# US 11,439,669 B2 · C. novyi for the treatment of solid tumors in humans > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,439,669 B2 - Document ID: US11439669B2 - Status: Granted - Kind: B2 - Application number: 16/836,003 - Filed: 2020-03-31 - Published: 2020-10-22 - Granted: 2022-09-13 - Earliest claimed: 2013-03-29 - Assignees: Biomed Valley Discoveries, Inc.; The Johns Hopkins University - Applicants: Biomed Valley Discoveries, Inc.; The Johns Hopkins University - Inventors: Saurabh Saha; Shibin Zhou; Bert Vogelstein; Kenneth W. Kinzler - Web page: https://patentgrep.com/patent/US11439669B2 ## CPC - A61K 35/74: Bacteria (therapeutic use of a bacterial protein A61K38/00) - A61K 31/65: Tetracyclines - A61K 35/742: Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61N 5/10: X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy (A61N5/01 takes precedence) - A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics - A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes - A61P 15/08: for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis - A61P 17/00: Drugs for dermatological disorders - A61P 21/00: Drugs for disorders of the muscular or neuromuscular system - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 35/00: Antineoplastic agents - A61P 35/04: specific for metastasis - A61P 37/02: Immunomodulators - A61P 37/04: Immunostimulants - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61K 2035/11: {Medicinal preparations comprising living procariotic cells} - 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) - A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention provides, inter alia, methods for treating or ameliorating an effect of a solid tumor present in a human. These methods include administering intratumorally to the human a unit dose of C. novyi, preferably C. novyi NT, colony forming units (CFUs), which contains about 1×103-1×107 CFUs suspended in a pharmaceutically acceptable carrier or solution. Methods for debulking a solid tumor present in a human, methods for ablating a solid tumor present in a human, a method for microscopically precise excision of tumor cells in a human, methods for treating or ameliorating an effect of a solid tumor that has metastasized to one or more sites in a human, unit doses of C. novyi, preferably C. novyi NT, CFUs, and kits for treating or ameliorating an effect of a solid tumor present in a human are also provided. ## Claims ### Claim 1 A method for debulking or abalating a solid tumor present in a human comprising administering intratumorally to the human a unit dose of C. novyi colony forming units (CFUs) comprising 1×103-1×106 CFUs suspended in a pharmaceutically acceptable carrier or solution, wherein the C. novyi is effective to debulk or ablate the solid tumor without administration of additional anti-cancer agents. ### Claim 2 (depends on 1) The method according to claim 1, wherein the solid tumor is selected from the group consisting of soft tissue sarcoma, hepatocellular carcinoma, breast cancer, pancreatic cancer, and melanoma. ### Claim 3 (depends on 1) The method according to claim 1, wherein the solid tumor is leiomyosarcoma. ### Claim 4 (depends on 3) The method according to claim 3, wherein the solid tumor is retroperitoneal leiomyosarcoma. ### Claim 5 (depends on 1) The method according to claim 1, wherein the unit dose comprises about 1×104-1×106 C. novyi CFUs. ### Claim 6 (depends on 1) The method according to claim 1, wherein the C. novyi CFUs are selected from the group consisting of vegetative and spore forms. ### Claim 7 (depends on 1) The method according to claim 1, wherein the C. novyi is C. novyi NT. ### Claim 8 (depends on 7) The method according to claim 7, wherein the unit dose comprises 1×104-1×106 C. novyi NT spores. ### Claim 9 (depends on 8) The method according to claim 8, wherein the unit dose comprises 1×105-1×106 C. novyi NT spores. ### Claim 10 (depends on 1) The method according to claim 1, wherein the administering step comprises injecting the unit dose at a single location into the tumor. ### Claim 11 (depends on 1) The method according to claim 1, wherein the administering step comprises injecting the unit dose at multiple unique locations into the tumor. ### Claim 12 (depends on 1) The method according to claim 1, wherein the administering step comprises injecting the unit dose at 1-5 unique locations into the tumor. ### Claim 13 (depends on 1) The method according to claim 1, wherein the administering step comprises injecting the unit dose at 5 or more unique locations into the tumor. ### Claim 14 (depends on 1) The method according to claim 1 further comprising administering a plurality of treatment cycles to the human, each treatment cycle comprising injecting one unit dose of the C. novyi CFUs into the solid tumor. ### Claim 15 (depends on 14) The method according to claim 14, wherein 2-10 treatment cycles are administered. ### Claim 16 (depends on 14) The method according to claim 14, wherein 2-4 treatment cycles are administered. ### Claim 17 (depends on 14) The method according to claim 14, wherein an interval between each treatment cycle is about 5-100 days. ### Claim 18 (depends on 14) The method according to claim 14, wherein an interval between each treatment cycle is about 7 days. ### Claim 19 (depends on 7) The method according to claim 7 further comprising administering IV fluids to the human before, during, and/or after each administration of the C. novyi NT spores. ### Claim 20 (depends on 7) The method according to claim 7 further comprising administering a plurality of treatment cycles to the human, each treatment cycle comprising injecting one unit dose of the C. novyi NT spores into the solid tumor. ### Claim 21 (depends on 20) The method according to claim 20, wherein 2-4 treatment cycles are administered. ### Claim 22 (depends on 1) The method according to claim 1 further comprising administering IV fluids to the human before, during, and/or after each administration of the C. novyi. ### Claim 23 (depends on 1) The method according to claim 1 further comprising providing the human with a first course of antibiotics for a period of time and at a dosage that is effective to treat or alleviate an adverse side effect selected from the group consisting of infections, vomiting, hematochezia, fever, and combinations thereof caused by the C. novyi. ### Claim 24 (depends on 23) The method according to claim 23, wherein the antibiotics are administered for two weeks post C. novyi administration. ### Claim 25 (depends on 23) The method according to claim 23, wherein the antibiotics are selected from the group consisting of amoxicillin, clavulanate, metronidazole, and combinations thereof. ### Claim 26 (depends on 23) The method according to claim 23 further comprising providing the human with a second course of antibiotics for a period of time and at a dosage that is effective to treat or alleviate an adverse side effect selected from the group consisting of infections, vomiting, hematochezia, fever, and combinations thereof caused by the C. novyi. ### Claim 27 (depends on 26) The method according to claim 26, wherein the second course of antibiotics is initiated after completion of the first course of antibiotics and is carried out for 1-6 months. ### Claim 28 (depends on 26) The method according to claim 26, wherein the second course of antibiotics is initiated after completion of the first course of antibiotics and is carried out for 3 months. ### Claim 29 (depends on 26) The method according to claim 26, wherein the antibiotic used in the second course is doxycycline. ### Claim 30 (depends on 1) The method according to claim 1, further comprising administering to the human an anti-cancer agent selected from the group consisting of chemotherapy, radiation therapy, immunotherapy, and combinations thereof, after the C. novyi have acted to debulk or ablate the solid tumor. ### Claim 31 (depends on 30) The method according to claim 30, wherein the immunotherapy comprises administering to the human an immune checkpoint inhibitor. ### Claim 32 (depends on 1) The method according to claim 1, wherein the solid tumor is resistant to a therapy selected from the group consisting of chemotherapy, radiation therapy, immunotherapy, and combinations thereof. ### Claim 33 (depends on 30) The method according to claim 30, wherein the chemotherapy comprises administering to the human an agent selected from the group consisting of an anti-metabolite, a microtubule inhibitor, a DNA damaging agent, an antibiotic, an anti-angiogenesis agent, a vascular disrupting agent, a molecularly targeted agent, and combinations thereof. ### Claim 34 (depends on 30) The method according to claim 30, wherein the chemotherapy comprises administering to the human an agent selected from the group consisting of gemcitabine, taxol, adriamycin, ifosfamide, trabectedin, pazopanib, abraxane, avastin, everolimus, and combinations thereof. ### Claim 35 (depends on 1) The method according to claim 1, wherein the solid tumor is refractory to standard therapy or the solid tumor is without an available standard therapy. ### Claim 36 (depends on 1) The method according to claim 1, wherein the unit dose of C. novyi induces a potent localized inflammatory response and an adaptive immune response in the human. ### Claim 37 A method for microscopically precise excision of tumor cells in a human comprising administering intratumorally to the human a unit dose of C. novyi NT colony forming units (CFUs) comprising 1×103-1×106 CFUs suspended in a pharmaceutically acceptable carrier or solution, wherein the C. novyi is effective for microscopically precise excision of the tumor cells without administration of additional anti-cancer agents. ### Claim 38 A method for debulking or ablating a solid tumor that has metastasized to one or more sites in a human comprising administering intratumorally to the human a unit dose of C. novyi NT colony forming units (CFUs) comprising 1×103-1×106 CFUs suspended in a pharmaceutically acceptable carrier or solution, wherein the C. novyi is effective to debulk or ablate the solid tumor without administration of additional anti-cancer agents. ### Claim 39 (depends on 38) The method according to claim 38, wherein at least one site is distal to the original solid tumor. ### Claim 40 A method for debulking a solid tumor present in a human comprising administering intratumorally to the human a unit dose of C. novyi CFUs comprising 1×103-1×106 CFUs suspended in a pharmaceutically acceptable carrier or solution, wherein the C. novyi is effective to debulk the solid tumor without administration of additional anti-cancer agents. ### Claim 41 (depends on 40) The method according to claim 40, wherein the solid tumor is selected from the group consisting of soft tissue sarcoma, hepatocellular carcinoma, breast cancer, pancreatic cancer, and melanoma. ### Claim 42 A method for debulking a solid tumor present in a human comprising administering intratumorally to the human one to four cycles of a unit dose of C. novyi NT spores comprising 1×103-1×106 spores per cycle, each unit dose of C. novyi NT being suspended in a pharmaceutically acceptable carrier or solution, wherein the C. novyi is effective to debulk the solid tumor without administration of additional anti-cancer agents. ### Claim 43 A method for debulking or ablating a solid tumor present in a human comprising administering intratumorally to the human one to four cycles of a unit dose of C. novyi NT spores comprising 1×103-1×106 spores per cycle, each unit dose of C. novyi NT spores being suspended in a pharmaceutically acceptable carrier or solution, wherein the C. novyi is effective to debulk or ablate the solid tumor without administration of additional anti-cancer agents. ### Claim 44 A method for ablating a solid tumor present in a human comprising administering intratumorally to the human a unit dose of C. novyi CFUs comprising 1×103-1×106 CFUs suspended in a pharmaceutically acceptable carrier or solution, wherein the C. novyi is effective to ablate the solid tumor without administration of additional anti-cancer agents leaving a margin of normal tissue. ### Claim 45 (depends on 44) The method according to claim 44, wherein the tumor is a sarcoma.