ANTI-PD-L1 ANTIBODIES
Aspects of the invention include isolated anti-PD-L1 antibodies, as well as compositions containing such antibodies, and methods of using the same in the treatment of diseases or conditions that are mediated by PD-L1 signaling.
1 . A method of inhibiting the growth of a tumor cell that expresses PD-L1, the method comprising administering an isolated anti-PD-L1 antibody, or an antigen-binding fragment thereof, to a subject having the tumor cell, thereby (i) inhibiting growth or proliferation of the tumor cell, or (ii) inducing death of the tumor cell, wherein the anti-PD-L1 antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the antibody or antigen-binding fragment thereof comprises:
(i) an HVR-H1 comprising the sequence of GFSLTSYDIS (SEQ ID NO: 4);
(ii) an HVR-H2 comprising the sequence of VIWTGVGTN (SEQ ID NO: 5); and
(iii) an HVR-H3 comprising the sequence of DPYYYGMDY (SEQ ID NO: 6);
(iv) an HVR-L1 comprising the sequence of RASQDISIWLS (SEQ ID NO: 1);
(v) an HVR-L2 comprising the sequence of KASNLHT (SEQ ID NO: 2); and
(vi) an HVR-L3 comprising the sequence of LQSQSFPRT (SEQ ID NO: 3); and
wherein the anti-PD-L1 antibody is capable of binding to human and cynomolgus monkey PD-L1.
2 . The method of claim 1 , wherein the anti-PD-L1 antibody or an antigen-binding fragment thereof comprises a VH having at least 90% sequence identity to SEQ ID NO: 45 and a VL having at least 90% sequence identity to SEQ ID NO: 46.
3 . The method of claim 1 , wherein the anti-PD-L1 antibody or an antigen-binding fragment thereof is a chimeric antibody or a humanized antibody.
4 . The method of claim 1 , wherein the anti-PD-L1 antibody or an antigen-binding fragment thereof comprises a VH having at least 90% sequence identity to the sequence of any one of SEQ ID NOS: 36, 37, 38, 39, 40, 41 or 42 and a VL having at least 90% sequence identity to any one of SEQ ID NOS: 43 or 44.
5 . The method of claim 4 , wherein the VH comprises the sequence of SEQ ID NO: 36, 37, 38, 39, 40, 41 or 42 and the VL comprises SEQ ID NO: 43 or 44.
6 . The method of claim 1 , wherein the anti-PD-L1 antibody or an antigen-binding fragment thereof is bispecific.
7 . The method of claim 6 , wherein the bispecific antibody or antigen-binding fragment binds to a PD-L1 protein and a cell surface protein.
8 . The method of claim 7 , wherein the cell surface protein is selected from the group consisting of: CD20, EGFR, HER2, CTLA-4, TIM3, LAG3, VISTA and TIGIT.
9 . The method of claim 1 , wherein the antigen-binding fragment is selected from the group consisting of: Fab, Fab′, F(ab) 2 , F(ab′) 2 , Fv, and scFv.
10 . The method of claim 1 , wherein the antibody is an IgG, IgM, IgA, IgD, or IgE isotype.
11 . The method of claim 10 , wherein the antibody is an IgM isotype.
12 . The method of claim 11 , wherein the antibody comprises a J-chain.
13 . The method of claim 10 , wherein the antibody is an IgA isotype, wherein the antibody is a subclass selected from the group consisting of: IgA1 and IgA2, and wherein the antibody comprises a J-chain.
14 . The method of claim 12 , wherein the J-chain is a modified J-chain comprising an extraneous binding moiety.
15 . The method of claim 1 , wherein the anti-PD-L1 antibody or an antigen-binding fragment thereof is a PD-L1 antagonist.
16 . The method of claim 1 , wherein the VH comprises the amino acid sequence SEQ ID NO: 45 and the VL comprises the amino acid sequence SEQ ID NO: 46.
17 . The method of claim 1 , wherein the VH comprises the amino acid sequence SEQ ID NO: 37 and the VL comprises the amino acid sequence SEQ ID NO: 44.