0 11 mutant IL-2 polypeptide variable domain constant domain Fc domain 1-1 o r cc 00 O O (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 11 October 2018 (11.10.2018) WIPO I PCT onion °nolo moimmiinimiflo oimIE (10) International Publication Number WO 2018/184964 Al (51) International Patent Classification: C07K 14/55 (2006.01) C07K 16/28 (2006.01) A61K 38/20 (2006.01) A61K 39/00 (2006.01) (21) International Application Number: PCT/EP2018/058034 (22) International Filing Date: 29 March 2018 (29.03.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 17164533.6 03 April 2017 (03.04.2017) EP (71) Applicant (for all designated States except US): F. HOFF- MANN-LA ROCHE AG [CH/CH]; Grenzacherstrasse 124, 4070 Basel (CH). (71) Applicant (for US only): HOFFMANN-LA ROCHE INC. [US/US]; Overlook at Great Notch, 150 Clove Road, 8th Floor, Suite 8 - Legal Department, Little Falls, New Jer- sey 07424 (US). (72) Inventors: CODARRI DEAK, Laura; c/o Roche Glycart AG, Wagistrasse 10, 8952 Schlieren (CH). KLEIN, Chris- tian; c/o Roche Glycart AG, Wagistrasse 10, 8952 Sch- lieren (CH). LAUENER, Laura; c/o Roche Glycart AG, Wagistrasse 10, 8952 Schlieren (CH). NICOLINI, Valeria G.; c/o Roche Glycart AG, Wagistrasse 10, 8952 Schlieren (CH). SEEBER, Stefan; Mitterweg 2, 82404 Sindelsdorf (DE). UMASTA, Pablo; c/o Roche Glycart AG, Wagistrasse 10, 8952 Schlieren (CH). WALDHAUER, Inja; c/o Roche Glycart AG, Wagistrasse 10, 8952 Schlieren (CH). (74) Agent: KASCHAU, Nikolai; Grenzacherstrasse 124, 4070 Basel (CH). (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: IMMUNOCONJUGATES OF AN ANTI-PD-1 ANTIBODY WITH A MUTANT IL-2 OR WITH IL-15 Figure 1 (57) : The present invention generally relates to immunoconjugates, particularly immunoconjugates comprising a mutant interleukin-2 polypeptide and an antibody that binds to PD-1. In addition, the invention relates to polynucleotide molecules encoding the immunoconjugates, and vectors and host cells comprising such polynucleotide molecules. The invention further relates to methods for producing the mutant immunoconjugates, pharmaceutical compositions comprising the same, and uses thereof. [Continued on next page] WO 2018/184964 Al MIDEDIMOMOIDEIREEMOMOHMOIEIHNHIMMI 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)) — with sequence listing part of description (Rule 5.2(a))
IMMUNOCONJUGATES OF AN ANTI-PD-1 ANTIBODY WITH A MUTANT IL-2 OR WITH IL-15