Patent SG-11201906452P-A (SG)
Title: Treatment of mucopolysaccharidosis i with fully-human glycosylated human alpha-l-iduronidase (idua)
Inventor: YOO STEPHEN
IPC: A61K48/00
Filed: 2018-01-30
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 09 August 2018 (09.08.2018) WIPO I PCT o mono °nolo Ho Ho Ho Ho mil Hio oimIE (10) International Publication Number WO 2018/144441 Al (51) International Patent Classification: A61K 38/00 (2006.01) A61P 25/00 (2006.01) A61K 38/43 (2006.01) A61P 25/28 (2006.01) A61K 48/00 (2006.01) Cl 2N 15/09 (2006.01) (21) International Application Number: PCT/US2018/015910 (22) International Filing Date: 30 January 2018 (30.01.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/452,769 31 January 2017 (31.01.2017) US 62/485,655 14 April 2017 (14.04.2017) US 62/529,366 06 July 2017 (06.07.2017) US 62/579,690 31 October 2017 (31.10.2017) US 62/616,234 11 January 2018 (11.01.2018) US (71) Applicant: REGENXBIO INC. [US/US]; 9712 Medical Center Drive, Suite 100, Rockville, MD 20850 (US). = (72) Inventors: YOO, Stephen; 5521 Southwick Street, Bethes- da, MD 20817 (US). REINHARDT, Rickey Robert; 108 Apple Grove Road, Silver Spring, MD 20904 (US). SIM- PSON, Curran Matthew; 2149 Thurston Road, Frederick, MD 21704 (US). WU, Zhuchun; 14716 Soft Wind Drive, North Potomac, MD 20878 (US). (74) Agent: MARTINEK, Sebastian et al.; Jones Day, 250 Vesey Street, New York, NY 10281-1047 (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). (54) Title: TREATMENT OF MUCOPOLYSACCHARIDOSIS I WITH FULLY-HUMAN GLYCOSYLATED HUMAN ALPHA-L- = IDURONIDASE (IDUA) (57) : Compositions and methods are described for the delivery of a fully human-glycosylated (HuGly) ct-L-iduronidase (IDUA) to the cerebrospinal fluid of the central nervous system (CNS) of a human sub- ject diagnosed with mucopolysaccharidosis I (MPS I). W O 20 18/ 144441 Al Iuman Alpha-l-dduronidase (hu:DUA) 4Signal --4Alpha-L-iduronidase 10 10 30 cp 50 M1 , FL?E , RML LALLAS:.. ;A PPVUARAPH LVHVDAARAI WPLRRFWRST 60 T BO 90 _0( GFCPPLPHSQ ADQ1VLSWDQ QLNLAYVGAV PHRGIKQVRT HWI.L.LVTTR L10 i - i0 130 14( .5( GSTGRGISYN FTHLDGYLDL LRENQLLPGF ELNGSASGHF TDFEDKQQVF 160 L70 _90 190 ITO MODIVSSLA RRYIGRYGTA HV(\"MNFETW NEPDHHDFDN \". , SMTMQGP7,N 210 220 230 240 250 YYDACSEGLR AASPALRIGG PGDSFHTPPR SPLSWGLLRH CHDGINFETG !60 '0 !BO J90 10( OAGVPIDYIS LERKGARSSI SILEQEKVVA QQIRQLFPKF ADTP:YYDEA 310 320 330 140 35C D'IVGWSLPQ PWRADVTYAA MNVISVIAQHQ NLLLANTTSA FPYAILSNDN M. 72 req'd fc -- ' .nding & activity 360 370 180 190 40C ATISYHFHPF AQRTLTARFQ VNNTRRPHVQ LLEREV=AM GLLAILUSEQ 410 420 431 440 450 LWAEVSQAGT V1DSNHTVGV LASAHRPQGP ADAWRAAVLT YASDDTRAHP 460 470 430 490 50C NRSVAVTLRL RGVPPGPGLV YVTRYLDNGL CSPDGEWRRI GRPVEPTAEQ Dieu .fide 510 520 30 541 550 FRRMRAALOP 7AAAPRPLPA GGRILLRPAL LPS..LLVHV CARPEEPPGQ Bond 560 570 580 590 60( VIRLRAIPuT QGQLVIVWSD EHVGSKCIWT YE:QFSQIGK A'TPVSREPS 610 6 630 64( 650 TFNLFVFSPD TGAVSGSYRV RALDYWARPG PFSDPVPYLE VPVPRGPPSP GNP N =N-linked glycosylation site (GIcNac...) Y. Y-sulfation site C. Disulfide Bond FIG. 1 [Continued on next page] WO 2018/144441 Al MIDEDIM31010101g0E1010MOIOHOHOHOIMINEVOIMIE Published: — with international search report (Art. 21(3)) with sequence listing part of description (Rule 5.2(a))