USRE50268EActiveUtility

Broadly neutralizing antibody and uses thereof

93
Assignee: INT AIDS VACCINE INITIATIVEPriority: Jun 11, 2014Filed: Apr 8, 2022Granted: Jan 14, 2025
Est. expiryJun 11, 2034(~7.9 yrs left)· nominal 20-yr term from priority
Inventors:Dennis R. BurtonMarit J. Van GilsWayne KoffPascal Raymond Georges PoignardRogier W. SandersMelissa Danielle De Jean De St. Marcel Simek-LemosDevin Sok
C07K 16/1145C07K 2317/565C07K 2317/55C07K 2317/76C07K 2317/21C07K 16/1063
93
PatentIndex Score
2
Cited by
20
References
30
Claims

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 IC50 of 0.003 μg/ml, compositions containing the same and uses thereof.

Claims

exact text as granted — not AI-modified
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 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 of  claim 1 . 
     
     
       4. A pharmaceutical composition comprising the antibody 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. An isolated polypeptide comprising an antigen-binding antibody fragment of an anti-HIV-1 antibody, wherein the antibody fragment comprises
 (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,   wherein the isolated polypeptide is not an intact antibody.   
     
     
       8. The isolated polypeptide of  claim 7 , wherein the antibody fragment comprises 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 isolated polypeptide of  claim 7 , wherein the antibody fragment comprises the heavy chain CDR3 of SEQ ID NO: 40, and the light chain CDR3 of SEQ ID NO: 58. 
     
     
       10. The isolated polypeptide 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. The isolated polypeptide of  claim 7 , wherein the antibody fragment comprises
 (a) a heavy chain variable region 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 variable region 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.   
     
     
       12. The isolated polypeptide of  claim 11 , wherein the heavy chain sequence is encoded by SEQ ID NO: 1 and the light chain sequence is encoded by SEQ ID NO: 14. 
     
     
       13. The isolated polypeptide of  claim 7 , wherein the antibody fragment comprises
 (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.   
     
     
       14. The isolated polypeptide of  claim 13 , wherein the antibody fragment comprises the heavy chain CDR3 of SEQ ID NO: 40, and the light chain CDR3 of SEQ ID NO: 58. 
     
     
       15. The isolated polypeptide of  claim 13 , 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. An isolated polypeptide comprising an antigen-binding antibody fragment of an anti-HIV-1 antibody, wherein the antibody fragment comprises
 (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 isolated polypeptide interacts with HIV gp120 V1/V2 domain of BG505, and   wherein the isolated polypeptide is not an intact antibody.   
     
     
       17. The isolated polypeptide of  claim 16 , 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. 
     
     
       18. The isolated polypeptide of  claim 16 , 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. 
     
     
       19. A pharmaceutical composition comprising the isolated polypeptide of  claim 7  and a pharmaceutically acceptable carrier. 
     
     
       20. A pharmaceutical composition comprising the isolated polypeptide of  claim 8  and a pharmaceutically acceptable carrier. 
     
     
       21. A pharmaceutical composition comprising the isolated polypeptide of  claim 9  and a pharmaceutically acceptable carrier. 
     
     
       22. A pharmaceutical composition comprising the isolated polypeptide of  claim 10  and a pharmaceutically acceptable carrier. 
     
     
       23. A pharmaceutical composition comprising the isolated polypeptide of  claim 11  and a pharmaceutically acceptable carrier. 
     
     
       24. A pharmaceutical composition comprising the isolated polypeptide of  claim 12  and a pharmaceutically acceptable carrier. 
     
     
       25. A pharmaceutical composition comprising the isolated polypeptide of  claim 13  and a pharmaceutically acceptable carrier. 
     
     
       26. A pharmaceutical composition comprising the isolated polypeptide of  claim 14  and a pharmaceutically acceptable carrier. 
     
     
       27. A pharmaceutical composition comprising the isolated polypeptide of  claim 15  and a pharmaceutically acceptable carrier. 
     
     
       28. A pharmaceutical composition comprising the isolated polypeptide of  claim 16  and a pharmaceutically acceptable carrier. 
     
     
       29. A pharmaceutical composition comprising the isolated polypeptide of  claim 17  and a pharmaceutically acceptable carrier. 
     
     
       30. A pharmaceutical composition comprising the isolated polypeptide of  claim 18  and a pharmaceutically acceptable carrier.

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