# US 11,993,816 B2 · Circulating microRNA as biomarkers for endometriosis > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,993,816 B2 - Document ID: US11993816B2 - Status: Granted - Kind: B2 - Application number: 15/129,663 - Filed: 2015-03-27 - Published: 2017-06-22 - Granted: 2024-05-28 - Earliest claimed: 2014-03-27 - Assignees: Yale University - Applicants: Yale University - Inventors: Hugh Taylor; SiHyun Cho - Web page: https://patentgrep.com/patent/US11993816B2 ## CPC - C12Q 1/6883: for diseases caused by alterations of genetic material - C12Q 2600/118: Prognosis of disease development - C12Q 2600/156: Polymorphic or mutational markers - C12Q 2600/158: Expression markers - C12Q 2600/178: miRNA, siRNA or ncRNA - 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 The invention includes compositions and methods useful for the diagnosis, assessment, and characterization of endometriosis in a subject in need thereof, based upon the expression level of at least one miRNA that is associated with endometriosis. ## Claims ### Claim 1 A noninvasive method of detecting miRNA in a subject, the method comprising: (a) providing a biological sample comprising saliva from the subject, wherein the subject has endometriosis or is suspected of having endometriosis, and wherein the biological sample comprises at least one miRNA that is a biomarker for endometriosis, wherein at least one miRNA that is a biomarker for endometriosis comprises let-7b miRNA; and (b) performing an in vitro amplification procedure on the at least one miRNA that is a biomarker for endometriosis; and (c) detecting a level of the at least one miRNA that is a biomarker for endometriosis in the biological sample comprising saliva from the subject; and (d) treating the subject for endometriosis based on the detected level of the at least one miRNA that is a biomarker for endometriosis in the biological sample comprising saliva from the subject, wherein the treating the subject comprises administering a hormonal treatment, an oral contraceptive, a progestin, a GnRH agonist, an androgen, an aromatase inhibitor, a non-steroidal anti-inflammatory drug, or a combination thereof, wherein the detected level of the let-7b miRNA is downregulated, and wherein the downregulation is statistically significant. ### Claim 2 (depends on 1) The method of claim 1, wherein the method further comprises detecting at least one miRNA selected from the group consisting of let-7a, let-7c, let-7d, let-7e, let-7f, mir135a, and mir135b. ### Claim 3 (depends on 1) The method of claim 1, wherein the method further comprises detecting at least one miRNA selected from the group consisting of let-7d and let-7f. ### Claim 4 (depends on 1) The method of claim 1, wherein the subject is human. ### Claim 5 (depends on 1) The method of claim 1, wherein the in vitro amplification procedure comprises at least one technique selected from the group consisting of reverse transcription, PCR, sequencing and a microarray. ### Claim 6 (depends on 1) The method of claim 1 wherein the treating the subject comprises administering an oral contraceptive to the subject. ### Claim 7 (depends on 1) The method of claim 1, wherein the treating the subject comprises administering a progestin to the subject. ### Claim 8 (depends on 1) The method of claim 1, wherein the treating the subject comprises administering to the subject a GnRH agonist, an androgen, an aromatase inhibitor, a non-steroidal anti-inflammatory drug, or combination thereof. ### Claim 9 (depends on 1) The method of claim 1, wherein the detected level of the at least one miRNA that is a biomarker for endometriosis is a statistically significant indication of endometriosis. ### Claim 10 (depends on 1) The method of claim 1, wherein the biological sample is acellular. ### Claim 11 (depends on 1) The method of claim 1, wherein the method is at least 90% sensitive for detecting endometriosis. ### Claim 12 (depends on 1) The method of claim 1, wherein the method is at least 90% specific for detecting endometriosis. ### Claim 13 (depends on 1) The method of claim 1, wherein the method is at least 90% accurate for detecting endometriosis. ### Claim 14 (depends on 1) The method of claim 1, wherein a source of the at least one miRNA is an exosome. ### Claim 15 (depends on 1) The method of claim 1, wherein the at least one miRNA is detected at multiple time points. ### Claim 16 (depends on 1) The method of claim 1, further comprising diagnosing or providing a prognosis for endometriosis in a subject, based on the detected level of the at least one miRNA that is a biomarker for endometriosis. ### Claim 17 (depends on 16) The method of claim 16, wherein the diagnosing comprises diagnosing endometriosis during a proliferative phase of endometriosis in the subject. ### Claim 18 (depends on 1) The method of claim 1, wherein treating the subject comprises administering a hormonal treatment to the subject. ### Claim 19 (depends on 1) The method of claim 1, wherein the method is at least 80% sensitive for detecting endometriosis. ### Claim 20 (depends on 1) The method of claim 1, wherein the method is at least 80% specific for detecting endometriosis. ### Claim 21 (depends on 1) The method of claim 1, wherein the sample is a saliva sample and further comprising extracting RNA comprising the at least one miRNA that is a biomarker for endometriosis from the saliva sample prior to (b). ### Claim 22 (depends on 1) The method of claim 1, wherein the treating the subject for endometriosis based on the detected level of the at least one miRNA that is a biomarker for endometriosis in the saliva sample comprises administering a progestin to the subject. ### Claim 23 (depends on 1) The method of claim 1, wherein the treating the subject for endometriosis based on the detected level of the at least one miRNA that is a biomarker for endometriosis in the saliva sample comprises administering a GnRH agonist to the subject. ### Claim 24 (depends on 1) The method of claim 1, wherein the in vitro amplification procedure comprises a sequencing assay. ### Claim 25 (depends on 24) The method of claim 24, wherein the sequencing assay is a next generation sequencing assay. ### Claim 26 A noninvasive method of detecting endometriosis in a subject, the method comprising detecting in a biological sample obtained from a body fluid altered expression of at least one miRNA selected from the group consisting of let-7a, let-7b, and let-7d, in a subject suspected of or having endometriosis; and treating the subject for endometriosis based on the detected level of the at least one miRNA in the subject, wherein the treating the subject comprises administering a hormonal treatment, an oral contraceptive, a progestin, a GnRH agonist, an androgen, an aromatase inhibitor, a non-steroidal anti-inflammatory drug, or a combination thereof, wherein the detected level of let-7a, let-7b, or let-7d is downregulated, and wherein the downregulation is statistically significant. ### Claim 27 (depends on 26) The method of claim 26, wherein the at least one gene comprises let-7b. ### Claim 28 (depends on 26) The method of claim 26, wherein the biological sample is at least one biological sample selected from the group consisting of blood, serum, plasma, saliva, and urine. ### Claim 29 (depends on 26) The method of claim 26, wherein treating the subject comprises administering a hormonal treatment to the subject. ### Claim 30 (depends on 26) The method of claim 26, wherein the at least one miRNA comprises let-7b. ### Claim 31 (depends on 26) The method of claim 26, wherein the biological sample is selected from the group consisting of blood, serum, and plasma. ### Claim 32 (depends on 26) The method of claim 26, wherein the biological sample is serum. ### Claim 33 (depends on 26) The method of claim 26, wherein the biological sample is plasma. ### Claim 34 (depends on 26) The method of claim 26, wherein the method is at least 80% sensitive for detecting endometriosis. ### Claim 35 (depends on 26) The method of claim 26, wherein the method is at least 80% specific for detecting endometriosis. ### Claim 36 (depends on 32) The method of claim 32, wherein the at least one miRNA comprises let-7a or let-7b. ### Claim 37 (depends on 33) The method of claim 33, wherein the at least one miRNA comprises let-7a or let-7b. ### Claim 38 (depends on 36) The method of claim 36, further comprising extracting RNA comprising the at least one miRNA from the serum sample. ### Claim 39 (depends on 37) The method of claim 37, further comprising extracting RNA comprising the at least one miRNA from the plasma sample. ### Claim 40 (depends on 32) The method of claim 32, wherein the at least one miRNA comprises let-7b. ### Claim 41 (depends on 33) The method of claim 33, wherein the at least one miRNA comprises let-7b. ### Claim 42 (depends on 40) The method of claim 40, wherein the detected level of the let-7b is downregulated. ### Claim 43 (depends on 41) The method of claim 41, wherein the detected level of the let-7b is downregulated. ### Claim 44 (depends on 38) The method of claim 38, wherein the treating the subject for endometriosis based on the detected level of the at least one miRNA that is a biomarker for endometriosis in the saliva sample comprises administering a progestin to the subject. ### Claim 45 (depends on 39) The method of claim 39, wherein the treating the subject for endometriosis based on the detected level of the at least one miRNA that is a biomarker for endometriosis in the saliva sample comprises administering a progestin to the subject. ### Claim 46 (depends on 38) The method of claim 38, wherein the treating the subject for endometriosis based on the detected level of the at least one miRNA that is a biomarker for endometriosis in the saliva sample comprises administering a GnRH agonist to the subject. ### Claim 47 (depends on 39) The method of claim 39, wherein the treating the subject for endometriosis based on the detected level of the at least one miRNA that is a biomarker for endometriosis in the saliva sample comprises administering a GnRH agonist to the subject. ### Claim 48 (depends on 38) The method of claim 38, wherein the detecting comprises a sequencing assay. ### Claim 49 (depends on 48) The method of claim 48, wherein the sequencing assay is a next generation sequencing assay. ### Claim 50 (depends on 39) The method of claim 39, wherein the detecting comprises a sequencing assay. ### Claim 51 (depends on 50) The method of claim 50, wherein the sequencing assay is a next generation sequencing assay.