Patent SG-11201407512V-A (SG)
Title: High-concentration monoclonal antibody formulations
Inventor: ARMSTRONG NICHOLAS J
IPC: A61K9/10
Filed: 2013-05-17
Abstract: (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 21 November 2013 (21.11.2013) WIPOIPCT (10) International Publication Number WO 2013/173687 Al (51) International Patent Classification: A61K 9/00 (2006.01) A61K 9/16 (2006.01) A61K 9/10 (2006.01) (21) International Application Number: PCT/US2013/041532 (22) International Filing Date: 17 May 2013 (17.05.2013) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 61/649,146 18 May 2012 (18.05.2012) US (71) Applicant: GENENTECH, INC. [US/US]; 1 Dna Way, South San Francisco, California 94080 (US). (72) Inventors: ARMSTRONG, Nicholas J.; c/o Genentech, Inc., 1 DNA Way, South San Francisco, California 94080 (US). BOWEN, Mayumi N.; c/o Genentech, Inc., DNA 1 Way, South San Francisco, California 94080 (US). MAA, Yuh-Fun; c/o Genentech, Inc., 1 DNA Way, South San Francisco, California 94080 (US). (74) Agents: LEE, Wendy M. et al.; GENENTECH, INC., Mail Stop 49, South San Francisco, California 94080 (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. [Continued on next page] (54) Title: HIGH-CONCENTRATION MONOCLONAL ANTIBODY FORMULATIONS l> 00 m i> w o o w > 250 200 0 a un 01 13 150 Q? o 100 50 o Bevadzumab Suspension (Pilot Scale) * Bevaoizumab Suspension Suspension Suspension (Bench-Top) o o o Trastuzumab Suspension (Pilot Scale) Scale) Scale) • Trastuzumab Suspension (Bench-Top) A A A Rituximab Suspension Suspension Suspension (Pilot Scale) & & & Rituximab Suspension Suspension Suspension (Bench-Top) - - - - - - - Theoretical Fitting Equation Fitting Equation Fitting Equation of of of 4 4 4 • Bevacizumab Liquid --J --J --J H H H Trastuzumab Liquid & & & Rituximab Liquid —— Empirical Fitting o Bevadzumab Suspension (Pilot Scale) * Bevaoizumab (Bench-Top) Trastuzumab Suspension (Pilot • Trastuzumab Suspension (Bench-Top) Rituximab (Pilot Scale) Rituximab (Bench-Top) - Theoretical • Bevacizumab Liquid Trastuzumab Liquid Rituximab Liquid —— Empirical Fitting & 0 o Bevadzumab Suspension (Pilot Scale) * Bevaoizumab (Bench-Top) Trastuzumab Suspension (Pilot • Trastuzumab Suspension (Bench-Top) Rituximab (Pilot Scale) Rituximab (Bench-Top) - Theoretical • Bevacizumab Liquid Trastuzumab Liquid Rituximab Liquid —— Empirical Fitting O S3 & 8 A * • / & y = 6.2464e° 013 ^5 « ihrtrv- - - A sn «* ^ £3 & .I\" 50 100 150 200 250 mAb Concentration (mg/mL) (57) Abstract: The present application discloses high- concentration monoclonal antibody formulations suit­ able for subcutaneous administration, e.g. via a pre- filled syringe. In particular, it discloses a formulation comprising a spray dried monoclonal antibody at a con­ centration of about 200 mg/mL or more suspended in a non-aqueous suspension vehicle where the viscocity of the suspension vehicle is less than about 20 centipoise. Also disclosed are: a subcutaneous administration device with the formulation therein, a method of making the formulation, a method of making an article of manu­ facture comprising the suspension formulation, use of the formulation in the preparation of medicament, and a a method of treating patient with a the formulation. 300 FIG. 2 WO 2013/173687 Al I lllll llllllll II llllll III lllll lllll III III III lllll lllll lllll llll lllll lllll llll lllllll llll llll (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, 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, ML, MR, NE, SN, TD, TG). Published: — with international search report (Art. 21(3)) — with sequence listing part of description (Rule 5.2(a))