Inhalable vaccine compositions and methods

• US 10,159,644 B2
• Filed: 10/25/2013
• Issued: 12/25/2018
• Est. Priority Date: 10/26/2012
• Status: Active Grant

• Current Assignee: Mannkind Corporation, TechnoVax Inc.
• Original Assignee: Mannkind Corporation, TechnoVax Inc.
• Inventors: Smutney, Chad C., Leone-Bay, Andrea, Galarza, Jose M., Munoz, Hector, Martin, George R., Grant, Marshall L.
• Primary Examiner(s): Chestnut, Barry A
• Application Number:
  US14/438,582
• Publication Number:
  US 20150283069A1
• Time in Patent Office: 1,887 Days
• CPC Class Codes: A61K 2039/525 Virus
• CPC Class Codes: A61K 2039/544 to the airways
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 39/07 Bacillus
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/145 Orthomyxoviridae, e.g. influenza virus
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61M 15/0021 Mouthpieces therefor
• CPC Class Codes: A61M 15/003 using capsules, e.g. to be perforated or broken-up
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: C12N 2760/16134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 7/00 Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

Abstract

Dry powder inhalable compositions and methods for using and making the compositions are disclosed for vaccinating a subject against disease. In particular, the compositions are inhalable dry powders useful for preventing and/or treating diseases caused by microorganisms, for example, microorganisms such as viral or bacterial pathogens, including, the influenza virus. In particular, the method comprises the administration of an inhalable composition comprising virus-like particles and/or specific protein/s or antigenic peptides, peptide fragments and/or derivatives thereof using a dry powder drug delivery system.

Claims

1. An influenza vaccine comprising a dry powder composition comprising a diketopiperazine and at least one of influenza virus-like particles, an antigenic protein, an antigenic peptide, fragments of said influenza virus-like particle, a subunit protein or multiple subunit proteins or fragments of said antigenic protein(s), fragments of said antigenic peptide, or combinations thereof.

2. The influenza vaccine of claim 1, wherein the virus-like particle comprises a hemagglutinin and/or a neuraminidase protein and/or a matrix protein, or peptide or fragments thereof.

3. The influenza vaccine of claim 1, wherein the antigenic protein or peptide is neuraminidase derived for influenza virus type A, B or C, or any subtype of influenza A, or fragments thereof or combinations thereof.

4. The influenza vaccine of claim 1, wherein the antigenic protein or peptide is hemagglutinin derived from influenza A, B or C or any subtype of influenza A, or fragments thereof, or combinations thereof.

5. The influenza vaccine of claim 4, wherein the antigenic protein or antigenic peptide is hemagglutinin A, or wherein the antigenic protein or subunit is another protein of the influenza virus such as NP, M1, M2, NS1, NS2, polymerase subunits PB1, PB2 or PA or fragments thereof or combinations thereof.

6. The influenza vaccine of claim 1, wherein the diketopiperazine is 3,6-bis-(N-X-4-aminobutyl)]-2,5-diketopiperazine.

7. The influenza vaccine of claim 6, wherein X is fumaryl, glutaryl, succinyl, maleyl, malonyl, or oxalyl.

8. The influenza vaccine of claim 1, wherein the diketopiperazine is 3,6-bis-(N-fumaryl-4-aminobutyl)]-2,5-diketopiperazine.

9. An influenza vaccine, comprising an inhalation system comprising a dry powder inhaler comprising a dry powder formulation comprising microparticles of 3,6-bis-(N-fumaryl-4-aminobutyl)]-2,5-diketopiperazine salt and an antigen selected from influenza virus protein consisting of hemagglutinin A or neuraminidase A, or other influenza protein and/or combinations thereof.

10. The influenza vaccine of claim 9, wherein the hemagglutinin A is a recombinant HA3 antigen.

11. The influenza vaccine of claim 9, wherein the dry powder inhaler is configured as a single use disposable inhaler for self-administration.

17. A method of immunizing a subject against an influenza viral infection comprising, administering to said subject in need of immunization the influenza vaccine of claim 9.

18. The method of claim 17, further comprising providing a booster vaccine dose to said subject, said booster vaccine comprising the influenza vaccine of claim 9.

19. The method of claim 18, wherein said booster vaccine is administered within a month of administration of the initial dose.

20. The method of claim 19, wherein said booster vaccine is administered one week after administration of the initial dose.

12. A method for immunizing a subject against an influenza virus infection, comprising administering to the subject a therapeutically effective amount of a dry powder vaccine comprising a diketopiperazine and a virus-like particle, an antigenic protein, an antigenic peptide, fragments of said virus-like particle, or a subunit protein or multiple distinct subunits proteins or fragments of said antigenic protein/s, fragments of said antigenic peptide, or combinations thereof, wherein the vaccine is self-administered by inhalation.

13. The method of claim 12, wherein the diketopiperazine is 3,6-bis-(N-X-4-aminobutyl)]-2,5-diketopiperazine.

14. The method of claim 13, wherein X is fumaryl, glutaryl, succinyl, maleyl, malonyl, or oxalyl.

15. The method of claim 14, wherein the diketopiperazine is 3,6-bis-(N-fumaryl-4-aminobutyl)]-2,5-diketopiperazine.

16. The method of claim 12, wherein the antigenic peptide is a recombinant HA3 antigen or fragment thereof.