Patent SG-11201407337Q-A (SG)
Title: Cyclodextrin complexation methods for formulating peptide proteasome inhibitors
Inventor: LEWIS EVAN
IPC: A61K47/40
Filed: 2013-05-08
Abstract: (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 14 November 2013 (14.11.2013) WIPOIPCT (10) International Publication Number WO 2013/169897 A1 (51) International Patent Classification: A61K 47/40 (2006.01) (21) International Application Number: (22) International Filing Date: (25) Filing Language: (26) Publication Language: PCT/US2013/040127 8 May 2013 (08.05.2013) English English (30) Priority Data: 61/644,122 61/777,475 8 May 2012 (08.05.2012) US 12 March 2013 (12.03.2013) US (71) Applicant: ONYX THERAPEUTICS, INC. [US/US]; 249 E. Grand Avenue, South San Francisco, California 94080 (US). (72) Inventors: LEWIS, Evan; 631 Miller Ave, Pacifica, Cali­ fornia 64044 (US). SHWONEK, Peter; 436 Capistrano Ave, San Francisco, California 94112 (US). DALZIEL, Sean; 400 Beale Street, Apt. 1901, San Francisco, Califor­ nia 64105 (US). JUMAA, Mouhannad; 363 Catamaran St, Foster City, California 94404 (US). (74) Agent: KENDALL, John T.; Fish & Richardson, P.C., P.O. Box 1022, Minneapolis, Minnesota 55440-1022 (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, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, 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, 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, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, [Continued on next page] (54) Title: CYLODEXTRIN COMPLEXATION METHODS FOR FORMULATING PEPTIDE PROTEASOME INHIBITORS OR 2 O r>^ VAVYV* (57) Abstract: This disclosure provides methods for formulating compositions comprising one or more peptide proteasome inhibitors and a cyclodextrin, particularly a substituted cyclodextrin. As well as cyclodextrin complexation methods of formulating peptide pro a - teasome inhibitor (e.g., a compound of formula (1) (5) - or a pharmaceutical^ acceptable salt thereof) with one or more cyclodextrins. Such methods substantially increase the solu­ bility and stability of these proteasome inhibitors and facilitate both their manufacture and administration. For example, homogenous solutions of a compound of formula (5) (car- filzomib) can be obtained at a pharmaceutically useful pH (e.g., about 3.5) and at higher concentrations (e.g., about 5 mg/mL) than could be obtained without one or more cyclodex­ trins and the processes of complexation between the compound and one or more cyclodex­ trins provided herein. R' O R R J O R\" O R 5 0 R 7 O l> 0\ 00 0\ i-H en i-H o CJ o & WO 2013/169897 A11 lllll llllllll II llllll III lllll lllll III III III lllll lllll lllll lllll lllll llll llll lllllll llll llll TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, Pu 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, ML, MR, NE, SN, TD, TG). 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 of receipt of amendments (Rule 48.2(h))