Checkpoint blockade and microsatellite instability

Patent metadata

Field	Value
Publication number	US-11718668-B2
Application number	US-202217739274-A
Country	US
Kind code	B2
Filing date	May 9, 2022
Priority date	Nov 13, 2014
Publication date	Aug 8, 2023
Grant date	Aug 8, 2023

Abstract

Blockade of immune checkpoints such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) shows promise in patients with cancer. Inhibitory antibodies directed at these receptors have been shown to break immune tolerance and promote anti-tumor immunity. These agents work particularly well in patients with a certain category of tumor. Such tumors may be particularly susceptible to treatment because of the multitude of neoantigens which they produce.

First claim

We claim:

1. A method of treating colorectal cancer in a human patient, the method comprising
testing or having tested a biological sample obtained from a patient having colorectal cancer, thereby determining that the patient's colorectal cancer is microsatellite instability high or DNA mismatch repair deficient; and
in response to determining that the colorectal cancer is microsatellite instability high or DNA mismatch repair deficient, treating the patient determined to have microsatellite instability high or DNA mismatch repair deficient colorectal cancer with a therapeutically effective amount of an anti-PD-1 antibody.

2. The method of claim 1 , wherein the biological sample is tumor tissue.

3. The method of claim 1 , wherein the biological sample is a body fluid.

4. The method of claim 1 , wherein the anti-PD-1 antibody is pembrolizumab or nivolumab.

5. The method of claim 1 , wherein the colorectal cancer is determined to be microsatellite instability high.

6. The method of claim 1 , wherein the colorectal cancer is determined to be DNA mismatch repair deficient.

7. The method of claim 1 , wherein the patient had previously been treated with a prior cancer therapy drug and the patient's colorectal cancer had progressed after the patient was treated with the prior cancer therapy drug.

8. The method of claim 1 , wherein the testing or having tested comprises carrying out or having carried out next generation sequencing on the sample.

9. The method of claim 1 , wherein the anti-PD-1 antibody is administered to the patient intravenously.

10. The method of claim 5 , wherein the anti-PD-1 antibody is administered to the patient intravenously.

11. The method of claim 6 , wherein the anti-PD-1 antibody is administered to the patient intravenously.

12. The method of claim 1 further comprising testing or having tested the patient for progression of the colorectal cancer after the treatment.

13. The method of claim 1 , wherein the colorectal cancer is metastatic colorectal cancer.

14. A method of reducing the risk of cancer progression or increasing overall survival in a human patient, the method comprising:
testing, or having tested, a biological sample obtained from a patient having colorectal cancer, thereby determining that the patient's colorectal cancer is microsatellite instability high or DNA mismatch repair deficient; and
in response to determining that the colorectal cancer is microsatellite instability high or DNA mismatch repair deficient, treating the patient determined to have microsatellite instability high or DNA mismatch repair deficient colorectal cancer with a therapeutically effective amount of an anti-PD-1 antibody.

15. The method of claim 14 , wherein the biological sample is a tumor tissue sample from the patient.

16. The method of claim 14 , wherein the biological sample is a body fluid from the patient.

17. The method of claim 14 , wherein the anti-PD-1 antibody is pembrolizumab or nivolumab.

18. The method of claim 14 , wherein the colorectal cancer is determined to be microsatellite instability high.

19. The method of claim 14 , wherein the colorectal cancer is determined to be DNA mismatch repair deficient.

20. The method of claim 14 , wherein, the patient had previously been treated with a prior cancer therapy drug and the patient's colorectal cancer had progressed after the patient was treated with the prior cancer therapy drug.

21. The method of claim 14 , wherein the testing or having tested comprises carrying out or having carried out next generation sequencing on the sample.

22. The method of claim 14 , wherein the anti-PD-1 antibody is administered to the patient intravenously.

23. The method of claim 18 , wherein the anti-PD-1 antibody is administered to the patient intravenously.

24. The method of claim 19 , wherein the anti-PD-1 antibody is administered to the patient intravenously.

25. The method of claim 14 further comprising testing or having tested the patient for progression of the colorectal cancer after the treatment.

26. The method of claim 14 , wherein the colorectal cancer is metastatic colorectal cancer.

27. The method of claim 1 , wherein the anti-PD-1 antibody is pembrolizumab.

28. The method of claim 1 , wherein the anti-PD-1 antibody is nivolumab.

29. The method of claim 14 , wherein the anti-PD-1 antibody is pembrolizumab.

30. The method of claim 14 , wherein the anti-PD-1 antibody is nivolumab.

Assignees

• Univ Johns Hopkins

Inventors

• Diaz Luis
• Vogelstein Bert
• Kinzler Kenneth W
• Papadopoulos Nickolas
• Le Dung
• Pardoll Drew M
• Topalian Suzanne L

Classifications

• C07K16/2803 Primary

  against the immunoglobulin superfamily · CPC title

• C07K16/2818 Primary

  against CD28 or CD152 · CPC title

• C07K16/2827

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

• C07K16/30

  from tumour cells · CPC title

• C07K16/40

  against enzymes · CPC title