Patent SG-11201810550W-A (SG)
Title: Generation of human pluripotent stem cell derived functional beta cells showing a glucose-dependent mitochondrial respiration and two-phase insulin secretion response
Inventor: RIECK SEBASTIAN
IPC: C12N5/071
Filed: 2017-06-14
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property 1111111011111111101 11111111111111111111111111111111111111111111111111111111111110111111 Organization International Bureau (10) International Publication Number (43) International Publication Date .....0\"\"\" WO 2017/222879 Al 28 December 2017 (28.12.2017) WIP0 I PCT — (51) (21) (22) (25) Filing Language: (26) (30) (71) (72) International Patent Classification: (74) Agent: SHIRTZ, Joseph F. et al.; JOHNSON & C12N 5/071 (2010.01) JOHNSON, One Johnson & Johnson Plaza, New International Application Number: Brunswick, New Jersey 08933 (US). PCT/US2017/037373 (81) Designated States (unless otherwise indicated, for every International Filing Date: kind of national protection available): AE, AG, AL, AM, 14 June 2017 (14.06.2017) 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, English DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, Publication Language: English 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, Priority Data: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 62/352,968 21 June 2016 (21.06.2016) US 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, Applicant: JANSSEN BIOTECH, INC. [US/US]; TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. 800/850 Ridgeview Drive, Horsham, Pennsylvania 19044 (US). (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, Inventors: RIECK, Sebastian; 3210 Merryfield Row, San GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, Diego, California 92121 (US). REZANIA, Alireza; 3550 UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, General Atomics Court, San Diego, California 92121 (US). 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, = Title: GENERATION OF HUMAN PLURIPOTENT -DEPENDENT MITOCHONDRIAL RESPIRATION AND TWO-PHASE INSULIN SECRETION RESPONSE FIG. 2A 140 120 - 100 - T. ( 1) 8° - ED .5 60 - a .7 2 1 AD - - 45 0 (54) GLUCOSE STEM CELL DERIVED FUNCTIONAL MA FA BETA CELLS SHOWING A = _ . _ = = = = = = = = = _ = NO ALK5 NO ALK5 NO ALK5 NO ALAS LOW T3 LOW T3 LOW T3 LOW T3 ZM H ZM H ZM H ZM H NAG Fl NAG Fl NAG Fl NAC Fl BLAR001 BLAR001 BLAR001 BLAR001 + 5uM + luM + 10uM AZT DEZA DEZA : The invention provides for methods of differentiating pancreatic endocrine cells into pancreatic beta cells expressing NI(X6.1, MAFA, UCN3 and SLC2A. These pancreatic beta cells may be obtained by step-wise differentiation of pluripotent cells. The pancreatic beta cells exhibit glucose-dependent mitochondrial respiration and glucose-stimulated insulin secretion sim- to islet cells. 1-1 ON IN GC N N N ----- (57) IN ,1 PDX1, 0 stem \" ilar C [Continued on next page] WO 2017/222879 Al IMEDIMOM0101011MMEMOOMOHOHMOICHMEMNIE 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 for and be granted a patent (Rule 4.17(H)) — as to the applicant's entitlement to claim the priority of the earlier application (Rule 4.17(iii)) 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))