Web App Helps Flag Antibodies Where Manufacturability Might Be an Issue

Researchers have developed an open-source web app to help drug manufacturers and developers identify unstable antibodies prone to aggregation. The team from Oxford University says the Therapeutic Antibody Profiler 2 (TAP2) can compare the fragment variable component of a proposed antibody to successful clinical-stage antibodies.

According to Clare Gillis, a researcher in bioinformatics and computational biology, the app has the potential to help companies begin process development. “It can help them if they already know their antibody binds as they want, but they need to know if it will pass through the whole developability and manufacturability pipeline,” she says.

TAP2 uses five easily calculable physiochemical metrics based on surface residues of the antibody, Gillis says. These are more likely to affect manufacturability.

The web app metrics are selected to model aspects of antibody behavior, such as hydrophobicity, she adds. If there are big patches of hydrophobic residues on the outside of the antibody, then it’s more likely to be reactive and, thus, less likely to remain stable as a formulated drug product.

Likewise, Gillis explains, if the surface of the antibody features large patches of positive or negative charge, it is likely to have nonspecific reactions that will cause destabilization and aggregation.

With the TAP2 app, companies can flag early amber or red warnings for antibodies where manufacturability might be an issue. In addition, the group also offers a web app profiler for therapeutic nanobodies, TNP, as well as Humatch, an app that can help tweak antibodies to be more ”human-like” and less likely to cause immune reactions in patients, she says.

About Humatch, Gillis says, “you can add a best single point mutation and then iterate over and over until the model believes the antibody is fully humanized.” The app works for any antibody with paired heavy and light chain variable domains (VH and VL), she says, and can potentially help manufacturers of harder-to-produce products that don’t exist in nature.

The post Web App Helps Flag Antibodies Where Manufacturability Might Be an Issue appeared first on GEN - Genetic Engineering and Biotechnology News.