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

Patent metadata

Field	Value
Publication number	US-10323093-B2
Application number	US-201816230657-A
Country	US
Kind code	B2
Filing date	Dec 21, 2018
Priority date	May 15, 2012
Publication date	Jun 18, 2019
Grant date	Jun 18, 2019

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 tumor derived from a metastatic non-small cell lung cancer (NSCLC) in a human subject, comprising administering to the subject a therapeutically effective amount of an anti-PD-1 antibody; wherein the anti-PD-1 antibody is administered by intravenous infusion; and wherein at least 20% of tumor cells in the tumor exhibit membrane PD-L1 expression.

2. The method of claim 1 , wherein the therapeutically effective amount of the anti-PD-1 antibody is administered once every 3 weeks.

3. The method of claim 1 , wherein the anti-PD-1 antibody is formulated in a pharmaceutical composition.

4. The method of claim 3 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable salt, an adjuvant, an anti-oxidant, an aqueous carrier, a non-aqueous carrier, or any combination thereof.

5. The method of claim 4 , wherein the salt comprises a sodium salt.

6. The method of claim 4 , wherein the salt comprises sodium chloride.

7. The method of claim 1 , wherein the tumor is refractory to a platinum based chemotherapy.

8. The method of claim 7 , wherein the platinum-based chemotherapy comprises cisplatin, carboplatin, or both.

9. The method of claim 1 , wherein the membranous PD-L1 expression on the tumor cells is measured prior to administering the anti-PD-1 antibody.

10. The method of claim 9 , wherein the measuring comprises an immunohistochemistry.

11. The method of claim 10 , wherein the immunohistochemistry is performed using an antibody comprising:
(a) a heavy chain (HC) complementarity determining region (CDR) 1 comprising the amino acid sequence set forth in the HC-CDR1 of SEQ ID NO: 35;
(b) an HC-CDR2 comprising the amino acid sequence set forth in the HC-CDR2 of SEQ ID NO: 35;
(c) an HC-CDR3 comprising the amino acid sequence set forth in the HC-CDR3 of SEQ ID NO: 35;
(d) a light chain (LC) CDR1 comprising the amino acid sequence set forth in the LC-CDR1 of SEQ ID NO: 36;
(e) an LC-CDR2 comprising the amino acid sequence set forth in the LC-CDR2 of SEQ ID NO: 36; and
(f) an LC-CDR3 comprising the amino acid sequence set forth in the LC-CDR3 of SEQ ID NO: 36.

12. A method of treating a tumor derived from a metastatic NSCLC in a human subject, comprising administering to the subject a therapeutically effective amount of an anti-PD-1 antibody once every 3 weeks;
wherein the anti-PD-1 antibody is administered by intravenous infusion;
wherein the tumor is refractory to a platinum-based chemotherapy; and
wherein at least 20% of tumor cells in the tumor exhibit membrane PD-L1 expression, as determined using an immunohistochemistry.

13. The method of claim 12 , wherein the anti-PD-1 antibody is formulated in a pharmaceutical composition.

14. The method of claim 13 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable salt, an adjuvant, an anti-oxidant, an aqueous carrier, a non-aqueous carrier, or any combination thereof.

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

16. The method of claim 15 , wherein the salt comprises sodium chloride.

17. The method of claim 12 , wherein the platinum-based chemotherapy comprises cisplatin, carboplatin, or both.

18. The method of claim 12 , wherein the immunohistochemistry is performed using an antibody comprising:
(a) a heavy chain (HC) complementarity determining region (CDR) 1 comprising the amino acid sequence set forth in the HC-CDR1 of SEQ ID NO: 35;
(b) an HC-CDR2 comprising the amino acid sequence set forth in the HC-CDR2 of SEQ ID NO: 35;
(c) an HC-CDR3 comprising the amino acid sequence set forth in the HC-CDR3 of SEQ ID NO: 35;
(d) a light chain (LC) CDR1 comprising the amino acid sequence set forth in the LC-CDR1 of SEQ ID NO: 36;
(e) an LC-CDR2 comprising the amino acid sequence set forth in the LC-CDR2 of SEQ ID NO: 36; and
(f) an LC-CDR3 comprising the amino acid sequence set forth in the LC-CDR3 of 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

• A61P43/00

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

• A61P35/04

  specific for metastasis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07K16/18

  against material from animals or humans · CPC title

• C07K16/2827

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