Microneedle compositions and methods of using same

• US 10,022,436 B2
• Filed: 01/11/2017
• Issued: 07/17/2018
• Est. Priority Date: 01/11/2016
• Status: Active Grant

• Current Assignee: Verndari, Inc.
• Original Assignee: Verndari, Inc.
• Inventors: Henderson, Daniel R.
• Primary Examiner(s): Blumel, Benjamin P
• Application Number:
  US15/403,989
• Publication Number:
  US 20170196966A1
• Time in Patent Office: 552 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/5256 expressing foreign proteins
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 2039/645 Dendrimers; Multiple antigen peptides
• CPC Class Codes: A61K 2039/70 Multivalent vaccine
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/145 Orthomyxoviridae, e.g. influenza virus
• CPC Class Codes: A61K 48/005 characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61K 9/5146 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: C12N 15/89 using microinjection
• 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 2760/16234 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2770/36143 viral genome or elements thereof as genetic vector
• 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
• 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

Described herein, are microneedle devices comprising a recombinant alphavirus replicon encoding an exogenous polypeptide, wherein the recombinant alphavirus replicon is coated onto or embedded into a plurality of microneedles. Also described herein are methods of preparing a microneedle device comprising a recombinant alphavirus replicon encoding an exogenous polypeptide. Also disclosed herein are methods of inducing an immune response in an individual comprising contacting the individual with a microneedle device comprising a recombinant alphavirus replicon encoding an exogenous polypeptide.

Claims

1. A microneedle device for administering a recombinant alphavirus replicon, comprising:

(a) a dehydrated composition comprising the recombinant alphavirus replicon encoding an exogenous polypeptide; and

(b) a substrate comprising a sheet and a plurality of microneedles extending therefrom, each of said microneedles comprising a tip, a base, a hinge at the base connecting the microneedle to the sheet, and a well comprising the dehydrated composition.

2. The microneedle device of claim 1, wherein the exogenous polypeptide is an antigen associated with an infectious agent.

3. The microneedle device of claim 1, wherein the recombinant alphavirus replicon is present in an amount effective to induce an immune response in an individual in need thereof to the exogenous polypeptide following expression of the exogenous polypeptide by the recombinant alphavirus replicon.

4. The microneedle device of claim 1, wherein the exogenous polypeptide is an influenza virus HA or NA polypeptide.

5. The microneedle device of claim 4, wherein the influenza virus HA polypeptide is an influenza A virus HA polypeptide or an influenza B virus HA polypeptide.

6. The microneedle device of claim 5, wherein the influenza virus HA polypeptide is from a viral strain of a group 1 influenza A virus subtype selected from H1, H2, H5, H6, H8, H9, H11, H12, H13, H16, H17, or H18.

7. The microneedle device of claim 5, wherein the influenza virus HA polypeptide is from a viral strain of a group 2 influenza A virus subtype selected from H3, H4, H7, H10, H14, or H15.

8. The microneedle device of claim 5, wherein the influenza virus HA polypeptide is from a viral strain of an influenza B virus.

9. The microneedle device of claim 6, wherein the influenza virus HA polypeptide is from a viral strain of an influenza A virus H1 subtype.

10. The microneedle device of claim 7, wherein the influenza virus HA polypeptide is from a viral strain of an influenza A virus H3 subtype.

11. The microneedle device of claim 8, wherein the influenza virus HA polypeptide is from a viral strain of an influenza B virus Yamagata or Victoria lineage.

12. The microneedle device of claim 1, wherein the recombinant alphavirus replicon encodes an exogenous polypeptide comprising:

a) an HA polypeptide from a viral strain of an influenza A virus H1 subtype;

b) an HA polypeptide from a viral strain of an influenza A virus H3 subtype;

c) an HA polypeptide from a viral strain of an influenza B virus Yamagata lineage;

d) an HA polypeptide from a viral strain of an influenza B virus Victoria lineage;

or

e) any combinations thereof.

13. The microneedle device of claim 12, wherein the recombinant alphavirus replicon encodes at least two exogenous polypeptides comprising:

a) an HA polypeptide from a viral strain of an influenza A virus H1 subtype;

b) an HA polypeptide from a viral strain of an influenza A virus H3 subtype;

c) an HA polypeptide from a viral strain of an influenza B virus Yamagata lineage;

or

d) an HA polypeptide from a viral strain of an influenza B virus Victoria lineage.

14. The microneedle device of claim 13, wherein each of the exogenous polypeptides are encoded on a single recombinant alphavirus replicon.

15. The microneedle device of claim 13, wherein the exogenous polypeptides are encoded on different recombinant alphavirus replicons.

16. The microneedle device of claim 1, wherein the exogenous polypeptide is a hepatitis B virus surface antigen (HBsAg).

17. The microneedle device of claim 1, wherein the recombinant alphavirus replicon is formulated as a dendrimer-replicon nanoparticle.

18. The microneedle device of claim 17, wherein the dendrimer is a PAMAM dendrimer.

19. The microneedle device of claim 18, wherein the PAMAM dendrimer comprises amino surface reactive groups.

20. The microneedle device of claim 19, wherein the PAMAM dendrimer is a G5 or G9 PAMAM dendrimer comprising amino surface reactive groups.

21. The microneedle device of claim 19, wherein the PAMAM dendrimer comprises modified amino surface reactive groups.

22. The microneedle device of claim 17, wherein the dendrimer-replicon nanoparticle is formulated by a microfluidic mixing device.

23. The microneedle device of claim 17, wherein the composition further comprises a pharmaceutically acceptable excipient.

24. The microneedle device of claim 1, wherein the tip is bent about 90 degrees from the sheet about the hinge.

25. The microneedle device of claim 1, wherein the dehydrated composition is loaded onto the well of each microneedle by a microfluidic dispensing device.

26. The microneedle device of claim 1, wherein each well comprises a coating comprising the dehydrated composition.

27. The microneedle device of claim 1, wherein each well comprises a printed coating comprising the dehydrated composition.