Anti-SARS-CoV-2 antigen-binding polypeptide, polypeptide complex, and method of using the same

Abstract

Antigen-binding polypeptides and antigen-binding polypeptide complexes (e.g., antibodies and antigen-binding fragments thereof) having certain structural and / or functional features are disclosed. Also disclosed are polynucleotides and vectors encoding such polypeptides and polypeptide complexes; host cells, pharmaceutical compositions and kits containing such polypeptides and polypeptide complexes; and methods of using such polypeptides and polypeptide complexes.

Claims

1. VL1 - L1 - VL2 - L2 - VH2 - L3 - VH1; VL1 - L1 - VH2 - L2 - VL2 - L3 - VH1; VH1 - L4 - VH2 - L5 - VL2 - L6 - VL1; or VH1 - L4 - VL2 - L5 - VH2 - L6 - VL1 An antigen - binding polypeptide having a structure represented by; wherein VL1 is a first immunoglobulin light - chain variable region that specifically binds to a severe acute respiratory syndrome coronavirus 2 (SARS - CoV - 2) protein; VL2 is a second immunoglobulin light - chain variable region that specifically binds to a SARS - CoV - 2 protein; VH1 is a first immunoglobulin heavy - chain variable region that specifically binds to a SARS - CoV - 2 protein; VH2 is a second immunoglobulin heavy - chain variable region that specifically binds to a SARS - CoV - 2 protein; and L1 to L6 are amino - acid linkers, said antigen - binding polypeptide.

2. The formula: VL1 - L1 - VL2 - L2 - VH2 - L3 - VH1; or VH1 - L4 - VH2 - L5 - VL2 - L6 - VL1 having, wherein VL1 is a first immunoglobulin light - chain variable region that specifically binds to a severe acute respiratory syndrome coronavirus 2 (SARS - CoV - 2) protein; VL2 is a second immunoglobulin light - chain variable region that specifically binds to a SARS - CoV - 2 protein; VH1 is a first immunoglobulin heavy - chain variable region that specifically binds to a SARS - CoV - 2 protein; VH2 is a second immunoglobulin heavy - chain variable region that specifically binds to a SARS - CoV - 2 protein; and L1 to L6 are amino - acid linkers, the antigen - binding polypeptide according to claim 1.

3. An antigen - binding polypeptide complex comprising a first polypeptide and a second polypeptide; wherein the first polypeptide has a structure represented by VL1 - L1 - VL2 - L2 - VH2 - L3 - VH1; has a structure represented by VL1 - L1 - VH2 - L2 - VL2 - L3 - VH1; VH1-L4-VH2-L5-VL2-L6-VL1; or has a structure represented by VH1 - L4 - VL2 - L5 - VH2 - L6 - VL1 ; wherein the second polypeptide has a structure represented by VL3 - L7 - VL4 - L8 - VH4 - L9 - VH3; has a structure represented by VL3 - L7 - VH4 - L8 - VL4 - L9 - VH3; has a structure represented by VH3 - L10 - VH4 - L11 - VL4 - L12 - VL3; or has a structure represented by VH3 - L10 - VL4 - L11 - VH4 - L12 - VL3 having a structure represented by; wherein, VL1 is the first immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL2 is the second immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL3 is the third immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL4 is the fourth immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VH1 is the first immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH2 is the second immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH3 is the third immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH4 is the fourth immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; and L1 to L12 are amino acid linkers, the antigen-binding polypeptide complex.

4. comprising a first polypeptide and a second polypeptide; the first polypeptide VL1 - L1 - VL2 - L2 - VH2 - L3 - VH1; or having a structure represented by VH1-L4-VH2-L5-VL2-L6-VL1; the second polypeptide is VL3-L7-VL4-L8-VH4-L9-VH3; or having a structure represented by VH3-L10-VH4-L11-VL4-L12-VL3 wherein, VL1 is the first immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL2 is the second immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL3 is the third immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL4 is the fourth immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VH1 is the first immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH2 is the second immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH3 is the third immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH4 is the fourth immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH4 is the fourth immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; and L1 to L12 are amino acid linkers, The antigen-binding polypeptide complex according to claim 3.

5. VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc; VL1-L1-VH2-L2-VL2-L3-VH1-L4-Fc; VH1-L5-VH2-L6-VL2-L7-VL1-L8-Fc; or VH1-L5-VL2-L6-VH2-L7-VL1-L8-Fc An antigen-binding polypeptide having a structure represented by; Here, VL1 is the first immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL2 is the second immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VH1 is the first immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH2 is the second immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; Fc is a region containing immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1 to L8 are amino acid linkers, The antigen-binding polypeptide.

6. VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc; Or VH1-L5-VH2-L6-VL2-L7-VL1-L8-Fc Having a structure represented by; Here, VL1 is the first immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL2 is the second immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VH1 is the first immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH2 is the second immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; Fc is a region containing immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1 to L8 are amino acid linkers, The antigen-binding polypeptide according to claim 5.

7. An antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; The first polypeptide is, VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc; VL1-L1-VH2-L2-VL2-L3-VH1-L4-Fc; VH1-L5-VH2-L6-VL2-L7-VL1-L8-Fc; or VH1-L5-VL2-L6-VH2-L7-VL1-L8-Fc having a structure represented by; said second polypeptide is, Fc; VL3-L9-VL4-L10-VH4-L11-VH3-L12-Fc; VL3-L9-VH4-L10-VL4-L11-VH3-L12-Fc; VH3-L13-VH4-L14-VL4-L15-VL3-L16-Fc; or VH3-L13-VL4-L14-VH4-L15-VL3-L16-Fc having a structure represented by; wherein, VL1 is the first immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL2 is the second immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL3 is the third immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL4 is the fourth immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VH1 is the first immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH2 is the second immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH3 is the third immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH4 is the fourth immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; Fc is a region containing immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1 to L16 are amino acid linkers, said antigen-binding polypeptide complex.

8. comprising a first polypeptide and a second polypeptide; said first polypeptide is, VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc; or VH1-L5-VH2-L6-VL2-L7-VL1-L8-Fc having a structure represented by; said second polypeptide is, Fc; VL3-L9-VL4-L10-VH4-L11-VH3-L12-Fc; or VH3-L13-VH4-L14-VL4-L15-VL3-L16-Fc having a structure represented by; wherein, VL1 is the first immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL2 is the second immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL3 is the third immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL4 is the fourth immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VH1 is the first immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH2 is the second immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH3 is the third immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH4 is the fourth immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; Fc is a region containing immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; L1 to L16 are amino acid linkers, The antigen-binding polypeptide complex according to claim 7.

9. VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL; VL1-L1-VH2-L2-VL2-L3-VH1-L4-CH1-L5-CL; VH1-L6-VH2-L7-VL2-L8-VL1-L9-CH1-L10-CL; VH1-L6-VL2-L7-VH2-L8-VL1-L9-CH1-L10-CL; VL1-L11-VL2-L12-VH2-L13-VH1-L14-CL-L15-CH1; VL1-L11-VH2-L12-VL2-L13-VH1-L14-CL-L15-CH1; VH1-L16-VH2-L17-VL2-L18-VL1-L19-CL-L20-CH1; or VH1-L16-VL2-L17-VH2-L18-VL1-L19-CL-L20-CH1 An antigen-binding polypeptide having a structure represented by; Here, VL1 is the first immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL2 is the second immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VH1 is the first immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH2 is the second immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; CH1 is the immunoglobulin heavy chain constant region 1; CL is the immunoglobulin light chain constant region; and L1 to L20 are amino acid linkers, the antigen-binding polypeptide. **Claim 10** VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL; VH1-L6-VH2-L7-VL2-L8-VL1-L9-CH1-L10-CL; VL1 - L11 - VL2 - L12 - VH2 - L13 - VH1 - L14 - CL - L15 - CH1; or VH1-L16-VH2-L17-VL2-L18-VL1-L19-CL-L20-CH1 having a structure represented by; wherein, VL1 is the first immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL2 is the second immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VH1 is the first immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH2 is the second immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; CH1 is the immunoglobulin heavy chain constant region 1; CL is the immunoglobulin light chain constant region; and L1 to L20 are amino acid linkers, the antigen-binding polypeptide according to claim 9. **Claim 11** An antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide, wherein; the first polypeptide is VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL; VL1-L1-VH2-L2-VL2-L3-VH1-L4-CH1-L5-CL; VH1-L6-VH2-L7-VL2-L8-VL1-L9-CH1-L10-CL; VH1-L6-VL2-L7-VH2-L8-VL1-L9-CH1-L10-CL; VL1-L11-VL2-L12-VH2-L13-VH1-L14-CL-L15-CH1; VL1-L11-VH2-L12-VL2-L13-VH1-L14-CL-L15-CH1; VH1-L16-VH2-L17-VL2-L18-VL1-L19-CL-L20-CH1; or VH1-L16-VL2-L17-VH2-L18-VL1-L19-CL-L20-CH1 having a structure represented by; the second polypeptide is VL3-L21-VL4-L22-VH4-L23-VH3-L24-CH1-L25-CL; VL3-L21-VH4-L22-VL4-L23-VH3-L24-CH1-L25-CL; VH3-L26-VH4-L27-VL4-L28-VL3-L29-CH1-L30-CL; VH3-L26-VL4-L27-VH4-L28-VL3-L29-CH1-L30-CL; VL3-L31-VL4-L32-VH4-L33-VH3-L34-CL-L35-CH1; VL3-L31-VH4-L32-VL4-L33-VH3-L34-CL-L35-CH1; VH3-L36-VH4-L37-VL4-L38-VL3-L39-CL-L40-CH1; or VH3-L36-VL4-L37-VH4-L38-VL3-L39-CL-L40-CH1 and has a structure represented by; wherein, VL1 is a first immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL4 is a fourth immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; CH1 is an immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1 to L40 are amino acid linkers, the antigen-binding polypeptide complex.

12. comprising a first polypeptide and a second polypeptide; the first polypeptide is VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL; VH1-L6-VH2-L7-VL2-L8-VL1-L9-CH1-L10-CL; VL1 - L11 - VL2 - L12 - VH2 - L13 - VH1 - L14 - CL - L15 - CH1; or VH1-L16-VH2-L17-VL2-L18-VL1-L19-CL-L20-CH1 has a structure represented by; said second polypeptide is VL3-L21-VL4-L22-VH4-L23-VH3-L24-CH1-L25-CL; VH3-L26-VH4-L27-VL4-L28-VL3-L29-CH1-L30-CL; VL3-L31-VL4-L32-VH4-L33-VH3-L34-CL-L35-CH1; or VH3-L36-VH4-L37-VL4-L38-VL3-L39-CL-L40-CH1 has a structure represented by; wherein VL1 is the first immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL2 is the second immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL3 is the third immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL4 is the fourth immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VH1 is the first immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH2 is the second immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH3 is the third immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH4 is the fourth immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; CH1 is the immunoglobulin heavy chain constant region 1; CL is the immunoglobulin light chain constant region; and L1 to L40 are amino acid linkers, The antigen-binding polypeptide complex according to claim 11.

13. VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-L6-Fc; VL1-L1-VH2-L2-VL2-L3-VH1-L4-CH1-L5-CL-L6-Fc; VH1-L7-VH2-L8-VL2-L9-VL1-L10-CH1-L11-CL-L12-Fc; VH1-L7-VL2-L8-VH2-L9-VL1-L10-CH1-L11-CL-L12-Fc; VL1-L13-VL2-L14-VH2-L15-VH1-L16-CL-L17-CH1-L18-Fc; VL1-L13-VH2-L14-VL2-L15-VH1-L16-CL-L17-CH1-L18-Fc; VH1-L19-VH2-L20-VL2-L21-VL1-L22-CL-L23-CH1-L24-Fc; or VH1-L19-VL2-L20-VH2-L21-VL1-L22-CL-L23-CH1-L24-Fc An antigen-binding polypeptide having a structure represented by; where VL1 is the first immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL2 is the second immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VH1 is the first immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH2 is the second immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; CH1 is the immunoglobulin heavy chain constant region 1; CL is the immunoglobulin light chain constant region; Fc is a region containing the immunoglobulin heavy chain constant region 2 (CH2), the immunoglobulin heavy chain constant region 3 (CH3), and optionally the immunoglobulin hinge; and L1 to L24 are amino acid linkers, Said antigen-binding polypeptide.

14. VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-L6-Fc; VH1-L7-VH2-L8-VL2-L9-VL1-L10-CH1-L11-CL-L12-Fc; VL1-L13-VL2-L14-VH2-L15-VH1-L16-CL-L17-CH1-L18-Fc; or VH1-L19-VH2-L20-VL2-L21-VL1-L22-CL-L23-CH1-L24-Fc having a structure represented by; where VL1 is the first immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL2 is the second immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VH1 is the first immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH2 is the second immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; CH1 is the immunoglobulin heavy chain constant region 1; CL is the immunoglobulin light chain constant region; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1 to L24 are amino acid linkers, The antigen-binding polypeptide according to claim 13.

15. An antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide, wherein the first polypeptide is VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-L6-Fc; VL1-L1-VH2-L2-VL2-L3-VH1-L4-CH1-L5-CL-L6-Fc; VH1-L7-VH2-L8-VL2-L9-VL1-L10-CH1-L11-CL-L12-Fc; VH1-L7-VL2-L8-VH2-L9-VL1-L10-CH1-L11-CL-L12-Fc; VL1-L13-VL2-L14-VH2-L15-VH1-L16-CL-L17-CH1-L18-Fc; VL1-L13-VH2-L14-VL2-L15-VH1-L16-CL-L17-CH1-L18-Fc; VH1-L19-VH2-L20-VL2-L21-VL1-L22-CL-L23-CH1-L24-Fc; or VH1-L19-VL2-L20-VH2-L21-VL1-L22-CL-L23-CH1-L24-Fc has a structure represented by; the second polypeptide is Fc; VL3-L25-VL4-L26-VH4-L27-VH3-L28-CH1-L29-CL-L30-Fc; VL3-L25-VH4-L26-VL4-L27-VH3-L28-CH1-L29-CL-L30-Fc; VH3-L31-VH4-L32-VL4-L33-VL3-L34-CH1-L35-CL-L36-Fc; VH3-L31-VL4-L32-VH4-L33-VL3-L34-CH1-L35-CL-L36-Fc; VL3-L37-VL4-L38-VH4-L39-VH3-L40-CL-L41-CH1-L42-Fc; VL3-L37-VH4-L38-VL4-L39-VH3-L40-CL-L41-CH1-L42-Fc; VH3-L43-VH4-L44-VL4-L45-VL3-L46-CL-L47-CH1-L48-Fc; or VH3-L43-VL4-L44-VH4-L45-VL3-L46-CL-L47-CH1-L48-Fc having a structure represented by; wherein, VL1 is the first immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL2 is the second immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL3 is the third immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL4 is the fourth immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VH1 is the first immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH2 is the second immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH3 is the third immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH4 is the fourth immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; CH1 is the immunoglobulin heavy chain constant region 1; CL is the immunoglobulin light chain constant region; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1 to L48 are amino acid linkers, the antigen-binding polypeptide complex.

16. comprising a first polypeptide and a second polypeptide; the first polypeptide is VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-L6-Fc; VH1-L7-VH2-L8-VL2-L9-VL1-L10-CH1-L11-CL-L12-Fc; VL1-L13-VL2-L14-VH2-L15-VH1-L16-CL-L17-CH1-L18-Fc; or VH1-L19-VH2-L20-VL2-L21-VL1-L22-CL-L23-CH1-L24-Fc having a structure represented by; wherein, the second polypeptide is Fc; VL3-L25-VL4-L26-VH4-L27-VH3-L28-CH1-L29-CL-L30-Fc; VH3-L31-VH4-L32-VL4-L33-VL3-L34-CH1-L35-CL-L36-Fc; VL3-L37-VL4-L38-VH4-L39-VH3-L40-CL-L41-CH1-L42-Fc; or VH3-L43-VH4-L44-VL4-L45-VL3-L46-CL-L47-CH1-L48-Fc having a structure represented by; VL1 is a first immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL4 is a fourth immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; CH1 is the immunoglobulin heavy chain constant region 1; CL is the immunoglobulin light chain constant region; Fc is a region comprising the immunoglobulin heavy chain constant region 2 (CH2), the immunoglobulin heavy chain constant region 3 (CH3), and optionally the immunoglobulin hinge; and L1 to L48 are amino acid linkers, The antigen-binding polypeptide complex according to claim 15.

17. VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc-L5-Fc; VL1-L1-VH2-L2-VL2-L3-VH1-L4-Fc-L5-Fc; VH1-L6-VH2-L7-VL2-L8-VL1-L9-Fc-L10-Fc; or VH1-L6-VL2-L7-VH2-L8-VL1-L9-Fc-L10-Fc An antigen-binding polypeptide or antigen-binding polypeptide complex comprising a polypeptide having a structure represented by; wherein Here,[[]]END]] VL1 is a first immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH2 is the second immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; Fc is a region containing immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1 to L10 are amino acid linkers, the antigen-binding polypeptide or antigen-binding polypeptide complex.

18. VL1 - L1 - VL2 - L2 - VH2 - L3 - VH1 - L4 - Fc - L5 - Fc; or a polypeptide having a structure represented by VH1-L6-VH2-L7-VL2-L8-VL1-L9-Fc-L10-Fc comprising; where VL1 is the first immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL2 is the second immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VH1 is the first immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH2 is the second immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; Fc is a region containing immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; L1 to L10 are amino acid linkers, the antigen-binding polypeptide or antigen-binding polypeptide complex according to claim 17.

19. The antigen-binding polypeptide or antigen-binding polypeptide complex according to any one of claims 1 to 18, wherein VH1, VH2, VH3 and VH4 each contain the same heavy chain variable region, and VL1, VL2, VL3 and VL4 each contain the same light chain variable region.

20. The antigen-binding polypeptide or antigen-binding polypeptide complex according to any one of claims 1 to 18, wherein VH1 contains the same heavy chain variable region as VH3, and VL1 contains the same light chain variable region as VL3.

21. The antigen-binding polypeptide or antigen-binding polypeptide complex according to any one of claims 1 to 18, wherein VH2 contains the same heavy chain variable region as VH4, and VL2 contains the same light chain variable region as VL4.

22. The antigen-binding polypeptide complex according to any one of claims 1 to 18, wherein two of VH1, VH2, VH3 and VH4 contain the same heavy chain variable region, and two of VL1, VL2, VL3 and VL4 contain the same light chain variable region.

23. The antigen-binding polypeptide complex according to any one of claims 1 to 18, wherein VH2 contains the same heavy-chain variable region as VH4, and VL2 contains the same light-chain variable region as VL4.

24. The antigen-binding polypeptide complex according to any one of claims 1 to 18, wherein VH2 contains the same heavy-chain variable region as VH3, and VL2 contains the same light-chain variable region as VL3.

25. The antigen-binding polypeptide complex according to any one of claims 1 to 18, wherein VH1 contains the same heavy-chain variable region as VH4, and VL1 contains the same light-chain variable region as VL4.

26. The antigen-binding polypeptide complex according to any one of claims 1 to 18, wherein VH1 contains the same heavy-chain variable region as VH3, and VL1 contains the same light-chain variable region as VL3.

27. The antigen-binding polypeptide or antigen-binding polypeptide complex according to any one of claims 1 to 18, wherein the immunoglobulin hinge contains an upper hinge region, a central hinge region, a lower hinge region, or a combination thereof.

28. The antigen-binding polypeptide or antigen-binding polypeptide complex according to any one of claims 1 to 27, wherein the linkers L1 to L48 each independently have a length of 0 amino acids to about 50 amino acids.

29. The linkers L1 to L48 that do not have a length of 0 amino acids each independently contain an amino acid sequence having at least 80%, at least 85%, at least 90%, or at least 95% identity with any one of SEQ ID NOs: 1 to 34. SEQ ID NO: 1 has the amino acid sequence of G, SEQ ID NO: 2 has the amino acid sequence of A, SEQ ID NO: 3 has the amino acid sequence of GSS, and SEQ ID NO: 4 has the amino acid sequence of ASG. The antigen-binding polypeptide or antigen-binding polypeptide complex according to any one of claims 1 to 28.

30. The antigen-binding polypeptide or antigen-binding polypeptide complex according to any one of claims 1 to 29, wherein one or more of the linkers L1 to L48 are non-immunogenic.

31. The antigen-binding polypeptide or antigen-binding polypeptide complex according to any one of claims 1 to 30, wherein one or more of the linkers L1 to L48 do not contain a consensus T cell epitope.

32. The Fc region contains at least one knob-into-hole modification or Fc effector function knockout mutation, and the antigen-binding polypeptide or antigen-binding polypeptide complex according to any one of claims 1 to 31.

33. The antigen-binding polypeptide complex is an IgG1 or IgG4 antibody, and the knob-into-hole modification is based on the EU numbering scheme, (i) knob substitutions of S354C and T366W and hole substitutions of Y349C, T366S, L368A and Y407V; (ii) hole substitutions of M428L and N434S or N434A; (iii) hole substitutions of M252Y, S254T and T256E; or (iv) a combination thereof The antigen-binding polypeptide complex according to claim 32.

34. The antigen-binding polypeptide complex is an IgG1 or IgG4 antibody, and the Fc effector function knockout mutation is L234A, L235A, P239A or a combination thereof based on the EU numbering scheme, and the antigen-binding polypeptide complex according to claim 32.

35. The antigen-binding polypeptide or antigen-binding polypeptide complex according to any one of claims 1 to 34, comprising a detectable label.

36. The detectable label is a radioactive label, chemiluminescent label, fluorescent label, enzyme, peptide tag, or a combination thereof, and the antigen-binding polypeptide or antigen-binding polypeptide complex according to claim 35.

37. The peptide tag is a polyhistidine tag consisting of about 4 to about 10 histidine residues, and the antigen-binding polypeptide or antigen-binding polypeptide complex according to claim 36.

38. The polyhistidine tag consists of about 8 histidine residues, and the antigen-binding polypeptide or antigen-binding polypeptide complex according to claim 37.

39. An antigen-binding polypeptide or antigen-binding polypeptide complex according to any one of claims 1 to 38, which specifically binds to a SARS-CoV-2 protein with an equilibrium dissociation constant (K Ｄ ) of from about 10 μM to about 1 pM.

40. The antigen-binding polypeptide complex is bispecific, trispecific or quadrispecific, and has a neutralizing potency against SARS-CoV-2 virus that is higher than that of a monospecific antigen-binding polypeptide complex that specifically binds to one of the same antigens as the bispecific, trispecific or quadrispecific antigen-binding polypeptide complex. The antigen-binding polypeptide complex according to any one of claims 1 to 39.

41. The antigen-binding polypeptide complex is Bispecific, trispecific or quadrispecific and having a neutralizing potency against SARS-CoV-2 that is higher than that of a mixture of monospecific antigen-binding polypeptide complexes that specifically bind to the same antigen as the bispecific, trispecific or quadrispecific antigen-binding polypeptide complex The antigen-binding polypeptide complex according to any one of claims 1 to 40. **Claim 42** The antigen-binding polypeptide complex according to claim 40 or 41, wherein the SARS-CoV-2 virus is the original Wuhan strain (WA1), D614G spike protein variant (D614G), alpha variant (B.1.1.7), beta variant (B.1.351), gamma variant (P.1), delta variant, epsilon variant (B.1.427), or omicron variant (B.1.1.529), or a combination thereof. **Claim 43** An antibody or an antigen-binding fragment thereof comprising the antigen-binding polypeptide or antigen-binding polypeptide complex according to any one of claims 1 to 42. **Claim 44** The antibody or antigen-binding fragment thereof according to claim 43, wherein the antibody is IgG, IgM, IgE, IgA or IgD. **Claim 45** The antibody or antigen-binding fragment thereof according to claim 44, wherein the IgG is IgG1, IgG2, IgG3 or IgG4. **Claim 46** The antigen-binding fragment is Fab, scFab, Fab', F(ab'), ２ Fv or scFv, the antibody or antigen-binding fragment thereof according to claim 43. **Claim 47** The antibody or antigen-binding fragment thereof according to claim 43, wherein the antibody is human or humanized. **Claim 48** The antibody or antigen-binding fragment thereof according to claim 43, wherein the antibody is a monoclonal antibody, a grafted antibody, or a chimeric antibody. **Claim 49** A polyvalent anti-SARS-CoV2 antibody, (i) a monovalent anti-SARS-CoV2 antibody that binds to one of the same antigens as the polyvalent anti-SARS-CoV2 antibody, and / or (ii) a combination of monovalent anti-SARS-CoV2 antibodies that bind to the same antigen as the polyvalent anti-SARS-CoV2 antibody The polyvalent anti-SARS-CoV2 antibody, showing an improved prevention of immune evasion as compared to. **Claim 50** A pharmaceutical composition comprising the antigen-binding polypeptide or antigen-binding polypeptide complex according to any one of claims 1 to 42. **Claim 51** A pharmaceutical composition comprising the antigen-binding polypeptide or antigen-binding polypeptide complex according to any one of claims 1 to 42 and an additional pharmaceutical agent. **Claim 52** A pharmaceutical composition comprising the antigen-binding polypeptide or antigen-binding polypeptide complex according to any one of claims 1 to 42 and a pharmaceutically acceptable carrier.

53. A pharmaceutical composition comprising the antigen-binding polypeptide or antigen-binding polypeptide complex according to any one of claims 1 to 42, an additional pharmaceutical agent, and a pharmaceutically acceptable carrier.

54. A pharmaceutical composition comprising the antibody according to any one of claims 43 to 49 or an antigen-binding fragment thereof.

55. A pharmaceutical composition comprising the antibody according to any one of claims 43 to 49 or an antigen-binding fragment thereof and an additional pharmaceutical agent.

56. A pharmaceutical composition comprising the antibody according to any one of claims 43 to 49 or an antigen-binding fragment thereof and a pharmaceutically acceptable carrier.

57. A pharmaceutical composition comprising the antibody according to any one of claims 43 to 49 or an antigen-binding fragment thereof, an additional pharmaceutical agent, and a pharmaceutically acceptable carrier.

58. The pharmaceutical composition according to any one of claims 51, 53, 55, and 57, wherein the additional pharmaceutical agent is 25-hydroxyvitamin D, an agent that enhances the action of vitamin D, an antiviral agent, an antimalarial agent, an antibiotic, or a combination thereof.

59. The pharmaceutical composition according to claim 58, wherein the additional pharmaceutical agent is 25-hydroxyvitamin D.

60. The pharmaceutical composition according to claim 58, wherein the agent that enhances the action of vitamin D is a CYP24 inhibitor, a 1,25-dihydroxyvitamin D compound, or a combination thereof.

61. The pharmaceutical composition according to claim 58, wherein the antiviral agent is an antiretroviral agent, an antibody against the SARS-CoV-2 virus, an inhibitor of reverse transcriptase, or a combination thereof.

62. The antiviral agent is maraviroc, enfuvirtide, amantadine, lamivudine, nevirapine, efavirenz, dolutegravir, elvitegravir, raltegravir, acyclovir and any nucleoside analog of acyclovir, ganciclovir, cidofovir, foscarnet, ribavirin, interferon alpha, PEGylated interferon alpha, boceprevir, atazanavir, darunavir, indinavir, oseltamivir, zanamivir, rimantadine, peramivir, valacyclovir, penciclovir, valganciclovir, phosphonoformic acid, tenofovir, adefovir, entecavir, lamivudine, telbivudine, ribavirin, grazoprevir, glecaprevir, paritaprevir, simeprevir, voxilaprevir, daclatasvir, elbasvir, ledipasvir, ombitasvir, pibrentasvir, velpatasvir, dasabuvir, famciclovir, remdesivir, trifluridine, sofosbuvir, bebtelovimab, or a combination thereof, the pharmaceutical composition according to claim 58.

63. The antiviral agent is bebtelovimab, the pharmaceutical composition according to claim 62.

64. The antiviral agent is Retrovir (registered trademark) (3'-azido-3'-deoxypyrimidine, zidovudine), 3'-azido-3'-deoxythymidine (AZT), HMD (registered trademark) (2',3'-dideoxycytidine, zalcitabine), Videx EC (registered trademark) (2',3'-dideoxyinosine, didanosine), Epivir (registered trademark) (lamivudine), Zerit (registered trademark) (stavudine), Viread (registered trademark) (tenofovir DF), Ziagen (registered trademark) (abacavir), Emtriva (registered trademark) (emtricitabine, FTC), Rescriptor (registered trademark) (delavirdine), Sustiva (registered trademark) (efavirenz), Viramune (registered trademark) (nevirapine, 11-cyclopropyl-4-methyl-5,11-dihydro-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one), trisodium phosphonoformate, ammonium-21-tungstato-9-antimonate, 1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide, Agenerase (registered trademark) (amprenavir), Reyataz (registered trademark) (atazanavir), Lexiva (registered trademark) (fosamprenavir), Crixivan (registered trademark) (indinavir), Viracept (registered trademark) (nelfinavir), Norvir (registered trademark) (ritonavir), Fortovase (registered trademark) or Invirase (registered trademark) (saquinavir), lasinavir (5(S)-(tert-butoxycarbonylamino)-4(S)-hydroxy-6-phenyl-2(R)(2,3,4-(Trimethoxyphenylmethyl)-hexanoyl-(L)-valyl-N-(2-methoxy-ethyl)-amide), Adriamycin, KVX-478, VX-478, 141W94, AG-1343, KNI-272, U-96988, BILA-2011BS (parinamivir), polymannose acetate, Fuzeon® (enfuvirtide, T-20), Epzicom® (abacavir and lamivudine), Trizivir® (abacavir, lamivudine and zidovudine), Truvada® (emtricitabine and tenofovir DF), Combivir® (lamivudine and zidovudine), Kaletra® (lopinavir and ritonavir), bevacizumab, or a combination thereof, the pharmaceutical composition according to claim 58.,

65. The antiviral agent is bebtelovimab, the pharmaceutical composition according to claim 64.

66. A kit comprising the antigen-binding polypeptide or antigen-binding polypeptide complex according to any one of claims 1 to 42, or the antibody or antigen-binding fragment thereof according to any one of claims 43 to 49.

67. (i) The antigen-binding polypeptide or antigen-binding polypeptide complex according to any one of claims 1 to 42, or the antibody or antigen-binding fragment thereof according to any one of claims 43 to 49, and (ii) An additional pharmaceutical agent A kit comprising.

68. A kit comprising the pharmaceutical composition according to any one of claims 50 to 65.

69. (i) The pharmaceutical composition according to any one of claims 50 to 65, and (ii) An additional pharmaceutical agent A kit comprising.

70. (i) The pharmaceutical composition according to any one of claims 50 to 65, and (ii) A pharmaceutical composition comprising an additional pharmaceutical agent A kit comprising.

71. (i) The pharmaceutical composition according to any one of claims 50 to 65, and (ii) A pharmaceutical composition comprising an additional pharmaceutical agent and a pharmaceutically acceptable carrier A kit comprising

72. The kit according to any one of claims 66 to 71, further comprising instructions for use.

73. A method for preventing or treating SARS-CoV-2 virus infection in a subject in need thereof, administering to the subject a therapeutically effective amount of an antigen-binding polypeptide or polypeptide complex according to any one of claims 1 to 42, an antibody or antigen-binding fragment thereof according to any one of claims 43 to 49, a pharmaceutical composition according to any one of claims 50 to 65, or a combination thereof comprising the above method.

74. A method for preventing or treating coronavirus disease 2019 (COVID-19) in a subject in need thereof, administering to the subject a therapeutically effective amount of an antigen-binding polypeptide or polypeptide complex according to any one of claims 1 to 42, an antibody or antigen-binding fragment thereof according to any one of claims 43 to 49, a pharmaceutical composition according to any one of claims 50 to 65, or a combination thereof comprising the above method.

75. A method for diagnosing a subject as being infected with SARS-CoV-2 virus or suspected of being infected with SARS-CoV-2 virus, (i) contacting a sample obtained from the subject with an antigen-binding polypeptide or polypeptide complex according to any one of claims 1 to 42 or an antibody or antigen-binding fragment thereof according to any one of claims 43 to 49; (ii) detecting the presence or absence of a virus complex containing the polypeptide, polypeptide complex, antibody or fragment and SARS-CoV-2 virus, its virion or fragment; and (iii) diagnosing the subject as being infected with SARS-CoV-2 virus or suspected of being infected with SARS-CoV-2 virus when the presence of the virus complex is detected comprising the above method.

76. A method for diagnosing a subject as not being infected with SARS-CoV-2 virus or having no suspicion of being infected with SARS-CoV-2 virus, (i) contacting a sample obtained from the subject with an antigen-binding polypeptide or polypeptide complex according to any one of claims 1 to 42, or an antibody or antigen-binding fragment thereof according to any one of claims 43 to 49; (ii) detecting the presence or absence of a virus complex containing the polypeptide, polypeptide complex, antibody or fragment and the SARS-CoV-2 virus, its virion or fragment; and (iii) diagnosing the subject as not infected with the SARS-CoV-2 virus or having no suspicion of being infected with the SARS-CoV-2 virus when the presence of the virus complex is not detected The method comprising the above.

77. A method for diagnosing a subject as having COVID-19 or having a suspicion of having COVID-19, (i) contacting a sample obtained from the subject with an antigen-binding polypeptide or polypeptide complex according to any one of claims 1 to 42, or an antibody or antigen-binding fragment thereof according to any one of claims 43 to 49; (ii) detecting the presence or absence of a virus complex containing the polypeptide, polypeptide complex, antibody or fragment and the SARS-CoV-2 virus, its virion or fragment; and (iii) diagnosing the subject as having COVID-19 or having a suspicion of having COVID-19 when the presence of the virus complex is detected The method comprising the above.

78. A method for diagnosing a subject as not having COVID-19 or having no suspicion of having COVID-19, (i) contacting a sample obtained from the subject with an antigen-binding polypeptide or polypeptide complex according to any one of claims 1 to 42, or an antibody or antigen-binding fragment thereof according to any one of claims 43 to 49; (ii) detecting the presence or absence of a virus complex containing the polypeptide, polypeptide complex, antibody or fragment and the SARS-CoV-2 virus, its virion or fragment; and (iii) diagnosing the subject as not having COVID-19 or having no suspicion of having COVID-19 when the presence of the virus complex is not detected The method comprising the above.

79. The method according to any one of claims 75 to 78, wherein the sample is a nasal swab, a tissue sample, saliva, plasma or blood.

80. The method according to any one of claims 75 to 79, wherein detecting the presence or absence of the virus complex comprises an enzyme-linked immunosorbent assay (ELISA), an immunospot assay, a lateral flow assay, flow cytometry, immunohistochemistry or Western blot.

81. The polypeptide, polypeptide complex, antibody or fragment is bispecific, trispecific or quadrispecific, and has a neutralizing potency against the SARS-CoV-2 virus that is higher than that of a monospecific polypeptide, polypeptide complex, antibody or fragment that specifically binds to one of the same antigens as the bispecific, trispecific or quadrispecific polypeptide, polypeptide complex, antibody or fragment. The method according to any one of claims 73 to 80.

82. The polypeptide, polypeptide complex, antibody or fragment is bispecific, trispecific or quadrispecific, and has a neutralizing potency against the SARS-CoV-2 virus that is higher than that of a mixture of monospecific polypeptides, polypeptide complexes, antibodies or fragments that specifically bind to the same antigen as the bispecific, trispecific or quadrispecific polypeptide, polypeptide complex, antibody or fragment. The method according to any one of claims 73 to 81.

83. The method according to any one of claims 73 to 82, wherein the SARS-CoV-2 virus is the original Wuhan strain (WA1), the D614G spike protein variant (D614G), the alpha variant (B.1.1.7), the beta variant (B.1.351), the gamma variant (P.1), the delta variant, the epsilon variant (B.1.427), the omicron variant (B.1.1.529), or a combination thereof.

84. A method for preventing immune evasion of the SARS-CoV2 virus in a subject infected with the SARS-CoV2 virus, comprising (i) a monovalent anti-SARS-CoV2 antibody that binds to one of the same antigens as the anti-SARS-CoV2 polyvalent antibody, and / or (ii) a combination of monovalent anti-SARS-CoV2 antibodies that bind to the same antigen as the anti-SARS-CoV2 polyvalent antibody administering to the subject an effective amount of said anti-SARS-CoV-2 polyvalent antibody that exhibits improved prevention of immune escape as compared thereto The method comprising the same. **Claim 85** A method of increasing the neutralizing potency against SARS-CoV-2 virus in a subject infected with SARS-CoV-2 virus, comprising: (i) a monovalent anti-SARS-CoV-2 antibody that binds to one of the same antigens as said anti-SARS-CoV-2 polyvalent antibody, and / or (ii) a combination of monovalent anti-SARS-CoV-2 antibodies that bind to the same antigen as said anti-SARS-CoV-2 polyvalent antibody administering to the subject an effective amount of said anti-SARS-CoV-2 polyvalent antibody that exhibits increased neutralizing potency as compared to a combination of (i) and (ii) above The method comprising the same. **Claim 86** The method according to claim 84 or 85, wherein said anti-SARS-CoV-2 polyvalent antibody exhibits improved prevention of immune escape as compared to a monovalent anti-SARS-CoV-2 antibody that binds to one of the same antigens as said anti-SARS-CoV-2 polyvalent antibody. **Claim 87** The method according to any one of claims 84 to 86, wherein said anti-SARS-CoV-2 polyvalent antibody exhibits increased neutralizing potency as compared to a combination of monovalent anti-SARS-CoV-2 antibodies that bind to the same antigen as said anti-SARS-CoV-2 polyvalent antibody. **Claim 88** The method according to any one of claims 84 to 87, wherein said anti-SARS-CoV-2 multispecific antibody prevents immune escape of said anti-SARS-CoV-2 polyvalent antibody for at least 2, at least 3, at least 4, at least 5, at least 6, or at least 7 rounds of selection when measured by an antibody escape assay. **Claim 89** The method according to any one of claims 84 to 88, wherein said anti-SARS-CoV-2 multispecific antibody prevents immune escape of said anti-SARS-CoV-2 polyvalent antibody after at least 2, at least 3, at least 4, at least 5, at least 6, or at least 7 exposures of said subject to the SARS-CoV-2 virus. **Claim 90** Said anti-SARS-CoV-2 multispecific antibody comprises: (i) a monovalent anti-SARS-CoV-2 antibody that binds to one of the same antigens as said anti-SARS-CoV-2 polyvalent antibody, and / or (ii) a combination of monovalent anti-SARS-CoV-2 antibodies that bind to the same antigen as said anti-SARS-CoV-2 polyvalent antibody At least 100-fold, at least 500-fold, at least 1,000-fold, or at least 2,000-fold more effective in inhibiting the growth of the SARS-CoV-2 virus compared to The method according to any one of claims 84 to 89.

91. The method according to any one of claims 84 to 90, wherein the anti-SARS-CoV-2 polyvalent antibody comprises a first antigen-binding site that specifically binds to the SARS-CoV-2 protein and a second antigen-binding site that specifically binds to the SARS-CoV-2 protein.

92. The method according to claim 91, wherein the first antigen-binding site is different from the second antigen-binding site.

93. The method according to claim 91 or 92, wherein the first antigen-binding site comprises a first heavy-chain variable domain and a first light-chain variable domain, and the second antigen-binding site comprises a second heavy-chain variable domain and a second light-chain variable domain.

94. The method according to claim 93, wherein the first and second heavy-chain variable regions each comprise CDR1, CDR2, and CDR3 regions, and the first and second light-chain variable regions each comprise CDR1, CDR2, and CDR3 regions.

95. The CDR1 of the first heavy-chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with any one of SEQ ID NOs: 43, 51, 59, 67, 75, 171, 179, 187, 264, 272, 280, 288, 513, 521, 529, 537, 545, 553, 561, 569, 577, 585, 593, 601, 609, 617, 639, 647, 656, and 664; The CDR2 of the first heavy-chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with any one of SEQ ID NOs: 44, 52, 60, 68, 76, 172, 180, 188, 265, 273, 281, 289, 514, 522, 530, 538, 546, 554, 562, 570, 578, 586, 594, 602, 610, 618, 640, 648, 657, and 665; The CDR3 of the first heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 45, 53, 61, 69, 77, 173, 181, 189, 266, 274, 282, 290, 515, 523, 531, 539, 547, 555, 563, 571, 579, 587, 595, 603, 611, 619, 641, 649, 658 and 666; The CDR1 of the first light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 39, 47, 55, 63, 71, 167, 175, 183, 260, 268, 276, 284, 517, 525, 533, 541, 549, 557, 565, 573, 581, 589, 597, 605, 613, 621, 643, 651, 660 and 668; The CDR2 of the first light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 40, 48, 56, 64, 72, 168, 176, 184, 261, 269, 277 (having the sequence of LGS), 285, 518 (having the sequence of DAS), 526 (having the sequence of DVS), 534 (having the sequence of EDS), 542 (having the sequence of KDS), 550 (having the sequence of DAS), 558 (having the sequence of AAS), 566 (having the sequence of GAS), 574 (having the sequence of DDS), 582 (having the sequence of KDS), 590 (having the sequence of SAS), 598 (having the sequence of SAS), 606 (having the sequence of GAS), 614 (having the sequence of GAS), 622 (having the sequence of GAS), 644 (having the sequence of GAS), 652 (having the sequence of SAS), 661 (having the sequence of GAS) and 669 (having the sequence of DAS); The CDR3 of the first light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 41, 49, 57, 65, 73, 169, 177, 185, 262, 270, 278, 286, 519, 527, 535, 543, 551, 559, 567, 575, 583, 591, 599, 607, 615, 623, 645, 653, 662 and 670; The CDR1 of the second heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 43, 51, 59, 67, 75, 171, 179, 187, 264, 272, 280, 288, 513, 521, 529, 537, 545, 553, 561, 569, 577, 585, 593, 601, 609, 617, 639, 647, 656 and 664; The CDR2 of the second heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 44, 52, 60, 68, 76, 172, 180, 188, 265, 273, 281, 289, 514, 522, 530, 538, 546, 554, 562, 570, 578, 586, 594, 602, 610, 618, 640, 648, 657 and 665; The CDR3 of the second heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 45, 53, 61, 69, 77, 173, 181, 189, 266, 274, 282, 290, 515, 523, 531, 539, 547, 555, 563, 571, 579, 587, 595, 603, 611, 619, 641, 649, 658 and 666; The CDR1 of the second light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 39, 47, 55, 63, 71, 167, 175, 183, 260, 268, 276, 284, 517, 525, 533, 541, 549, 557, 565, 573, 581, 589, 597, 605, 613, 621, 643, 651, 660 and 668; The CDR2 of the second light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 40, 48, 56, 64, 72, 168, 176, 184, 261, 269, 277 (having the sequence of LGS), 518 (having the sequence of DAS), 526 (having the sequence of DVS), 534 (having the sequence of EDS), 542 (having the sequence of KDS), 550 (having the sequence of DAS), 558 (having the sequence of AAS), 566 (having the sequence of GAS), 574 (having the sequence of DDS), 582 (having the sequence of KDS), 590 (having the sequence of SAS), 598 (having the sequence of SAS), 606 (having the sequence of GAS), 614 (having the sequence of GAS), 622 (having the sequence of GAS), 644 (having the sequence of GAS), 652 (having the sequence of SAS), 661 (having the sequence of GAS) and 669 (having the sequence of DAS); and The CDR3 of the second light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 41, 49, 57, 65, 73, 169, 177, 185, 262, 270, 278, 286, 519, 527, 535, 543, 551, 559, 567, 575, 583, 591, 599, 607, 615, 623, 645, 653, 662 and 670. The method according to any one of claims 84 to 94. [

96. ] The first heavy-chain variable domain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity with any one of SEQ ID NOs: 42, 50, 58, 66, 74, 170, 178, 186, 263, 271, 279, 287, 510, 512, 520, 528, 536, 544, 552, 560, 568, 576, 584, 592, 600, 608, 616, 624, 626, 628, 630, 632, 634, 636, 638, 646, 654, 663, 779, 781, 785, and 787; The first light-chain variable domain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity with any one of SEQ ID NOs: 38, 46, 54, 62, 70, 166, 174, 182, 259, 267, 275, 283, 508, 509, 511, 516, 524, 532, 540, 548, 556, 564, 572, 580, 588, 596, 604, 612, 620, 625, 627, 629, 631, 633, 635, 637, 642, 650, 659, and 667; The second heavy-chain variable domain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity with any one of SEQ ID NOs: 42, 50, 58, 66, 74, 170, 178, 186, 263, 271, 279, 287, 510, 512, 520, 528, 536, 544, 552, 560, 568, 576, 584, 592, 600, 608, 616, 624, 626, 628, 630, 632, 634, 636, 638, 646, 654, 663, 779, 781, 785, and 787; and The second light-chain variable domain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity with any one of SEQ ID NOs: 38, 46, 54, 62, 70, 166, 174, 182, 259, 267, 275, 283, 508, 509, 511, 516, 524, 532, 540, 548, 556, 564, 572, 580, 588, 596, 604, 612, 620, 625, 627, 629, 631, 633, 635, 637, 642, 650, 659, and 667. The method according to any one of claims 84 to 95.

97. The method according to any one of claims 84 to 96, wherein the anti-SARS-CoV-2 polyvalent antibody further comprises a third antigen-binding domain.

98. The method according to claim 97, wherein the third antigen-binding site is different from the first antigen-binding site, different from the second antigen-binding site, or different from both the first and second antigen-binding sites.

99. The method according to claim 97 or 98, wherein the third antigen-binding site comprises a third heavy-chain variable domain and a third light-chain variable domain.

100. The third heavy-chain variable domain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity with any one of SEQ ID NOs: 42, 50, 58, 66, 74, 170, 178, 186, 263, 271, 279, 287, 510, 512, 520, 528, 536, 544, 552, 560, 568, 576, 584, 592, 600, 608, 616, 624, 626, 628, 630, 632, 634, 636, 638, 646, 654, 663, 779, 781, 785, and 787; and the third light-chain variable domain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity with any one of SEQ ID NOs: 38, 46, 54, 62, 70, 166, 174, 182, 259, 267, 275, 283, 508, 509, 511, 516, 524, 532, 540, 548, 556, 564, 572, 580, 588, 596, 604, 612, 620, 625, 627, 629, 631, 633, 635, 637, 642, 650, 659, and 667. The method according to any one of claims 84 to 99.

101. The method according to any one of claims 84 to 100, wherein the third heavy-chain variable region comprises CDR1, CDR2, and CDR3 regions.

102. The CDR1 of the third heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 43, 51, 59, 67, 75, 171, 179, 187, 264, 272, 280, 288, 513, 521, 529, 537, 545, 553, 561, 569, 577, 585, 593, 601, 609, 617, 639, 647, 656 and 664; The CDR2 of the third heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 44, 52, 60, 68, 76, 172, 180, 188, 265, 273, 281, 289, 514, 522, 530, 538, 546, 554, 562, 570, 578, 586, 594, 602, 610, 618, 640, 648, 657 and 665; The CDR3 of the third heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 45, 53, 61, 69, 77, 173, 181, 189, 266, 274, 282, 290, 515, 523, 531, 539, 547, 555, 563, 571, 579, 587, 595, 603, 611, 619, 641, 649, 658 and 666; The CDR1 of the third light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 39, 47, 55, 63, 71, 167, 175, 183, 260, 268, 276, 284, 517, 525, 533, 541, 549, 557, 565, 573, 581, 589, 597, 605, 613, 621, 643, 651, 660 and 668; The CDR2 of the third light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 40, 48, 56, 64, 72, 168, 176, 184, 261, 269, 277 (having the sequence of LGS), 285, 518 (having the sequence of DAS), 526 (having the sequence of DVS), 534 (having the sequence of EDS), 542 (having the sequence of KDS), 550 (having the sequence of DAS), 558 (having the sequence of AAS), 566 (having the sequence of GAS), 574 (having the sequence of DDS), 582 (having the sequence of KDS), 590 (having the sequence of SAS), 598 (having the sequence of SAS), 606 (having the sequence of GAS), 614 (having the sequence of GAS), 622 (having the sequence of GAS), 644 (having the sequence of GAS), 652 (having the sequence of SAS), 661 (having the sequence of GAS) and 669 (having the sequence of DAS); and The CDR3 of the third light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 41, 49, 57, 65 and 73, 169, 177, 185, 262, 270, 278, 286, 519, 527, 535, 543, 551, 559, 567, 575, 583, 591, 599, 607, 615, 623, 645, 653, 662 and 670, The method according to any one of claims 84 to 101.

103. The method according to any one of claims 84 to 102, wherein the anti-SARS-CoV-2 polyvalent antibody further comprises a fourth antigen-binding domain.

104. The method according to claim 103, wherein the fourth antigen-binding site is different from one or more of the first, second and third antigen-binding sites.

105. The method according to claim 103 or 104, wherein the first, second, third and fourth antigen-binding sites are different.

106. The method according to any one of claims 84 to 105, wherein the fourth antigen-binding site comprises a third heavy chain variable domain and a fourth light chain variable domain.

107. The fourth heavy chain variable domain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity with any one of SEQ ID NOs: 42, 50, 58, 66, 74, 170, 178, 186, 263, 271, 279, 287, 510, 512, 520, 528, 536, 544, 552, 560, 568, 576, 584, 592, 600, 608, 616, 624, 626, 628, 630, 632, 634, 636, 638, 646, 654, 663, 779, 781, 785, and 787; and the fourth light chain variable domain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity with any one of SEQ ID NOs: 38, 46, 54, 62, 70, 166, 174, 182, 259, 267, 275, 283, 508, 509, 511, 516, 524, 532, 540, 548, 556, 564, 572, 580, 588, 596, 604, 612, 620, 625, 627, 629, 631, 633, 635, 637, 642, 650, 659, and 667. The method according to any one of claims 84 to 106.

108. The method according to any one of claims 84 to 107, wherein the fourth heavy chain variable region comprises CDR1, CDR2, and CDR3 regions.

109. The CDR1 of the fourth heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with any one of SEQ ID NOs: 43, 51, 59, 67, 75, 171, 179, 187, 264, 272, 280, 288, 513, 521, 529, 537, 545, 553, 561, 569, 577, 585, 593, 601, 609, 617, 639, 647, 656, and 664; The CDR2 of the fourth heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 44, 52, 60, 68, 76, 172, 180, 188, 265, 273, 281, 289, 514, 522, 530, 538, 546, 554, 562, 570, 578, 586, 594, 602, 610, 618, 640, 648, 657 and 665; The CDR3 of the fourth heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 45, 53, 61, 69, 77, 173, 181, 189, 266, 274, 282, 290, 515, 523, 531, 539, 547, 555, 563, 571, 579, 587, 595, 603, 611, 619, 641, 649, 658 and 666; The CDR1 of the fourth light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 39, 47, 55, 63, 71, 167, 175, 183, 260, 268, 276, 284, 517, 525, 533, 541, 549, 557, 565, 573, 581, 589, 597, 605, 613, 621, 643, 651, 660 and 668; The CDR2 of the fourth light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 40, 48, 56, 64, 72, 168, 176, 184, 261, 269, 277 (having the sequence of LGS), 285, 518 (having the sequence of DAS), 526 (having the sequence of DVS), 534 (having the sequence of EDS), 542 (having the sequence of KDS), 550 (having the sequence of DAS), 558 (having the sequence of AAS), 566 (having the sequence of GAS), 574 (having the sequence of DDS), 582 (having the sequence of KDS), 590 (having the sequence of SAS), 598 (having the sequence of SAS), 606 (having the sequence of GAS), 614 (having the sequence of GAS), 622 (having the sequence of GAS), 644 (having the sequence of GAS), 652 (having the sequence of SAS), 661 (having the sequence of GAS), and 669 (having the sequence of DAS); and the CDR3 of the fourth light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 41, 49, 57, 65, 73, 169, 177, 185, 262, 270, 278, 286, 519, 527, 535, 543, 551, 559, 567, 575, 583, 591, 599, 607, 615, 623, 645, 653, 662, and 670, The method according to claim 108.

110. The method according to any one of claims 84 to 109, wherein the anti-SARS-CoV-2 polyvalent antibody is the antibody according to any one of claims 43 to 48 or an antigen-binding fragment thereof.

111. The method according to any one of claims 84 to 110, wherein the antigen is a SARS-CoV-2 protein.

112. The method according to any one of claims 84 to 111, wherein the SARS-CoV-2 virus is a SARS-CoV-2 variant.

113. The method according to claim 112, wherein the SARS-CoV-2 variant is an alpha variant (B.1.1.7), a beta variant (B.1.351), a gamma variant (P.1), a delta variant, an epsilon variant (B.1.427), or an omicron variant (B.1.1.529), or a combination thereof.

114. The method according to claim 113, wherein the omicron variant is BA.1, BA.2, BA.2.12.1, BA.4, BA.4 / 5, BA.5, BQ.1, BQ.1.1, BA.2.75, BA.2.75.2, BA.4.6, BQ.1.1, BJ.1, XBB, XBB1.5, BF.7, CH.1.1, or a combination thereof.

115. The method according to any one of claims 73 to 114, further comprising administering to the subject an effective amount of an additional pharmaceutical agent.

116. The method according to any one of claims 73 to 114, further comprising administering to the subject an effective amount of a pharmaceutical composition comprising (i) an additional pharmaceutical agent and (ii) a pharmaceutically acceptable carrier.

117. The method according to claim 115 or 116, wherein the additional pharmaceutical agent is 25-hydroxyvitamin D, an agent that enhances the action of vitamin D, an antiviral agent, an antimalarial agent, an antibiotic, or a combination thereof.

118. The method according to claim 115, wherein the additional pharmaceutical agent is 25-hydroxyvitamin D.

119. The method according to claim 117, wherein the agent that enhances the action of vitamin D is a CYP24 inhibitor, a 1,25-dihydroxyvitamin D compound, or a combination thereof.

120. The method according to claim 117, wherein the antiviral agent is an antiretroviral agent, an antibody against the SARS-CoV-2 virus, an inhibitor of reverse transcriptase, or a combination thereof.

121. The antiviral agent is maraviroc, enfuvirtide, amantadine, lamivudine, nevirapine, efavirenz, dolutegravir, elvitegravir, raltegravir, acyclovir and any nucleoside analog of acyclovir, ganciclovir, cidofovir, foscarnet, ribavirin, interferon alpha, PEGylated interferon alpha, boceprevir, atazanavir, darunavir, indinavir, oseltamivir, zanamivir, rimantadine, peramivir, valacyclovir, penciclovir, valganciclovir, phosphonoformic acid, tenofovir, adefovir, entecavir, lamivudine, telbivudine, ribavirin, grazoprevir, glecaprevir, paritaprevir, simeprevir, voxilaprevir, daclatasvir, elbasvir, ledipasvir, ombitasvir, pibrentasvir, velpatasvir, dasabuvir, famciclovir, remdesivir, trifluridine, sofosbuvir, bebtelovimab, or a combination thereof, according to the method of claim 117.

122. The antiviral agent is bebtelovimab, according to the method of claim 117.

123. The antiviral agent is Retrovir (registered trademark) (3'-azido-3'-deoxypyrimidine, zidovudine), 3'-azido-3'-deoxythymidine (AZT), HMD (registered trademark) (2',3'-dideoxycytidine, zalcitabine), VidexEC (registered trademark) (2',3'-dideoxyinosine, didanosine), Epivir (registered trademark) (lamivudine), Zerit (registered trademark) (stavudine), Viread (registered trademark) (tenofovir DF), Ziagen (registered trademark) (abacavir), Emtriva (registered trademark) (emtricitabine, FTC), Rescriptor (registered trademark) (delavirdine), Sustiva (registered trademark) (efavirenz), Viramune (registered trademark) (nevirapine, 11-cyclopropyl-4-methyl-5,11-dihydro-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one), trisodium phosphonoformate, ammonium-21-tungstato-9-antimonate, 1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide, Agenerase (registered trademark) (amprenavir), Reyataz (registered trademark) (atazanavir), Lexiva (registered trademark) (fosamprenavir), Crixivan (registered trademark) (indinavir), Viracept (registered trademark) (nelfinavir), Norvir (registered trademark) (ritonavir), Fortovase (registered trademark) or Invirase (registered trademark) (saquinavir), lasinavir (5(S)-(tert-butoxycarbonylamino)-4(S)-hydroxy-6-phenyl-2(R)(2,3,4-(Trimethoxyphenylmethyl)-hexanoyl-(L)-valyl-N-(2-methoxy-ethyl)-amide), Adriamycin, KVX-478, VX-478, 141W94, AG-1343, KNI-272, U-96988, BILA-2011BS (parinamivir), polymannose acetate, Fuzeon® (enfuvirtide, T-20), Epzicom® (abacavir and lamivudine), Trizivir® (abacavir, lamivudine and zidovudine), Truvada® (emtricitabine and tenofovir DF), Combivir® (lamivudine and zidovudine), Kaletra® (lopinavir and ritonavir), bevacizumab, or a combination thereof, the method according to claim 117.,

124. The additional pharmaceutical agent is administered before the antigen-binding polypeptide, antigen-binding polypeptide complex, antibody or antigen-binding fragment thereof, according to the method of any one of claims 115 to 123.

125. The additional pharmaceutical agent is administered after the antigen-binding polypeptide, antigen-binding polypeptide complex, antibody or antigen-binding fragment thereof, according to the method of any one of claims 115 to 123.

126. The additional pharmaceutical agent is administered simultaneously with the antigen-binding polypeptide, antigen-binding polypeptide complex, antibody or antigen-binding fragment thereof, according to the method of any one of claims 115 to 123.

127. The additional pharmaceutical agent and the antigen-binding polypeptide, antigen-binding polypeptide complex, antibody or antigen-binding fragment thereof are administered in the same pharmaceutical composition, according to the method of any one of claims 115 to 126.

128. The additional pharmaceutical agent and the antigen-binding polypeptide, antigen-binding polypeptide complex, antibody or antigen-binding fragment thereof are administered in different pharmaceutical compositions, according to the method of any one of claims 115 to 126.

129. An antigen-binding polypeptide having a structure represented by (a) VL1-L1-VH1 or VH1-L2-VL1, wherein, here, VL1 is a first immunoglobulin light chain variable region that specifically binds to a SARS-CoV-2 protein, VH1 is a first immunoglobulin heavy chain variable region that specifically binds to a SARS-CoV-2 protein, and L1 and L2 are amino acid linkers, said antigen-binding polypeptide; or An antigen-binding polypeptide having a structure represented by VL1-L1-VL2-L2-VH2-L3-VH1, VL1-L1-VH2-L2-VL2-L3-VH1, VH1-L4-VH2-L5-VL2-L6-VL1, or VH1-L4-VL2-L5-VH2-L6-VL1 wherein, here, VL1 is a first immunoglobulin light chain variable region that specifically binds to a SARS-CoV-2 protein, VL2 is a second immunoglobulin light chain variable region that specifically binds to a SARS-CoV-2 protein, VH1 is a first immunoglobulin heavy chain variable region that specifically binds to a SARS-CoV-2 protein, VH2 is a second immunoglobulin heavy chain variable region that specifically binds to a SARS-CoV-2 protein, and L1 to L6 are amino acid linkers, said antigen-binding polypeptide (wherein (a) is selected from any one of the more specific embodiments provided herein for the antigen-binding polypeptide in an antigen-binding polypeptide complex having three or fewer polypeptide chains); (b) An antigen-binding polypeptide complex comprising a first polypeptide, a second polypeptide, a third polypeptide, and a fourth polypeptide, wherein the first polypeptide has a structure represented by VL1-L1-CL, the second polypeptide has a structure represented by VH1-L2-CH1, the third polypeptide has a structure represented by VH2-L3-VH3-L4-CH1, the fourth polypeptide has a structure represented by VL3-L5-VL2-L6-CL, and here, VL1 is a first immunoglobulin light chain variable region that specifically binds to a SARS-CoV-2 protein, VL2 is the second immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein, VL3 is the third immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein, VH1 is the first immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein, VH2 is the second immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein, VH3 is the third immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein, CH1 is the immunoglobulin heavy chain constant region 1, CL is the immunoglobulin light chain constant region, and L1 to L6 are amino acid linkers, the antigen-binding polypeptide complex; and (c) an antigen-binding polypeptide having a structure represented by VL1-L1-VH1 or VH1-L2-VL1 wherein, here, VL1 is the first immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VH1 is the first immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein, and L1 and L2 are amino acid linkers, the antigen-binding polypeptide; or VL1-L1-VL2-L2-VH2-L3-VH1, VL1-L1-VH2-L2-VL2-L3-VH1, VH1-L4-VH2-L5-VL2-L6-VL1, or VH1-L4-VL2-L5-VH2-L6-VL1 wherein, here, VL1 is the first immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein, VL2 is the second immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein, VH1 is the first immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein, VH2 is the second immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein, and L1 to L6 are amino acid linkers, the antigen-binding polypeptide (where (c) is selected from any one of the more specific embodiments provided herein for the antigen-binding polypeptide in an antigen-binding polypeptide complex having three or fewer polypeptide chains) A multispecific antibody selected from the group consisting of, wherein the antigen-binding polypeptide further comprises one or more immunoglobulin heavy chain constant region 1 (CH1) and / or one or more immunoglobulin light chain constant regions (CL) between any one of the variable regions and / or amino acid linkers (e.g., between VL1 and L1, between L1 and VH1, between VH1 and L2, between L2 and VL1, between L1 and VL2, between VL2 and L2, between L2 and VH2, between VH2 and L3, between L3 and VH1, between VL1 and L1, between L1 and VH2, between VH2 and L2, between L2 and VL2, between VL2 and L3, between L3 and VH1, between VH1 and L4, between L4 and VH2, between VH2 and L5, between L5 and VL2, between VL2 and L6, between L6 and VL1, between VH1 and L4, between L4 and VL2, between L4 and VL2, between VL2 and L5, between L5 and VH2, between VH2 and L6, or between L6 and VL1). The multispecific antibody. **Claim 130** A multispecific antibody comprising a first polypeptide, a second polypeptide, a third polypeptide, and a fourth polypeptide; wherein the first polypeptide has a structure represented by VL1-L1-CL; wherein the second polypeptide has a structure represented by VH1-L2-CH1-L3-Fc; wherein the third polypeptide has a structure represented by VH2-L4-VH3-L5-CH1-L6-Fc; wherein the fourth polypeptide has a structure represented by VL3-L7-VL2-L8-CL; and where VL1 is a first immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to the SARS-CoV-2 protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to the SARS-CoV-2 protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is immunoglobulin heavy chain constant region 1; CL is the immunoglobulin light chain constant region; and L1 to L8 are amino acid linkers, said multispecific antibody.

131. VH1, VH2 and / or VH3 are CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 43, 51, 59, 67, 75, 171, 179, 187, 264, 272, 280, 288, 513, 521, 529, 537, 545, 553, 561, 569, 577, 585, 593, 601, 609, 617, 639, 647, 656 and 664; CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 44, 52, 60, 68, 76, 172, 180, 188, 265, 273, 281, 289, 514, 522, 530, 538, 546, 554, 562, 570, 578, 586, 594, 602, 610, 618, 640, 648, 657 and 665; and / or CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 45, 53, 61, 69, 77, 173, 181, 189, 266, 274, 282, 290, 515, 523, 531, 539, 547, 555, 563, 571, 579, 587, 595, 603, 611, 619, 641, 649, 658 and 666 comprise; and / or, VL1, VL2 and / or VL3 are CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 43, 51, 59, 67, 75, 171, 179, 187, 264, 272, 280, 288, 513, 521, 529, 537, 545, 553, 561, 569, 577, 585, 593, 601, 609, 617, 639, 647, 656 and 664; CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 44, 52, 60, 68, 76, 172, 180, 188, 265, 273, 281, 289, 514, 522, 530, 538, 546, 554, 562, 570, 578, 586, 594, 602, 610, 618, 640, 648, 657 and 665; and / or CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 45, 53, 61, 69, 77, 173, 181, 189, 266, 274, 282, 290, 515, 523, 531, 539, 547, 555, 563, 571, 579, 587, 595, 603, 611, 619, 641, 649, 658 and 666 comprising the multispecific antibody according to claim 129 or 130.

132. VH1, VH2 and / or VH3 comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity with any one of SEQ ID NOs: 42, 50, 58, 66, 74, 170, 178, 186, 263, 271, 279, 287, 510, 512, 520, 528, 536, 544, 552, 560, 568, 576, 584, 592, 600, 608, 616, 624, 626, 628, 630, 632, 634, 636, 638, 646, 654, 663, 779, 781, 785 and 787; and / or VL1, VL2, and / or VL3 comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with any one of SEQ ID NOs: 38, 46, 54, 62, 70, 166, 174, 182, 259, 267, 275, 283, 508, 509, 511, 516, 524, 532, 540, 548, 556, 564, 572, 580, 588, 596, 604, 612, 620, 625, 627, 629, 631, 633, 635, 637, 642, 650, 659, and 667, The multispecific antibody according to any one of claims 129 to 131.

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