PD-L1 antibodies and uses thereof

1. A method of detecting human PD-L1 in a biological sample, the method comprising:

(a) contacting the sample with an antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment comprises a heavy chain (HC) immunoglobulin variable domain sequence and a light chain (LC) immunoglobulin variable domain sequence, wherein:

(a1) the HC immunoglobulin variable domain sequence comprises

(a1a) a HC CDR1 comprising the amino acid sequence NHAIS (SEQ ID NO: 14); and

(a1b) a HC CDR2 comprising the amino acid sequence TINSDTHTYYATWPKG (SEQ ID NO: 15); and

(a1c) a HC CDR3 comprising the amino acid sequence RIFSSSNI (SEQ ID NO: 16); and

(a2) the LC immunoglobulin variable domain sequence comprises

(a2a) a LC CDR1 comprising the amino acid sequence QASQSIYNNNWLS (SEQ ID NO: 17); and

(a2b) a LC CDR2 comprising the amino acid sequence LASTLAS (SEQ ID NO: 12); and

(a2c) a LC CDR3 comprising the amino acid sequence IGGESSNNDGIA (SEQ ID NO: 18); and

(b) detecting a complex formed by the binding of the antibody or antigen binding fragment to PD-L1.

2. The method of claim 1 , wherein the HC immunoglobulin variable domain sequence comprises the amino acid sequence of SEQ ID NO: 2.

3. The method of claim 1 , wherein the LC immunoglobulin variable domain sequence comprises the amino acid sequence of SEQ ID NO: 3.

4. The method of claim 1 , wherein the HC immunoglobulin variable domain sequence comprises the amino acid sequence of SEQ ID NO: 2, and wherein the LC immunoglobulin variable domain sequence comprises the amino acid sequence of SEQ ID NO: 3.

5. The method of claim 1 , wherein the antibody is a monoclonal antibody.

6. The method of claim 1 , wherein the sample comprises a cell or a tissue sample.

7. The method of claim 1 , wherein the sample is obtained from a subject that is diagnosed as having, suspected as having, or at risk of having cancer.

8. The method of claim 7 , wherein the cancer is selected from the group consisting of bladder transitional cell carcinoma, lung adenocarcinoma, breast ductal carcinoma, Hodgkin's lymphoma, pancreas adenocarcinoma, prostate adenocarcinoma, cervical squamous cell carcinoma, skin squamous cell carcinoma, and non-small cell lung cancer.

9. The method of claim 1 , wherein the detection comprises one or more of immunohistochemistry (IHC), Western blotting, flow cytometry or ELISA.

10. A method of detecting a cancer cell in a sample isolated from a subject, the method comprising

(a) contacting the sample with an antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment comprises a heavy chain (HC) immunoglobulin variable domain sequence and a light chain (LC) immunoglobulin variable domain sequence, wherein:

(a1) the HC immunoglobulin variable domain sequence comprises

(a1a) a HC CDR1 comprising the amino acid sequence NHAIS (SEQ ID NO: 14); and

(a1b) a HC CDR2 comprising the amino acid sequence TINSDTHTYYATWPKG (SEQ ID NO: 15); and

(a1c) a HC CDR3 comprising the amino acid sequence RIFSSSNI (SEQ ID NO: 16); and

(a2) the LC immunoglobulin variable domain sequence comprises

(a2a) a LC CDR1 comprising the amino acid sequence QASQSIYNNNWLS (SEQ ID NO: 17); and

(a2b) a LC CDR2 comprising the amino acid sequence LASTLAS (SEQ ID NO: 12); and

(a2c) a LC CDR3 comprising the amino acid sequence IGGESSNNDGIA (SEQ ID NO: 18); and

(b) detecting a level of complex formed by the binding of the antibody or antigen binding fragment to PD-L1, wherein the level of complex is indicative of a level of PD-L1 protein in the sample; and

(c) comparing the level of PD-L1 protein detected in step (b) with the level of PD-L1 protein detected in a control biological sample;

wherein the cancer cell is detected when the level of PD-L1 detected in step (b) is elevated compared to that detected in the control biological sample and the cancer cell is not detected when the level of PD-L1 detected in step (b) is not elevated as compared to that detected in the control biological sample.

11. The method of claim 10 , wherein the biological sample of the subject comprises one or more of a sample isolated from lung, kidney, bladder, breast, pancreas, prostate, cervix or skin.

12. The method of claim 10 , wherein the detection comprises one or more of immunohistochemistry (IHC), Western Blotting, Flow cytometry or ELISA.

13. A method of detecting PD-L1 in a formalin-fixed, paraffin embedded tumor sample, the method comprising:

(a) immunohistochemically staining the tumor sample with an antibody or an antigen binding fragment of the antibody and a chromogen, wherein the antibody or the antigen-binding fragment of the antibody comprises a heavy chain (HC) immunoglobulin variable domain sequence and a light chain (LC) immunoglobulin variable domain sequence, wherein:

(a)(i) the HC immunoglobulin variable domain sequence comprises

(i)(a) a HC CDR1 comprising the amino acid sequence NHAIS (SEQ ID NO: 14);

(i)(b) a HC CDR2 comprising the amino acid sequence TINSDTHTYYATWPKG (SEQ ID NO: 15); and

(i)(c) a HC CDR3 comprising the amino acid sequence RIFSSSNI (SEQ ID NO: 16); and

(a)(ii) the LC immunoglobulin variable domain sequence comprises

(ii)(a) a LC CDR1 comprising the amino acid sequence QASQSIYNNNWLS (SEQ ID NO: 17);

(ii)(b) a LC CDR2 comprising the amino acid sequence LASTLAS (SEQ ID NO: 12); and

(ii)(c) a LC CDR3 comprising the amino acid sequence IGGESSNNDGIA (SEQ ID NO: 18); and

(b) detecting chromogen deposited on the sample as a result of the immunohistochemical staining of (a).

14. The method of claim 13 , wherein the antibody or antigen binding fragment of the antibody binds to an epitope of the amino acid sequence CGIQDTNSKKQSDTHLEET (SEQ ID NO: 1).

15. The method of claim 13 , wherein the antibody or antigen binding fragment of the antibody has a half maximal effective concentration (EC 50 ) of at least 1.5×10 −11 M.