Composition for inducing proliferation or accumulation of regulatory T cells

Patent metadata

Field	Value
Publication number	US-11090343-B2
Application number	US-202016780116-A
Country	US
Kind code	B2
Filing date	Feb 3, 2020
Priority date	Jun 4, 2010
Publication date	Aug 17, 2021
Grant date	Aug 17, 2021

Abstract

It was found that bacteria belonging to the genus Clostridium induce accumulation of regulatory T cells (Treg cells) in the colon. Moreover, the present inventors found that regulatory T cells (Treg cells) induced by from these bacteria suppressed proliferation of effector T-cells. From these findings, the present inventors found that the use of bacteria belonging to the genus Clostridium or a physiologically active substance derived therefrom made it possible to induce proliferation or accumulation of regulatory T cells (Treg cells), and further to suppress immune functions.

First claim

The invention claimed is:

1. A pharmaceutical composition, comprising one or more purified live bacterial strains belonging to Clostridium clusters IV or XIVa,
wherein the one or more bacterial strains induces proliferation and/or accumulation of regulatory T cells,
wherein the one or more bacterial strains are human commensal bacteria, and
wherein the pharmaceutical composition is formulated for delivery to the intestine.

2. The pharmaceutical composition of claim 1 , wherein the one or more bacterial strains belonging to Clostridium clusters IV or XIVa comprises one or more bacterial strains belonging to Clostridium cluster IV.

3. The pharmaceutical composition of claim 1 , wherein the one or more bacterial strains belonging to Clostridium clusters IV or XIVa comprises one or more bacterial strains belonging to Clostridium cluster XIVa.

4. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises one or more bacterial strains belonging to a Clostridium cluster other than Clostridium cluster IV or Clostridium cluster XIVa.

5. The pharmaceutical composition of claim 1 , wherein at least one of the one or more bacterial strains is a spore forming bacteria.

6. The pharmaceutical composition of claim 1 , wherein at least one of the one or more bacterial strains is in the form of spores.

7. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises a pharmacologically acceptable excipient.

8. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for oral administration.

9. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.

10. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is in the form of a capsule.

11. A method of treating a human subject having an autoimmune disease, the method comprising administering to the human subject the composition of claim 1 .

12. The method of claim 11 , wherein the autoimmune disease is organ transplant rejection, inflammatory bowel disease (IBD), ulcerative colitis, Crohn's disease, sprue, rheumatoid arthritis, Type 1 diabetes, graft versus host disease, or multiple sclerosis.

13. The method of claim 11 , wherein the autoimmune disease is organ transplant rejection, inflammatory bowel disease (IBD), ulcerative colitis, or Crohn's disease.

14. A method of treating a human subject having an allergic disease, the method comprising administering to the human subject the composition of claim 1 .

15. The method of claim 14 , wherein the allergic disease is food allergy.

16. A method of treating a human subject having an infectious disease, the method comprising administering to the human subject the composition of claim 1 .

17. The method of claim 16 , wherein the infectious disease is Clostridium difficile infection.

18. A pharmaceutical composition, comprising one or more purified bacterial strains belonging to Clostridium clusters IV or XIVa,
wherein the one or more bacterial strains induces proliferation and/or accumulation of regulatory T cells,
wherein the one or more bacterial strains are isolated from a human, and
wherein the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.

19. The pharmaceutical composition of claim 18 , wherein the one or more bacterial strains belonging to Clostridium clusters IV or XIVa comprises one or more bacterial strains belonging to Clostridium cluster IV.

20. The pharmaceutical composition of claim 18 , wherein the one or more bacterial strains belonging to Clostridium clusters IV or XIVa comprises one or more bacterial strains belonging to Clostridium cluster XIVa.

21. The pharmaceutical composition of claim 18 , wherein the pharmaceutical composition further comprises one or more bacterial strains belonging to a Clostridium cluster other than Clostridium cluster IV or Clostridium cluster XIVa.

22. The pharmaceutical composition of claim 18 , wherein at least one of the one or more bacterial strains is a spore forming bacteria.

23. The pharmaceutical composition of claim 18 , wherein at least one of the one or more bacterial strains is in the form of spores.

24. The pharmaceutical composition of claim 18 , wherein the pharmaceutical composition further comprises a pharmacologically acceptable excipient.

25. The pharmaceutical composition of claim 18 , wherein the pharmaceutical composition is formulated for oral administration.

26. The pharmaceutical composition of claim 18 , wherein the pharmaceutical composition is in the form of a capsule.

27. A method of treating a human subject having an autoimmune disease, the method comprising administering to the human subject the composition of claim 18 .

28. The method of claim 27 , wherein the autoimmune disease is organ transplant rejection, inflammatory bowel disease (IBD), ulcerative colitis, Crohn's disease, sprue, rheumatoid arthritis, Type 1 diabetes, graft versus host disease, or multiple sclerosis.

29. The method of claim 27 , wherein the autoimmune disease is organ transplant rejection, inflammatory bowel disease (IBD), ulcerative colitis, or Crohn's disease.

30. A method of treating a human subject having an allergic disease, the method comprising administering to the human subject the composition of claim 18 .

31. The method of claim 30 , wherein the allergic disease is food allergy.

32. A method of treating a human subject having an infectious disease, the method comprising administering to the human subject the composition of claim 18 .

33. The method of claim 32 , wherein the infectious disease is Clostridium difficile infection.

Assignees

• Univ Tokyo

Inventors

• Honda Kenya
• Atarashi Koji
• Itoh Kikuji
• Tanoue Takeshi

Classifications

• A61P1/04

  for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• G01N2333/33

  from Clostridium (G) · CPC title

• A61K35/00

  Medicinal preparations containing materials or reaction products thereof with undetermined constitution · CPC title

• G01N2500/10

  involving cells · CPC title