Patent SG-11201900402U-A (SG)
Title: Combination of a bcl-2 inhibitor and a mcl-1 inhibitor, uses and pharmaceutical compositions thereof
Inventor: WEI ANDREW
IPC: A61P35/00
Filed: 2017-07-21
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property MD HIM 0 11101 HOE 3E1 0 0111111 011110110101111111110 1111 OEN Organization International Bureau (10) International Publication Number (43) International Publication Date .....0\"\"\" WO 2018/015526 Al 25 January 2018 (25.01.2018) WIP0 I PCT (51) (21) (22) (25) Filing Language: (26) (30) (71) Applicants: LES LABORATOIRES SERVIER [ (72) International Patent Classification: 13 Parfrey avenue, Victoria, Lalor, Victoria 3075 (AU). A61K 31/436 (2006.01) A61K 31/55 (2006.01) POMILIO, Giovanna; 1 Hyde Street, Victoria, Hadfield, A61K 31/407 (2006.01) A61K 31/675 (2006.01) Victoria 3046 (AU). MARAGNO, Ana Leticia; 4, Al- A61K 31/4353 (2006.01) A61P 35/00 (2006.01) lee Anastasi, 78290 Croissy-sur-Seine (FR). GENESTE, A61K 31/519 (2006.01) Olivier; Batiment A, 17, rue Crevel Duval, 92500 RUEIL International Application Number: MALMAISON (FR). CLAPERON, Audrey; 30, rue du PCT/EP2017/068453 22 septembre, 92400 Courbevoie (FR). MAACKE, Heiko; c/o Novartis Pharma AG, Postfach, Novartis Institutes for International Filing Date: Biomed. Research, 4002 Basel (CH). HALILOVIC, En- 21 July 2017 (21.07.2017) sar; c/o Novartis Institutes for Biomedical Research, Inc., 250 Massachusetts Avenue, Cambridge, Massachusetts MA English 02139 (US). PORTER, Dale; c/o Novartis Institutes for Publication Language: English Biomedical Research, Inc., 250 Massachusetts Avenue, Cambridge, Massachusetts MA 02139 (US). MORRIS, Priority Data: Erick; c/o Novartis Institutes for Biomedical Research, 16180918.1 22 July 2016 (22.07.2016) EP Inc., 250 Massachusetts Avenue, Cambridge, Massachu- 16306420.7 28 October 2016 (28.10.2016) EP setts 02139 (US). WANG, Youzhen; c/o Novartis Insti- 62/464,554 28 February 2017 (28.02.2017) US tutes for Biomedical Research, Inc., 250 Massachusetts Av- 62/517,252 09 June 2017 (09.06.2017) US enue, Cambridge, Massachusetts MA 02139 (US). SANG- /FR]; HAVI, Sneha; c/o Novartis Institutes for Biomedical Re- rue de Verdun, 92284 SURESNES (FR). NOVARTIS search, Inc., 250 Massachusetts Avenue, Cambridge, Mass- AG [CH/CH]; Lichtstrasse 35, 4056 Basel (CH). achusetts MA 02139 (US). MISTRY, Prakash; c/o Novar- tis Pharma AG, Postfach, Novartis Institutes for Biomed. Inventors: WEI, Andrew; 14 The Avenue, Victoria, Sur- Research, 4002 Basel (CH). rey Hills, Victoria 3127 (AU). MOUJALLED, Donia; __35 = (54) Title: COMBINATION OF A BCL-2 THEREOF Figure 5. Anti-tumor effects of Compound POSITIONS 1, model in rats. t INHIBITOR AND A MCL-1 INHIBITOR, USES AND PHARMACEUTICAL COM- HCI, Compound 3 and the combination of Compound 1, HCl + Compound 3 in -0 Vehicle + Vehicle, n=5 -a Compound 3 20mpk + Vehicle, n=5 ^sir Vehicle + Compound 1 150mpk, n=5 - - 4 Compound 3 20mpk + Compound 1 150mpk, n=5 = = lymphoma Karpass422 xenograft 4800- 4000- c , --- i E E 2 3200- a) LLJ E u) D — L 2400- TD co > 0 8 E 1600- E M I - 800- o 1 : A combination comprising = = = — = = = _ = — _ = _ 1-1 .4 ei kin kin 1-1 © --.... 1-1 0 ei (57) 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 Days post first dose a BCL-2 inhibitor and a MCL1 inhibitor, and compositions and uses thereof. [Continued on next page] WO 2018/015526 Al MIDEDIMOMOIDEIREEMOOMMOUNIOHEOMEEN (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, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, 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, SA, 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, ST, 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: — with international search report (Art. 21(3))