CPC C07K 16/2809 (2013.01) [A61K 9/0019 (2013.01); A61K 39/3955 (2013.01); A61K 47/65 (2017.08); A61P 35/00 (2018.01); A61P 35/02 (2018.01); C07K 16/1063 (2013.01); C07K 16/2803 (2013.01); C07K 16/2818 (2013.01); C07K 16/32 (2013.01); C07K 16/468 (2013.01)] | 24 Claims |
1. A bispecific antigen-binding molecule that specifically binds CD3 and HER2 comprising a monovalent arm and a bivalent arm, wherein:
(a) the monovalent arm comprises a FabA that specifically binds CD3, wherein the C-terminus of the FabA is fused to an N-terminus of a first Fc subunit, and wherein the FabA comprises the following HVRs:
(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1,
(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2,
(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3,
(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4,
(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and
(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6;
(b) the bivalent arm comprises a FabB1 and a FabB2 that each specifically binds HER2, wherein the C-terminus of the FabB2 is fused to the N-terminus of the FabB1, and the C-terminus of the FabB1 is fused to an N-terminus of a second Fc subunit, wherein the FabB1 and the FabB2 each comprise the following HVRs:
(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 11,
(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 36,
(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 37,
(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 38,
(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and
(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 26; and
(c) the first Fc subunit is associated with the second Fc subunit to form an Fc domain.
|