IP Library › Granted Patent US 12,371,478
Granted Patent B2
US 12,371,478 · App. 18/630,437 · Granted Jul 29, 2025

Antibody neutralizing human respiratory syncytial virus

Inventors: Kalpit A. Vora (Yardley, PA); Kara S. Cox (Harleysville, PA); Aimin Tang (Lansdale, PA); Zhifeng Chen (Warrington, PA); Daniel DiStefano (Harleysville, PA); Lan Zhang (Chalfont, PA); Hua-Poo Su (Phoenixville, PA)
Assignee: Merck Sharp & Dohme LLC
C07K16/1027A61K39/42A61P31/14A61K2039/505A61K2039/54A61K2039/545C07K2317/14C07K2317/21C07K2317/34C07K2317/41C07K2317/524C07K2317/565C07K2317/732C07K2317/76C07K2317/92C07K2317/94
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Quick Facts
Patent No.
US 12,371,478
App. No.
18/630,437
Granted
Jul 29, 2025
Kind
B2
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.

Claims (23)

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.

Assignments (2)
MERGER Recorded Apr 12, 2024
From: MERCK SHARP & DOHME CORP.
To: MERCK SHARP & DOHME LLC
Reel/Frame 067085/0948 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 10, 2024
From: VORA, KALPIT A.; COX, KARA S.; TANG, AIMIN; CHEN, ZHIFENG; DISTEFANO, DANIEL; ZHANG, LAN; SU, HUA-POO
To: MERCK SHARP & DOHME CORP.
Reel/Frame 067062/0488 →
Continuity (8)
Continuation 18065172 · Dec 13, 2022
Continuation 17115510 · Dec 8, 2020
Continuation 16434729 · Jun 7, 2019
Continuation 15928438 · Mar 22, 2018
Division 15335560 · Oct 27, 2016
Provisional Application 62367359 · Jul 27, 2016
Provisional Application 62247841 · Oct 29, 2015
Related Publication 20240247052A1 · Jul 25, 2024
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