Developing unique conjugation (PEGylation) technology and commercial spinout through PolyTherics Ltd.
Submitting InstitutionImperial College London
Unit of AssessmentClinical Medicine
Summary Impact TypeTechnological
Research Subject Area(s)
Chemical Sciences: Organic Chemistry
Biological Sciences: Biochemistry and Cell Biology
Medical and Health Sciences: Medical Biochemistry and Metabolomics
Summary of the impact
A novel conjugation technology has been developed to enable site-specific
attachment of polyethylene glycol (PEG) to proteins to extend the in vivo
half-life of biopharmaceuticals. The technology has been commercialised by
an Imperial College spin-out company, PolyTherics Limited. In 2013, the
merger of PolyTherics with Antitope Limited, enhanced the company's
biopharmaceutical technology development offering. PolyTherics issued new
shares to the value of £13.5 million to investors and Antitope
shareholders in connection with the merger.
The company has enabled the development of novel forms of interferon 03b2
(for the treatment of multiple sclerosis) and blood factors VIIA, VIII and
IX (for the treatment of haemophilia A and B) utilising original Imperial
TheraPEG™ technology. This is achieved through licences granted by
PolyTherics to Nuron Biotech and Celtic Pharma Holdings who are in early
pre-clinical development. PolyTherics has further developed the
conjugation technology (ThioBridge™) for its application in the creation
of stable, homogeneous antibody-drug conjugates for the targeted cancer
Polytherics has impacted the UK economy generating intellectual capital,
capital investment, new employment and novel compounds to treat disease.
Key Imperial College London researchers:
Professor Sunil Shaunak, Professor of Infectious Diseases (1991-present)
PEGylation is a clinically proven strategy for increasing the therapeutic
efficacy of protein-based medicines. PEGylation is the process of covalent
attachment of polyethylene glycol (PEG) polymer chains to another
molecule, normally a drug or therapeutic protein. The application of this
technology is best illustrated in the development of PEGylated
interferon-α which is used to treat and cure Hepatitis C infection.
However, before the Imperial work, earlier technologies for PEGylation
produced very heterogeneous products based on conjugation to ε-amino
groups of lysines, with multiple isomers produced with varying activity
and pharmacokinetic profiles and introducing significant complexity into
the production and analytical processes.
In 2004-2005, Professor Shaunak, in collaboration with Professor
Brocchini (London School of Pharmacy), developed a novel approach to
site-specific PEGylation based on equilibrium transfer alkylation
crosslinking through the reduction of protein di-sulphide bonds (1).
Specifically, this approach exploits thiol selective chemistry via a
multi-step reaction pathway that leads from controlled reduction of
accessible disulphide bonds of proteins, through two-step Michael
additions using α-β-unsaturated--β'-mono-sulfone functionalized PEG
reagents, to introduce a three-carbon bridge into the former disulphide
bond with PEG covalently attached to the three carbon bridge.
This technology ensures that that only one PEG molecule is conjugated at
each disulphide bond. The research was published in academic journals
(2-5) and has led to the PEGylation reagents (TheraPEG™). TheraPEG™
technology was developed and commercialised through collaborations between
Imperial and PolyTherics Ltd (2003-2005). It enabled the therapeutic
efficacy of protein-based medicines to be significantly improved. The
conjugation process and the resulting products becoming the subject of
granted patents in Europe, US, India, China, Japan, South Korea and
Initial Imperial research focused on the application of TheraPEG™
technology to interferon α as a potential alternative to other pegylated
interferon α products for the treatment of Hepatitis C infection. Further
research studies conducted by PolyTherics with a range of different
proteins and peptides under commercial contracts. TheraPEG™ technology
enabled enzymes and antibody fragments to be site-specifically PEGylated
using a native and accessible disulphide bond without destroying the
molecules' tertiary structure or abolishing its biological activity.
References to the research
(1) Core technology patent — awarded: A. Godwin, E. Pedone, J. Choi, S.
Brocchini, S. Shaunak. Conjugated biological molecules and their
preparation. World — WO2005/007197A3(2005);
US — US7595292B2(2009)
— awarded; Europe — EP04743335(2009) — awarded.
(2) Shaunak, S., Godwin, A., Choi, J., Balan, S., Pedone, E.,
Vijayarangam, D., Heidelberger, S., Teo, I., Zloh, M., Brocchini, S.
(2006). Site-specific PEGylation of native disulfide bonds in therapeutic
proteins. Nat. Chem. Biol, 2, 312-313. DOI.
Times cited: 87 (as at 7th November 2013 on ISI Web of
Science). Journal Impact Factor: 12.94
(3) Brocchini, S., Balan, S., Godwin, A., Choi, J.W., Zloh, M., Shaunak,
S. (2006). PEGylation of native disulfide bonds in proteins. Nat
Protocols, 1 (5), 2241-2252. DOI.
Times cited: 29 (as at 7th November 2013 on ISI Web of
Science). Journal Impact Factor: 7.96
(4) Balan, S., Choi, J., Godwin, A., Teo, I., Laborde, C., Heidelberger,
S., Zloh, M., Brocchini, S., Shaunak, S. (2007). Site-specific PEGylation
of protein disulfide bonds using a three-carbon bridge. Bioconjug Chem.
18 (1) (2007) 61-76. DOI.
Times cited: 57 (as at 7th November 2013 on ISI Web of
Science). Journal Impact Factor: 4.58
(5) Zloh, M., Shaunak, S., Balan, S., Brocchini, S. (2007).
Identification and insertion of 3-carbon bridges in protein disulfide
bonds: a computational approach. Nature Protocols, 2, 1070-1083. DOI. Times cited:
10 (as at 7th November 2013 on ISI Web of Science). Journal
Impact Factor: 7.96
• Conjugated biological molecules and their preparation. Godwin, A.R.,
Pedone, E., Choi, J.W., Shaunak, S., Brocchini, S.J. World Patent WO
• European Patent: EP 04743335 (2009) — granted.
• US Patent: US 10564340 (2009) — granted.
• Wellcome Trust (2002-2006; £500,000), Principal Investigator (PI), S.
Shaunak, The design, synthesis and testing of novel polymer therapeutics.
• Bloomsbury Bioseed University Challenge Fund (2002-2006; £250,000), PI
S. Shaunak, The design, synthesis and testing of novel polymer
• Department of Trade and Industry (2004-2007; £160,706), PI S. Shaunak,
Rapid development of protein-based medicines using a precise conjugation
• Biotechnology and Biological Sciences Research Council (2006-2008;
£280,932), PI S. Shaunak, Disulfide bridging protein conjugation.
Details of the impact
Impacts include: commercial
Main beneficiaries include: industry
PolyTherics was established as a joint spin-out company of Imperial
College and London School of Pharmacy. By 2013, following four successful
rounds (2007, 2010, 2011 and 2013) of venture capital funding, PolyTherics
had raised over £20 million of funding (£2.5 million raised prior to
2008). This established PolyTherics as one of London's leading life
sciences companies, with revenues of £3.2 million in 2012 , and licence
agreements (detailed below & [4-6]) with the potential to deliver
significant milestone and royalty payments from exploitation of the
Imperial conjugation technology (TheraPEG™) developed by Professor Shaunak
as applied to novel protein therapeutics.
PolyTherics has 45 highly skilled employees commercially exploiting and
developing the TheraPEG™ technology based at the London Bioscience
Innovation Centre and at its site on the University of Warwick Science
Park . The company has recruited a strong management team, experienced
in the pharmaceutical and biotech industries, led by John Burt who has
strong links to Imperial. PolyTherics has been successful at
commercialising the technology developed at Imperial through commercial
licence agreements with Nuron Biotech (TheraPEG interferon 03b2)  and
Celtic Pharma  and Pro Bono Bio (TheraPEG FVIIA, FVIII & FIX) .
In July 2013 PolyTherics announced its merger with Antitope Limited, the
leading provider of antibody engineering and immunogenicity screening
services . The expanded offering will provide the PolyTherics group
with a broad technology platform for growth and a solid financial base
with sustainable revenue streams over the short-, medium- and longer-term.
The enlarged company will deliver a more extensive suite of services and
technologies for the development of better biopharmaceuticals. PolyTherics
issued new shares to a value of £13.5 million to fund the merger and
provide working capital. Imperial Innovations led the investment and
brought in new investor Invesco Perpetual with further funds provided by
Mercia Fund Management and Advantage Enterprise & Innovation Fund.
The successful merger and development of Polytherics demonstrated the
strength of the company founded on Imperial technology. The company has
impacted the UK economy generating intellectual capital, capital
investment, new employment and novel compounds to treat disease.
Sources to corroborate the impact
 Polytherics raised $3.5 million in venture capital.
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 Company employee information: http://www.Polytherics.com/index.php/about-us/management
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 Nuron Biotech and interferon-β.
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 Milestone payment from Celtic Pharma Ltd in 2013.
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 Pro Bono Ltd and haemophilia A treatment.
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 Merger of PolyTherics and Antitope July 2013
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