# US 2021/0333286 A1 · Activity sensor controls > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2021/0333286 A1 - Document ID: US20210333286A1 - Status: Published application - Kind: A1 - Application number: 17/238,599 - Filed: 2021-04-23 - Published: 2021-10-28 - Earliest claimed: 2020-04-24 - Assignees: Glympse Bio, Inc. - Applicants: Glympse Bio, Inc. - Inventors: James Bowen; Faycal Touti - Web page: https://patentgrep.com/patent/US20210333286A1 ## CPC - G01N 33/57595: {involving intracellular compounds} - G01N 33/6803: {General methods of protein analysis not limited to specific proteins or families of proteins} - C12Q 1/37: involving peptidase or proteinase - G01N 33/5759: {involving compounds localised on the membrane of tumour or cancer cells} - G01N 2333/96433: Serine endopeptidases (3.4.21) - G01N 2333/96466: Cysteine endopeptidases (3.4.22) - G01N 2333/96494: Matrix metalloproteases, e. g. 3.4.24.7 - 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) - 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 An activity sensor sensitive to enzymes indicative of tissue condition are co-administered with control or normalizing activity sensors providing levels of the same enzyme in other tissues or levels of control enzymes indicative of assay success. Levels of control reporters can be used to normalize activity sensor data across samples such as in analyte velocity analyses. Control reporters can also be used to differentiate localized enzyme activity from systemic activity and to confirm activity sensor localization or to troubleshoot activity sensor uptake problems. Activity sensors and controls sensitive to immunological enzymes are particularly useful in assessing immuno-oncology treatments. ## Claims ### Claim 1 A method of monitoring cancer progression comprising: administering to a patient suspected of having cancer an activity sensor comprising a carrier linked to a reporter molecule by a cleavable linker that is cleaved in the presence of a characteristic of a tumor; administering to the patient a control activity sensor comprising a carrier linked to a control reporter molecule by a control cleavable linker that is cleaved by a control molecule; collecting a sample from the patient; analyzing the sample to detect the presence or lack of the reporter and the control reporter, wherein presence of the reporter is indicative of the characteristic. ### Claim 2 (depends on 1) The method of claim 1, wherein absence of the control reporter in the sample is indicative of a failed assay. ### Claim 3 (depends on 1) The method of claim 1, wherein said characteristic is an enzyme present in a tumor. ### Claim 4 (depends on 1) The method of claim 1, wherein said control molecule is an enzyme. ### Claim 5 (depends on 1) The method of claim 1, wherein the analyzing step further comprises quantifying a level of the reporter and a level of the control reporter in the sample, the method further comprising: dividing the level of the reporter by the level of the control reporter to determine a normalized reporter level. ### Claim 6 (depends on 5) The method of claim 5, further comprising: periodically repeating the administering, collecting, and analyzing steps to prepare a chronological series of normalized reporter levels, and determining a velocity of the characteristic of the tumor environment ### Claim 7 (depends on 3) The method of claim 3, wherein the enzyme is an immunological enzyme. ### Claim 8 (depends on 7) The method of claim 7, wherein the patient is undergoing immuno-oncological treatment and the presence of the reporter is indicative of therapeutic effect of the immuno-oncological treatment. ### Claim 9 (depends on 8) The method of claim 8, wherein the activity sensor further comprises a tuning domain operable to localize the activity sensor in a target tumor. ### Claim 10 (depends on 7) The method of claim 7, wherein the patient has not undergone immuno-oncological treatment and the presence of the reporter is indicative of a predicted therapeutic response to a checkpoint inhibitor therapy. ### Claim 11 (depends on 1) The method of claim 1, further comprising stratifying the patient in a clinical trial based on the detection of the reporter in the sample. ### Claim 12 (depends on 7) The method of claim 7, wherein the immunological enzyme is selected from the group consisting of a caspase and a serine protease. ### Claim 13 (depends on 1) The method of claim 1, wherein the activity sensor comprises a tuning domain operable to localize the activity sensor in a target tumor. ### Claim 14 (depends on 13) The method of claim 13, wherein the control activity sensor comprises the tuning domain and the control enzyme is not an immunological enzyme but is differentially expressed in the target tumor, and wherein presence of the control reporter is indicative of target localization. ### Claim 15 (depends on 14) The method of claim 14, wherein the reporter molecule and the control reporter molecule are both linked to the same carrier. ### Claim 16 (depends on 13) The method of claim 13, wherein the control activity sensor does not comprise the targeting domain and the control enzyme is the immunological enzyme, wherein presence of the control reporter is indicative of target localization, and wherein the analyzing step further comprises quantifying a level of the reporter and a level of the control reporter in the sample, the method further comprising: comparing the level of the reporter to the level of the control reporter to identify a tumor-specific immune response.