SG11201901081XA - Process for the preparation of highly concentrated liquid formulations containing biomolecules - Google Patents

Abstract

INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property 1#1110111101110101011111 3E1 0 0111E11 0011111101011111110 1111 011 Organization International Bureau (10) International Publication Number (43) International Publication Date ......0\" WO 2018/033482 Al 22 February 2018 (22.02.2018) WIP0 I PCT (51) International Patent Classification: MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, CO7K 1/34 (2006.01) TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). (21) International Application Number: PCT/EP2017/070423 Published: (22) International Filing Date: — with international search report (Art. 21(3)) 11 August 2017 (11.08.2017) — with sequence listing part of description (Rule 5.2(a)) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 16184502.9 17 August 2016 (17.08.2016) EP (71) Applicant: BOEHRINGER INGELHEIM INTER- NATIONAL GMBH [DE/DE]; Binger Str. 173, 55216 In- gelheim am Rhein (DE). (72) Inventors: GARIDEL, Patrick; Binger StraBe 173, 55216 Ingelheim am Rhein (DE). BAHRENBURG, Sven; Binger StraBe 173, 55216 Ingelheim am Rhein (DE). SCHULTZ- — FADEMRECHT, Torsten; Binger StraBe 173, 55216 Ingelheim am Rhein (DE). EIPERLE, Andrea; Binger — StraBe 173, 55216 Ingelheim am Rhein (DE). = Agent: HOFER, Friederike; Dreikoniggasse 10, 89073 = (74) Ulm (DE). Designated States (unless otherwise indicated, for every = (81) 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. = = Designated States (unless otherwise indicated, for every (84) = 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, = Title: PROCESS FOR THE PREPARATION OF HIGHLY CONCENTRATED LIQUID FORMULATIONS CONTAINING (54) 1-1 BIOMOLECULES (57) : It is disclosed an improved multi-step process for the preparation of a highly concentrated liquid formulation containing ei biomolecules comprising the steps of (a) a first ultrafiltration UF1; (b) a first diafiltration DF 1; (c) a second diafiltration DF2; and (d) WD a second ultrafiltration UF2; wherein an aqueous solution of one or more salts, medium B, is used for step (b) and water or an as liquid 71' M aqueous solution of one or more salts, as liquid medium C, is used for step (c), wherein the one or more salts used for step (b) are the fr) same or different from the one or more salts used for step (c) and wherein the liquid medium B has an ionic strength which is higher 5.\"_. :, : : than the ionic strength of the liquid medium C. The process according to the present invention allows the preparation of well-defined Ot highly concentrated formulations containing biomolecules, particularly proteins, intended for pharmaceutical or non-pharmaceutical 1-1 c:::: , use. Unwanted excipient(s) of the starting liquid biomolecule formulation, may be reduced under solution conditions, to very low levels N or levels lower than the detection limit. C