# US 7,439,042 B2 · Yeast-based therapeutic for chronic hepatitis C infection

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 7,439,042 B2
- Document ID: US7439042B2
- Status: Granted
- Kind: B2
- Application number: 11/254,252
- Filed: 2005-10-18
- Published: 2006-05-25
- Granted: 2008-10-21
- Earliest claimed: 2002-12-16
- Assignees: GlobeImmune, Inc.
- Inventors: Richard C. Duke; Alex Franzusoff; Aurelia Haller; Thomas H. King
- Web page: https://patentgrep.com/patent/US7439042B2

## CPC

- C07K 14/005: from viruses
- A61K 39/12: Viral antigens
- A61K 39/29: Hepatitis virus
- A61K 40/10: characterised by the cell type used
- A61K 40/46: Viral antigens
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- A61K 2039/523: {expressing foreign proteins}
- A61K 2039/5252: {inactivated (killed)}
- A61K 2039/55516: {Proteins; Peptides}
- C12N 2770/24222: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2770/24234: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Disclosed are compositions, including vaccines, and methods for vaccinating an animal against hepatitis C virus (HCV) and for treating or preventing hepatitis C viral infection in an animal. The invention includes a variety of novel HCV fusion proteins that can be used directly as a vaccine or in conjunction with a yeast-based vaccine vehicle to elicit an immune response against HCV in an animal. The invention also includes the use of the HCV fusion gene and protein described herein in any diagnostic or therapeutic protocol for the detection and/or treatment or prevention of HCV infection.

## Claims

### Claim 1

An HCV Core-E1-E2 fusion protein comprising HCV sequences, wherein the HCV sequences consist essentially of an HCV fusion protein comprising a full-length HCV Core protein fused to a full-length HCV E1 protein fused to a full-length HCV E2 protein, wherein the full-length HCV Core protein is linked at its N-terminus to the amino acid sequence represented by SEQ ID NO:9 (MADEAP).

### Claim 2 (depends on 1)

The fusion protein of claim 1, wherein the fusion protein consists essentially of SEQ ID NO:12.

### Claim 3 (depends on 1)

The fusion protein of claim 1, wherein the HCV fusion protein has been appended to include two amino acids, glutamate and aspartate.

### Claim 4 (depends on 1)

The fusion protein of claim 1, wherein the HCV fusion protein has been appended to include the amino acid sequence of G-G-G-H-H-H-H-H-H (SEQ ID NO:10).

### Claim 5 (depends on 1)

An isolated nucleic acid molecule comprising a nucleic acid sequence encoding the HCV Core-E1-E2 fusion protein of claim 1.

### Claim 6 (depends on 5)

The isolated nucleic acid molecule of claim 5, wherein the expression of the fusion protein is under the control of an inducible promoter.

### Claim 7 (depends on 6)

The isolated nucleic acid molecule of claim 6, wherein the inducible promoter is CUP1.

### Claim 8 (depends on 5)

A recombinant nucleic acid molecule comprising the isolated nucleic acid molecule of claim 5.

### Claim 9 (depends on 8)

A recombinant cell that has been transfected with the recombinant nucleic acid molecule of claim 8.

### Claim 10 (depends on 9)

The recombinant cell of claim 9, wherein the cell is a yeast cell.

### Claim 11 (depends on 5)

A composition comprising the nucleic acid molecule of claim 5.

### Claim 12 (depends on 1)

A composition comprising the HCV Core-E1-E2 fusion protein of claim 1.

### Claim 13 (depends on 1)

A composition comprising:
a) a yeast vehicle; and
b) the HCV Core-E1-E2 fusion protein of claim 1.

### Claim 14 (depends on 13)

The composition of claim 13, wherein the HCV Core-E1-E2 fusion protein consists essentially of SEQ ID NO:14.

### Claim 15 (depends on 13)

The composition of claim 13, wherein the expression of the fusion protein is under the control of an inducible promoter.

### Claim 16 (depends on 13)

The composition of claim 13, wherein the composition further comprises a dendritic cell, wherein the dendritic cell has been loaded intracellularly with the yeast vehicle that recombinantly expresses the HCV Core-E1-E2 fusion protein.

### Claim 17 (depends on 13)

The composition of claim 13, further comprising at least one biological response modifier.

### Claim 18 (depends on 2)

A composition comprising:
a) a yeast vehicle; and
b) an HCV Core-E1-E2 fusion protein according to claim 2, wherein the HCV Core-E1-E2 fusion protein is under the control of the promoter CUP1;
wherein the HCV Core-E1-E2 fusion protein is expressed by the yeast vehicle.

### Claim 19

An HCV Core-E1-E2 fusion protein comprising HCV sequences, wherein the HCV sequences consist essentially of a truncated HCV Core protein fused to an HCV E1 protein with deleted transmembrane domain and an HCV E2 protein with deleted transmembrane domain, wherein the truncated HCV Core protein is linked at its N-terminus to the amino acid sequence represented by SEQ ID NO:9 (MADEAP).

### Claim 20 (depends on 19)

The fusion protein of claim 19, wherein the truncated HCV Core protein consists essentially of positions 2 to 140 of HCV Core protein (positions 2 to 140, with respect to SEQ ID NO:20).

### Claim 21 (depends on 19)

The fusion protein of claim 19, wherein the HCV E1 protein with deleted transmembrane domain consists essentially of positions 1 to 156 of HCV E1 protein (positions 192 to 31, with respect to SEQ ID NO:20).

### Claim 22 (depends on 19)

The fusion protein of claim 19, wherein the HCV E2 protein with deleted transmembrane domain consists essentially of positions 1 to 334 of HCV E2 protein (positions 384 to 717, with respect to SEQ ID NO:20).

### Claim 23 (depends on 19)

The fusion protein of claim 19, wherein the fusion protein consists essentially of SEQ ID NO:14.

### Claim 24 (depends on 23)

A composition comprising:
a) a yeast vehicle; and
b) an HCV Core-E1-E2 fusion protein according to claim 23, wherein the HCV Core-E1-E2 fusion protein is under the control of the promoter CUP1;
wherein the HCV Core-E1-E2 fusion protein is expressed by the yeast vehicle.

### Claim 25 (depends on 19)

A composition comprising:
a) a yeast vehicle; and
b) the HCV Core-E1-E2 fusion protein of claim 19.

### Claim 26 (depends on 25)

The composition of claim 25, wherein the fusion protein consists essentially of SEQ ID NO:14.

### Claim 27

An HCV E1-E2 fusion protein comprising HCV sequences, wherein the HCV sequences consist of a an HCV E1 protein fused to an HCV E2 protein, wherein the HCV E1 protein is linked at its N-terminus to the amino acid sequence represented by SEQ ID NO:9 (MADEAP).

### Claim 28 (depends on 27)

The HCV E1-E2 fusion protein of claim 27, wherein the fusion protein consists essentially of SEQ ID NO:6.

### Claim 29 (depends on 27)

The fusion protein of claim 27, wherein the HCV fusion protein has been appended to include two amino acids, glutamate and aspartate.

### Claim 30 (depends on 27)

The fusion protein of claim 27, wherein the HCV fusion protein has been appended to include the amino acid sequence of G-G-G-H-H-H-H-H-H (SEQ ID NO:10).

### Claim 31 (depends on 27)

An isolated nucleic acid molecule comprising a nucleic acid sequence encoding the HCV E1-E2 fusion protein of claim 27.

### Claim 32 (depends on 31)

The isolated nucleic acid molecule of claim 31, wherein the nucleic acid sequence is SEQ ID NO:5.

### Claim 33 (depends on 31)

The isolated nucleic acid molecule of claim 31, wherein the expression of the fusion protein is under the control of an inducible promoter.

### Claim 34 (depends on 32)

The isolated nucleic acid molecule of claim 32, wherein the inducible promoter is CUP1.

### Claim 35 (depends on 27)

A recombinant nucleic acid molecule comprising the isolated nucleic acid molecule of claim 27.

### Claim 36 (depends on 35)

A recombinant cell that has been transfected with the recombinant nucleic acid molecule of claim 35.

### Claim 37 (depends on 36)

The recombinant cell of claim 36, wherein the cell is a yeast cell.

### Claim 38 (depends on 27)

A composition comprising the HCV E1-E2 fusion protein of claim 27.

### Claim 39 (depends on 27)

A composition comprising:
a) a yeast vehicle; and
b) the HCV E1-E2 fusion protein of claim 27.

### Claim 40 (depends on 39)

The composition of claim 39, wherein the HCV E1-E2 fusion protein consists essentially of SEQ ID NO:6.

### Claim 41 (depends on 28)

A composition comprising:
a) a yeast vehicle; and
b) an HCV E1-E2 fusion protein according to claim 28, wherein the HCV E1-E2 fusion protein is under the control of the promoter CUP1;
wherein the HCV E1-E2 fusion protein is expressed by the yeast vehicle.

### Claim 42 (depends on 41)

The composition of claim 41, wherein the HCV E1-E2 fusion protein has been appended to include the amino acid sequence of G-G-G-H-H-H-H-H-H (SEQ ID NO:10).