US 12,479,929 B2
Cytotoxicity-inducing therapeutic agent
Junichi Nezu, Shizuoka (JP); Takahiro Ishiguro, Kanagawa (JP); Atsushi Narita, Shizuoka (JP); Akihisa Sakamoto, Shizuoka (JP); Yumiko Kawai, Kanagawa (JP); Tomoyuki Igawa, Shizuoka (JP); and Taichi Kuramochi, Shizuoka (JP)
Assigned to Chugai Seiyaku Kabushiki Kaisha, Tokyo (JP)
Filed by Chugai Seiyaku Kabushiki Kaisha, Tokyo (JP)
Filed on Mar. 20, 2024, as Appl. No. 18/611,460.
Application 18/611,460 is a division of application No. 18/590,651, filed on Feb. 28, 2024.
Application 18/590,651 is a division of application No. 17/367,909, filed on Jul. 6, 2021.
Application 17/367,909 is a division of application No. 13/990,088, granted, now 11,066,483, issued on Jul. 20, 2021, previously published as PCT/JP2011/077603, filed on Nov. 30, 2011.
Claims priority of application No. 2010-266760 (JP), filed on Nov. 30, 2010; application No. 2011-121771 (JP), filed on May 31, 2011; and application No. 2011-238818 (JP), filed on Oct. 31, 2011.
Prior Publication US 2024/0262933 A1, Aug. 8, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/46 (2006.01); C07K 16/28 (2006.01); C07K 16/30 (2006.01); A61K 39/00 (2006.01)
CPC C07K 16/46 (2013.01) [C07K 16/2809 (2013.01); C07K 16/2863 (2013.01); C07K 16/30 (2013.01); C07K 16/303 (2013.01); A61K 2039/505 (2013.01); C07K 2317/31 (2013.01); C07K 2317/35 (2013.01); C07K 2317/41 (2013.01); C07K 2317/52 (2013.01); C07K 2317/55 (2013.01); C07K 2317/56 (2013.01); C07K 2317/60 (2013.01); C07K 2317/622 (2013.01); C07K 2317/64 (2013.01); C07K 2317/71 (2013.01); C07K 2317/73 (2013.01); C07K 2317/94 (2013.01); C07K 2319/00 (2013.01); C07K 2319/30 (2013.01)] 21 Claims
 
1. An antibody that comprises:
a first polypeptide chain comprising a first light chain variable region (VL) and a first heavy chain constant region, wherein the first heavy chain constant region is a non-wild-type heavy chain constant region comprising the sequence of SEQ ID NO: 23 with one or more amino acid substitutions, and wherein the first VL associates with a first heavy chain variable region (VH) to form a first antigen-binding domain that binds to CD3;
a second polypeptide chain comprising a second VH and a second heavy chain constant region, wherein the second heavy chain constant region is a non-wild-type heavy chain constant region comprising the sequence of SEQ ID NO: 23 with one or more amino acid substitutions, and wherein the second VH associates with a second VL to form a second antigen-binding domain that binds to CD20;
a third polypeptide chain comprising the first VH and a first light chain constant region; and
a fourth polypeptide chain comprising the second VL and a second light chain constant region,
wherein the first VL and second VL each contains a light chain CDR1, a light chain CDR2, and a light chain CDR3,
wherein the first VH and second VH each contains a heavy chain CDR1, a heavy chain CDR2, and a heavy chain CDR3,
wherein the first heavy chain constant region associates with the second heavy chain constant region,
wherein, when assessed by a surface plasmon resonance technique, the ability of the associated first and second heavy chain constant regions to bind to a given human Fcγ receptor is reduced, compared to the ability of a wild-type human IgG1 antibody to bind to the human Fcγ receptor, as a result of at least one of the one or more amino acid substitutions within the first and second heavy chain constant regions, wherein the human Fcγ receptor is a human FcγRI receptor, a human FcγRIIA receptor, or a human FcγRIIIA receptor, and
wherein at least one of the amino acid substitutions that result in the reduced ability to bind to the human Fcγ receptor is at a position selected from EU numbering positions 220, 226, 229, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 264, 265, 266, 267, 269, 270, 295, 296, 297, 298, 299, 300, 325, 327, 328, 329, 330, 331, and 332, in each of the first and second heavy chain constant regions.