Antibodies specific to glycosylated PD-L1 and methods of use thereof

Patent metadata

Field	Value
Publication number	US-10836827-B2
Application number	US-201615559513-A
Country	US
Kind code	B2
Filing date	Mar 29, 2016
Priority date	Mar 30, 2015
Publication date	Nov 17, 2020
Grant date	Nov 17, 2020

Abstract

Antibodies that bind specifically to glycosylated PD-L1 relative to unglycosylated PD-L1 are provided. Antibodies that recognize specific epitopes of glycosylated PD-L1 protein and can block the binding of PD-L1 to PD-1 are provided. In some aspects, PD-L1 polypeptides comprising glycosylated amino acid residues at amino and carboxy terminal positions of the PD-L1 extracellular domain are also provided. Methods for making and using such antibodies and polypeptides (e.g., for the treatment of cancer) are also provided.

First claim

What is claimed is:

1. An isolated antibody which binds to glycosylated PD-L1,
wherein said antibody has a VH domain comprising CDRs H1, H2 and H3 having the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 6, and SEQ ID NO: 8, respectively, or having the amino acid sequences of SEQ ID NO: 5, SEQ ID NO: 7, and SEQ ID NO: 9, respectively; and
wherein said antibody has a VL domain comprising CDRs L1, L2 and L3 having the amino acid sequences of SEQ ID NO: 12, SEQ ID NO: 14, and SEQ ID NO: 16, respectively.

2. An isolated antibody having a VH domain comprising SEQ ID NO: 3 and VL domain comprising SEQ ID NO: 11.

3. An isolated antibody which binds to glycosylated PD-L1, wherein said antibody has a VH domain comprising CDRs H1, H2 and H3 having the amino acid sequences of SEQ ID NO: 20, SEQ ID NO: 22, and SEQ ID NO: 24, respectively, or SEQ ID NO: 21, SEQ ID NO: 23, and SEQ ID NO: 25, respectively; and
wherein said antibody has a VL domain comprising CDRs L1, L2 and L3 having the amino acid sequences of SEQ ID NO: 28, SEQ ID NO: 30, and SEQ ID NO: 32, respectively.

4. The antibody according to claim 1 , wherein the antibody is one selected from the group consisting of a Fab′, a F(ab′)2, a F(ab′)3, a monovalent scFv, a bivalent scFv, an IgG antibody, an IgM antibody, an IgA antibody, and an antigen binding fragment of an IgG, IgM, or IgA antibody.

5. A composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier, diluent, excipient, or vehicle.

6. The isolated antibody according to claim 3 , wherein the antibody is one selected from the group consisting of a Fab′, a F(ab′)2, a F(ab′)3, a monovalent scFv, a bivalent scFv, an IgG antibody, an IgM antibody, an IgA antibody, and an antigen binding fragment of an IgG, IgM, or IgA antibody.

7. An isolated antibody having a VH domain comprising SEQ ID NO: 19 and VL domain comprising SEQ ID NO: 27.

8. A composition comprising the antibody of claim 3 and a pharmaceutically acceptable carrier, diluent, excipient, or vehicle.

9. The isolated antibody of claim 1 , wherein the antibody comprises a human framework regions.

10. The isolated antibody of claim 9 , wherein the antibody comprises a human constant domains.

11. The isolated antibody of claim 10 , wherein the antibody is an IgG antibody, an IgM antibody, or an IgA antibody.

12. The isolated antibody of claim 3 , wherein the antibody comprises a human framework regions.

13. The isolated antibody of claim 12 , wherein the antibody comprises a human constant domains.

14. The isolated antibody of claim 13 , wherein the antibody is an IgG antibody, an IgM antibody, or an IgA antibody.

15. A method of treating a PD-L1 positive cancer in a subject in need of said treatment, said method comprising
administering to the subject an effective amount of the antibody according to claim 1 .

16. The method of claim 15 , wherein the cancer is at least one cancer selected from the group consisting of a hematological cancer, a breast cancer, a lung cancer, a head & neck cancer, a prostate cancer, an esophageal cancer, a tracheal cancer, a skin cancer, a brain cancer, a liver cancer, a bladder cancer, a stomach cancer, a pancreatic cancer, an ovarian cancer, a uterine cancer, a cervical cancer, a testicular cancer, a colon cancer, a rectal cancer, and a skin cancer.

17. A method of assaying for the presence of glycosylated PD-L1 in a biological sample, said method comprising
contacting a biological sample with an antibody according to claim 1 , wherein detection of binding of said antibody indicates that the sample comprises glycosylated PD-L1.

18. The method of claim 17 , wherein the sample is a cell sample from a cancer or tumor of a subject.

19. A method of identifying a candidate cancer patient for treatment with an agent that blocks binding of PD-L1 with PD-1, the method comprising
testing for the presence of glycosylated PD-L1 on cells derived from a sample of the patient's cancer cells comprising contacting a sample from the patient with an antibody of claim 1 , wherein if said cells are positive for glycosylated PD-L1, said patient is a candidate for said treatment.

20. The method of claim 19 , which further comprises administering to a patient identified as a candidate for said treatment an effective amount of an agent that prevents binding of glycosylated PD-L1 to PD-1.

21. A method of treating a PD-L1 positive cancer in a subject in need of said treatment, said method comprising
administering to the subject an effective amount of the antibody according to claim 3 .

22. The method of claim 21 , wherein the cancer is at least one cancer selected from the group consisting of a hematological cancer, a breast cancer, a lung cancer, a head & neck cancer, a prostate cancer, an esophageal cancer, a tracheal cancer, a skin cancer, a brain cancer, a liver cancer, a bladder cancer, a stomach cancer, a pancreatic cancer, an ovarian cancer, a uterine cancer, a cervical cancer, a testicular cancer, a colon cancer, a rectal cancer, and a skin cancer.

23. A method of assaying for the presence of glycosylated PD-L1 in a biological sample, said method comprising
contacting a biological sample with an antibody according to claim 3 , wherein detection of binding of said antibody indicates that the sample comprises glycosylated PD-L1.

24. The method of claim 23 , wherein the sample is a cell sample from a cancer or tumor of a subject.

Assignees

• Stcube Inc
• Board Of Regents The Univ Of Texas
• Univ Texas

Inventors

• Yoo Stephen S
• Chung Ezra M
• Kim Yong-Soo
• Hung Mien-Chie
• Li Chia-Wei
• Lim Seung-Oe

Classifications

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• C07K16/2827 Primary

  against B7 molecules, e.g. CD80, CD86 · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K16/3092

  against tumour-associated mucins · CPC title