Anti-PD-L1 antibodies
The present invention relates to antigen binding molecules, particularly antibodies, fragments and variants thereof, that bind to the programmed death-ligand 1 (PD-L1) in a pH-dependant manner, competing with PD-L1 binding to the inhibitory receptor programmed death 1 polypeptide (PD-1) and co-stimulatory molecule CD80, and the use of said antigen binding molecules in treating and/or preventing diseases such as cancer.
1 . An anti-PD-L1 antigen binding molecule comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein:
(a) the VH comprises:
a VHCDR1 comprising the amino acid sequence of SEQ ID NO: 6,
a VHCDR2 comprising the amino acid sequence of SEQ ID NO: 7, and
a VHCDR3 comprising the amino acid sequence of SEQ ID NO: 8; and
(b) the VL comprises:
(i) a VLCDR1 comprising the amino acid sequence of SEQ ID NO: 16,
a VLCDR2 comprising the amino acid sequence of SEQ ID NO: 3, and
a VLCDR3 comprising the amino acid sequence of SEQ ID NO: 4;
(ii) a VLCDR1 comprising the amino acid sequence of SEQ ID NO: 12,
a VLCDR2 comprising the amino acid sequence of SEQ ID NO: 3, and
a VLCDR3 comprising the amino acid sequence of SEQ ID NO: 4;
(iii) a VLCDR1 comprising the amino acid sequence of SEQ ID NO: 10,
a VLCDR2 comprising the amino acid sequence of SEQ ID NO: 3, and
a VLCDR3 comprising the amino acid sequence of SEQ ID NO: 4;
(iv) a VLCDR1 comprising the amino acid sequence of SEQ ID NO: 14,
a VLCDR2 comprising the amino acid sequence of SEQ ID NO: 3, and
a VLCDR3 comprising the amino acid sequence of SEQ ID NO: 4; or
(v) a VLCDR1 comprising the amino acid sequence of SEQ ID NO: 18,
a VLCDR2 comprising the amino acid sequence of SEQ ID NO: 3, and
a VLCDR3 comprising the amino acid sequence of SEQ ID NO: 4.
2 . The anti-PD-L1 antigen binding molecule of claim 1 , wherein:
the VH comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 5; and
the VL comprises an amino acid sequence having at least 80% identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 15, SEQ ID NO: 11, SEQ ID NO: 9, SEQ ID NO: 13, and SEQ ID NO: 17.
3 . The anti-PD-L1 antigen binding molecule of claim 1 , wherein:
the VH comprises the amino acid sequence SEQ ID NO: 5;
and
the VL comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 15, SEQ ID NO: 11, SEQ ID NO: 9, SEQ ID NO: 13, and SEQ ID NO: 17.
4 . The anti-PD-L1 antigen binding molecule of claim 1 , wherein:
(a) the VH comprises the amino acid sequence of SEQ ID NO: 5 and the VL comprises the amino acid sequence of SEQ ID NO: 15;
(b) the VH comprises the amino acid sequence of SEQ ID NO: 5 and the VL comprises the amino acid sequence of SEQ ID NO: 11;
(c) the VH comprises the amino acid sequence of SEQ ID NO: 5 and the VL comprises the amino acid sequence of SEQ ID NO: 9;
(d) the VH comprises the amino acid sequence of SEQ ID NO: 5 and the VL comprises the amino acid sequence of SEQ ID NO: 13; or
(e) the VH comprises the amino acid sequence of SEQ ID NO: 5 and the VL comprises the amino acid sequence of SEQ ID NO: 17.
5 . The anti-PD-L1 antigen binding molecule of claim 1 , wherein the anti-PD-L1 antigen binding molecule is an antibody or antigen binding fragment or derivative thereof, optionally wherein the antibody, antigen binding fragment or derivative is a Fab, F(ab′)2, Fv, scFv, dAb, Fd, or a diabody.
6 . The anti-PD-L1 antigen binding molecule of claim 5 , wherein the antibody or antigen binding fragment or derivative thereof is an IgA, IgD, IgE, IgG, IgM or IgY antibody.
7 . The anti-PD-L1 antigen binding molecule of claim 6 , wherein the antibody or antigen binding fragment or derivative thereof is bispecific.
8 . The anti-PD-L1 antigen binding molecule of claim 1 wherein the anti-PD-L1 antigen binding molecule specifically binds to PD-L1 in a pH-dependent manner.
9 . The anti-PD-L1 antigen binding molecule of claim 1 , wherein the anti-PD-L1 antigen binding molecule has a higher affinity for PD-L1 at pH 6.0 than at pH 7.4.
10 . The anti-PD-L1 antigen binding molecule of claim 1 , wherein the anti-PD-L1 antigen binding molecule
a. reverses immune suppression; or
b. enhances T cell immunity when administered in vivo or in vitro.
11 . A pharmaceutical composition comprising the anti-PD-L1 antigen binding molecule of claim 1 and a pharmaceutically acceptable excipient.
12 . The pharmaceutical composition of claim 11 , further comprising an additional therapeutically active agent.
13 . A method of treating cancer in a subject in need thereof comprising:
administering the anti-PD-L1 antigen binding molecule according to claim 1 ; or administering a pharmaceutical composition comprising the anti-PD-L1 antigen binding molecule according to claim 1 ; wherein the cancer is selected from the group consisting of melanoma, metastatic cancer, non-small cell lung cancer, head and neck cancer, Hodgkin's lymphoma, urothelial carcinoma, gastric cancer, cervical cancer, hepatocellular carcinoma, and bladder cancer.