Controlling the quality of novel glycoprotein therapeutics

Therapeutic proteins are one of the most valuable medicinal products currently on the market, because of their cost and importance a significant amount of money is spent on them. A large portion of this money is spent during the production and development of these drugs. One of the most important factors relating to production and development of therapeutic proteins is N-linked glycosylation. The process is defined as the addition of glycans (complex carbohydrates) to a nitrogen atom of an asparagine residue within the protein. N-linked glycosylation has a variety of effects on biologics including: safety, half-life, and efficacy of the drug. Due to the significant effect that glycosylation has on these drugs, it has been deemed a critical quality attribute (CQA) under Quality by Design (QbD). Quality by Design is a process put forward by the FDA in order to speed the process of drug design while also decreasing cost. The basis of this idea is that the quality of the product should be built into the design rather than an emphasis on testing the quality after the process is completed. This paradigm increases the efficiency and reduces the cost of the whole design process leading to more products and hopefully better ones. In regards to glycosylation it has been reported that the culture conditions of the cells grown to produce the desired therapeutic proteins can directly affect the glycomic profile of the proteins. With this known hopes can be made to use the culture conditions to optimize and control the glycomic profile produced. The basis of the PhD to be undertaken is to examine how culture conditions can affect the glycosylation of non-antibody therapeutic proteins. This data could then be used to control the glycosylation patterns of the proteins to one desired and potentially create a model of how the culture conditions affect non-mAb proteins.

Aims
- Investigate the effect of culture conditions on non-mAb proteins
- Expand a existing model used for mAb glycosylation to non-mAb
- Ultimately develop a model to produce a narrow and desired glyco profile