Antibodies and immunocytokines
The present invention relates to anti-PD-L1 antibodies, bispecific antibodies containing one domain with specificity to PD-L1, and to immunocytokines comprising an anti-PD-L1 antibody fused to a cytokine, such as IL-2. The present invention also provides methods of treatment, uses and pharmaceutical compositions comprising the antibodies, bispecific antibodies and immunocytokines.
1. An antibody or a fragment thereof which specifically binds to hPD-L1, wherein the antibody or fragment thereof comprises a V H domain which comprises a CDRH3 sequence of SEQ ID NO: 9 or 12 and competes for binding to said hPD-L1 with the antibody 84G09, which antibody 84G09 comprises the V H amino acid sequence of SEQ ID NO:13 and the V L amino acid sequence of SEQ ID NO:23.
2. The antibody or fragment thereof according to claim 1 , wherein the V H domain comprises the CDRH1 amino acid sequence of SEQ ID NO:7 or 10.
3. The antibody or fragment thereof according to claim 1 , wherein the V H domain comprises the CDRH1 amino acid sequence of SEQ ID NO:7 or 10 and the CDRH2 amino acid sequence of SEQ ID NO:8 or 11.
4. The antibody or fragment thereof according to claim 1 , wherein the V H domain comprises the amino acid sequence of SEQ ID NO:13.
5. The antibody or fragment thereof according to claim 1 , wherein the V H domain comprises the CDRH1 amino acid sequence of SEQ ID NO:7 or 10 and the CDRH2 amino acid sequence of SEQ ID NO:8 or 11, and further comprising a V L domain, which comprises the CDRL1 amino acid sequence of SEQ ID NO:17 or 20.
6. The antibody or fragment thereof according to claim 1 , wherein the V H domain comprises the CDRH1 amino acid sequence of SEQ ID NO:7 or 10 and the CDRH2 amino acid sequence of SEQ ID NO:8 or 11, and further comprising a V L domain, which comprises the CDRL1 amino acid sequence of SEQ ID NO:17 or 20, and the CDRL2 amino acid sequence of SEQ ID NO:18 or 21.
7. The antibody or fragment thereof according to claim 1 , wherein the V H domain comprises the CDRH1 amino acid sequence of SEQ ID NO:7 or 10 and the CDRH2 amino acid sequence of SEQ ID NO:8 or 11, and further comprising a V L domain, which comprises the CDRL1 amino acid sequence of SEQ ID NO:17 or 20, the CDRL2 amino acid sequence of SEQ ID NO:18 or 21, and the CDRL3 amino acid sequence of SEQ ID NO:19 or 22.
8. The antibody or fragment thereof according to claim 1 , wherein the V H domain comprises the amino acid sequence of SEQ ID NO:13, and further comprising a V L domain which comprises the amino acid sequence of SEQ ID NO:23.
9. The antibody or fragment thereof according to claim 1 , comprising two copies of said V H domain.
10. The antibody or fragment thereof according to claim 1 , further comprising a second antibody or fragment thereof that specifically binds to a target antigen other than hPD-L1.
11. The antibody or fragment thereof according to claim 10 , wherein the first antibody or fragment thereof specifically binds to hPD-L1 and the second antibody or fragment thereof specifically binds another target antigen selected from the group consisting of: PD-1, CTLA-4, TIGIT, TIM-3, LAG-3 VISTA, BTLA, HVEM, CSF1R, CCR4, CD39, CD40, CD73, CD96, CXCR2, CXCR4, CD200, GARP, SIRPα, CXCL9, CXCL10, CD155, CD137, CSF1R, CD137, GITR, OX40, CXCR3, CD3, and ICOS.
12. The antibody or fragment thereof according to claim 1 , comprising two copies of said VH domain and said VL domain.
13. The antibody or a fragment thereof according to claim 1 , comprised within a bispecific antibody which comprises specificity for hPDL-1 and a target antigen other than hPDL-1.
14. The antibody or a fragment thereof according to claim 1 , wherein said antibody is comprised within an immunocytokine and wherein said antibody is fused to a cytokine molecule.
15. A composition comprising the antibody of claim 1 , and a pharmaceutically acceptable excipient, diluent, or carrier.
16. A method of treating a malignant tumour in a human in need thereof, the method comprising administering to the human the antibody or fragment thereof according to any one of claim 15 .
17. The method of claim 16 , wherein the malignant tumour is selected from the group consisting of: melanoma, Merkel cell carcinoma, squamous non-small cell lung cancer, non-squamous non-small cell lung cancer, renal cell cancer, bladder cancer, head and neck squamous cell carcinoma, mesothelioma, virally induced cancers, cervical cancer, nasopharyngeal cancer, soft tissue sarcomas, haematological malignancies, Hodgkin's and non-Hodgkin's disease, and diffuse large B-cell lymphoma.
18. The method of claim 17 , wherein the malignant tumour is melanoma.
19. The method of claim 17 , wherein the malignant tumour is non-small cell lung cancer.
20. The method of claim 17 , wherein the malignant tumour is bladder cancer.