Patent SG-11201808941P-A (SG)
Title: Adeno-associated virus vector delivery of micro-dystrophin to treat muscular dystrophy
Inventor: RODINO-KLAPAC LOUISE
IPC: C12N15/86
Filed: 2017-04-14
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2017/181015 Al 19 October 2017 (19.10.2017) WIPO I PCT 111111111111110111011111111111010111110 0111H 0101111101111111111111111110111111 International Patent Classification: Nationwide, Children's Hospital, 700 Children's Drive, A61K 48/00 (2006.01) C07K 14/47 (2006.01) Columbus, OH 43205 (US). A61P 21/00 (2006.01) C12N 15/86 (2006.01) (74) Agents: SINTICH, Sharon, M. et al.; Marshall, Gerstein (51) (21) International Application Number: PCT/US2017/027636 (22) International Filing Date: 14 April 2017 (14.04.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/323,163 15 April 2016 (15.04.2016) US 62/473,253 17 March 2017 (17.03.2017) US (71) Applicant: RESEARCH INSTITUTE AT NATION- WIDE CHILDREN'S HOSPITAL [US/US]; 700 Chil- dren's Drive, Room W172, Columbus, OH 43205 (US). (72) Inventors: RODINO-KLAPAC, Louise; 4912 Bixby Ridge Drive E, Groveport, OH 43125 (US). MENDELL, Jerry, R.; 8176 Copperfield Drive, Columbus, OH 43235 (US). HELLER, Kristin, N.; The Research Institute At & Boron 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, 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, 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, [Continued on next page] (54) Title: ADENO-ASSOCIATED VIRUS VECTOR DELIVERY OF MICRO-DYSTROPHIN TO TREAT MUSCULAR DYS- TROPHY Figure 1 (57) : The invention provides for recombinant AAV vectors comprising a miniaturized human micro-dystrophin gene and methods of using the recombinant vectors to reduce or prevent fibrosis in subjects suffering from muscular dys- trophy. scAANit.74.CMV.WR29c SEQ ID NO: 2: miR-29C IN A miR-30 BACKBONE (1(11'101(0(y(gaggrItst(AtatocafflatC(FITI)CCTGCACATCTTGGANACACTFGCT(;(;(ATTACT II \"I 1 CAGGrTAAI 11'NACIGAAGGCTCGAGAAGGTATATTGCTGITGACAGIGAGCGCAACCGA ITT( NT.QCFC.( rtc. , , T .TCTACCACCATTTC. ARTCCGTTAMMFAM iKASAUAIRAAUWAX1ACIIIAUSAGUAT1AMISAIIACAAAAICWAA1ACCOLUCIA IEICELMALVArAGGCCGG€C cut site (restriction site) miR - .39.hachbone de - ei stein loop (EWA 41'1'('ACACATG: SF() V) NO. 1.1 ni11-29c target (sense) strand (ACCGATTTEMATGETECTAGA; SEQ ID NO:3)) 1ri12-29e guidelantisenseJ strand LICTACCACCATTTGA(IATCGCTI4LSEQ ID NO: 4j Predicted hairpin structure (SEQ ID N0,6) G UTICA A C - --U CUG CAGUG GCG AACCGAUUUCAAAUGGUGCUAGA GUG A I III 11111 III 1 11111111111 III - - -A GGC GUCAU CGU UUGGCUAAAGUUUACCACGAUCU CAC G A UCC C A GUAGA C W O 20 17 / 18 10 15 Al miR-29C miR-30a shRNA-miR(luc) ggc acc Ca agatanalatac Captor. cagag 11111111111 III11111111 (Milli 11111 u aaCggegasag accacga paaga mu mu 12 a liC gag cuacaaacaucc gaccagaagau pug a 111 111111111111 11111111111 111 cc, gacculluguagg cugacaumagg can g Mika c Moshe Dicer WO 2017/181015 Al 1#11101MOIMEIMMEMOMIIIMMIIMOIMOVOIS DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, Published: LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, with international search report (Art. 21(3)) GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). with sequence listing part of description (Rule 5.2(a))