# US 5,705,336 A · Assay for sensitivity of tumors to DNA-platinating chemotherapy > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,705,336 A - Document ID: US5705336A - Status: Granted - Kind: A - Application number: 08/399,617 - Filed: 1995-03-07 - Granted: 1998-01-06 - Earliest claimed: 1995-03-07 - Assignees: The United States of America as represented by the Department of Health and Human Services - Inventors: Eddie Reed; Meenakshi Dabholkar - Web page: https://patentgrep.com/patent/US5705336A ## CPC - C07K 14/47: from mammals - C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575) - C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism - 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) - 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 Assay of the mRNA levels of ERCC1 and XPAC, two genes whose products are involved in DNA repair, provides a method for determining the sensitivity of tumors to treatment by platinum-based chemotherapy. Tumors that are resistant to cisplatin tend to express high levels of the mRNA for ERCC1 which includes exon VIII. In some tumor types, concurrent expression of ERCC1 and XPAC mRNAs is also an indicator of cisplatin resistance. ## Claims ### Claim 1 A method for assaying sensitivity of ovarian tumor tissue to treatment with DNA platinating agents, comprising: i) measuring the amount of mRNA from said ovarian tumor tissue that encodes XPAC; ii) measuring the amount of mRNA from said ovarian tumor tissue that encodes ERCC1; iii) determining the ratio of XPAC mRNA measured in step (i) to the amount of ERCC1 mRNA measured in step (ii); iv) comparing the ratio of XPAC mRNA to ERCC1 mRNA measured in step (iii) with the ratio found in cells that are resistant to DNA platinating agents; and v) comparing the ratio of XPAC mRNA to ERCC1 mRNA measured in step (iii) with the ratio found in cells that are sensitive to DNA platinating agents; wherein observing that the ratio of the amount of XPAC mRNA to the amount of ERCC1 mRNA is similar to that ratio in cells sensitive to DNA platinating agents and observing that said ratio of the amount of XPAC mRNA to the amount of ERCC1 mRNA is dissimilar to that ratio in cells resistant to DNA platinating agents results in an assessment that said ovarian tumor tissue is sensitive to treatment with DNA platinating agents. ### Claim 2 (depends on 1) The method of claim 1, wherein an assessment that said ovarian tumor tissue is sensitive to treatment with DNA platinating agents is obtained when the ratio of the amount of XPAC mRNA to the amount of ERCC1 mRNA is 0.17 or lower. ### Claim 3 A method for assaying the sensitivity of ovarian tumor tissue to treatment with DNA platinating agents, comprising: i) measuring the amount of mRNA that encodes ERCC1 including exon VIII in said ovarian tumor tissue; ii) comparing the amount of mRNA that encodes ERCC1 including exon VIII in said ovarian tumor tissue to the amount of said mRNA found in cells that are sensitive to DNA platinating agents; and iii) comparing the amount of mRNA that encodes ERCC1 including exon VIII to the amount of said mRNA found in cells that are resistant to DNA platinating agents; wherein observing that the amount of said mRNA in said ovarian tumor tissue is similar to the amount of said mRNA in cells sensitive to DNA platinating agents and observing that the amount of said mRNA is dissimilar to the amount in cells resistant to DNA platinating agents results in an assessment that said ovarian tumor tissue is sensitive to treatment with DNA platinating agents. ### Claim 4 (depends on 1) The method of claim 1, wherein the amount of said ERCC1 mRNA is measured using a polymerase chain reaction technique and a primer that hybridizes to a nucleotide sequence in ERCC1 exon VIII. ### Claim 5 (depends on 1) The method of claim 1, wherein the amount of said ERCC1 mRNA is measured by a polymerase chain reaction technique and a set of primers that flank the ERCC1 exon VIII, and further wherein the amount of ERCC1 mRNA equals the sum of the amounts of ERCC1 exon VIII.sup.+ and ERCC1 exon VIII.sup.- mRNA. ### Claim 6 (depends on 1) The method of claim 1, wherein said ERCC1 mRNA is measured by a polymerase chain reaction technique and a set of primers that flank the ERCC1 exon VIII, and further wherein the amount of ERCC1 mRNA equals the amount of ERCC1 exon VIII.sup.+ mRNA. ### Claim 7 (depends on 1) The method of claim 1, wherein said ERCC1 mRNA is measured by a polymerase chain reaction technique and a set of primers that flank the ERCC1 exon VIII, and further wherein the amount of ERCC1 mRNA equals the amount of ERCC1 exon VIII.sup.- mRNA. ### Claim 8 (depends on 4) The method of claim 4, wherein said primers have the sequence of SEQ. ID. NOS. 1 and 2. ### Claim 9 (depends on 5) The method of claim 5, wherein said primers have the sequence of SEQ. ID. NOS. 1 and 3. ### Claim 10 (depends on 6) The method of claim 6, wherein said primers have the sequence of SEQ. ID. NOS. 1 and 3. ### Claim 11 A method for assaying the sensitivity of a T cell to treatment with DNA platinating agents, comprising: i) measuring the amount of mRNA that encodes ERCC1 lacking exon VIII in said T cell; ii) comparing the amount of mRNA that encodes ERCC1 lacking exon VIII in said T cell to the amount of said mRNA found in cells that are sensitive to DNA platinating agents; and iii) comparing the amount of mRNA that encodes ERCC1 lacking exon VIII in said T cell to the amount of said mRNA found in cells that are resistant to DNA platinating agents; wherein observing that the amount of said mRNA in said T cell is similar to the amount of said mRNA in cells sensitive to DNA platinating agents and observing that the amount of said mRNA in said T cell is dissimilar to the amount in cells resistant to DNA platinating agents results in an assessment that said T cell is sensitive to treatment with DNA platinating agents. ### Claim 12 (depends on 11) The method of claim 11, wherein the amount of said ERCC1 mRNA lacking exon VIII is measured by a polymerase chain reaction technique and a set of primers that flank the ERCC1 exon VIII. ### Claim 13 (depends on 12) The method of claim 12, wherein said primers have the sequence of SEQ. ID. NOS. 1 and 3.