Compositions and Methods for the Treatment or Prevention of Hepatitis B Virus Infection

• US 20130243805A1
• Filed: 03/13/2013
• Published: 09/19/2013
• Est. Priority Date: 02/12/2011
• Status: Active Grant

• Current Assignee: GLOBEIMMUNE, INC.
• Original Assignee: GLOBEIMMUNE, INC.
• Inventors: King, Thomas H., Coeshott, Claire, Apelian, David, Guo, Zhimin
• Granted Patent: US 8,722,054 B2
• Time in Patent Office: Days
• 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 80% identical to positions 52 to 126 of a full-length HBV X antigen;

ii) an HBV surface antigen having an amino acid sequence that is at least 95% identical to an amino acid sequence of a full-length HBV large surface antigen (L), and;

iii) an HBV core antigen having an amino acid sequence that is at least 95% identical to an amino acid sequence of a full-length HBV core protein;

wherein the composition elicits an HBV-specific immune response.

2. The immunotherapeutic composition of claim 1, wherein the amino acid sequence of HBV X antigen is at least 95% identical to positions 1-60 of SEQ ID NO:

130 or a corresponding sequence from a different HBV strain.

3. 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 or a corresponding sequence from a different HBV strain.

4. The immunotherapeutic composition of claim 1, wherein the amino acid sequence of the HBV surface antigen is at least 95% identical to positions 63-461 of SEQ ID NO:

130 or a corresponding sequence from a different HBV strain.

5. 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 or a corresponding sequence from a different HBV strain.

6. The immunotherapeutic composition of claim 1, wherein the amino acid sequence of the HBV core antigen is at least 95% identical to positions 462 to 643 of SEQ ID NO:

130 or a corresponding sequence from a different HBV strain.

7. 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 or a corresponding sequence from a different HBV strain.

9. 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.

12. 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.

13. The immunotherapeutic composition of claim 1, wherein the fusion protein is expressed by the yeast vehicle.

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

16. The immunotherapeutic composition of claim 14, wherein the whole yeast is heat-inactivated.

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

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

19. The immunotherapeutic composition of claim 18, wherein the excipient is suitable for administration by injection.

45. A method to treat hepatitis B virus (HBV) infection or at least one symptom resulting from HBV infection in a subject, comprising administering to a subject that has been infected with HBV the composition of claim 1, wherein administration of the composition to the subject reduces HBV infection or at least one symptom resulting from HBV infection in a subject.

54. A method to elicit an antigen-specific, cell-mediated immune response against an HBV antigen, comprising administering to a subject the composition according to claim 1.

55. A method to prevent HBV infection or ameliorate symptoms of HBV infection in a subject, comprising administering to a subject that has not been infected with HBV, the composition according to claim 1.

56. A method to immunize a population of individuals against HBV, comprising administering to the population of individuals the composition according to claim 1.

8. (canceled)

10. (canceled)

11. (canceled)

15. (canceled)

20. 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.

21. (canceled)

22. 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.

23. (canceled)

24. A yeast that has expressed 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 80% identical to positions 52 to 126 of a full-length HBV X antigen;

b) an HBV surface antigen having an amino acid sequence that is at least 95% identical to an amino acid sequence of a full-length HBV large surface antigen (L), and;

c) an HBV core antigen having an amino acid sequence that is at least 95% identical to an amino acid sequence of a full-length HBV core protein.

25-39. -39. (canceled)

40. 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.

41. A recombinant nucleic acid molecule encoding the fusion protein of claim 40.

42. The recombinant nucleic acid molecule of claim 41, wherein the recombinant nucleic acid molecule comprises a nucleic acid sequence of SEQ ID NO:

129.

43. An isolated cell transfected with the recombinant nucleic acid molecule of claim 41.

44. (canceled)

46-53. -53. (canceled)