Award details

Translation of Step-changing Bioprocesses and Expression System Technologies for Next Generation Protein Biologics Production in CHO Cells

Reference	BB/N023501/1
Principal Investigator / Supervisor	Professor Christopher Smales
Co-Investigators / Co-Supervisors
Institution	University of Kent
Department	Sch of Biosciences
Funding type	Research
Value (£)	746,256
Status	Completed
Type	Research Grant
Start date	01/07/2016
End date	29/02/2020
Duration	44 months

Abstract

This proposal's overall output is a novel integrated pipeline for difficult to express (DTE) biologics production. A 3-fold approach to realising the commercial potential of the technology will be adopted. Firstly, a lipid suplementation strategy will be developed to improve existing CHO processes. Secondly, a suite of expression vectors will be created comprising new marker genes that complement CHO auxotrophies and lipid biosynthesis genes. Thirdly, engineered CHO chassis will be generated that stably express the lipid metabolism genes and/or combinations of these. The final, and preferred, embodiment of the technology will be a combination of new cell chassis and improved processes. This approach will maximise the realisation of value by ensuring early implmentation and broad application (both existing and new cell lines) and also mitigates against the failure of any one approach. WPs 1-4 are based upon innovations that both teams together were involved in developing. Specific milestones: 1. Appointment of staff/training (Q1, y1). 2. 3/4 gene cassette vectors available (Q2, y1). 3. Vectors with novel metabolic selection markers (tyrosine/proline) available (Q4, y1). 4. New lipid supplementation processes for DTE proteins in existing technologies developed (Q4, y1). 5. Initial lipid engineered Xceed host cell line available and validated for enhanced DTE protein yield/quality (Q2, y2). 6. Cell line construction and process development validated for novel lipid engineered Xceed hosts (Q2, y3). 7. cGMP cell banks available (Q2, y3). 8. cGMP cell bank testing complete, novel cell lines and upload of process conditions suitable for cGMP use into Lonza's GMP document management system and release of a process uptake to Lonza's GS Licensees (Q4, y3).

Summary

Chinese hamster ovary (CHO) cells are the main production host for >US$145billion/yr of protein biologics used as medicines for a range of diseases. The CHO platform is mature when considering production of monoclonal antibodies, but new format non-native molecules such as fusion proteins, antibody fragments and other exotic molecules remain difficult to express (DTE) in this, or any other host. This project builds upon proof of concept work demonstrating that engineering the CHO chassis, together with growth media manipulation, increases both the yield and quality of a number of DTE proteins that are in development for application to unmet clinical needs and diseases with no current treatments. The project will advance the technology readiness level of our preliminary findings beyond proof-of-concept to deliver the commercialization of new CHO cell systems for DTE proteins and associated bioprocesses ready for industrial application to produce these important new medicines.

Impact Summary

As described in proposal submitted to IUK

Committee	Research Committee A (Animal disease, health and welfare)
Research Topics	Industrial Biotechnology, Pharmaceuticals
Research Priority	X – Research Priority information not available
Research Initiative	Industrial Biotechnology Catalyst (IBCAT) [2014-2015]
Funding Scheme	X – not Funded via a specific Funding Scheme

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