Patent SG-11201810210U-A (SG)
Title: Engineered botulinum neurotoxins
Inventor: ZHANG SICAI
IPC: A61K38/48
Filed: 2017-06-08
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization 111111111111111111111111111111111111111111111111111111111111111111111111111111111111 International Bureau (10) International Publication Number (43) International Publication Date .....0\"\" WO 2017/214447 Al 14 December 2017 (14.12.2017) WIP0 I PCT (51) International Patent Classification: (74) Agent: EL-HAYEK, Roque; Wo1f, Greenfield & Sacks, C07K 14/33 (2006.01) A61K 38/48 (2006.01) P.c., 600 Atlantic Avenue, Boston, MA 02210-2206 (US). A61K 38/00 (2006.01) (81) Designated States (unless otherwise indicated, for every (21) International Application Number: PCT/US2017/036628 kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, (22) International Filing Date: 08 June 2017 (08.06.2017) 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, (25) Filing Language: English KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, (26) Publication Language: English 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, (30) Priority Data: SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, 62/347,579 08 June 2016 (08.06.2016) US TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (71) Applicant. CHILDREN'S MEDICAL CENTER COR- (84) Designated States (unless otherwise indicated, for every PORATION [US/US]; 55 Shattuck Street, Boston, MA kind of regional protection available): ARIPO (BW, GH, 02115 (US). GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, (72) Inventor; and UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, (71) Applicant: STENMARK, Paul [SE/SE]; Svantearrhenius- EE, ES, FL FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, — vag 16c, 10691 Stockholm (SE). MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, Inventors: ZHANG, Sicai; En 1070, 300 Longwood Ave, (72) TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, = Boston, MA (US). DONG, Min; 12 Croft Lane, Weatogue, CT 06089 (US). KM, ML, MR, NE, SN, TD, TG). = Title: ENGINEERED BOTULINUM NEUROTOXINS (54) = (57) : Disclosed herein are modified Clostridial Botulinum neurotoxin (BoNT) polypep- 3 tides with a modified receptor binding domain of Clostridial Botulinum serotype B, compris- = — ing one or more substitution mutations at positions corresponding 1248 or 1249 in serotype B, Z strain 1. Specific substitution mutations include I1248F, I1248Y, I1248H, I1248W, V1249W, = g g. V1249F, V1249Y, V1249H, I1248WN1249F, I1248WN1249Y, I1248WN1249H, I1248F/ = = = 1 V1249Y, I1248FN1249H, I1248YN1249H, I1248F/V1249W, I1248YN1249W, I1248H/ bind i V 1249W, I1248Y/V1249F, I1248H/V1249F, or I1248HN1249Y. Other substitution mutations are = = also disclosed. Isolated modified receptor binding domains, chimeric molecules, pharmaceutical _ total compositions, and methods of using the same are also disclosed. = ..... actin = = FIG. 4A 4 = — = 2 1 — Il Ir ... ' Il ei 4. 1' ‘., IN 4B FIG. P S I ei C [Continued on next page] WO 2017/214447 Al MIDEDIMOMMIDIRMEM001101011101110HOHNEVOIMIE 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 amendments (Rule 48.2(h)) of receipt of