# US 10,765,729 B2 · Tumor antigen peptide > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,765,729 B2 - Document ID: US10765729B2 - Status: Granted - Kind: B2 - Application number: 15/534,315 - Filed: 2015-12-08 - Published: 2017-12-21 - Granted: 2020-09-08 - Earliest claimed: 2014-12-09 - Assignees: Sapporo Medical University; Sumitomo Dainippon Pharma Co., Ltd. - Applicants: Sapporo Medical University; Sumitomo Dainippon Pharma Co., Ltd. - Inventors: Noriyuki Sato; Toshihiko Torigoe; Yoshihiko Hirohashi; Takayuki Kanaseki; Sho Miyamoto; Vitaly Kochin; Masashi Goto - Web page: https://patentgrep.com/patent/US10765729B2 ## CPC - G01N 33/575: for cancer - A61K 39/0011: {Cancer antigens} - A61K 39/00118: {from embryonic or fetal origin} - A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells - A61K 40/42: Cancer antigens - A61K 40/46: Viral antigens - A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy - A61P 35/00: Antineoplastic agents - C07K 7/06: having 5 to 11 amino acids - C07K 14/47: from mammals - C07K 14/4748: {Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE} - C07K 16/2833: {against MHC-molecules, e.g. HLA-molecules} - C07K 16/30: from tumour cells - C12N 5/0638: {Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]} - C12Q 1/68: involving nucleic acids - C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575) - G01N 33/5011: {for testing antineoplastic activity} - G01N 33/5088: {of vertebrates} - G01N 33/5758: {involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites} - A61K 2039/572: {cytotoxic response} - A61K 2039/82: {Colon} - C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues - C12Q 2600/136: Screening for pharmacological compounds - C12Q 2600/158: Expression markers - C12Q 2600/178: miRNA, siRNA or ncRNA - G01N 2333/46: from vertebrates - G01N 2333/70539: MHC-molecules, e.g. HLA-molecules - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - 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) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - 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 ## Abstract The purpose of the present invention is to provide: a detection agent for specifically detecting a cancer stem cell; a tumor antigen peptide specifically presented by cancer stem cells; a medicinal composition useful in preventing and/or treating cancer, said medicinal composition comprising the aforementioned tumor antigen peptide as an active ingredient; a method for screening the tumor antigen peptide; etc. To achieve the above-mentioned purpose, provided are: peptides represented by YO-XO-ZO; a polyepitope peptide consisting of a plurality of epitope peptides connected together, said polyepitope peptide containing at least one of the above-mentioned peptides as one of the epitope peptides; a polynucleotide encoding the aforementioned peptides and/or polyepitope peptide; a medicinal composition comprising the same as an active ingredient; a prophylactic and/or therapeutic agent for cancer characterized by inducing CTL; etc. ## Claims ### Claim 1 An antigen peptide represented by Y0-X0-Z0, wherein X0 is any of (1) to (2) below: (1) SEQ ID NO: 3 in which the second amino acid from the N terminal is replaced by leucine, isoleucine or methionine, and/or the amino acid at the C terminal is replaced by leucine or isoleucine; or (2) SEQ ID NO: 3 in which the second amino acid from the N terminal is replaced by phenylalanine, methionine or tryptophan, and/or the amino acid at the C terminal is replaced by leucine, isoleucine or phenylalanine; and, Y0 and Z0 are mutually independently a peptide consisting of 0 to 5 amino acids. ### Claim 2 (depends on 1) The antigen peptide according to claim 1, wherein X0 consists of an amino acid sequence represented by SEQ ID NO: 3, in which the second amino acid from the N terminal is replaced by methionine, leucine or isoleucine, and/or the amino acid at the C terminal is replaced by leucine or isoleucine; and Y0 and Z0 are not present. ### Claim 3 (depends on 1) The antigen peptide according to claim 1, wherein X0 consists of an amino acid sequence represented by SEQ ID NO: 3, in which the second amino acid from the N terminal is replaced by methionine, and/or the amino acid at the C terminal is replaced by leucine, isoleucine or phenylalanine; and Y0 and Z0 are not present. ### Claim 4 An antigen peptide represented by Y0-X0-Z0 wherein X0 consists of an amino acid sequence represented by SEQ ID NO: 3, either one of Y0 or Z0 is one amino acid, and the other is not present, provided that Y0 is not arginine and Z0 is not isoleucine. ### Claim 5 (depends on 1) A polyepitope peptide which comprises a plurality of epitope peptides linked together, wherein the polyepitope peptide comprises at least one antigen peptide according to claim 1 or any of a peptide represented by Y0-X0-Z0, wherein X0 is SEQ ID NO. 3, and Y0 and Z0 are mutually independently a peptide consisting of 0 to 5 amino acids as the epitope peptide. ### Claim 6 (depends on 1, 4) A polynucleotide encoding at least one of the antigen peptide according to claim 1 or claim 4. ### Claim 7 (depends on 6) An expression vector comprising the polynucleotide according to claim 6. ### Claim 8 (depends on 7) A gene transfer composition comprising the expression vector according to claim 7. ### Claim 9 (depends on 1, 4) A pharmaceutical composition comprising as an active ingredient any of (a) to (c) below: (a) the antigen peptide according to claim 1 or claim 4, (b) a polynucleotide encoding the peptide according to claim 1 or claim 4, (c) an expression vector comprising the polynucleotide encoding the peptide according to claim 1 or claim 4. ### Claim 10 (depends on 9) The pharmaceutical composition according to claim 9, wherein the active ingredient is (a) the antigen peptide. ### Claim 11 (depends on 9) The pharmaceutical composition according to claim 9, further comprising an adjuvant. ### Claim 12 (depends on 9) The pharmaceutical composition according to claim 9, wherein the pharmaceutical composition is an agent against recurrence and metastasis of cancer and/or therapeutic agent for cancer. ### Claim 13 (depends on 9) The pharmaceutical composition according to claim 9, wherein the pharmaceutical composition is a vaccine for the prevention of recurrence and metastasis and/or treatment of a cancer. ### Claim 14 (depends on 1, 4) An agent for inducing cytotoxic T cells, the agent comprising as an active ingredient any of (a) to (c) below: (a) the antigen peptide according to claim 1 or claim 4, (b) a polynucleotide encoding the peptide according to claim 1 or claim 4, (c) an expression vector comprising the polynucleotide encoding the peptide according to claim 1 or claim 4. ### Claim 15 (depends on 1) A method for producing an antigen-presenting cell, the method comprising contacting in vitro a cell having an antigen-presenting ability with (A) the antigen peptide according to claim 1 or any of a peptide represented by Y0-X0-Z0, wherein X0 is SEQ ID NO. 3, and Y0 and Z0 are mutually independently a peptide consisting of 0 to 5 amino acids, or (B) a polynucleotide encoding at least one of the peptide of (A). ### Claim 16 (depends on 1) A method for inducing a cytotoxic T cell, the method comprising contacting in vitro a peripheral blood lymphocyte with (A) the antigen peptide according to claim 1 or any of a peptide represented by Y0-X0-Z0, wherein X0 is SEQ ID NO. 3, and Y0 and Z0 are mutually independently a peptide consisting of 0 to 5 amino acids, or (B) a polynucleotide encoding at least one of the antigen peptide of (A). ### Claim 17 (depends on 1, 4) An HLA multimer comprising an HLA and the antigen peptide according to claim 1 or claim 4. ### Claim 18 (depends on 17) A diagnostic agent comprising the HLA multimer according to claim 17. ### Claim 19 (depends on 1) The antigen peptide according to claim 1, wherein X0 consists of an amino acid sequence represented by SEQ ID NO: 3, in which the second amino acid from the N terminal is replaced by methionine, leucine or isoleucine, and/or the amino acid at the C terminal is replaced by leucine or isoleucine, either one of Y0 or Z0 is one amino acid, and the other is not present. ### Claim 20 (depends on 1) The antigen peptide according to claim 1, wherein X0 consists of an amino acid sequence represented by SEQ ID NO: 3, in which the second amino acid from the N terminal is replaced by methionine, and/or the amino acid at the C terminal is replaced by leucine, isoleucine or phenylalanine, either one of Y0 or Z0 is one amino acid, and the other is not present. ### Claim 21 (depends on 1, 4) A method for treating a subject having cancer comprising administering to the subject an effective amount of the peptide according to claim 1 or claim 4. ### Claim 22 (depends on 6) A method for treating a subject having cancer comprising administering to the subject an effective amount of the polynucleotide according to claim 6. ### Claim 23 (depends on 16) A method for treating a subject having cancer comprising administering to the subject an effective amount of CTLs induced by the method according to claim 16. ### Claim 24 (depends on 15) A method for treating a subject having cancer comprising administering to the subject an effective amount of antigen presenting cells produced by the method according to claim 15. ### Claim 25 A pharmaceutical composition comprising as an active ingredient a peptide represented by Y0-X0-Z0, wherein X0 is SEQ ID NO. 3, and Y0 and Z0 are mutually independently a peptide consisting of 0 to 5 amino acids; and an adjuvant. ### Claim 26 A method for treating a subject having cancer comprising administering to the subject an effective amount of a peptide represented by Y0-X0-Z0, wherein X0 is SEQ ID NO. 3 and Y0 and Z0 are mutually independently a peptide consisting of 0 to 5 amino acids. ### Claim 27 A method for treating a subject having cancer comprising administering to the subject an effective amount of a polynucleotide encoding a peptide represented by Y0-X0-Z0, wherein X0 is SEQ ID NO. 3 and Y0 and Z0 are mutually independently a peptide consisting of 0 to 5 amino acids. ### Claim 28 An antigen peptide represented by Y0-X0-Z0, wherein X0 is any of (1) to (2) below: (1) SEQ ID NO: 28 in which the second amino acid from the N terminal is replaced by leucine or methionine, and/or the amino acid at the C terminal is replaced by leucine or isoleucine; or (2) SEQ ID NO: 28 in which the second amino acid from the N terminal is replaced by tyrosine, phenylalanine, methionine or tryptophan, and/or the amino acid at the C terminal is replaced by leucine, isoleucine or phenylalanine; and, Y0 and Z0 are mutually independently a peptide consisting of 0 to 5 amino acids. ### Claim 29 An antigen peptide represented by Y0-X0-Z0, wherein X0 is any of (1) to (2) below: (1) SEQ ID NO: 4 in which the second amino acid from the N terminal is replaced by isoleucine or methionine, and/or the amino acid at the C terminal is replaced by leucine or isoleucine; or (2) SEQ ID NO: 4 in which the second amino acid from the N terminal is replaced by tyrosine, phenylalanine, methionine or tryptophan, and/or the amino acid at the C terminal is replaced by leucine, isoleucine or phenylalanine; and, Y0 and Z0 are mutually independently a peptide consisting of 0 to 5 amino acids.