Epitope of RSV fusion protein and antibody recognizing the same

Patent metadata

Field	Value
Publication number	US-9856313-B2
Application number	US-201414777275-A
Country	US
Kind code	B2
Filing date	Mar 17, 2014
Priority date	Mar 15, 2013
Publication date	Jan 2, 2018
Grant date	Jan 2, 2018

Abstract

The present invention relates to an epitope peptide (or a variant thereof) which can be used in the prevention of respiratory syncytial virus (RSV) infection, a recombinant protein comprising the epitope peptide (or a variant thereof) and a carrier protein, and uses of the epitope peptide (or a variant thereof) and the recombinant protein. The present invention also relates to an antibody against the epitope peptide, a cell line for generating the antibody, and uses thereof. Furthermore, the present invention also relates to a vaccine or a pharmaceutical composition comprising the recombinant protein or the antibody according to the invention, for preventing one or more symptoms associated with RSV infection.

First claim

The invention claimed is:

1. A monoclonal antibody and an antigen binding fragment thereof, wherein the monoclonal antibody can specifically bind to amino acid residues from positions 148 to 216 of respiratory syncytial virus (RSV) fusion protein (F protein) or a fragment thereof, and/or amino acid residues from positions 62 to 69 or positions 62 to 76 of RSV F protein, wherein the monoclonal antibody comprises the following CDRs: 1) a heavy chain CDR1 set forth in SEQ ID NO:20; 2) a heavy chain CDR2 set forth in SEQ ID NO:21; 3) a heavy chain CDR3 set forth in SEQ ID NO:22; 4) a light chain CDR1 set forth in SEQ ID NO:23; 5) a light chain CDR2 set forth in SEQ ID NO:24; and, 6) a light chain CDR3 set forth in SEQ ID NO:25, and the F protein has an amino acid sequence as set forth in SEQ ID NO. 15.

2. An isolated nucleic acid molecule, encoding the monoclonal antibody or antigen binding fragment thereof according to claim 1 .

3. A vector, comprising the isolated nucleic acid molecule according to claim 2 .

4. A host cell, comprising the isolated nucleic acid molecule according to claim 2 or a vector comprising the isolated nucleic acid molecule.

5. A hybridoma cell line RSV-Y-5C4-2, which is deposited in China Center for Type Culture Collection (CCTCC), and has a deposit number of CCTCC NO: C2012147.

6. A method for stabilizing pre-F protein, comprising contacting the monoclonal antibody or antigen binding fragment thereof according to claim 1 with a sample comprising pre-F protein.

7. A kit comprising the monoclonal antibody or antigen binding fragment thereof according to claim 1 .

8. A pharmaceutical composition comprising the monoclonal antibody or antigen binding fragment thereof according to claim 1 , and a pharmaceutically acceptable carrier and/or excipient.

9. A method for preventing or treating RSV infection, comprising administering a prophylactically or therapeutically effective amount of the monoclonal antibody or antigen binding fragment thereof according to claim 1 to a subject in need thereof.

10. A method for expressing pre-F protein or an antigen-antibody complex, comprising co-expressing a nucleic acid encoding the monoclonal antibody or antigen binding fragment thereof according to claim 1 , and a nucleic acid encoding F protein in a cell.

11. A kit comprising a nucleic acid encoding the monoclonal antibody or antigen binding fragment thereof according to claim 1 , and a nucleic acid encoding F protein.

12. The monoclonal antibody or antigen binding fragment thereof according to claim 1 , wherein the monoclonal antibody has one or more of the following features:
(1) the monoclonal antibody comprises a) a heavy chain variable region set forth in SEQ ID NO:17; and b) a light chain variable region set forth in SEQ ID NO:19;
(2) the monoclonal antibody or antigen binding fragment thereof is selected from Fab, Fab′, F(ab′)2, Fd, Fv, dAb, complementary determining region fragment, single chain antibody, mouse antibody, humanized antibody, chimeric antibody, or bispecific or poly-specific antibody,
(3) the monoclonal antibody comprises non-CDR region, and the non-CDR region is from species other than murine species;
(4) the monoclonal antibody specifically binds to RSV, and has a neutralizing activity for the virus;
(5) the monoclonal antibody does not bind to post-F protein, but binds and stabilizes pre-F protein; and
(6) the monoclonal antibody is derived from or is the following monoclonal antibody: monoclonal antibody produced by hybridoma cell line RSV-Y-5C4-2, wherein hybridoma cell line RSV-Y-5C4-2 is deposited in China Center for Type Culture Collection (CCTCC), and has a deposit number of CCTCC NO: C2012147.

13. The monoclonal antibody or antigen binding fragment thereof according to claim 12 , wherein the single chain antibody is scFv.

14. The monoclonal antibody or antigen binding fragment thereof according to claim 12 , wherein the chimeric antibody is human mouse chimeric antibody.

15. The monoclonal antibody or antigen binding fragment thereof according to claim 12 , wherein the non-CDR region is from human antibody.

16. A method for detecting the presence or level of pre-F protein in a sample, comprising the steps of contacting the monoclonal antibody or antigen binding fragment thereof according to claim 1 with a sample having or suspected to have pre-F protein, and detecting any binding between the monoclonal antibody or antigen binding fragment thereof and pre-F protein.

17. A method for diagnosing whether a subject is infected by RSV, comprising the steps of contacting the monoclonal antibody or antigen binding fragment thereof according to claim 1 with a sample from a subject that is suspected to be infected by RSV, and detecting the presence of RSV in the sample by detecting any binding between the monoclonal antibody or antigen binding fragment thereof and pre-F protein of RSV.

Assignees

• Univ Xiamen
• Us Health
• Xiamen Innovax Biotech Co Ltd

Inventors

• Zheng Zizheng
• Mclellan Jason S
• Chen Man
• Zhao Min
• Huang Liangmin
• Graham Barney S
• Xia Ningshao

Classifications

• A61P31/12

  Antivirals · CPC title

• A61P31/14

  for RNA viruses · CPC title

• C12N2760/18522

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• A61K39/155

  Paramyxoviridae, e.g. parainfluenza virus · CPC title