Awaiting Public Project Summary
"POCKiT diagnostics is a UK company focused on the research and development of point-of-care diagnostic devices. Our main target is to develop a device for diagnosis of brain stroke. Stroke is the third leading cause of death and the first cause of physical disability and dementia worldwide. In stroke, the brain is damaged by restricted blood flow to the brain, which leads to death of brain cells. Two main types of stroke exist with patients having similar symptoms: ischemic stroke (IS) and intracerebral hemorrhage (ICH); whilst they have similar symptoms, treatment is opposite. IS is caused by a clot in the brain- and treated with 'clotbusting' drugs which dissolve the clot. If the clotbusting drug given fast enough (within 3-4 hours) the patient may recover with little or no damage to the brain. ICH is caused by bleeding in the brain. Clotbusting drugs incorrectly given to ICH patient prevents clotting and healing, which is a disaster.
Therefore, accurate diagnosis of stroke subtype is paramount to inform appropriate treatment, as administration of the wrong treatment can lead to patient death. Unfortunately, if treatment is delayed- for example to wait for results of slow diagnostic tests, or during transport of patient to the hospital- it becomes less effective. Currently, diagnosis of stroke is performed with CT imaging- a brain scan- which takes a significant length of time, it is not always available and the patient must be taken to equipped hospital, and is not accurate enough.
""Fplus1"" is a revolutionary innovation in that it combines ultra-rapid (<20 minutes) detection of blood biomarkers that are highly specific for stroke subtypes, within a point-of-care device. In other words, the brain scan is replaced by a rapid blood test. Moreover, ""Fplus1"" will be low-cost and will reduce the need for specialized medical personnel, ultimately resulting in significant cost reduction for healthcare providers. Currently, there are no point-of-care devices on the market for the accurate and rapid diagnosis of brain stroke subtype. In the virtual absence of competition, our innovation has the potential to disrupt and revolutionise current diagnosis of brain stroke and significantly reduce stroke-induced death and disabilities. The collaborative network brought together within this project aims at bringing forward the ""Fplus1"" prototype towards full development of a product upon regulatory approval, ""Fplus1"" will initially be introduced in the United Kingdom market, with the final goal of expansion to the European and global market."
A platform for rapidly producing rationally engineered vaccines is urgently required to combat the threat of epidemic or pandemic pathogen outbreaks. Most existing vaccines are multicomponent products that are challenging to manufacture. The slowest step is typically transfer from preclinical proof-of-concept to GMP manufacture for human use. Manufacturing processes often require many product-specific steps precluding a standardised manufacturing platform. By contrast, advances made through significant and sustained investment into therapeutic monoclonal antibody (mAb) discovery and manufacture has made biosynthetic mass-production of high-yield, high-quality antibodies routine and broadly applicable, largely irrespective of the mAb's identity.
We have exploited a protein engineering approach to vaccine development by combining target pathogen-specific proteins fused with the immunoglobulin heavy chain Fc domain. Fc fusion proteins are self-adjuvanting, targeting the antigen presenting cell through engagement with the Fc receptor. In this project we propose to combine state-of-the-art mAb manufacturing technology with several antigen-Fc fusion proteins, including some with novel modifications that increase potency, to assess the feasibility of a rapid and responsive "concept-to-human" platform for subunit vaccine discovery.
A previous Innovate UK Biomedical Catalyst project has allowed us to apply our technology to MERS as a target pathogen. Targeting the major surface glycoprotein, S, we have produced several MERS candidate vaccines and shown good expression, purification and demonstrated immunogenicity in small mammals. Building on this we wish to address manufacturing possibilities that exploit the similarities between these Fc-containing candidates and traditional antibodies. By implication, successful application of mAb manufacturing to our current candidates should also apply to other targets suitable for Fc fusion technology making the routine rapid discovery and production of potent subunit vaccines using existing UK GMP therapeutic mAb facilities to protect against a range of known and emerging pathogens a realizable goal. Questions to be addressed include the yield of the product, its homogeneity, glycosylation status and oligomerisation, ease of purification and immunogenicity on a weight-to-weight basis, in comparison to established current materials.
The project will combine the expertise of Anglo Biopharma, a British start-up biotechnology company focusing on rapid vaccine discovery for infections with unmet need, with Absolute Antibody, another British SME who are established leaders in rapid biosynthetic monoclonal antibody production. The third partner, the University of Reading, completes the team bringing experts in vaccine bioengineering and adjuvant formulation who will compare MERS subunit candidate vaccine produced by the new manufacturing process with existing material produced using current insect cell expression.
Awaiting Public Project Summary
Antibodies are outstanding tools for biomedical research and essential components of a
myriad of diagnostic tests. They are also the largest and fastest growing source of new drugs
with 39 approved to date and hundreds more in the pipeline. The vast majority of therapeutic
antibodies are made using recombinant DNA technology, which has enabled the engineering
of specific functions and the reduction or elimination of undesirable side-effects. However,
protein engineering has largely been ignored during the development of antibodies for
research and diagnosis, where most are still made by immunising goats or rabbits
("polyclonal" antibodies) or by the hybrid myeloma technique invented by Kohler and
Milstein in 1975 ("monoclonal" antibodies). Engineered antibodies could have many benefits,
bringing new specificities, simpler assay protocols and reduced "noise", to allow more reliable
and more reproducible tests.
Our plan is to develop an efficient method to quickly sequence desired antibodies and
transiently express them in a reproducible fashion to make economical and powerful reagents
for the research market.
This proof-of-concept project will develop the platform technologies necessary to move into
routine production. Looking further ahead, we anticipate that these