# US 11,026,948 B2 · Platinum-resistant cancer treatment > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,026,948 B2 - Document ID: US11026948B2 - Status: Granted - Kind: B2 - Application number: 16/810,160 - Filed: 2020-03-05 - Published: 2020-06-25 - Granted: 2021-06-08 - Earliest claimed: 2017-05-16 - Assignees: BTG International Limited - Applicants: BTG International Limited - Inventors: Udai Banerji - Web page: https://patentgrep.com/patent/US11026948B2 ## CPC - A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine - A61K 31/282: Platinum compounds - A61K 31/337: having four-membered rings, e.g. taxol - A61K 31/4745: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48) - A61K 31/502: ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine - A61K 31/519: ortho- or peri-condensed with heterocyclic rings - A61K 31/704: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} - A61K 31/7048: having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin} - A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid - A61K 33/243: Platinum; Compounds thereof - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - A61K 47/643: {Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]} - A61K 47/6929: {the form being a nanoparticle, e.g. an immuno-nanoparticle} - A61P 35/00: Antineoplastic agents - A61K 2039/545: {characterised by the dose, timing or administration schedule} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract A compound of formula I or a pharmaceutically acceptable salt or ester thereof is provided for the treatment of cancer wherein (i) the cancer is one that has the characteristic of being a type prone to being or becoming refractory or resistant to platinum drug based therapy and (ii) the treatment is with a dose of between 1 mg/m2 and 30 mg/m2 of compound per patient body surface area per administration. Method of treatment and novel dosage forms are also provided. Particularly treated arc ovarian cancers, particularly those expressing a-folate receptors, including epithelial ovarian, fallopian tube or peritoneal cancer. ## Claims ### Claim 1 A method of treating ovarian cancer that is platinum refractory or resistant in a patient in need thereof comprising administering to the patient in need thereof a compound of formula I or a pharmaceutically acceptable salt or ester thereof wherein (i) the treatment is with a dose of from 8 mg/m2 to 15 mg/m2 of compound per patient body surface area per administration, and (ii) the treatment is administered by infusions of the dose, wherein the infusions are spaced from 10 to 21 days apart. ### Claim 2 (depends on 1) The method according to claim 1, wherein the ovarian cancer is selected from those expressing α-folate receptors (FR-α). ### Claim 3 (depends on 1) The method according to claim 1, wherein the ovarian cancer is epithelial ovarian, fallopian tube, or peritoneal cancer. ### Claim 4 (depends on 1) The method according to claim 1, wherein the ovarian cancer is serous ovarian cancer. ### Claim 5 (depends on 1) The method according to claim 1, wherein the ovarian cancer is High-Grade Serous Ovarian Cancer (HGSOC). ### Claim 6 (depends on 1) The method according to claim 1, wherein the dose is administered intraperitoneally (IP) or intravenously (IV). ### Claim 7 (depends on 1) The method according to claim 1, wherein the infusions are administered at dosing interval of about 14 days. ### Claim 8 (depends on 1) The method according to claim 1, wherein the treatment is with a cumulative maximum of 150 mg/m2 of compound per patient body surface area over the course of all the infusions. ### Claim 9 (depends on 1) The method according to claim 1, wherein the maximum cumulative dose is 144 mg/m2. ### Claim 10 (depends on 1) The method according to claim 1, wherein the treatment is with an infusion of from 10 mg/m2 to 15 mg/m2 per administration. ### Claim 11 (depends on 1) The method according to claim 1, wherein the treatment is with an infusion of from 11.5 mg/m2 to 12.5 mg/m2 per administration. ### Claim 12 (depends on 1) The method according to claim 1, wherein the treatment is with an infusion of about 12 mg/m2 per administration. ### Claim 13 (depends on 1) The method according to claim 1, wherein the infusions are administered at dosing interval of about 14 days and the treatment is with an infusion of about 12 mg/m2 per administration. ### Claim 14 (depends on 1) The method according to claim 1, wherein the compound is the trisodium salt of formula II: ### Claim 15 A method of treating ovarian cancer that is platinum refractory or resistant in a patient in need thereof comprising administering to the patient in need thereof a trisodium salt of formula II: wherein (i) the treatment is with a dose of from 8 mg/m2 to 15 mg/m2 of compound per patient body surface area per administration, and (ii) the treatment is administered by infusions of the dose, wherein the infusions are spaced from 10 to 21 days apart. ### Claim 16 (depends on 15) The method according to claim 15, wherein the ovarian cancer is selected from those expressing α-folate receptors (FR-α). ### Claim 17 (depends on 15) The method according to claim 15, wherein the ovarian cancer is epithelial ovarian, fallopian tube, or peritoneal cancer. ### Claim 18 (depends on 15) The method according to claim 15, wherein the ovarian cancer is serous ovarian cancer. ### Claim 19 (depends on 15) The method according to claim 15, wherein the ovarian cancer is High-Grade Serous Ovarian Cancer (HGSOC). ### Claim 20 (depends on 15) The method according to claim 15, wherein the dose is administered intraperitoneally (IP) or intravenously (IV). ### Claim 21 (depends on 15) The method according to claim 15, wherein the infusions are administered at dosing interval of about 14 days. ### Claim 22 (depends on 15) The method according to claim 15, wherein the treatment is with a cumulative maximum of 150 mg/m2 of compound per patient body surface area over the course of all the infusions. ### Claim 23 (depends on 15) The method according to claim 15, wherein the maximum cumulative dose is 144 mg/m2. ### Claim 24 (depends on 15) The method according to claim 15, wherein the treatment is with an infusion of from 10 mg/m2 to 15 mg/m2 per administration. ### Claim 25 (depends on 15) The method according to claim 15, wherein the treatment is with an infusion of from 11.5 mg/m2 to 12.5 mg/m2 per administration. ### Claim 26 (depends on 15) The method according to claim 15, wherein the treatment is with an infusion of about 12 mg/m2 per administration. ### Claim 27 (depends on 15) The method according to claim 15, wherein the infusions are administered at dosing interval of about 14 days and the treatment is with an infusion of about 12 mg/m2 per administration. ### Claim 28 A method of treating ovarian cancer that is platinum refractory or resistant in a patient in need thereof comprising administering to the patient in need thereof a compound of formula I or a pharmaceutically acceptable salt or ester thereof wherein (i) the treatment is with a dose of 12 mg/m2 of compound per patient body surface area per administration, and (ii) the treatment is administered by infusions of the dose, wherein the infusions are spaced from 10 to 21 days apart. ### Claim 29 (depends on 1) The method according to claim 1, wherein the method further comprises administering to the patient in need thereof a therapeutically effective amount of a poly-ADP ribose polymerase (PARP) inhibitor. ### Claim 30 (depends on 29) The method according to claim 29, wherein the compound of formula I or the pharmaceutically acceptable salt or ester thereof and the poly-ADP ribose polymerase (PARP) inhibitor are administered to the patient in need thereof separately. ### Claim 31 (depends on 1) The method according to claim 1, wherein the method further comprises administering to the patient in need thereof a therapeutically effective amount of one or more further anticancer agents selected from olaparib, rucaparib, and niraparib. ### Claim 32 (depends on 15) The method according to claim 15, wherein the method further comprises administering to the patient in need thereof a therapeutically effective amount of a poly-ADP ribose polymerase (PARP) inhibitor. ### Claim 33 (depends on 32) The method according to claim 32, wherein the trisodium salt of formula II and the poly-ADP ribose polymerase (PARP) inhibitor are administered to the patient in need thereof separately. ### Claim 34 (depends on 15) The method according to claim 15, wherein the method further comprises administering to the patient in need thereof a therapeutically effective amount of one or more further anticancer agents selected from olaparib, rucaparib, and niraparib.