INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 13 September 2018 (13.09.2018) WIP0 I PCT ill~~~~~~~~ 0111111010VIIIOH oI0 VIIIVIIIOH0111010u Oil m° oimIE (10) International Publication Number WO 2018/162517 Al (51) International Patent Classification: C07K 16/00 (2006.01) C12N 15/67(2006.01) C07K 16/46 (2006.01) C12N 15/85 (2006.01) (21) International Application Number: PCT/EP2018/055532 (22) International Filing Date: 07 March 2018 (07.03.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 17160415.0 10 March 2017 (10.03.2017) EP (71) Applicant (for all designated States except JO, US): F. HOFFMANN-LA ROCHE AG [CH/CH]; Grenzacher- strasse 124, 4070 Basel (CH). (71) Applicant (for US only): HOFFMANN-LA ROCHE INC. [US/US]; Great Notch, 150 Clove Road, 8th Floor, Little Falls, New Jersey 07424 (US). (72) Inventors: SEEBER, Stefan; c/o Roche Diagnos- tics GmbH, Nonnenwald 2, 82377 Penzberg (DE). GOEPFERT, Ulrich; c/o Roche Diagnostics GmbH, Non- nenwald 2, 82377 Penzberg (DE). OSTERLEHNER, An- drea; c/o Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg (DE). KETTENBERGER, Hubert; c/o Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg (DE). PAUL, Wolfgang; c/o Roche Diagnostics GmbH, Nonnen- wald 2, 82377 Penzberg (DE). (74) Agent: SKOLAUT, Alexander et al.; Roche Diagnostics GmbH, Patent Department (LPP 6164), P.O.Box 11 52, 82372 Penzberg (DE). (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, (54) Title: METHOD FOR PRODUCING MULTISPECIFIC ANTIBODIES Figure 1D Re l. a bu ndance —> 100 90 80 70 60 50 40 30 20 10 0 N 00 O C 2800 3000 3020 3040 3060 3080 3100 3120 mh-> (57) : Herein are provided a method for producing a multispecific antibody comprising the steps of providing a mammalian cell expressing the antibody, transfecting said mammalian cell with an expression vector comprising an expression cassette encoding a polypeptide of the antibody that has a domain crossover, cultivating the transfected cell and recovering the antibody from the cell or the cultivation medium and thereby producing the multispecific antibody. [Continued on next page] WO 2018/162517 Al MIDEDIMOMOIDEIREEMOMOHIMOMMERMIS 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). Declarations under Rule 4.17: of inventorship (Rule 4.17(iv)) Published: — with international search report (Art. 21(3))
METHOD FOR PRODUCING MULTISPECIFIC ANTIBODIES