# US 7,744,898 B2 · Peptides for inducing cytotoxic T lymphocyte responses to hepatitis B virus

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- Number: US 7,744,898 B2
- Document ID: US7744898B2
- Status: Granted
- Kind: B2
- Application number: 11/221,470
- Filed: 2005-09-08
- Published: 2006-03-09
- Granted: 2010-06-29
- Earliest claimed: 1991-08-26
- Assignees: The Scripps Research Institute
- Inventors: Francis V. Chisari
- Web page: https://patentgrep.com/patent/US7744898B2

## CPC

- C07K 14/005: from viruses
- A61K 39/29: Hepatitis virus
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/46: Viral antigens
- A61P 31/12: Antivirals
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- A61K 39/12: Viral antigens
- A61K 2039/57: {characterised by the type of response, e.g. Th1, Th2}
- A61K 2039/572: {cytotoxic response}
- C12N 2730/10122: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2730/10134: 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Peptides are used to define epitopes that stimulate HLA-restricted cytotoxic T lymphocyte activity against hepatitis B virus antigens. The peptides are derived from regions of HBV polymerase, and are particularly useful in treating or preventing HBV infection, including methods for stimulating the immune response of chronically infected individuals to respond to HBV antigens.

## Claims

### Claim 1

An HBV immunogenic peptide of 50 amino acids or less in length, wherein said immunogenic peptide comprises HBpol 526-535 (Phe-Leu-Leu-Ala-Gln-Phe-Thr-Ser-Ala-Ile; SEQ ID NO:30), and wherein said immunogenic peptide binds to an appropriate HLA molecule to form a complex recognized by cytotoxic T cells wherein said cytotoxic T cells recognize a native HBV antigen.

### Claim 2 (depends on 1)

The HBV immunogenic peptide of claim 1, wherein said immunogenic peptide is 25 amino acids or less in length.

### Claim 3 (depends on 1)

The HBV immunogenic peptide of claim 1, wherein said immunogenic peptide is 10 or 11 amino acids in length.

### Claim 4 (depends on 1)

The HBV immunogenic peptide of claim 1, wherein said immunogenic peptide consists of HBpol 526-535 (Phe-Leu-Leu-Ala-Gln-Phe-Thr-Ser-Ala-Ile; SEQ ID NO:30).

### Claim 5

An immunogenic composition comprising an HBV immunogenic peptide of 50 amino acids or less in length and a pharmaceutically acceptable carrier, wherein said immunogenic peptide comprises HBpol 526-535 (Phe-Leu-Leu-Ala-Gln-Phe-Thr-Ser-Ala-Ile; SEQ ID NO:30), and wherein said immunogenic peptide binds to an appropriate HLA molecule to form a complex recognized by cytotoxic T cells wherein said cytotoxic T cells recognize a native HBV antigen.

### Claim 6 (depends on 5)

The immunogenic composition of claim 5, wherein said immunogenic peptide is 25 amino acids or less in length.

### Claim 7 (depends on 5)

The immunogenic composition of claim 5, wherein said immunogenic peptide is 10 or 11 amino acids in length.

### Claim 8 (depends on 5)

The immunogenic composition of claim 5, wherein said immunogenic peptide consists of HBpol 526-535 (Phe-Leu-Leu-Ala-Gln-Phe-Thr-Ser-Ala-Ile; SEQ ID NO:30).

### Claim 9 (depends on 5)

The immunogenic composition of claim 5, wherein said peptide is in an immunogenically effective human dose and said pharmaceutically acceptable carrier is in a human dose.

### Claim 10 (depends on 5)

The immunogenic composition of claim 5, wherein said pharmaceutically acceptable carrier comprises a liposome.

### Claim 11 (depends on 1)

The immunogenic peptide of claim 1, wherein said peptide is located in a host cell, and is the result of expression of a recombinant nucleic acid molecule that encodes said immunogenic peptide and has been introduced into the host cell.

### Claim 12 (depends on 11)

The immunogenic peptide of claim 11, wherein said recombinant nucleic acid molecule that encodes said immunogenic peptide also encodes at least one additional peptide.

### Claim 13 (depends on 5)

The immunogenic composition of claim 5, wherein said composition further comprises a second immunogenic peptide.

### Claim 14 (depends on 13)

The immunogenic composition of claim 13, wherein said second immunogenic peptide elicits a T-helper cell-mediated immune response.

### Claim 15 (depends on 13)

The immunogenic composition of claim 13, wherein said second immunogenic peptide elicits a cytotoxic T lymphocyte response.

### Claim 16 (depends on 13)

The immunogenic composition of claim 13, wherein said immunogenic peptide and said second immunogenic peptide are conjugated to form a heteropolymer.

### Claim 17 (depends on 5)

The immunogenic composition of claim 5, wherein said peptide is in an immunogenically effective human dose and said pharmaceutically acceptable carrier is in a human dose.

### Claim 18 (depends on 1)

The HBV immunogenic peptide of claim 1, further comprising a carrier coupled thereto.

### Claim 19 (depends on 1)

The HBV immunogenic peptide of claim 1, further comprising a lipid coupled thereto.

### Claim 20 (depends on 1)

A method of stimulating a cytotoxic T cell response, said method comprising administering the peptide of claim 1, or a nucleic acid encoding said peptide, to a subject.

### Claim 21 (depends on 1)

A method of stimulating a cytotoxic T cell response, said method comprising administering the peptide of claim 1, or a nucleic acid encoding said peptide, to lymphocytes ex vivo.

### Claim 22 (depends on 21)

The method of claim 21, further comprising administering the lymphocytes to a subject.
