Patent SG-11201907119X-A (SG)
Title: An inhibitor of atr kinase for use in a method of treating a hyper-proliferative disease
Inventor: WENGNER ANTJE
IPC: C12Q1/6886
Filed: 2018-02-22
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 30 August 2018 (30.08.2018) WIPO I PCT ill~~~~~~~~ 011101010VIIIOH olo 1101H I10111111 oimIE (10) International Publication Number WO 2018/153968 Al (51) International Patent Classification: C12Q 1/6886 (2018.01) (21) International Application Number: PCT/EP2018/054361 (22) International Filing Date: 22 February 2018 (22.02.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/463,125 24 February 2017 (24.02.2017) US 62/589,837 22 November 2017 (22.11.2017) US (71) Applicants: BAYER AKTIENGESELLSCHAFT [DE/DE]; Kaiser-Wilhelm-Allee 1, 51373 Leverkusen (DE). BAYER PHARMA AKTIENGESELLSCHAFT [DE/DE]; Miillerstr. 178, 13353 Berlin (DE). (72) Inventors: WENGNER, Antje, Margret; Borkumstr. 12 e, 13189 Berlin (DE). SIEMEISTER, Gerhard; Reimerswalder Steig 26, 13503 Berlin (DE). HANDLER, Bernard; Am Biberbau 8, 13465 Berlin (DE). GOLFIER, Sven; Stolpchenweg 12E, 14109 Berlin (DE). SCHLICK- ER, Andreas; Rigaer Str. 17, 10247 Berlin (DE). LIU, Li; 11 Hillside Drive, East Hanover, NJ 07936 (US). (74) Agent: BIP PATENTS; Alfred-Nobel-Str. 10, 40789 Mon- heim am Rhein NRW (DE). (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)) before the expiration of the time limit for amending the claims and to be republished in the event of receipt of amendments (Rule 48.2(h)) with sequence listing part of description (Rule 5.2(a)) (54) Title: AN INHIBITOR OF ATR KINASE FOR USE IN A METHOD OF TREATING A HYPER-PROLIFERATIVE DISEASE (57) : The present invention covers 2-[(3R)-3-methylmorpholin-4-y1]-4-(1-methy1-1H-pyrazol-5-y1)-8-(1H- pyra- zol-5-yl)-1,7-naphthyridine (in the following called \"Compound A\"), an inhibitor of ATR kinase, for use in a method of treating a hyper-proliferative disease in a subject. Preferably the hyper-proliferative disease or the subject is characterized by one or more biomarker(s) selected from a) one or more functional mutation(s) in one or more gene(s)/protein(s) selected from APC, ATG5, ARID1A, ATM, ATR, ATRIP, ATRX, BAP1, BARD1, BLM, BRAF, BRCA1, BRCA2, BRIP1, CCND1, CCNE1, CCNE2, CDC7, CDK12, CHEK1, CHEK2, DCLRE1A, DCLRE1B, DCLRE1C, DYRK1A, EGFR, ERBB2, ERBB3, ERCC2, ERCC3, ERCC4, ER- CC5, FAM175A, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, FBXO18, FBXW7, FEN1, GEN1, HDAC2, H2AFX, HRAS, KRAS, LIG4, MDC1, MLH1, MLH3, MRE11A, MSH2, MSH3, MSH6, MYC, NBN, NRAS, PALB2, PARP1, PARP2, PARP3, PARP4, PCNA, PIK3CA, PMS2, POLA1, POLB, POLH, POLL, POLN, POLQ, PRKDC, PTEN, RAD9A, RAD17, RAD18, RAD50, RAD51, RAD52, RAD54B, RAD54L, RB1, REV3L, RPA1, RPA2, SLX4, TDP1, TDP2, TM- PRSS2, TMPRSS2-ERG, TOPBP1, TOP2A, TOP2B, TP53, TP53BP1, TRRAP, UBE2N, UIMC1, USP1, WDR48, WRN, XPA, XR- CC1, XRCC2, XRCC3, XRCC4 and/or XRCC6 gene/protein; and/or b) the activation of the ALT pathway; and/or c) microsatellite instability. The present invention also covers a kit comprising Compound A together with means to detect one or more of the afore- mentioned biomarker(s) and a method for identifying a subject having a hyper- proliferative disease disposed to respond favorably to Compound A, wherein the method comprises the detection of one or more of the aforementioned biomarker(s). Further, the invention covers a method of determining whether a subject having a hyper-proliferative disease will respond to the treatment with Compound A, wherein the method comprises the detection of one or more of the aforementioned biomarker(s) in a sample of the subject.