Patent SG-11201408679X-A (SG)
Title: Methods for treating tyrosine-kinase-inhibitor-resistant malignancies in patients with genetic polymorphisms or ahi1 dysregulations or mutations employing dianhydrogalactitol, diacetyldianhydrogalactitol, dibromodulcitol, or analogs or derivatives thereof
Inventor: BROWN DENNIS M
IPC: A61K38/12
Filed: 2013-06-24
Abstract: (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 3 January 2014 (03.01.2014) WIPOIPCT (10) International Publication Number WO 2014/004376 A2 (51) International Patent Classification: A61K 31/047 ( 2006.01) (21) International Application Number: (22) International Filing Date: (25) Filing Language: (26) Publication Language: PCT/US2013/047320 24 June 2013 (24.06.2013) English English (30) Priority Data: 61/664,279 61/824,672 26 June 2012 (26.06.2012) US 17 May 2013 (17.05.2013) US (71) Applicant: DEL MAR PHARMACEUTICALS [CA/CA]; 999 West Broadway, Suite 720, Vancouver, British Columbia V57 1K5 (CA). (72) Inventors; and (71) Applicants : BROWN, Dennis M. [US/US]; 3475 Edison Way, Suite R, Menlo Park, California 94025 (US). BACHA, Jeffrey A. [CA/CA]; c/o Del Mar Pharmaceutic­ als, Suite 115, Vancouver, British Columbia V5T 4T5 (CA). GARNER, William J. [US/US]; 1701 Jackson Street, #102, San Francisco, California 94109 (US). (74) Agents: DITTHAVONG MORI & STEINER P.C. et al.; 44 Canal Center Plaza, Suite 322, Alexandria, Virginia 22314 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available)'. AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, 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, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available)'. ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Published: — without international search report and to be republished upon receipt of that report (Rule 48.2(g)) CJ i> m o o o CJ O & (54) Title: METHODS FOR TREATING TYROSINE-KINASE-INHIBITOR-RESISTANT MALIGNANCIES IN PATIENTS WITH GENETIC POLYMORPHISMS OR AHI1 DYSREGULATIONS OR MUTATIONS EMPLOYING DIANHYDROGALACTITOL, DIACETYLDIANHYD- ROGALACTITOL, DIBROMODULCITOL, OR ANALOGS OR DERIVATIVES THEREOF (57) Abstract: Methods and compositions suitable for the treatment of malignancies in subjects with germline deletion a polymorph­ ism that blocks the activity of thymidine kinase inhibitors in triggering apoptosis in tumor cells or in subjects having mutation in a or a dysregulation of the AHI1 gene are disclosed. These methods employ an alkylating hexitol derivative such as dianhydrogalactitol, a derivative or analog of dianhydrogalactitol, diacetyldianhydrogalactitol, derivative a or analog of diacetyldianhydrogalactitol, dibro - modulcitol, and a derivative or analog of dibromodulcitol. The compositions can include such alkylating hexitol derivatives. The methods can further include administration of BH3 a mimetic, and the compositions can further include a BH3 mimetic. In subjects having dysregulation of a the AHI1 gene, the methods can further include the administration of an agent modulating the expression or activity of the AHI1 gene or AHI1 protein, and the compositions can further include such an agent.