# US 8,784,806 B2 · Screening method > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,784,806 B2 - Document ID: US8784806B2 - Status: Granted - Kind: B2 - Application number: 12/294,603 - Filed: 2007-03-27 - Published: 2009-12-17 - Granted: 2014-07-22 - Earliest claimed: 2006-03-27 - Assignees: Isis Innovation Limited - Applicants: Nicholas B. La Thangue; Susan Fotheringham - Inventors: Nicholas B. La Thangue; Susan Fotheringham - Web page: https://patentgrep.com/patent/US8784806B2 ## CPC - G01N 33/57595: {involving intracellular compounds} - A61P 35/00: Antineoplastic agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C12N 15/111: {General methods applicable to biologically active non-coding nucleic acids} - C12N 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)} - C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575) - C12Y 305/01098: Histone deacetylase (3.5.1.98), i.e. sirtuin deacetylase - G01N 33/5011: {for testing antineoplastic activity} - G01N 33/575: for cancer - 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} - C12N 2310/14: interfering nucleic acids [NA] - C12N 2320/10: in screening processes - C12N 2330/31: Libraries, arrays - C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism - C12Q 2600/156: Polymorphic or mutational markers - C12Q 2600/158: Expression markers - G01N 2333/4706: stimulating, promoting or activating activity - G01N 2333/91045: Acyltransferases (2.3) - G01N 2333/98: acting on amide bonds in linear amides (3.5.1) - G01N 2500/10: involving cells - G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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 - C12Y: ENZYMES ## Abstract This invention relates to a novel screening method that identifies simple molecular markers that are predictive of whether a particular disease condition is responsive to a specific treatment. Also, a method of diagnosing the susceptibility of an individual suffering from a disease to treatment with an HDAC inhibitor is provided. Also provided is a method of treating a proliferative disease or a condition which involves a change in cell differentiation or growth rate in a patient. ## Claims ### Claim 1 A method for identifying a candidate biomarker that correlates with sensitivity of a disease to a drug that kills tumour cells, the method comprising; a) exposing a tumour cell to: i) the drug at a concentration capable of killing all the tumour cells; ii) a compound which inhibits the level or activity of a protein in the cell; b) monitoring for survival of the cell or cells; wherein if the cell survives despite the presence of the drug, the protein or its encoding gene is identified as a candidate biomarker that correlates with drug sensitivity. ### Claim 2 (depends on 1) A method according to claim 1, wherein the compound is a nucleic acid. ### Claim 3 (depends on 1) A method according to claim 1, wherein the compound is siRNA. ### Claim 4 (depends on 1) A method according to claim 1, wherein the compound reduces the expression level of the protein. ### Claim 5 (depends on 4) A method according to claim 4, wherein the compound knocks out the expression of the protein. ### Claim 6 (depends on 1) A method according to claim 1, wherein the exposing step involves incubating the cell in the presence of the drug. ### Claim 7 (depends on 1) A method according to claim 1, wherein a population of cells exposed to the drug. ### Claim 8 (depends on 7) A method according to claim 7, wherein the population of cells are exposed to a library of compounds. ### Claim 9 (depends on 8) A method according to claim 8, wherein the library of compounds is an siRNA library. ### Claim 10 (depends on 9) A method according to claim 9, wherein the library of compounds is a vectored RNA interference library. ### Claim 11 (depends on 10) A method according to claim 10, wherein the library is a viral vectored RNA interference library. ### Claim 12 (depends on 1) A method according to claim 1, wherein the cell or cells are isolated from a patient. ### Claim 13 (depends on 1) A method according to claim 1, wherein the drug is an HDAC inhibitor. ### Claim 14 (depends on 1) A method according to claim 1, wherein the cell or cells are exposed to a combination of drugs. ### Claim 15 (depends on 1) A method according to claim 1, wherein the phenotype is the survival or growth characteristics of the cell or cells. ### Claim 16 (depends on 1) A method according to claim 1, wherein the drug is selected from the group consisting of aurora kinase inhibitors, cdk inhibitors, mTOR inhibitors and natural products such as quercetin and analogues thereof. ### Claim 17 (depends on 1) A method according to claim 1, wherein the appearance of colonies on plates co-treated with drug and the compound indicates cell survival. ### Claim 18 (depends on 1) A method according to claim 1, wherein the compound is shRNA. ### Claim 19 (depends on 1) A method according to claim 1, wherein the method further comprises isolating the cells that have survived, determining the identity of the inhibited gene and, thereafter, validating the role of the gene in functional assays to determine if they are biomarkers. ### Claim 20 A method for identifying a candidate biomarker that correlates with the sensitivity of a disease to a drug, the method comprising: a) exposing a cell to: i) the drug; ii) a compound which inhibits the level or activity of a protein in the cell; b) monitoring for survival of the cell or cells; wherein the outcome of treatment with the drug alone is apoptosis of all cells, and wherein if the cell survives despite the presence of the drug, the protein or its encoding gene is identified as a candidate biomarker that correlates with drug sensitivity. ### Claim 21 (depends on 20) A method according to claim 20, wherein the appearance of colonies on plates co-treated with drug and the compound indicates cell survival. ### Claim 22 (depends on 20) A method according to claim 20, wherein the method further comprises isolating the cells that have survived, determining the identity of the inhibited gene and, thereafter, validating the role of the gene in functional assays.