Patent SG-11201811022T-A (SG)
Title: An oxazine derivative for use in the prevention of alzheimer's disease in at risk patients
Inventor: LOPEZ-LOPEZ CRISTINA
IPC: A61P25/28
Filed: 2017-07-17
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property :::` , Organization MD 1101111 II DOI HIM 011101 0 01111 11111HIIIIIH111111111011111111 International Bureau (10) International Publication Number i (43) International Publication Date .....•' WO 2018/015868 Al 25 January 2018 (25.01.2018) WI P0 I P C T — (51) (21) (22) (25) Filing Language: (26) (30) (71) (72) International Patent Classification: (74) Agent: NOVARTIS AG; Lichtstrasse 35, 4056 Basel A61K 31/5377 (2006.01) A61P 25/28 (2006.01) (CH). International Application Number: (81) Designated States (unless otherwise indicated, for every PCT/IB2017/054307 kind of national protection available): AE, AG, AL, AM, International Filing Date: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, 17 July 2017 (17.07.2017) 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, English HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, Publication Language: English 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, Priority Data: OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, 16180233.5 19 July 2016 (19.07.2016) EP SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 16193779.2 13 October 2016 (13.10.2016) EP TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. Applicant: NOVARTIS AG [CH/CH]; Lichtstrasse 35, (84) Designated States (unless otherwise indicated, for every 4056 Basel (CH). kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, Inventors: LOPEZ-LOPEZ, Cristina; Novartis Pharma UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, AG, Postfach, 4002 Basel (CH). NEUMANN, Ulf; Novar-TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, tis Pharma AG, Postfach, Novartis Institutes for Biomed. EE, ES, FL FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, Rarch, 4002 Basel (CH). ese MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, = = (54) © Alzheimer's Title: AN OXAZINE DERIVATIVE FOR USE IN THE PREVENTION OF ALZHEIMER'S DISEASE IN AT RISK PATIENTS Figure 1: Fur colour scores of C57BL/6 mice chronically treated with Compound 1 or NB-360 for 8 weeks (mean ± SEM) = = 5 O 19 E =0 Relevant score level 10 20 30 Days compositions compris- clinical symptoms of Alzheimer's disease carries one = = 1 Lastnsdoer,te b by 1 people = _ ---- 40 50 = — = = = = s- Vehicle (0/8) I I -A- Compound 1: 8 pmoUkg p.o. (0/8) 1 -11- Compound 1: 50 prnolikg p.o. (118) I -V- NB-360: 5 limoliko p.o. (0/9) Af• NB-360: 201Jrnol/kg p.o. (0/8) (number of responders/total group size) _ P S I GC GC ir) Il 0 ---. (57) GC • 1-1 mg N or two Stets: Kruskal-Wallis with Dunn's post-hoc C. p <0.05, ''\": p < 0.01 versus Vehicle) : The present invention relates to an oxazine derivative BACE-1 inhibitor and pharmaceutical such oxazine derivative for use in the prevention of Alzheimer's disease in a patient at risk of developing disease, and in particular, wherein the patient at risk of developing clinical symptoms of copies of the ApoE4 allele. C [Continued on next page] WO 2018/015868 Al MIDEDIM1111011111111111111111111111111111111111111111111111011110111110111111111111 TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Declarations under Rule 4.17: — as to applicant's entitlement to apply patent (Rule 4.17(11)) for and be granted a Published: — with international search report (Art. 21(3))