# US 7,612,052 B2 · Combinations comprising epothilones and pharmaceutical uses thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,612,052 B2 - Document ID: US7612052B2 - Status: Granted - Kind: B2 - Application number: 12/019,294 - Filed: 2008-01-24 - Published: 2008-05-22 - Granted: 2009-11-03 - Earliest claimed: 2001-07-19 - Assignees: Novartis AG - Inventors: John David Rothermel; Markus Wartmann; Jeanette Marjorie Wood - Web page: https://patentgrep.com/patent/US7612052B2 ## CPC - A61K 31/663: Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid - A61K 31/427: not condensed and containing further heterocyclic rings - A61K 31/502: ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine - A61K 31/555: containing heavy metals, e.g. hemin, hematin, melarsoprol - A61K 33/243: Platinum; Compounds thereof - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants - A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics - A61P 11/00: Drugs for disorders of the respiratory system - A61P 13/08: of the prostate - A61P 13/12: of the kidneys - A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives - A61P 25/00: Drugs for disorders of the nervous system - A61P 35/00: Antineoplastic agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - 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 The invention relates to a combination which comprises (a) a bisphosphonate, a platinum compound or a vasculostatic compound and (b) an epothilone derivative of formula I wherein A represents O or NRN, wherein RN is hydrogen or lower alkyl, R is hydrogen or lower alkyl, and Z is O or a bond, in which the active ingredients (a) and (b) are present in each case in free form or in the form of a pharmaceutically acceptable salt and optionally at least one pharmaceutically acceptable carrier for simultaneous, separate or sequential use, in particular for the delay of progression or treatment of a proliferative disease, especially a solid tumor disease; a pharmaceutical composition, a commercial package or product comprising such a combination; the use of such a combination for the preparation of a medicament for the delay of progression or treatment of a proliferative disease and to a method of treatment of a warm-blooded animal. ## Claims ### Claim 1 A combination which comprises (a) a vasculostatic compound which is a VEGFR inhibitor and (b) an epothilone derivative of formula I wherein A represents O or NRN, wherein RN is hydrogen or lower alkyl, R is hydrogen or lower alkyl, and Z is O or a bond, in which the active ingredients (a) and (b) are present in each case in free form or in the form of a pharmaceutically acceptable salt and optionally at least one pharmaceutically acceptable carrier; for simultaneous, separate or sequential use. ### Claim 2 (depends on 1) Combination according to claim 1 wherein the vasculostatic compound is PTK787. ### Claim 3 (depends on 1) Combination according to claim 1 comprising an epothilone derivative of formula I wherein A represents O, R is lower alkyl or hydrogen and Z is O or a bond. ### Claim 4 (depends on 1) Combination according to claim 1, which is a combined preparation or a pharmaceutical composition. ### Claim 5 (depends on 1) Method of treating a warm-blooded animal having a solid tumor disease comprising administering to the animal a combination according to claim 1 in a quantity which is jointly therapeutically effective against a proliferative disease and in which the compounds can also be present in the form of their pharmaceutically acceptable salts. ### Claim 6 (depends on 5) Method of treating according to claim 5 wherein PTK787 is employed and the solid tumor disease is ovarian cancer, lung cancer, head or neck cancer, cervix cancer, prostate cancer or colon cancer. ### Claim 7 (depends on 1) A pharmaceutical composition comprising a quantity which is jointly therapeutically effective against a solid tumor disease of a pharmaceutical combination according to claim 1 and at least one pharmaceutically acceptable carrier. ### Claim 8 A commercial package comprising (a) a vasculostatic compound which is a VEGFR inhibitor and (b) an epothilone derivative of formula I wherein A represents O or NRN, wherein RN is hydrogen or lower alkyl, R is hydrogen or lower alkyl, and Z is O or a bond, together with instructions for simultaneous, separate or sequential use thereof in the delay of progression or treatment of a solid tumor disease. ### Claim 9 (depends on 2) A combination of claim 2 wherein the epothilone derivative is epothilone B.