US 12,460,000 B2
Anti-CD19 and anti-CD3 bispecific antigen binding proteins and uses thereof
Zhihua Huang, Shanghai (CN); Yiqun Rao, Shanghai (CN); Wuzhong Shen, Shanghai (CN); Yumin Cui, Shanghai (CN); and Xiaoqiang Yan, Shanghai (CN)
Assigned to ITabMed (HK) Limited, Hong Kong (CN)
Appl. No. 17/273,955
Filed by ITabMed (HK) Limited, Hong Kong (CN)
PCT Filed Sep. 6, 2019, PCT No. PCT/CN2019/104680
§ 371(c)(1), (2) Date Mar. 5, 2021,
PCT Pub. No. WO2020/048525, PCT Pub. Date Mar. 12, 2020.
Claims priority of application No. 201811041588.X (CN), filed on Sep. 7, 2018.
Prior Publication US 2021/0301018 A1, Sep. 30, 2021
Int. Cl. C07K 16/28 (2006.01); A61K 39/00 (2006.01); A61P 35/00 (2006.01)
CPC C07K 16/2809 (2013.01) [A61P 35/00 (2018.01); A61K 2039/505 (2013.01); C07K 2317/31 (2013.01); C07K 2317/522 (2013.01); C07K 2317/55 (2013.01); C07K 2317/56 (2013.01); C07K 2317/622 (2013.01); C07K 2317/73 (2013.01); C07K 2317/92 (2013.01)] 20 Claims
 
1. A bispecific antigen binding protein (BSAP) comprising:
(I) an anti-CD19 Fab specifically recognizing CD19, wherein the anti-CD19 Fab comprises:
(a) an immunoglobulin (Ig) heavy chain variable region (VH) and an Ig heavy chain constant region 1 (CH1), and
(b) an Ig light chain variable region (VL) and an Ig light chain constant region (CL);
wherein:
(i) the VH of the anti-CD19 Fab comprises: a heavy chain hypervariable region 1 (HVR-H1) comprising the amino acid sequence of SEQ ID NO: 1, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and the VL of the anti-CD19 Fab comprises: a light chain hypervariable region 1 (HVR-L1) comprising the amino acid sequence of SEQ ID NO: 4, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6; or
(ii) the VH of the anti-CD19 Fab comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and the VL of the anti-CD19 Fab comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 37, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 38, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 39; and
(II) an anti-CD3 scFv specifically recognizing CD3;
wherein the anti-CD3 scFv comprises a VH and a VL;
wherein the VH of the anti-CD3 scFv comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 10, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 11; and wherein the VL of the anti-CD3 scFv comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 12, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 13, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 14:
wherein:
(1) the anti-CD3 scFv is connected to the N-terminus of the VH or the VL of the anti-CD19 Fab via an optional linker; or
(2) the BSAP comprises a first anti-CD3 scFv and a second anti-CD3 scFv, wherein the first anti-CD3 scFv is connected to the N-terminus of the VH of the anti-CD19 Fab via an optional first linker, and the second anti-CD3 scFv is connected to the N-terminus of the VL of the anti-CD19 Fab via an optional second linker.
 
12. A method of treating a CD19-expressing cancer in an individual in need thereof, comprising administering to the individual an effective amount of the BSAP of claim 1.