Summary
LY-CoV1404 is a highly potent, neutralizing, SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody identified from a convalescent COVID-19 patient approximately 60 days after symptom onset. In pseudovirus studies, LY-CoV1404 retains potent neutralizing activity against numerous variants including B.1.1.7, B.1.351, B.1.427/B.1.429, P.1, and B.1.526 and binds to these variants in the presence of their underlying RBD mutations (which include K417N, L452R, E484K, and N501Y). LY-CoV1404 also neutralizes authentic SARS-CoV-2 in two different assays against multiple isolates. The RBD positions comprising the LY-CoV1404 epitope are highly conserved, with the exception of N439 and N501; notably the binding and neutralizing activity of LY-CoV1404 is unaffected by the most common mutations at these positions (N439K and N501Y). The breadth of variant binding, potent neutralizing activity and the relatively conserved epitope suggest that LY-CoV1404 is one in a panel of well-characterized, clinically developable antibodies that could be deployed rapidly to address current and emerging variants. New variant-resistant treatments such as LY-CoV1404 are desperately needed, given that some of the existing therapeutic antibodies are less effective or ineffective against certain variants and the impact of variants on vaccine efficacy is still poorly understood.
In Brief LY-CoV1404 is a potent SARS-CoV-2-binding antibody that neutralizes all known variants of concern and whose epitope is rarely mutated.
Highlights
LY-CoV1404 potently neutralizes SARS-CoV-2 authentic virus and all known variants of concern
No loss of potency against current variants
Binding epitope on RBD of SARS-CoV-2 is rarely mutated in GISAID database
Breadth of neutralizing activity and potency supports clinical development
Competing Interest Statement
D.F., P. V., A.P., J.H., J.M.S., R.W.S, J.C., I. H., J. J. F., S. H., H. C. P., B. R., B. A. H., R. W. S., J. C., J. M. S., R. E. H., N. K., and B.E.J. are employees and/or stockholders of Eli Lilly and Company. K.W., S. Z., M.W., E.L., L.K., Y.H., K.J., R.G., M.A.S., D.W.C., D.P., P.X., V.d.P., M.R., L.D., C.P., I.L., L.A., P.S., T.L.F., C.L.H, E.F., and B.C.B are employees and stockholders of AbCellera Biologics Inc. AbCellera Biologics Inc. and National Institutes of Health have filed patent applications related to the work described herein (US Patent Application No. 17/192243 and International Patent Application No. PCT/US21/20843, both titled Anti-Coronavirus Antibodies and Methods of Use).
Footnotes
↵# Lead contact bo.barnhart{at}abcellera.com