HUMAN MONOCLONAL ANTIBODY AGAINST THE VP1 PROTEIN OF JC VIRUS

• US 20150191530A1
• Filed: 06/26/2013
• Published: 07/09/2015
• Est. Priority Date: 06/27/2012
• Status: Active Grant

• Current Assignee: Pomona Ricerca S.R.L.
• Original Assignee: Pomona Ricerca S.R.L.
• Inventors: Clementi, Massimo, Burioni, Roberto
• Granted Patent: US 10,011,648 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: C07K 16/081 from DNA viruses
• CPC Class Codes: C07K 16/084 Papovaviridae, e.g. papillomavirus, polyomavirus, SV40, BK virus, JC virus
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/30 characterized by aspects of specificity or valency
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• 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: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: G01N 2469/10 Detection of antigens from microorganism in sample from host
• CPC Class Codes: G01N 33/56983 Viruses
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

A human neutralizing monoclonal antibody is directed against the VP1 protein of JC virus. The JC virus is responsible for progressive multifocal leukoencephalopathy (PML). The antibody is used in a therapeutic or prophylactic treatment of a JCV infection or of a disease associated with a JCV infection, such as progressive multifocal leukoencephalopathy (PML). The antibody is also used in the diagnosis of JCV infections or of diseases associated with JCV infections.

Claims

1. A monoclonal antibody directed against the VP1 protein of JC virus, wherein the monoclonal antibody is a human antibody and is capable of neutralizing the JC virus.

2. The monoclonal antibody according to claim 1, which is capable of binding to a conformational epitope of the JCV VP1 protein, comprising at least one amino acid residue of the primary sequence of the JCV VP1 protein selected from the group consisting of I62, S65, A127, D130, N131, A133, A175, and any combination thereof.

3. The monoclonal antibody according to claim 2, wherein the conformational epitope of the JCV VP1 protein comprises the amino acid residues I62, S65, A127, D130, N131, A133 and A175 of the primary sequence of the JCV VP1 protein.

4. The monoclonal antibody according to claim 1, which is a full-length immunoglobulin or a functional immunoglobulin fragment selected from the group consisting of Fab, Fab′

, F(ab′

)₂, Fv, single chain antibodies (scFv) and single domain antibodies.

5. The monoclonal antibody according to claim 1, comprising at least a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region has the sequence SEQ ID NO:

1 and the light chain variable region has the sequence SEQ ID NO;

2, or the heavy chain variable region is encoded by the sequence SEQ ID NO;

3 and the light chain variable region is encoded by the sequence SEQ ID NO;

4.

6. The monoclonal antibody according to claim 1, for use in the therapeutic or prophylactic treatment of a JCV infection or of a disease associated with a JCV infection.

7. A monoclonal antibody for use according to claim 6, wherein the disease associated with a JCV infection is progressive multifocal leukoencephalopathy (PML).

8. A pharmaceutical composition comprising a monoclonal antibody according to claim 1.

9. The pharmaceutical composition according to claim 8, wherein the pharmaceutical composition is adapted for use in the therapeutic or prophylactic treatment of a JCV infection or of a disease associated with a JCV infection.

10. A pharmaceutical composition for use according to claim 9, wherein the disease associated with a JCV infection is progressive multifocal leukoencephalopathy (PML).

11. An in vitro method of diagnosis of a JCV infection or of a disease associated with a JCV infection, the method comprising the steps of:

contacting a biological sample from a patient suspected of being infected with JCV with a monoclonal antibody according to claim 1, under suitable conditions for the monoclonal antibody to bind the JCV VP1 antigen, if present in the sample, and

qualitatively or quantitatively detecting the binding of the monoclonal antibody to the JCV VP1 antigen, said binding being indicative of JCV infection or of a disease associated with a JCV infection.

12. The method according to claim 11, wherein the disease associated with a JCV infection is progressive multifocal leukoencephalopathy (PML).

13. The method according to claim 11, which is an immunological ELISA assay or an immunological fluorescent assay or an immunohistochemical assay.

14. An immunodiagnostic kit for the diagnosis of a JCV infection or of a disease associated with a JCV infection, the kit comprising a monoclonal antibody according to claim 1 and instructions for carrying out an in vitro immunodiagnostic method.

15. An immunodiagnostic kit, the kit comprising a monoclonal antibody directed against the VP1 protein of JC virus, wherein the monoclonal antibody is a human antibody and is capable of neutralizing the JC virus, and instructions for carrying out an in vitro immunodiagnostic method, wherein the in vitro immunodiagnostic method is a method according to claim 11.

16. The kit according to claim 14, wherein the disease associated with a JCV infection is progressive multifocal leukoencephalopathy (PML).

17. A neutralizing method for the JCV virus in a human patient suffering from a JCV infection, the method comprising administering to a human patient an effective amount of a monoclonal antibody according to claim 1.