Broadly neutralizing antibody and uses thereof

Patent metadata

Field	Value
Publication number	US-RE49037-E
Application number	US-201916726453-A
Country	US
Kind code	E1
Filing date	Dec 24, 2019
Priority date	Jun 11, 2014
Publication date	Apr 19, 2022
Grant date	Apr 19, 2022

Abstract

The present invention relates to an exceptionally broad and potent neutralizing antibody which may comprise cross-clade neutralizing coverage of 83% at a median IC 50 of 0.003 μg/ml, compositions containing the same and uses thereof.

First claim

What is claimed is:

1. A non-naturally occurring anti-HIV-1 monoclonal antibody or antigen binding portion thereof, comprising (a) a heavy chain sequence comprising an amino acid sequence encoded by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, or SEQ ID NO: 13 and (b) a light chain sequence comprising an amino acid sequence encoded by SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO: 26.

2. The non-naturally occurring anti-HIV-1 monoclonal antibody or antigen binding portion of claim 1 , wherein the heavy chain sequence is encoded by SEQ ID NO: 1 and the light chain sequence is encoded by SEQ ID NO: 14.

3. A composition comprising the antibody or antigen binding portion of claim 1 .

4. A pharmaceutical composition comprising the antibody or antigen binding portion of claim 1 and a pharmaceutically acceptable carrier.

5. The antibody or antigen binding portion of claim 1 , wherein the heavy chain sequence comprises a third complementarity determining region (CDRE3) of 33 to 34 amino acid residues.

6. The antibody or antigen binding portion of claim 5 , wherein a triad of aspartic acid residues at the tip of CDRH3 provides an anionic potential to the CDRH3.

7. A non-naturally occurring anti-HIV-1 monoclonal antibody or antigen binding portion thereof, comprising
(a) the heavy chain CDRs of a heavy chain sequence encoded by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, or SEQ ID NO: 13, and (b) the light chain CDRs of a light chain sequence encoded by SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO: 26.

8. The antibody or antigen binding portion of claim 7 comprising the heavy chain CDR3 of any one of SEQ ID NO: 40-52 and the light chain CDR3 of any one of SEQ ID NO: 58-70.

9. The antibody or antigen binding portion of claim 7, wherein the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 40, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 58.

10. The antibody or antigen binding portion of claim 8, wherein a triad of aspartic acid residues at the tip of heavy chain CDR3 provides an anionic potential to the heavy chain CDR3.

11. A non-naturally occurring anti-HIV-1 monoclonal antibody or antigen binding portion thereof comprising
(a) a heavy chain variable region comprising an amino acid sequence with at least 90% identity to the amino acid sequence encoded by SEQ ID NO:1, and (b) a light chain variable region comprising an amino acid sequence with at least 90% identity to the amino acid sequence encoded by SEQ ID NO: 14.

12. The antibody or antigen binding portion of claim 11, wherein the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 40, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 58.

13. The antibody or antigen binding portion of claim 11, wherein the heavy chain variable region comprises an amino acid sequence with at least 95% identity to the amino acid sequence encoded by SEQ ID NO: 1, and the light chain variable region comprises an amino acid sequence with at least 95% identity to the amino acid sequence encoded by SEQ ID NO: 14.

14. A non-naturally occurring anti-HIV-1 monoclonal antibody or antigen binding portion thereof comprising
(a) a heavy chain variable region comprising an amino acid sequence with at least 90% identity to the amino acid sequence encoded by SEQ ID NO:1, and (b) a light chain variable region comprising an amino acid sequence with at least 90% identity to the amino acid sequence encoded by SEQ ID NO: 14, wherein the antibody interacts with HIV gp120 V1/V2 domain of BG505.

15. The antibody or antigen binding portion of claim 14, wherein the heavy chain variable region comprises an amino acid sequence with at least 95% identity to the amino acid sequence encoded by SEQ ID NO: 1, and the light chain variable region comprises an amino acid sequence with at least 95% identity to the amino acid sequence encoded by SEQ ID NO: 14.

16. The antibody or antigen binding portion of claim 14, wherein the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 40, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 58.

17. A non-naturally occurring anti-HIV-1 monoclonal antibody or antigen binding portion thereof comprising
(a) a heavy chain variable region comprising an amino acid sequence with at least 90% identity to the amino acid sequence encoded by SEQ ID NO:1, and (b) a light chain variable region comprising an amino acid sequence with at least 90% identity to the amino acid sequence encoded by SEQ ID NO: 14, wherein the antibody has a minimal cross-clade neutralization coverage of 80% on the 106-virus panel shown in FIG. 9.

18. The antibody or antigen binding portion of claim 17, wherein the heavy chain variable region comprises an amino acid sequence with at least 95% identity to the amino acid sequence encoded by SEQ ID NO: 1, and the light chain variable region comprises an amino acid sequence with at least 95% identity to the amino acid sequence encoded by SEQ ID NO: 14.

19. The antibody or antigen binding portion of claim 17, wherein the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 40, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 58.

20. A non-naturally occurring anti-HIV-1 monoclonal antibody or antigen binding portion thereof comprising
(a) a heavy chain variable region comprising an amino acid sequence with at least 90% identity to the amino acid sequence encoded by SEQ ID NO: 1, wherein the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 40, and (b) a light chain variable region comprising an amino acid sequence with at least 90% identity to the amino acid sequence encoded by SEQ ID NO: 14, wherein the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 58, wherein the antibody interacts with HIV gp120 V1/V2 domain of BG505, and has a minimal cross-clade neutralization coverage of 80% on the 106-virus panel shown in FIG. 9, and wherein a triad of aspartic acid residues at the tip of the heavy chain CDR3 provides an anionic potential to the heavy chain CDR3.

21. A pharmaceutical composition comprising the antibody or antigen binding portion of claim 7 and a pharmaceutically acceptable carrier.

22. A pharmaceutical composition comprising the antibody or antigen binding portion of claim 11 and a pharmaceutically acceptable carrier.

23. An isolated polypeptide comprising the amino acid sequence of any one of SEQ ID NO: 40-52.

Assignees

• Int Aids Vaccine Initiative
• Scripps Research Inst
• Univ Cornell

Inventors

• Burton Dennis R
• Van Gils Marit J
• Koff Wayne
• Poignard Pascal R G
• Sanders Rogier W
• Simek-Lemos Melissa D J S
• Sok Devin

Classifications

• C07K16/1145 Primary

  Env proteins, e.g. gp41, gp110/120, gp160, V3, principal neutralising domain [PND] or CD4-binding site · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/55

  Fab or Fab' · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title