Antigen binding proteins that bind PD-L1
View Patent ↗There is disclosed compositions and methods relating to or derived from anti-PD-L1 antibodies. More specifically, there is disclosed fully human antibodies that bind PD-L1, PD-L1-binding fragments and derivatives of such antibodies, and PD-L1-binding polypeptides comprising such fragments. Further still, there is disclosed nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating or diagnosing subjects having PD-L1 related disorders or conditions, including various inflammatory disorders and various cancers.
1. A fully human antibody of an IgG class that binds to a PD-L1 epitope, that has a heavy chain variable domain sequence that is at least 95% identical to the amino acid sequences selected from the group consisting of SEQ ID NO. 35, SEQ ID NO. 51, SEQ ID NO. 137, SEQ ID NO. 155, SEQ ID NO. 157, SEQ ID NO. 159, SEQ ID NO. 161, SEQ ID NO. 163, SEQ ID NO. 165, SEQ ID NO. 179, SEQ ID NO. 183, SEQ ID NO. 185, SEQ ID NO. 213, SEQ ID NO. 215, SEQ ID NO. 217, and SEQ ID NO. 219, and that has a light chain variable domain sequence that is at least 95% identical to the amino acid sequences selected from the group consisting of SEQ ID NO. 36, SEQ ID NO. 52, SEQ ID NO. 138, SEQ ID NO. 156, SEQ ID NO. 158, SEQ ID NO. 160, SEQ ID NO. 162, SEQ ID NO. 164, SEQ ID NO. 166, SEQ ID NO. 180, SEQ ID NO. 184, SEQ ID NO. 186, SEQ ID NO. 214, SEQ ID NO. 216, SEQ ID NO. 218, and SEQ ID NO. 220, and wherein the antibody has a heavy chain/light chain variable domain sequence selected from the group consisting of SEQ ID NO. 35/SEQ ID NO. 36 (called H6 herein), SEQ ID NO. 51/SEQ ID NO. 52 (called RC5 herein), SEQ ID NO. 137/SEQ ID NO. 138 (called SH1A1Q herein), SEQ ID NO. 155/SEQ ID NO. 156 (called SH1B3 herein), SEQ ID NO. 157/SEQ ID NO. 158 (called SH1D1 herein), SEQ ID NO. 159/SEQ ID NO. 160 (called SH1D2 herein), SEQ ID NO. 161/SEQ ID NO. 162 (called SH1D12 herein), SEQ ID NO. 163/SEQ ID NO. 164 (called SH1E1 herein), SEQ ID NO. 165/SEQ ID NO. 166 (called SH1G9 herein SEQ ID NO. 179/SEQ ID NO. 180 (called SH1E6 herein), SEQ ID NO. 183/SEQ ID NO. 184 (called SH1A2 herein), SEQ ID NO. 185/SEQ ID NO. 186 (called SH1B1 herein), SEQ ID NO. 213/SEQ ID NO. 214 (called H6B1L herein), SEQ ID NO. 215/SEQ ID NO. 216 (called H6A1 herein), SEQ ID NO. 217/SEQ ID NO. 218 (called H6B1 herein), and SEQ ID NO. 219/SEQ ID NO. 220 (called H6B2 herein).
2. A Fab fully human antibody fragment that binds to a PD-L1 epitope, having a variable domain region from a heavy chain and a variable domain region from a light chain, wherein the heavy chain variable domain sequence that is at least 95% identical to the amino acid sequences selected from the group consisting of SEQ ID NO. 35, SEQ ID NO. 51, SEQ ID NO. 137, SEQ ID NO. 155, SEQ ID NO. 157, SEQ ID NO. 159, SEQ ID NO. 161, SEQ ID NO. 163, SEQ ID NO. 165, SEQ ID NO. 179, SEQ ID NO. 183, SEQ ID NO. 185, SEQ ID NO. 213, SEQ ID NO. 215, SEQ ID NO. 217, and SEQ ID NO. 219, and that has a light chain variable domain sequence that is at least 95% identical to the amino acid sequences selected from the group consisting of SEQ ID NO. 36, SEQ ID NO. 52, SEQ ID NO. 138, SEQ ID NO. 156, SEQ ID NO. 158, SEQ ID NO. 160, SEQ ID NO. 162, SEQ ID NO. 164, SEQ ID NO. 166, SEQ ID NO. 180, SEQ ID NO. 184, SEQ ID NO. 186, SEQ ID NO. 214, SEQ ID NO. 216, SEQ ID NO. 218, and SEQ ID NO. 220, and wherein the antibody has a heavy chain/light chain variable domain sequence selected from the group consisting of SEQ ID NO. 35/SEQ ID NO. 36, SEQ ID NO. 51/SEQ ID NO. 52, SEQ ID NO. 137/SEQ ID NO. 138, SEQ ID NO. 155/SEQ ID NO. 156, SEQ ID NO. 157/SEQ ID NO. 158, SEQ ID NO. 159/SEQ ID NO. 160, SEQ ID NO. 161/SEQ ID NO. 162, SEQ ID NO. 163/SEQ ID NO. 164, SEQ ID NO. 165/SEQ ID NO. 166, SEQ ID NO. 179/SEQ ID NO. 180, SEQ ID NO. 183/SEQ ID NO. 184, SEQ ID NO. 185/SEQ ID NO. 186, SEQ ID NO. 213/SEQ ID NO. 214, SEQ ID NO. 215/SEQ ID NO. 216, SEQ ID NO. 217/SEQ ID NO. 218, and SEQ ID NO. 219/SEQ ID NO. 220.
3. A single chain human antibody that binds to a PD-L1 epitope, having a variable domain region from a heavy chain and a variable domain region from a light chain and a peptide linker connection the heavy chain and light chain variable domain regions, wherein the heavy chain variable domain sequence that is at least 95% identical to the amino acid sequences selected from the group consisting of SEQ ID NO. 35, SEQ ID NO. 51, SEQ ID NO. 137, SEQ ID NO. 155, SEQ ID NO. 157, SEQ ID NO. 159, SEQ ID NO. 161, SEQ ID NO. 163, SEQ ID NO. 165, SEQ ID NO. 179, SEQ ID NO. 183, SEQ ID NO. 185, SEQ ID NO. 213, SEQ ID NO. 215, SEQ ID NO. 217, and SEQ ID NO. 219, and that has a light chain variable domain sequence that is at least 95% identical to the amino acid sequences selected from the group consisting of SEQ ID NO. 36, SEQ ID NO. 52, SEQ ID NO. 138, SEQ ID NO. 156, SEQ ID NO. 158, SEQ ID NO. 160, SEQ ID NO. 162, SEQ ID NO. 164, SEQ ID NO. 166, SEQ ID NO. 180, SEQ ID NO. 184, SEQ ID NO. 186, SEQ ID NO. 214, SEQ ID NO. 216, SEQ ID NO. 218, and SEQ ID NO. 220, and wherein the single chain fully human antibody has a heavy chain/light chain variable domain sequence selected from the group consisting of SEQ ID NO. 35/SEQ ID NO. 36, SEQ ID NO. 51/SEQ ID NO. 52, SEQ ID NO. 137/SEQ ID NO. 138, SEQ ID NO. 155/SEQ ID NO. 156, SEQ ID NO. 157/SEQ ID NO. 158, SEQ ID NO. 159/SEQ ID NO. 160, SEQ ID NO. 161/SEQ ID NO. 162, SEQ ID NO. 163/SEQ ID NO. 164, SEQ ID NO. 165/SEQ ID NO. 166, SEQ ID NO. 183/SEQ ID NO. 184, SEQ ID NO. 185/SEQ ID NO. 186, SEQ ID NO. 213/SEQ ID NO. 214, SEQ ID NO. 215/SEQ ID NO. 216, SEQ ID NO. 217/SEQ ID NO. 218, and SEQ ID NO. 219/SEQ ID NO. 220.
4. A method for treating a broad spectrum of mammalian cancers, comprising administering an effective amount of an anti-PD-L1 polypeptide, wherein the anti-PD-L1 polypeptide is selected from the group consisting of a fully human antibody of an IgG class that binds to a PD-L1 epitope a Fab fully human antibody fragment, having a variable domain region from a heavy chain and a variable domain region from a light chain, a single chain human antibody, having a variable domain region from a heavy chain and a variable domain region from a light chain and a peptide linker connection the heavy chain and light chain variable domain regions, and combinations thereof;
wherein the fully human antibody has a heavy chain variable domain sequence that is at least 95% identical to the amino acid sequences selected from the group consisting of SEQ ID NO. 35, SEQ ID NO. 51, SEQ ID NO. 137, SEQ ID NO. 155, SEQ ID NO. 157, SEQ ID NO. 159, SEQ ID NO. 161, SEQ ID NO. 163, SEQ ID NO. 165, SEQ ID NO. 179, SEQ ID NO. 183, SEQ ID NO. 185, SEQ ID NO. 213, SEQ ID NO. 215, SEQ ID NO. 217, and SEQ ID NO. 219, and that has a light chain variable domain sequence that is at least 95% identical to the amino acid sequences selected from the group consisting of SEQ ID NO. 36, SEQ ID NO. 52, SEQ ID NO. 138, SEQ ID NO. 156, SEQ ID NO. 158, SEQ ID NO. 160, SEQ ID NO. 162, SEQ ID NO. 164, SEQ ID NO. 166, SEQ ID NO. 180, SEQ ID NO. 184, SEQ ID NO. 186, SEQ ID NO. 214, SEQ ID NO. 216, SEQ ID NO. 218, and SEQ ID NO. 220, and wherein the fully human antibody has a heavy chain/light chain variable domain sequence selected from the group consisting of SEQ ID NO. 35/SEQ ID NO. 36, SEQ ID NO. 51/SEQ ID NO. 52, SEQ ID NO. 137/SEQ ID NO. 138, SEQ ID NO. 155/SEQ ID NO. 156, SEQ ID NO. 157/SEQ ID NO. 158, SEQ ID NO. 159/SEQ ID NO. 160, SEQ ID NO. 161/SEQ ID NO. 162, SEQ ID NO. 163/SEQ ID NO. 164, SEQ ID NO. 165/SEQ ID NO. 166, SEQ ID NO. 179/SEQ ID NO. 180, SEQ ID NO. 183/SEQ ID NO. 184, SEQ ID NO. 185/SEQ ID NO. 186, SEQ ID NO. 213/SEQ ID NO. 214, SEQ ID NO. 215/SEQ ID NO. 216, SEQ ID NO. 217/SEQ ID NO. 218, and SEQ ID NO. 219/SEQ ID NO. 220;
wherein the Fab fully human antibody fragment has the heavy chain variable domain sequence that is at least 95% identical to the amino acid sequences selected from the group consisting of SEQ ID NO. 35, SEQ ID NO. 51, SEQ ID NO. 137, SEQ ID NO. 155, SEQ ID NO. 157, SEQ ID NO. 159, SEQ ID NO. 161, SEQ ID NO. 163, SEQ ID NO. 165, SEQ ID NO. 179, SEQ ID NO. 183, SEQ ID NO. 185, SEQ ID NO. 213, SEQ ID NO. 215, SEQ ID NO. 217, and SEQ ID NO. 219, and that has the light chain variable domain sequence that is at least 95% identical to the amino acid sequences selected from the group consisting of SEQ ID NO. 36, SEQ ID NO. 52, SEQ ID NO. 138, SEQ ID NO. 156, SEQ ID NO. 158, SEQ ID NO. 160, SEQ ID NO. 162, SEQ ID NO. 164, SEQ ID NO. 166, SEQ ID NO. 180, SEQ ID NO. 184, SEQ ID NO. 186, SEQ ID NO. 214, SEQ ID NO. 216, SEQ ID NO. 218, and SEQ ID NO. 220, and wherein the fully human antibody Fab fragment has a heavy chain/light chain variable domain sequence selected from the group consisting of SEQ ID NO. 35/SEQ ID NO. 36, SEQ ID NO. 51/SEQ ID NO. 52, SEQ ID NO. 137/SEQ ID NO. 138, SEQ ID NO. 155/SEQ ID NO. 156, SEQ ID NO. 157/SEQ ID NO. 158, SEQ ID NO. 159/SEQ ID NO. 160, SEQ ID NO. 161/SEQ ID NO. 162, SEQ ID NO. 163/SEQ ID NO. 164, SEQ ID NO. 165/SEQ ID NO. 166, SEQ ID NO. 179/SEQ ID NO. 180, SEQ ID NO. 183/SEQ ID NO. 184, SEQ ID NO. 185/SEQ ID NO. 186, SEQ ID NO. 213/SEQ ID NO. 214, SEQ ID NO. 215/SEQ ID NO. 216, SEQ ID NO. 217/SEQ ID NO. 218, and SEQ ID NO. 219/SEQ ID NO. 220; and
wherein the single chain human antibody has the heavy chain variable domain sequence that is at least 95% identical to the amino acid sequences selected from the group consisting of SEQ ID NO. 35, SEQ ID NO. 51, SEQ ID NO. 137, SEQ ID NO. 155, SEQ ID NO. 157, SEQ ID NO. 159, SEQ ID NO. 161, SEQ ID NO. 163, SEQ ID NO. 165, SEQ ID NO. 179, SEQ ID NO. 183, SEQ ID NO. 185, SEQ ID NO. 213, SEQ ID NO. 215, SEQ ID NO. 217, and SEQ ID NO. 219, and that has the light chain variable domain sequence that is at least 95% identical to the amino acid sequences selected from the group consisting of SEQ ID NO. 36, SEQ ID NO. 52, SEQ ID NO. 138, SEQ ID NO. 156, SEQ ID NO. 158, SEQ ID NO. 160, SEQ ID NO. 162, SEQ ID NO. 164, SEQ ID NO. 166, SEQ ID NO. 180, SEQ ID NO. 184, SEQ ID NO. 186, SEQ ID NO. 214, SEQ ID NO. 216, SEQ ID NO. 218, and SEQ ID NO. 220, and wherein the single chain human antibody has a heavy chain/light chain variable domain sequence selected from the group consisting of SEQ ID NO. 35/SEQ ID NO. 36, SEQ ID NO. 51/SEQ ID NO. 52, SEQ ID NO. 137/SEQ ID NO. 138, SEQ ID NO. 155/SEQ ID NO. 156, SEQ ID NO. 157/SEQ ID NO. 158, SEQ ID NO. 159/SEQ ID NO. 160, SEQ ID NO. 161/SEQ ID NO. 162, SEQ ID NO. 163/SEQ ID NO. 164, SEQ ID NO. 165/SEQ ID NO. 166, SEQ ID NO. 179/SEQ ID NO. 180, SEQ ID NO. 183/SEQ ID NO. 184, SEQ ID NO. 185/SEQ ID NO. 186, SEQ ID NO. 213/SEQ ID NO. 214, SEQ ID NO. 215/SEQ ID NO. 216, SEQ ID NO. 217/SEQ ID NO. 218, and SEQ ID NO. 219/SEQ ID NO. 220.
5. The method for treating a broad spectrum of mammalian cancers of claim 4 , wherein the broad spectrum of mammalian cancers to be treated is selected from the group consisting of ovarian, colon, breast, lung cancers, myelomas, neuroblastic-derived CNS tumors, monocytic leukemias, B-cell derived leukemias, T-cell derived leukemias, B-cell derived lymphomas, T-cell derived lymphomas, mast cell derived tumors, and combinations thereof.