One of the major hurdles for producing monoclonal antibodies (mAbs) that are targeted for geographically diverse populations is the need to produce a mAb that is manufacturable, thermally stable, and low cost. By using a combination of in silico molecular design, activity assays, and biophysical tools, we will show how this can be accomplished. First, variants of a parental antibody are defined in silico based on sequence and structural considerations using a combination of molecular design tools. Next, a suite of biophysical and activity assays are used to characterize and identify the most suitable variants. Based on these results, another round of modifications may be designed to enhance the variants that demonstrated measurable improvements. This new set of variants are tested using an expanded suite of biophysical assays to identify the variant most suitable for production. Specifically, we will discuss how the combination of biophysical assays such as differential scanning fluorimetry, chemical unfolding, low pH stability, and others together with activity, helped identify variants with significantly improved manufacturability characteristics. Additionally, these variants demonstrated decreases up to 6-fold in sub-visible particle formation during storage at 40oC. This approach can be used to optimize antibody therapeutics for improved manufacturability, stability, and lower overall costs leading to expanded access to important biotherapeutics.

Optimizing a monoclonal antibody for manufacturability, stability, and cost

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.