Circulation
2004; 110: 2460-2466.
molecules. The vaccinia virus CC chemokine binding protein
blocks macrophage recruitment by binding to a wide range
of CC chemokines and preventing them from interacting
with their cellular receptors.
Researchers in Oxford have shown that transfer of a
chemokine binding protein from vaccinia virus to a
recombinant adenovirus can significantly reduce the host
immune response at the site of adenovirus gene delivery
and that the circulating levels of CC chemokine binding
protein can significantly reduce the development of atherosclerosis
through reducing macrophage recruitment 1 .
Isis Innovation is seeking commercial partners to develop
this technology to develop new treatments for inflammatory
disease and to improve the effectiveness of adenoviral gene
transfer technologies.
1. Bursill et al. Circulation 2004; 110: 2460-2466.
This technology may find
application in the treatment of
other inflammatory diseases
including rheumatoid arthritis,
inflammatory bowel disease,
asthma and psoriasis.
Contact
Dr James Hamilton
Life Science Project Manager
T 01865 280843
E james.hamilton@isis.ox.ac.uk
W www.isis-innovation.com
12

Spin-outs – growth and change
A round-up of spin-out news
New CEOs
Two spin-outs founded in the millennium year have taken
on new CEOs, reflecting the increased maturity of the
businesses and addressing the next set of growth challenges
that the respective businesses will face.
Oxford Biosensors welcomed Dr David Hawksworth as
CEO in September 2004. David has previously spent many
years with Siemens, Oxford Instruments and associated
companies. He has succeeded Neil Butler, who led the
business ably from start-up through two funding rounds
raising a total of £6.2 million. David graduated with a first
class degree in physics from the University of Bath, and
gained his Materials Science PhD from the University of
Wisconsin where he was later honoured with the
Distinguished Service Award from the College of
Engineering. In 1996 he became the managing director of
the Oxford Instruments / Siemens joint venture Oxford
Magnet Technology, and chaired the Transition Board when
Siemens acquired full control of the business in 2003. The
company had over 700 employees, and during David’s
tenure annual sales increased from £70 million to over
£120 million. Point of care sensors to assess cardiac risk and
risk of renal failure are Biosensors’ leading products. Medical
device approval in the USA is anticipated in early 2005, and
product should be on the market later in the year.
Earlier, in March 2004, Oxford Biosignals welcomed
Matthew Walls as CEO. Biosignals received equity investment
of £3.2 million from Rolls Royce in October 2003, and is a
pioneer in the use of neural net software to provide
automated multi-parameter monitoring in both industrial
and healthcare applications. Matthew spent a number of
years with Zeneca before running venture funded business
Zylepsis. He has succeeded Dr Pauline Hobday who steered
Biosignals through its initial formation and recent funding
round. Oxford Biosignals’ leading product, QUICK
Technology, provides expert on-the-ground, on-the-engine
and on-the-airframe jet engine health monitoring systems.
QUICK acquires data from vibration sensors and shaft
tachometers along with other performance parameters.
Usage of these systems also provides the latest fan trim
balancing capabilities which allows optimum balancing
solutions based on either flight or ground acquired data.
QUICK solutions are readily applied to other gas turbine
plant including in marine and energy applications. Oxford
BioSignals is developing and exploiting the technology
originated by Professor Tarassenko from the Department of
Engineering in the University of Oxford.
IPO News
October saw the successful flotation of Oxford spin-out
VASTox. Founded in February 2003, VASTox raised
£15 million (before expenses) at 135p per share. This valued
the company at £42.3 million. A fuller description of VASTox
is given on Page 9.
At the time of writing flat panel display company
Cambridge Display Technology has filed its registration
documents in anticipation of a Nasdaq IPO. Although not a
spin-out from Oxford, in 2002 CDT acquired the technology
of the Oxford flat panel display spin-out Opsys in a complex
transaction. A successful IPO for CDT will increase the
returns for Opsys investors, so we remain hopeful of good
news from the Fens.
Contact
James Mallinson
Portfolio Manager
T 01865 280903
E james.mallinson@isis.ox.ac.uk
W www.isis-innovation.com
13

Isis Angels Network
Investment Meeting 28 th October 2004
A successful presentation meeting was held at the Martin
Wood Lecture Theatre on 28 October 2004 in conjunction
with OION, the Oxford Investment Opportunity Network. An
audience of around 100 business angels heard from three
new Isis spin-out businesses, and two introduced by OION,
Risk Decisions, a provider of risk management software, and
Oxsensis, a spin-out from the Rutherford Appleton
Laboratory.
Angela Britton, Private Client Services Partner at Grant
Thornton, gave a brief and informative presentation of
areas where tax planning can contribute substantial value in
Angel-type transactions.
Alan Edwards presented Ori Instruments Ltd, a company
which has been formed to exploit patented novel mechanical
structures, for application in the field of stents. These
structures have been invented and developed by Dr Zhong
You and his team in the Department of Engineering at the
University of Oxford. The new designs can be folded for
deployment using minimally invasive techniques. The first
application for the structures is in high-value implantable
cardiovascular devices, specifically for a Thoracic and
Abdominal Aortic Aneurysm Stent Graft also known as EVAR
(Endovascular Aneurysm Repair). The company is seeking
£1 million to build working prototypes and conduct early trials.
From left to right: Dr David Eastham, Isis Innovation Ltd; Dr John Gregg,
Oxford RF Sensors; Mr Chris Padbury, Oxford RF Sensors.
Dr Trevor Langley presented Cytox Ltd which has been
formed to commercialise leading research from the
University of Oxford in the field of Alzheimer’s disease. The
business model is based on:
A new understanding of Alzheimer’s disease pathology
providing new drugable targets and methods for
developing therapeutic products.
A blood based diagnostic test, proven in human trials, for
very early detection of Alzheimer’s disease.
Development models and demonstrated proof-ofprinciple
that drugs which regulate cell cycle events can
be used to treat Alzheimer’s.
Dr John Gregg introduced Oxford RF Sensors Ltd. The
company uses radio frequency technology for sensors that
can be used simultaneously to determine both the electrical
and magnetic properties of any material
presented to them. The sensors can be used in a wide
range of applications, typical of which are rotational speed
and position sensing in mechanical applications, oil condition
monitoring and materials recycling. Potential markets
include the automotive and related sectors where stricter
requirements on emissions and fuel consumption require
ever more precise measurements from sensors operating
under extreme environmental issues. The company was
formed in September 2004 by Dr Gregg and has already
generated income from options signed with potential
customers. It expects to grant its first licence of the technology
in early 2005. First round funding of £1 million is
now sought to finance the development of further products
for the automotive and process monitoring markets.
Provisional discussions with major pharmaceutical companies
have already indicated an extremely high level of interest
stemming from the range of new treatments, which might
be developed rapidly, to address this multi-billion dollar
market. £2 million is sought.
Business angels or investment professionals wishing to
obtain further information about these proposals, or wishing
to register with the Isis Angels Network, should contact
James Mallinson at Isis.
Contact
James Mallinson
Portfolio Manager
T 01865 280903
E james.mallinson@isis.ox.ac.uk
W www.isis-innovation.com
14

Echocardiographic image analysis
Isis Projects 1283, 676, 874 and 1095
Ultrasound imaging has tremendous utility in a wide range
of medical imaging applications. Echocardiography benefits
from being easy to use, safe, and generally non-invasive
(apart from injection of contrast agents and cardiac stress
inducing drugs in some specialist examinations). It also
allows image sequences to be acquired in real time with
high spatial resolution.
Researchers at the University of Oxford’s Wolfson Medical
Vision Laboratory, part of the Department of Engineering
Science, in partnership with Mirada Solutions Ltd
(a subsidiary of CTI Molecular Imaging Inc and an Oxford
University spin-out company) have created a portfolio of
intellectual property related to the analysis, motion tracking
and quantification of ultrasound images that is particularly
applicable to functional analysis of the heart and soft tissue
elastography. The resulting work is embedded in a software
application that can assist clinicians in the assessment of
heart performance from echocardiographic images.
Professor Alison Noble, a founding director of the Wolfson
Medical Vision Laboratory, pioneered the work. The thrust
of the Wolfson Medical Vision laboratory’s research involves
the development of 2D and 3D functional image analysis
techniques for quantifying disease progression and regression
and organ function. Professor Noble’s own research interests
are in in-vivo soft tissue analysis. She leads the group’s
research on cardiac image analysis comprising 2D and 3D
echocardiography and cardiac Magnetic Resonance (MR), as
well as breast ultrasound image analysis research. Her group
also works in generic ultrasound image analysis, with
particular interest in ultrasound image segmentation. The
Wolfson Medical Vision Laboratory research is highly
multidisciplinary and prides itself on working closely with
departments in the Oxford University Medical Sciences
Division and Oxford Radcliffe Hospitals NHS Trust.
Echocardiographic diagnosis of Coronary Artery Disease
(CAD) is based on global (whole heart) and regional (wall
segment) assessment of cardiac pumping function. The
accurate assessment of cardiac function is important to
clinical investigations. Performance of the left or right
ventricle assessed via ventricular measurements, such as
chamber dimensions, volume and ejection fraction is
increasingly undertaken in clinical practice. In the presence
of blockages in the coronary arteries, blood supply to the
cardiac muscle is reduced impairing proper contraction and
relaxation.
A typical application is identifying heart muscle that has
become ischemic (deficient in blood) which will become
evident by immediate changes in heart motion, characterised
by changes in (regional) heart motion.
Conventionally, diagnostic parameters are extracted in a
semi-quantitative fashion from echocardiographs by visually
assessing and scoring the motion of segments of the ventricle
walls. Visual assessment is a limitation of the technique
since it requires experienced users to perform the acquisition
and interpretation of the images. A contrast agent can also
be used to enhance the quality of the image, but the
assessment, if visual, still requires similar expertise.
Software tools, based on the inventions presented here,
enables the tracking and analysis of the motion of the left
ventricle (Figure 1) or contrast enhanced images in order to
derive accurate quantitative parameters like regional wall
motion and ejection fraction.
Echocardiographic sequence analysis
– Projects 1283 and 676
These two technologies are newly developed and enhanced
methods for extracting cardiac boundary pixels from
echocardiographic sequences.
There are many instances in which a subject in an image is
moving, and it is necessary to track the subject as it moves
from frame to frame; this movement is known as optical
flow or image velocity. Such measurement of optical flow
may be undertaken to improve the image encoding
efficiency, or allow enhancement of the display of the
movement of some particular tracked part of the image to
assist an observer attempting to interpret the image. Optical
flow determination methods fit into one of three groups:
differential techniques, frequency based methods and
matching techniques.
Medical images present many difficulties in image processing
because of their typically high noise level. This problem is
particularly significant in the tracking of cardiac walls by
15

Figure 1: B-mode long axis frames (a) B-Mode grey level 4 chamber view showing the left ventricle (LV) right ventricle (RV), left and right atria (LA,RA) and the
mitral valve (MV). (b) Traced Endocardial and Epicardial contours.
ultrasound methods, and is compounded by the way in
which cardiac motion varies during the cardiac cycle. Several
means of identifying and tracking cardiac walls in echocardiograms
are conventionally available but have inherent
faults.
The Oxford invention for identifying boundary pixels in
echocardiographic sequences or other ultrasound image
sequences consists of a phase boundary detection stage
followed by an optical flow estimation stage based on block
matching methods. New contributions by Oxford
researchers to the basic computer vision processes have
resulted in a system that is both faster and more robust than
conventional alternatives, delivering information on both
the inner and outer boundaries of the organ.
The system is most beneficial when data is medium to lowcontrast,
when methods for detecting boundaries based on
contrast differences do not work well. Professor Noble said
“In experiments we have done, we have shown that this is
far better than the conventional method which doesn’t use
our novel physics-based approach.”
These methods can be applied to magnetic resonance and
X-ray images as well as ultrasound images for automatic
quantification and analysis.
An image-centric software tool based on these inventions
enables the tracking and analysis of the motion of the left
ventricle in B-mode (Figure 1) or contrast enhanced image
sequences in order to derive accurate quantitative key
parameters like regional wall motion and ejection fraction.
Detection of features in images
– Project 874
This invention relates to an image processing method,
embedded in software, which enables the user to automatically
detect particular features of interest within an image.
The method is particularly useful where the user is attempting
to detect the features in noisy 2D or 3D images, and thus is
particularly useful in medical imaging, for instance using
ultrasound.
The Oxford invention
overcomes the problem by
detecting image features based
on the shape of the intensity
profile of the feature, rather
than just its intensity
Conventional methods for enhancing such noisy images
have relied on examining the intensity of the image, for
instance by smoothing the intensity to reduce noise or by
setting a detection threshold based on amplitude.
However, these conventional thresholding techniques suffer
from the difficulty of setting a suitable global threshold for
the image that will reduce noise yet retain all the features of
interest.
16

Figure 2: This screen shot shows a tracked short axis
contour and two displays of quantitative information.
A contraction image showing endocardial velocities
around the contour over time and a plot of cavity
area, both of which are key properties of interest to
the clinician.
Reproduced from the Quamus ® software package (an
automated echocardiographic analysis tool) courtesy
of Mirada Solutions.
The Oxford invention overcomes the problem by detecting
image features based on the shape of the intensity profile of
the feature, rather than just its intensity. This is achieved by
an intensity independent comparison of the intensity profile
across the image with a shape model of features of interest.
Subsequent image processing is further improved using a
feature labelling process to describe the feature’s properties.
The label can include such information as feature orientation,
or velocity of features in image sequences. By setting the
shape model appropriately the invention is adaptable to the
detection of any features corresponding to a step change in
intensity, such as accurate identification of ventricular walls
in echocardiograms.
By applying the same force and distortion to the tissue
during the scan, change in shape during the scan can be
prevented. A mechanical sweep probe, or constraining the
target object and scanning through a window rather than
making direct contact with the skin will achieve this, but the
scan geometry is limited in both cases limiting their usefulness
in clinical diagnosis.
The Oxford development constructs a scan that would have
been produced if there had been no contact between the
skin and the probe. Using an elastic model specified a priori
the method corrects the deformation applied by the probe,
providing more accurate reconstruction and improved
compounding performance.
Improved Ultrasound Imaging
– Project 1095
To create an ultrasound image the ultrasound probe must be
placed in contact with the skin. This contact force, although
small, is sufficient to distort the skin and soft
tissues beneath. Correction of this contact deformation is
important when the tissue geometry must be known
accurately such as in image guided surgery and in 3D ultrasound
where several 2D images are acquired at different
positions in a volume of tissue. The tissue will only be
accurately reconstructed if its shape is the same in each scan.
Combining or compounding these scans makes an assumption
of constant tissue shape, but if the tissue has been distorted
differently in each scan direct compounding of the
data sets leads to a blurred image.
Unusually, the inventions presented here exist in an implemented
software form (Figure 2), the result of collaboration
between Oxford University and Mirada Solutions. This work
is covered in four patent applications and Isis Innovation is
currently seeking partners to exploit this technology.
Contact
Dr David Churchman
Project Manager Physical Group
T 01865 280857
E david.churchman@isis.ox.ac.uk
W www.isis-innovation.com
17

Brain connectivity mapping
Isis Project 1341
A new and simple method that allows the creation of a
dataset by mapping MRI brain scans of individuals with
brain disorders has been developed and can be used to
determine a pattern of connectivity for certain conditions
such as schizophrenia enabling a better, more accurate
diagnosis of the condition and therefore an improvement in
treatment targeting accuracy and outcome.
The unique connectivity pattern of a brain region
determines the type of information available to it, and
hence influences its function. Defining these patterns
enhances our knowledge of human brain architecture and
function. Non-invasive in vivo definition of brain
connectivity patterns complements functional imaging
and provides new understanding of disorders associated
with developmental or regional alterations of brain
connectivity. There are extensions to this approach to
clinically important issues. As an example, brain
connectivity problems are important in developmental
and acquired brain disorders.
Researchers working within the University of Oxford Clinical
Neurology Department have developed a technique that is
able to provide non-invasive identification of boundaries
between major nuclei in a patient undergoing surgery,
thereby improving both targeting accuracy and outcomes.
The invention relates to mapping the connectivity of the
brain’s nervous system in a human and uses imaging data
derived from magnetic resonance imaging. New computer
methods derive the anatomical connectivity patterns and
analyse the structure of the nervous system.
Testing the hypothesis that changes in fronto-thalamic
circuitry i.e. thalamic dysfunction is a factor in schizophrenia,
becomes a reality using this methodology. Impairments in
cortico-cortical connectivity are found in individuals with
learning disabilities.
The new method allows a quantitative approach to the
differences so that actual variations in learning abilities and
performance can be determined. At present localisation in
stereotactic neurosurgery or deep brain stimulation of
specific thalamic nuclei in movement disorders remains
difficult. This approach to grey matter segmentation has the
potential to improve targeting accuracy and outcomes.
Thalamus – connectivity pattern dataset.
The invention relates to
mapping the connectivity of
the brain’s nervous system in a
human, and uses imaging data
derived from magnetic
resonance imaging. New
computer methods derive the
anatomical connectivity
patterns, and analyse the
structure of the nervous system
Contact
Dr David Eastham
Physical Sciences Project Manager
T 01865 280855
E david.eastham@isis.ac.ox.uk
W www.isis-innovation.com
18

Your gateway to the expertise of the
University of Oxford
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provides independent, confidential,
authoritative consultancy drawn
from the expertise of the University
of Oxford.
We are actively engaged in the
following areas:
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When you contact Oxford University
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Meetings
Forthcoming meetings of the
Oxford Innovation Society
will be held on the following dates:
Thursday 9 th December 2004
Thursday 7 th April 2005
Thursday 29 th September 2005
Meetings are held in Oxford for OIS Members and invited guests, and are followed by a formal reception
and dinner in an Oxford college hall.
For information about the OIS contact Cynthia Warmington, Marketing Communications Administrator:
T +44 (0)1865 280837 E cynthia.warmington@isis.ox.ac.uk
Published by Isis Innovation Ltd The Technology Transfer Company of the University of Oxford
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Cover photo: Nancy Kedersha / UCLA / Science Photo Library