US 12,139,536 B2
Guided combinational therapeutic antibody
Guan Yongjun, Clarksville, MD (US)
Assigned to Antibody Biopharm Inc.
Appl. No. 16/619,769
Filed by Antibody BioPharm, Inc., Clarksville, MD (US)
PCT Filed Jun. 7, 2018, PCT No. PCT/US2018/036497
§ 371(c)(1), (2) Date Dec. 5, 2019,
PCT Pub. No. WO2018/226985, PCT Pub. Date Dec. 13, 2018.
Claims priority of provisional application 62/516,683, filed on Jun. 8, 2017.
Prior Publication US 2021/0332135 A1, Oct. 28, 2021
Int. Cl. C07K 16/28 (2006.01); C07K 16/32 (2006.01)
CPC C07K 16/2827 (2013.01) [C07K 16/32 (2013.01); C07K 2317/31 (2013.01); C07K 2317/92 (2013.01)] 6 Claims
 
1. An engineered bi-specific antibody, comprising:
(i) a first chain comprising a first antigen binding single domain linked to the N-terminal of CH1 of IgG heavy chain that binds a first target, and having a first affinity in a range between 10−5 and 10−8M; and
(ii) a second chain comprising a second antigen binding single domain linked to the N-terminal of CL of light chain that binds a second target, and having a second affinity in a range between 10−5 and 10−8M;
(iii) a third chain that is same as the first chain;
(iv) a fourth chain that is the same as the second chain;
wherein said first chain is linked to said second chain to form a first arm through dimerization between CH1 and CL, said third chain is linked to said fourth chain to form a second arm through dimerization between CH1 and CL,
wherein said first arm is identical to said second arm, and said first arm and said second arm is linked by the IgG Fc dimerization,
wherein said first target and second target are both co-localized on a target cell;
wherein said bi-specific antibody more specifically binds to said target cell than to cells only expressing either said first target or said second target, with an avidity in a range between 10−9 and 10−12M;
wherein said affinity and avidity are measured by ELISA binding activity assay; and
wherein
(i) the heavy chain comprises any one of the sequences of SEQ ID No. 2, No. 4, No. 37, No. 41; and
(ii) the light chain comprises any one of the sequences of SEQ ID No. 6, No. 8, No. 39, No. 43, wherein said antibody binds to Her2 and CD47 double positive target cell; or
wherein
(iii) the heavy chain comprises any one of the sequences of SEQ ID No. 6, No. 8, No. 29, No. 33; and
(iv) the light chain comprises any one of the sequences of SEQ ID No. 10, No. 12, No. 31, No. 35, wherein said antibody binds to PD-L1 and CD47 double positive target cell.