Compositions and methods for the therapy and diagnosis of influenza

• US 8,114,402 B2
• Filed: 03/17/2010
• Issued: 02/14/2012
• Est. Priority Date: 11/12/2007
• Status: Expired due to Fees

• Current Assignee: Theraclone Sciences, Inc.
• Original Assignee: Theraclone Sciences, Inc.
• Inventors: Grandea, Andres III, King, Gordon, Cox, Thomas, Olsen, Ole, Mitcham, Jennifer, Moyle, Matthew
• Primary Examiner(s): Blumel, Benjamin P
• Application Number:
  US12/726,297
• Publication Number:
  US 20100178295A1
• Time in Patent Office: 699 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: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 16/1018 Orthomyxoviridae, e.g. influenza virus
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/32 specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C12N 2760/16122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: G01N 33/56983 Viruses

Abstract

The present invention provides novel human anti-influenza antibodies and related compositions and methods. These antibodies are used in the diagnosis and treatment of influenza infection.

Claims

1. An isolated fully human monoclonal antibody, wherein said monoclonal antibody has the following characteristics

a) binds to an epitope in the extracellular domain of the matrix 2 ectodomain (M2e) polypeptide of an influenza A virus;

b) binds to influenza A infected cells; and

c) binds to influenza A virus, and wherein said antibody comprises a V_HCDR1 comprising the amino acid sequence of SNYMS (SEQ ID NO;

     103);

a V_H CDR2 region comprising amino acid sequence of VIYSGGSTYYADSVK (SEQ ID NO;

     105), a V_H CDR3 region comprising the amino acid sequence of CLSRMRGYGLDV (SEQ ID NO;

     107);

a V_L CDR1 region comprising the amino acid sequence of RTSQSISSYLN (SEQ ID NO;

     92);

a V_L CDR2 region comprising the amino acid sequence of AASSLQSGVPSRF (SEQ ID NO;

     94); and

a V_L CDR3 region comprising the amino acid sequence of QQSYSMPA (SEQ ID NO;

     96).

4. A composition comprising the antibody of claim 1.

5. The composition of claim 4, further comprising an anti-viral drug, a viral entry inhibitor or a viral attachment inhibitor.

6. The composition of claim 5, wherein said anti-viral drug is a neuraminidase inhibitor, a HA inhibitor, a sialic acid inhibitor or an M2 ion channel inhibitor.

7. The composition of claim 6, wherein said neuraminidase inhibitor is zanamivir, or oseltamivir phosphate.

8. The composition of claim 4, further comprising a second anti-influenza A antibody.

9. The antibody of claim 1, wherein said antibody is operably-linked to a therapeutic agent or a detectable label.

10. A diagnostic kit comprising the antibody according to claim 1.

2. An isolated anti-matrix 2 ectodomain (M2e) antibody, wherein said antibody comprises a V_H CDR1 region comprising the amino acid sequence of SNYMS (SEQ ID NO:

103);

a V_H CDR2 region comprising the amino acid sequence of VIYSGGSTYYADSVK (SEQ ID NO;

     105), a V_H CDR3 region comprising the amino acid sequence of CLSRMRGYGLDV (SEQ ID NO;

     107);

a V_L CDR1 region comprising the amino acid sequence of RTSQSISSYLN (SEQ ID NO;

     92);

a V_L CDR2 region comprising the amino acid sequence of AASSLQSGVPSRF (SEQ ID NO;

     94); and

a V_L CDR3 region comprising the amino acid sequence of QQSYSMPA (SEQ ID NO;

     96);

wherein the M2e is of an influenza A virus.

3. An isolated fully human monoclonal anti-matrix 2 ectodomain (M2e) antibody comprising

a heavy chain sequence comprising the amino acid sequence of SEQ ID NO:

50 and a light chain sequence comprising the amino acid sequence SEQ ID NO;

52;

wherein the M2e is of an influenza A virus.