Antibody developability refers to a series of properties linked to the development of antibodies as therapeutics. These arise because natural antibodies do not possess them to begin with, or because they arise during optimization as a consequence of affinity maturation via techniques such as Yeast display.
General observations
- Raybould et al. (1) outlined five criteria (in a parallel to Lepinski’s rule of five):
- Length of CDRs, specifically CDRH3
- Hydrophobic patches
- Negative patches
- Positive patches
- Viscosity
Thermostability
See Stability and thermostability
Immunogenicity
- Glycine residues doesn’t cause immunogenicity as much as other residues (2). This makes them used for including during design of cyclic peptides or peptide therapeutics.
- Antibody humanization can lead to immunogenic reactions.
1.
Raybould MIJ, Marks C, Krawczyk K, Taddese B, Nowak J, Lewis AP, et al. Five computational developability guidelines for therapeutic antibody profiling. Proceedings of the National Academy of Sciences. 2019;116(10):4025–30. Available from: https://doi.org/10.1073/pnas.1810576116
2.
Aina A, Hsueh SCC, Gibbs E, Peng X, Cashman NR, Plotkin SS. De Novo Design of a β-Helix Tau Protein Scaffold: An Oligomer-Selective Vaccine Immunogen Candidate for Alzheimer’s Disease. ACS Chemical Neuroscience. 2023;14(15):2603–17. Available from: https://doi.org/10.1021/acschemneuro.3c00007