US 12,404,328 B2
Multi-specific binding proteins and methods of use thereof
Patrick A. Baeuerle, Cambridge, MA (US); Jennifer Michaelson, Brighton, MA (US); Bochong Li, Boston, MA (US); and Naveen Mehta, Cambridge, MA (US)
Assigned to Cullinan Management, Inc., Cambridge, MA (US)
Appl. No. 16/972,460
Filed by Cullinan Management, Inc., Cambridge, MA (US)
PCT Filed Jun. 7, 2019, PCT No. PCT/US2019/036177
§ 371(c)(1), (2) Date Aug. 11, 2023,
PCT Pub. No. WO2019/237081, PCT Pub. Date Dec. 12, 2019.
Claims priority of provisional application 62/681,784, filed on Jun. 7, 2018.
Prior Publication US 2021/0238286 A1, Aug. 5, 2021
Int. Cl. C07K 16/28 (2006.01); A61K 39/00 (2006.01); A61P 35/00 (2006.01); C07K 16/18 (2006.01)
CPC C07K 16/2809 (2013.01) [A61P 35/00 (2018.01); C07K 16/18 (2013.01); C07K 16/2803 (2013.01); A61K 2039/505 (2013.01); C07K 2317/31 (2013.01); C07K 2317/565 (2013.01); C07K 2317/569 (2013.01); C07K 2317/622 (2013.01); C07K 2317/73 (2013.01); C07K 2317/76 (2013.01); C07K 2317/92 (2013.01)] 26 Claims
 
1. A multi-specific binding protein comprising:
(a) a first antigen-binding site that binds to human CD19 comprising heavy chain complementarity determining regions (HCDR) and light chain complementarity determining regions (LCDR), wherein:
HCDR1 comprises the amino acid sequence of SEQ ID NO: 3, HCDR2 comprises the amino acid sequence of SEQ ID NO: 4, HCDR3 comprises the amino acid sequence of SEQ ID NO: 5, LCDR1 comprises the amino acid sequence of SEQ ID NO: 6, LCDR2 comprises the amino acid sequence of SEQ ID NO: 7, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 8;
(b) a second antigen-binding site that binds to human CD3 comprising heavy chain complementarity determining regions (HCDR) and light chain complementarity determining regions (LCDR), wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 99, HCDR2 comprises the amino acid sequence of SEQ ID NO: 100, HCDR3 comprises the amino acid sequence of SEQ ID NO: 101, LCDR1 comprises the amino acid sequence of SEQ ID NO: 102, LCDR2 comprises the amino acid sequence of SEQ ID NO: 103, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 104;
(c) a third antigen-binding site that binds to human serum albumin (HSA) comprising a heavy chain complementarity determining regions (HCDR) wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 122 or 123, HCDR2 comprises the amino acid sequence of SEQ ID NO: 124 or 125, HCDR3 comprises the amino acid sequence of SEQ ID NO: 126,
and wherein the first antigen-binding site and second antigen-binding site comprise a single-chain variable fragment (scFv) and the third antigen-binding site comprises a single-domain antibody (sdAb).