Antigen binding molecules targeting SARS-CoV-2
The invention provides, in various embodiments, polypeptides that specifically bind to Spike glycoprotein of severe acute respiratory syndrome coronavirus (e.g., SARS-CoV-2-Spike). The invention also provides, in various embodiments, fusion proteins comprising one or more of the polypeptides, polynucleotides encoding the polypeptides, vectors and host cells suitable for expressing the polypeptides, and methods for treating viral infections (e.g., COVID-19).
1. A polypeptide that specifically binds a severe acute respiratory syndrome coronavirus 2 Spike glycoprotein (SARS-CoV-2-Spike), comprising:
a) an immunoglobulin heavy chain variable region (V H ) comprising a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2) and a heavy chain complementarity determining region 3 (HCDR3) that are identical to the HCDR1, HCDR2 and HCDR3, respectively, of SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 27, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39 or SEQ ID NO: 40; and
b) an immunoglobulin light chain variable region (V L ) comprising a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2) and a light chain complementarity determining region 3 (LCDR3) that are identical to the LCDR1, LCDR2 and LCDR3, respectively, of SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 28, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50 or SEQ ID NO: 51.
2. The polypeptide of claim 1 , comprising the HCDR1, HCDR2 and HCDR3, and LCDR1, LCDR2 and LCDR3, of an antibody selected from:
an antibody comprising SEQ ID NO: 4 and SEQ ID NO: 9;
an antibody comprising SEQ ID NO: 5 and SEQ ID NO: 8;
an antibody comprising SEQ ID NO: 6 and SEQ ID NO: 10;
an antibody comprising SEQ ID NO: 27 and SEQ ID NO: 28;
an antibody comprising SEQ ID NO: 33 and SEQ ID NO: 43;
an antibody comprising SEQ ID NO: 34 and SEQ ID NO: 44;
an antibody comprising SEQ ID NO: 33 and SEQ ID NO: 45;
an antibody comprising SEQ ID NO: 35 and SEQ ID NO: 46;
an antibody comprising SEQ ID NO: 36 and SEQ ID NO: 47;
an antibody comprising SEQ ID NO: 37 and SEQ ID NO: 48;
an antibody comprising SEQ ID NO: 38 and SEQ ID NO: 49;
an antibody comprising SEQ ID NO: 39 and SEQ ID NO: 50; or
an antibody comprising SEQ ID NO: 40 and SEQ ID NO: 51.
3. The polypeptide of claim 1 , wherein:
a) the V H comprises SEQ ID NO: 4; and
b) the V L comprises SEQ ID NO: 9.
4. The polypeptide of claim 1 , wherein:
a) the V H comprises SEQ ID NO: 5; and
b) the V L comprises SEQ ID NO: 8.
5. The polypeptide of claim 1 , wherein:
a) the V H comprises SEQ ID NO: 6; and
b) the V L comprises SEQ ID NO: 10.
6. The polypeptide of claim 1 , wherein:
a) the V H comprises SEQ ID NO: 33; and
b) the V L comprises SEQ ID NO: 43.
7. The polypeptide of claim 1 , wherein:
a) the V H comprises SEQ ID NO: 34; and
b) the V L comprises SEQ ID NO: 44.
8. The polypeptide of claim 1 , wherein:
a) the V H comprises SEQ ID NO: 33; and
b) the V L comprises SEQ ID NO: 45.
9. The polypeptide of claim 1 , wherein:
a) the V H comprises SEQ ID NO: 35; and
b) the V L comprises SEQ ID NO: 46.
10. The polypeptide of claim 1 , wherein:
a) the V H comprises SEQ ID NO: 36; and
b) the V L comprises SEQ ID NO: 47.
11. The polypeptide of claim 1 , wherein:
a) the V H comprises SEQ ID NO: 37; and
b) the V L comprises SEQ ID NO: 48.
12. The polypeptide of claim 1 , wherein:
a) the V H comprises SEQ ID NO: 38; and
b) the V L comprises SEQ ID NO: 49.
13. The polypeptide of claim 1 , wherein:
a) the V H comprises SEQ ID NO: 39; and
b) the V L comprises SEQ ID NO: 50.
14. The polypeptide of claim 1 , wherein:
a) the VII comprises SEQ ID NO: 40; and
b) the V L comprises SEQ ID NO: 51.
15. The polypeptide of claim 1 , wherein the polypeptide is an antibody or an antigen-binding fragment thereof.
16. The polypeptide of claim 15 , wherein the antigen binding fragment is selected from Fab, F(ab′) 2 , Fab′, scFv, or Fv.
17. The polypeptide of claim 15 , further comprising an antibody heavy chain constant region sequence, an antibody light chain constant region sequence, or both an antibody heavy chain constant region sequence and an antibody light chain constant region sequence.
18. The polypeptide of claim 17 , wherein the antibody heavy chain constant region is selected from the group consisting of an IgA constant region, an IgD constant region, an IgE constant region, an IgG constant region and an IgM constant region.
19. A fusion protein comprising the polypeptide of claim 1 .
20. A polynucleotide comprising a sequence encoding the polypeptide of claim 1 .
21. An expression vector comprising the polynucleotide of claim 20 .
22. A host cell comprising the polynucleotide of claim 20 .
23. A composition comprising the polypeptide of claim 1 and one or more pharmaceutical excipients, diluents, or carriers.
24. A method of treating a SARS-CoV-2 infection in a subject in need thereof, comprising administering an effective amount of the composition of claim 23 to the subject.
25. A method of inhibiting fusion between SARS-CoV-2-Spike and a cell in a subject, comprising contacting the cell with an effective amount of the composition of claim 23 .