Compounds specific to coronavirus s protein and uses thereof

Abstract

The present disclosure is directed to antibodies, and antigen binding fragments thereof, having binding specificity for the S protein of coronaviruses (CoV-S), such as the S protein of the SARS coronavirus (SARS-CoV-S) and/or the S protein of the SARS coronavirus 2 (SARS-CoV-2-S), including neutralizing antibodies and antibodies that bind to and/or compete for binding to the same linear or conformational epitope(s) on CoV-S. Further disclosed are conjugates of anti-CoV-S antibodies, and binding fragments thereof, conjugated to one or more functional or detectable moieties. Methods of making said anti-CoV-S antibodies and antigen binding fragments thereof are also contemplated. Other embodiments of the disclosure include the use of anti-CoV-S antibodies, and binding fragments thereof, for the diagnosis, assessment, and treatment of diseases and disorders associated with coronaviruses, or the S protein thereof, and conditions where neutralization or inhibition of coronaviruses, or the S protein thereof, would be therapeutically and/or prophylactically beneficial.

1 - 46 . (canceled) 
     
     
         47 . An isolated antibody, or antigen-binding fragment thereof, which specifically binds to the spike protein of a coronavirus (“CoV-S”), wherein said antibody, or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising a sequence having at least 90% identity to SEQ ID NO:22302 and a light chain variable region (VL) comprising a sequence having at least 90% sequence identity to SEQ ID NO:22312. 
     
     
         48 . The isolated antibody, or antigen-binding fragment thereof, of  claim 47 , comprising a VH comprising a sequence having at least 95% identity to SEQ ID NO:22302 and a VL comprising a sequence having at least 95% identity to SEQ ID NO:22312. 
     
     
         49 . The isolated antibody, or antigen-binding fragment thereof, of  claim 48 , wherein the VH comprises SEQ ID NO:22302 and the VL comprises SEQ ID NO:22312. 
     
     
         50 . The isolated antibody, or antigen-binding fragment thereof, of  claim 49 , wherein the VH consists of SEQ ID NO:22302 and the VL consists of SEQ ID NO:22312. 
     
     
         51 . The isolated antibody, or antigen-binding fragment thereof, of  claim 47 , wherein the antibody, or antigen-binding fragment thereof, cross-reacts with SARS-CoV-S and SARS-CoV-2-S. 
     
     
         52 . The isolated antibody, or antigen-binding fragment thereof, of  claim 51 , wherein SARS-CoV-S comprises an amino acid sequence of SEQ ID NO:1, and wherein SARS-CoV-2-S comprises an amino acid sequence of SEQ ID NO:5. 
     
     
         53 . The isolated antibody, or antigen-binding fragment thereof, of  claim 47 , which neutralizes SARS-CoV and/or SARS-CoV-2. 
     
     
         54 . The isolated antibody, or antigen-binding fragment thereof, of  claim 53 , which neutralizes SARS-CoV and/or SARS-CoV-2 with an IC50 of about 100 nM or lower. 
     
     
         55 . The isolated antibody, or antigen-binding fragment thereof, of  claim 47 , which binds to SARS-CoV-S with a KD value of about 100 nM or lower. 
     
     
         56 . The isolated antibody, or antigen-binding fragment thereof, of  claim 47 , wherein the antibody is human, humanized, primatized, chimeric, bispecific or multispecific. 
     
     
         57 . The isolated antibody, or antigen-binding fragment thereof, of  claim 47 , wherein the antigen-binding fragment thereof comprises a Fab, Fab2, or scFv. 
     
     
         58 . A method of treating a coronavirus infection, or treating a condition, symptom, disease, or disorder associated with said infection in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the antibody, or antigen-binding fragment thereof, of  claim 47 , thereby treating the infection. 
     
     
         59 . A method of preventing a coronavirus infection, in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the antibody, or antigen-binding fragment thereof, of  claim 47 , thereby preventing the infection. 
     
     
         60 . A method of inducing an immune response against a coronavirus in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibody, or antigen-binding fragment thereof, of  claim 47 , thereby inducing the immune response against the coronavirus. 
     
     
         61 . A method of decreasing the risk of mortality, hospitalization, mechanical ventilation, or a combination thereof, in a subject infected by a coronavirus, comprising administering to the subject a therapeutically effective amount of the antibody, or antigen-binding fragment thereof, of  claim 47 , thereby decreasing the risk of mortality, hospitalization, mechanical ventilation, or a combination thereof, in the subject. 
     
     
         62 . An isolated antibody, or antigen-binding fragment thereof, which specifically binds to the spike protein of a coronavirus (“CoV-S”), wherein said antibody, or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising at least 90% sequence identity to the sequence of SEQ ID NO:21902 and a light chain variable region (VL) comprising at least 90% sequence identity to the sequence of SEQ ID NO:21912. 
     
     
         63 . The isolated antibody, or antigen-binding fragment thereof, of  claim 62 , comprising a VH comprising a sequence having at least 95% identity to SEQ ID NO:21902 and a VL comprising a sequence having at least 95% identity to SEQ ID NO:21912. 
     
     
         64 . The isolated antibody, or antigen-binding fragment thereof, of  claim 63 , wherein the VH comprises SEQ ID NO:21902 and the VL comprises SEQ ID NO:21912. 
     
     
         65 . The isolated antibody, or antigen-binding fragment thereof, of  claim 64 , wherein the VH consists of SEQ ID NO:21902 and the VL consists of SEQ ID NO:21912. 
     
     
         66 . The isolated antibody, or antigen-binding fragment thereof, of  claim 62 , wherein the antibody, or antigen-binding fragment thereof, cross-reacts with SARS-CoV-S and SARS-CoV-2-S. 
     
     
         67 . The isolated antibody, or antigen-binding fragment thereof, of  claim 66 , wherein SARS-CoV-S comprises an amino acid sequence of SEQ ID NO:1, and wherein SARS-CoV-2-S comprises an amino acid sequence of SEQ ID NO:5. 
     
     
         68 . The isolated antibody, or antigen-binding fragment thereof, of  claim 62 , which neutralizes SARS-CoV and/or SARS-CoV-2. 
     
     
         69 . The isolated antibody, or antigen-binding fragment thereof, of  claim 68 , which neutralizes SARS-CoV and/or SARS-CoV-2 with an IC50 of about 100 nM or lower. 
     
     
         70 . The isolated antibody, or antigen-binding fragment thereof, of  claim 62 , which binds to SARS-CoV-S with a KD value of about 100 nM or lower. 
     
     
         71 . The isolated antibody, or antigen-binding fragment thereof, of  claim 62 , wherein the antibody is human, humanized, primatized, chimeric, bispecific or multispecific. 
     
     
         72 . The isolated antibody, or antigen-binding fragment thereof, of  claim 62 , wherein the antigen-binding fragment thereof comprises a Fab, Fab2, or scFv. 
     
     
         73 . A method of treating a coronavirus infection, or treating a condition, symptom, disease, or disorder associated with said infection in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the antibody, or antigen-binding fragment thereof, of  claim 62 , thereby treating the infection. 
     
     
         74 . A method of preventing a coronavirus infection, in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the antibody, or antigen-binding fragment thereof, of  claim 62 , thereby preventing the infection. 
     
     
         75 . A method of inducing an immune response against a coronavirus in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibody, or antigen-binding fragment thereof, of  claim 62 , thereby inducing the immune response against the coronavirus. 
     
     
         76 . A method of decreasing the risk of mortality, hospitalization, mechanical ventilation, or a combination thereof, in a subject infected by a coronavirus, comprising administering to the subject a therapeutically effective amount of the antibody, or antigen-binding fragment thereof, of  claim 62 , thereby decreasing the risk of mortality, hospitalization, mechanical ventilation, or a combination thereof, in the subject.