Patent SG-11201807591V-A (SG)
Title: Crystalline(2s,4r)-5-(5'-chloro-2'-fluoro-[1,1'-biphenyl]-4-yl)-2-(ethoxymethyl)-4-(3-hydroxyisoxazole-5-carboxamido)-2-methylpentanoic acid and uses thereof
Inventor: HUGHES ADAM D
IPC: A61P9/00
Filed: 2017-03-07
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2017/156009 Al 14 September 2017 (14.09.2017) WIPO I PCT (51) International Patent Classification: CO7D 261/18 (2006.01) A61P 9/00 (2006.01) A61K 31/42 (2006.01) (21) International Application Number: PCT/US2017/021172 (22) International Filing Date: 7 March 2017 (07.03.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/305,393 8 March 2016 (08.03.2016) US 62/346,336 6 June 2016 (06.06.2016) US (71) Applicant: THERAVANCE BIOPHARMA R&D IP, LLC [US/US]; 901 Gateway Boulevard, South San Fran- cisco, California 94080 (US). (72) Inventors: HUGHES, Adam D.; 2029 Touraine Lane, Half Moon Bay, California 94019 (US). FLEURY, Melissa; 47D Joy Avenue, Brisbane, California 94005 (US). RAPTA, Miroslav; 1240 Highland Court, San Car- los, California 94070 (US). THALLADI, Venkat R.; 888 Foster City Boulevard, Apt. E3, Foster City, California 94404 (US). FASS, Gene Timothy; 998 Burnett Avenue, San Francisco, California 94131 (US). SIMEONE, Mi- chael; 75 Heather Avenue #6, San Francisco, California 94118 (US). BALDWIN, R. Michael; 1720 2nd Avenue, San Mateo, California 94401 (US). BOURDET, David L.; 614 Bayview Avenue, Millbrae, California 94030 (US). (74) Agents: HAGENAH, Jeffrey A. et al.; THERAVANCE BIOPHARMA US, INC., 901 Gateway Boulevard, South San Francisco, California 94080 (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, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, 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)) — (54) Title: CRYSTALLINE(2S,4R)-5-(5'-CHLOR0-2'-FLUOR041,1'-BIPHENYL]-4-YL)-2-(ETHOXYMETHYL)-4-(3-HY- DROXYISOXAZOLE-5-CARBOXAMIDO)-2-METHYLPENTANOIC ACID AND USES THEREOF OW N OH 0 HO CI (I), , (57) : In one aspect, the invention relates to a crystalline form of the structure: or a pharmaceutically acceptable salt thereof, having neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising this crystal- line form; methods of using this crystalline form and its soluble form (I); and processes for preparing soluble (I) and crystalline (I') forms. 1111111111111101110101011111010111110 011111111100111111101110111111111110111111 W O 20 17 / 15 6009 Al