In Silico Development Assessment
Antibody Discovery Services
In Silico Development Assessment Overview
Early assessment of lead monoclonal antibody candidates can help prevent delays in the later stages of development, making developability assessment increasingly important. The concept of developability is based on insights gained from the successful development of approximately 80 marketed antibody and Fc-fusion protein drug products, as well as lessons learned from numerous failed development programs over the past 30 years.
Without comprehensive characterization to understand the biochemical and biophysical properties of the selected candidates, unexpected modifications, stability issues, or adverse PK and PD can lead to project delays or even termination. Development risks are often related to the inherent properties of candidate drugs. Therefore, conducting a developability assessment before entering process development is crucial. Developability assessment is a systematic evaluation of candidate drugs, including structural evaluation, safety, PK and PD, and manufacturability.
Early assessment of lead monoclonal antibody candidates can help prevent delays in the later stages of development, making developability assessment increasingly important. The concept of developability is based on insights gained from the successful development of approximately 80 marketed antibody and Fc-fusion protein drug products, as well as lessons learned from numerous failed development programs over the past 30 years. Without comprehensive characterization to understand the biochemical and biophysical properties of the selected candidates, unexpected modifications, stability issues, or adverse PK and PD can lead to project delays or even termination. Development risks are often related to the inherent properties of candidate drugs. Therefore, conducting a developability assessment before entering process development is crucial. Developability assessment is a systematic evaluation of candidate drugs, including structural evaluation, safety, PK and PD, and manufacturability.
KYinno has developed a computer-assisted antibody developability analysis system based on antibody sequences and structural information. First, using the sequence information of the antibody variable regions, we analyze a series of drugability and developability parameters. These parameters include post-translational modification sites analysis, solubility and aggregation analysis in the CDR regions, length analysis, charge analysis, and stability analysis of the CDR regions. We have compiled sequence information from all approved antibody drug products and summarized primary sequence properties of the CDRs in all these approved antibody drugs. The sequence information of the target antibody is color-coded to indicate whether it falls within the range of these approved drugs. Regions that require special attention are marked in red. See the table below for details.
We will also perform Homology Modeling based on the sequence of the target antibody’s variable regions. During modeling, we will select crystal structures of the heavy chain framework region, heavy chain CDR, light chain framework region, and light chain CDR as reference templates for homology modeling, striving to accurately predict the antibody’s structure.
Using the accurately predicted structure of the antibody’s variable regions, we will conduct structure-related developability analysis, including analysis of the hydrophobic and hydrophilic properties on the antibody CDR surface, charge distribution on the CDR surface, hydrogen bonds and salt bridges within the CDR structure, as well as translation modification site analysis based on the CDR surface structure, and more.
Finally, a comprehensive assessment of the target antibody’s developability will be made based on all of this information.
Figure: Surface charge analysis: Blue color is positive charge aera of CDR, red color is negative charge aera of CDR
Figure: Surface dyrogen bond analysis of CDR
Figure: Saltbridge analysis of CDR
Figure: Posttranslational modifications (PTMs) analysis of CDR
All Antibody Discovery Services
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