Compositions and methods for the treatment or prevention of hepatitis B virus infection

• US 8,722,054 B2
• Filed: 03/13/2013
• Issued: 05/13/2014
• Est. Priority Date: 02/12/2011
• Status: Active Grant

• Current Assignee: GLOBEIMMUNE, INC.
• Original Assignee: GLOBEIMMUNE, INC.
• Inventors: Apelian, David, King, Thomas H., Guo, Zhimin, Coeshott, Claire
• Primary Examiner(s): Boesen, Agnieszka
• Application Number:
  US13/798,837
• Publication Number:
  US 20130243805A1
• Time in Patent Office: 426 Days
• Field of Search: None
• US Class Current: 424/189.1
• CPC Class Codes: A61K 2039/51 comprising whole cells, viruses or DNA/RNA
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 2039/521 inactivated (killed)
• CPC Class Codes: A61K 2039/523 expressing foreign proteins
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2039/55 characterised by the host/recipient, e.g. newborn with maternal antibodies
• CPC Class Codes: A61K 2039/55516 Proteins; Peptides
• CPC Class Codes: A61K 2039/55588 Adjuvants of undefined constitution
• CPC Class Codes: A61K 2039/6006 Cells recombinantly expressing antigens A61K2039/5156, A61K2039/523
• CPC Class Codes: A61K 2039/70 Multivalent vaccine
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 36/06 Fungi, e.g. yeasts
• CPC Class Codes: A61K 36/12 Filicopsida or Pteridopsida
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/29 Hepatitis virus
• CPC Class Codes: A61K 39/292 Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/464838 Viral antigens
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/46 Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
• CPC Class Codes: A61P 1/16 : for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/20 : for DNA viruses
• CPC Class Codes: A61P 37/02 : Immunomodulators
• 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 14/005 : from viruses
• CPC Class Codes: C07K 14/02 : Hepadnaviridae, e.g. hepatitis B virus
• CPC Class Codes: C07K 2319/00 : Fusion polypeptide
• CPC Class Codes: C12N 2710/00022 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2710/00034 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2730/10122 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2730/10134 : 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

Disclosed are yeast-based immunotherapeutic compositions, hepatitis B virus (HBV) antigens, and fusion proteins for the treatment and/or prevention of HBV infection and symptoms thereof, as well as methods of using the yeast-based immunotherapeutic compositions, HBV antigens, and fusion proteins for the prophylactic and/or therapeutic treatment of HBV and/or symptoms thereof.

Claims

1. An immunotherapeutic composition comprising:

a) a yeast vehicle; and

b) a fusion protein comprising HBV antigens, wherein the HBV antigens consist of;

i) an HBV X antigen having an amino acid sequence that is at least 95% identical to positions 1-60 of SEQ ID NO;

130;

ii) an HBV surface antigen having an amino acid sequence that is at least 95% identical to positions 63-461 of SEQ ID NO;

130; and

iii) an HBV core antigen having an amino acid sequence that is at least 95% identical to positions 462 to 643 of SEQ ID NO;

130;

wherein the composition elicits an HBV-specific immune response and wherein the fusion protein is expressed by the yeast vehicle.

2. The immunotherapeutic composition of claim 1, wherein the amino acid sequence of HBV X antigen consists of positions 1-60 of SEQ ID NO:

130.

3. The immunotherapeutic composition of claim 1, wherein the amino acid sequence of the HBV surface antigen consists of positions 63-461 of SEQ ID NO:

130.

4. The immunotherapeutic composition of claim 1, wherein the amino acid sequence of the HBV core antigen consists of positions 462 to 643 of SEQ ID NO:

130.

5. The immunotherapeutic composition of claim 1, wherein the HBV antigens are arranged in the following order, from N- to C-terminus, in the fusion protein:

HBV X antigen, HBV surface antigen, HBV core antigen.

6. The immunotherapeutic composition of claim 1, wherein the fusion protein comprises an amino acid sequence of SEQ ID NO:

130 or SEQ ID NO;

150.

7. The immunotherapeutic composition of claim 1, wherein the yeast vehicle is a whole yeast.

8. The immunotherapeutic composition of claim 7, wherein the whole yeast is heat-inactivated.

9. The immunotherapeutic composition of claim 1, wherein the yeast vehicle is from Saccharomyces cerevisiae.

10. The immunotherapeutic composition of claim 1, comprising a pharmaceutically acceptable excipient.

11. The immunotherapeutic composition of claim 1, wherein the immunotherapeutic composition contains greater than 90% yeast protein and is formulated for administration by injection of a patient.

16. The immunotherapeutic composition of claim 1, wherein the HBV antigens consist of an amino acid sequence that is at least 95% identical to SEQ ID NO:

130.

17. The immunotherapeutic composition of claim 1, wherein the HBV antigens consist of an amino acid sequence of SEQ ID NO:

130.

18. The immunotherapeutic composition of claim 7, wherein the whole yeast is killed.

19. The immunotherapeutic composition of claim 8, wherein the whole yeast has been lyophilized.

20. The immunotherapeutic composition of claim 7, wherein the whole yeast is from Saccharomyces cerevisiae.

12. An immunotherapeutic composition comprising:

a) a whole, heat-inactivated yeast from Saccharomyces cerevisiae; and

b) an HBV fusion protein expressed by the yeast, wherein the fusion protein comprises SEQ ID NO;

130.

13. An immunotherapeutic composition comprising:

a) a whole, heat-inactivated yeast from Saccharomyces cerevisiae; and

b) an HBV fusion protein expressed by the yeast, wherein the fusion protein comprises SEQ ID NO;

150.

14. A yeast expressing a fusion protein comprising HBV antigens, wherein the HBV antigens consist of:

a) an HBV X antigen having an amino acid sequence that is at least 95% identical to positions 1-60 of SEQ ID NO;

130;

b) an HBV surface antigen having an amino acid sequence that is at least 95% identical to positions 63-461 of SEQ ID NO;

130; and

c) an HBV core antigen having an amino acid sequence that is at least 95% identical to positions 462 to 643 of SEQ ID NO;

130.

21. The yeast of claim 14, wherein the amino acid sequence of HBV X antigen consists of positions 1-60 of SEQ ID NO:

130.

22. The yeast of claim 14, wherein the amino acid sequence of the HBV surface antigen consists of positions 63-461 of SEQ ID NO:

130.

23. The yeast of claim 14, wherein the amino acid sequence of the HBV core antigen consists of positions 462 to 643 of SEQ ID NO:

130.

24. The yeast of claim 14, wherein the HBV antigens consist of an amino acid sequence that is at least 95% identical to SEQ ID NO:

130.

25. The yeast of claim 14, wherein the HBV antigens consist of an amino acid sequence of SEQ ID NO:

130.

26. The yeast of claim 14, wherein the fusion protein comprises an amino acid sequence of SEQ ID NO:

150.

27. The yeast of claim 14, wherein the yeast is from Saccharomyces cerevisiae.

15. A fusion protein comprising HBV antigens, wherein the fusion protein comprises an amino acid sequence that is at least 95% identical to an amino acid sequence of SEQ ID NO:

130 or SEQ ID NO;

150.

28. A fusion protein comprising HBV antigens, wherein the fusion protein comprises an amino acid sequence of SEQ ID NO:

130 or SEQ ID NO;

150.