# US 12,216,123 B2 · Extracellular vesicle derived MASP-2 directed cancer treatment methods > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,216,123 B2 - Document ID: US12216123B2 - Status: Granted - Kind: B2 - Application number: 18/650,778 - Filed: 2024-04-30 - Published: 2024-10-31 - Granted: 2025-02-04 - Earliest claimed: 2023-04-25 - Assignees: Nuvance Health - Applicants: Nuvance Health - Inventors: Richard C. Frank; Shatovisha Dey; Deep Siddhartha Pandya - Web page: https://patentgrep.com/patent/US12216123B2 ## CPC - G01N 33/57525: of the liver or pancreas - G01N 33/5076: {involving cell organelles, e.g. Golgi complex, endoplasmic reticulum} - G01N 2333/96433: Serine endopeptidases (3.4.21) - 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) ## Abstract The present disclosure provides for cancer treatment methods related to the unexpected discovery of the role of mannan-binding protein-associated serine protease-2 (MASP-2) in cancer. Improved cancer treatment methods are disclosed that are determined by measuring changes in levels of MASP-2, a previously unknown biomarker for cancer. It has been discovered that changes in MASP-2 levels are useful as indications of cancer progression, chemotherapeutic responsiveness, and cancer remission, such as in pancreatic cancers. More particularly, changes of levels in MASP-2 in extracellular vesicles (EVs), i.e. EV-MASP2, from patient blood samples are useful for providing effective and targeted cancer treatment regimens, such as in pancreatic cancers. The present disclosure further includes compositions and methods related to inhibiting MASP-2 for the treatment of cancers. ## Claims ### Claim 1 A method for determining whether to continue or discontinue a first-line cancer therapy in a pancreatic cancer patient in need thereof, the method comprising the steps of: (a) obtaining a blood sample from the patient prior to or at commencement of a first-line cancer therapy; (b) isolating extracellular vesicles from the blood sample and determining, from the isolated extracellular vesicles, a baseline extracellular vesicle-derived mannan-binding protein-associated serine protease-2 (EV-MASP-2) level for the patient, (c) administering the first-line cancer therapy to the patient according to a treatment regimen over a treatment time period, (d) obtaining a blood sample from the patient during the treatment time period; (e) isolating extracellular vesicles from the blood sample obtained during the treatment time period and determining, from the isolated extracellular vesicles, a treatment EV-MASP-2 level; (f) determining whether the treatment EV-MASP-2 level has decreased relative to the baseline EV-MASP-2 level; and (g-i) continuing administering the first-line cancer therapy according to the treatment regimen if the treatment EV-MASP-2 level has decreased relative to the baseline EV-MASP-2 level, or (g-ii) discontinuing administering the first-line cancer therapy according to the treatment regimen if the treatment EV-MASP-2 level has not decreased relative to the baseline EV-MASP-2 level. ### Claim 2 (depends on 1) The method of claim 1, wherein discontinuing administering the first-line cancer therapy according to the treatment regimen comprises: (g-ii-a) commencing administering the first-line cancer therapy according to a different treatment regimen; or (g-ii-b) discontinuing administering the first-line cancer therapy and administering no further cancer therapy; and/or (g-ii-c) commencing administering of second-line cancer therapy according to a treatment regimen. ### Claim 3 (depends on 1) The method of claim 1, wherein the pancreatic cancer is advanced pancreatic cancer. ### Claim 4 (depends on 3) The method of claim 3, wherein the advanced pancreatic cancer is stage III or stage IV pancreatic cancer. ### Claim 5 (depends on 1) The method of claim 1, wherein the first-line cancer therapy is one or more of chemotherapy, biological therapy, immunotherapy, and hormonal therapy. ### Claim 6 (depends on 1) The method of claim 1, wherein the first-line cancer therapy is 5-fluorouracil, FOLFIRINOX, or gemcitabine alone or in combination with nab-paclitaxel, capecitabine, cisplatin, and/or oxaliplatin. ### Claim 7 (depends on 1) The method of claim 1, wherein the blood sample of step (d) is collected during the treatment time period at a time point from about 2 weeks to about 4 months after commencement of the first-line cancer therapy to determine the treatment EV-MASP-2 level. ### Claim 8 (depends on 7) The method of claim 7, wherein the time point is about 2 months after commencement of the first-line cancer therapy. ### Claim 9 (depends on 1) The method of claim 1, wherein the first-line cancer therapy is administered at a first dosage and then, if the EV-MASP-2 level has not decreased relative to the baseline EV-MASP-2 level, the first-line cancer treatment is administered at a higher, second dosage. ### Claim 10 (depends on 1) The method of claim 1, comprising: continuing administering the first-line cancer therapy according to the treatment regimen in step (g-i), or commencing administering a second-line cancer therapy according to a treatment regimen in step (g-ii). ### Claim 11 A method for determining whether to continue or discontinue a first-line cancer therapy in a pancreatic cancer patient in need thereof, the method comprising the steps of: (a) obtaining a blood sample from the patient prior to or at commencement of a first-line cancer therapy; (b) isolating extracellular vesicles from the blood sample and determining, from the isolated extracellular vesicles, a baseline extracellular vesicle-derived mannan-binding protein-associated serine protease-2 (EV-MASP-2) level for the patient, (c) administering the first-line cancer therapy to the patient according to a treatment regimen over a treatment time period, (d) obtaining a blood sample from the patient during the treatment time period; (e) isolating extracellular vesicles from the blood sample obtained during the treatment time period and determining, from the isolated extracellular vesicles, a treatment EV-MASP-2 level; (f) comparing the treatment EV-MASP-2 level to the baseline EV-MASP-2 level; and (g-i) continuing administering the first-line cancer therapy according to the treatment regimen if the treatment EV-MASP-2 level has decreased from the baseline EV-MASP-2 level by 10% or greater; or (g-ii) discontinuing administering the first-line cancer therapy according to the treatment regimen if the treatment EV-MASP-2 level has not decreased from the baseline EV-MASP-2 level, or if the treatment EV-MASP-2 level has decreased from the baseline EV-MASP-2 level by less than 10%. ### Claim 12 (depends on 11) The method of claim 11, wherein discontinuing administering the first-line cancer therapy according to the treatment regimen comprises: (g-ii-a) commencing administering the first-line cancer therapy according to a different treatment regimen; or (g-ii-b) discontinuing administering the first-line cancer therapy and administering no further cancer therapy; and/or (g-ii-c) commencing administering of second-line cancer therapy according to a treatment regimen. ### Claim 13 (depends on 11) The method of claim 11, wherein the pancreatic cancer is advanced pancreatic cancer. ### Claim 14 (depends on 13) The method of claim 13, wherein the advanced pancreatic cancer is stage III or stage IV pancreatic cancer. ### Claim 15 (depends on 11) The method of claim 11, wherein the first-line cancer therapy is one or more of chemotherapy, biological therapy, immunotherapy, and hormonal therapy. ### Claim 16 (depends on 11) The method of claim 11, wherein the first-line cancer therapy is 5-fluorouracil, FOLFIRINOX, or gemcitabine alone or in combination with nab-paclitaxel, capecitabine, cisplatin, and/or oxaliplatin. ### Claim 17 (depends on 11) The method of claim 11, wherein the blood sample of step (d) is collected during the treatment time period at a time point from about 2 weeks to about 4 months after commencement of the first-line cancer therapy to determine the treatment EV-MASP-2 level. ### Claim 18 (depends on 17) The method of claim 17, wherein the time point is about 2 months after commencement of the first-line cancer therapy. ### Claim 19 (depends on 11) The method of claim 11, wherein the first-line cancer therapy is administered at a first dosage and then, if the treatment EV-MASP-2 level has not decreased from the baseline EV-MASP-2 level, or if the treatment EV-MASP-2 level has decreased from the baseline EV-MASP-2 level by less than 10%, the first-line cancer treatment is administered at a higher, second dosage. ### Claim 20 (depends on 11) The method of claim 11, comprising: continuing administering the first-line cancer therapy according to the treatment regimen in step (g-i), or commencing administering a second-line cancer therapy according to a treatment regimen in step (g-ii).