Patent AU-2012321106-C1 (AU)
Title: Administration of NEDD8-activating enzyme inhibitor and hypomethylating agent
Inventor: SMITH PETER G
IPC: C07D487/00
Filed: 2012-11-02
Granted: 2016-11-24
Abstract: (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date W O 2013/067396 A2 10 May 2013 (10.05.2013) W I PO I P CT (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A61K31/706 (2006.01) A61P 35/02 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, A61P 35/00 (2006.01) DO, DZ, EC, EE, EG, ES, Fl, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (21) International Application Number: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, PCT/US2012/063382 ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, (22) International Filing Date: NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, 2 November 2012 (02.11.2012) RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, (25) Filing Language: English ZM, ZW. (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 61/555,049 3 November 2011 (03.11.2011) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (71) Applicant: MILLENNIUM PHARMACEUTICALS, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, INC. [US/US]; 40 Landsdowne Street, Cambridge, Mas- EE, ES, Fl, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, sachusetts 02139 (US). MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, (72) Inventor: SMITH, Peter G.; 173A Franklin Street, Ar- TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, lington, Massachusetts 02474 (US). ML, MR, NE, SN, TD, TG). (74) Agent: HERZFELD, Deborah M.; Finnegan, Henderson, Declarations under Rule 4.17: Farabow, Garrett & Dunner LLP, 901 New York Avenue, - as to applicant's entitlement to applyfor and be granted a NW, Washington, D.C., District of Columbia 20001-4413 patent (Rule 4.17(ii)) (US). Published: (81) Designated States (unless otherwise indicated, for every without international search report and to be republished kind of national protection available): AE, AG, AL, AM, upon receipt of that report (Rule 48.2(g)) (54) Title: ADMINISTRATION OF NEDD8-ACTIVATING ENZYME INHIBITOR AND HYPOMETHYLATING AGENT OCI-M2 Xenografts -4-Vehicle -W- MLN4924 180 mg/kg -M-Aza 5mg/kg -0-MLN4924 180 mg/kg +Aza 5mg/kg lo 0 5 10 15 20 25 30 35 40 45 Day (57) Abstract: The present disclosure relates to methods for the treatment of cancer in patients in recognized need of such treatment. The methods comprise administering to such a patient an NAE inhibitor or a pharmaceutically acceptable salt thereof, such as N ((1S,2S,4R)-4-(4-((IS)-2,3-dihydro-1H-inden-1-ylamino)-7H-pyrrolo[2,3 d]pyrimidin 7-yl)-2-hydroxycyclopentyl)methy sulfamate (MLN4924) or {(IS,2S,4R)-4-[(6-{[(1R,2S)-5-chloro-2 methoxy-2,3-dihydro-1H-inden-1-yl]amino}pyrimidin-4-yl)oxy]-2-hy droxycyclopentyl} -methyl sulfamate (1-216), and a hypomethylating agent or a pharmaceutically acceptable salt thereof, such as aza citidine or decitabine. Also disclosed are medicaments for use in the treatment of cancer.