COMPOUNDS SPECIFIC TO CORONAVIRUS S PROTEIN AND USES THEREOF
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.