Patent SG-11201905508V-A (SG)
Title: Hsd17b13 variants and uses thereof
Inventor: ABUL-HUSN NOURA
IPC: C12Q1/6883
Filed: 2018-01-19
Abstract: HSDb13Expression in Liver (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 26 July 2018 (26.07.2018) WIPO I PCT (51) International Patent Classification: Cl 2N 15/113 (2010.01) C12Q 1/6883 (2018.01) (21) International Application Number: PCT/US2018/014454 (22) International Filing Date: 19 January 2018 (19.01.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/449,335 23 January 2017 (23.01.2017) US 62/472,972 17 March 2017 (17.03.2017) US 62/581,918 06 November 2017 (06.11.2017) US (71) Applicant: REGENERON PHARMACEUTICALS, INC. [US/US]; 777 Old Saw Mill River Road, Tarrytown, NY 10591-6707 (US). (72) Inventors: ABUL-HUSN, Noura, S.; c/o Regeneron Phar- maceuticals, Inc., 777 Old Saw Mill River Road, Tarry- town, NY 10591-6707 (US). GOTTESMAN, Omri; c/o Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill Riv- er Road, Tarrytown, NY 10591-6707 (US). LI, Alexan- der; c/o Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591-6707 (US). CHENG, Xiping; c/o Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591-6707 (US). XIN, Yurong; c/o Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591-6707 (US). PE- FANIS, Evangelos; c/o Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591-6707 (US). HARTFORD, Suzanne; c/o Regeneron Pharmaceu- ticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591-6707 (US). GROMADA, Jesper; c/o Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tar- rytown, NY 10591-6707 (US). DEWEY, Frederick, E.; c/ o Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591-6707 (US). BARAS, Aris; c/ o Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill Riv- er Road, Tarrytown, NY 10591-6707 (US). SHULDINER, Alan; c/o Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591-6707 (US). (74) Agent: SCHILLING, Stephen, H. et al.; Alston & Bird LLP, Bank of America Plaza, 101 South Tryon Street, Suite 4000, Charlotte, NC 28280-4000 (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, 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, (54) Title: HSD17B13 VARIANTS AND USES THEREOF omit IIl °nolo Imo oimIE (10) International Publication Number WO 2018/136758 Al Cas9-ready mice WT mice FIG. 17A I= Guide 1 Li Guide 2 Guide 3 to Guide 4 Guide 5 ®Guides 1-5 cc N 00 O C (57) : Provided are compositions related to HSD17B13 variants, including isolated nucleic acids and proteins related to vari- ants of HSD17B13, and cells comprising those nucleic acids and proteins. Also provided are methods related to HSD17B13 variants. Such methods include methods for modifying a cell through use of any combination of nuclease agents, exogenous donor sequences, transcriptional activators, transcriptional repressors, and expression vectors for expressing a recombinant HSD17B13 gene or a nucleic acid encoding an HSD17B13 protein. Also provided are therapeutic and prophylactic methods for treating a subject having or at risk of developing chronic liver disease. [Continued on next page] WO 2018/136758 Al 11I111E11I11111110111101111101111111 130111 0111 11111 1111 11111110 ME HOED 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). Declarations under Rule 4.17: as to the identity of the inventor (Rule 4.17(1)) as to applicant's entitlement to apply for and be granted a patent (Rule 4.17(11)) 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)) with sequence listing part of description (Rule 5.2(a))