Anti-influenza neuraminidase monoclonal antibodies and uses thereof
The present invention relates to broadly neutralizing anti-influenza monoclonal antibodies or antigen-binding fragments thereof. The present invention further relates to therapeutic uses of the isolated antibody or the antigen-binding fragment thereof.
1. An isolated antibody or antigen-binding fragment thereof that specifically binds to a neuraminidase of influenza virus, comprising:
(i) a heavy chain variable region that comprises HCDR1, HCDR2, and HCDR3 comprising the respective sequences of a HCDR of SEQ ID NOs: 27-29, and
(ii) a light chain variable region that comprises LCDR1, LCDR2 and LCDR3 comprising the respective sequences of a LCDR of SEQ ID NOs: 30-32.
2. The isolated antibody or the antigen-binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 25, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 26.
3. The isolated antibody or the antigen-binding fragment thereof of claim 1 , further comprising a variant Fc constant region.
4. The isolated antibody or the antigen-binding fragment thereof of claim 1 , wherein the antibody is a chimeric antibody, a humanized antibody, or a human antibody.
5. The isolated antibody or the antigen-binding fragment thereof of claim 1 , wherein the antibody or fragment is conjugated to a therapeutic agent, a polymer, a detectable label, or an enzyme.
6. The isolated antibody or the antigen-binding fragment thereof of claim 5 , wherein the polymer is polyethylene glycol (PEG).
7. The isolated antibody or the antigen-binding fragment thereof of claim 5 , wherein the therapeutic agent is cytotoxic agent.
8. An isolated nucleic acid encoding the heavy or light chain variable region of the antibody, or antigen binding portion thereof, of claim 1 .
9. An expression vector comprising the nucleic acid of claim 8 .
10. A cultured host cell comprising the expression vector of claim 9 .
11. A method of preparing an antibody, or antigen-binding portion thereof, comprising: obtaining a cultured host cell comprising a vector comprising a nucleic acid sequence encoding a CDR, a heavy chain variable region, or a light chain variable region of the antibody or antigen binding portion thereof of claim 1 ;
culturing the cell in a medium under conditions permitting expression of a polypeptide encoded by the vector and assembling of an antibody or fragment thereof, and
purifying the antibody or fragment from the cultured cell or the medium of the cell.
12. A pharmaceutical composition comprising the antibody or the antigen-binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier.
13. A method of neutralizing influenza virus in a subject comprising administering to the subject a therapeutically effective amount of the antibody or the antigen-binding fragment thereof of claim 1 .
14. The method of claim 13 , further comprising administering to the subject a therapeutically effective amount of a second antibody or an antigen-binding fragment thereof.
15. A method of treating an influenza virus infection comprising administering to a subject in need thereof therapeutically effective amount of the antibody or the antigen-binding fragment thereof of claim 1 .
16. The method of claim 15 , further comprising administering to the subject a therapeutically effective amount of a second antibody or an antigen-binding fragment thereof.