	US 12,479,915 B2
	Cytotoxicity-inducing therapeutic agent
Shogo Kamikawaji, Kanagawa (JP); Yasuko Kinoshita, Kanagawa (JP); and Shinya Ishii, Singapore (SG)
Assigned to CHUGAI SEIYAKU KABUSHIKI KAISHA, Tokyo (JP)
Filed by Chugai Seiyaku Kabushiki Kaisha, Tokyo (JP)
Filed on May 2, 2023, as Appl. No. 18/310,829.
Application 18/310,829 is a division of application No. 16/957,837, granted, now 11,667,713, previously published as PCT/JP2018/048409, filed on Dec. 28, 2018.
Claims priority of application No. 2017-254279 (JP), filed on Dec. 28, 2017.
Prior Publication US 2024/0150465 A1, May 9, 2024
Int. Cl. A61P 35/00 (2006.01); C07K 16/28 (2006.01)

CPC C07K 16/2809 (2013.01) [A61P 35/00 (2018.01); C07K 16/28 (2013.01); C07K 2317/52 (2013.01); C07K 2317/56 (2013.01)]

31 Claims

1. A method of treating cancer, which comprises administering to a patient in need thereof a multispecific antigen-binding molecule that comprises:

(1) a first domain comprising a first antigen-binding domain that binds to human DLL3, and

(2) a second domain comprising a second antigen-binding domain that binds to T-cell receptor complex,

wherein the first antigen-binding domain comprises any one of (a1) to (a9) below:

(a1) an antibody variable fragment comprising the HVR-H1 sequence of SEQ ID NO: 27, the HVR-H2 sequence of SEQ ID NO: 28, the HVR-H3 sequence of SEQ ID NO: 29, the HVR-L1 sequence of SEQ ID NO: 30, the HVR-L2 sequence of SEQ ID NO: 31, and the HVR-L3 sequence of SEQ ID NO: 32;

(a2) an antibody variable fragment comprising the HVR-H1 sequence of SEQ ID NO: 33, the HVR-H2 sequence of SEQ ID NO: 34, the HVR-H3 sequence of SEQ ID NO: 35, the HVR-L1 sequence of SEQ ID NO: 36, the HVR-L2 sequence of SEQ ID NO: 37, and the HVR-L3 sequence of SEQ ID NO: 38;

(a3) an antibody variable fragment comprising the HVR-H1 sequence of SEQ ID NO: 39, the HVR-H2 sequence of SEQ ID NO: 40, the HVR-H3 sequence of SEQ ID NO: 41, the HVR-L1 sequence of SEQ ID NO: 42, the HVR-L2 sequence of SEQ ID NO: 43, and the HVR-L3 sequence of SEQ ID NO: 44;

(a4) an antibody variable fragment comprising the HVR-H1 sequence of SEQ ID NO: 45, the HVR-H2 sequence of SEQ ID NO: 46, the HVR-H3 sequence of SEQ ID NO: 47, the HVR-L1 sequence of SEQ ID NO: 48, the HVR-L2 sequence of SEQ ID NO: 49, and the HVR-L3 sequence of SEQ ID NO: 50;

(a5) an antibody variable fragment comprising the HVR-H1 sequence of SEQ ID NO: 27, the HVR-H2 sequence of SEQ ID NO: 75, the HVR-H3 sequence of SEQ ID NO: 29, the HVR-L1 sequence of SEQ ID NO: 30, the HVR-L2 sequence of SEQ ID NO: 31, and the HVR-L3 sequence of SEQ ID NO: 32;

(a6) an antibody variable fragment comprising the HVR-H1 sequence of SEQ ID NO: 27, the HVR-H2 sequence of SEQ ID NO: 76, the HVR-H3 sequence of SEQ ID NO: 29, the HVR-L1 sequence of SEQ ID NO: 30, the HVR-L2 sequence of SEQ ID NO: 31, and the HVR-L3 sequence of SEQ ID NO: 32;

(a7) an antibody variable fragment comprising the HVR-H1 sequence of SEQ ID NO: 77, the HVR-H2 sequence of SEQ ID NO: 78, the HVR-H3 sequence of SEQ ID NO: 79, the HVR-L1 sequence of SEQ ID NO: 36, the HVR-L2 sequence of SEQ ID NO: 37, and the HVR-L3 sequence of SEQ ID NO: 38;

(a8) an antibody variable fragment comprising the HVR-H1 sequence of SEQ ID NO: 77, the HVR-H2 sequence of SEQ ID NO: 78, the HVR-H3 sequence of SEQ ID NO: 80, the HVR-L1 sequence of SEQ ID NO: 36, the HVR-L2 sequence of SEQ ID NO: 37, and the HVR-L3 sequence of SEQ ID NO: 38; and

(a9) an antibody variable fragment comprising the HVR-H1 sequence of SEQ ID NO: 77, the HVR-H2 sequence of SEQ ID NO: 78, the HVR-H3 sequence of SEQ ID NO: 80, the HVR-L1 sequence of SEQ ID NO: 36, the HVR-L2 sequence of SEQ ID NO: 37, and the HVR-L3 sequence of SEQ ID NO: 81, wherein the cancer expresses DLL3.