Antibodies against sars-cov-2 and methods of using the same

Abstract

The instant disclosure provides antibodies and antigen-binding fragments thereof that can bind to a SARS-CoV-2 antigen and, in certain embodiments, are capable of neutralizing a SARS-CoV-2 infection. Also provided are polynucleotides that encode an antibody or antigen-binding fragment, vectors and host cells that comprise a polynucleotide, pharmaceutical compositions, and methods of using the presently disclosed antibodies, antigen-binding fragments, polynucleotides, vectors, host cells, and compositions to treat or diagnose a SARS-CoV-2 infection.

What is claimed is: 
     
         1 - 30 . (canceled) 
     
     
         31 . A composition comprising:
 (1) an anti-SARS-CoV-2 antibody or an antigen-binding fragment thereof, comprising a heavy chain variable domain (VH) that comprises the complementarity determining region (CDR)H1 amino acid sequence set forth in SEQ ID NO.:106, the CDRH2 amino acid sequence set forth in SEQ ID NO.:121, and the CDRH3 amino acid sequence set forth in SEQ ID NO.:108, and a light chain variable domain (VL) that comprises the CDRL1 amino acid sequence set forth in SEQ ID NO.:169, the CDRL2 amino acid sequence set forth in SEQ ID NO.:170, and the CDRL3 amino acid sequence set forth in SEQ ID NO.:171; and   (2) a pharmaceutically acceptable excipient, carrier, or diluent.   
     
     
         32 . The composition of  claim 31 , wherein:
 (i) the VH comprises or consists of an amino acid sequence having at least 85% identity to the amino acid sequence set forth in SEQ ID NO.:113; and/or   (ii) the VL comprises or consists of an amino acid sequence having at least 85% identity to the amino acid sequence set forth in SEQ ID NO.:168.   
     
     
         33 . The composition of  claim 31 , wherein:
 (i) the VH comprises or consists of an amino acid sequence having at least 90% identity to the amino acid sequence set forth in SEQ ID NO.:113; and/or   (ii) the VL comprises or consists of an amino acid sequence having at least 90% identity to the amino acid sequence set forth in SEQ ID NO.:168.   
     
     
         34 . The composition of  claim 31 , wherein:
 (i) the VH comprises or consists of an amino acid sequence having at least 95% identity to the amino acid sequence set forth in SEQ ID NO.:113; and/or   (ii) the VL comprises or consists of an amino acid sequence having at least 95% identity to the amino acid sequence set forth in SEQ ID NO.:168.   
     
     
         35 . The composition of  claim 31 , wherein:
 (i) the VH comprises or consists of an amino acid sequence having at least 99% identity to the amino acid sequence set forth in SEQ ID NO.:113; and/or   (ii) the VL comprises or consists of an amino acid sequence having at least 99% identity to the amino acid sequence set forth in SEQ ID NO.:168.   
     
     
         36 . The composition of  claim 31 , wherein the anti-SARS-CoV-2 antibody or antigen-binding fragment further comprises a Fc polypeptide or a fragment thereof. 
     
     
         37 . The composition of  claim 36 , wherein the Fc polypeptide or fragment thereof comprises:
 (i) a mutation that enhances binding to a FcRn as compared to a reference Fc polypeptide that does not comprise the mutation; and/or   (ii) a mutation that enhances binding to a FcγR as compared to a reference Fc polypeptide that does not comprise the mutation.   
     
     
         38 . The composition of  claim 37 , wherein the mutation that enhances binding to a FcRn comprises:
 (i) M428L/N434S;   (ii) M252Y/S254T/T256E;   (iii) T250Q/M428L;   (iv) P257I/Q311I;   (v) P257I/N434H;   (vi) D376V/N434H;   (vii) T307A/E380A/N434A; or   (viii) any combination of (i)-(vii).   
     
     
         39 . The composition of  claim 38 , wherein the mutation that enhances binding to a FcRn comprises M428L/N434S. 
     
     
         40 . The composition of  claim 37 , wherein the mutation that enhances binding to a FcγR comprises S239D, I332E, A330L, G236A, or any combination thereof. 
     
     
         41 . The composition of  claim 40 , wherein the mutation that enhances binding to a FcγR comprises:
 (i) S239D/I332E; 
 (ii) S239D/A330L/I332E; 
 (iii) G236A/S239D/I332E; or 
 (iv) G236A/A330L/I332E. 
 
     
     
         42 . The composition of  claim 41 , wherein the mutation that enhances binding to a FcγR comprises G236A/A330L/I332E. 
     
     
         43 . The composition of  claim 31 , wherein the anti-SARS-CoV-2 antibody or antigen-binding fragment comprises two heavy (H) chains and two light (L) chains, wherein each of the two heavy chains comprises a VH as in  claim 31  and each of the two light chains comprises a VL as in  claim 31 . 
     
     
         44 . A composition comprising:
 (1) an anti-SARS-CoV-2 antibody or an antigen-binding fragment thereof, comprising a heavy chain variable domain (VH) that comprises or consists of the amino acid sequence set forth in SEQ ID NO.: 113, and a light chain variable domain (VL) that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:168; and   (2) a pharmaceutically acceptable excipient, carrier, or diluent.   
     
     
         45 . The composition of  claim 44 , wherein the anti-SARS-CoV-2 antibody or antigen-binding fragment further comprises a Fc polypeptide or a fragment thereof. 
     
     
         46 . The composition of  claim 45 , wherein the Fc polypeptide or fragment thereof comprises:
 (i) a mutation that enhances binding to a FcRn as compared to a reference Fc polypeptide that does not comprise the mutation; and/or   (ii) a mutation that enhances binding to a FcγR as compared to a reference Fc polypeptide that does not comprise the mutation.   
     
     
         47 . The composition of  claim 46 , wherein the mutation that enhances binding to a FcRn comprises:
 (i) M428L/N434S;   (ii) M252Y/S254T/T256E;   (iii) T250Q/M428L;   (iv) P257I/Q311I;   (v) P257I/N434H;   (vi) D376V/N434H;   (vii) T307A/E380A/N434A; or   (viii) any combination of (i)-(vii).   
     
     
         48 . The composition of  claim 47 , wherein the mutation that enhances binding to a FcRn comprises M428L/N434S. 
     
     
         49 . The composition of  claim 46 , wherein the mutation that enhances binding to a FcγR comprises S239D, I332E, A330L, G236A, or any combination thereof. 
     
     
         50 . The composition of  claim 49 , wherein the mutation that enhances binding to a FcγR comprises:
 (i) S239D/I332E; 
 (ii) S239D/A330L/I332E; 
 (iii) G236A/S239D/I332E; or 
 (iv) G236A/A330L/I332E. 
 
     
     
         51 . The composition of  claim 50 , wherein the mutation that enhances binding to a FcγR comprises G236A/A330L/I332E. 
     
     
         52 . The composition of  claim 44 , wherein the anti-SARS-CoV-2 antibody or antigen-binding fragment comprises two heavy (H) chains and two light (L) chains, wherein each of the two heavy chains comprises as VH as in  claim 44  and each of the two light chains comprises a VL as in  claim 44 . 
     
     
         53 . The composition of  claim 44 , wherein the anti-SARS-CoV-2 antibody or antigen-binding fragment comprises:
 (i) a heavy chain comprising (i)(1) a VH that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:113, and (i)(2) a CH1-CH3 that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:173; and   (ii) a light chain comprising (ii)(1) a VL that comprises or consists of the amino acid sequence set forth in SEQ ID NO.: 168, and (ii)(2) a CL that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:174.   
     
     
         54 . The composition of  claim 44 , wherein the anti-SARS-CoV-2 antibody or antigen-binding fragment comprises:
 (i) two heavy chains, each comprising (i)(1) a VH that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:113, and (i)(2) a CH1-CH3 that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:173; and   (ii) two light chains, each comprising (ii)(1) a VL that comprises or consists of the amino acid sequence set forth in SEQ ID NO.: 168, and (ii)(2) a CL that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:174.   
     
     
         55 . The composition of  claim 44 , wherein the anti-SARS-CoV-2 antibody or antigen-binding fragment comprises:
 (i) a heavy chain comprising (i)(1) a VH that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:113, and (i)(2) a CH1-CH3 that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:175; and   (ii) a light chain comprising (ii)(1) a VL that comprises or consists of the amino acid sequence set forth in SEQ ID NO.: 168, and (ii)(2) a CL that comprises or consists of the amino acid sequence set forth in SEQ ID NO.:174.   
     
     
         56 . An anti-SARS-CoV-2 antibody or an antigen-binding fragment thereof, comprising a heavy chain variable domain (VH) that comprises the complementarity determining region (CDR)H1 amino acid sequence set forth in SEQ ID NO.:106, the CDRH2 amino acid sequence set forth in SEQ ID NO.:107, and the CDRH3 amino acid sequence set forth in SEQ ID NO.:108, and a light chain variable domain (VL) that comprises the CDRL1 amino acid sequence set forth in SEQ ID NO.:169, the CDRL2 amino acid sequence set forth in SEQ ID NO.:170, and the CDRL3 amino acid sequence set forth in SEQ ID NO.:171. 
     
     
         57 . A composition comprising:
 (1) the anti-SARS-CoV-2 antibody or antigen-binding fragment of  claim 56 ; and   (2) a pharmaceutically acceptable carrier, excipient, or diluent.