Hepler, N. L.; Hill, A. J.; Jaffe, D. B.; Gibbons, M. C.; Pfeiffer, K. A.; Hilton, D. M.; Freeman, M.; McDonnell, W. J.

GLIMPSE-1 is a protein language model trained solely on paired human antibody sequences. It captures immunological features and achieves best-in-class performance in humanization benchmarks. We demonstrate the utility of GLIMPSE-1 in humanization; engineering of antibodies for affinity, species cross-reactivity, and key developability parameters; and the creation of highly divergent functional variants with <90% sequence identity to a marketed antibody. Learning exclusively from human antibody data enables GLIMPSE-1 to enhance therapeutics and native antibodies based on patterns in the human repertoire.