Antibody neutralizing human respiratory syncytial virus

Patent metadata

Field	Value
Publication number	US-12371478-B2
Application number	US-202418630437-A
Country	US
Kind code	B2
Filing date	Apr 9, 2024
Priority date	Oct 29, 2015
Publication date	Jul 29, 2025
Grant date	Jul 29, 2025

Abstract

The present invention relates to monoclonal antibodies which have high anti-RSV neutralizing titers. The invention further provides for isolated nucleic acids encoding the antibodies of the invention and host cells transformed therewith. The invention yet further provides for diagnostic, prophylactic and therapeutic methods employing the antibodies and nucleic acids of the invention, particularly as a passive immunotherapy agent in infants and the elderly.

First claim

The invention claimed is:

1. An isolated antibody or antigen binding fragment thereof that binds to human RSV F protein, wherein the antibody or antigen binding fragment comprises a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:1, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:2, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:3, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:4, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:5, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:6.

2. The isolated antibody or antigen binding fragment thereof of claim 1 , further comprising modifications to the constant domain to increase the biological half-life of the antibody.

3. The isolated antibody of claim 2 , wherein the modifications to increase the antibody's biological half-life correspond to
a) one or more of the mutations T252L, T254S, T256F,
b) a mutation within the CH1 or CL region to contain a salvage receptor binding epitope taken from two loops of a CH2 domain of an Fc region of an IgG, or
c) the triple mutation M252Y/S254T/T256E (YTE).

4. The isolated antibody of claim 2 , wherein the modifications to increase the antibody's biological half-life correspond to the triple mutation M252Y/S254T/T256E (YTE).

5. The isolated antibody or antigen binding fragment thereof of claim 2 , comprising a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 7.

6. The isolated antibody or antigen binding fragment thereof of claim 2 , comprising a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 7.

7. The isolated antibody or antigen binding fragment thereof of claim 2 , comprising a heavy chain variable region comprising an amino acid sequence that is at least 98% identical to SEQ ID NO: 7.

8. The isolated antibody or antigen binding fragment thereof of claim 2 , comprising a light chain variable region comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 8.

9. The isolated antibody or antigen binding fragment thereof of claim 2 , comprising a light chain variable region comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 8.

10. The isolated antibody or antigen binding fragment thereof of claim 2 , comprising a light chain variable region comprising an amino acid sequence that is at least 98% identical to SEQ ID NO: 8.

11. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the antibody is produced in a CHO cell.

12. A composition comprising the antibody or antigen binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier or diluent.

13. The composition of claim 12 , further comprising an antibody or an antigen binding fragment thereof against a respiratory pathogen which is influenza, human cytomegalovirus (hCMV), human metapneumovirus (hMPV), human parainfluenza (hP1V), human rhinovirus (hRV), mycoplasma pneumonia, streptococcus pneumoniae, adenovirus, bocavirus, enterovirus, norovirus or BK virus.

14. The composition of claim 13 , wherein the respiratory pathogen is influenza, hCMV, hMPV, hP1V, norovirus, or BK virus.

15. An immunogenic composition comprising the antibody or antigen binding fragment thereof of claim 1 and an antigen which is RSV F protein or RSV G protein or fragments thereof.

16. An isolated antibody or antigen binding fragment thereof that binds to human RSV F protein, wherein the antibody or antigen binding fragment comprises a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:1, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:2, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:3, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:4, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:5, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:6,
wherein the amino acid sequence of the heavy chain variable region is not SEQ ID NO: 9.

17. The isolated antibody or antigen binding fragment thereof of claim 16 , comprising a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 7 and a light chain variable region comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 8.

18. The isolated antibody or antigen binding fragment thereof of claim 16 , comprising a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 7 and a light chain variable region comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 8.

19. The isolated antibody or antigen binding fragment thereof of claim 16 , comprising a heavy chain variable region comprising an amino acid sequence that is at least 98% identical to SEQ ID NO: 7 and a light chain variable region comprising an amino acid sequence that is at least 98% identical to SEQ ID NO: 8.

Assignees

• Merck Sharp & Dohme Llc

Inventors

• Vora Kalpit A
• Cox Kara S
• Tang Aimin
• Chen Zhifeng
• Distefano Daniel
• Zhang Lan
• Su Hua-Poo

Classifications

• C07K16/11 Primary

  Paramyxoviridae (F); Pneumoviridae (F), e.g. respiratory syncytial virus [RSV] · CPC title

• C07K2317/732

  Antibody-dependent cellular cytotoxicity [ADCC] · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/41

  Glycosylation, sialylation, or fucosylation · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title