Patent SG-11201810777W-A (SG)
Title: Purification of multispecific antibodies
Inventor: GIESE GLEN SCOTT
IPC: C07K1/18
Filed: 2017-06-16
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 21 December 2017 (21.12.2017) WIP0 I PCT Iiiimmonits Hommiololinomolluoill (10) International Publication Number WO 2017/218977 A3 (51) International Patent Classification: CO7K 1/18 (2006.01) C07K 16/06 (2006.01) CO7K 1/22 (2006.01) C07K 16/22 (2006.01) (21) International Application Number: PCT/US2017/038007 (22) International Filing Date: 16 June 2017 (16.06.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/351,908 17 June 2016 (17.06.2016) US (71) Applicant (for all designated States except AL, AT, BA, BE, BG, CH, CN, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IN, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR): GENENTECH, INC. [US/US]; 1 Dna Way, South San Francisco, CA 94080-4990 (US). (71) Applicant (for all designated States except AM, AZ, BF, BJ, BW, BY, CF, CG, CI, CM, GA, GH, GM, GN, GQ, GW, KE, KG, KM, KZ, LR, LS, MD, ML, MR, MW, MZ, NA, NE, RU, RTY, SD, SL, S1V, ST, SZ, TD, TG, TJ, TM, TZ, UG, ZM, ZW): F. HOFFMANN LA-ROCHE AG [CH/CH]; Grenzacher- strasse 124, 4070 Basel (CH). (72) Inventors: GIESE, Glen; c/o Genentech, Inc., 1 Dna Way, South San Francisco, CA 94080 (US). ROSENBERG, Eva; c/o F. Hoffmann La-Roche AG, Grenzacherstrasse 124, 4070 Basel (CH). SALLIER, Bernard; c/o F. Hoff- mann La-Roche AG, Grenzacherstrasse 124, 4070 Basel (CH). KONRAD, Susanne; c/o F. Hoffmann La-Roche AG, Grenzacherstrasse 124, 4070 Basel (CH). KOEHN- LEIN, Wolfgang; c/o F. Hoffmann La-Roche AG, Gren- zacherstrasse 124, 4070 Basel (CH). WILLMANN, St- effen; c/o F. Hoffmann La-Roche AG, Grenzacherstrasse 124, 4070 Basel (CH). BIALAS, Agathe; c/o F. Hoffmann La-Roche AG, Grenzacherstrasse 124, 4070 Basel (CH). KALEAS, Kimberly; c/o Genentech, Inc., 1 Dna Way, South San Francisco, CA 94080 (US). YIGZAW, Yinges; c/o Genentech, Inc., 1 Dna Way, South San Francisco, CA 94080 (US). (54) Title: PURIFICATION OF MULTISPECIFIC ANTIBODIES FIG. 1 A. aX1 (knob) aY1 (hole) • If protein A capture chromatography (bind and elute mode) 1 protein A capture chromatography (bind and elute mode) N N cc N O C assemble purified aX1 and aY1 to form aX1/Y1 bispecific Ab multimodal cation exchange chromatography (bind and elute mode) 4, multimodal anion exchange chromatography (flow through mode) (57) : The present invention provides methods of purifying multispecific antibodies. The methods comprise the sequential steps of performing a capture chromatography, a first mixed mode chromatography and a second mixed mode chromatography. In some aspects, the invention provides compositions of multispecific antibodies, which compositions have reduced levels of one or more product-specific impurities and/or process-specific impurities. [Continued on next page] WO 2017/218977 A3 MIDEDIMOMOIDEIRMEMOOlilliOROBERE# (74) Agent: ONUFRYK, Christina et al.; Morrison & Foerster LLP, 755 Page Mill Road, Palo Alto, CA 94304-1018 (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, 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. (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, 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, 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, KM, ML, MR, NE, SN, TD, TG). 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 of receipt of amendments (Rule 48.2(h)) with sequence listing part of description (Rule 5.2(a)) (88) Date of publication of the international search report: 18 January 2018 (18.01.2018)