Anti-Coronavirus Antibodies and Methods of Use

Abstract

Antibodies that bind SARS-CoV Spike protein, SARS-CoV-2 Spike protein, and methods of using same for treating or preventing conditions associated with SARS or COVID-19 and for detecting SARS-CoV or SARS-CoV-2.

1 . An antibody or antigen-binding fragment thereof that specifically binds to SARS-CoV-2 Spike protein, wherein the antibody or antigen-binding fragment thereof has comprises:
 (a) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 4949 and three CDRs of a light chain variable region set forth as SEQ ID NO: 4950; or   (b) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 3275 and three CDRs of a light chain variable region set forth as SEQ ID NO: 3276; or   (c) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 3361 and three CDRs of a light chain variable region set forth as SEQ ID NO: 3362; or   (d) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 3365 and three CDRs of a light chain variable region set forth as SEQ ID NO: 3366; or   (e) three CDRs of a heavy chain variable region set forth as SEQ ID NO:3421 and three CDRs of a light chain variable region set forth as SEQ ID NO: 3422; or   (f) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 3447 and three CDRs of a light chain variable region set forth as SEQ ID NO: 3448; or   (g) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 3515 and three CDRs of a light chain variable region set forth as SEQ ID NO: 3516; or   (h) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 3605 and three CDRs of a light chain variable region set forth as SEQ ID NO: 3606; or   (i) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 3647 and three CDRs of a light chain variable region set forth as SEQ ID NO: 3648; or   (j) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 3649 and three CDRs of a light chain variable region set forth as SEQ ID NO: 3650; or   (k) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 3725 and three CDRs of a light chain variable region set forth as SEQ ID NO: 3726; or   (l) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 3835 and three CDRs of a light chain variable region set forth as SEQ ID NO: 3836; or   (m) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 3845 and three CDRs of a light chain variable region set forth as SEQ ID NO: 3846; or   (n) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 3853 and three CDRs of a light chain variable region set forth as SEQ ID NO: 3854; or   (o) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 3873 and three CDRs of a light chain variable region set forth as SEQ ID NO: 3874; or   (p) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 5029 and three CDRs of a light chain variable region set forth as SEQ ID NO: 5030; or   (q) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 5131 and three CDRs of a light chain variable region set forth as SEQ ID NO: 5132; or   (r) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 5217 and three CDRs of a light chain variable region set forth as SEQ ID NO: 5218; or   (s) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 5311 and three CDRs of a light chain variable region set forth as SEQ ID NO: 5312.   
     
     
         2 . The antibody or antigen-binding fragment thereof of  claim 1 , wherein the antibody or fragment thereof comprises:
 (a) CDR-H1 comprising residues 31-35 of the heavy chain variable region (VH), CDR-H2 comprising residues 50-65 of the VH, and CDR-H3 comprising residues 95-102 of the VH; and   (b) CDR-L1 comprising residues 24-34 of the light chain variable region (VL), CDR-L2 comprising residues 50-56 of the VL, and CDR-L3 comprising residues 89-97 of the VL; and   wherein the CDR numbering is according to Kabat.   
     
     
         3 . The antibody or antigen-binding fragment thereof of  claim 1 , wherein the antibody or fragment thereof comprises:
 (a) CDR-H1 comprising residues 26-32 of the VH, CDR-H2 comprising residues 50-58 of the VH, and CDR-H3 comprising residues 95-102 of the VH; and   (b) CDR-L1 comprising residues 24-34 of the VL, CDR-L2 comprising residues 50-56 of the VL, and CDR-L3 comprising residues 89-97 of the VL; and   wherein the CDR numbering is according to Chothia.   
     
     
         4 . The antibody or antigen-binding fragment thereof of  claim 1 , wherein the antibody or fragment thereof comprises:
 (a) CDR-H1 comprising residues 30-35 of the VH, CDR-H2 comprising residues 47-58 of the VH, and CDR-H3 comprising residues 93-101 of the VH; and   (b) CDR-L1 comprising residues 30-36 of the VL, CDR-L2 comprising residues 46-55 of the VL, and CDR-L3 comprising the residues 89-96 of the VL; and   wherein the CDR numbering is according to MacCallum.   
     
     
         5 . The antibody or antigen-binding fragment thereof of  claim 1 , comprising a heavy chain variable region having an amino acid sequence that is at least 95% identical to the heavy chain variable region sequence set forth in (a)-(s) and a light chain variable region having an amino acid sequence that is at least 95% identical to one of the corresponding light chain variable region sequences set forth in the same (a)-(s). 
     
     
         6 . The antibody or antigen-binding fragment thereof of  claim 1 , wherein the antibody or antigen-binding fragment thereof comprises:
 (a) a heavy chain variable region set forth as SEQ ID NO: 4949 and a light chain variable region set forth as SEQ ID NO: 4950; or   (b) a heavy chain variable region set forth as SEQ ID NO: 3275 and a light chain variable region set forth as SEQ ID NO: 3276; or   (c) a heavy chain variable region set forth as SEQ ID NO: 3361 and a light chain variable region set forth as SEQ ID NO: 3362; or   (d) a heavy chain variable region set forth as SEQ ID NO: 3365 and a light chain variable region set forth as SEQ ID NO: 3366; or   (e) a heavy chain variable region set forth as SEQ ID NO: 3421 and a light chain variable region set forth as SEQ ID NO: 3422; or   (f) a heavy chain variable region set forth as SEQ ID NO: 3447 and a light chain variable region set forth as SEQ ID NO: 3448; or   (g) a heavy chain variable region set forth as SEQ ID NO: 3515 and a light chain variable region set forth as SEQ ID NO: 3516; or   (h) a heavy chain variable region set forth as SEQ ID NO: 3605 and a light chain variable region set forth as SEQ ID NO: 3606; or   (i) a heavy chain variable region set forth as SEQ ID NO: 3647 and a light chain variable region set forth as SEQ ID NO: 3648; or   (j) a heavy chain variable region set forth as SEQ ID NO: 3649 and a light chain variable region set forth as SEQ ID NO: 3650; or   (k) a heavy chain variable region set forth as SEQ ID NO: 3725 and a light chain variable region set forth as SEQ ID NO: 3726; or   (l) a heavy chain variable region set forth as SEQ ID NO: 3835 and a light chain variable region set forth as SEQ ID NO: 3836; or   (m) a heavy chain variable region set forth as SEQ ID NO: 3845 and a light chain variable region set forth as SEQ ID NO: 3846; or   (n) a heavy chain variable region set forth as SEQ ID NO: 3853 and a light chain variable region set forth as SEQ ID NO: 3854; or   (o) a heavy chain variable region set forth as SEQ ID NO: 3873 and a light chain variable region set forth as SEQ ID NO: 3874; or   (p) a heavy chain variable region set forth as SEQ ID NO: 5029 and a light chain variable region set forth as SEQ ID NO: 5030; or   (q) a heavy chain variable region set forth as SEQ ID NO: 5131 and a light chain variable region set forth as SEQ ID NO: 5132; or   (r) a heavy chain variable region set forth as SEQ ID NO: 5217 and a light chain variable region set forth as SEQ ID NO: 5218; or   (s) a heavy chain variable region set forth as SEQ ID NO: 5311 and a light chain variable region set forth as SEQ ID NO: 5312.   
     
     
         7 . The antibody of  claim 1 , wherein the antibody comprises:
 (a) a heavy chain comprising SEQ ID NO: 5735 and a light chain comprising SEQ ID NO: 5736; or   (b) a heavy chain comprising SEQ ID NO: 5707 and a light chain comprising SEQ ID NO: 5708; or   (c) a heavy chain comprising SEQ ID NO: 5709 and a light chain comprising SEQ ID NO: 5710; or   (d) a heavy chain comprising SEQ ID NO: 5711 and a light chain comprising SEQ ID NO: 5712; or   (e) a heavy chain comprising SEQ ID NO: 5713 and a light chain comprising SEQ ID NO: 5714; or   (f) a heavy chain comprising SEQ ID NO: 5715 and a light chain comprising SEQ ID NO: 5716; or   (g) a heavy chain comprising SEQ ID NO: 5717 and a light chain comprising SEQ ID NO: 5718; or   (h) a heavy chain comprising SEQ ID NO: 5719 and a light chain comprising SEQ ID NO: 5720; or   (i) a heavy chain comprising SEQ ID NO: 5721 and a light chain comprising SEQ ID NO: 5722; or   (j) a heavy chain comprising SEQ ID NO: 5723 and a light chain comprising SEQ ID NO: 5724; or   (k) a heavy chain comprising SEQ ID NO: 5725 and a light chain comprising SEQ ID NO: 5726; or   (l) a heavy chain comprising SEQ ID NO: 5727 and a light chain comprising SEQ ID NO: 5728; or   (m) a heavy chain comprising SEQ ID NO: 5729 and a light chain comprising SEQ ID NO: 5730; or   (n) a heavy chain comprising SEQ ID NO: 5731 and a light chain comprising SEQ ID NO: 5732; or   (o) a heavy chain comprising SEQ ID NO: 5733 and a light chain comprising SEQ ID NO: 5734; or   (p) a heavy chain comprising SEQ ID NO: 5737 and a light chain comprising SEQ ID NO: 5738; or   (q) a heavy chain comprising SEQ ID NO: 5739 and a light chain comprising SEQ ID NO: 5740; or   (r) a heavy chain comprising SEQ ID NO: 5741 and a light chain comprising SEQ ID NO: 5742; or   (s) a heavy chain comprising SEQ ID NO: 5743 and a light chain comprising SEQ ID NO: 5744.   
     
     
         8 . The antibody of  claim 1 , wherein the antibody has an IgG1 isotype. 
     
     
         9 . The antibody of  claim 1 , wherein the antibody has an IgG1m3 allotype. 
     
     
         10 . The antibody of  claim 1 , wherein the antibody comprises an Fc region comprising N-glycoside-linked sugar chains bound to the Fc region, wherein said sugar chains do not contain fucose. 
     
     
         11 . The antibody of  claim 1 , wherein the antibody neutralizes SARS-CoV-2. 
     
     
         12 . The antibody or antigen-binding fragment thereof of  claim 1 , which is conjugated to an immunomodulator, a cytokine, a cytotoxic agent, a chemotherapeutic agent, a diagnostic agent, an antiviral agent, an antimicrobial agent, or a drug. 
     
     
         13 . An antibody conjugate comprising the antibody or antigen-binding fragment thereof of  claim 1  conjugated to an immunomodulator, a cytokine, a cytotoxic agent, a chemotherapeutic agent, a diagnostic agent, an antiviral agent, an antimicrobial agent, or a drug. 
     
     
         14 . A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of  claim 1 , and one or more pharmaceutically acceptable carriers, diluents, or excipients. 
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein the pharmaceutical composition comprises at least one additional antibody that binds the SARS-CoV-2 Spike protein. 
     
     
         16 . The pharmaceutical composition of  claim 14 , wherein the pharmaceutical composition further comprises histidine, sodium chloride, sucrose, and polysorbate 80. 
     
     
         17 . The pharmaceutical composition of  claim 14 , wherein the pharmaceutical composition has a pH of about 6.0. 
     
     
         18 . The pharmaceutical composition of  claim 14 , wherein the pharmaceutical composition comprises 5 mM histidine, 50 mM NaCl, 6% sucrose, and 0.05% polysorbate 80 and has a pH of about 6.0. 
     
     
         19 . The pharmaceutical composition of  claim 14 , wherein the antibody concentration in the pharmaceutical composition is about 35 mg/mL to about 125 mg/mL. 
     
     
         20 . A nucleic acid encoding:
 (a) a heavy chain variable region having an amino acid sequence that is identical to one of the heavy chain variable region sequences set forth in  claim 1 ; or   (b) a light chain variable region having an amino acid sequence that is at identical to one of the light chain variable region sequences set forth in  claim 1 ; or   (c) a heavy chain variable region having an amino acid sequence that is identical to one of the heavy chain variable region sequences set forth in  claim 1  and a light chain variable region having an amino acid sequence that is at identical to the light chain variable region sequence corresponding to the heavy chain variable region sequence.   
     
     
         21 . A nucleic acid encoding the heavy chain, the light chain, or both the heavy chain and the light chain, of the antibody of  claim 1 . 
     
     
         22 . A vector comprising the nucleic acid of  claim 20 . 
     
     
         23 . A host cell comprising the nucleic acid of  claim 20 . 
     
     
         24 . A process for producing an antibody comprising:
 (a) cultivating the host cell of  claim 23  under conditions such that the antibody is expressed; and   (b) recovering the expressed antibody.   
     
     
         25 . An article of manufacture useful for diagnosing or treating a SARS-CoV-2-linked disease comprising a receptacle comprising the antibody or antigen-binding fragment thereof of  claim 1  and instructional materials for using the same to treat or diagnose the SARS-CoV-2-linked disease. 
     
     
         26 . A method of identifying a SARS-CoV-2-infected cell comprising:
 (a) contacting a cell with the antibody or antigen-binding fragment thereof of  claim 1 , which is conjugated to a detectable agent; and   (b) detecting specific binding of the antibody or antigen-binding fragment thereof to the cell.   
     
     
         27 . A method of diagnosing a SARS-CoV-2 infection in a patient comprising:
 (a) contacting a sample obtained from a patient with the antibody or antigen-binding fragment thereof of  claim 1 , which is conjugated to a detectable agent; and   (b) detecting specific binding of the antibody or antigen-binding fragment thereof to a SARS-CoV-2 antigen present in the sample.   
     
     
         28 . A method of treating or preventing a SARS-CoV-2-linked disease comprising administering to a patient a therapeutically effective amount of the antibody or antigen-binding fragment thereof of  claim 1 . 
     
     
         29 . A method of treating or preventing COVID-19 comprising administering to a patient a therapeutically effective amount of the antibody or antigen-binding fragment thereof of  claim 1 . 
     
     
         30 . A method of treating or preventing COVID-19 comprising:
 (a) contacting a sample obtained from a patient with the antibody or antigen-binding fragment thereof of  claim 1 , conjugated to a detectable agent;   (b) detecting specific binding of the antibody or antigen-binding fragment thereof to a SARS-CoV-2 antigen present in the sample; and   (c) administering to the patient a therapeutically effective amount of the antibody or antigen-binding fragment thereof of  claim 1 .   
     
     
         31 . The method of  claim 29 , wherein the antibody is administered to the patient intravenously or subcutaneously at about 35 mg to about 7000 mg. 
     
     
         32 . The method of  claim 29 , wherein the method further comprises administering to the patient another antibody that binds the SARS-CoV-2 S protein. 
     
     
         33 . The method of  claim 29 , wherein the patient has mild to moderate COVID-19. 
     
     
         34 . The method of  claim 29 , wherein the patient is at risk for contracting COVID-19. 
     
     
         35 . The method of  claim 29 , wherein the patient is at high risk for progressing to severe COVID-19 or hospitalization. 
     
     
         36 .- 38 . (canceled) 
     
     
         39 . A method of testing an anti-coronavirus vaccine, comprising:
 (a) contacting a sample of an anti-coronavirus vaccine with the antibody or antigen-binding fragment thereof of  claim 1 , conjugated to a detectable agent; and   (b) detecting specific binding of the antibody or antigen-binding fragment thereof to the anti-coronavirus vaccine present in the sample;   wherein the anti-coronavirus vaccine comprises a coronavirus subunit or fragment thereof.