Patent SG-11201804641W-A (SG)
Title: Methods for generating functional hematopoietic stem cells
Inventor: SHAH DHVANIT I
IPC: C12N5/071
Filed: 2016-12-02
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property -' Organization International Bureau .... ...Yeid (43) International Publication Date .... ..sr ,„„..) 8 June 2017 (08.06.2017) W I P0 1 PCT (10) WO International 111111111111311111111111111111111111111111111111111111111111111111111311111111111111111 2017/096215 Publication Al Number (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A01N 63/00 (2006.01) C12N 5/02 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, C12N 5/071 (2010.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (21) International Application Number: KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, PCT/US2016/064706 MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (22) International Filing Date: OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, 2 December 2016 (02.12.2016) 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, (25) Filing Language: English ZW. (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 62/262,464 3 December 2015 (03.12.2015) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 62/332,853 6 May 2016 (06.05.2016) US TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (71) Applicant . THE BRIGHAM AND WOMEN'S HOS- DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, PITAL, INC. [US/US]; 75 Francis Street, Boston, MA LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, 02115 (US). SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, (72) Inventors: SHAH, Dhvanit I.; 1036 Main Street, Apt. 5, GW, KM, ML, MR, NE, SN, TD, TG). Malden, Massachusetts 02148 (US). DALEY, George Q.; Published: 50 Young Road, Weston, Massachusetts 02193 (US). — with international search report (Art 21(3)) (74) Agents: DEYOUNG, Janice Kugler et al.; Fish & before the expiration of the time limit for amending the Richardson P.C., P.O. Box 1022, Minneapolis, Minnesota claims and to be republished in the event of receipt of 55440-1022 (US). amendments (Rule 48.2(h)) (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, (54) Title: METHODS FOR GENERATING FUNCTIONAL HEMATOPOIETIC STEM CELLS Il .4t * * /0 / 1 , • 4- , • • , - .; . - S ,,„ „ rt 1 Sei % ) w., CAM R n GSkir 4 -Pr m G5K2'35 GSK r in KTE720 Il N FIG. 9B Ct\ 0 ----. (57) : Methods for preparing populations of hematopoietic stem cells (HSCs), e.g., autologous and/or allogenic HSCs, us - I I: ing mechanical stretching or transient receptor potential cation channel-subfamily vanilloid member 4 (Trpv4) agonists, and methods c:::, of use of the HSCs in transplantation are provided. Specifically, the methods comprising providing a population cells comprising el hemogenic endothelial (HE) cells, contacting the HE cells with an amount of an agonist of Trpv4; and/or subjecting the cells to cyc - 0 lic 2-dimensional stretching, for a time and under conditions sufficient to stimulating endothelial-to-HSC transition. Further dis- closed are methods of treating malignant or non-malignant hematologic, metabolic, or immune disorders comprising administering to a subject a therapeutically effective amount of HSCs obtained by the methods.