# US 2019/0376146 A1 · Method for predicting sensitivity of cancer to treatment with pd-1 immune checkpoint inhibitor > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0376146 A1 - Document ID: US20190376146A1 - Status: Published application - Kind: A1 - Application number: 16/462,469 - Filed: 2017-11-22 - Published: 2019-12-12 - Earliest claimed: 2016-11-24 - Assignees: Daiichi Sankyo Company, Limited - Applicants: Daiichi Sankyo Company, Limited - Inventors: Shinnosuke YAMADA; Naoki KIYOSAWA - Web page: https://patentgrep.com/patent/US20190376146A1 ## CPC - C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575) - A61P 35/00: Antineoplastic agents - C07K 16/28: against receptors, cell surface antigens or cell surface determinants - C07K 16/2818: {against CD28 or CD152} - C07K 16/2827: {against B7 molecules, e.g. CD80, CD86} - C12N 15/09: Recombinant DNA-technology - C12Q 1/68: involving nucleic acids - G01N 33/50: Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing (measuring or testing processes involving enzymes or microorganisms, compositions or test papers therefor; processes for forming such compositions, condition responsive control in microbiological or enzymological processes C12Q) - G01N 33/68: involving proteins, peptides or amino acids {(involving lipoproteins G01N33/92)} - G01N 37/00: Details not covered by any other group of this subclass - C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism - C12Q 2600/158: Expression markers - 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 - 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) - 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) ## Abstract The present invention provides a gene set for predicting the sensitivity of a cancer to a treatment with a PD-1 immune checkpoint inhibitor. More specifically, the present invention provides one or more genes selected from the group consisting of ADAM8, VCL, LEF1-AS1, TSPAN32, CTBP2, RXRA, PTGDS, ITGB1, KLRD1, RAB11FIP5, SLC4A8, NIN, GCNT2, ASB2, HNRPLL, AMPD3, SIRPG, PTPN13, MYB, ASAP1, MBOAT1, COTL1, ICOS, ST8SIA1, PASK, SGPP2, PDCD1, TBC1D4, EMP3, FAM65B, GBP1, FAM211B, PRR5, C17orf67, FAM101B and TBL1X, and a method for predicting the sensitivity of a cancer to a treatment with a PD-1 immune checkpoint inhibitor by using the genes. ## Claims ### Claim 1 A method for predicting sensitivity of a cancer or a tumor of a subject to a treatment with a PD-1 immune checkpoint inhibitor, comprising measuring an expression level(s) of one or more genes selected from the group consisting of the following genes: ADAM8, VCL, LEF1-AS1, TSPAN32, CTBP2, RXRA, PTGDS, ITGB1, KLRD1, RAB11FIP5, SLC4A8, NIN, GCNT2, ASB2, HNRPLL, AMPD3, SIRPG, PTPN13, MYB, ASAP1, MBOAT1, COTL1, ICOS, ST8SIA1, PASK, SGPP2, PDCD1, TBC1D4, EMP3, FAM65B, GBP1, FAM211B, PRR5, C17orf67, FAM101B and TBL1X in a sample obtained from the subject. ### Claim 2 (depends on 1) The method according to claim 1, comprising measuring expression levels of two or more genes selected from the group. ### Claim 3 (depends on 1) The method according to claim 1, comprising measuring an expression level(s) of at least one or more genes selected from TBL1X, FAM101B, TBC1D4, PRR5 and PTGDS. ### Claim 4 (depends on 3) The method according to claim 3, comprising measuring an expression level of a TBL1X gene and an expression level(s) of 1, 2, 3, 4, 5, 6, 7 or 8 or more genes selected from the group consisting of ADAM8, VCL, LEF1-AS1, TSPAN32, CTBP2, RXRA, PTGDS, ITGB1, KLRD1, RAB11FIP5, SLC4A8, NIN, GCNT2, ASB2, HNRPLL, AMPD3, SIRPG, PTPN13, MYB, ASAP1, MBOAT1, COTL1, ICOS, ST8SIA1, PASK, SGPP2, PDCD1, TBC1D4, EMP3, FAM65B, GBP1, FAM211B, PRR5, C17orf67 and FAM101B. ### Claim 5 (depends on 4) The method according to claim 4, comprising measuring expression levels of at least both TBL1X and FAM101B genes. ### Claim 6 (depends on 5) The method according to claim 5, comprising measuring expression levels of at least TBL1X, PTGDS, FAM101B, FAM211B, TBC1D4, PRR5 and C17orf67 genes. ### Claim 7 (depends on 1) The method according to claim 1, wherein the sample obtained from the subject is a biopsy tissue sample of a cancer or a tumor, or a biopsy tissue sample of a tissue suspected as being a cancer or a tumor. ### Claim 8 (depends on 7) The method according to claim 7, wherein an expression level of at least a PDCD1 gene is measured. ### Claim 9 (depends on 1) The method according to claim 1, wherein the treatment with a PD-1 immune checkpoint inhibitor is administration of an anti PD-1 antibody or an anti PD-L1 antibody. ### Claim 10 (depends on 1) A pharmaceutical composition comprising an anti PD-1 antibody or an anti PD-L1 antibody, for use in treating or preventing the cancer or the tumor in a subject having a cancer or a tumor predicted to be sensitive to a treatment with a PD-1 immune checkpoint inhibitor by the method according to claim 1. ### Claim 11 A gene signature comprising one or more genes selected from the group consisting of ADAM8, VCL, LEF1-AS1, TSPAN32, CTBP2, RXRA, PTGDS, ITGB1, KLRD1, RAB11FIP5, SLC4A8, NIN, GCNT2, ASB2, HNRPLL, AMPD3, SIRPG, PTPN13, MYB, ASAP1, MBOAT1, COTL1, ICOS, ST8SIA1, PASK, SGPP2, PDCD1, TBC1D4, EMP3, FAM65B, GBP1, FAM211B, PRR5, C17orf67, FAM101B and TBL1X, for use in predicting whether or not a cancer or a tumor is sensitive to a treatment with a PD-1 immune checkpoint inhibitor. ### Claim 12 (depends on 11) The gene signature according to claim 11, comprising at least one or more genes selected from TBL1X, FAM101B, TBC1D4, PRR5 and PTGDS. ### Claim 13 (depends on 12) The gene signature according to claim 12, comprising at least TBL1X and FAM101B. ### Claim 14 (depends on 13) The gene signature according to claim 13, comprising at least TBL1X, PTGDS, FAM101B, FAM211B, TBC1D4, PRR5 and C17orf67. ### Claim 15 A combination of nucleic acid probes or primer sets for a plurality of genes selected from the group consisting of ADAM8, VCL, LEF1-AS1, TSPAN32, CTBP2, RXRA, PTGDS, ITGB1, KLRD1, RAB11FIP5, SLC4A8, NIN, GCNT2, ASB2, HNRPLL, AMPD3, SIRPG, PTPN13, MYB, ASAP1, MBOAT1, COTL1, ICOS, ST8SIA1, PASK, SGPP2, PDCD1, TBC1D4, EMP3, FAM65B, GBP1, FAM211B, PRR5, C17orf67, FAM101B and TBL1X. ### Claim 16 (depends on 15) The combination of nucleic acid probes or primer sets according to claim 15, wherein the plurality of genes comprises at least one or more genes selected from TBL1X, FAM101B, TBC1D4, PRR5 and PTGDS. ### Claim 17 (depends on 16) The combination of nucleic acid probes or primer sets according to claim 16, wherein the plurality of genes comprises at least TBL1X, PTGDS, FAM101B, FAM211B, TBC1D4, PRR5 and C17orf67. ### Claim 18 (depends on 15) A microarray comprising the nucleic acid probes defined in claim 15. ### Claim 19 A kit for use in determining sensitivity to a treatment with a PD-1 immune checkpoint inhibitor, comprising means for measuring an expression level(s) of one or more genes selected from the group consisting of ADAM8, VCL, LEF1-AS1, TSPAN32, CTBP2, RXRA, PTGDS, ITGB1, KLRD1, RAB11FIP5, SLC4A8, NIN, GCNT2, ASB2, HNRPLL, AMPD3, SIRPG, PTPN13, MYB, ASAP1, MBOAT1, COTL1, ICOS, ST8SIA1, PASK, SGPP2, PDCD1, TBC1D4, EMP3, FAM65B, GBP1, FAM211B, PRR5, C17orf67, FAM101B and TBL1X. ### Claim 20 (depends on 19) The kit according to claim 19, wherein the one or more genes comprise at least one or more genes selected from TBL1X, FAM101B, TBC1D4, PRR5 and PTGDS. ### Claim 21 (depends on 20) The kit according to claim 20, wherein the one or more genes comprise at least TBL1X, PTGDS, FAM101B, FAM211B, TBC1D4, PRR5 and C17orf67. ### Claim 22 (depends on 2) A pharmaceutical composition comprising an anti PD-1 antibody or an anti PD-L1 antibody, for use in treating or preventing the cancer or the tumor in a subject having a cancer or a tumor predicted to be sensitive to a treatment with a PD-1 immune checkpoint inhibitor by the method according to claim 2. ### Claim 23 (depends on 3) A pharmaceutical composition comprising an anti PD-1 antibody or an anti PD-L1 antibody, for use in treating or preventing the cancer or the tumor in a subject having a cancer or a tumor predicted to be sensitive to a treatment with a PD-1 immune checkpoint inhibitor by the method according to claim 3. ### Claim 24 (depends on 4) A pharmaceutical composition comprising an anti PD-1 antibody or an anti PD-L1 antibody, for use in treating or preventing the cancer or the tumor in a subject having a cancer or a tumor predicted to be sensitive to a treatment with a PD-1 immune checkpoint inhibitor by the method according to claim 4. ### Claim 25 (depends on 5) A pharmaceutical composition comprising an anti PD-1 antibody or an anti PD-L1 antibody, for use in treating or preventing the cancer or the tumor in a subject having a cancer or a tumor predicted to be sensitive to a treatment with a PD-1 immune checkpoint inhibitor by the method according to claim 5. ### Claim 26 (depends on 6) A pharmaceutical composition comprising an anti PD-1 antibody or an anti PD-L1 antibody, for use in treating or preventing the cancer or the tumor in a subject having a cancer or a tumor predicted to be sensitive to a treatment with a PD-1 immune checkpoint inhibitor by the method according to claim 6. ### Claim 26 (depends on 7) A pharmaceutical composition comprising an anti PD-1 antibody or an anti PD-L1 antibody, for use in treating or preventing the cancer or the tumor in a subject having a cancer or a tumor predicted to be sensitive to a treatment with a PD-1 immune checkpoint inhibitor by the method according to claim 7. ### Claim 27 (depends on 8) A pharmaceutical composition comprising an anti PD-1 antibody or an anti PD-L1 antibody, for use in treating or preventing the cancer or the tumor in a subject having a cancer or a tumor predicted to be sensitive to a treatment with a PD-1 immune checkpoint inhibitor by the method according to claim 8. ### Claim 28 (depends on 9) a pharmaceutical composition comprising an anti PD-1 antibody or an anti PD-L1 antibody, for use in treating or preventing the cancer or the tumor in a subject having a cancer or a tumor predicted to be sensitive to a treatment with a PD-1 immune checkpoint inhibitor by the method according to claim 9.