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 a SARS-CoV-2 spike protein, wherein the antibody or antigen-binding fragment thereof comprises:
 (a) three CDRs of a heavy chain variable region (VH) set forth as SEQ ID NO: 729 and three CDRs of a light chain variable region (VL) set forth as SEQ ID NO: 730; or   (b) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 763 and three CDRs of a light chain variable region set forth as SEQ ID NO: 764; or   (c) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 873 and three CDRs of a light chain variable region set forth as SEQ ID NO: 874; or   (d) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 891 and three CDRs of a light chain variable region set forth as SEQ ID NO: 892; or   (e) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 921 and three CDRs of a light chain variable region set forth as SEQ ID NO: 922; or   (f) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 961 and three CDRs of a light chain variable region set forth as SEQ ID NO: 962; or   (g) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 973 and three CDRs of a light chain variable region set forth as SEQ ID NO: 974; or   (h) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 979 and three CDRs of a light chain variable region set forth as SEQ ID NO: 980; or   (i) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 983 and three CDRs of a light chain variable region set forth as SEQ ID NO: 984; or   (e) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 1029 and three CDRs of a light chain variable region set forth as SEQ ID NO: 1030; or   (k) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 1035 and three CDRs of a light chain variable region set forth as SEQ ID NO: 1036; or   (l) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 1039 and three CDRs of a light chain variable region set forth as SEQ ID NO: 1040; or   (m) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 1069 and three CDRs of a light chain variable region set forth as SEQ ID NO: 1070; or   (n) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 1103 and three CDRs of a light chain variable region set forth as SEQ ID NO: 1104; or   (o) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 1107 and three CDRs of a light chain variable region set forth as SEQ ID NO: 1108; or   (p) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 1111 and three CDRs of a light chain variable region set forth as SEQ ID NO: 1112; or   (q) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 1121 and three CDRs of a light chain variable region set forth as SEQ ID NO: 1122; or   (r) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 1133 and three CDRs of a light chain variable region set forth as SEQ ID NO: 1134; or   (s) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 1157 and three CDRs of a light chain variable region set forth as SEQ ID NO: 1158; or   (t) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 1225 and three CDRs of a light chain variable region set forth as SEQ ID NO: 1226; or   (u) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 1243 and three CDRs of a light chain variable region set forth as SEQ ID NO: 1244; or   (v) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 1251 and three CDRs of a light chain variable region set forth as SEQ ID NO: 1252; or   (w) three CDRs of a heavy chain variable region set forth as SEQ ID NO: 1269 and three CDRs of a light chain variable region set forth as SEQ ID NO: 1270.   
     
     
         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 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 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 90% identical to the heavy chain variable region sequence set forth in (a)-(x) and a light chain variable region having an amino acid sequence that is at least 90% identical to one of the corresponding light chain variable region sequences set forth in the same (a)-(x). 
     
     
         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: 729 and a light chain variable region set forth as SEQ ID NO: 730; or   (b) a heavy chain variable region set forth as SEQ ID NO: 763 and a light chain variable region set forth as SEQ ID NO: 764; or   (c) a heavy chain variable region set forth as SEQ ID NO: 873 and a light chain variable region set forth as SEQ ID NO: 874; or   (d) a heavy chain variable region set forth as SEQ ID NO: 891 and a light chain variable region set forth as SEQ ID NO: 892; or   (e) a heavy chain variable region set forth as SEQ ID NO: 921 and a light chain variable region set forth as SEQ ID NO: 922; or   (f) a heavy chain variable region set forth as SEQ ID NO: 961 and a light chain variable region set forth as SEQ ID NO: 962; or   (g) a heavy chain variable region set forth as SEQ ID NO: 973 and a light chain variable region set forth as SEQ ID NO: 974; or   (h) a heavy chain variable region set forth as SEQ ID NO: 979 and a light chain variable region set forth as SEQ ID NO: 980; or   (i) a heavy chain variable region set forth as SEQ ID NO: 983 and a light chain variable region set forth as SEQ ID NO: 984; or   (j) a heavy chain variable region set forth as SEQ ID NO: 1029 and a light chain variable region set forth as SEQ ID NO: 1030; or   (k) a heavy chain variable region set forth as SEQ ID NO: 1035 and a light chain variable region set forth as SEQ ID NO: 1036; or   (l) a heavy chain variable region set forth as SEQ ID NO: 1039 and a light chain variable region set forth as SEQ ID NO: 1040; or   (m) a heavy chain variable region set forth as SEQ ID NO: 1069 and a light chain variable region set forth as SEQ ID NO: 1070; or   (n) a heavy chain variable region set forth as SEQ ID NO: 1103 and a light chain variable region set forth as SEQ ID NO: 1104; or   (o) a heavy chain variable region set forth as SEQ ID NO: 1107 and a light chain variable region set forth as SEQ ID NO: 1108; or   (p) a heavy chain variable region set forth as SEQ ID NO: 1111 and a light chain variable region set forth as SEQ ID NO: 1112; or   (q) a heavy chain variable region set forth as SEQ ID NO: 1121 and a light chain variable region set forth as SEQ ID NO: 1122; or   (r) a heavy chain variable region set forth as SEQ ID NO: 1133 and a light chain variable region set forth as SEQ ID NO: 1134; or   (s) a heavy chain variable region set forth as SEQ ID NO: 1157 and a light chain variable region set forth as SEQ ID NO: 1158; or   (t) a heavy chain variable region set forth as SEQ ID NO: 1225 and a light chain variable region set forth as SEQ ID NO: 1226; or   (u) a heavy chain variable region set forth as SEQ ID NO: 1243 and a light chain variable region set forth as SEQ ID NO: 1244; or   (v) a heavy chain variable region set forth as SEQ ID NO: 1251 and a light chain variable region set forth as SEQ ID NO: 1252; or   (w) a heavy chain variable region set forth as SEQ ID NO: 1269 and a light chain variable region set forth as SEQ ID NO: 1270.   
     
     
         7 . The antibody of  claim 1 , wherein the antibody comprises:
 (a) a heavy chain comprising SEQ ID NO: 5319 and a light chain comprising SEQ ID NO: 5320; or   (b) a heavy chain comprising SEQ ID NO: 5321 and a light chain comprising SEQ ID NO: 5322; or   (c) a heavy chain comprising SEQ ID NO: 5323 and a light chain comprising SEQ ID NO: 5324; or   (d) a heavy chain comprising SEQ ID NO: 5325 and a light chain comprising SEQ ID NO: 5326; or   (e) a heavy chain comprising SEQ ID NO: 5327 and a light chain comprising SEQ ID NO: 5328; or   (f) a heavy chain comprising SEQ ID NO: 5329 and a light chain comprising SEQ ID NO: 5330; or   (g) a heavy chain comprising SEQ ID NO: 5331 and a light chain comprising SEQ ID NO: 5332; or   (h) a heavy chain comprising SEQ ID NO: 5333 and a light chain comprising SEQ ID NO: 5334; or   (i) a heavy chain comprising SEQ ID NO: 5335 and a light chain comprising SEQ ID NO: 5336; or   (j) a heavy chain comprising SEQ ID NO: 5337 and a light chain comprising SEQ ID NO: 5338; or   (k) a heavy chain comprising SEQ ID NO: 5339 and a light chain comprising SEQ ID NO: 5340; or   (l) a heavy chain comprising SEQ ID NO: 5341 and a light chain comprising SEQ ID NO: 5342; or   (m) a heavy chain comprising SEQ ID NO: 5343 and a light chain comprising SEQ ID NO: 5344; or   (n) a heavy chain comprising SEQ ID NO: 5345 and a light chain comprising SEQ ID NO: 5346; or   (o) a heavy chain comprising SEQ ID NO: 5347 and a light chain comprising SEQ ID NO: 5348;   (p) a heavy chain comprising SEQ ID NO: 5349 and a light chain comprising SEQ ID NO: 5350; or   (g) a heavy chain comprising SEQ ID NO: 5351 and a light chain comprising SEQ ID NO: 5352; or   (r) a heavy chain comprising SEQ ID NO: 5353 and a light chain comprising SEQ ID NO: 5354; or   (s) a heavy chain comprising SEQ ID NO: 5355 and a light chain comprising SEQ ID NO: 5356; or   (t) a heavy chain comprising SEQ ID NO: 5357 and a light chain comprising SEQ ID NO: 5358; or   (u) a heavy chain comprising SEQ ID NO: 5359 and a light chain comprising SEQ ID NO: 5360; or   (v) a heavy chain comprising SEQ ID NO: 5361 and a light chain comprising SEQ ID NO: 5362; or   (w) a heavy chain comprising SEQ ID NO: 5365 and a light chain comprising SEQ ID NO: 5366.   
     
     
         8 .- 15 . (canceled) 
     
     
         16 . The antibody of  claim 1 , wherein the antibody has an IgG1m3 allotype. 
     
     
         17 . The antibody of  claim 16 , wherein the antibody comprises an Fc region comprising N-glycoside-linked sugar chains bound to the Fc region, wherein the sugar chains do not contain fucose. 
     
     
         18 .- 23 . (canceled) 
     
     
         24 . The antibody or antigen-binding fragment thereof of  claim 1 , which comprises at least one amino acid substitution. 
     
     
         25 . The antibody or antigen-binding fragment thereof of  claim 24 , wherein the at least one amino acid substitution is a conservative substitution. 
     
     
         26 . The antibody or antigen-binding fragment thereof of  claim 24 , wherein the at least one amino acid substitution is a substitution of an amino acid for a non-genetically encoded amino acid or a synthetic amino acid. 
     
     
         27 . 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. 
     
     
         28 . 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. 
     
     
         29 . A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of  claim 1 , and one or more pharmaceutically acceptable carriers, diluents, or excipients. 
     
     
         30 . The pharmaceutical composition of  claim 29 , wherein the pharmaceutical composition comprises at least one additional antibody that binds the SARS-CoV-2 spike protein. 
     
     
         31 . The pharmaceutical composition of  claim 29 , wherein the pharmaceutical composition further comprises histidine, sodium chloride, sucrose, and polysorbate 80. 
     
     
         32 . The pharmaceutical composition of  claim 29 , wherein the pharmaceutical composition has a pH of about 6.0. 
     
     
         33 . The pharmaceutical composition of  claim 29 , 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. 
     
     
         34 . The pharmaceutical composition of  claim 29 , wherein the antibody concentration in the pharmaceutical composition is about 35 mg/mL to about 125 mg/mL. 
     
     
         35 .- 37 . (canceled) 
     
     
         38 . 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 . 
     
     
         39 . A vector comprising the nucleic acid of  claim 38 . 
     
     
         40 . A host cell comprising the nucleic acid of  claim 38 . 
     
     
         41 . A process for producing an antibody comprising:
 (a) cultivating the host cell of  claim 40  under conditions such that the antibody is expressed; and   (b) recovering the expressed antibody.   
     
     
         42 . An article of manufacture useful for diagnosing or treating a SARS-Co-V or SARS-Co-V-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-Co-V or SARS-Co-V-2-linked disease. 
     
     
         43 . A method of identifying a SARS-Co-V or 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.   
     
     
         44 . A method of diagnosing a SARS-Co-V or 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-Co-V or SARS-CoV-2 antigen present in the sample.   
     
     
         45 . A method of treating or preventing a SARS-Co-V or SARS-Co-V-2-linked disease comprising administering to a patient a therapeutically effective amount of the antibody or antigen-binding fragment thereof of  claim 1 . 
     
     
         46 . 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 . 
     
     
         47 . 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 .   
     
     
         48 . The method of  claim 46 , wherein the antibody is administered to the patient intravenously or subcutaneously at about 700 mg to about 7000 mg. 
     
     
         49 . (canceled) 
     
     
         50 . The method of  claim 46 , wherein the method further comprises administering to the patient another antibody that binds the SARS-CoV-2 S protein. 
     
     
         51 .- 56 . (canceled) 
     
     
         57 . 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.