Patent SG-11201803911P-A (SG)
Title: Encapsulation of ultra-stable insulin analogues with polymer melts
Inventor: WEISS MICHAEL
IPC: C07K14/62
Filed: 2016-12-23
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property -' Organization International Bureau res., 00) (43) International Publication Date .... ..sr ,„„..) 29 June 2017(29.06.2017) WIPO I PCT II (10) 11111111111111111111 WO International IIIIIIIIII II III 2017/112952 III Publication IIIIIIIIIIIIIII IIIII IIII Number Al RIO IIII IIIIIIII (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A61K 38/28 (2006.01) C07K 14/62 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, A61K 47/30 (2006.01) A61P 3/10 (2006.01) 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, (21) International Application Number: KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, PCT/US2016/068572 MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, (22) International Filing Date: NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, 23 December 2016 (23.12.2016) 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, (25) Filing Language: English ZA, ZM, ZW. (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 62/387,459 23 December 2015 (23.12.2015) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, (71) Applicant: CASE WESTERN RESERVE UNIVER- TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, SITY [US/US]; 10900 Euclid Avenue, Cleveland, Ohio DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, 44106 (US). 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, (72) Inventors: WEISS, Michael; 70 Woodburn Drive, More- land Hills, Ohio 44022 (US). POKORSKI, Jon; 1881 E. GW, KM, ML, MR, NE, SN, TD, TG). 119th Street, Cleveland, Ohio 44106 (US). Published: (74) Agents: CUNNIFF, John J. et al.; Hahn Loeser and Parks — with international search report (Art 21(3)) LLP, 200 Public Square, Suite 2800, Cleveland, Ohio before the expiration of the time limit for amending the 44114 (US). claims and to be republished in the event of receipt of Designated States indicated, amendments (Rule 48.2(h)) (81) (unless otherwise for every kind of national available): AE, AG, AL, AM, protection _ with sequence listing part of description (Rule 5.2(a)) Title: ENCAPSULATION OF ULTRA INSULIN ANALOGUES WITH POLYMER MELTS (54) -STABLE (57) : An insulin composition comprises an in- sulin analogue and polymer blend. The insulin analogue P 0C l ' ye contains cysteine substitutions at positions B4 and A10 foiin B4 (to cystine -A10), and one or more additional from substitutions selected the group consisting of: a ( connecting domain of 5-11 amino acids between insulin A- and B domains; a non-beta-branched amino-acid substitution at position A8; a non-beta-branched acidic , SEC/ ID NO.1 or polar side chain at position A14; a halogenic modi- fication PheB24 of at the ortho position; and substitu- tion of lysine at position B29 by Glu, Ala, Val, Ile, Leu, amino-propionic acid, amino-butryic acid, or Norleu- --‘ 0 - , '26 .,. . -. The insulin is JO cine. analogue compatible with a process WH2 n E hi • V = includes '' = F of manufacture that one or more steps within -: f 1 the temperature range 90-120 oC. The encapsulated in- \ t., (R. sulin analogue may optionally contain free PEG or be PEGylated. The insulin analogue-encapsulated polymer --\ blend may be cast as a microneedle patch for topical ad- Il ministration or as micropellets for subcutaneous injec - .4t el Fit un (PFROR 0\ PAW N 1-1 1-1 It -- - 1-1 C N ART) NSULIN PIA tion. O