Anti-pd-l1 antibodies and diagnostic uses thereof

Patent metadata

Field	Value
Publication number	US-2016009805-A1
Application number	US-201514726329-A
Country	US
Kind code	A1
Filing date	May 29, 2015
Priority date	Jul 11, 2014
Publication date	Jan 14, 2016
Grant date	—

Abstract

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

First claim

1 . An isolated antibody that specifically binds to PD-L1, wherein the antibody binds to an epitope comprising amino acid residues 279-290 of human PD-L1 polypeptide (SEQ ID NO: 1).

2 . The antibody of claim 1 , wherein the antibody 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); and (c) an HVR-H3 comprising the amino acid sequence of IAFKTGTSI (SEQ ID NO: 4).

3 . The antibody of claim 2 , further comprising 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).

4 . The antibody of claim 2 , further comprising the following HVRs:
(a) an HVR-L1 comprising the amino acid sequence of QASESVYSNNYLS (SEQ ID NO: 9); (b) an HVR-L2 comprising the amino acid sequence of LASTLAS (SEQ ID NO: 10); and (c) an HVR-L3 comprising the amino acid sequence of IGGKSSSTDGNA (SEQ ID NO: 11).

5 . The antibody of claim 4 , further comprising the following light chain variable domain 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

6 . The antibody of claim 1 , wherein the antibody comprises the following HVRs:
(a) an HVR-L1 comprising the amino acid sequence of QASESVYSNNYLS (SEQ ID NO: 9); (b) an HVR-L2 comprising the amino acid sequence of LASTLAS (SEQ ID NO: 10); and (c) an HVR-L3 comprising the amino acid sequence of IGGKSSSTDGNA (SEQ ID NO: 11).

7 . The antibody of claim 6 , further comprising the following light chain variable domain 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).

8 . The antibody of claim 1 , comprising (a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 16; (b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 17; or (c) a VH sequence as in (a) and a VL sequence as in (b).

9 - 10 . (canceled)

11 . An isolated antibody that specifically binds PD-L1, wherein the antibody comprises the following 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).

12 . The antibody of claim 11 , wherein the antibody further comprises the following heavy chain variable domain and light chain variable domain 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); (d) FR-H4 comprising the amino acid sequence of WGPGTLVTVSS (SEQ ID NO: 8); (e) FR-L1 comprising the amino acid sequence of AIVMTQTPSPVSAAVGGTVTINC (SEQ ID NO: 12); (f) FR-L2 comprising the amino acid sequence of WFQQKPGQPPKLLIY (SEQ ID NO: 13); (g) FR-L3 comprising the amino acid sequence of GVPSRFKGSGSGTQFTLTISGVQCDDAATYYC (SEQ ID NO: 14); and (h) FR-L4 comprising the amino acid sequence of FGGGTEVVVR (SEQ ID NO: 15).

13 . The antibody of claim 11 , wherein the antibody comprises a VH sequence of SEQ ID NO: 16 and a VL sequence of SEQ ID NO: 17.

14 . An isolated antibody that competes for binding to PD-L1 with the antibody of claim 1 .

15 . An isolated antibody that binds to the same epitope as the antibody of claim 1 .

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

17 . (canceled)

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

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

20 . The antibody of claim 19 , 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.

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

22 . A vector comprising the nucleic acid of claim 21 .

23 . A host cell comprising the vector of claim 22 .

24 . An immunoconjugate comprising the antibody of claim 1 .

25 . The antibody of claim 1 for use in detecting the presence or expression level of PD-L1 in a biological sample.

26 . The antibody of claim 25 , wherein the detecting is by immunohistochemistry (IHC), immunofluorescence (IF), flow cytometry, Enzyme-Linked Immunosorbant Assay (ELISA), or immunoblotting.

27 . (canceled)

28 . The antibody of claim 25 , wherein the sample comprises a fixed tissue.

29 . (canceled)

30 . The antibody of claim 25 , wherein the sample is from a subject having, or at risk of, a cancer or an immune dysfunction.

31 - 32 . (canceled)

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

34 . The method of claim 33 , wherein the detecting is by IHC, IF, flow cytometry, ELISA, or immunoblotting.

35 . (canceled)

36 . The method of claim 33 , wherein the sample comprises a fixed tissue.

37 . (canceled)

38 . The method of claim 33 , wherein the sample is from a subject having, or at risk of, a cancer or an immune dysfunction.

39 . The method of claim 38 , wherein the immune dysfunction is a T-cell dysfunctional disorder.

40 - 41 . (canceled)

42 . The method of claim 33 , wherein the presence or expression level of PD-L1 in the sample indicates that the subject is likely to respond to treatment with an anti-cancer therapy.

43 - 44 . (canceled)

45 . The method of claim 42 , wherein the method further comprises selecting an anti-cancer therapy for the subject based on the presence or expression level of PD-L1 in the sample.

46 . The method of claim 42 , wherein the method further comprises admini

Assignees

• Genentech Inc
• Spring Bioscience Corp
• Ventana Med Syst Inc

Inventors

• Kowanetz Marcin
• Koeppen Hartmut
• Boyd Zachary
• Liao Zhiming
• Zhu Yifei
• Vennapusa Bharathi
• Roche Patrick C

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• G01N33/5758

  involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites · CPC title

• C07K2317/55

  Fab or Fab' · CPC title