Anti-PD-L1 antibodies and diagnostic uses thereof

• US 10,689,445 B2
• Filed: 10/06/2017
• Issued: 06/23/2020
• Est. Priority Date: 07/11/2014
• Status: Active Grant

• Current Assignee: Ventana Medical Systems Incorporated (Roche Holding AG)
• Original Assignee: Ventana Medical Systems Incorporated (Roche Holding AG)
• Inventors: Kowanetz, Marcin, Koeppen, Hartmut, Boyd, Zachary, Liao, Zhiming, Zhu, Yifei, Vennapusa, Bharathi, Roche, Patrick C.
• Primary Examiner(s): Roark, Jessica H
• Application Number:
  US15/727,388
• Publication Number:
  US 20180022809A1
• Time in Patent Office: 991 Days
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61N 2005/1021 Radioactive fluid
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/70532 B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 16/2827 against B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/54 F(ab')2
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: G01N 2500/10 involving cells
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/53 Immunoassay; Biospecific binding assay; Materials therefor
• CPC Class Codes: G01N 33/57484 involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites

Abstract

The invention provides programmed death-ligand 1 (PD-L1) antibodies and methods of using the same.

Claims

1. An isolated antibody that specifically binds PD-L1, wherein the antibody comprises a heavy chain variable domain (VH) and a light chain variable domain (VL) that comprises the following hypervariable regions (HVRs):

(a) an HVR-H1 comprising the amino acid sequence of SNGLT (SEQ ID NO;

     2);

(b) an HVR-H2 comprising the amino acid sequence of TINKDASAYYASWAKG (SEQ ID NO;

     3);

(c) an HVR-H3 comprising the amino acid sequence of IAFKTGTSI (SEQ ID NO;

4);

(d) an HVR-L1 comprising the amino acid sequence of QASESVYSNNYLS (SEQ ID NO;

     9);

(e) an HVR-L2 comprising the amino acid sequence of LASTLAS (SEQ ID NO;

     10); and

(f) an HVR-L3 comprising the amino acid sequence of IGGKSSSTDGNA (SEQ ID NO;

     11).

2. The antibody of claim 1, wherein the antibody further comprises the following heavy chain variable domain framework regions (FRs):

(a) FR-H1 comprising the amino acid sequence of QSLEESGGRLVKPDETLTITCTVSGIDLS (SEQ ID NO;

5);

(b) FR-H2 comprising the amino acid sequence of WVRQAPGEGLEWIG (SEQ ID NO;

     6);

(c) FR-H3 comprising the amino acid sequence of RLTISKPSSTKVDLKITSPTTEDTATYFCGR (SEQ ID NO;

     7); and

(d) FR-H4 comprising the amino acid sequence of WGPGTLVTVSS (SEQ ID NO;

     8).

3. The antibody of claim 1, wherein the anti bodyfurther comprises the following light chain variable domain framework regions (FRs) FRs:

(a) FR-L1 comprising the amino acid sequence of AIVMTQTPSPVSAAVGGTVTINC (SEQ ID NO;

     12);

(b) FR-L2 comprising the amino acid sequence of WFQQKPGQPPKLLIY (SEQ ID NO;

     13);

(c) FR-L3 comprising the amino acid sequence of GVPSRFKGSGSGTQFTLTISGVQCDDAATYYC (SEQ ID NO;

     14); and

(d) FR-L4 comprising the amino acid sequence of FGGGTEVVVR (SEQ ID NO;

     15).

4. The antibody of claim 1, wherein the antibody comprises a VH sequence of SEQ ID NO:

16 and a VL sequence of SEQ ID NO;

17.

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

6. The antibody of claim 1, wherein the antibody is an IgG antibody.

7. The antibody of claim 1, wherein the antibody is an anti body fragment that specifically binds PD-L1.

8. The antibody of claim 7, wherein the antibody fragment is selected from the group consisting of Fab, single chain variable fragment (scFv), Fv, Fab′

, Fab′

-SH, F(ab′

)₂, and diabody.

9. An immunoconjugate comprising the antibody of claim 1.

10. An isolated nucleic acid encoding an isolated antibody of claim 1.

11. A vector comprising the nucleic acid of claim 10.

12. A host cell comprising the vector of claim 11.

13. A method of detecting the presence or expression level of PD-L1 in a biological sample from a subject comprising contacting the biological sample with the antibody of claim 1 and detecting the presence of the bound antibody.

14. The method of claim 13, wherein the subject is a human.

15. The method of claim 13, wherein the detecting is by immunohistochemistry (IHC), immunofluorescence (IF), flow cytometry, enzyme-linked immunosorbent assay (ELISA) LISA, or immunoblotting.

16. The method of claim 13, wherein the sample comprises a fixed tissue.

17. The method of claim 13, wherein the sample is from a subject having, or at risk of, a cancer.

18. The method of claim 17, wherein the cancer is selected from the group consisting of non-small cell lung cancer, squamous cell cancer, small-cell lung cancer, cancer of the peritoneum, hepatocellular cancer, gastrointestinal cancer, pancreatic cancer, glioma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, breast cancer, colon cancer, colorectal cancer, endometrial or uterine carcinoma, salivary gland carcinoma, kidney cancer, liver cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma, leukemia, and head and neck cancer.

19. The method of claim 18, wherein the cancer is non-small cell lung cancer (NSCLC).

20. The method of claim 17, wherein the sample is a tumor sample.

21. The method of claim 20, wherein the tumor sample comprises tumor infiltrating immune cells, tumor cells, stromal cells, or any combination thereof.

22. The method of claim 21, wherein the tumor sample has a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise about 1% or more of the tumor sample by area.

23. The method of claim 21, wherein the tumor sample has a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise about 5% or more of the tumor sample by area.

24. The method of claim 21, wherein the tumor sample has a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise about 10% or more of the tumor sample by area.

25. The method of claim 21, wherein the tumor sample has a detectable expression level of PD-L1 in about 1% or more of the tumor cells in the tumor sample.

26. The method of claim 21, wherein the tumor sample has a detectable expression level of PD-L1 in about 5% or more of the tumor cells in the tumor sample.

27. The method of claim 21, wherein the tumor sample has a detectable expression level of PD-L1 in about 10% or more of the tumor cells in the tumor sample.

28. The method of claim 21, wherein the tumor sample has a detectable expression level of PD-L1 in about 50% or more of the tumor cells in the tumor sample.