# US 6,723,695 B1 · CTL epitopes from EBV

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- Number: US 6,723,695 B1
- Document ID: US6723695B1
- Status: Granted
- Kind: B1
- Application number: 09/462,453
- Filed: 2000-05-30
- Granted: 2004-04-20
- Earliest claimed: 1997-07-10
- Assignees: The Council of the Queensland Institute of Medical Research; Commonwealth Scientific and Industrial Research Organisation of Limestone Avenue; The University of Melbourne of Royal Parade; Walter and Elisa Hall Institute of Medical Research of Royal Melbourne Hospital; CSL Limited
- Inventors: Scott Renton Burrows; Rajiv Khanna; Martina Alison Sherritt
- Web page: https://patentgrep.com/patent/US6723695B1

## CPC

- C07K 14/005: from viruses
- 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
- A61P 31/20: for DNA viruses
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- C12N 2710/16222: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2710/16622: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- 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
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present invention provides cytotoxic Epstein-Barr virus (EBV) T-cell epitopes derived from EBV structural antigens. Preferred epitopes include YLLEMLWRL (SEQ ID NO:1), YFLEILWGL (SEQ ID NO:32), YLLEILWRL (SEQ ID NO:33), YLQQNWWTL (SEQ ID NO:6), LLLALLFWL (SEQ ID NO:2), LLVDLLWLL (SEQ ID NO:3), LLLIALWNL (SEQ ID NO:4), WLLLFLAIL (SEQ ID NO:5), TLLVDLLWL (SEQ ID NO:7), LLWLLLFLA (SEQ ID NO:8), ILLIIALYL (SEQ ID NO:9), VLFIFGCLL (SEQ ID NO:10), RLGATIWQL (SEQ ID NO:11), ILYFIAFAL (SEQ ID NO:15), SLVIVTTFV (SEQ ID NO:17), LMIIPLINV (SEQ ID NO:20), TLFIGSHVV (SEQ ID NO:24), LIPETVPYI (SEQ ID NO:26), VLQWASLAV (SEQ ID NO:27) and QLTPHTKAV (SEQ ID NO:29). The present invention also provides methods of treating or preventing EBV infection in subjects which involve administration of EBV cytotoxic T-cell epitopes.

## Claims

### Claim 1

An isolated peptide consisting of a cytotoxic T-cell epitope having an amino acid sequence selected from the group consisting of YLLEMLWRL (SEQ ID NO:1), YFLEILWGL (SEQ ID NO:32), YLLEILWRL (SEQ ID NO:33), YLQQNWWTL (SEQ ID NO:6), LLLALLFWL (SEQ ID NO:2), LLVDLLWLL (SEQ ID NO:3), LLLIALWNL (SEQ ID NO:4), WLLLFLAIL (SEQ ID NO:5), TLLVDLLWL (SEQ ID NO:7), LLWLLLFLA (SEQ NO:8), ILLIIALYL (SEQ ID NO:9), VLFIFGCLL (SEQ ID NO:10), RLGATIWQL (SEQ ID NO:11), ILYFIAFAL (SEQ ID NO:15), SLVIVTTFV (SEQ ID NO:17), LMIIPLINV (SEQ ED NO:20), TLFIGSHVV (SEQ ID NO:24), LIPETVPYI (SEQ ID NO:26), VLQWASLAV (SEQ ID. NO:27) and QLTPHTKAV (SEQ ID NO:29).

### Claim 2 (depends on 1)

The isolated peptide of claim 1 wherein the cytotoxic T-cell epitope has an amino acid sequence selected from the group consisting of YLLEMLWRL (SEQ ID NO:1), YLLEILWRL (SEQ ID NO:33), YLQQNWWTL (SEQ ID NO:6), LLVDLLWLL (SEQ ID NO:3), LLLIAIWNL (SEQ ID NO:4), TLLVDLLWL (SEQ ID NO:7), RLGATIWQL (SEQ ID NO:1), SLVIVTTFV (SEQ ID NO:17), LMIIPLINV (SEQ ID NO:20), TLFIGSHVV (SEQ ID NO:24), and VLQWASLAV (SEQ ID NO:27).

### Claim 3 (depends on 2)

The isolated peptide of claim 2 wherein the cytotoxic T-cell epitope has an amino acid sequence selected from the group consisting of YLLEMLWRL (SEQ ID NO:1), YLLEILWRL (SEQ ID NO:33), YLQQNWWTL (SEQ ID NO:6), SLVIVTTFV (SEQ ID NO:17), LMIIPLINV (SEQ ID NO:20), TLFIGSHVV (SEQ ID
NO:24), and VLQWASLAV (SEQ ID:NO:27).

### Claim 4

An isolated nucleic acid comprising a nucleotide sequence encoding a peptide consisting of a cytotoxic T-cell epitope having an amino acid sequence selected from the group consisting of YLLEMLWRL (SEQ ID NO:1), YFLEILWGL (SEQ ID NO:32), YLLEILWRL (SEQ ID NO:33), YLQQNWWTL (SEQ ID NO:6), LLLALLFWL (SEQ ID NO:2), LLVDLLWLL (SEQ ID NO:3), LLLIALWNL (SEQ ID NO:4), WLLLFLAIL (SEQ ID NO:5), TLLVDLLWL (SEQ ID NO:7), LLWLLLFLA (SEQ ID NO:8), ILLIIALYL (SEQ ID NO:9), VLFIFGCLL (SEQ ID NO:10), RLGATIWQL (SEQ ID NO:11), ILYFIAFAL (SEQ ID NO:15), SLVIVTTFV (SEQ ID NO:17), LMIIPLINV (SEQ ID NO:20), TLFIGSHVV (SEQ ID NO:24), LIPETVPYI (SEQ ID NO:26), VLQWASLAV (SEQ ID NO:27) and QLTPHTKAV (SEQ ID NO:29).

### Claim 5 (depends on 4)

The isolated nucleic acid as claimed in claim 4 wherein the epitope has a sequence selected from the group consisting of YLLEMLWRL (SEQ ID NO:1), YLQQNWWTL (SEQ ID NO:6), YFLEILWGL (SEQ ID NO:32), YLLEIWRL (SEQ ID NO:33), SLVIVTTFV (SEQ ID NO:17), LMIIPLINV (SEQ:ID NO:20), TLFIGSHVV (SEQ ID NO:24),and VLQWASLAV (SEQ ID NO:27).

### Claim 6 (depends on 4)

The isolated nucleic acid of claim 4 wherein the cytotoxic T-cell epitope has an amino acid sequence selected from the group consisting of YLLEMLWRL (SEQ ID NO:1), YLLEILWRL (SEQ ID NO:33), YLQQNWWTL (SEQ ID NO:6), LLVDLLWLL (SEQ ID NO:3), LLLIALWNL (SEQ ID NO:4), TLLVDLLWL (SEQ ID NO:7), RLGATIWQL (SEQ ID NO. 11), SLVIVTTFV (SEQ ID NO:17), LMIIPLINV (SEQ ID NO:20), TLFIGSHVV (SEQ ID NO:24), and VLQWASLAV (SEQ ID NO:27).

### Claim 7 (depends on 6)

The isolated nucleic acid of claim 6 wherein the cytotoxic T-cell epitope has an amino acid sequence selected from the group consisting of YLLEMLWRL (SEQ ID NO:1), YLLEILWRL (SEQ ID NO:33), YLQQNWWTL (SEQ ID NO:6), SLVIVTTFV (SEQ ID NO:17), LMIIPLINV (SEQ ID NO:20), TLFIGSHVV (SEQ ID NO:24), and VLQWASLAV (SEQ ID NO:27).

### Claim 8 (depends on 6)

The isolated nucleic acid of claim 6 wherein the cytotoxic T-cell epitope has an amino acid sequence selected from the group consisting of YLLEMLWRL (SEQ ID NO:1), LLVDLLWLL (SEQ ID NO:3), LLLIALWNL (SEQ ID NO:4), YLQQNWWTL (SEQ ID NO:6), TLLVDLLWL (SEQ ID NO:7) and RLGATIWQL (SEQ ID NO:11).

### Claim 9 (depends on 8)

A vaccinia virus vector comprising the isolated nucleic acid of claim 8.

### Claim 10 (depends on 4)

A vector comprising an isolated nucleic acid as claimed in claim 4.

### Claim 11 (depends on 10)

The vector as claimed in claim 10 consisting of a bacterial vector.

### Claim 12 (depends on 11)

The vector as claimed in claim 11 wherein the bacterial vector is Salmonella spp.

### Claim 13 (depends on 10)

The vector as claimed in claim 10 consisting of a virus vector.

### Claim 14 (depends on 13)

The vector as claimed in claim 13 wherein the virus vector is selected from the group consisting of Adenovirus vector, Retrovirus vector, and Vaccinia vector.

### Claim 15 (depends on 14)

The vector as claimed in claim 14 wherein the Vaccinia vector is a Modified Vaccinia Ankara.

### Claim 16

An isolated polypeptide comprising a plurality of isolated Epstein-Barr virus (EBV) CTL epitopes selected from the group consisting of YLLEMLWRL (SEQ ID NO:1), YFLEILWGL (SEQ ID NO:32), YLLEILWRL (SEQ ID NO:33), YLOONWWTL (SEQ ID NO:6). LLLALLFWL (SEQ ID NO:2), LLVDLLWLL (SEQ ID NO:3), LLLIALWNL (SEQ ID NO.4), WLLLFLAIL (SEQ ID NO:5). TLLVDLLWL (SEQ ID NO:7), LLWLLLFLA (SEQ ID NO:8). ILLIIALYL (SEQ ID NO:9). VLFIFGCLL (SEQ ID NO:10). RLGATIWQL (SEQ ID NO:11), ILYFIAFAL (SEQ ID NO:15), SLVIVTTFV (SEQ ID NO:17), LMIIPLINV.(SEQ ID NO:20). TLFIGSHVV (SEQ ID NO:24). LIPETVPYI (SEQ ID NO:26). VLQWASLAV (SEQ ID NO:27) and QLTPHTKAV (SEQ ID NO:29).

### Claim 17

A method of preparing a composition for use in inducing CTLs in a subject, the method comprising admixing at least one peptide selected from the group consisting of YLLEMLWRL (SEQ ID NO:1), YFLEILWGL (SEQ ID NO:32), YLLEILWRL (SEQ ID NO:33), YLOQNWWTL (SEQ ID NO:6), LLLALLFWL (SEQ ID NO:2), LLVDLLWLL (SEQ ID NO:3), LLLIALWNL (SEQ ID N0:4), WLLLFLAIL (SEQ ID NO:5), TLLVDLLWL (SEQ ID NO;7), LLWLLLFLA (SEQ ID NO:8), ILLIIALYL (SEQ ID NO:9). VLFIFGCLL (SEQ ID NO:10), RLGATIWQL (SEQ ID NO:11), ILYFIAFAL (SEQ ID NO:15). SLVIVTTFV (SEQ ID NO:17). LMIIPLINV (SEQ ID NO:20). TLFIGSHVV (SEQ ID NO:24). LIPETVPYI (SEQ ID NO:26), VLQWASLAV (SEQ ID NO:27) and OLTPHTKAV (SEQ ID NO:29). with a pharmaceutically acceptable carrier, diluent or excipient.