Granted Patent B2

US 12,630,890 · App. 17/927,649 · Granted May 19, 2026

Inventors: Alina Baum (Pleasantville, NY); Benjamin Fulton (New York, NY); Christos Kyratsous (Irvington, NY); George D. Yancopoulos (Yorktown Heights, NY)

Assignee: Regeneron Pharmaceuticals, Inc.

C12Q1/701A61P31/14C07K16/102C07K16/104G01N33/56983A61K2039/505A61K2039/507C07K2317/21C07K2317/24C07K2317/73C07K2317/732C07K2317/76C07K2317/92C12Q2600/136C12Q2600/156G01N2333/165G01N2500/10

Abstract

Claims (16)

1 . 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.

2 . The method of claim 1 , wherein said frequency of escape mutants is measured by:

a) contacting a population of cells with said first antibody or antigen-binding fragment thereof, and with a virus expressing said SARS-CoV-2 spike protein, sequencing nucleic acids from said population of cells, and determining a first frequency of SARS-CoV-2 spike protein mutations;

b) contacting a comparable population of cells with said second antibody or antigen-binding fragment thereof, and with a virus expressing said SARS-CoV-2 spike protein, sequencing nucleic acids from said population of cells, and determining a second frequency of SARS-CoV-2 spike protein mutations;

c) contacting a comparable population of cells with said first antibody or antigen-binding fragment thereof and said second antibody or antigen-binding fragment thereof, and with a virus expressing said SARS-CoV-2 spike protein, sequencing nucleic acids from said population of cells, and determining a third frequency of SARS-CoV-2 spike protein mutations; and

d) comparing said first frequency, said second frequency, and said third frequency.

Assignments (1)

Continuity (9)

References Cited (400)