US 12,240,918 B2
Bispecific antibodies against plasma kallikrein and factor XII
Stephen R. Comeau, Avon, NY (US); Andrew Nixon, Hanover, MA (US); Niksa Kastrapeli, Wellesley, MA (US); Jon A. Kenniston, Hingham, MA (US); Gregory P. Conley, Arlington, MA (US); Shauna Mason, Arlington, MA (US); Allison P. Lindberg, Arlington, MA (US); Kristopher Kopacz, Cumberland, RI (US); and Burt Adelman, Concord, MA (US)
Assigned to Takeda Pharmaceutical Company Limited, Osaka (JP)
Filed by Takeda Pharmaceutical Company Limited, Osaka (JP)
Filed on Jun. 13, 2022, as Appl. No. 17/838,769.
Application 17/838,769 is a continuation of application No. 15/541,066, granted, now 11,390,687, previously published as PCT/US2015/068238, filed on Dec. 31, 2015.
Claims priority of provisional application 62/261,609, filed on Dec. 1, 2015.
Claims priority of provisional application 62/200,363, filed on Aug. 3, 2015.
Claims priority of provisional application 62/099,236, filed on Jan. 2, 2015.
Prior Publication US 2023/0117565 A1, Apr. 20, 2023
Int. Cl. A61K 39/395 (2006.01); A61P 7/02 (2006.01); C07K 16/36 (2006.01); C07K 16/40 (2006.01); C12N 9/64 (2006.01)
CPC C07K 16/40 (2013.01) [A61K 39/395 (2013.01); A61P 7/02 (2018.01); C07K 16/36 (2013.01); C12N 9/64 (2013.01); C07K 2317/31 (2013.01); C07K 2317/51 (2013.01); C07K 2317/622 (2013.01); C07K 2317/64 (2013.01); C07K 2317/76 (2013.01); C07K 2317/94 (2013.01)] 16 Claims
 
1. A method of inhibiting plasma kallikrein (pKal) and Factor XII in diseases associated with contact activation system, comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition comprising a bispecific antibody and a pharmaceutically acceptable carrier, wherein the bispecific antibody comprises:
a first polypeptide that comprises a light chain of a first antibody, the light chain comprising a light chain variable region (VL) and a light chain constant region (CL); and
a second polypeptide that comprises a heavy chain of the first antibody, the heavy chain comprising a heavy chain variable region (VH) and a heavy chain constant region (CH),
wherein the first polypeptide or the second polypeptide further comprises a second antibody, which is a single chain antibody and is fused to the C-terminus of either the first polypeptide or the second polypeptide;
wherein the first antibody binds active pKal and comprises a heavy chain complementarity determining region (HCDR) 1 set forth as SEQ ID NO: 159, a HCDR2 set forth as SEQ ID NO: 160, and a HCDR3 set forth as SEQ ID NO: 161; and a light chain complementarity determining region (LCDR) 1 set forth as SEQ ID NO: 162, a LCDR2 set forth as SEQ ID NO: 163, and a LCDR3 set forth as SEQ ID NO: 164; and
wherein the second antibody binds active Factor XII (FXIIa) and comprises
(i) a heavy chain comprising a HCDR1 set forth as SEQ ID NO: 41, a HCDR2 set forth as SEQ ID NO: 43, and a HCDR3 set forth as SEQ ID NO: 45, and a light chain comprising a LCDR1 set forth as SEQ ID NO: 34, a LCDR2 set forth as SEQ ID NO: 36, and a LCDR3 set forth as SEQ ID NO: 37;
(ii) a heavy chain comprising a HCDR1 set forth as SEQ ID NO: 41, a HCDR2 set forth as SEQ ID NO: 43, and a HCDR3 set forth as SEQ ID NO: 45, and a light chain comprising a LCDR1 set forth as SEQ ID NO: 35, a LCDR2 set forth as SEQ ID NO: 36, and a LCDR3 set forth as SEQ ID NO: 38;
(iii) a heavy chain comprising a HCDR1 set forth as SEQ ID NO: 41, a HCDR2 set forth as SEQ ID NO: 43, and a HCDR3 set forth as SEQ ID NO: 45, and a light chain comprising a LCDR1 set forth as SEQ ID NO: 34, a LCDR2 set forth as SEQ ID NO: 36, and a LCDR3 set forth as SEQ ID NO: 39;
(iv) a heavy chain comprising a HCDR1 set forth as SEQ ID NO: 41, a HCDR2 set forth as SEQ ID NO: 43, and a HCDR3 set forth as SEQ ID NO: 45, and a light chain comprising a LCDR1 set forth as SEQ ID NO: 34, a LCDR2 set forth as SEQ ID NO: 36, and a LCDR3 set forth as SEQ ID NO: 40;
(v) a heavy chain comprising a HCDR1 set forth as SEQ ID NO: 42, a HCDR2 set forth as SEQ ID NO: 44, and a HCDR3 set forth as SEQ ID NO: 45, and a light chain comprising a LCDR1 set forth as SEQ ID NO: 34, a LCDR2 set forth as SEQ ID NO: 36, and a LCDR3 set forth as SEQ ID NO: 37;
(vi) a heavy chain comprising a HCDR1 set forth as SEQ ID NO: 132, a HCDR2 set forth as SEQ ID NO: 133, and a HCDR3 set forth as SEQ ID NO: 134, and a light chain comprising a LCDR1 set forth as SEQ ID NO: 131, a LCDR2 set forth as SEQ ID NO: 36, and a LCDR3 set forth as SEQ ID NO: 37;
(vii) a heavy chain comprising a HCDR1 set forth as SEQ ID NO: 135, a HCDR2 set forth as SEQ ID NO: 136, and a HCDR3 set forth as SEQ ID NO: 134, and a light chain comprising a LCDR1 set forth as SEQ ID NO: 131, a LCDR2 set forth as SEQ ID NO: 36, and a LCDR3 set forth as SEQ ID NO: 37;
(viii) a heavy chain comprising a HCDR1 set forth as SEQ ID NO: 137, a HCDR2 set forth as SEQ ID NO: 138, and a HCDR3 set forth as SEQ ID NO: 134, and a light chain comprising a LCDR1 set forth as SEQ ID NO: 131, a LCDR2 set forth as SEQ ID NO: 36, and a LCDR3 set forth as SEQ ID NO: 37; or
(ix) a heavy chain comprising a HCDR1 set forth as SEQ ID NO: 139, a HCDR2 set forth as SEQ ID NO: 140, and a HCDR3 set forth as SEQ ID NO: 134, and a light chain 12840112.1 comprising a LCDR1 set forth as SEQ ID NO: 131, a LCDR2 set forth as SEQ ID NO: 36, and a LCDR3 set forth as SEQ ID NO: 37.