Compositions and methods for the therapy and diagnosis of influenza

• US 8,057,796 B2
• Filed: 11/12/2008
• Issued: 11/15/2011
• Est. Priority Date: 11/12/2007
• Status: Active Grant

• Current Assignee: Spaltudaq Corporation
• Original Assignee: Theraclone Sciences, Inc.
• Inventors: Cox, Thomas, Grandea, Andres III, Mitcham, Jennifer, Moyle, Matthew, Olsen, Ole, King, Gordon
• Primary Examiner(s): Mosher; Mary E.
• Assistant Examiner(s): Blumel; Benjamin P
• Application Number:
  US12/269,781
• Publication Number:
  US 20090226433A1
• Time in Patent Office: 1,098 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 anti-matrix 2 ectodomain (M2e) antibody, where in the M2e is of an influenza A virus, and wherein said antibody comprises a VH CDR1 region comprising the amino acid sequence of NYYWS (SEQ ID NO:

72);

a VH CDR2 region comprising the amino acid sequence of FIYYGGNTKYNPSLKS (SEQ ID NO;

     74);

a VH CDR3 region comprising the amino acid sequence of ASCSGGYCILD (SEQ ID NO;

     76);

a VL CDR1 region comprising the amino acid sequence of RASQNIYKYLN (SEQ ID NO;

     59);

a VL CDR2 region comprising the amino acid sequence of AASGLQS (SEQ ID NO;

     61); and

a VL CDR3 region comprising the amino acid sequence of QQSYSPPLT (SEQ ID NO;

     63).

2. The antibody of claim 1, wherein said antibody is isolated from a B-cell from a human donor.

4. A composition comprising the antibody of claims 1 or 3.

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 method of claim 6, wherein said M2 ion channel inhibitor is amantadine or rimantadine.

8. The method of claim 6, wherein said neuraminidase inhibitor is zanamivir, or oseltamivir phosphate.

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

10. The antibody of claims 1 or 3, wherein said antibody is operably-linked to a therapeutic agent or a detectable label.

11. A diagnostic kit comprising the antibody according to claims 1 or 3.

3. An isolated anti-matrix 2 ectodomain (M2e) antibody, wherein the M2e is of an influenza A virus, and wherein said antibody comprises a V_H CDR1 region comprising the amino acid sequence of NYYWS (SEQ ID NO:

72);

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

     74);

a V_H CDR3 region comprising the amino acid sequence of ASCSGGYCILD (SEQ ID NO;

     76);

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

     59);

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

     61); and

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

     63).