# US 2021/0340628 A1 · Sensitivity marker for antibody-drug conjugate > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2021/0340628 A1 - Document ID: US20210340628A1 - Status: Published application - Kind: A1 - Application number: 17/269,615 - Filed: 2019-08-22 - Published: 2021-11-04 - Earliest claimed: 2018-08-23 - Assignees: Daiichi Sankyo Company, Limited - Applicants: Daiichi Sankyo Company, Limited - Inventors: Daisuke OKAJIMA; Satoru YASUDA; Kei ENOMOTO - Web page: https://patentgrep.com/patent/US20210340628A1 ## CPC - C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575) - C07K 16/30: from tumour cells - G01N 33/575: for cancer - C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism - C12Q 2600/158: Expression markers - G01N 2030/8827: {involving nucleic acids} - 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 - 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) - 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 A method for identifying a subject suffering from a cancer, comprising: obtaining a biological sample from the human patient diagnosed as suffering from a cancer; evaluating an amount of expression of the hTROP2 gene at mRNA level in the biological sample; evaluating an amount of expression of the SLFN11 gene at mRNA level in the biological sample, wherein the biological sample is one that is determined to have a high amount of expression of the hTROP2 gene; and identifying the human patient who provided the biological sample, wherein the biological sample is one that is determined to have a high amount of expression of the SLFN11 gene, as a subject to whom a medicament containing an anti-hTROP2 antibody is to be given. ## Claims ### Claim 1 A method for identifying a subject to whom a medicament containing an anti-hTROP2 antibody is to be given, wherein the subject is a human patient suffering from a cancer, the method comprising: 1) obtaining a biological sample from the human patient diagnosed as suffering from a cancer; 2) evaluating an amount of expression of the hTROP2 gene at mRNA level in the biological sample; 3) evaluating an amount of expression of the SLFN11 gene at mRNA level in the biological sample, wherein the biological sample is one that is determined to have a high amount of expression of the hTROP2 gene; and 4) identifying the human patient who provided the biological sample, wherein the biological sample is one that is determined to have a high amount of expression of the SLFN11 gene, as a subject to whom a medicament containing an anti-hTROP2 antibody is to be given. ### Claim 2 A method for identifying a subject to whom a medicament containing an anti-hTROP2 antibody is to be given, wherein the subject is a human patient suffering from a cancer, the method comprising: 1) obtaining a biological sample from the human patient diagnosed as suffering from a cancer; 2) evaluating an amount of expression of the hTROP2 gene and the SLFN11 gene at mRNA level in the biological sample; and 3) identifying the human patient who provided the biological sample, wherein the biological sample is one that is determined to have a high amount of expression of the hTROP2 gene and the SLFN11 gene, as a subject to whom a medicament containing an anti-hTROP2 antibody is to be given. ### Claim 3 (depends on 1) The method according to claim 1, wherein a log2[RPKM+1] value is measured by RNA sequencing from the biological sample obtained from the human patient diagnosed as suffering from a cancer, and the biological sample is determined to have a high amount of expression of the hTROP2 gene and/or the SLFN11 gene at mRNA level when the log2[RPKM+1] value exceeds a specific value. ### Claim 4 (depends on 3) The method according to claim 3, wherein the biological sample is determined to have a high amount of expression of the hTROP2 gene at mRNA level when the log2[RPKM+1] value exceeds any one selected from the group consisting of 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, and 9.0. ### Claim 5 (depends on 3) The method according to claim 3 or wherein the biological sample is determined to have a high amount of expression of the hTROP2 gene at mRNA level when the log2[RPKM+1] value exceeds any one selected from the group consisting of 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, and 8.0. ### Claim 6 (depends on 3) The method according to claim 3, wherein the biological sample is determined to have a high amount of expression of the hTROP2 gene at mRNA level when the log2[RPKM+1] value exceeds any one selected from the group consisting of 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, and 8.0. ### Claim 7 (depends on 3) The method according to claim 3, wherein the biological sample is determined to have a high amount of expression of the hTROP2 gene at mRNA level when the log2[RPKM+1] value exceeds any one selected from the group consisting of 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, and 8.0. ### Claim 8 (depends on 3) The method according to claim 3, wherein the biological sample is determined to have a high amount of expression of the hTROP2 gene at mRNA level when the log2[RPKM+1] value exceeds any one selected from the group consisting of 7.5, 7.6, 7.7, 7.8, 7.9, and 8.0. ### Claim 9 (depends on 3) The method according to claim 3, wherein the biological sample is determined to have a high amount of expression of the hTROP2 gene at mRNA level when the log2[RPKM+1] value exceeds any one selected from the group consisting of 7.0, 7.5, and 8.0. ### Claim 10 (depends on 9) The method according to claim 9, wherein the biological sample is determined to have a high amount of expression of the hTROP2 gene at mRNA level when the log2[RPKM+1] value exceeds 7.0. ### Claim 11 (depends on 9) The method according to claim 9, wherein the biological sample is determined to have a high amount of expression of the hTROP2 gene at mRNA level when the log2[RPKM+1] value exceeds 7.5. ### Claim 12 (depends on 9) The method according to claim 9, wherein the biological sample is determined to have a high amount of expression of the hTROP2 gene at mRNA level when the log2[RPKM+1] value exceeds 8.0. ### Claim 13 (depends on 3) The method according to claim 3, wherein the biological sample is determined to have a high amount of expression of the SLFN11 gene at mRNA level when the log2[RPKM+1] value exceeds any one selected from the group consisting of 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, and 4.0. ### Claim 14 (depends on 3) The method according to claim 3, wherein the biological sample is determined to have a high amount of expression of the SLFN11 gene at mRNA level when the log2[RPKM+1] value exceeds any one selected from the group consisting of 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, and 3.0. ### Claim 15 (depends on 3) The method according to claim 3, wherein the biological sample is determined to have a high amount of expression of the SLFN11 gene at mRNA level when the log2[RPKM+1] value exceeds any one selected from the group consisting of 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, and 3.0. ### Claim 16 (depends on 3) The method according to claim 3, wherein the biological sample is determined to have a high amount of expression of the SLFN11 gene at mRNA level when the log2[RPKM+1] value exceeds any one selected from the group consisting of 1.0, 2.0, and 3.0. ### Claim 17 (depends on 16) The method according to claim 16, wherein the biological sample is determined to have a high amount of expression of the SLFN11 gene at mRNA level when the log2[RPKM+1] value exceeds 1.0. ### Claim 18 (depends on 16) The method according to claim 16, wherein the biological sample is determined to have a high amount of expression of the SLFN11 gene at mRNA level when the log2[RPKM+1] value exceeds 2.0. ### Claim 19 (depends on 16) The method according to claim 16, wherein the biological sample is determined to have a high amount of expression of the SLFN11 gene at mRNA level when the log2[RPKM+1] value exceeds 3.0. ### Claim 20 (depends on 1) The method according to claim 1, wherein a log2[FPKM+1] value is measured by RNA sequencing from the biological sample obtained from the human patient diagnosed as suffering from a cancer, and the biological sample is determined to have a high amount of expression of the hTROP2 gene and/or the SLFN11 gene at mRNA level when the log2[FPKM+1] value exceeds a specific value. ### Claim 21 (depends on 20) The method according to claim 20, wherein the biological sample is determined to have a high amount of expression of the hTROP2 gene at mRNA level when the log2[FPKM+1] value exceeds any one selected from the group consisting of 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, and 8.0. ### Claim 22 (depends on 20) The method according to claim 20, wherein the biological sample is determined to have a high amount of expression of the hTROP2 gene at mRNA level when the log2[FPKM+1] value exceeds any one selected from the group consisting of 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, and 7.0. ### Claim 23 (depends on 20) The method according to claim 20, wherein the biological sample is determined to have a high amount of expression of the hTROP2 gene at mRNA level when the log2[FPKM+1] value exceeds 6.0 or 7.0. ### Claim 24 (depends on 23) The method according to claim 23, wherein the biological sample is determined to have a high amount of expression of the hTROP2 gene at mRNA level when the log2[FPKM+1] value exceeds 6.0. ### Claim 25 (depends on 23) The method according to claim 23, wherein the biological sample is determined to have a high amount of expression of the hTROP2 gene at mRNA level when the log2[FPKM+1] value exceeds 7.0. ### Claim 26 (depends on 20) The method according to claim 20, wherein the biological sample is determined to have a high amount of expression of the SLFN11 gene at mRNA level when the log2[FPKM+1] value exceeds any one selected from the group consisting of 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, and 4.0. ### Claim 27 (depends on 20) The method according to claim 20, wherein the biological sample is determined to have a high amount of expression of the SLFN11 gene at mRNA level when the log2[FPKM+1] value exceeds any one selected from the group consisting of 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, and 3.0. ### Claim 28 (depends on 20, 21, 22, 23, 24, 25, 26, 27) The method according to any onc of claims 20 to 27, wherein the biological sample is determined to have a high amount of expression of the SLFN11 gene at mRNA level when the log2[FPKM+1] value exceeds 2.0 or 3.0. ### Claim 29 (depends on 28) The method according to claim 28, wherein the biological sample is determined to have a high amount of expression of the SLFN11 gene at mRNA level when the log2[FPKM+1] value exceeds 2.0. ### Claim 30 (depends on 28) The method according to claim 28, wherein the biological sample is determined to have a high amount of expression of the SLFN11 gene at mRNA level when the log2[FPKM+1] value exceeds 3.0. ### Claim 31 (depends on 1) The method according to claim 1, wherein a log2[MNC +1] value is measured by an EdgeSeq Assay from the biological sample obtained from the human patient diagnosed as suffering from a cancer, and the biological sample is determined to have a high amount of expression of the hTROP2 gene and/or the SLFN11 gene at mRNA level when the log2[MNC+1] value exceeds a specific value. ### Claim 32 (depends on 31) The method according to claim 31, wherein the biological sample is determined to have a high amount of expression of the hTROP2 gene at mRNA level when the log2[MNC+1] value exceeds any one selected from the group consisting of 12.0, 12.1, 12.2, 12.3, 12.4, 12.5, 12.6, 12.7, 12.8, 12.9, 13.0. 13.1, 13.2, 13.3, 13.4, 13.5, 13.6, 13.7, 13.8, 13.9, 14.0, 14.1, 14.2, 14.3, 14.4, 14.5, 14.6, 14.7, 14.8, 14.9, and 15.0. ### Claim 33 (depends on 31) The method according to claim 31, wherein the biological sample is determined to have a high amount of expression of the hTROP2 gene at mRNA level when the log2[MNC+1] value exceeds any one selected from the group consisting of 12.0, 12.1, 12.2, 12.3, 12.4, 12.5, 12.6, 12.7, 12.8, 12.9, 13.0. 13.1, 13.2, 13.3, 13.4, 13.5, 13.6, 13.7, 13.8, 13.9, and 14.0. ### Claim 34 (depends on 31) The method according to claim 31, wherein the biological sample is determined to have a high amount of expression of the hTROP2 gene at mRNA level when the log2[MNC+1] value exceeds 12.0, 13.0, or 14.0. ### Claim 35 (depends on 34) The method according to claim 34, wherein the biological sample is determined to have a high amount of expression of the hTROP2 gene at mRNA level when the log2[MNC+1] value exceeds 12.0. ### Claim 36 (depends on 34) The method according to claim 34, wherein the biological sample is determined to have a high amount of expression of the hTROP2 gene at mRNA level when the log2[MNC+1] value exceeds 13.0. ### Claim 37 (depends on 34) The method according to claim 34, wherein the biological sample is determined to have a high amount of expression of the hTROP2 gene at mRNA level when the log2[MNC+1] value exceeds 14.0. ### Claim 38 (depends on 31) The method according to claim 31, wherein the biological sample is determined to have a high amount of expression of the SLFN11 gene at mRNA level when the log2[MNC+1] value exceeds any one selected from the group consisting of 11.5, 11.6, 11.7, 11.8, 11.9, 12.0, 12.1, 12.2, 12.3, 12.4, 12.5, 12.6, 12.7, 12.8, 12.9, 13.0, 13.1, 13.2, 13.3, 13.4, and 13.5. ### Claim 39 (depends on 31) The method according to claim 31, wherein the biological sample is determined to have a high amount of expression of the SLFN11 gene at mRNA level when the log2[MNC+1] value exceeds any one selected from the group consisting of 11.5, 11.6, 11.7, 11.8, 11.9, 12.0, 12.1, 12.2, 12.3, 12.4, and 12.5. ### Claim 40 (depends on 31) The method according to claim 31, wherein the biological sample is determined to have a high amount of expression of the SLFN11 gene at mRNA level when the log2[MNC+1] value exceeds any one selected from the group consisting of 11.5, 12.0, and 12.5. ### Claim 41 (depends on 40) The method according to claim 40, wherein the biological sample is determined to have a high amount of expression of the SLFN11 gene at mRNA level when the log2[MNC+1] value exceeds 11.5. ### Claim 42 (depends on 40) The method according to claim 40, wherein the biological sample is determined to have a high amount of expression of the SLFN11 gene at mRNA level when the log2[MNC+1] value exceeds 12.0. ### Claim 43 (depends on 40) The method according to claim 40, wherein the biological sample is determined to have a high amount of expression of the SLFN11 gene at mRNA level when the log2[MNC+1] value exceeds 12.5. ### Claim 44 (depends on 1) The method according to claim 1, wherein the biological sample includes a tumor sample. ### Claim 45 (depends on 1) The method according to claim 1, wherein the medicament containing an anti-hTROP2 antibody is an anti-hTROP2 antibody-drug conjugate. ### Claim 46 (depends on 45) The method according to claim 45, wherein the anti-hTROP2 antibody-drug conjugate is an antibody-drug conjugate in which a drug-linker represented by the formula: wherein A represents a connecting position to the anti-hTROP2 antibody, and the anti-hTROP2 antibody are conjugated to each other via a thioether bond. ### Claim 47 (depends on 46) The method according to claim 46, wherein the anti-hTROP2 antibody is an antibody consisting of a heavy chain consisting of an amino acid sequence consisting of amino acid residues 20 to 470 of SEQ ID NO: 1 and a light chain consisting of an amino acid sequence consisting of amino acid residues 21 to 234 of SEQ ID NO: 2. ### Claim 48 (depends on 47) The method according to claim 47, wherein a lysine residue at the carboxyl terminus of the heavy chain of the anti-hTROP2 antibody is deleted. ### Claim 49 (depends on 46) The method according to claim 46, wherein an average number of units of the drug-linker conjugated per antibody molecule ranges from 2 to 8. ### Claim 50 (depends on 46) The method according to claim 46, wherein an average number of units of the drug-linker conjugated per antibody molecule ranges from 3.5 to 4.5. ### Claim 51 (depends on 45) The method according to claim 45, wherein the anti-hTROP2 antibody-drug conjugate is Sacituzumab Govitecan (IMMU-132). ### Claim 52 (depends on 1) The method according to claim 1, wherein the cancer is a lung cancer, a kidney cancer, a urothelial cancer, a colorectal cancer, a prostate cancer, polymorphic glioblastoma, an ovarian cancer, a pancreatic cancer, a breast cancer, melanoma, a liver cancer, a bladder cancer, a gastric cancer, a cervical cancer, a uterine cancer, a head and neck cancer, an esophageal cancer, a biliary tract cancer, a thyroid cancer, lymphoma, acute myeloid leukemia, acute lymphoid leukemia, and/or multiple myeloma. ### Claim 53 (depends on 2) The method according to claim 2, wherein a log2[RPKM+1] value is measured by RNA sequencing from the biological sample obtained from the human patient diagnosed as suffering from a cancer, and the biological sample is determined to have a high amount of expression of the hTROP2 gene and/or the SLFN11 gene at mRNA level when the log2[RPKM+1] value exceeds a specific value. ### Claim 54 (depends on 2) The method according to claim 2, wherein a log2[FPKM+1] value is measured by RNA sequencing from the biological sample obtained from the human patient diagnosed as suffering from a cancer, and the biological sample is determined to have a high amount of expression of the hTROP2 gene and/or the SLFN11 gene at mRNA level when the log2[FPKM+1] value exceeds a specific value. ### Claim 55 (depends on 2) The method according to claim 2, wherein a log2[MNC+1] value is measured by an EdgeSeq Assay from the biological sample obtained from the human patient diagnosed as suffering from a cancer, and the biological sample is determined to have a high amount of expression of the hTROP2 gene and/or the SLFN11 gene at mRNA level when the log2[MNC+1] value exceeds a specific value. ### Claim 56 (depends on 2) The method according to claim 2, wherein the biological sample includes a tumor sample. ### Claim 57 (depends on 2) The method according to claim 2, wherein the medicament containing an anti-hTROP2 antibody is an anti-hTROP2 antibody-drug conjugate. ### Claim 58 (depends on 2) The method according to claim 2, wherein the cancer is a lung cancer, a kidney cancer, a urothelial cancer, a colorectal cancer, a prostate cancer, polymorphic glioblastoma, an ovarian cancer, a pancreatic cancer, a breast cancer, melanoma, a liver cancer, a bladder cancer, a gastric cancer, a cervical cancer, a uterine cancer, a head and neck cancer, an esophageal cancer, a biliary tract cancer, a thyroid cancer, lymphoma, acute myeloid leukemia, acute lymphoid leukemia, and/or multiple myeloma.