SG11201907753TA - Bispecific binding molecules that are capable of binding cd137 and tumor antigens, and uses thereof - Google Patents

Abstract

INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 30 August 2018 (30.08.2018) WIP0 I PCT mu °million °nolo moll loon Mo lio imio oimIE (10) International Publication Number WO 2018/156740 Al (51) International Patent Classification: A61K 39/395 (2006.01) A61P 35/00 (2006.01) (21) International Application Number: PCT/US2018/019188 (22) International Filing Date: 22 February 2018 (22.02.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/463,353 24 February 2017 (24.02.2017) US 62/597,594 12 December 2017 (12.12.2017) US (71) Applicant: MACROGENICS, INC. [US/US]; 9704 Med- ical Center Drive, Rockville, MD 20850 (US). (72) Inventors: LIU, Liqin; 13515 Stonebridge Terrace, Ger- mantown, MD 20874 (US). LAM, Chia-ying, Kao; 6020 Hawkcreek Place, San Jose, CA 95123 (US). DIEDRICH, Gundo; 13409 Bonnie Dale Drive, North Potomac, MD 20878 (US). JOHNSON, Leslie, S.; 14411 Poplar Hill Road, Darnestown, MD 20874 (US). MOORE, Paul, A.; 10 Turley Court, North Potomac, MD 20878 (US). BON- VINI, Ezio; 11136 Power Horn Drive, Potomac, MD 20854 (US). (74) Agent: AUERBACH, Jeffrey, I. et al.; Auerbachschrot LLC, 2200 Research Blvd., Suite 560, Rockville, MD 20850 (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, (54) Title: BISPECIFIC BINDING MOLECULES THAT ARE CAPABLE OF BINDING CD137 AND TUMOR ANTIGENS, AND USES THEREOF 0 5 10 15 20 25 30 35 40 45 Study Day -6- Vehicle - aPD1 (5 mg/kg) - N- TRIDENT-A2 (2.5 mg/kg) - TRIDENT-A2 + TA x CD3 - TA x CD3 (0.01 mg/kg) TRIDENT-A2 + TA x CD3 + aPD1 Figure 29 (57) : The present invention is directed to binding molecules that possess one or more epitope-binding sites specific for an epitope of CD137 and one or more epitope-binding sites specific for an epitope of a tumor antigen (\"TA\") (e.g., a \"CD137 x TA Binding Molecule\"). In one embodiment, such CD137 x TA Binding Molecules will be bispecific molecules, especially bispecific tetravalent diabodies. Alternatively, such CD137 x TA Binding molecules will be bispecific trivalent binding molecules. The CD137 x TA Binding Molecules of the invention are capable of simultaneous binding to CD137, and a TA. The invention is directed to pharmaceutical compositions comprising the CD137 x TA Binding Molecules, methods of using the same to treat cancer and other disease and conditions. The invention also provides novel CD137-binding molecules, and HER2/neu-binding molecules, as well as derivatives thereof and uses thereof. [Continued on next page] WO 2018/156740 Al MIDEDIMOMMIONER131111001MOMOVOIMIE 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))