Commercialisation of a Novel Diagnostic Test for Invasive Pulmonary Aspergillosis
Submitting InstitutionUniversity of Exeter
Unit of AssessmentBiological Sciences
Summary Impact TypeTechnological
Research Subject Area(s)
Medical and Health Sciences: Clinical Sciences, Immunology, Oncology and Carcinogenesis
Summary of the impact
Invasive pulmonary aspergillosis (IPA) is a frequently fatal disease of
haematological malignancy patients, caused by fungi from the genus Aspergillus.
Dr Christopher Thornton has developed and commercialised a novel
point-of-care test for the diagnosis of IPA with an Aspergillus-specific
monoclonal antibody (mAb) JF5 generated using hybridoma technology. Using
this mAb, he has developed a lateral-flow device (LFD) for the rapid
detection of Aspergillus antigen in human serum and
bronchoalveolar lavage fluids (BALf) that signifies active infection.
Commercial exploitation of the patented technology has been met through
the establishment of a University of Exeter spin-out company, Isca
Dr Thornton's (appointed to Exeter as Lecturer, 2003-07, Senior Lecturer
2007-present) research focuses on the development of next generation
monoclonal antibodies for use in fungal biology, and he has a particular
interest in IPA which is a leading cause of morbidity and mortality in
haematological malignancy patients and hematopoietic stem cell transplant
recipients , with an estimated 200,000 cases per year worldwide and a
death rate in excess of 50%. Diagnosis of IPA represents a formidable
diagnostic challenge and usually relies on a combination of clinical data,
microbiology and histopathology, none of which provide a definitive
differential diagnosis. There are no nucleic acid based tests and
currently available enzyme immunoassays are unreliable. The Thornton lab
has addressed this problem and developed a series of next-generation
monoclonal antibody (mAb)-based assays that detect markers of active
In 2008 Thornton described the generation of an Aspergillus-specific
mAb (JF5) using hybridoma technology, and its use to develop an
immuno-chromatographic lateral-flow device (LFD), similar to those used in
many pregnancy tests, for the rapid (10 min) point-of-care diagnosis of
IPA . Funding from the US National Institute of Allergy &
Infectious Diseases allowed Dr Thornton to validate the LFD in an animal
model of IPA [3, 4]. Subsequent funding from Pfizer Ltd allowed Dr
Thornton to collaborate with haemato-oncologists at St. Bartholomew's
hospital (London), King's College hospital (London), the Royal Devon and
Exeter hospital (Exeter), the Medical University of Graz (Austria) and
with medical mycologists at Cardiff University hospital, to undertake
clinical trials of the LFD in humans. Results of the LFD trials,
demonstrated a 100% negative predictive value for IPA diagnosis using
human BALf and 100% positive predictive value when used as an adjunct test
with PCR of human serum [4-6]. The specificity, ease-of-use, low cost
(~£10 per test), and compatibility of the Aspergillus LFD with
routine hospital practices [1, 5, 6] means that the onset of IPA can be
quickly and accurately monitored using a simple and cheap blood test for
circulating Aspergillus antigen [2, 5, 6] or with BALf collected
during bronchoscopy and lung biopsy [3,4]. Importantly the test does not
suffer from the false-positivity seen with commercial Beta-glucan and
galactomannan assays due to antibiotics, anti-cancer drugs or the presence
of other fungi [1, 2, 4-6]. This is vitally important in establishing a
differential diagnosis of IPA.
References to the research
Evidence of the quality of the research: this work has been
published in high quality peer reviewed journals, has attracted
significant external grant funding, has resulted in the granting of
patents and establishment of a spin-out company.
1. Thornton CR. Detection of Invasive Aspergillosis. (2010). Advances
in Applied Microbiology 70: 187-216.
2. Thornton CR. Development of an immunochromatographic lateral-flow
device for rapid serodiagnosis of invasive aspergillosis. (2008). Clinical
and Vaccine Immunology 15: 1095-1105.
3. Wiederhold NP, Najvar LK, Bocanegra R, Kirkpatrick WR, Patterson TF,
& Thornton CR. (2013). Inter-Laboratory and Inter-Study
Reproducibility of a Novel Lateral-Flow Device and the Influence of
Antifungal Therapy on the Detection of Invasive Pulmonary Aspergillosis. Journal
of Clinical Microbiology 51: 459-465.
4. Thornton C, Johnson G, & Agrawal S. Detection of invasive
pulmonary aspergillosis in haematological malignancy patients by using
lateral-flow technology. (2012). Journal of Visualised Experiments
61: e3721, DOI: 10.391/3721. URL:
5. Hoenigl M, Koidl C, Duettmann W, Seeber K, Wagner J, Wöfler A, Raggam
RB, Thornton C, & Krause, R. Bronchoalveolar lavage lateral-flow
device test for invasive pulmonary aspergillosis diagnosis in
haematological malignancy and solid organ transplant patients. (2012). Journal
of Infection 65: 588-591.
6. White PL, Parr C, Thornton CR, & Barnes RA. (2013). An Evaluation
of Real-Time PCR, Galactomannan ELISA and a Novel Lateral-Flow Device for
the Diagnosis of Invasive Aspergillosis. Journal of Clinical
Microbiology 51: 1510-1516.
7. Wiederhold N (University of Texas) and Thornton CR (UoE), Invasive
Aspergillosis Diagnosis by Antigen Capture with Lateral-Flow Technology,
US National Institutes of Health/National Institute of Allergy and
Infectious Diseases 01/06/10 to /05/12, $230,262.
8. Thornton CR. (UoE), Clinical Evaluation of a Lateral-Flow Device for
Rapid Diagnosis of Invasive Aspergillosis, Pfizer Ltd., 01/10/10 to
9. Thornton CR (UoE). Development of a lateral-flow device for rapid
serodiagnosis of invasive aspergillosis. Higher Education Innovation Fund
4, 2010, £15,000.
10. Thornton CR (UoE). Creation of Isca Diagnostics Ltd., a University of
Exeter Spin-Out Company. Higher Education Innovation Fund 5, 25/05/12 to
11. Thornton CR (Isca Diagnostics Ltd.). New Molecular-Functional Imaging
Technologies and Therapeutic Strategies for Theranostic of Invasive
Aspergillosis. European Commission FP7-HEALTH-2013-INNOVATION-1
SME-targeted Collaborative Project, 2013-2018, €1,397,800.
Details of the impact
The commercial value of Dr Thornton's research in fungal
immunodiagnostics has led to protection of his intellectual property
through a patent application in 2008 (section 5; source 1), and commercial
exploitation of the Aspergillus LFD through establishment of a
University of Exeter spin-out company, Isca Diagnostics Limited (www.iscadiagnostics.co.uk,
section 5; source 2-4), and a global distribution agreement with OLM
section 5; source 5).14 Dr Thornton, as CEO of Isca, was also
awarded€1.4M as an SME participant in a 5 year FP7 HEALTH-INNOVATION-1
consortium grant in 2013. Dr Thornton's role is to generate JF5 antibody
fragments (Fabs, scFvs, minibodies) and a humanised JF5 antibody for
radio-immunotherapy and Positron-Emission-Tomography/MRI imaging of IPA in
animal models and in human clinical trials (http://www.mathias-imaging.eu).
1. Intellectual Property Protection and Patenting of the LFD and mAb
A patent "New Method of Detecting and Diagnosing Invasive Aspergillosis",
with Dr Thornton as the named inventor, was filed by the University of
Exeter in the US in Jan 2009 (US61/145,282), and PCT filing
(PCT/GB2010/000064) in Jan 2010 (section 5; source 1). Regional and
National Phase registration was initiated in July 2011, with protection
being sought in the US, EU, Russia, China and India. In line with the
Budapest treaty, the variable heavy and light chains (VH and VL)
and Complementarity Determining Regions (CDRs) of mAb JF5 were sequenced
and published, and the hybridoma cell line deposited in the European
Collection of Cell Cultures (ECACC). The sequencing and deposition work
was funded by a HEIF 4 grant to Dr Thornton.
2. Establishment of University of Exeter Spin-Out Company Isca
On 29th March 2012, Dr Thornton, with financial and legal
support from the University of Exeter and funding of £85k from private
investors (section 5; source 3), established a spin-out company Isca
Diagnostics Ltd. (section 5; source 4), for commercial exploitation of mAb
JF5 and the Aspergillus- specific LFD. Subsequent funding in 2013
through an EC FP7 consortium grant has enabled Isca to expand its
portfolio of diagnostic and therapeutic agents for IPA over the next five
years (2013-2018). It has also enabled Isca to employ a full-time R&D
scientist and for Dr Thornton to spend 0.33FTE as an Isca employee
3. Distribution and Sales of the Aspergillus LFD
as a CE marked medical IVD.
MHRA CE marking of the LFD for use as a general medical IVD in the
European Union was obtained in 2013 and external US evaluation of the LFD,
conducted by the NIH/NIAID-funded Aspergillus Technology
will commence in Nov 2013, providing the data for a 510k FDA approval. An
agreement with OLM Medical has been signed for distribution and sales of
the LFD worldwide (section 5; source 5). Prior to September 2013, purchase
orders of the CE marked device had been received from Australian and
Canadian hospitals (section 5; source 6), and internal validation audits
of the LFD, prior to order placement, are currently being undertaken in
hospitals in the UK, US, France, Germany, Austria, Israel, Turkey, Peru,
Iran, and South Africa.
In addition to its commercial activities, Isca is a sponsor of the Global
Action Fund for Fungal Infection (www.gaffi.org/our-partners/),
a Geneva-based foundation whose vision is to reduce illness and death
associated with fungal diseases worldwide. As a GAFFI partner, Isca
supplies the Aspergillus LFD as a research tool for use by
Dr Thornton also entered into an IPR agreement with Pfizer Ltd. in
November 2013, allowing Pfizer to promote the LFD alongside its antifungal
voriconazole, VFend® (section 5; source 7).
The success of the LFD device, prompted by Dr Thornton's research and the
subsequent incorporation of Isca Diagnostics Ltd has stimulated a large
amount of interest in the media. A list of web references to these are
included as section 5; source 8.
Sources to corroborate the impact
- New Method of Detecting and Diagnosing Invasive Aspergillosis", with
Dr Thornton as the named inventor, was filed by the University of Exeter
in the US in Jan 2009 (US61/145,282), and PCT filing (PCT/GB2010/000064)
in Jan 2010.
Details of the Aspergillus LFD and mAb JF5 patent can be found
Supporting documents relating to the establishment of Isca Diagnostics
Ltd. and distribution and sales of the Aspergillus LFD.
- Isca Diagnostics IP License Agreement.
- Isca Diagnostics Shareholders Agreement and Written Resolutions.
- Isca Diagnostics Incorporation Certificate.
- OLM Medical Distribution Agreement.
- LFD purchase orders from Australian and Canadian hospitals.
- Isca Licence Agreement with Pfizer Ltd.
Reports in public domain (web links)
Media release by the Society for General Microbiology:
Other website coverage: