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LY-CoV1404 (also known as bebtelovimab) is a highly potent, neutralizing, SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody identified from a convalescent COVID-19 patient sample, obtained approximately 60 days after symptom onset. In pseudovirus studies, LY-CoV1404 retains potent neutralizing activity against numerous variants including B.1.617.2, B.1.1.7, B.1.351, B.1.427/B.1.429, P.1, and B.1.526, binding to these variants in the presence of their underlying RBD mutations (which include K417N, L452R, E484K, and N501Y). LY-CoV1404 also neutralizes multiple isolates of the authentic SARS-CoV-2 virus in two different assays. 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). 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. 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 as potentially long-term solutions to address current and emerging variants.

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