# US 10,767,232 B2 · Methods and biomarkers for predicting efficacy and evaluation of an OX40 agonist treatment > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,767,232 B2 - Document ID: US10767232B2 - Status: Granted - Kind: B2 - Application number: 15/836,729 - Filed: 2017-12-08 - Published: 2018-07-12 - Granted: 2020-09-08 - Earliest claimed: 2014-11-03 - Assignees: Genentech, Inc. - Applicants: Genentech, Inc. - Inventors: Mahrukh Huseni - Web page: https://patentgrep.com/patent/US10767232B2 ## CPC - C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575) - A61P 35/00: Antineoplastic agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95} - 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} - H04M 3/51: Centralised call answering arrangements requiring operator intervention {, e.g. call or contact centers for telemarketing} - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/75: Agonist effect on antigen - C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism - C12Q 2600/158: Expression markers - G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis - H04M 3/5238: {with waiting time or load prediction arrangements} - H04M 2203/402: Agent or workforce management - 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) - 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) - H04M: TELEPHONIC COMMUNICATION (circuits for controlling other apparatus via a telephone cable and not involving telephone switching apparatus G08) ## Abstract The present disclosure provides methods for predicting responsiveness of a subject having cancer to an OX40 agonist treatment by measuring the expression level of one or more biomarkers. Also provided are methods for monitoring pharmacodynamic activity of or responsiveness to an OX40 agonist treatment by measuring the expression level of one or more biomarkers. Further provided are methods related thereto for treating or delaying progression of cancer in a subject by administering an effective amount of an OX40 agonist to a subject. Specific biomarkers for all such methods are described herein. ## Claims ### Claim 1 A method for treating or delaying progression of cancer in a subject, comprising: (a) measuring the expression level of one or more marker genes in a sample comprising leukocytes obtained from the subject, wherein said one or more marker genes are selected from the group consisting of CD8a, CD8b, H2-d, CTLA4, CD64, CXCL9, IFNg, IDO1, GZMA, GZMB, PRF1, PDCA1, KLRK1, PTPRC, CXCL1, ITGAM, and IL7R; and (b) if the expression level of said one or more marker genes in the sample obtained from the subject is higher than a reference, administering to the subject an effective amount of an OX40 agonist; wherein the OX40 agonist is a monoclonal antibody that comprises: (1) HVR-H1 comprising the amino acid sequence of SEQ ID NO:2; (2) HVR-H2 comprising the amino acid sequence of SEQ ID NO:3; (3) HVR-H3 comprising the amino acid sequence of SEQ ID NO:4; (4) HVR-L1 comprising the amino acid sequence of SEQ ID NO:5; (5) HVR-L2 comprising the amino acid sequence of SEQ ID NO:6; and (6) HVR-L3 comprising the amino acid sequence of SEQ ID NO:7; or (1) HVR-H1 comprising the amino acid sequence of SEQ ID NO:29; (2) HVR-H2 comprising the amino acid sequence of SEQ ID NO:30; (3) HVR-H3 comprising the amino acid sequence of SEQ ID NO:33; (4) HVR-L1 comprising the amino acid sequence of SEQ ID NO:37; (5) HVR-L2 comprising the amino acid sequence of SEQ ID NO:39; and (6) HVR-L3 comprising the amino acid sequence of SEQ ID NO:42. ### Claim 2 A method for treating or delaying progression of cancer in a subject, comprising administering to the subject an effective amount of an OX40 agonist, wherein a sample comprising leukocytes obtained from the subject has increased expression of one or more marker genes selected from the group consisting of CD8a, CD8b, H2-d, CTLA4, CD64, CXCL9, IFNg, IDOL GZMA, GZMB, PRF1, PDCA1, KLRK1, PTPRC, CXCL1, ITGAM, and IL7R, as compared with a reference; and wherein the OX40 agonist is a monoclonal antibody that comprises: (1) HVR-H1 comprising the amino acid sequence of SEQ ID NO:2; (2) HVR-H2 comprising the amino acid sequence of SEQ ID NO:3; (3) HVR-H3 comprising the amino acid sequence of SEQ ID NO:4; (4) HVR-L1 comprising the amino acid sequence of SEQ ID NO:5; (5) HVR-L2 comprising the amino acid sequence of SEQ ID NO:6; and (6) HVR-L3 comprising the amino acid sequence of SEQ ID NO:7; or (1) HVR-H1 comprising the amino acid sequence of SEQ ID NO:29; (2) HVR-H2 comprising the amino acid sequence of SEQ ID NO:30; (3) HVR-H3 comprising the amino acid sequence of SEQ ID NO:33; (4) HVR-L1 comprising the amino acid sequence of SEQ ID NO:37; (5) HVR-L2 comprising the amino acid sequence of SEQ ID NO:39; and (6) HVR-L3 comprising the amino acid sequence of SEQ ID NO:42. ### Claim 3 (depends on 2) The method of claim 2, wherein said one or more marker genes are selected from the group consisting of CD8a, CD8b, IFNg, GZMA, GZMB, PRF1, and PDCA1. ### Claim 4 (depends on 2) The method claim 2, wherein said one or more marker genes are selected from the group consisting of H2-d, CTLA4, CXCL9, PTPRC, IL7R, KLRK1, and CXCL1. ### Claim 5 (depends on 2) The method of claim 2, wherein said one or more marker genes are selected from the group consisting of CD64, IDO1, and ITGAM. ### Claim 6 (depends on 2) The method of claim 2, wherein the leukocytes are in a tumor sample or a peripheral blood sample obtained from the subject. ### Claim 7 (depends on 2) The method of claim 2, wherein the expression level of said one or more marker genes is normalized to the expression level of a reference gene in the sample, and wherein the reference gene is a housekeeping gene. ### Claim 8 (depends on 2) The method of claim 2, wherein the expression level of said one or more marker genes is mRNA expression level. ### Claim 9 (depends on 2) The method of claim 2, wherein the expression level of said one or more marker genes is protein expression level. ### Claim 10 (depends on 2) The method of claim 2, wherein the cancer is selected from the group consisting of colorectal cancer, non-small cell lung cancer, renal cell carcinoma, bladder cancer, ovarian cancer, glioblastoma, neuroblastoma, melanoma, breast carcinoma, gastric cancer, and hepatocellular carcinoma. ### Claim 11 (depends on 10) The method of claim 10, wherein the breast carcinoma is triple-negative breast carcinoma. ### Claim 12 (depends on 2) The method of claim 2, wherein the antibody is a humanized antibody. ### Claim 13 (depends on 2) The method of claim 2, wherein the antibody comprises an IgG1 Fc region.