# US 6,297,050 B1 · Methods for treating subject with DAGE derived peptides

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- Number: US 6,297,050 B1
- Document ID: US6297050B1
- Status: Granted
- Kind: B1
- Application number: 09/322,360
- Filed: 1999-05-28
- Granted: 2001-10-02
- Earliest claimed: 1994-09-30
- Assignees: Ludwig Institute for Cancer Research
- Inventors: Pierre Coulie; Hideyuki Ikeda; Thierry Boon-Falleur
- Web page: https://patentgrep.com/patent/US6297050B1

## CPC

- C07K 14/4748: {Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE}
- A61P 35/00: Antineoplastic agents
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C12Q 2600/158: Expression markers
- Y10S 530/828: Cancer
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- 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)
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

A new family of tumor rejection antigen precursors, and the nucleic acid molecules which code for them, are disclosed. These tumor rejection antigen precursors are referred to as DAGE tumor rejection antigen precursors, and the nucleic acid molecules which code for them are referred to as GAGE coding molecules. Various diagnostic and therapeutic uses of the coding sequences and the tumor rejection antigens, and their precursor molecules are described.

## Claims

### Claim 1

A method for stimulating a cytotoxic T-cell response, comprising adding a peptide, whose sequence is set forth in SEQ ID NO:17, to a sample containing T-cells and cells expressing HLA molecules in an amount sufficient to bind to the HLA molecules on the surface of cells in said sample and to stimulate a cytotoxic T-cell response against complexes of said HLA molecule and said peptide, wherein said peptide consists of the amino acids sequence set forth at:
amino acids 28-36 of SEQ ID NO:17;
amino acids 40-48 of SEQ ID NO:17;
amino acids 48-56 of SEQ ID NO:17;
amino acids 80-88 of SEQ ID NO:17;
amino acids 100-108 of SEQ ID NO:17;
amino acids 118-126 of SEQ ID NO:17;
amino acids 150-158 of SEQ ID NO:17;
amino acids 156-164 of SEQ ID NO:17;
amino acids 184-192 of SEQ ID NO:17;
amino acids 195-203 of SEQ ID NO:17;
amino acids 198-206 of SEQ ID NO:17;
amino acids 204-212 of SEQ ID NO:17;
amino acids 254-262 of SEQ ID NO:17;
amino acids 355-364 of SEQ ID NO:17;
amino acids 375-383 of SEQ ID NO:17;
amino acids 447-455 of SEQ ID NO:17; or
the amino acid sequence set forth in SEQ ID NO:5.

### Claim 2 (depends on 1)

The method of claim 1, wherein said HLA molecule is an HLA-A2 molecule, and said peptide consists of amino acids 100-108 of SEQ ID NO:17, amino acids 355-364 of SEQ ID NO: 17.

### Claim 3 (depends on 1)

The method of claim 1, wherein said HLA molecule is HLA-A3 molecule, and said peptide consists of amino acids 28-36 of SEQ ID NO: 17, amino acids 80-88 of SEQ ID NO: 17; or amino acids 118-126 of SEQ ID NO: 17.

### Claim 4 (depends on 1)

The method of claim 1, wherein said HLA molecule is an HLA-A11 molecule, and said peptide consists of amino acids 150-158 of SEQ ID NO: 17, amino acids 195-203 of SEQ ID NO: 17; or amino acids 204-212 of SEQ ID NO: 17.

### Claim 5 (depends on 1)

The method of claim 1, wherein said HLA molecule is HLA-A24, and said peptide has the amino acid sequence of SEQ ID NO: 5, amino acids 254-262 of SEQ ID NO: 17; or amino acids 447-455 of SEQ ID NO: 17.

### Claim 6 (depends on 1)

The method of claim 1, wherein said HLA molecule is HLA-B7, and said peptide consists of amino acids 48-56 of SEQ ID NO: 17.

### Claim 7 (depends on 1)

The method of claim 1, wherein said HLA molecule is HLA-B8, and said peptide consists of amino acids 156-164 of SEQ ID NO: 17; or amino acids 198-206 of SEQ ID NO: 17.

### Claim 8 (depends on 1)

The method of claim 1, wherein said HLA molecule is HLA-B44, and said peptide consists of amino acids 184-192 of SEQ ID NO: 17.

### Claim 9 (depends on 1)

The method of claim 1, wherein said HLA molecule is HLA-Cw* 1601, and said peptide consists of amino acids 40-48 of SEQ ID NO: 17; or amino acids 375-383 of SEQ ID NO: 17.

### Claim 10

An isolated cytolytic T cell which specifically recognizes a complex of an HLA molecule and a peptide, wherein said peptide is selected from the group of peptides consisting of:
amino acids 28-36 of SEQ ID NO: 17;
amino acids 40-48 of SEQ ID NO: 17;
amino acids 48-56 of SEQ ID NO: 17;
amino acids 80-88 of SEQ ID NO: 17;
amino acids 100-108 of SEQ ID NO: 17;
amino acids 118-126 of SEQ ID NO: 17;
amino acids 150-158 of SEQ ID NO: 17;
amino acids 156-165 of SEQ ID NO: 17;
amino acids 184-192 of SEQ ID NO: 17;
amino acids 195-203 of SEQ ID NO: 17;
amino acids 198-206 of SEQ ID NO: 17;
amino acids 204-212 of SEQ ID NO: 17;
amino acids 254-262 of SEQ ID NO: 17;
amino acids 355-364 of SEQ ID NO: 17;
amino acids 375-383 of SEO ID NO: 17;
amino acids 447-455 of SEQ ID NO: 17; or
the amino acid sequence set forth in SEO ID NO: 5.

### Claim 11 (depends on 10)

The isolated cytolytic T cell of claim 10, specific for complexes of an HLA-B7 molecule and a peptide consisting of amino acids 48-56 of SEQ ID NO: 17.

### Claim 12 (depends on 10)

The isolated cytolytic T cell of claim 10, specific for complexes of an HLA-B8 molecule and a peptide consisting of amino acids 156-164 of SEQ ID NO: 17, or amino acids 198-206 of SEQ ID NO: 17.

### Claim 13 (depends on 10)

The isolated cytolytic T cell of claim 10, specific for a complex of an HLA-B44 molecule and a peptide consisting of amino acids 184-192 of SEQ ID NO: 17.

### Claim 14 (depends on 10)

The isolated cytolytic T cell of claim 10, specific for complexes of an HLA-Cw* 1601 molecule and a peptide consisting of amino acids 40-48 of SEQ ID NO: 17, or amino acids 375-383 of SEQ ID NO: 17.

### Claim 15 (depends on 10)

The isolated cytolytic T cell of claim 10, specific for a complex of an HLA-A2 molecule and a peptide consisting of amino acids 100-108 of SEQ ID NO: 17, or amino acids 355-364 of SEQ ID NO: 17.

### Claim 16 (depends on 10)

The isolated cytolytic T cell of claim 10, specific for a complex of an BLA-A3 molecule and a peptide consisting of amino acids 28-36 of SEQ ID NO: 17, amino acids 80-88 of SEQ ID NO: 17; or amino acids 118-126 of SEQ ID NO: 17.

### Claim 17 (depends on 16)

The isolated cytolytic T cell of claim 16, specific for a complex of an HLA-A11 molecule and a peptide consisting of amino acids 150-158 of SEQ ID NO: 17, amino acids 195-203 of SEQ ID NO: 17; or amino acids 204-212 of SEQ ID NO: 17.

### Claim 18 (depends on 10)

The isolated cytolytic T cell of claim 10, specific for a complex of an HLA-A24 molecule and a peptide consisting of SEQ ID NO: 5, amino acids 195-203 of SEQ ID NO: 17; or amino acids 204-212 of SEQ ID NO: 17.

### Claim 19

An isolated peptide, the amino acid sequence of which consists of:
amino acids 28-36 of SEQ ID NO: 17;
amino acids 40-48 of SEQ ID NO: 17;
amino acids 48-56 of SEQ ID NO: 17;
amino acids 80-88 of SEQ ID NO: 17;
amino acids 100-108 of SEQ ID NO: 17;
amino acids 118-126 of SEQ ID NO: 17;
amino acids 150-158 of SEQ ID NO: 17;
amino acids 156-164 of SEQ ID NO: 17;
amino acids 184-192 of SEQ ID NO: 17;
amino acids 195-203 of SEQ ID NO: 17;
amino acids 198-206 of SEQ ID NO: 17;
amino acids 204-212 of SEQ ID NO: 17;
amino acids 254-262 of SEQ ID NO: 17;
amino acids 355-364 of SEQ ID NO: 17;
amino acids 375-383 of SEQ ED NO: 17; or
amino acids 447-455 of SEQ ID NO: 17.