Anti-SARS-CoV-2-spike glycoprotein antibodies and antigen-binding fragments

A method for selecting a plurality of antibodies or antigen-binding fragments thereof for use in mitigating a frequency of escape mutants of a SARS-CoV-2 virus, comprising:

• a) obtaining a first antibody or antigen-binding fragment thereof that binds to a first epitope of a SARS-CoV-2 spike glycoprotein, the first epitope comprising the amino sequence set forth in SEQ ID NO:
• 836;
• b) obtaining a second antibody or antigen-binding fragment thereof that binds to a second epitope of the SARS-CoV-2 spike glycoprotein, the second epitope comprising the amino sequence set forth in SEQ ID NO:
• 839;
• c) determining whether said first antibody or antigen-binding fragment thereof and said second antibody or antigen-binding fragment thereof each exhibit neutralization potency against said virus;
• d) determining whether said first antibody or antigen-binding fragment thereof competes with said second antibody or antigen-binding fragment thereof for binding to said surface protein;
• e) if said first antibody or antigen-binding fragment thereof and said second antibody or antigen-binding fragment thereof each exhibit neutralization potency against said virus, and if said first antibody or antigen-binding fragment thereof and said second antibody or antigen-binding fragment thereof do not compete for binding to said surface protein, proceeding to steps f)-i);
• f) determining a first frequency of escape mutants resulting from said first antibody or antigen-binding fragment thereof alone;
• g) determining a second frequency of escape mutants resulting from said second antibody or antigen-binding fragment thereof alone;
• h) determining a third frequency of escape mutants resulting from a combination of said first antibody or antigen-binding fragment thereof and said second antibody or antigen-binding fragment thereof;
• and
• i) selecting said combination for use in mitigating the frequency of escape mutants if said third frequency is lower than said first frequency and said second frequency;
• wherein said escape mutants are mutants in said SARS-CoV-2 spike protein.