Checkpoint inhibitor bispecific antibodies
The present invention relates to antibodies that are heterodimeric and bind human PD-L1 and human PD-1, and may be useful for treating cancer alone and in combination with chemotherapy and other cancer therapeutics.
1. An antibody that binds human PD-L1 (SEQ ID NO: 1) and human PD-1 (SEQ ID NO: 2) comprising:
a) a first heavy chain (HC1) comprising, in order from the N-terminus to the C-terminus, a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 3, the amino acid sequence of SEQ ID NO: 9 in the CH1 domain, the amino acid sequence of SEQ ID NO: 10 in the CH2 domain, and the amino acid sequence of SEQ ID NO: 11 or SEQ ID NO: 12 in the CH3 domain;
b) a first light chain (LC1) comprising, in order from the N-terminus to the C-terminus, a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 4 and the amino acid sequence of SEQ ID NO: 14 in the constant region;
c) a second heavy chain (HC2) comprising, in order from the N-terminus to the C-terminus, a HCVR comprising the amino acid sequence of SEQ ID NO: 5, the amino acid sequence of SEQ ID NO: 13 in the CH1 domain, the amino acid sequence of SEQ ID NO: 10 in the CH2 domain, and the amino acid sequence of SEQ ID NO: 12 or the amino acid sequence of SEQ ID NO: 11 in the CH3 domain; and
d) a second light chain (LC2) comprising, in order from N-terminus, a LCVR comprising the amino acid sequence of SEQ ID NO: 8 and the amino acid sequence of SEQ ID NO: 15 in the constant region, provided that when the amino acid sequence of SEQ ID NO: 11 is present in the CH3 domain of said HC1, the amino acid sequence of SEQ ID NO: 12 is present in the CH3 domain of said HC2; or when the amino acid sequence of SEQ ID NO: 12 is present in the CH3 domain of said HC1, the amino acid sequence of SEQ ID NO: 11 is present in the CH3 domain of said HC2.
2. The antibody of claim 1 , wherein said HC1 comprises the amino acid sequence of SEQ ID NO: 11 in the CH3 domain, and wherein said HC2 comprises the HCVR comprising the amino acid sequence of SEQ ID NO: 6 and said HC2 comprises the amino acid sequence of SEQ ID NO: 12 in the CH3 domain.
3. The antibody of claim 1 , wherein said HC1, LC1, HC2, and LC2 comprises the amino acid sequences of SEQ ID NO: 49, SEQ ID NO: 30, SEQ ID NO 31, and SEQ ID NO: 34, respectively.
4. The antibody of claim 1 , wherein said HC1, LC1, HC2, and LC2 comprises the amino acid sequences of SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 33, and SEQ ID NO: 34, respectively.
5. A pharmaceutical composition, comprising the antibody of claim 3 and an acceptable carrier, diluent, or excipient.