Method for preventing or treating;infection

• US 9,056,913 B2
• Filed: 05/16/2013
• Issued: 06/16/2015
• Est. Priority Date: 04/29/2005
• Status: Expired due to Fees

• Current Assignee: Glaxosmithkline Biologicals SA (GlaxoSmithKline PLC), Infectious Disease Research Institute
• Original Assignee: Glaxosmithkline Biologicals SA (GlaxoSmithKline PLC)
• Inventors: Coler, Rhea, Lobet, Yves, Reed, Steven
• Primary Examiner(s): Swartz, Rodney P
• Application Number:
  US13/895,574
• Publication Number:
  US 20140050776A1
• Time in Patent Office: 761 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/523 expressing foreign proteins
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/55566 Emulsions, e.g. Freund's adjuvant, MF59
• CPC Class Codes: A61K 2039/55572 Lipopolysaccharides; Lipid A; Monophosphoryl lipid A
• CPC Class Codes: A61K 2039/55577 Saponins; Quil A; QS21; ISCOMS
• CPC Class Codes: A61K 2039/575 humoral response
• CPC Class Codes: A61K 31/4409 only substituted in position 4, e.g. isoniazid, iproniazid
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 39/04 Mycobacterium, e.g. Mycobacterium tuberculosis
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 31/06 for tuberculosis
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/35 from Mycobacteriaceae (F)

Abstract

The present invention is directed to methods of preventing reactivation of active and latent M. tuberculosis infections by administering a pharmaceutical composition comprising a nucleic acid encoding a Mtb72f fusion protein, or a Mtb72f fusion protein or an immunogenic fragment thereof, for example together with an adjuvant. The Mtb72f nucleic acid or fusion protein can be administered with one or more chemotherapeutic agents effective against a M. tuberculosis infection. The methods also provide for shortening the time course of a chemotherapeutic regimen against a M. tuberculosis infection.

Claims

1. A method for treating a subject infected with Mycobacterium tuberculosis comprising administering to a subject infected with M. tuberculosis

(a) a pharmaceutical composition comprising an immunologically effective amount of:

(i) a Mtb72f fusion protein or an immunogenic fragment thereof from a Mycobacterium species of the tuberculosis complex and an adjuvant;

or

(ii) a nucleic acid encoding a Mtb72f fusion protein or an immunogenic fragment thereof from a Mycobacterium species of the tuberculosis complex, and

(b) one or more chemotherapeutic agents effective against a M. tuberculosis infection

wherein the Mtb72f fusion protein or immunogenic fragment thereof of (i) or encoded by the nucleic acid of (ii) induces an immune response against M. tuberculosis in the subject.

2. The method of claim 1, wherein the pharmaceutical composition of (a) comprises a Mtb72f fusion protein or an immunogenic fragment thereof from a Mycobacterium species of the tuberculosis complex and an adjuvant.

3. The method of claim 1, wherein the pharmaceutical composition comprises a nucleic acid encoding a Mtb72f fusion protein or an immunogenic fragment thereof from a Mycobacterium species of the tuberculosis complex.

4. The method of claim 1, wherein the Mtb72f fusion protein is from Mycobacterium tuberculosis.

5. The method of claim 4, wherein the Mtb72f fusion protein is a polypeptide comprising residues 8-729 of SEQ ID NO:

2.

6. The method of claim 4, wherein the Mtb72f fusion protein is a polypeptide comprising residues 4-725 of SEQ ID NO:

4.

7. The method of claim 2, wherein the adjuvant is selected from the group consisting of

(i) 3D-MPL and QS21 in a liposome formulation, and

(ii) 3D-MPL and QS21 and an oil in water emulsion.

8. The method of claim 3, wherein the nucleic acid comprises nucleotides 63-2222 of SEQ ID NO:

1.

9. The method of claim 3, wherein the nucleic acid comprises nucleotides 10-2175 of SEQ ID NO:

3.

10. The method of claim 3, wherein the nucleic acid is administered in an adenovirus vector.

11. The method of claim 3, wherein the nucleic acid is administered in a mutant Mycobacterium or Bacillus host cell vector.

12. The method of claim 1, wherein the one or more chemotherapeutic agents effective against a M. tuberculosis infection of (b) is administered over a period of time.

13. The method of claim 12, wherein the one or more chemotherapeutic agents effective against a M. tuberculosis infection of (b) is administered over about 1 week, about 2 weeks, about 3 weeks, about 4 weeks, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 8 months or about 1 year.

14. The method of claim 1, wherein the one or more chemotherapeutic agents is selected from isoniazid and rifampin.

15. The method of claim 1, wherein the subject is first administered said one or more chemotherapeutic agents of (b) and then administered said pharmaceutical composition of (a).

16. The method of claim 1, wherein the subject is first administered said pharmaceutical composition of (a), and then administered said one or more chemotherapeutic agents of (b).

17. The method of claim 1, wherein administration of the one or more chemotherapeutic agents of (b) and the pharmaceutical composition of (a) is initiated concurrently.

18. A method for reducing the time course of chemotherapy for treating a subject infected with Mycobacterium tuberculosis, the method comprising administering to a subject infected with M. tuberculosis

(a) a pharmaceutical composition comprising an immunologically effective amount of:

(i) a Mtb72f fusion protein or an immunogenic fragment thereof from a Mycobacterium species of the tuberculosis complex and an adjuvant;

or

(ii) a nucleic acid encoding a Mtb72f fusion protein or an immunogenic fragment thereof from a Mycobacterium species of the tuberculosis complex, and

(b) one or more chemotherapeutic agents effective against a M. tuberculosis infection

wherein the Mtb72f fusion protein or immunogenic fragment thereof which is administered in (i) or encoded by the nucleic acid of (ii) induces an immune response against M. tuberculosis in the subject thereby, and

wherein the time course of chemotherapy against a M. tuberculosis infection in the subject is reduced.