SG11201804166YA - Materials and methods for treatment of titin-based myopathies and other titinopaties - Google Patents

Abstract

INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau 111111111M 11111111111111111111111111111111111111111111111111111111111111R111111111111111 (10) International Publication Number WO 2017/087395 Al WIPO I PCT (43) International Publication Date 26 May 2017 (26.05.2017) 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, 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, 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)) with sequence listing part of description (Rule 5.2(a)) (51) International Patent Classification: A61K 9/00 (2006.01) A61K 48/00 (2006.01) A61K 38/46 (2006.01) (21) International Application Number: PCT/US2016/062052 (22) International Filing Date: 15 November 2016 (15.11.2016) Filing Language: English (25) (26) (30) English Publication Language: Priority Data: 62/255,887 16 November 2015 (16.11.2015) US (71) Applicant: RESEARCH INSTITUTE AT NATION- WIDE CHILDREN'S HOSPITAL [US/US]; 700 Chil- dren's Drive, Room W172, Cumbus, OH 43205 (US). (72) Inventors: RODINO-KALAPAC, Louise; 4912 Bixby Ridge Drive, E. Groveport, OH 43125 (US). POTTER, Rachael; 7467 Achill Dr., Dublin, OH 43017 (US). (74) Agent: NOLAND, Greta, E.; Marshall, Gerstein & Dorun LLP, 233 S.wacker Drive, 6300 Willis Tower, Chicago, IL 60606-6357 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, (54) Title: MATERIALS AND METHODS FOR TREATMENT OF TITIN-BASED MYOPATHIES AND OTHER TITINO - PATIES I-band M-line A-band se - Nebulin 5,55.5, 555 2.S.S... 5 . 5 £ < 1.1 ye/ a -Actinin Myosin TacLTITV., ;, , a,Nrawo:u Actin Thin Filament \"Titan domain: tee N2 -B AM. PEVK eras* N2-A o kinase domain (TK) 5 FIGURE 1A I-band region A-band region M-line region a y co ro EnIENIMEECOOH Myosin MyBPC Calpan-1 -0-crystalin oactinin HSP27 Nebulin „I m P D P I r sirl -FHL1 Filamin c uuscunn -DRAUFHL2 sAnk 1 PKG T-cap/Tolothonin -PKA Z-disk region 1 6.1 illnailnlkillSignigliinigniniainnilinn 013-crYstalin S100A1 HSP27 Actin Smyd2-mHSP90 Nebulin i C g ain3/p94 -Calpain-1 -Tropomyosin MARPs: CARP nig-like domain /Z-repeat 1PEVK element _Protein binding site DARR IFN3 domain X12-bus finterdoman section Kinase domain I. Ankrd-2/arpp W O 20 17 /087 395 Al i m - yi tcunn -L Lamm CalpainMp94 M B i r itiein -Mvmesin ca gt ir rL2 Nbr1Ip62 MUR I FT F-I FIGURE 113 (57) : The present application provides materials and methods for treating a patient with a titin-based myopathy, particu- larly a titin-based cardiomyopathy, and/or other titinopathy. In addition, the present application provides materials and methods for editing the titin gene in a cell by genome editing.