Influenza hemagglutinin antibodies, compositions and related methods

• US 8,784,819 B2
• Filed: 09/29/2010
• Issued: 07/22/2014
• Est. Priority Date: 09/29/2009
• Status: Active Grant

• Current Assignee: iBio, Inc.
• Original Assignee: iBio, Inc.
• Inventors: Yusibov, Vidadi, Mett, Vadim, Chichester, Jessica, Goldschmidt, Lauren
• Primary Examiner(s): Horning, Michelle S
• Assistant Examiner(s): SALVOZA, M FRANCO G
• Application Number:
  US13/498,946
• Publication Number:
  US 20120315323A1
• Time in Patent Office: 1,392 Days
• Field of Search: None
• US Class Current: 424/147.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: C07K 16/1018 Orthomyxoviridae, e.g. influenza virus
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C12N 15/8258 for the production of oral vaccines (antigens) or immunoglobulins

Abstract

Antibodies against influenza hemagglutinin, compositions containing the antibodies, and methods of using the antibodies are provided herein.

Claims

1. An isolated monoclonal antibody that binds hemagglutinin, wherein the antibody has the ability to inhibit hemagglutination, and wherein the antibody is selected from the group consisting of:

an antibody comprising the light chain variable region amino acid sequence set forth in amino acids 1-97 of SEQ ID NO;

79, and the heavy chain variable region amino acid sequence set forth in amino acids 1-115 of SEQ ID NO;

78; and

an antibody comprising the light chain variable region amino acid sequence set forth in amino acids 1-96 of SEQ ID NO;

81, and the heavy chain variable region amino acid sequence set forth in amino acids 1-112 of SEQ ID NO;

80.

2. The antibody of claim 1, wherein the antibody comprises the light chain variable region amino acid sequence set forth in amino acids 1-97 of SEQ ID NO:

79, and the heavy chain variable region amino acid sequence set forth in amino acids 1-115 of SEQ ID NO;

78.

3. The antibody of claim 1, wherein the antibody comprises the light chain variable region amino set forth in amino acids 1-96 of SEQ ID NO:

81, and the heavy chain variable region amino acid sequence set forth in amino acids 1-112 of SEQ ID NO;

80.

9. The antibody of claim 1, wherein the antibody is a human, humanized, or part-human antibody.

10. The antibody of claim 1, wherein the antibody is a recombinant antibody.

11. The antibody of claim 1, wherein the antibody is produced in a plant.

12. The antibody of claim 1, wherein the antibody is operatively attached to a biological agent, an imaging agent, a detectable agent, or a diagnostic agent.

13. The antibody of claim 12, wherein the antibody is operatively attached to an agent that cleaves a substantially inactive prodrug to release a substantially active drug.

14. The antibody of claim 13, wherein the drug is an anti-influenza agent.

15. The antibody of claim 12, wherein the antibody is operatively attached to an anti-viral agent.

16. The antibody of claim 12, wherein the antibody is operatively attached to the biological agent as a fusion protein prepared by expressing a recombinant vector that comprises, in the same reading frame, a DNA segment encoding the antibody operatively linked to a DNA segment encoding the biological agent.

17. The antibody of claim 12, wherein the antibody is operatively attached to the biological agent via a biologically releasable bond or selectively cleavable linker.

18. The antibody of claim 12, wherein the antibody is operatively attached to an X-ray detectable compound, a radioactive ion or a nuclear magnetic spin-resonance isotope.

19. The antibody of claim 12, wherein the antibody is operatively attached to biotin, avidin or to an enzyme that generates a colored product upon contact with a chromogenic substrate.

20. A pharmaceutical composition comprising the antibody of claim 1, and a pharmaceutically acceptable carrier.

21. The composition of claim 20, wherein the composition is formulated for parenteral or topical administration.

22. The composition of claim 20, wherein the antibody is a recombinant, plant-produced antibody.

23. The composition of claim 20, wherein the pharmaceutically acceptable composition is an encapsulated or liposomal formulation.

4. An antibody that binds hemagglutinin, wherein the antibody has the ability to inhibit hemagglutination, and wherein the antibody is selected from the group consisting of:

an antibody comprising the light chain amino acid sequence set forth in SEQ ID NO;

79, and the heavy chain amino acid sequence set forth in SEQ ID NO;

78; and

an antibody comprising the light chain amino acid sequence set forth in SEQ ID NO;

81, and the heavy chain amino acid sequence set forth in SEQ ID NO;

80.

5. The antibody of claim 4, wherein the antibody comprises the light chain amino acid sequence set forth in SEQ ID NO:

79 and the heavy chain amino acid sequence set forth in SEQ ID NO;

78.

6. The antibody of claim 4, wherein the antibody comprises the light chain amino acid sequence set forth in SEQ ID NO:

81 and the heavy chain amino acid sequence set forth in SEQ ID NO;

80.

7. An antigen-binding fragment of an antibody that binds hemagglutinin and has the ability to inhibit hemagglutination, wherein the antigen-binding fragment comprises:

the light chain variable region amino acid sequence set forth in amino acids 1-97 of SEQ ID NO;

79, and the heavy chain variable region amino acid sequence set forth in amino acids 1-115 of SEQ ID NO;

78;

or

the light chain variable region amino acid sequence set forth in amino acids 1-96 of SEQ ID NO;

81, and the heavy chain variable region amino acid sequence set forth in amino acids 1-112 of SEQ ID NO;

80;

wherein the antigen-binding fragment is an scFv, Fv, Fab′

, Fab, diabody, linear antibody, or F(ab′

)₂ antigen-binding fragment.

8. The antigen-binding fragment of claim 7, wherein the antigen-binding fragment is a univalent fragment, or a single domain antibody.