Lanyu Fan
Improving the stability of therapeutic monoclonal antibodies during manufacture and storage.
Email: l.fan5@ncl.ac.uk
Supervisors
- School of Natural and Environmental Sciences
- School of Engineering
Project description
Therapeutic proteins have been approved for the treatment of different kinds of diseases in humans. These proteins include monoclonal antibodies (mAbs). They are often administered through subcutaneous injection. This requires high concentration formulations to reach the dosage in a limited volume. For a therapeutic protein to be commercially available, a shelf life of greater than 12 months is required.
The stability of mAbs during manufacturing and final storage is vital. Reducing the aggregation propensity is the key to success. We can add excipients to stabilise mAbs during manufacturing and storage. Altering the types and concentration of excipient molecules will vary the stability.
The project will focus on designing and optimising the formulation for aggregation-prone therapeutic monoclonal antibodies. The formulation will use cosolvent molecular dynamics (MD) simulations. These simulations are simple and effective techniques for predicting and characterising protein allosteric binding sites. Their applications to formulation development remains underexplored.
The Cosolvent Analysis Toolkit (CAT) was recently developed in Bronowska’s lab. I will use the toolkit to analyse trajectories of mAbs. I willl analyse them with different combinations and concentrations of excipients in different temperature and pressure ranges. CAT accurately ranks the interactions between mAb and excipients. Thus, we can identify the aggregation-prone “hot spots” within mAbs. We can also mitigate aggregation by adjusting the excipient molecules.
The EPSRC Doctoral Training Partnership is funding this project. It will be carried out in a dynamic multidisciplinary research environment comprising of researchers from the School of Natural and Environmental Sciences and the School of Engineering.
Interests
Development of monoclonal antibody formulations to decrease aggregation during long-term storage using molecular simulations.
Qualifications
- BSc Chemistry (Newcastle University)
- MSc Drug Chemistry (Newcastle University)