	US 12,421,322 B2
	Antibody variant and isoform with lowered biological activity
Kensaku Hosoguchi, Tokyo (JP); Maki Kuwayama, Tokyo (JP); Chifumi Seida, Tokyo (JP); Yosuke Watanabe, Tokyo (JP); Nobuyuki Tanaka, Tokyo (JP); Satoshi Saitoh, Tokyo (JP); and Masakazu Fukuda, Tokyo (JP)
Assigned to Chugai Seiyaku Kabushiki Kaisha, Tokyo (JP)
Appl. No. 16/758,128
Filed by Chugai Seiyaku Kabushiki Kaisha, Tokyo (JP)
PCT Filed Oct. 31, 2018, PCT No. PCT/JP2018/040436 § 371(c)(1), (2) Date Apr. 22, 2020, PCT Pub. No. WO2019/088143, PCT Pub. Date May 9, 2019.
Claims priority of application No. 2017-212179 (JP), filed on Nov. 1, 2017.
Prior Publication US 2020/0283544 A1, Sep. 10, 2020
Int. Cl. C07K 16/46 (2006.01); G01N 33/68 (2006.01); A61K 39/00 (2006.01)

CPC C07K 16/468 (2013.01) [G01N 33/6854 (2013.01); A61K 2039/505 (2013.01); C07K 2317/31 (2013.01); C07K 2317/51 (2013.01); C07K 2317/565 (2013.01); C07K 2317/71 (2013.01); C07K 2317/94 (2013.01)]

7 Claims

1. A purified variant of Emicizumab, wherein the variant is identical to Emicizumab except for modifications consisting of, in a heavy chain variable region that corresponds to SEQ ID NO: 13:

(1) the heavy chain variable region has a deletion of either (a) or (b):

(a) Arg at position 61; or

(b) Tyr-Tyr-Arg at positions 59-61,

and

(2) the heavy chain variable region is split into two fragments:

(i) an N-terminal fragment with a C-terminus that is either Tyr at position 60 or Thr at position 58, and

(ii) a C-terminal fragment with an N-terminus that is Arg at position 62,

wherein the two fragments are linked by a disulfide bond, and wherein all position numbers are based on numbering in SEQ ID NO: 13.