Anti-SARS-CoV-2-spike glycoprotein antibodies and antigen-binding fragments
The present disclosure provides antibodies and antigen-binding fragments thereof that bind specifically to a coronavirus spike protein and methods of using such antibodies and fragments for treating or preventing viral infections (e.g., coronavirus infections).
1. A vector comprising a polynucleotide encoding a heavy chain variable region (HCVR) of an antibody or antigen-binding fragment thereof that binds a SARS-CoV-2 spike protein comprising the amino acid sequence set forth in SEQ ID NO: 832, wherein said HCVR comprises three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within a HCVR comprising the amino acid sequence set forth in SEQ ID NO: 640.
2. The vector of claim 1 , wherein said HCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 642, said HCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 499, and said HCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 644.
3. The vector of claim 1 , wherein said HCVR comprises the amino acid sequence set forth in SEQ ID NO: 640.
4. The vector of claim 1 , wherein said polynucleotide further encodes an immunoglobulin constant region.
5. The vector of claim 4 , wherein said immunoglobulin constant region is an IgG1 constant region.
6. The vector of claim 1 , wherein said polynucleotide encodes a heavy chain amino acid sequence set forth in SEQ ID NO: 654.
7. The vector of claim 1 , wherein said vector is a lentivirus vector.
8. The vector of claim 1 , wherein said vector is an adeno-associated virus vector.
9. The vector of claim 1 , wherein said polynucleotide is a DNA polynucleotide.
10. The vector of claim 1 , wherein said polynucleotide is an RNA polynucleotide.
11. A vector comprising a polynucleotide encoding a light chain variable region (LCVR) of an antibody or antigen-binding fragment thereof that binds a SARS-COV-2 spike protein comprising the amino acid sequence set forth in SEQ ID NO: 832, wherein said LCVR comprises three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within a LCVR comprising the amino acid sequence set forth in SEQ ID NO: 646.
12. The vector of claim 11 , wherein said LCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 648, said LCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 650, and said LCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 652.
13. The vector of claim 11 , wherein said LCVR comprises the amino acid sequence set forth in SEQ ID NO: 646.
14. The vector of claim 11 , wherein said antibody comprises a light chain amino acid sequence set forth in SEQ ID NO: 656.
15. The vector of claim 11 , wherein said vector is a lentivirus vector.
16. The vector of claim 11 , wherein said vector is an adeno-associated virus vector.
17. The vector of claim 11 , wherein said polynucleotide is a DNA polynucleotide.
18. The vector of claim 11 , wherein said polynucleotide is an RNA polynucleotide.
19. An isolated host cell comprising the vector of any one of claims 1 - 18 .
20. A lipid nanoparticle comprising a polynucleotide encoding a heavy chain variable region (HCVR) of an antibody or antigen-binding fragment thereof that binds a SARS-COV-2 spike protein comprising the amino acid sequence set forth in SEQ ID NO: 832, wherein said HCVR comprises three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within a HCVR comprising the amino acid sequence set forth in SEQ ID NO: 640.
21. The lipid nanoparticle of claim 20 , wherein said HCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 642, said HCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 499, and said HCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 644.
22. The lipid nanoparticle of claim 20 , wherein said HCVR comprises the amino acid sequence set forth in SEQ ID NO: 640.
23. The lipid nanoparticle of claim 20 , wherein said polynucleotide further encodes an immunoglobulin constant region.
24. The lipid nanoparticle of claim 23 , wherein said immunoglobulin constant region is an IgG1 constant region.
25. The lipid nanoparticle of claim 20 , wherein said polynucleotide encodes a heavy chain amino acid sequence set forth in SEQ ID NO: 654.
26. The lipid nanoparticle of claim 20 , wherein said polynucleotide is a DNA polynucleotide.
27. The lipid nanoparticle of claim 20 , wherein said polynucleotide is an RNA polynucleotide.
28. A lipid nanoparticle comprising a polynucleotide encoding a light chain variable region (LCVR) of an antibody or antigen-binding fragment thereof that binds a SARS-COV-2 spike protein comprising the amino acid sequence set forth in SEQ ID NO: 832, wherein said LCVR comprises three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within a LCVR comprising the amino acid sequence set forth in SEQ ID NO: 646.
29. The lipid nanoparticle of claim 28 , wherein said LCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 648, said LCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 650, and said LCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 652.
30. The lipid nanoparticle of claim 28 , wherein said LCVR comprises the amino acid sequence set forth in SEQ ID NO: 646.
31. The lipid nanoparticle of claim 28 , wherein said polynucleotide encodes a light chain amino acid sequence set forth in SEQ ID NO: 656.
32. The lipid nanoparticle of claim 28 , wherein said polynucleotide is a DNA polynucleotide.
33. The lipid nanoparticle of claim 28 , wherein said polynucleotide is an RNA polynucleotide.
34. An isolated host cell comprising the lipid nanoparticle of any one of claims 20 - 33 .
35. A pharmaceutical composition comprising an isolated antibody or antigen-binding fragment thereof that binds a SARS-COV-2 spike protein comprising the amino acid sequence set forth in SEQ ID NO: 832, wherein said isolated antibody or antigen-binding fragment comprises three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) comprising the amino acid sequence set forth in SEQ ID NO: 640, and three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) comprising the amino acid sequence set forth in SEQ ID NO: 646, and a pharmaceutically acceptable carrier.
36. The pharmaceutical composition of claim 35 , wherein said HCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 642, said HCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 499, said HCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 644, said LCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 648, said LCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 650, and said LCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 652.
37. The pharmaceutical composition of claim 36 , wherein said HCVR comprises the amino acid sequence set forth in SEQ ID NO: 640.
38. The pharmaceutical composition of claim 36 , wherein said LCVR comprises the amino acid sequence set forth in SEQ ID NO: 646.
39. The pharmaceutical composition of claim 36 , wherein said HCVR comprises the amino acid sequence set forth in SEQ ID NO: 640 and said LCVR comprises the amino acid sequence set forth in SEQ ID NO: 646.
40. The pharmaceutical composition of claim 36 , wherein said antibody or antigen-binding fragment thereof comprises a heavy chain comprising a heavy chain amino acid sequence set forth in SEQ ID NO: 654.
41. The pharmaceutical composition of claim 36 , wherein said antibody or antigen-binding fragment thereof comprises a light chain comprising a light chain amino acid sequence set forth in SEQ ID NO: 656.
42. The pharmaceutical composition of claim 36 , wherein said isolated antibody or antigen-binding fragment thereof comprises an immunoglobulin constant region.
43. The pharmaceutical composition of claim 42 , wherein said immunoglobulin constant region is an IgG1 constant region.
44. The pharmaceutical composition of claim 35 , further comprising a further therapeutic agent.
45. The pharmaceutical composition of claim 44 , wherein said further therapeutic agent is an anti-viral drug or a vaccine.
46. The pharmaceutical composition of claim 44 , wherein said further therapeutic agent is selected from the group consisting of: an anti-inflammatory agent, an antimalarial agent, an antibody or antigen-binding fragment thereof that specifically binds TMPRSS2, and an antibody or antigen-binding fragment thereof that specifically binds to a spike protein of a coronavirus.
47. The pharmaceutical composition of claim 46 , wherein said anti-inflammatory agent is an antibody.
48. The pharmaceutical composition of claim 47 , wherein said antibody is sarilumab, tocilizumab, or gimsilumab.
49. The pharmaceutical composition of claim 44 , wherein the further therapeutic agent is a second antibody, or an antigen-binding fragment thereof, that binds a SARS-COV-2 spike protein comprising the amino acid sequence set forth in SEQ ID NO: 832, and wherein the second antibody or antigen-binding fragment thereof comprises three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within a HCVR, and three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within a LCVR, wherein the HCVR and the LCVR comprise, respectively, the amino acid sequences set forth in:
(a) SEQ ID NOs: 2 and 10;
(b) SEQ ID NOs: 22 and 30;
(c) SEQ ID NOs: 44 and 51;
(d) SEQ ID NOs: 65 and 73;
(e) SEQ ID NOs: 83 and 89;
(f) SEQ ID NOs: 99 and 107;
(g) SEQ ID NOs: 119 and 127;
(h) SEQ ID NOs: 137 and 145;
(i) SEQ ID NOs: 167 and 175;
(j) SEQ ID NOs: 185 and 191;
(k) SEQ ID NOs: 220 and 228;
(l) SEQ ID NOs: 238 and 242;
(m) SEQ ID NOs: 252 and 260;
(n) SEQ ID NOs: 268 and 276;
(o) SEQ ID NOs: 284 and 290;
(p) SEQ ID NOs: 302 and 306;
(q) SEQ ID NOs: 316 and 323;
(r) SEQ ID NOs: 333 and 338;
(s) SEQ ID NOs: 366 and 372;
(t) SEQ ID NOs: 381 and 387;
(u) SEQ ID NOS: 396 and 401;
(v) SEQ ID NOs: 409 and 416;
(w) SEQ ID NOs: 432 and 440;
(x) SEQ ID NOs: 451 and 457;
(y) SEQ ID NOs: 468 and 472;
(z) SEQ ID NOS: 480 and 487;
(aa) SEQ ID NOs: 495 and 503;
(bb) SEQ ID NOs: 510 and 514;
(cc) SEQ ID NOs: 524 and 530;
(dd) SEQ ID NOs: 548 and 556;
(ee) SEQ ID NOs: 574 and 580;
(ff) SEQ ID NOs: 594 and 600;
(gg) SEQ ID NOs: 608 and 614;
(hh) SEQ ID NOs: 624 and 630;
(ii) SEQ ID NOs: 202 and 210;
(jj) SEQ ID NOs: 658 and 666;
(kk) SEQ ID NOs: 678 and 686;
(ll) SEQ ID NOs: 708 and 713;
(mm) SEQ ID NOs: 723 and 727;
(nn) SEQ ID NOs: 737 and 741;
(00) SEQ ID NOs: 753 and 713;
(pp) SEQ ID NOs: 764 and 770;
(qq) SEQ ID NOs: 780 and 786;
(rr) SEQ ID NOs: 796 and 800;
(ss) SEQ ID NOs: 810 and 818; or
(tt) SEQ ID NOs: 202 and 210.
50. The pharmaceutical composition of claim 49 , wherein the second antibody or antigen-binding fragment thereof comprises three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within a HCVR comprising the amino acid sequence set forth in SEQ ID NO: 202, and three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within a LCVR comprising the amino acid sequence set forth in SEQ ID NO: 210.
51. The pharmaceutical composition of claim 50 , wherein the second antibody or antigen-binding fragment thereof comprises: HCDR1, comprising the amino acid sequence set forth in SEQ ID NO: 204; HCDR2, comprising the amino acid sequence set forth in SEQ ID NO: 206; HCDR3, comprising the amino acid sequence set forth in SEQ ID NO: 208; LCDR1, comprising the amino acid sequence set forth in SEQ ID NO: 212; LCDR2, comprising the amino acid sequence set forth in SEQ ID NO: 55; and LCDR3, comprising the amino acid sequence set forth in SEQ ID NO: 214.