US 11,866,498 B2
Bispecific antigen-binding molecules and methods of use
Diego Ellerman, San Francisco, CA (US); Teemu T. Junttila, San Mateo, CA (US); Twyla Noelle Lombana, San Francisco, CA (US); Dionysos Slaga, Richmond, CA (US); and Christoph Spiess, Mountain View, CA (US)
Assigned to Genentech, Inc., South San Francisco, CA (US)
Filed by Genentech, Inc., South San Francisco, CA (US)
Filed on Feb. 8, 2019, as Appl. No. 16/271,410.
Claims priority of provisional application 62/628,088, filed on Feb. 8, 2018.
Prior Publication US 2019/0270814 A1, Sep. 5, 2019
Int. Cl. C07K 16/28 (2006.01); A61P 35/00 (2006.01); C07K 16/32 (2006.01); A61K 39/395 (2006.01); A61K 47/65 (2017.01); A61K 9/00 (2006.01); C07K 16/46 (2006.01); C07K 16/10 (2006.01); A61P 35/02 (2006.01)
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.