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Discovery and Development of Human SARS-CoV-2 Neutralizing Antibodies using an Unbiased Phage Display Library Approach

By Xia Cao, Junki Maruyama, Heyue Zhou, Lisa Kerwin, Rachel Sattler, John T. Manning, Sachi Johnson, Susan Richards, Yan Li, Weiqun Shen, Benjamin Blair, Na Du, Kyndal Morais, Kate Lawrence, Lucy Lu, Chin-I Pai, Donghui Li, Mark Brunswick, Yanliang Zhang, Henry Ji, Slobodan Paessler, Robert D. Allen

Posted 28 Sep 2020
bioRxiv DOI: 10.1101/2020.09.27.316174

SARS-CoV-2 neutralizing antibodies represent an important component of the ongoing search for effective treatment of and protection against COVID-19. We report here on the use of a naïve phage display antibody library to identify a panel of fully human SARS-CoV-2 neutralizing antibodies. Following functional profiling in vitro against an early pandemic isolate as well as a recently emerged isolate bearing the D614G Spike mutation, the clinical candidate antibody, STI-1499, and the affinity-engineered variant, STI-2020, were evaluated for in vivo efficacy in the Syrian golden hamster model of COVID-19. Both antibodies demonstrated potent protection against the pathogenic effects of the disease and a dose-dependent reduction of virus load in the lungs, reaching undetectable levels following a single dose of 500 micrograms of STI-2020. These data support continued development of these antibodies as therapeutics against COVID-19 and future use of this approach to address novel emerging pandemic disease threats. ### Competing Interest Statement Sorrento authors own options and/or stock of the company. This work has been described in one or more provisional patent applications. HJ is an officer at Sorrento Therapeutics, Inc..

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