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					                                                      The latest from




                                            NEWS
                                                      Isis Innovation Ltd
                                                      The University of Oxford’s
                                                      Technology Transfer
                                                      company

                                                      Edition 59 Spring 2010




Research to remedy




   Reviewing the latest innovations, collaborations and technology transfer
Contents

                                              NEWS
                                                        The latest from
                                                        Isis Innovation Ltd
                                                        The University of Oxford’s
                                                        Technology Transfer
                                                                                     Research to remedy
                                                        company

                                                        Edition 59 Spring 2010




 Research to remedy                                                                  Cover: ‘Best Research for Best Health’ is the NIHR’s programme to establish
                                                                                     the NHS as an internationally recognised centre of research excellence through
                                                                                     supporting outstanding individuals, working in world-class facilities, conducting
                                                                                     leading-edge research focused on the needs of patients and the public. The Oxford
                                                                                     Biomedical Research Centre is funded to undertake ‘translational research’ – first
                                                                                     time studies in patients of innovations, intended to improve healthcare.


                                                                                     (Photo courtesy of Shutterstock)
     Reviewing the latest innovations, collaborations and technology transfer




03   Introduction and news
     The latest developments in Oxford and
                                                                                                                     20   Probing the possibilities
                                                                                                                          Isis project number 3164
     the world of technology transfer
                                                                                                                     21   The culture of today
04   Getting with the programme
     Oxford Innovation Society meeting
                                                                                                                          Isis project number 4231


                                                                                                                     22   Brains behind the operation
06   Preventing childhood meningitis
     Oxford Innovation Society meeting
                                                                                                                          Isis project number 3966


                                                                                                                     23   The exosome factor: delivering genes to cells
08   Innovative technologies for molecular medicine
     Oxford Innovation Society Member
                                                                                                                          Isis project numbers 4096 and 4208


                                                                                                                     24   A bone of contention
09   Investing in innovation
     Isis Angels Network
                                                                                                                          Isis project number 4203


                                                                                                                     25   Pixel perfect
10   New licence agreements
     A round up of new licence agreements
                                                                                                                          Isis project number 6614


                                                                                                                     26   Work smarter, not harder
12   Pay as you go
     Isis project number 3044
                                                                                                                          Isis project number 3471


                                                                                                                     27   Fuel for thought
14   Commercial catalyst
     Isis project number 4296
                                                                                                                          Isis project number 4326


                                                                                                                     28   Changing climate for business
15   Capturing carbon dioxide
     Isis project number 4425
                                                                                                                          Oxford University Consulting


                                                                                                                     29   Unlocking drug discovery
16   Time for innovation
     Isis project number 3162
                                                                                                                          Oxford University Consulting


                                                                                                                     30   Spin-out portfolio news
17   OWL 2 the world wise web
     Isis project number 3567
                                                                                                                          Oxford Spin-out Equity Management


                                                                                                                     31   Unearthing enterprise
18   DNA-binding brought to light
     Isis project number 3196
                                                                                                                          Isis Enterprise


                                                                                                                     32   Future Oxford Innovation Society meetings
19   The big screen
     Isis project number 3715




                                                                                                                 2
Introduction
Latest developments in Oxford and the world of technology transfer

                     Welcome to Isis News 59, covering the          This year, we will also be celebrating the Oxford Innovation
                     lectures given at the December meeting         Society’s 20th Anniversary. Established in 1990, the Society
                     of the Oxford Innovation Society and           has welcomed over 150 members and continues to be the
                     featuring a wide range of Isis business        leading forum for open innovation, fostering links between
                     activities and opportunities. In this          business and the academic community. More details of the
                     first issue of 2010, Isis reflects on          events which celebrate this landmark will be available in the
                     more than 20 years of tradition and            months to come.
excellence, whilst looking forward to a promising future of
new challenges and innovation in the year ahead.                    Yours


The December 2009 OIS meeting was held at Trinity College
and sponsored by the Oxford Centre for Biomedical Research.
Professor Keith Channon of the BRC and Professor Andrew             Tom Hockaday, Managing Director
Pollard of the University’s Department of Paediatrics talked
about the changing healthcare environment, with a focus
on translational medicine and the prevention of childhood
meningitis. Details of these talks can be found on pages 4-7.




News
Seed Fund report published                  The Oxfordshire IGT                          Isis Innovation in Hong Kong


In December 2009, Isis published a          In collaboration with a number of            Isis Enterprise continues to develop in the
report celebrating 10 years of the Oxford   local groups, including NESTA and            Far East, providing technology transfer
University Challenge Seed Fund (UCSF).      the Oxfordshire County Council, Isis         and innovation management consulting
                                            Enterprise has set up the Oxfordshire        to university, industry and government
The report highlights some of the best      Innovation and Growth Team (IGT).            clients. To support these activities Isis
examples from the last 10 years of where                                                 has established a subsidiary in Hong
awards from the Fund of up to £250,000      Funded by the South East England             Kong, to provide the platform from which
enabled researchers to develop their        Development Agency, the IGT aims to be       to develop activities in the region.
ideas and overcome the challenges of        a sustainable community of innovative,
proving, prototyping and planning their     high growth businesses, which can            Isis Enterprise will continue to offer
way to a commercial deal or a new           offer business support to a number of        advice    on   innovation     policy   and
company.                                    organisations.                               technology transfer services in the region
                                                                                         through Isis Innovation Hong Kong. Its
Since it was first launched in 1999 the     Research Reagents                            consultants currently provide training
UCSF has awarded £5.7m, financing 102                                                    and support to public and private sector
projects and prompting the formation        Isis has recently launched its new           clients worldwide.
of 31 spin-out companies and the            website    catalogue      covering    the
completion of 51 commercial deals.          Research Reagents or materials available     In 2009, Isis also established a presence
                                            from   Oxford    researchers      through    in Singapore, from which it works with
A PDF of the report is available for        reagents@isis.ox.ac.uk.                      local and regional research institutions,
download on the Isis website.                                                            government bodies and corporations.




                                                                3
                                    Getting with the programme
OxfORD INNOvATION SOCIETY MEETINg




                                    Enabling translational research through partnership.

                                    Background                                                           •	 Energise clinical research activity in an NHS hospital,
                                                                                                            and contribute to clinical excellence through recruitment,
                                    The Oxford Comprehensive Biomedical Research Centre                     retention, innovation and education
                                    (BRC) is a partnership between the Oxford Radcliffe Hospitals        •	 Develop innovation, commercial interactions and intellectual
                                    NHS Trust and the University of Oxford. It has been made                property, for the benefit of NHS patients
                                    possible by a grant from the Department of Health’s National
                                    Institute for Health Research (NIHR) under the programme             Three years on, the Oxford BRC has funded or part funded
                                    ‘Best Research for Best Health’.                                     more than 185 research projects and recruited 370 staff
                                                                                                         with BRC funding/NHS and University. 75 consultants now
                                    The BRC was founded on 1 April 2007 through a competitively          have dedicated research time – including new posts, some
                                    awarded grant of £57.5m over five years from the NIHR. The           shared between the BRC and the University – in areas such as
                                    BRC is built on the research expertise of the University of          cardiology, diabetes, neurology, stroke and oncology.
                                    Oxford and the Oxford Radcliffe Hospitals NHS Trust, and is
                                    part of the Government’s initiative to make the UK a global          Strategic and operational developments
                                    leader in research, healthcare education and training.
                                                                                                         The central programme of the Oxford BRC remains focussed
                                    It is the aim of the BRC to develop a research portfolio and         around fourteen research themes, which include ten with a
                                    enhance its international reputation to reflect the importance       specific clinical focus, and four ‘cross cutting’ themes. The latter,
                                    of Oxford as a centre for world-class medical and bio-medical        providing technology and innovation platforms and infrastructure,
                                    research.                                                            with broad application across the clinical themes.


                                    Philosophy                                                           The BRC has also made important steps in aligning research
                                                                                                         processes across the Partnership, through the establishment
                                    The philosophy of the BRC is that high quality training,             of joint appointments and shared operational structures
                                    research and healthcare delivery drive each other and are            in Trust R+D and University Research Services offices.
                                    co-dependent. This also reflects the aims of the NIHR                This has enabled more seamless management of important
                                    programme ‘Best Research for Best Health’. The Oxford                research functions such as research governance, grants and
                                    partnership brings together these three components and the           contracts.
                                    BRC is the vehicle to make it happen. The drivers for success
                                    in the BRC are to connect different scientific disciplines,          Recruitment of academic clinicians to lead research has remained
                                    healthcare professionals and patients to advance medical             a priority during 2008-9. We undertook a major recruitment
                                    research and healthcare delivery.                                    initiative in Autumn 2008 that has led to active recruitment
                                                                                                         processes in women’s health, brain, cardiovascular/stroke,
                                    Our activities have focused on core aims to:                         gastroenterology/immunology, vascular surgery, paediatrics,
                                                                                                         respiratory medicine, cancer, pathology and diabetes; several
                                    •	 Strengthen the existing partnership between the University        of which have now completed the recruitment.
                                      and the ORH Trust, in order to catalyse translational
                                      research                                                           More broadly, the Oxford Cancer Centre (OCC) opened earlier
                                    •	 Build research capacity and infrastructure within the             in 2009. Located on the Churchill hospital site, alongside the
                                      hospital environment                                               new Radiation Oncology and Biology Institute, the £108m



                                    Three years on, the Oxford BRC has funded or part funded more
                                    than 185 research projects and recruited 370 staff with BRC
                                    funding/NHS and University.

                                                                                                     4
OCC forms part of a major new investment in cancer and                •	 Establishing state-of-the-art genetics technology and
cancer research by the Oxford Radcliffe Hospitals NHS Trust,             processes for high-throughput DNA sequencing and
MRC, CRUK and EPSRC; and Oxford University. These                        mutation detection in inherited cardiac and neurological
developments bring together NHS clinicians, scientists, and              diseases, cancer and micro-organisms
University departments in a single facility on one campus. The        •	 Support of internationally leading vaccine developments
OCC will underpin the work of the BRC cancer and imaging                 in paediatrics (e.g. meningitis), TB and influenza, including
themes, and have additional major impact in genetics, blood              ‘first in man’ testing of a novel influenza vaccine strategy
and tissue banking/cohorts themes.                                    •	 Translation and application of new immune phenotyping
                                                                         techniques, initially established in the basic science
Within the themes, particular research highlights include:               research laboratory, to clinical laboratory tests for use
                                                                         in allergic skin diseases, HIV and hepatitis C infection,
•	 The completion of construction of the Acute Vascular                  autoimmune disease and transplantation
  Imaging Centre (AVIC), an internationally unique facility           •	 New programmes of work in gastroenterology and
  incorporating interventional cardiology/radiology and state-           respiratory medicine, through links with the immunity,
  of-the-art MRI scanning. AVIC will allow new diagnostic                infection, imaging and tissue banking/cohorts themes
  approaches and treatments to be developed in the
  emergency presentation of heart attack and stroke, that will        The upcoming year will be critical for the NHS/University research
  underpin major research programmes in the heart, stroke,            community to demonstrate to the public, and Government,
  brain and imaging themes                                            that the funding for translational research must continue. We
•	 Application of innovative technology to clinical problems          have started down a path of discovery which provides huge
  including data fusion to improve patient monitoring in              opportunities to develop speciality services, and drive forward
  the emergency department and ITU, and mobile phone                  innovation and improvements in patient care, whilst reducing
  technology to optimise personal blood glucose monitoring,           costs for a challenged health economy, and delivering care in
  whilst aiding rapid decision making and triage in acute             settings more appropriate and convenient for patients; as well
  stroke management                                                   as fostering a whole new generation of clinician scientists.
•	 New approaches to diagnosis and tracking hospital-
  acquired infection (MRSA, Clostridium Difficile), and their         Biomedical Research Centres are a critical factor in delivering
  relationship to infection in the community, using statistical       the UK’s biomedical research vision and capability. We look
  and genetic techniques to rapidly identify individual               forward to working with our partners to help ensure that `Best
  organisms and reveal routes of transmission                         Research for Best Health’ becomes a reality.

CONTACT Jen Shanahan NIHR Biomedical Research Centre Oxford T 01865 743294 E jennifer.shanahan@orh.nhs.uk W www.oxfordbrc.org

                                                                  5
                                    Preventing childhood meningitis
OxfORD INNOvATION SOCIETY MEETINg




                                    Challenges in design and policy.

                                    Vaccines are the most cost-effective public health intervention         Individuals suffering from meningitis classically complain
                                    with a particular impact on the health of children under 5 years        of severe headache, high temperature, vomiting, stiff neck
                                    of age. Today global immunisation efforts save the lives of             and fear of bright lights (those with meningococcal disease
                                    several million children each year but many more lives could            may also have a non-blanching rash that looks like bruising;
                                    be saved in the developing world by improving access to                 see www.meningitis.org.uk for further information). The
                                    the vaccines that our own children are privileged to receive.           symptoms are very difficult to recognise in young children
                                    Furthermore, several major diseases, if targeted for vaccine            who may just be hot and irritable. About 1 in 10 of those
                                    prevention could transform global health. Putting vaccines              affected die and survivors may suffer hearing loss or brain
                                    at the top of the health agenda, Oxford University has the              damage. New guidelines have been developed (due to
                                    largest academic vaccine research programme in the UK with              be published this year by the National Institute for Clinical
                                    a pipeline of new vaccines in development (including vaccines           Excellence) to try and improve the way cases are managed
                                    for TB, Influenza, malaria, hepatitis C, HIV and childhood              and reduce the risk of complication; but vaccine prevention
                                    meningitis), as well as expertise in the immunological evaluation       is the only rational approach to reduce the morbidity from
                                    of vaccine responses and strong links with industrial partners.         this rapidly devastating disease.
                                    Vaccinology in Oxford is supported by the National Institute for
                                    Health Research’s Oxford Biomedical Research Centre, which              A vaccine for Hib was studied in Oxford from 1989-1992 (led
                                    has allowed substantial progress in the development of these            by Professor Richard Moxon) and was introduced throughout
                                    life-saving vaccines.                                                   the UK in 1992 (given to babies at 2, 3 and 4 months of age),
                                                                                                            subsequently preventing in the region of 10,000 cases of this
                                    Whilst two thirds of the global deaths of children under 5 years        serious disease in the UK. A vaccine for MenC was studied
                                    of age are caused by infectious diseases, childhood death               during the 1990s and following its introduction a decade ago
                                    in wealthy countries is now uncommon, with most deaths                  has prevented approximately 15,000 cases. A vaccine for 7
                                    attributed to accidents and malignancy. Meningococcal disease           types of Pneumo was introduced for babies in 2006 and may
                                    (caused by the bacterium, Neisseria meningitidis) is the leading        have prevented as many as 1000 cases of disease caused by
                                    infectious cause of childhood death in the UK and as such               these 7 types already.
                                    has been a major priority for vaccine prevention for the past 2
                                    decades. Most cases of meningitis (inflammation around the              These meningitis vaccines protect the individual who is
                                    brain) are caused by 3 different families of bacteria including         vaccinated by stimulating part of the immune system, called
                                    Neisseria meningitidis (Men), and also Haemophilus influenzae           antibodies. Although protection is very good initially, the
                                    type b (Hib) and Streptococcus pneumoniae (Pneumo). To                  level of antibody falls quite rapidly when young children are
                                    complicate matters there are 5 types of Men (A, C, Y and W);            immunised. However, when older individuals are vaccinated,
                                    some 91 types of Pneumo (assigned various numbers and                   especially those over 10 years of age, antibody levels are more
                                    letters, e.g. 6A and 22F) but only one type of Hib.                     sustained. We now know that one of the most important ways
                                                                                                            in which the vaccines protect populations from meningitis is
                                                                                                            through herd immunity. The meningitis bacteria normally live
                                    A vaccine for 7 types of Pneumo                                         harmlessly in the nose or throat of healthy people (carriers) and
                                                                                                            it is only rarely that they are acquired by a susceptible individual
                                    was introduced for babies in                                            and cause the disease. It is recognised that most transmission
                                                                                                            of the bacteria to susceptible individuals comes from these
                                    2006 and may have prevented                                             “carriers”. In the case of Hib and Pneumo, most carriage is
                                                                                                            among preschool children and for MenC it is teenagers and
                                    as many as 1000 cases of                                                young adults. When carriers are immunised against Hib,
                                                                                                            Pneumo and MenC, transmission is reduced and the rest of
                                    disease caused by these 7                                               the population (including those who have not been vaccinated)
                                                                                                            receive the benefits of herd immunity as transmission of the
                                    types already.                                                          organisms is blocked, leading to a more dramatic reduction in




                                                                                                        6
                                                                                                                                              Image of children susceptible to disease in Africa, courtesy of Stock.Xchg
the disease than could be predicted from the direct protection          therefore seen as “self” by the human immune system. Despite
of the vaccines alone. Since immunity has waned rapidly in              this difficulty MenB is one of the major targets for development
those individuals who were immunised in early infancy, the              by vaccine manufacturers in view of the importance of the
low rate of MenC disease today in the UK can be attributed              disease to child health, as a result of its position as the leading
to herd immunity. We have undertaken a series of studies in             infectious cause of death in childhood.
Oxford that show that adolescent booster doses of MenC will
be needed in the future to sustain population immunity and              In Oxford we are developing a novel MenB vaccine that
these studies have already been used to support the decision            uses extensive data from molecular epidemiological studies
in Canada to introduce the boosters.                                    (Professor Maiden, Zoology) to design a vaccine that has high
                                                                        coverage of MenB strains and uses proteins that we know
Most meningitis in the UK in 2010 will be caused by MenB                (from genetic evidence of immune selection) are seen by
or types of Pneumo that are not in the current vaccine. To              the immune system. This major new vaccine, funded by the
improve control of the Pneumo infections, new vaccines                  Wellcome Trust, should enter phase 1 trials in early 2011.
against Pneumo have been developed and are expected to be
introduced in Europe in the next year. MenB remains a major
challenge for vaccine development. The germ has adopted a
clever “cloaking” mechanism to hide by covering itself in sugars
that decorate the brain cells of the human foetus and are



CONTACT Professor Andrew Pollard Oxford Biomedical Research Centre T +44 (0)1865 857420 E andrew.pollard@paediatrics.ox.ac.uk

                                                                    7
                                   Innovative technologies for molecular medicine
OxfORD INNOvATION SOCIETY MEMBER




                                   Oxford Gene Technology’s insight into commercial strategy.



                                   Founded in 1995 by Professor Ed Southern, Oxford Gene
                                   Technology (OGT) boasts over 40 high-profile licensees
                                   of microarray technology. The licensing strategy originally
                                   employed has not only been successful in generating robust
                                   revenue growth, but also forging strong relationships with
                                   major international corporations including Agilent, Illumina, and
                                   Roche.


                                   With a view to decreasing its reliance on licensing-derived
                                   revenue, OGT has recently revised its commercial strategy
                                   and activities. The new corporate structure has three core
                                   commercial arms: Clinical and Genomic Solutions, Biomarker
                                   Discovery, and Licensing. In addition, an Exploratory
                                   Research division, headed by Professor Southern, focuses
                                   on developing new diagnostic techniques with potential for
                                   in-house commercialisation or partnering with diagnostic and            To further support its commercialisation strategy in molecular
                                   pharmaceutical organisations.                                           medicine and diagnostics, OGT recently acquired Sense
                                                                                                           Proteomic Ltd – a UK-based company specialising in the
                                   The company is now focused on providing advanced genomic                discovery of disease-specific biomarkers through the use
                                   solutions and innovative molecular diagnostics. This is                 of novel functional protein arrays. Projects for creating and
                                   exemplified though the Genefficiency™ Plus microarray service           validating biomarker panels for a range of diseases, including
                                   which successfully undertook a project for the Wellcome                 prostate cancer and colorectal cancer, are already at an
                                   Trust Case Control Consortium to identify the impact of copy            advanced stage.
                                   number variation (CNV) in the human genome. During this
                                   project, OGT used its high throughput technology to screen              OGT’s enhanced focus has seen significant investments in
                                   DNA samples from over 21,000 clinical and control samples               employees and facilities. The total workforce has doubled over
                                   in less than 20 weeks, generating over 2 billion high quality           the last 2 years to over 60 people and, in 2007, in anticipation
                                   data points. The first findings of this study have recently been        of this rapid expansion, OGT moved to a new, purpose-built
                                   published in Nature.                                                    facility located in the Begbroke Science Park near Oxford.
                                                                                                           These strategic decisions are clearly paying off with strong
                                   The technical expertise and experience generated though                 year on year revenue growth across all business units, and
                                   providing high-quality microarray services has enabled OGT to           the future of OGT looks both assured and exciting with further
                                   identify and develop optimised products to meet emerging and            expansion plans on the horizon.
                                   growing applications. One example is the OGT CytoSure™
                                   product range, which is widely regarded as the “gold-standard”
                                   for cytogenetic analysis and is used by many highly respected
                                   scientists and research institutions to identify the plethora of
                                                                                                           Disclaimer: CytoSure products are provided under an agreement
                                   genetic aberrations that can cause disease or developmental
                                                                                                           between Agilent Technologies, Inc. and OGT. The manufacture,
                                   disorders (e.g., DiGeorge and Williams-Beuren).                         use, sale or import of these products may be subject to one or
                                                                                                           more of U.S. patents, pending applications, and corresponding

                                   These strategic decisions are                                           international equivalents, owned by Agilent Technologies, Inc. The
                                                                                                           purchaser has the non-transferable right to use and consume the
                                                                                                           products FOR RESEARCH USE ONLY AND NOT for DIAGNOSTICS
                                   clearly paying off with strong                                          PROCEDURES. They are not intended for use, and should not be
                                                                                                           used, for the diagnosis, prevention, monitoring, treatment or alleviation

                                   year on year revenue growth.                                            of any disease or condition, or for the investigation of any physiological
                                                                                                           process, in any identifiable human, or for any other medical purpose.


                                   CONTACT Stephen Archibald Marketing Communications Manager T +44(0)1865 856828 E stephen.archibald@ogt.co.uk

                                                                                                       8
Investing in innovation




                                                                                                                                                                           ISIS ANgElS NETWORK
The Isis Angels Network (IAN) hosted its annual investors meeting in collaboration with OION at the Saïd
Business School on 25 November 2009.

The meeting, which attracted an audience of more than                  and diagnostic capabilities based on the company’s proprietary
one hundred business angels and venture companies both                 screening technology. Despite membrane proteins representing
nationally and internationally, featured eight presentations,          around half of all marketed drug targets, the limitations of
including four young technology companies from the OION                existing high-throughput screens have been identified as a
network, and four prospective Oxford University spin-outs, all         major challenge for future drug discovery and drug safety
seeking to raise finance from specialist investors.                    screening. The Oxford technology provides a major advance
                                                                       in throughput, cost, reliability, and data quality for such
Amongst the proposed Oxford University spin-out companies              applications.
was OxEmS, who delivered a talk on their novel electronic
solution for use by utility companies to identify and maintain         Spin-out Oxford EMA Imaging sought investment in their 3D
buried infrastructures. The Oxford technology can locate               high quality imaging system that is non-ionising and achieves a
and easily identify different pipework at varying depths, and          resolution and contrast similar to Magnetic Resonance Imaging
is the only solution that enables utility companies to prevent         (MRI), at the price of ultrasound imaging. The Oxford invention
leaks and minimise disruption. The ability to locate the exact         can be applied to investigate human tissues and organs, and
source of the problem and consequently save money using                could also potentially be applied to non-medical applications.
this method has proved pertinent in the growing global utility         Over the last decade, the researchers behind this imaging
infrastructures market. Consequently, clients have already             technique have been successful in commercialisation of their
requested trials of the OxEmS technology at their own sites.           work, and a number of products based on their technologies
                                                                       are currently on the market. The team is currently building the
Diagnostic spin-out, Oxford Contrast, discussed their mission          first prototype and requires investment in order to bring this
to develop novel, targeted contrast agents for use in Magnetic         product to the market.
Resonance Imaging (MRI) and Positron Emission Tomography
(PET). Using a first-in-class in-vivo diagnostic platform, they        All Oxford proposed spin-outs are in negotiations with potential
are able to provide earlier and more precise                              investors through Isis.
diagnosis in a range of major diseases, in
particular multiple sclerosis. Furthermore, the                                        Established in 1999, the Isis Angels Network
technology enables monitoring of disease                                                  (IAN) is a not-for-profit company limited
progression and evaluation of response                                                    by guarantee that provides a vehicle
to treatment. Their pioneering technology                                                 for the introduction of private individuals
represents a fundamental breakthrough,                                                    and companies with potential interest in
moving       away       from    existing                                                   investing in spin-outs from the University
non-specific MRI contrast agents,                                                           of Oxford.
by using an active molecular
targeting approach, which                                                                       IAN membership is currently free, and
is currently the fastest way                                                                    open to both investment professionals
of detecting pathology in                                                                           and private investors.
the early stages of disease
progression in the world.                                                                             Isis seeks first-round investment
                                                                                                                                            Photo courtesy of Stock.Xchg




                                                                                                      in spin-outs from all investors
Oxford     Cytologic,     leader                                                                     including business angels, private
in   the   field   of   membrane                                                                    equity, institutional investors, seed
protein analysis, demonstrated                                                                      and venture capitalists from the UK
high-throughput drug discovery                                                                   and internationally.




CONTACT Andrea Alunni Seed Investment Manager T +44 (0) 1865 280843 E andrea.alunni@isis.ox.ac.uk W www.isis-innovation.com

                                                                   9
                         New licence agreements
NEW lICENCE AgREEMENTS




                         Isis licences the latest Oxford software and medical questionnaire.

                         Augmented reality software


                         Isis Innovation has licensed Oxford augmented reality software
                         to QderoPateo LLC, an augmented reality hardware and
                         software platform company, for the provision of advertising and
                         other services on mobile phones.


                         Augmented reality (AR) combines a live view of a physical
                         real-world environment combined with virtual, computer-
                         generated images creating a mixed (augmented) view.
                         Annotated images in a TV programme (such as sports scoring)
                         are an early example of AR. Current applications include the
                         use of avatars placed in the real-world environment to offer           The Oxford PTAM software in action.
                         advertisement or other information to the user. The advent
                         of smartphones, equipped with a camera, has provided a                 software. Phone cameras offer a narrow field-of-view that
                         platform that can be exploited in a number or ways to deliver          makes robust tracking harder. Slow frame rates result in
                         internet-based content to users in a novel and appealing way.          significant motion blur, and the rolling shutter causes severe
                                                                                                smearing effects. MiniPTAM mitigates the impact of these
                         The Oxford PTAM (Parallel Tracking and Mapping) software               deficiencies and is capable of generating maps for, and
                         is a camera tracking system that establishes a ground plane            augmenting, simple scenes.
                         (or any other horizontal surface) in a real-world video feed,
                         which can be used to supplement the live image with stable             QderoPateo has developed MyLenns, a hosted mobile
                         3D augmentations. The Oxford PTAM software requires no                 application service allowing third party application developers
                         markers, pre-made maps, scene templates, or inertial sensors.          to implement AR social networking, search engines and
                                                                                                advertising applications for smartphone users. QderoPateo
                         The core system is designed to track a hand-held camera in             plans to integrate the Oxford software into their software to
                         a small workspace. Tracking and mapping are processed in               improve the end-user experience.
                         parallel; one thread deals with the task of robustly tracking
                         erratic hand-held motion, while the other produces a 3D map            Steve Chao, cofounder of QderoPateo said “Our goal in the
                         of point features from previously observed video frames. This          next ten years is to grow the mobile computer vision market
                         allows the use of batch optimisation techniques not usually            in both Greater China and North America, from a simple AR
                         associated with real-time operation.                                   information browser, to a fully blown AR search engine running
                                                                                                on our next generation smartphones”. Chao’s vision is to
                         The result is a system that produces detailed maps with                implement what he calls “articulated naturality”. Articulated
                         thousands of landmarks that can be tracked at frame-rate,              naturality (AN) combines AR, artificial intelligence and image
                         with an accuracy and robustness rivalling that of state-of-            recognition to merge the real-world views of two or more
                         the-art model-based systems.                                           individuals who are physically separated, but connected
                                                                                                through a centralised service provider. This will be achieved
                         An extension to the core software called PTAMM (Parallel               using smartphones with two cameras facing in opposite
                         Tracking and Multi-Mapping) allows maps of many environments           directions, such that each user sees his own environment
                         to be made and different augmentations to be associated with           augmented by a virtual image of the other user or users. The
                         each. As the user explores the real world, the system is able          system will recognise gestures and motion in the real world
                         to automatically re-localise into previously mapped areas and          of one user, and translate this into virtual motion in the other
                         control the desired augmentation.                                      users’ views.


                         MiniPTAM provides augmentation on smart phones equipped                QderoPateo has created the Institute of Augmented and
                         with a camera that can generate a live video feed to the               Articulated Urban Planning (IAAUP) in Shanghai to bring

                         CONTACT Roy Azoulay Project Manager T +44 (0)1865 280969 E roy.azoulay@isis.ox.ac.uk W www.isis-innovation.com

                                                                                           10
together the talent, technology and expertise to create and                Improvements in portable processing power and software
realise the vision of an articulated naturality web (ANW).                 algorithms in smartphones enable elements of AN to be
ANW will introduce a new era of human-machine-world                        experienced now.
interfaces using the Oxford AR software alongside technologies
developed by other members of the IAAUP.                                   Chao said “IAAUP is developing a portfolio of projects in
                                                                           three broad areas: applications for today’s AN-ready markets;
Today, people see the world through their eyes and access                  platform development to prepare the systems required for the
electronic information through a screen. Through AN, what                  next generation of AN applications; and experimental labs to
we will see is a blend of digital information with real-world              innovate for the future. The future of AR as a practical part
information. We will then interact with the information using              of our lives depends on further advances in technology and
natural gestures rather than a keyboard and mouse.                         manufacturing.”




                                                                                                                                                Photo courtesy of Stock.Xchg
Oxford Parkinson’s disease questionnaire


Japan-based pharmaceutical company Kyowa Hakko Kirin                       life and has been used by pharmaceutical companies, clinical
Co, has signed a non-exclusive licence agreement to use the                research organisations and other research institutes to assess
Oxford Parkinson’s Disease Questionnaire (PDQ-39) in clinical              patient health outcomes in over 60 clinical trials.
trials of its leading Parkinson’s drug, Istradefylline.
                                                                           Parkinson’s disease is a progressive neurological condition
Oxford’s PDQ-39 questionnaire was used by Kyowa Hakko                      affecting sufferer’s motor skills and speech. Parkinson’s
Kirin in Phase II/III clinical trials to assess the efficacy of            affects around 4 million people worldwide and roughly 1 in
istradefylline as a secondary endpoint in the treatment of over            500 people in the UK. The risk of developing Parkinson’s
1300 patients.                                                             increases with age, and as life-expectancies continue to rise,
                                                                           drugs that can control the symptoms of Parkinson’s are in
The PDQ-39 questionnaire, which is completed by patients                   growing demand.
rather than physicians or carers, is used to quantify the impact
on quality of life of medical interventions aimed at maintaining or        For more information about PDQ-39 and other health outcome
improving the well-being of Parkinson’s sufferers. The PDQ-39              questionnaires available from Isis, visit: www.isis-innovation.com
is widely regarded as the gold-standard measure of quality of              /licensing/healthoutcomes/

CONTACT Dr Emma Sceats Project Manager T +44 (0)1865 280856 E emma.sceats@isis.ox.ac.uk W www.isis-innovation.com

                                                                      11
                           Pay as you go
ISIS PROjECT NUMBER 3044




                           Oxford technology to allow mobile phone payments to replace cheques.

                           The Oxford invention                                                   applications) generated within their own phone is the same
                                                                                                  as the one generated by the payee. This number is random
                           The announcement on 16 December by the board of the                    and does not have to be kept secret. This ensures that the
                           UK Payments Council that cheques are to be phased out                  customer’s mobile is connected to the correct store, or to the
                           by 2018 has heightened the need for secure replacement                 mobile of the person they wish to pay. Payment then occurs
                           payment systems.                                                       without the exchange of sensitive details such as credit card
                                                                                                  numbers or PIN. It is expected that no hardware modifications
                           New security technology developed at the University of Oxford          to the phones will be needed, and the Oxford team have built
                           by Professor Bill Roscoe and his team that allows people to            demonstration systems to show a variety of uses.
                           make payments via mobile phones, offers a solution. The
                           technology is designed to work in almost all situations: person        The payment itself could be made in a number of ways:
                           to person, in a shop or restaurant, at a vending machine,              using electronic cash or credit stored on a mobile phone, via
                           online, or as part of a telephone conversation.                        authorisation of a credit card payment, or by instructing a bank
                                                                                                  to pay a merchant or another person a certain amount.
                           “A key requirement of new payment systems will be the ability
                           to make payments from person to person, such as paying a               “The technology is designed to put the payer in charge of the
                           builder or a friend,” said Professor Roscoe.                           connection and let him or her have direct control over how
                                                                                                  much is paid and to whom – very much like a cheque,” said
                           “What we have is technology which enables anyone to easily             Professor Roscoe.
                           create a secure connection between two devices: it can work
                           via Bluetooth, WiFi, the internet or across ordinary telephone         “It is clear that banks will be looking for innovative solutions to
                           or SMS connections.                                                    avoid the limitations of current technology and that the ability
                                                                                                  to pay using mobile phones in the same way that you do now
                           “The core of our technology is a new security protocol                 using a cheque will need to be phased in over the next eight
                           that enables strong cryptographic keys to be created with              years. The beauty of this system is that it can be used for
                           the least possible work. The key to the protocol is that it            many different methods of payment.”
                           prevents anyone from doing any searching to break into the
                           transaction.”                                                          Consider the following scenarios:


                           Marketing opportunity                                                  1. Emma chooses a ticket online on her PC and pays with her
                                                                                                     phone. Her phone and the agency connect by telephony.
                           The Oxford technology uses a system in which the payer                    She enters the code and confirms the payment, perhaps
                           checks whether a short numeric code (4-8 digits for most                  by entering her PIN.




                           It is clear that banks will be looking for innovative solutions to
                           avoid the limitations of current technology.




                                                                                             12
                                                                                                                                           Images courtesy of Stock.Xchg
2. Jim wants to make a low-value payment, say for a bus                 Roscoe is an Oxford University computer scientist who is an
   ticket. His phone makes a Bluetooth connection with the              expert in cryptographic protocols and the theory of security. He
   bus, and he confirms that the codes displayed on his                 has consulted with industry for many years on topics including
   phone and the ticket machine are equal by buying the                 security. His focus in recent years has been on the security
   ticket of this choice.                                               aspects of cheap and portable devices such as mobile phones
3. A child has run out of credit. He rings his mother, who              and Personal Digital Assistants, with the aim of creating high
   transfers money without fuss: she has previously created             quality security flexibly and without the need for impersonal
   a permanent key between their phones that allows her to              and expensive infrastructures.
   transfer credit without the child needing to take any action.
4. Jim has just finished replacing a tap for Liz. Liz pays Jim          Status
   phone to phone: they simply make contact by telephone and
   ensure that two codes calculated by their phones agree.              The next steps are for further demonstrators of the technology
                                                                        to be built and for these to be taken through industry testing.
In each case the comparison of the codes makes it pointless             Standards will need to be developed for how the protocols
for a “man-in-the-middle” to attempt to break the payment,              are to be used and how to prevent unauthorised use of the
particularly since the payee will transfer details such as              payment features on phones. Isis welcomes inquiries from
a name, logo or photograph that is then checked by the                  commercial partners interested in being involved in further
payer and included in the electronic payment instruction that           development.
automatically goes to the bank.




“The beauty of this system is that it can be used for many
different methods of payment.”




CONTACT Brendan Spillane Project Manager T +44 (0)1865 614423 E brendan.spillane@isis.ox.ac.uk W www.isis-innvation.com

                                                                   13
                           Commercial catalyst
ISIS PROjECT NUMBER 4296




                           Polyethylene production is made easy with a new highly active catalyst.



                           Polymers


                           Polymers play a critical part in our daily lives, from commonly
                           used plastics and elastomers such as polyethylene, Bakelite
                           and neoprene, to naturally occurring polymers such as DNA
                           and proteins. The production of synthetic polymers could be
                           compared to molecular Lego® – even though the individual
                           pieces (monomers) may be identical, they can be combined to
                           build completely different structures.




                                                                                                                                                                       Photo courtesy of Stock.Xchg
                           Catalysts


                           In making polymers, the most important tools chemists have at
                           their disposal are “catalysts.” Catalysts control and accelerate
                           chemical reactions without themselves being consumed in
                           the process. Furthermore, catalysts control polymer structure,
                           the length of the polymer chains, how they are entangled
                                                                                                    The production of synthetic
                           and cross-linked. These factors influence the properties and
                           hence the value of the polymer. The polymer industry has
                                                                                                    polymers could be compared to
                           invested heavily in the development of catalysts to improve
                           yield, reduce operating costs and to produce polymers with
                                                                                                    molecular Lego®.
                           favourable properties. Indeed, industry leaders typically provide
                           turnkey solutions to others in the form of polymerisation plants         5%. In 2007, the annual global production of polyethylene
                           operating their licensed processes and catalysts systems.                was 60 million tonnes, with most being used in packing and
                                                                                                    construction applications. Proprietary catalysts and processes
                           The Oxford invention                                                     tightly control the polyolefin market. Therefore, new highly
                                                                                                    active metallocene catalysts, which produce polyethylene with
                           It is well known that ethylene can be readily polymerised (to            desirable properties, are highly attractive.
                           produce polyethylene) at low or medium pressures in the
                           presence of certain transition metal catalysts. Today, more              Scientists working at Oxford University have developed a
                           efficient metallocene catalysts have largely replaced Ziegler            series of early transition metal metallocene catalysts based
                           Natta catalysts in producing polyethylene and polypropylene.             on linked alkyl indenyl ligand. These new catalysts have been
                           However, there remains a need for new metallocene catalysts              tested under industrial conditions and have been found to be
                           with high polymerisation activities/efficiencies that can produce        amongst the most active in the open literature. In addition, the
                           polyethylene with particular characteristics. For example,               Oxford catalysts have been found to produce commercially
                           catalysts capable of producing linear high-density polyethylene          attractive linear high-density polyethylene (LHDPE) with a
                           (LHDPE) with a relatively narrow dispersion in polymer chain             relatively narrow dispersion in polymer chain length.
                           length are desirable.
                                                                                                    Status
                           Marketing opportunity
                                                                                                    The Oxford invention is the subject of a UK patent application.
                           Polyolefins are the most widely used thermoplastic materials,            Isis would like to talk to companies interested to take this
                           which according to Frost and Sullivan have a total market                Oxford developed IP through to commercialisation. Please
                           value of US$100bn and a compound annual growth rate of                   contact the Isis Project Manager.




                           CONTACT Dr Jamie Ferguson Project Manager T +44 (0)1865 280851 E jamie.ferguson@isis.ox.ac.uk W www.isis-innovation.com

                                                                                               14
Capturing carbon dioxide




                                                                                                                                                                                            ISIS PROjECT NUMBER 4425
Isis Innovation is working with University of Oxford chemists who have developed a new process for
capturing and storing carbon dioxide.

University of Oxford chemists have developed a new process
for capturing and storing carbon dioxide. Professor Dermot
O’Hare and Dr Andrew Ashley have developed the process,
which operates under mild conditions and converts carbon
dioxide (CO2) to methanol – a useful industrial chemical and
fuel. The ability to capture and efficiently store or use CO2 in an
environmentally friendly manner is highly desirable. The work
has been published in premier chemistry journal Angewandte
Chemie.




                                                                                                                                              Image of power plant courtesy of Stock.Xchg
Nearly a third of the world’s energy consumption and 36
per cent of CO2 emissions are attributable to manufacturing
industries. Effective carbon capture technologies are an
important part of any overall strategy for reducing the
environmental impact of industry.


Marketing opportunity


“The Oxford technique offers a cheaper and more robust                     O’Hare also explained that the reaction is not poisoned by
process for removing waste CO2 before it enters the                        carbon monoxide, which is often a problematic gas present in
atmosphere,” said Professor O’Hare of Oxford’s Chemistry                   industrial output as it is created during incomplete combustion.
Research Laboratory, the lead scientist on the project. “We
expect this to be attractive to industry because of a number               Methanol, the product of the Oxford carbon capture process,
of key aspects.                                                            is widely used as a solvent and also as a fuel. The current
                                                                           technique for making methanol also relies on using fossil fuels;
“It works at low temperatures and pressures, easily achievable             therefore as well as removing CO2 from the atmosphere, the
in most industrial environments without added equipment and                Oxford process also creates a useful by-product.
costs.
                                                                           Current status
“It doesn’t require expensive and toxic transition metal catalysts,
but uses what’s known as a ‘frustrated Lewis acid base pair’               The chemistry team who developed the technology also
that is commonly available, and converts the CO2 to methanol               included Dr Amber Thompson.
without producing undesirable side-products such as carbon
monoxide or methane.                                                       O’Hare’s group are currently working on further developments
                                                                           to the technology to make the process suitable for industry.
“Current technology is not selective for methanol and therefore
not carbon efficient. Side products of other carbon capture                Isis has patented the technology and is working with
technologies such as carbon monoxide and methane can also                  the inventors to put in place a strategy for commercial
be just as undesirable as CO2.”                                            development.


Nearly a third of the world’s energy consumption and 36 per cent
of CO2 emissions are attributable to manufacturing industries.
A. E. Ashley, A.L. Thompson, D.M.O Hare, ‘Non-Metal-Mediated Homogeneous Hydrogenation of CO2 to CH3OH’ Angew. Chem. Int. Ed. 2009,
48, 1 – 6

CONTACT Dr Jamie Ferguson Project Manager T +44 (0)1865 280851 E jamie.ferguson@isis.ox.ac.uk W www.isis-innovation.com

                                                                      15
                           Time for innovation
ISIS PROjECT NUMBER 3162




                           A new atomic clock based on nanotechnology may be developed for use in portable, GPS-independent
                           networked devices.

                           Background


                           Caesium atomic clocks achieve an accuracy of about 1 part
                           in 1015, equivalent to a loss of less than 1/10,000,000,000
                           of a second per day. Networked devices such as internet
                           servers, mobile phones and GPS receivers synchronise their
                           local clocks to atomic clocks in GPS satellites to ensure
                           that time-ordered events, such as the steps in a multi-party
                           transaction, are properly sequenced regardless of location. The
                           smallest Caesium clocks are about the size of a small suitcase.
                           Rubidium clocks the size of a cigarette packet may be used in
                           network servers, but are impractical for use in mobile phones
                           or GPS receivers.


                           A problem arises when a networked device loses contact
                           with a GPS satellite and must rely on its local clock; after a
                           short time, time sensitive functions must be suspended. The
                           more accurate the local clock, the longer the device can
                           continue to operate in the absence of synchronisation with
                           a satellite. Better clocks can also enable faster data rates in
                           communications. Oxford’s miniature atomic clock is expected
                           to find application in the growing range of hand-held devices               The UK’s “fountain” Caesium clock at the National Physical Laboratory.
                                                                                                       (Photo courtesy of the NPL)
                           for both commercial and military applications.


                           For example, the US global positioning system transmits two                 These arrays may take the form of nanodots, high aspect ratio
                           primary signals that can be used for position location: one,                nanoneedles or nanorings, and may be precisely positioned.
                           labelled the C/A code, is primarily for civilian use; the other,            The fabrication process is fast, low cost, convenient and
                           labelled the P(Y) code, is used primarily by the military. The              efficient; and does not use wet chemical etchants.
                           P(Y) code is much less susceptible to jamming through RF
                           interference than the C/A code. However, to acquire the P(Y)                While these nanoclocks are not intended to provide the same
                           code without a local time reference (accurate to 1/1000 part                accuracy as Caesium clocks, experiments with                      15
                                                                                                                                                                              N@12C60
                           of a second) may take several hours. Current low-power                      show significant advantages in size and power consumption
                           quartz oscillators are unable to maintain this timing stability             and would provide a significant stability improvement over
                           over periods long enough to be useful. Microfabricated atomic               the current technology used in hand-held devices. Preliminary
                           clocks could therefore have critical utility to military positioning        data suggests that such nanoclocks could be six orders of
                           and timing.                                                                 magnitude more accurate than a quartz crystal, for portable
                                                                                                       or small scale applications. Temperature control could provide
                           The Oxford invention                                                        higher precision where weight and power consumption are
                                                                                                       less critical.
                           Oxford researchers working in the field of nanotechnology have
                           discovered a new time standard based on the energy levels                   Status
                           in atoms contained within fullerene cages (“buckyballs”). The
                           fullerene cage isolates the atom and provides an environment                The Oxford invention is the subject of an international patent
                           for very stable nuclear spin resonance. An ion sputtering                   application. Isis would like to talk to companies interested in
                           method is used to form arrays of buckyballs that are required               developing the commercial opportunity.
                           to produce sufficient signal strength for a single “nanoclock”.

                           CONTACT Dr Rakesh Roshan Project Manager T +44 (0)1865 280853 E rakesh.roshan@isis.ox.ac.uk W www.isis-innovation.com

                                                                                                  16
OWL 2 the world wise web




                                                                                                                                                                                                  ISIS PROjECT NUMBER 3567
The HermIT Reasoner developed by the University of Oxford is one of the first to be compliant with
OWL 2, an important extension to Ontology Web Language.

Background


There is an increasing demand from organisations in all industry                               2 technical standard, have recently released version 2 of the
sectors to capture detailed domain knowledge (called an                                        HermIT Reasoner. Whilst version 1 of HermIT had already
ontology), and combine this with data from multiple sources to                                 introduced the ability to reason over several ontologies that
answer complex questions about the domain of knowledge. At                                     have defeated existing state of the art reasoning systems,
the same time, organisations are seeking to exploit the World                                  including the GALEN ontology, HermIT V2 pushes the envelope
Wide Web in new ways by analysing the contextual meaning                                       further by introducing itself as one of the first OWL 2 compliant
of web content (the semantic web), and using the web as a                                      Reasoners, and the only one written by individuals so intimately
source of knowledge. Oxford University now offers a new piece                                  involved in the development of the OWL 2 standard.
of software that enhances this capability and is compliant with
the latest de facto standard.                                                                  Marketing opportunity


Recognising this need, the World Wide Web Consortium set up                                    OWL is the de facto standard for all knowledge representation
a group to standardise the Ontology Web Language (OWL). A                                      applications. It has been used by the developers of several large
software application called a Reasoner exploits the knowledge                                  biomedical ontologies, including the BioPAX biological pathway
represented in OWL ontologies and data by inferring logical                                    ontology and the GALEN medical terminology ontology.
consequences and answering specific queries.
                                                                                               OWL has also found a place in general business activities such
OWL 2, an extension and revision of the OWL Ontology Web                                       as service management and business analytics.
Language developed by the W3C (World Wide Web Consortium)
OWL Working Group, became a W3C recommendation in                                              As the industry transitions into the OWL 2 standard, the need
October 2009. The ‘recommendation’ stage means that                                            for a robust, best of breed OWL 2 Reasoner is apparent.
the standard has undergone extensive review and testing
and is now endorsed by the W3C as a standard suitable for                                      Software status
widespread use.
                                                                                               The software has been developed using the Java programming
The Oxford invention                                                                           language. Isis would like to talk to companies interested in
                                                                                               licensing this software for use in knowledge representation
Professor Ian Horrocks, Chair of the OWL 2 Working Group,                                      tools and applications. Please contact the Isis Project Manager
and Dr Boris Motik, author of a significant portion of the OWL                                 to discuss this further.
                                                                                                                                                                   Photo courtesy of Stock.Xchg




                                                        Trusted SW

                                                Proof

                                           Logic
                                                                             Encryption
                                                                 Signature




                                     Rules / Query

                                     Ontology

                            RDF Model & Syntax

                 XML Query               XML Schema

                   XML                             Namespaces

              URI/IRI                                Unicode

Diagram of the Semantic Web Stack.




CONTACT Roy Azoulay Project Manager T +44 (0)1865 280969 E roy.azoulay@isis.ox.ac.uk W www.isis-innovation.com

                                                                                          17
                           DNA-binding brought to light
ISIS PROjECT NUMBER 3196




                           A fluorescence-based method and assay platform has been developed for the detection and quantification
                           of DNA-binding molecules, such as DNA-binding drugs, proteins and their ligands.



                           The Oxford invention
                                                                                                                       G

                           The Oxford invention uses single molecule fluorescence
                           spectroscopy for detection of DNA-binding molecules and
                           their ligands (such as transcription factors or DNA-binding
                           drugs, sugars or cAMP), or DNA-binding drugs. The assay
                           measures coincidence of red and green fluorophores. The                                                                           R
                           red label is attached to a DNA molecule bearing half of the
                           binding site sequence needed by the DNA-binding molecule
                           in question to stably bind the DNA, and the green label is
                           attached to a DNA molecule bearing the other half of the
                           binding site sequence. When the DNA-binding molecule is                                                        Transcription Factor
                           added to a mixture of these two labelled DNAs, it binds and                    G
                           brings together the two halves of the binding site, resulting in
                           coincidence of the red and green fluorophores. Overlapping
                                                                                                                                                             R
                           red and green dots are then detected with a sensitive camera.
                           Using cameras currently available, up to 30,000 molecules
                           may be imaged in one field of view, making the assay scalable
                           for high throughput screening.


                           Existing methods to detect DNA-binding molecules such as                 Marketing opportunity
                           transcription factors are typically expensive, time consuming,
                           only qualitative, require amplification and large quantities of          DNA-binding proteins include transcription factors, DNA-repair
                           sample. These attributes mean that such methods are not                  proteins and DNA-processing proteins, e.g. DNA and RNA
                           amenable to high throughput screening. They are also unable              polymerases. Transcription factors play an important role in
                           to detect low abundance DNA-binding proteins. The need                   gene expression. Alterations in their levels or activity (e.g. due
                           therefore exists for new methods that do not suffer from these           to mutations) can lead to a variety of diseases, including cancer.
                           problems.                                                                Changes in p53 activity are involved in 50% of all human
                                                                                                    cancers. The ability to detect transcription factors’ profiles is
                           The Oxford invention offers these key benefits:                          therefore extremely useful for the development of sensitive
                                                                                                    diagnostics. Furthermore, nuclear receptors and the design
                           •	 Detection of DNA-binding proteins at low concentrations               of DNA-binding drugs that target these are of key importance
                              (<1nM or down to 1-10 copies per cell) and in low volumes             in many therapeutic areas, such as cancer, osteoporosis
                              (<1µL)                                                                and diabetes. Consequently this technology is likely to be of
                           •	 No amplification, washes or antibodies required. However,             interest to drug discovery and diagnostics companies, as well
                              microfluidics may be incorporated to look at on/off rates             as those offering assay/instrument products.
                           •	 Detection and quantification of one or more DNA-binding
                              proteins in the same solution; extensive multiplexing                 Patent status
                              possible
                           •	 Suitability for use on solid supports                                 The Oxford invention is the subject of a published International
                           •	 Potential for real time monitoring of DNA-binding proteins            patent and a peer-reviewed scientific publication. Isis would like
                              in living cells                                                       to talk to companies interested in developing the commercial
                           •	 Short time-to-results (30 minutes)                                    opportunity. Please contact the Isis Project Manager.




                           CONTACT Dr Ruth Barrett Project Manager T +44 (0)1865 614425 E ruth.barrett@isis.ox.ac.uk W www.isis-innovation.com

                                                                                               18
The big screen




                                                                                                                                                                                            ISIS PROjECT NUMBER 3715
A robust and cheap assay that is quick to perform has been developed and validated for use in the clinical
diagnosis and monitoring of patients with lysosomal storage diseases, such as Gaucher, Niemann-Pick
Type C and Fabry.

The Oxford invention


Lysosomal storage disorders are characterised by a change                                                                            or
(typically an increase) in volume of the late endosome/
lysosomal (Le/Lys) system. Oxford researchers have developed
a robust, scalable assay that is able to detect an increase in
volume and/or changes in pH of the Le/Lys system in sample
cells. The assay uses a fluorescent marker, the signal from
which has been shown to accurately and sensitively correlate
to the volume of the Le/Lys system. The assay can be used
to achieve early diagnosis of lysosomal storage diseases, to             Above: The assay. Cells are grown overnight or isolated from blood with
monitor the efficacy of patients’ treatments, or as the basis for        antibodies. The lysosomes are then stained. Finally, the staining is quantified in
                                                                         a plate reader.
a drug screen to identify compounds able to exert therapeutic
effects. Experimental validation at Oxford has demonstrated              Below: The assay can distinguish between different diseases, using patient-
the assay’s applicability to drug screening, diagnosis and               derived cells.

monitoring of Niemann-Pick Type C disease. The assay can
                                                                                                    30000
detect different lysosomal storage diseases, as determined
                                                                         Lysotracker fluorescence




                                                                                                    25000
with patient-derived skin cells. Furthermore, the assay can
be used with blood cell-capture technology, allowing for                                            20000

straightforward analysis of patients’ blood samples (scientific
                                                                                                    15000
publication in preparation). The scalability of the assay to
multiwell plate format (up to 1536 well plates) has also been                                       10000

confirmed, enabling high throughput screening of compound                                            5000
libraries for the identification of new therapies. The assay can
                                                                                                            0
be utilised in the majority of hospital laboratories, as the only
                                                                                                                                 s


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essential piece of equipment is a fluorescent plate reader.
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                                                                                                                Patient fibroblasts
Marketing opportunity


The market for lysosomal storage diseases is not yet mature              go undiagnosed for months or even years after birth. A robust
They represent a large number of diseases, which are classed             assay able to confirm Le/Lys dysfunction quickly would be a
as orphan indications. For example, the Gaucher disease                  valuable clinical tool in terms of initial diagnosis of the type of
market segment is considered to be at an early growth stage,             disease. It would further enable patient screening to facilitate
and with yearly therapy prices of around $200,000 to $300,000,           recruitment in clinical trials of new therapies, and similarly for
this lucrative segment is set to grow at a CAGR of 11.4%.                monitoring progress of patient treatment.


Despite the commercial successes of therapies such as                    Patent status
Genzyme’s Cerezyme and Actelion’s Zavesca for Gaucher
Disease, diagnosis and treatment of lysosomal storage                    The Oxford invention is the subject of a patent application.
disorders are generally recognised to be clinically suboptimal.          Isis would like to talk to companies interested in developing
Indeed, Frost and Sullivan consider the top market restraint             the commercial opportunity. Please contact the Isis Project
in Gaucher to be inaccurate diagnosis, due to the complex                Manager.
nature of the disease. Early diagnosis is critical to maximise
                        1


the chances of effective therapy, yet it remains a challenge,            1: European Orphan Diseases Market M34D-52. Frost and Sullivan
                                                                         2008.
and many such disorders (for example Niemann-Pick Type C)

CONTACT Dr Ruth Barrett Project Manager T +44 (0)1865 614425 E ruth.barrett@isis.ox.ac.uk W www.isis-innovation.com

                                                                    19
                           Probing the possibilities
ISIS PROjECT NUMBER 3164




                           Achieving unparalleled analysis of drug/target interactions, light-reactive biological and non-biological
                           samples is possible using a new low-cost microscope stage incorporating an integrated light source.

                           The Oxford invention                                                       Before irradiation                              After irradiation
                                                                                                                                    Subunit of
                                                                                                                                    receptor
                           Working together, University of Oxford and Nippon Telegraph                                              protein
                           and Telephone researchers have developed a removable
                           microscope stage suitable for use on any Atomic Force
                           Microscope (AFM) to investigate the effects of light from an                                             Ligand                                         Bound
                                                                                                                                    binding site                                   ligand
                           optical light source on biological or non-biological samples.
                           Currently there is no commercially available attachment tailored
                                                                                                                                    Lipid
                           for illuminating AFM samples in this way; previous attempts to                                           membrane
                           meet market need have been unwieldy, microscope-specific
                           and not user-friendly.                                                     Analysis of drug/target interaction: A drug target (‘receptor protein’) is surrounded
                                                                                                      by a caged drug held in solution (left panel). Using the invention, a pulse of light
                                                                                                      releases the drug that then binds its target at the ligand binding site, causing
                           The invention can be used to analyse individual receptors in               the target to change shape (right panel). Individual target molecules can be
                                                                                                      examined before and after drug-binding, using an AFM.
                           drug/target interactions and is already supported by proof-
                           of-concept data, specifically in relation to this application (see
                           figure: caged drug in solution around a target is released by              Marketing opportunity
                           light and binds the target). Releasing caged drugs around a
                           target allows imaging of the same individual target receptor               SPMs are widely used by academia and industry alike in
                           before and after a drug has bound. Alternative applications                biological and non-biological areas. The global SPM market
                           include analysis of other light-reactive biological processes              stands at around $565.2m (2010) with a CAGR of 15.3%
                           (e.g. photosynthesis), addressing the damaging effects of UV               (2006-2013)1. Intense demand from these sectors is expected
                           on biological samples, or applying broad-spectrum light on                 to drive growth over the short, medium and long term. This
                           light-cured resins.                                                        technology offers a wide customer base and the potential for
                                                                                                      a solid revenue stream. Attachments for AFMs typically retail
                           Different light emitting diodes may be used in the stage to study          for a four-figure sum, whereas the build cost for this stage is
                           the effects of a particular wavelength light, a range of particular        projected to be at least an order of magnitude lower.
                           wavelengths or alternatively natural light wavelengths. The
                           stage is applicable for wet or solid-state samples and easy to             This invention is likely to be of interest to manufacturers of
                           move between microscopes.                                                  SPMs and their attachments for sale into research labs, or into
                                                                                                      businesses engaged in drug discovery or the development of
                           The microscope stage offers many other benefits:                           other light-reactive materials. This technology may also be of
                                                                                                      direct interest to drug discovery companies or light-reactive
                           •	 Low-cost manufacturing process resulting in a large profit              material businesses.
                              margin
                           •	 Robust and simple to use on any AFM and many other                      Patent status
                              scanning probe microscopes (SPMs); many stage designs
                              are envisaged to enable a range of experimental conditions              The invention is the subject of a published patent application
                           •	 Reduced electromagnetic and mechanical noise                            and a scientific publication. Isis would like to talk to companies
                           •	 High level of irradiation at specific wavelengths chosen by             interested in developing the commercial opportunity. Please
                              the experimental operator                                               contact the Isis Project Manager.

                                                                                                      1: World Microscope Markets 2007, #F027-30, Frost and Sullivan




                           CONTACT Dr Ruth Barrett Project Manager T +44 (0)1865 614425 E ruth.barrett@isis.ox.ac.uk W www.isis-innovation.com

                                                                                                 20
The culture of today




                                                                                                                                              ISIS PROjECT NUMBER 4231
A fast, cheap method to detect and identify pathogens (bacteria or fungi) present in blood or tissue
samples that enables correct diagnosis and same-day initiation of treatment.

Nucleus            Bacterium                                                 Bacteria
                                                                             spared
                                     Incubate with                                                Bacteria isolated/
                                     reagents                                                                           PCR +
                                                                                                  DNA prepped

                                                                                                                        DIAGNOSIS


White blood cell               Mitochondrion         Removal of           Bacteria proliferate, depending
                                                     mammalian DNA        on incubation conditions

Enrichment of pathogen DNA signal prior to preparing DNA for PCR.


The Oxford invention


In clinical microbiology diagnostic laboratories, the current             The Oxford Invention is supported by proof-of-concept data
gold standard method for the detection of pathogenic                      from blood samples containing typhoid Salmonella pathogens.
microorganisms in patients suspected of systemic infection is
the culturing of blood samples to amplify the pathogen. Many              Marketing opportunity
microorganisms are pathogenic at very low copy numbers and
so blood samples may need to be cultured for up to 5 days to              It is envisaged that kits with the appropriate reagents and
amplify the pathogen to detectable levels. It is then too late to         information may be produced to allow diagnostic labs to easily
initiate proper antibiotic therapy. Furthermore, some microbes            follow the straightforward protocol. This technology will be of
cannot be cultured, and prior use of antibiotics may have                 interest to companies involved in the production of bacterial
decreased pathogen count to non-detectable levels.                        or fungal diagnostic products. It may also be used in the
                                                                          development of anti-microbial therapeutics to follow efficacy,
PCR has been employed to avoid the need for lengthy                       such as vaccines for use in the adult world traveller market.
culturing of blood samples. However, the use of PCR to
identify blood-borne pathogens is often technically challenging           This diagnostic may find its most immediate application in
as the pathogen’s signal can be swamped by the signal arising             Typhoid, which remains a major health problem worldwide.
from the patient’s blood cell DNA, especially if the pathogen is          Each year there are an estimated 216,000 deaths resulting
present at low numbers.                                                   from around 21 million new cases, with children being at
                                                                          particular risk. The test currently available for detection of
The Oxford invention details a fast and highly sensitive method           Typhoid (the Widal test) has such low sensitivity and specificity
by which enrichment of pathogens in clinical blood samples                that it is of no practical use, but it continues to be used in
may be achieved through specific removal of mammalian DNA                 the absence of a viable alternative. In comparison, the Oxford
and/or amplification of the pathogen, if required. Pathogen               invention allows same-day initiation of treatment after accurate
identification by PCR is then straightforward due to the                  diagnosis.
favourable signal to noise ratio. The method is easy to perform
and results may be achieved in under 8 hours, allowing                    Patent status
treatment to begin the same day. Sensitivity is increased to
as low as 0.75 CFU/ml in 4ml blood. The protocol requires                 The Invention is the subject of a patent application. Isis would
equipment found in any typical hospital laboratory making it              like to talk to companies interested in developing the commercial
widely applicable.                                                        opportunity. Please contact the Isis Project Manager.




CONTACT Dr Ruth Barrett Project Manager T +44 (0)1865 614425 E ruth.barrett@isis.ox.ac.uk W www.isis-innovation.com

                                                                     21
                           Brains behind the operation
ISIS PROjECT NUMBER 3966




                           A new flow-diverting stent for direct treatment of brain aneurysms, that reduces cost and risk by removing
                           the need for open-brain surgery or time-consuming endovascular coiling.




                                                                                                                                                                            Image of brain scan sourced by Aron Balogh courtesy of of Stock.Xchg
                           The Oxford invention                                                         permit the aneurysm to shrink as the clot breaks down.
                                                                                                        The manufacturing process is currently being optimised in
                           Brain aneurysms – localised widening of blood vessels – can                  preparation for preclinical testing.
                           be caused by high blood pressure or head trauma. The
                           weakened wall of the blood vessel balloons to form a cavity                  Advantages of the Oxford invention are:
                           that fills with blood. These are prone to rupture and bleed into
                           the brain causing a hemorrhagic stroke, leading to disability or             •	 Small packing design with strength and flexibility suitable
                           even death.                                                                     for brain arteries
                                                                                                        •	 Minimally invasive with significantly reduced operating time
                           The existing treatments involve either open-brain surgery to place              relative to coil implantation
                           a metal clip around the aneurysm, or newer minimally invasive                •	 Straightforward, low-cost manufacture from widely-used
                           techniques. Minimally invasive techniques use a small incision                  biocompatible nitinol
                           in the groin to thread a catheter through networks of arteries to            •	 Suitable for treatment of both ‘saccular’ and ‘non-saccular’
                           reach arteries in the brain. Due to the fact that cerebral arteries             aneurysms, including difficult to coil ‘wide-necked’
                           are small in size and highly convoluted, they are difficult to access           aneurysms
                           and there are a variety of complications that can occur such as
                           injuries to the blood vessel from the catheter, arterial puncture,           Marketing opportunity
                           damage to the lining of the vessel, cerebral artery dissection,
                           bleeding into the brain, or stroke from artery blockage. The main            Intracranial aneurysms occur in 2-5% of the US population,
                           existing minimally invasive technique is endovascular coiling                with 27,000 suffering ruptures of saccular aneurysms each
                           which uses a metal wire coil to fill the aneurysm cavity.                    year. Medtech Ventures estimates the global market for the
                                                                                                        endovascular treatment of intracranial aneurysms was $660m
                           While both the clipping and coiling treatments do prevent and                in 20081 and is forecast to double by 2015, driven by newly
                           stem bleeding, the resulting blood clot is unable to break down              emerging flow-diverting stents such as the present invention.
                           and reabsorb after it has healed, maintaining pressure on the
                           surrounding brain area.                                                      Patent status


                           Oxford researchers have developed a novel design for a                       The Oxford invention is subject to an international patent
                           flow-diverting intracranial stent.                                           application. Isis would like to talk to companies and investors
                                                                                                        interested in commercialising this opportunity.
                           The Oxford invention has a leaf design to shield the aneurysm
                           from arterial pressure, whilst leaving suitable gaps that                    1 Endovascular Cerebral Aneurysm Repair Market, Medtech Ventures,
                                                                                                        July 2008

                           CONTACT Dr Brijesh Roy Project Manager T +44 (0)1865 280842 F +44 (0)1865 280831 E brijesh.roy@isis.ox.ac.uk W www.isis-innovation.com

                                                                                                   22
The exosome factor: delivering genes to cells




                                                                                                                                                                                                        ISIS PROjECT NUMBERS 4096 AND 4208
A natural carrier which can smuggle genetic material such as RNAi past the immune system to target cells
could be a breakthrough for gene therapy.

The Oxford invention


RNA interference (RNAi) holds promise as a powerful, novel
therapy for a wide range of diseases. Its potential ability




                                                                                                                                           DNA image courtesy of Ivan Petrov, sourced from Stock.Xchg
to selectively silence any gene of interest has led to a
huge amount of investment and scientific research into the
technology.


Despite this, RNAi delivery remains a major obstacle to RNAi
therapy. Naked RNA/DNA is rapidly cleared by the body and
shows a lack of organ-specific distribution, as well as low
efficiency of cellular uptake; therefore there is a need for an
efficient delivery vehicle.


Current delivery vehicles such as viral vectors and cationic            ideal candidates for use for in vivo delivery of genetic cargo.
liposomes have significant limitations. The use of viral vectors        The ability to load genetic material into these immunotolerant
can lead to immune recognition, which results in acute                  nanoparticles, and to target these to selected tissues, holds
inflammatory responses. Liposomes can cause inflammatory                great promise to overcome the major obstacle in RNAi therapy;
toxicity and can be rapidly cleared. These limitations have             RNAi delivery.
restricted the use of RNAi to life-threatening diseases, or
immuno-privileged sites such as the eye. Consequently, a                Marketing opportunity
delivery technology that avoids immune recognition and retains
good delivery efficiencies is needed.                                   The RNAi therapeutics market is expected to reach sales
                                                                        of >$1bn by 2015. However, despite significant investment,
Researchers within the laboratory of Dr Wood, located at                current research is concentrated on life threatening diseases or
the Department of Physiology, Anatomy and Genetics at the               immuno-privileged sites due to the delivery issues highlighted
University of Oxford, have developed a novel delivery vehicle           above.
based on exosomes. Exosomes are membrane-bound vesicles
of nanoparticle size (40-100nm) of endocytotic origin. They are         Exosomes, with appropriate targeting moieties, represent a
released by numerous cell types and are found in abundance              paradigm shift away from foreign delivery vehicles, towards
in body fluids where they act as natural carriers of mRNA,              natural nanoparticles capable of systemic RNAi delivery; with
miRNA and proteins.                                                     the additional benefit of immune evasion allowing for repeat
                                                                        administration. This novel delivery platform has the potential
Oxford researchers have utilised this natural carrier capability        to revolutionise RNAi therapy by opening up the range of
to develop a method to load murine exosomes with exogenous              diseases treatable using this approach.
genetic cargo. The researchers have demonstrated efficient
loading and delivery of exogenous plasmid and siRNA, both in            Patent status
vitro and in vivo. Furthermore, researchers have successfully
introduced peptide targeting moieties into exosomes to target           The invention is the subject of an International patent
exosomes to selected tissues.                                           application and Isis would like to talk to companies interested
                                                                        in developing the commercial opportunity. Please contact the
The exosomes utilised in the research were isolated from                Isis Project Manager for further details.
immature dendritic cells. Immature dendritic cells do not
stimulate a T-cell mediated immune response and are therefore




CONTACT Andy Self Project Manager T +44 (0)1865 614422 E andy.self@isis.ox.ac.uk W www.isis-innovation.com

                                                                   23
                           A bone of contention
ISIS PROjECT NUMBER 4203




                           A better low-cost therapeutic treatment for rheumatoid arthritis.

                           The Oxford inventions


                           Recent research led by Professor Graham Russell from
                           the Botnar Research Centre and Nuffield Department of
                           Orthopaedics, Rheumatology & Musculoskeletal Sciences has
                           generated an entirely new family of bisphosphonates, for use
                           initially in the treatment of Rheumatoid Arthritis. Beyond RA,
                           the therapeutics have the potential for many other applications,
                           including osteoporosis and oncology.


                           Three new bisphosphonate classes have been synthesised
                           and developed jointly in Oxford and in P&G’s laboratories in




                                                                                                                                                                      Bone x-ray courtesy of Stock.Xchg
                           Cincinnati. The properties of each bisphosphonate have been
                           shown to be predominantly attributable to two key features:
                           firstly their affinity for hydroxyapatite and bone mineral, and
                           secondly their inhibitory potency on farnesyl pyrophosphate
                           synthase (FPPS), an enzyme in the mevalonate pathway
                           leading to cholesterol biosynthesis. By coupling this new
                           scientific knowledge with P&G’s extensive clinical experience             Novel bisphosphonates are obvious candidates for new
                           with consumers, it has been possible to create a novel                    low-cost RA therapeutics because of their:
                           chemical design platform technology that has produced
                           several potential drug candidates for development.                        •	 Low cost of development
                                                                                                     •	 Established efficacy and safety aided by a clear regulatory
                           Marketing opportunity                                                       path
                                                                                                     •	 High likelihood of technical success for preventing disease
                           Today, the global RA therapeutic market value is of the order of            progression
                           $10Bn, comprising four main types of treatment:                           •	 Potential for follow-on applications to osteoporosis,
                                                                                                       oncology, orthopaedic indications, parasitic infections and
                           •	 Non-steroidal anti-inflammatory drugs (NSAIDs)                           in other autoimmune and inflammation disorders
                           •	 Glucocorticoids
                           •	 Traditional disease-modifying anti-rheumatic drugs                     Interest in this new technology has rapidly resulted in a
                              (DMARDs)                                                               6-month non-exclusive evaluation licence with a pharmaceutical
                           •	 and the newer biologic therapies ‘biologics’                           company. This evaluation will focus on the cost of manufacture
                                                                                                     and efficacy studies. Assuming this evaluation is successful,
                           The higher-priced biologics account for the greatest proportion           the licensee and Isis Innovation will be seeking suitable
                           of sales value, although the majority of patients are treated with        partners for the development and commercialisation of this
                           the traditional DMARDs.                                                   technology platform.


                           The RA market is expected to more than double in value by                 Patent status
                           2015 due to the anticipated increased prescription of the
                           higher-priced biologics. Concerns about the financial strain              Isis Innovation has filed three International PCT patent
                           that this will place on healthcare systems worldwide has led              applications on the new technology. We welcome discussions
                           many to suggest that the introduction of biologics will stall, and        with companies who have an interest in driving the commercial
                           instead alternative low-cost solutions will be needed.                    development of the technology.




                           CONTACT Dr John Wilson Project Manager T +44 (0)1865 280844 E john.wilson@isis.ox.ac.uk W www.isis-innovation.com

                                                                                                24
Pixel perfect




                                                                                                                                                                                              ISIS PROjECT NUMBER 6614
A new camera image pixel design for a wider dynamic range and improved low light performance.

The Oxford invention


The Oxford invention uses a pixel design that is similar to a
conventional integrating pixel, but with a wide dynamic range
and improved low light sensitivity. The new pixel is controlled
by the user and can create either a true logarithmic response,
or a response equivalent to a global tone-mapping generator.




                                                                                                                                            Photo of CMOS Image pixel courtesy of Wikipedia
This pixel is also easy to describe mathematically, which
means that it is easy to determine the reference voltage that
will create a particular pixel response.


This new design offers a better quality of image, including more
detailed information, as well as better signal to noise ratios. A
prototype has been built and development is ongoing. The
new design will be ideal for low-cost, high volume consumer
products but also for demanding specialist applications, such
as automotive sensors.
                                                                           The new design will be ideal
Marketing opportunity
                                                                           for low-cost, high volume
Electronic imaging sensors are incorporated in a wide-range of
systems, including digital cameras, mobile telephones, computers
                                                                           consumer products but also
and sensors and the market is huge and growing. These cost
sensitive markets have spurred the development of single chip
                                                                           for demanding specialist
CMOS cameras and the vast majority of these cameras create
an image by integrating the photocurrent within each pixel for a
                                                                           applications, such as
predetermined period. This creates a voltage that is proportional
to the photon flux at the corresponding pixel, and is a simple
                                                                           automotive sensors.
imaging strategy that achieves a large enough dynamic range
for scenes with relatively uniform levels of illumination. However,        a logarithmic sensor. The logarithmic response is obtained by
many scenes can have a much wider dynamic range and as                     integrating the photocurrent for a time that depends upon the
a result, scenes are either underexposed in the darker areas,              photocurrent. The result is a CMOS pixel with a high dynamic
overexposed in the brighter areas, or both. This is a particular           range, with the added improvement of low light performance
problem for surveillance systems and is actually dangerous for             response.
certain applications, such as automotive.
                                                                           Patent status
Solutions developed to date have technical drawbacks that
limit their application or add unreasonable costs. A new pixel             This work is the subject of a group of patent applications and
design has therefore been developed to increase the dynamic                Isis would like to talk to companies interested in developing
range of imaging sensors, combining the speed of response                  commercial opportunities. Please contact the Isis Project
of an integrating pixel, with the dynamic range compression of             Manager.




CONTACT Evert Geurtsen Project Manager T +44 (0)1865 614424 E evert.geurtsen@isis.ox.ac.uk W www.isis-innovation.com

                                                                      25
                           Work smarter, not harder
ISIS PROjECT NUMBER 3471




                           Oxford technology now makes possible the next generation of affordable, non-contact, non-invasive
                           material separator systems.

                           Researchers at the University of Oxford have developed                                              Pressure antinodes
                           smart acoustic separators that are affordable, non-contact,
                           non-invasive, with unique diagnostic and adaptive functionalities.
                           The invention overcomes long recognised technical challenges
                           in pharmaceutical, biomedical and industrial materials
                           separation, filtration and monitoring.


                           The Oxford invention


                           Acoustic separators exploit acoustic standing waves (sound
                           waves similar to those generated in the pipes of a church organ)
                           to provide contact-free removal or localisation of particles
                           suspended in liquids or gases. The Oxford invention is a novel                                         Pressure nodes
                           acoustic standing wave control architecture, which enables
                           a new class of smart acoustic separator, with compelling
                           commercial advantages over current technologies including:


                           •	 In-situ reconfigurable acoustic architecture: supports
                              switchable, multi-function devices
                           •	 Real-time diagnostic capability: direct measurement and
                              monitoring of physical properties of separator fluids and
                              suspensions
                           •	 Affordability: significantly reduced hardware complexity and
                              cost


                           The fully scalable technology is designed for applications in
                           biological and biochemical sample preparation, integrated
                           microfluidics; and non-invasive clinical and industrial fluid
                           filtration, processing, characterisation and monitoring.


                           Marketing opportunity


                           The   Oxford     invention   provides    numerous    commercial           At the heart of an acoustic separator device is an active volume. A specially
                                                                                                     engineered sound field in this volume – comprising alternating nodal and
                           opportunities, from low-cost off-the-shelf devices, to high-value
                                                                                                     antinodal pressure planes – enables the removal or localisation of suspended
                           bespoke solutions for specialised separation systems. A large-            particles. The Oxford invention combines non-invasive particle separation
                           scale prototype has been built, tested and evaluated for                  functionality with a smart adaptive architecture and diagnostic capability.

                           clinical separation applications. The technology is ready for
                           application-specific commercial development.
                                                                                                     Oxford technology now makes
                           Patent status
                                                                                                     possible the next generation
                           This technology is the subject of an international PCT patent
                           application, and Isis would like to talk to companies interested          of affordable, non-contact,
                           in commercialising this opportunity. Please contact the Isis
                           Project Manager to discuss this further.                                  non-invasive separator systems.
                           CONTACT Chim K Chu Project Manager T +44 (0)1865 280832 E chim.chu@isis.ox.ac.uk W www.isis-innovation.com

                                                                                                26
Fuel for thought




                                                                                                                                                                         ISIS PROjECT NUMBER 4326
A new approach for local generation of hydrogen as a fuel for applications such as laptops and communi-
cation devices. The method operates cleanly, at low temperatures, for long periods and at high yield.

The Oxford invention


Researchers at Oxford University have found a way to prepare
silicon to make it suitable for sustained local generation of
hydrogen. The reaction of silicon with water to form silica and
hydrogen gas is an alternative sustainable ‘green’ route for
the supply of hydrogen. However silicon is largely unreactive
towards water under normal conditions, as the rapid initial
reaction stops abruptly upon formation of a passivating oxide
layer. The Oxford invention overcomes this problem and
demonstrates the feasibility of a silicon-enabled hydrogen fuel
economy.


There is little question that reduction of the amount of carbon
dioxide produced by energy generation and transport would
be highly desirable. The Hydrogen Economy is a proposed
replacement for fossil fuels in which renewably produced
hydrogen would be the primary energy carrier. To achieve this




                                                                                                                                          Images courtesy of Wikipedia
paradigm shift, advancements must be made in the production
and storage of hydrogen, as well as in release of the stored
energy using fuel cells. Indeed, safe storage of hydrogen is a
key challenge, on which numerous researchers are working.


The Oxford technology offers a number of benefits:


•	 An innovative approach for local hydrogen supply
•	 Low grade silicon can be used as a feedstock
•	 Hydrogen generated at low temperatures (70-90°C)
•	 Long duration (12 hours)
•	 High yield of hydrogen (36-58%)
•	 Uses non-corrosive and easily disposed-of chemicals


Marketing opportunity


There is a great deal of work ongoing on hydrogen storage
materials i.e. those that absorb hydrogen and release it on
heating. The key difference of the Oxford approach is to utilise
the earth’s vast resources of silica, with water as the hydrogen
storage medium. The initial step involves the green conversion
of silica (sand) to silicon nanopowder, which can then release          Status
hydrogen on demand, upon the addition of water. Silica,
which is regenerated as a by-product, can either be safely              The Oxford invention is the subject of a UK patent application.
disposed or recycled. This technology could be used as an               Isis would like to talk to companies interested in developing
emergency hydrogen source in hydrogen fuel cell vehicles, as            the commercial opportunity. Please contact the Isis Project
well as in lower power fuel cell applications such as laptops or        Manager.
communication devices.

CONTACT Dr Jamie Ferguson Project Manager T +44 (0)1865 280851 E jamie.ferguson@isis.ox.ac.uk W www.isis-innovation.com

                                                                   27
                               Changing climate for business
OxfORD UNIvERSITY CONSUlTINg




                               Helping businesses plan for climate change.

                               The Copenhagen Climate Change conference demonstrated                       bodies will be asked to report to the Secretary of State for the
                               just how difficult it is to convert well-meaning intentions into the        Environment, on how they are planning to, or have already
                               reality of implementation. Scientifically and politically everyone          adapted to, the challenges that our changing climate will
                               now agrees that global temperature rise must be checked                     bring.
                               to 2ºC but achieving this is proving very difficult to realise.
                               So what would a world that’s 2ºC warmer look like and why                   The UK Climate Impacts Programme (UKCIP) was established
                               should businesses care?                                                     in 1997 to help co-ordinate scientific research into the impacts
                                                                                                           of climate change, and to help organisations adapt to these
                               From a global perspective, there will be a potential decrease               unavoidable impacts. Based at the Environmental Change
                               in water availability in regions like Southern Africa and the               Institute at Oxford University it comprises a team dedicated to
                               Mediterranean. There will be declines in crop yields of 5%-10%              providing training and knowledge transfer about the science,
                               in tropical regions and up to 60 million more people exposed                effects of climate change on businesses and adaptation
                               to malaria in Africa. We can expect 10 million more people                  strategies.
                               worldwide exposed to costal flooding and species extinction
                               will increase 15%-40% including caribou and polar bears.                    Acting to coordinate and influence research into our future
                                                                                                           climate, its objective is to disseminate the outputs and to
                               From a local perspective, asking the question ‘what does a                  help interpret the data in terms of the effect on businesses
                               2ºC rise in temperature mean for your organisation?’ exposes                in the UK. UKCIP aims to provide climate scenarios and
                               many uncertainties, which could have a positive or negative                 corresponding adaptation strategies for all regions of the UK,
                               effect to the bottom line. Will demand for your products or                 based on models from the UK Met Office Hadley Centre.
                               service increase or decrease? Will your markets be completely
                               wiped out, or will there be new opportunities that you hadn’t               UKCIP, in conjunction with Oxford University Consulting, is




                                                                                                                                                                              Image courtesy of Stock.Xchg
                               considered? What are the strategic investment implications                  finalising a new range of courses and services that will assist
                               over the next decade? Can you increase production capacity                  businesses in understanding the basic models that underpin
                               elsewhere in the world, or should you invest in flood defences              the science of climate change, coupled with interactive tools
                               to protect your manufacturing plants in the UK? Understanding               that will allow you to assess the impacts on your business.
                               how to best adapt to changes that a 2ºC rise will bring could               The tools focus on the six areas common to all business,
                               avert massive disruption to your business and possibly even                 those of Markets, Finance, Logistics, Premises, People and
                               give you a competitive advantage.                                                         Process. Pilot sessions will occur during the
                                                                                                                               second quarter of 2010, followed by a
                               The Climate Change Act commits the                                                                  national roll out programme. If you
                               UK to lower its 2050 green house                                                                       would like to know more please
                               gas emissions to 80% of the 1990                                                                          contact Richard Lamb, Training
                               baseline. As a consequence of                                                                              Manager, 01865 285717 or
                               this act, many public sector                                                                                training@ukcip.org.uk in the
                                                                                                                                            first instance.




                               CONTACT Gurinder Punn Project Manager T +44 (0)1865 280826 E gurinder.punn@isis.ox.ac.uk W www.isis-innovation.com

                                                                                                      28
Unlocking drug discovery




                                                                                                                                                         OxfORD UNIvERSITY CONSUlTINg
Making the most of COOT macromolecular modelling software.

Almost all drug discovery programmes are directed towards
the design of small ligands that act selectively on specific
targets relevant to human disease. Once a target is identified
and validated, the design and optimisation of ligands is a
crucial step towards the development of a final drug candidate
to enter pre-clinical studies.


Computational approaches that allow the efficient capture of
complex data and their conversion to useful information have
been used to aid the design and discovery of new ligands. This
relies on the timely and sustained interpretation of experimental
3D data from X-ray crystallography. Recent advances in
computational methods have increased the throughput and
viability of structure-based drug design.                                Model building using COOT. The picture shows the interactions of Nilotinib (a
                                                                         drug for the treatment of chronic myelogenous leukemia) with Protein Kinase
                                                                         11. The structure solution of the complex was carried out by the Structural
The Crystallographic Object-Oriented Toolkit (COOT) is an                Genomics Consortium, University of Oxford.
innovative 3D molecular graphics computational application that
has been developed by Dr Paul Emsley from the Department of              release cycles. COOT is delivered as an easy-to-install package
Biochemistry, in collaboration with researchers throughout the           for Microsoft Windows, Macintosh and Linux platforms.
UK. It has been designed for model-building and the validation
of targets and target-ligand complexes.                                  Using COOT in the drug discovery pipeline to turn around 3D
                                                                         target-ligand structures in a number of days is now routine.
The software has popularised a number of novel techniques,               Oxford University Consulting has managed Dr Paul Emsley’s
such as: embedded 3D Fast Fourier Transforms, marching                   consultancy to provide expert advice in the use and application
cube representation of electron density with dynamic                     of COOT. Pharmaceutical companies such as GlaxoSmithKline,
contouring, dynamic graphs and sophisticated handling of                 Wyeth Pharmaceuticals, Bristol-Myers Squibb and others have
non-crystallographic symmetry. Using such techniques the                 already benefited from this support.
COOT software accelerates ligand optimisation by rapidly
integrating experimental 3D data into ‘series design’, thereby           If you are using X-ray data for structure-guided drug design
enabling faster generation of potential drug candidates. By              and need expertise or advice on using COOT, please contact
providing a single environment for model-building of target-             Oxford University Consulting.
ligand complexes, COOT allows rapid examination and
validation of experimental data.
                                                                     “Drug design is like picking a
COOT has a powerful, easy-to-use, interface designed
for non-experts, and it has also become popular amongst
                                                                      lock – with time and skill you
academic scientists. A scientific article describing the methods
of the COOT software has recently become the second most
                                                                      can do it blind, but with a 3D
highly cited article in the last five years.                          X-ray image of the lock before
However, COOT has readily found applications outside of               you start, it’s a lot easier. COOT
academic research as it can be easily customised for use
by the pharmaceutical sector. Indeed, the distribution and            is the tool to understand the
development approach taken to the software suits this sector
as it can be easily tailored to match specific needs in short         structure of the lock.”
timescales, comparing very favourable with traditional software
                                                                                                          Dr Paul Emsley, University of Oxford.

CONTACT Andrew Goff Project Manager T+44 (0)1865 280866 E Andrew.goff@isis.ox.ac.uk W www.isis-innovation.com

                                                                    29
                                    Spin-out portfolio news
OxfORD SPIN-OUT EqUITY MANAgEMENT




                                    The latest news, events and funding developments from Oxford’s spin-out portfolio.




                                    Oxford spin-outs raise £55m in 2009


                                    Oxford spin-outs raised an aggregate of £55.2m in 2009,
                                    despite the challenging funding environment. This is a great
                                    reflection on the quality of the management teams, the investor
                                    syndicates and the technology underlying these businesses.
                                    We look forward to the continued success of Oxford spin-outs
                                    in 2010 and beyond.


                                    Oxagen raises £16m for Phase IIb clinical trial


                                    Oxagen recently completed a £16 Million ($26.7 Million) Series
                                    C financing led by Novartis Venture Funds. The proceeds of             Steven Lee PhD, CEO of Summit

                                    the funding are being used primarily to advance the Company’s
                                    CRTH2 antagonist programme in inflammatory and respiratory             Summit awarded funding to develop C. difficile programme
                                    diseases, including the completion of this Phase IIb clinical
                                    study in moderate persistent asthma.                                   Summit Corporation plc (AIM: SUMM) has raised £5.4m which,
                                                                                                           excluding milestone payments from existing and future deals,
                                    The Phase IIb trial follows the successful completion of a             will provide the business with cash resources until at least
                                    Phase IIa programme in which four Phase IIa trials were                December 2011.
                                    completed with efficacy demonstrated in asthma and allergic
                                    rhinoconjunctivitis. Over 600 subjects have been treated to            Steven Lee PhD, CEO of Summit, said, “This re-financing will
                                    date and results so far indicate the drug to be well tolerated.        re-launch Summit and enable the Company to exploit the
                                                                                                           potential offered by our proprietary iminosugar technology
                                    The purpose of the study is to determine the magnitude of              platform and also receive the benefit from existing programme
                                    improvement in lung function and asthma symptoms on longer             deals as we seek to increase shareholder value.”
                                    term therapy and to define the optimal once daily oral dose.
                                                                                                           Summit has also recently announced that it has been awarded
                                    Mark Payton PhD, Oxagen’s CEO said “This represents                    £2.2m from the Wellcome Trust to fund the development of the
                                    an exciting time for Oxagen and a key phase in the clinical            Company’s infectious disease programme targeting Clostridium
                                    development of this compound. This study maintains Oxagen’s            difficile, a bacteria that is posing a significant and growing
                                    position as one of the leading players in this field.”                 healthcare threat. The award is made through the Wellcome
                                                                                                           Trust’s Seeding Drug Discovery Initiative and provides over two
                                    Anja König PhD, Managing Director at Novartis Venture Funds            years of funding to develop Summit’s programme through to
                                    commented “We are joining Oxagen in their exciting effort              the end of preclinical development.
                                    to deliver their first in class medicine to asthma patients.
                                    Oxagen’s lead compound has the potential to become a                   Following the award, Summit’s C. difficile programme becomes
                                    blockbuster.”                                                          part of the Company’s expanded Partnered Product Portfolio
                                                                                                           that now comprises eight drug programmes. This portfolio
                                    www.oxagen.co.uk                                                       requires no further investment from Summit but has regulatory
                                                                                                           and sales milestones worth over $160m plus sales royalties. In
                                                                                                           addition, Summit retains significant territory rights in some of
                                                                                                           the programmes, including C. difficile.


                                                                                                           www.summitplc.com

                                    CONTACT James Mallinson Portfolio Director, OSEM T +44 (0)1865 280 903 E james.mallinson@osem.ox.ac.uk W www.osem.ox.ac.uk

                                                                                                      30
Unearthing enterprise




                                                                                                                                                                                               ISIS ENTERPRISE
British Antarctic Survey (BAS) hosted a conference in November 2009 to explore potential biotechnological
discovery and development of the unique collections of their Antarctic microorganisms, flora and data.
The conference was lead by BAS, UK Biosciences Knowledge Transfer Network and Isis Enterprise.

Untouched by humans until the 19th century, Antarctica is the
coldest, highest, windiest and driest continent on Earth, with
99% of its surface covered by ice up to 4km thick. Beneath
this icy wilderness lies a hidden world of mountain chains,




                                                                                                                                              Image courtesy of the British Antarctic Survey
lakes and rivers. The secrets of our Earth’s history are locked
in the ice, rock and sea-bed sediments. Its chilly waters are
home to whales, seals, penguins, seabirds, fish and krill. The
least understood region of our planet – it is now recognised for
its significance as a unique natural laboratory.


Polar explorers like Scott and Amundsen opened up Antarctica
for science. This early exploration led to one of the world’s most
successful international agreements – the 1961 Antarctic Treaty.          Geographic centre, Royal Botanic Gardens, Kew and BAS,
The agreement promoted a level of co-operation between                    gave their business perspectives regarding the development
nations not seen elsewhere and paved the way for many                     and marketing of their science and specimen collections,
ground-breaking discoveries. Today, British Antarctic Survey              issues of bringing natural molecules to market, with added
scientists use their extensive knowledge and expertise and                information on what they are looking for from discovery
the latest technology to investigate, monitor and understand              initiatives and open innovation. Professor Sir Brian Heap
the changes to the polar environment. Satellites, airborne                joined the expert panel discussions and gave a presentation
instruments and ground-based technologies reveal a hidden                 concerning Zygem of New Zealand. Mr Meredith Lloyd-Evans
world beneath the ice. Lakes, buried under kilometres of ice for          of BioBridge Ltd chaired the day.
hundreds of thousands of years, may contain micro-organisms
that would help us understand more about the existence of life            Of particular note were the platforms developed by organisations
on other planets.                                                         such as Aquapharm® and CABI to increase the hit ratio for the
                                                                          discovery of novel molecules. The Antarctic and organisms
British Antarctic Survey houses a unique collection of                    found in most extreme environments are still rich grounds of
Antarctic microorganisms collected over the last 50 years and             biotechnological development.
other specimen collections dating from the late 1700s. The
collections are recognised as being world class with respect              Isis Enterprise worked with the NERC commercialisation team
to their unique properties and the collation of information               and BAS scientists to prepare the conference strategy, objectives
underpinning them.                                                        and speaker themes. The Isis Enterprise team then coordinated
                                                                          the event within NERC systems and acted as facilitator between
The most relevant collections for biotechnological discovery              the UK Bioscience Knowledge Transfer Network, BAS and
and development are thought to be the 1,000 living cultures               NERC. We worked with NERC and BAS to produce literature,
housed with CABI and over 50,000 herbaria and other                       web presence, email registration, delegate invites and helped
specimens that have been collected from the Antarctic; a                  facilitate the general running of the conference.
pristine ecosystem that became isolated 30 million years
ago. The discovery that Antarctica’s microbial organisms can              For further information regarding the conference and BAS
adapt and survive extreme freezing and thawing has provided               collections, please contact Mr Bevan McWilliam of the Natural
opportunities to isolate and understand these biochemical                 Environment Research Council (NERC), commercialisation
characteristics leading to commercialisation opportunities.               team on +44 (0) 1223 221290 or bewi@nerc.ac.uk.


Speakers from Procter & Gamble, Croda, Galapos SASU,                      For further information concerning Isis Enterprise services,
Aquapharm®, Biotech Marin Biochemicals, CABI, National                    please contact the Isis Project Manager.


CONTACT Dr Sam Gallagher Project Manager T +44 (0)1865 280849 E samantha.gallagher@isis.ox.ac.uk W www.isis-innovation.com

                                                                     31
        an intelligent partnership


        Providers of innovative banking, legal, accountancy
        and business advisory solutions for technology
        based businesses in Oxford and beyond.




        for further information on how our services can help you, contact:

        Andrew Davies                                                 Nicola McConville                           Sue Staunton
        Corporate Technology Manager                                  Partner – Biotechnology team                Partner – Technology group
        Barclays Bank                                                 Blake lapthorn                              james Cowper
        T: 07775 548803                                               T: 01865 253284                             T: 01865 200500
        E: andrew.j.davies@barclayscorporate.com                      E: nicola.mcconville@bllaw.co.uk            E: sstaunton@jamescowper.co.uk




         Oxford Innovation Society




         forthcoming meetings of the Oxford Innovation Society will be held on the following dates:
         • Thursday 25 March 2010 • Wednesday 22 September 2010 • Thursday 8 December 2010
         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 Renate Krelle,
         Business Relationship Manager on: T +44 (0)1865 280850 E renate.krelle@isis.ox.ac.uk




Published by Isis Innovation Ltd
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