Composition for inducing proliferation or accumulation of regulatory T cells

Patent metadata

Field	Value
Publication number	US-10588925-B2
Application number	US-201916389380-A
Country	US
Kind code	B2
Filing date	Apr 19, 2019
Priority date	Jun 4, 2010
Publication date	Mar 17, 2020
Grant date	Mar 17, 2020

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 a purified bacterial mixture of at least two live bacterial strains belonging to Clostridium clusters IV and/or XIVa,
wherein the bacterial mixture induces proliferation and/or accumulation of regulatory T cells,
wherein the 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 at least two live bacterial strains belonging to Clostridium clusters IV and/or XIVa comprise two or more strains belonging to Clostridium cluster IV.

3. The pharmaceutical composition of claim 1 , wherein the at least two live bacterial strains belonging to Clostridium clusters IV and/or XIVa comprise two or more strains belonging to Clostridium cluster XIVa.

4. The pharmaceutical composition of claim 1 , wherein the at least two live bacterial strains belonging to Clostridium clusters IV and/or XIVa comprise one or more strains belonging to Clostridium cluster IV and one or more strains belonging to Clostridium cluster XIVa.

5. 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.

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

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

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

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

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

11. The method of claim 10 , 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.

12. The method of claim 10 , wherein the autoimmune disease is organ transplant rejection, inflammatory bowel disease (IBD), ulcerative colitis, or Crohn's disease.

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

14. The method of claim 13 , wherein the allergic disease is food allergy.

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

16. The method of claim 14 , wherein the infectious disease is Clostridium difficile infection.

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

18. The pharmaceutical composition of claim 17 , wherein the at least two live bacterial strains belonging to Clostridium clusters IV and/or XIVa comprise two or more strains belonging to Clostridium cluster IV.

19. The pharmaceutical composition of claim 17 , wherein the at least two live bacterial strains belonging to Clostridium clusters IV and/or XIVa comprise two or more strains belonging to Clostridium cluster XIVa.

20. The pharmaceutical composition of claim 17 , wherein the at least two live bacterial strains belonging to Clostridium clusters IV and/or XIVa comprise one or more strains belonging to Clostridium cluster IV and one or more strains belonging to Clostridium cluster XIVa.

21. The pharmaceutical composition of claim 17 , 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 17 , wherein the pharmaceutical composition further comprises a pharmacologically acceptable excipient.

23. The pharmaceutical composition of claim 17 , wherein the pharmaceutical composition is formulated for oral administration.

24. The pharmaceutical composition of claim 17 , wherein the pharmaceutical composition is in the form of a capsule.

25. A method of treating a human subject having an autoimmune disease, the method comprising administering the composition of claim 17 .

26. The method of claim 25 , 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.

27. The method of claim 25 , wherein the autoimmune disease is organ transplant rejection, inflammatory bowel disease (IBD), ulcerative colitis, or Crohn's disease.

28. A method of treating a human subject having an allergic disease, the method comprising administering the composition of claim 17 .

29. The method of claim 28 , wherein the allergic disease is food allergy.

30. A method of treating a human subject having an infectious disease, the method comprising administering the composition of claim 17 .

31. The method of claim 30 , wherein the infectious disease is Clostridium difficile infection.

32. A pharmaceutical composition, comprising a purified bacterial mixture of at least two live bacterial strains belonging to Clostridium clusters IV and/or XIVa,
wherein the bacterial mixture induces proliferation and/or accumulation of regulatory T cells,
wherein the bacterial strains are human commensal bacteria, and
wherein the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.

33. The pharmaceutical composition of claim 32 , wherein the at least two live bacterial strains belonging to Clostridium clusters IV and/or XIVa comprise two or more strains belonging to Clostridium cluster IV.

34. The pharmaceutical composition of claim 32 , wherein the at least two live bacterial strains belonging to Clostridium clusters IV and/or XIVa comprise two or more strains belonging to Clostridium cluster XIVa.

35. The pharmaceutical composition of claim 32 , wherein the at least two live bacterial strains belonging to Clostridium clusters IV and/or XIVa comprise one or more strains belonging to Clostridium cluster IV and one or more strains belonging to Clostridium cluster XIVa.

36. The pharmaceutical composition of claim 32 , 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.

37. The pharmaceutical composition of claim 32 , wherein the pharmaceuti

Assignees

• Univ Tokyo

Inventors

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

Classifications

• A61P43/00

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

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P37/02

  Immunomodulators · CPC title