Address Antibody Aggregation Issues in Early Development
Aggregation is a common and well-known problem for biotherapeutics during all stages of their production and use. The presence of aggregates has been known to increase production costs and lead to problems with product stability and regulatory compliance. More importantly, aggregation has the potential to be a significant safety risk as it can enhance immunogenicity.
Lonza offers two service options for aggregation assessment:
1. As part of our Physical stability assessment service
2. Sentinel APART™ server-based tool available for use in Customers’ facilities
Introducing the SENTINEL APART ™ Platform for Antibody Prediction and Re-engineering
Sentinel APART™ platform is a highly-secure, server-based antibody aggregation prediction and re-engineering tool. It is available to Customers using a dedicated address to access their system. Lonza developed the Sentinel APART™ platform based on our extensive knowledge and expertise in antibody production and antibody engineering. The tool was built and validated on experimental aggregation data for over 500 antibodies. Using the primary sequence as input, it provides qualitative prediction (High or Low) of aggregation risk for antibodies.
The antibody re-engineering functionality of the platform identifies residues that contribute to aggregation and provides a guided approach for suitable amino acid substitutions. The tool calculates the change in aggregation risk for either one or two position substitutions taking into consideration the potential impact on post translational modifications (PTMs) in the re-engineered antibody sequence.
There are three types of computations and output provided by the Sentinel APART™ tool:
- Aggregation Prediction is performed by screening one or multiple antibodies for potential aggregation risk
- Antibody Re-engineering 1-point Randomization explores the change in predicted aggregation risk due to a single substitution in the antibody sequence. This is done by predicting the aggregation risk and score for all possible single- residue substitution variants.
- Antibody Re-engineering 2-point Randomization calculates the change in predicted aggregation risk due to two substitutions in the antibody sequence. In this case the aggregation risk and score are predicted for all possible two-residue substitution variants.
Although a substitution may be beneficial to reduce the aggregation risk, it may have a negative impact on an antibody’s structural integrity and binding. The Sentinel APART™ platform incorporates elements of antibody engineering knowledge and provides information which can help the user to select suitable substitutions. The additional information includes positional frequencies of amino acids, solvent accessibility of residues and their involvement in antigen and chain contact, amino acid type and possible sites of notable post translational modifications.
Access to the Sentinel APART™ platform is available through an annual fee based on customer usage. For more information, contact email@example.com.