# US 8,569,244 B2 · FOXM1 peptide and medicinal agent comprising the same

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- Number: US 8,569,244 B2
- Document ID: US8569244B2
- Status: Granted
- Kind: B2
- Application number: 12/673,432
- Filed: 2008-08-12
- Published: 2011-08-11
- Granted: 2013-10-29
- Earliest claimed: 2007-08-20
- Assignees: Oncotherapy Science, Inc.
- Applicants: Yasuharu Nishimura; Kazunori Yokomine; Takuya Tsunoda; Yusuke Nakamura
- Inventors: Yasuharu Nishimura; Kazunori Yokomine; Takuya Tsunoda; Yusuke Nakamura
- Web page: https://patentgrep.com/patent/US8569244B2

## CPC

- C12N 5/0636: {T lymphocytes}
- A61K 39/001152: {Transcription factors, e.g. SOX or c-MYC}
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 35/00: Antineoplastic agents
- A61P 37/04: Immunostimulants
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 7/06: having 5 to 11 amino acids
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- C12N 5/0638: {Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]}
- 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)
- A61K 2039/57: {characterised by the type of response, e.g. Th1, Th2}
- A61K 2039/572: {cytotoxic response}
- A61K 2039/585: {wherein the target is cancer}
- C12N 2501/998: Proteins not provided for elsewhere
- C12N 2502/11: blood or immune system cells
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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
- 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)

## Abstract

An objective of the present invention is to provide a means for enabling cancer immunotherapy that targets approximately 30% of various cancer patients that highly express forkhead box M1 (FOXM1) among the Japanese, by identifying FOXM1-derived peptides that can activate cancer cell-damaging human killer T cells by binding to HLA-A2. The present invention provides a peptide of (A) or (B) below: (A) a peptide including the amino acid sequence of any one of SEQ ID NOs: 1 to 3; (B) a peptide which includes the amino acid sequence of any one of SEQ ID NOs: 1 to 3, wherein one, two, or several amino acid(s) are substituted, deleted, inserted, and/or added, and wherein the peptide shows cytotoxic (killer) T cell-inducing activity.

## Claims

### Claim 1

An isolated peptide of (A) or (B) below:
(A) a peptide of less than 15 amino acids comprising the amino acid sequence of SEQ ID NO: 1;
(B) a peptide of less than 15 amino acids which comprises the amino acid sequence of SEQ ID NO: 1, in which one or two amino acid(s) are substituted, deleted, inserted, and/or added, wherein the peptide shows cytotoxic (killer) T cell-inducing activity.

### Claim 2 (depends on 1)

The peptide of claim 1, wherein the second amino acid from the N terminus of the amino acid sequence of SEQ ID NO: 1 is substituted with methionine.

### Claim 3 (depends on 1)

The peptide of claim 1, wherein the C-terminal amino acid of the amino acid sequence of SEQ ID NO: 1 is substituted with leucine.

### Claim 4 (depends on 1)

An agent for inducing cytotoxic activity against a cancer cell expressing FOXM1, which comprises one or more peptide(s) of claim 1 as an active ingredient.

### Claim 5 (depends on 1)

An agent comprising one or more peptide(s) of claim 1 as an active ingredient.

### Claim 6 (depends on 1)

An agent for inducing an antigen-presenting cell that shows cytotoxic (killer) T cell-inducing activity, wherein said agent comprises one or more peptide(s) of claim 1 as an active ingredient.

### Claim 7 (depends on 1)

An agent for inducing a cytotoxic (killer) T cell, wherein said agent comprises one or more peptide(s) of claim 1 as an active ingredient.

### Claim 8 (depends on 1)

A method for inducing an antigen-presenting cell that shows cytotoxic (killer) T cell-inducing activity, which comprises the step of contacting an antigen-presenting cell with the peptide of claim 1.

### Claim 9 (depends on 1)

A method for inducing a cytotoxic (killer) T cell, which comprises the step of contacting a T cell with the peptide of claim 1.

### Claim 10 (depends on 1)

A method for inducing cytotoxicity against cancer, which comprises the step of administering the peptide of claim 1 to a subject.

### Claim 11 (depends on 1)

A method for inducing a cytotoxic (killer) T cell, which comprises the steps of:
(A) contacting an antigen-presenting cell with the peptide of claim 1; and
(B) mixing and co-culturing the antigen-presenting cell of step (A) with a CD8+ T cell.