US 12,168,697 B2
Bispecific antibodies which bind blood coagulation factor VIII and have enhanced activity, and methods of use thereof for treating bleeding and associated conditions
Tomoyuki Igawa, Shizuoka (JP); and Yuri Teranishi, Shizuoka (JP)
Assigned to Chugai Seiyaku Kabushiki Kaisha, Tokyo (JP)
Filed by Chugai Seiyaku Kabushiki Kaisha, Tokyo (JP)
Filed on Dec. 28, 2021, as Appl. No. 17/563,149.
Application 17/563,149 is a division of application No. 16/061,429, abandoned, previously published as PCT/JP2016/088299, filed on Dec. 22, 2016.
Claims priority of application No. 2015-253324 (JP), filed on Dec. 25, 2015.
Prior Publication US 2022/0119551 A1, Apr. 21, 2022
Int. Cl. C07K 16/36 (2006.01)
CPC C07K 16/36 (2013.01) [C07K 2317/526 (2013.01); C07K 2317/53 (2013.01)] 16 Claims
 
1. A bispecific antibody comprising:
a first heavy chain comprising
(i) a first heavy chain variable region comprising the heavy chain variable region amino acid sequence of SEQ ID NO: 1 with no modifications, and
(ii) a first heavy chain constant region comprising the heavy chain constant region amino acid sequence of SEQ ID NO: 1 with no modifications, or with at least one modification in the first heavy chain constant region compared to the heavy chain constant region amino acid sequence of SEQ ID NO: 1;
a second heavy chain comprising
(iii) a second heavy chain variable region comprising the heavy chain variable region amino acid sequence of SEQ ID NO: 2 with no modifications, and
(iv) a second heavy chain constant region comprising the heavy chain constant region amino acid sequence of SEQ ID NO: 2 with no modifications, or with at least one modification in the second heavy chain constant region compared to the heavy chain constant region amino acid sequence of SEQ ID NO: 2;
a first light chain comprising the amino acid sequence of SEQ ID NO: 3; and
a second light chain comprising the amino acid sequence of SEQ ID NO: 3,
wherein one of the two heavy chain constant regions includes one or both of the following modifications (a) and (b), and the other of the two heavy chain constant regions includes one or both or neither of the following modifications (a) and (b):
(a) a tyrosine (Y) at EU numbering position 434,
(b) the amino acid sequence AAAC replacing the residues at EU numbering positions 216 to 230;
wherein the first heavy chain constant region optionally includes one or more other modifications compared to the heavy chain constant region amino acid sequence of SEQ ID NO: 1;
wherein the second heavy chain constant region optionally includes one or more other modifications compared to the heavy chain constant region amino acid sequence of SEQ ID NO: 2; and
wherein the first heavy chain associates with the first light chain, and the second heavy chain associates with the second light chain.