Patent SG-11202000274R-A (SG)
Title: Oligonucleotide compositions and methods thereof
Inventor: VARGEESE CHANDRA
IPC: C12N15/113
Filed: 2018-08-07
Abstract: INTERNATIONAL APPLICATION (19) World Intellectual Property Organization International Bureau PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) IiiiionolivivivillEviiliololviiiilviviiEmolivimovois (10) International Publication Number WO 2019/032612 Al (43) International Publication Date 14 February 2019 (14.02.2019) WIPO I PCT (51) International Patent Classification: (72) Inventors; and A61K 31/711 (2006.01) A61K 31/7125 (2006.01) (71) Applicants (for US only): VARGEESE, Chandra A61K 31/712 (2006.01) C12N 15/113 (2010.01) [US/US]; c/o WAVE LIFE SCIENCES LTD., 733 Concord (21) International Application Number: PCT/US2018/045659 Avenue, Cambridge, Massachusetts 02138 (US). ZHONG, Zhong [US/US]; c/o WAVE LIFE SCIENCES LTD., 733 Concord Avenue, Cambridge, Massachusetts 02138 (US). IWAMOTO, Naoki [JP/US]; c/o WAVE LIFE (22) International Filing Date: SCIENCES LTD., 733 Concord Avenue, Cambridge, Mass- 07 August 2018 (07.08.2018) achusetts 02138 (US). ZHANG, Jason Jingxin [US/US]; (25) Filing Language: English c/o WAVE LIFE SCIENCES LTD., 733 Concord Avenue, Cambridge, Massachusetts 02138 (US). DODART, Jean- English (26) Publication Language: Cosme [US/US]; c/o WAVE LIFE SCIENCES LTD., 733 (30) Priority Data: Concord Avenue, Cambridge, Massachusetts 02138 (US). 62/542,778 08 August 2017 (08.08.2017) US LIU, Yuanjing [CN/US]; c/o WAVE LIFE SCIENCES LTD., 733 Concord Avenue, Cambridge, Massachusetts (71) Applicant: WAVE LIFE SCIENCES LTD. [SG/SG]; 7 02138 (US). KANDASAMY, Pachamuthu [CA/US]; c/ Straits View #12-00, Marina One East Tower, Singapore o WAVE LIFE SCIENCES LTD., 733 Concord Avenue, 018936 (SG). Cambridge, Massachusetts 02138 (US). DIVAKARA- (54) Title: OLIGONUCLEOTIDE COMPOSITIONS AND METHODS THEREOF FIG. 4 mRNA Vi V3 V2 Pa Ioaical allele PGGGCC)30+ lb 2 34 5 6 7 8 91011 ViDet—E}Filia arefl—OH-Eli11-14-414 V3 Det -- EN - 00 - 4} - 04÷00 MUM Vi vs V2 Era min 81111111111111IM V2 13-EIHEHHHHO Pathological b V1 /Y3 + intronl ace Stabilized in tron 1 4 AS RNA Almi— acts I~tItII IIt (57) : Among other things, the present disclosure provides oligonucleotides, compositions, and methods thereof. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., knockdown ability, stability, delivery, etc. In some embodiments, the oligonucleotides decrease the expression, activity and/or level of a C9orf72 gene, including but not limited to, one comprising a repeat expansion, or a gene product thereof. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions, for example, in treatment of C9orf72-related disorders. [Continued on next page] Healthy allele NAM VIII WO 2019/032612 Al MIDEDIMOMOIDEIROM010101110010HEMOHHIMEMOIMIE MENON, Sethumadhavan [IN/US]; c/o WAVE LIFE SCIENCES LTD., 733 Concord Avenue, Cambridge, Mass- achusetts 02138 (US). LU, Genliang [US/US]; c/o WAVE LIFE SCIENCES LTD., 733 Concord Avenue, Cambridge, Massachusetts 02138 (US). MARAPPAN, Subramanian [US/US]; c/o WAVE LIFE SCIENCES LTD., 733 Concord Avenue, Cambridge, Massachusetts 02138 (US). (74) Agent: LI, Xiaodong et al.; Choate, Hall & Stewart LLP, Two International Place, Boston, Massachusetts 02110 (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, 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 applicant's entitlement to apply for and be granted a patent (Rule 4.17(ii)) Published: — with international search report (Art. 21(3))