Our in silico assessment toolbox was designed for clients evaluating multiple lead molecule candidates to make economical and efficient CMC product development decisions. This in silico analysis could predict and mitigate the risks of subsequent development issues due to manufacturability, stability, immunogenicity and other issues. These in silico services can be integrated into a CLD program or provided to you as a customized standalone service.
Our in silico assessment contains three core-aspects:
- Sequence analysis
- Aggregation propensity
- Determination of immunogenicity
For sequence analysis, we first check the sequence elements and identify the unknown domain/motif. Then, we verify if there are any sequence areas (“hot spots”) that could potentially be susceptible to chemical and enzymatic modifications.
For aggregation propensity, we calculate the aggregation probability based on the surface hydrophobicity, charge, and free-cysteine residues of the protein.
Lastly, we evaluate the immunogenicity risk of the molecule by computing the sequence binding possibility to MHC molecules, and also comparing the sequence similarity to the human BCR database.
Through in silico assessment, the molecule candidates with higher CMC risks could be eliminated from further development to save cost and ensure development timeline milestones are met. Below we provide typical data or analysis resulting from our in silico biomolecule assessment program.