Cancer immunotherapy by disrupting PD-1/PD-L1 signaling

Patent metadata

Field	Value
Publication number	US-12590154-B2
Application number	US-202519193652-A
Country	US
Kind code	B2
Filing date	Apr 29, 2025
Priority date	May 15, 2012
Publication date	Mar 31, 2026
Grant date	Mar 31, 2026

Abstract

The disclosure provides a method for immunotherapy of a subject afflicted with cancer, comprises administering to the subject a composition comprising a therapeutically effective amount of an antibody that inhibits signaling from the PD-1/PD-L1 signaling pathway. This disclosure also provides a method for immunotherapy of a subject afflicted with cancer comprising selecting a subject that is a suitable candidate for immunotherapy based on an assessment that the proportion of cells in a test tissue sample from the subject that express PD-L1 on the cell surface exceeds a predetermined threshold level, and administering a therapeutically effective amount of an anti-PD-1 antibody to the selected subject. The invention additionally provides rabbit mAbs that bind specifically to a cell surface-expressed PD-L1 antigen in a FFPE tissue sample, and an automated IHC method for assessing cell surface expression in FFPE tissues using the provided anti-PD-L1 Abs.

First claim

What is claimed is:

1 . A method of treating a a hepatocellular carcinoma (HCC) in a human subject in need thereof, comprising administering to the subject 1 mg/kg of nivolumab and 3 mg/kg of ipilimumab every 3 weeks for 4 cycles, followed by subsequently administering the nivolumab alone.

2 . The method of claim 1 , wherein the HCC is refractory after at least one prior anti-angiogenic TKI-based therapy or mTOR inhibitor-based therapy.

3 . The method of claim 2 , wherein the at least one prior anti-angiogenic TKI-based therapy comprises sorafenib, sunitinib, pazopanib, axitinib, tivozanib, or a combination thereof.

4 . The method of claim 2 , wherein the at least one prior mTOR inhibitor-based therapy comprises everolimus or temsirolimus.

5 . The method of claim 1 , wherein the nivolumab is formulated in a pharmaceutical composition comprising a pharmaceutically acceptable carrier.

6 . The method of claim 5 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable salt, an adjuvant, an anti-oxidant, or any combination thereof.

7 . The method of claim 6 , wherein the salt comprises a sodium salt.

8 . The method of claim 6 , wherein the salt comprises sodium chloride.

9 . The method of claim 1 , wherein at least 10% of tumor cells of the HCC exhibit membrane PD-L1 expression.

10 . The method of claim 9 , wherein the membranous PD-L1 expression on the tumor cells is measured prior to the administering of the nivolumab.

11 . The method of claim 10 , wherein the measuring comprises an immunohistochemistry.

12 . The method of claim 11 , wherein the immunohistochemistry is performed using an antibody comprising (a) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 35, and (b) a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 36.

13 . A method of treating a hepatocellular carcinoma (HCC) in a human subject in need thereof comprising administering to the subject 1 mg/kg of nivolumab and 3 mg/kg of ipilimumab every 3 weeks for 4 cycles, followed by subsequently administering the nivolumab alone;
wherein the HCC is refractory after at least one prior anti-angiogenic TKI-based therapy comprising sorafenib.

14 . The method of claim 13 , wherein the nivolumab is formulated in a pharmaceutical composition comprising a pharmaceutically acceptable carrier, a pharmaceutically acceptable salt, an adjuvant, an anti-oxidant, or any combination thereof.

15 . The method of claim 14 , wherein the salt comprises a sodium salt.

16 . The method of claim 14 , wherein the salt comprises sodium chloride.

17 . The method of claim 13 , wherein at least 10% of tumor cells of the HCC exhibit membrane PD-L1 expression.

18 . The method of claim 17 , wherein the membranous PD-L1 expression on the tumor cells is measured prior to the administering of the nivolumab.

19 . The method of claim 18 , wherein the measuring comprises an immunohistochemistry.

20 . The method of claim 19 , wherein the immunohistochemistry is performed using an antibody comprising (a) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 35, and (b) a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 36.

Assignees

• Bristol Myers Squibb Co

Inventors

• Cogswell John P
• Goldberg Stacie M
• Gupta Ashok K
• Jure-Kunkel Maria
• Wang xi-tao
• Wigginton Jon M

Classifications

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• G01N2333/70596

  Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705 · CPC title

• C07K16/2803

  against the immunoglobulin superfamily · CPC title

• C07K16/18

  against material from animals or humans · CPC title

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title