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. 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 VH CDR1 comprising SEQ ID NO:21904, a VH CDR2 comprising SEQ ID NO:21906, and a VH CDR3 comprising SEQ ID NO:21908, and a light chain variable region (VL) comprising a VL CDR1 comprising SEQ ID NO:21914, a VL CDR2 comprising SEQ ID NO:21916, and a VL CDR3 comprising SEQ ID NO:21918.
2. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein the VH comprises SEQ ID NO:21902 and the VL comprises SEQ ID NO:21912.
3. The isolated antibody, or antigen-binding fragment thereof, of claim 2 , wherein the VH consists of SEQ ID NO:21902 and the VL consists of SEQ ID NO:21912.
4. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein the CoV-S is a spike protein of SARS-CoV (“SARS-CoV-S”) or a spike protein of SARS-CoV-2 (“SARS-CoV-2-S”).
5. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antibody, or antigen-binding fragment thereof, cross-reacts with SARS-CoV-S and SARS-CoV-2-S.
6. The isolated antibody, or antigen-binding fragment thereof, of claim 5 , 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.
7. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , which neutralizes SARS-CoV and/or SARS-CoV-2.
8. The isolated antibody, or antigen-binding fragment thereof, of claim 7 , which neutralizes SARS-CoV and/or SARS-CoV-2 with an IC50 of about 100 nM or lower.
9. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , which binds to SARS-CoV-S with a K D value of about 100 nM or lower.
10. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antibody is human, humanized, primatized, chimeric, bispecific or multispecific.
11. The isolated antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antigen-binding fragment thereof comprises a Fab, Fab2, or scFv.
12. A pharmaceutical composition comprising the antibody, or antigen-binding fragment thereof, of claim 1 , and a pharmaceutically acceptable carrier.
13. A pharmaceutical composition comprising the antibody, or antigen-binding fragment thereof, of claim 2 , and a pharmaceutically acceptable carrier.
14. A pharmaceutical composition comprising the antibody, or antigen-binding fragment thereof, of claim 3 , and a pharmaceutically acceptable carrier.
15. The pharmaceutical composition of claim 12 , further comprising a second antibody, or antigen-binding fragment thereof, wherein the second antibody, or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising a VH CDR1 comprising SEQ ID NO:22304, a VH CDR2 comprising SEQ ID NO:22306, and a VH CDR3 comprising SEQ ID NO:22308, and a light chain variable region (VL) comprising a VL CDR1 comprising SEQ ID NO:22314, a VL CDR2 comprising SEQ ID NO:22316, and a VL CDR3 comprising SEQ ID NO:22318.
16. The pharmaceutical composition of claim 15 , wherein the VH of the second antibody, or antigen-binding fragment thereof, comprises SEQ ID NO:22302 and wherein the VL of the second antibody, or antigen-binding fragment thereof, comprises SEQ ID NO:22312.
17. The pharmaceutical composition of claim 16 , wherein the VH of the second antibody, or antigen-binding fragment thereof, consists of SEQ ID NO:22302 and wherein the VL of the second antibody, or antigen-binding fragment thereof, consists SEQ ID NO:22312.
18. The pharmaceutical composition of claim 13 , further comprising a second antibody, or antigen-binding fragment thereof, wherein the second antibody, or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising a VH CDR1 comprising SEQ ID NO:22304, a VH CDR2 comprising SEQ ID NO:22306, and a VH CDR3 comprising SEQ ID NO:22308, and a light chain variable region (VL) comprising a VL CDR1 comprising SEQ ID NO:22314, a VL CDR2 comprising SEQ ID NO:22316, and a VL CDR3 comprising SEQ ID NO:22318.
19. The pharmaceutical composition of claim 18 , wherein the VH of the second antibody, or antigen-binding fragment thereof, comprises SEQ ID NO:22302 and wherein the VL of the second antibody, or antigen-binding fragment thereof, comprises SEQ ID NO:22312.
20. The pharmaceutical composition of claim 19 , wherein the VH of the second antibody, or antigen-binding fragment thereof, consists of SEQ ID NO:22302 and wherein the VL of the second antibody, or antigen-binding fragment thereof, consists SEQ ID NO:22312.
21. The pharmaceutical composition of claim 14 , further comprising a second antibody, or antigen-binding fragment thereof, wherein the second antibody, or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising a VH CDR1 comprising SEQ ID NO:22304, a VH CDR2 comprising SEQ ID NO:22306, and a VH CDR3 comprising SEQ ID NO:22308, and a light chain variable region (VL) comprising a VL CDR1 comprising SEQ ID NO:22314, a VL CDR2 comprising SEQ ID NO:22316, and a VL CDR3 comprising SEQ ID NO:22318.
22. The pharmaceutical composition of claim 21 , wherein the VH of the second antibody, or antigen-binding fragment thereof, comprises SEQ ID NO:22302 and wherein the VL of the second antibody, or antigen-binding fragment thereof, comprises SEQ ID NO:22312.
23. The pharmaceutical composition of claim 22 , wherein the VH of the second antibody, or antigen-binding fragment thereof, consists of SEQ ID NO:22302 and wherein the VL of the second antibody, or antigen-binding fragment thereof, consists SEQ ID NO:22312.