Methods for treating inflammatory bowel disease II

Abstract

The therapeutic needs of patients with IBD and / or related conditions or symptoms remain unmet, and new treatment options are needed. [Solution] This disclosure relates to a method for treating or preventing inflammatory bowel disease (IBD) in a subject in need thereof, comprising administering a composition comprising mesenchymal lineage progenitor or stem cell (MLPSC) to the subject.

Claims

1. A method for treating or preventing inflammatory bowel disease in human subjects who require it, Administering a composition containing mesenchymal lineage progenitor or stem cells (MLPSCs) to the subject. The method comprising, wherein the subject is refractory to at least one biological therapy.

2. The method according to claim 1, wherein the subject is refractory to a single biological therapy.

3. A method for treating or preventing inflammatory bowel disease in human subjects who are refractory to a single biological therapy, Administering a composition containing mesenchymal lineage progenitor or stem cells (MLPSCs) to the subject. The method comprises administering a total dose of less than 600 million mesenchymal lineage progenitors or stem cells.

4. The method according to any one of claims 1 to 3, wherein the biological therapy is anti-TNF therapy.

5. The method according to any one of claims 1 to 3, wherein the biological therapy is infliximab, adalimumab, certolizumab pegol, vedolizumab, or ustekinumab.

6. The method according to any one of claims 1 to 4, wherein the biological therapy is infliximab or adalimumab.

7. The aforementioned subject is, Azathioprine, mercaptopurine (6-MP), methotrexate, cyclosporine, or steroids The method according to any one of claims 1 to 6, which is unresponsive to one or more of the following.

8. The method according to any one of claims 1 to 7, wherein the inflammatory bowel disease is Crohn's disease or ulcerative colitis.

9. The method according to claim 8, wherein the inflammatory bowel disease is Crohn's disease.

10. The method according to claim 9, wherein the Crohn's disease manifests in the rectum and / or colon of the subject.

11. The method according to any one of claims 1 to 10, wherein the C-reactive protein (CRP) level of the subject is less than 23.

12. The method according to any one of claims 1 to 10, wherein the C-reactive protein (CRP) level of the subject is less than 20.

13. The method according to any one of claims 1 to 12, wherein the subject has a partial clinical and / or endoscopic response at least 28 days after treatment.

14. The method according to any one of claims 1 to 12, wherein the subject has a partial clinical and / or endoscopic response at least 28 to 56 days after treatment.

15. The aforementioned partial clinical response, - A reduction of more than 25% in C-reactive protein (CRP); - A decrease of less than 100 points in the CDA Activity Index (CDAI); - Radiographic healing with improvement of inflammation as evaluated by MR enterography The method according to claim 13 or claim 14, characterized by one or more or all of the above.

16. The aforementioned partial endoscopic response, - Crohn's disease plain endoscopic score (SES-CD) decreased by more than 25%, and SES-CD < 50%; - SES-CD scores for 10-15 The method according to claim 13 or claim 14, characterized by one or both of the above.

17. The method according to any one of claims 1 to 12, wherein the subject has a clinical and / or endoscopic response at least 28 days after treatment.

18. The method according to any one of claims 1 to 12, wherein the subject has a clinical and / or endoscopic response at least 28 to 56 days after treatment.

19. The aforementioned clinical response, - A reduction of more than 50% in CRP; - Normalization of CRP levels; - A decrease of 100 points or more in the CDAI score; - Radiographic healing with improvement of inflammation as evaluated by MR enterography The method according to claim 17 or claim 18, characterized by one or more or all of the above.

20. The aforementioned endoscopic response, - SES-CD decreased by more than 25% but less than 50%; - SES-CD scores for 5-10 The method according to claim 17 or claim 18, characterized by one or both of the above.

21. The method according to any one of claims 1 to 12, wherein the subject is in a state of clinical and / or endoscopic remission at least 28 days after treatment.

22. The method according to any one of claims 1 to 12, wherein the subject is in a state of clinical and / or endoscopic remission at least 28 to 56 days after treatment.

23. The aforementioned clinical remission, - Normalization of CRP to less than 2.87 mg per liter; - Radiographic healing with improvement of inflammation as evaluated by MR enterography The method according to claim 21 or claim 22, characterized by one or both of the above.

24. The aforementioned endoscopic remission, - Absence of mucosal ulceration; - SES-CD score (0-5) The method according to claim 21 or claim 22, characterized by one or both of the above.

25. The method according to any one of claims 1 to 24, wherein the composition is administered to the gastrointestinal wall of the target.

26. The method according to any one of claims 1 to 25, wherein the composition is administered to the submucosal layer of the gastrointestinal wall of the target.

27. The method according to any one of claims 1 to 26, wherein the composition is administered to the site of inflammation in the wall of the gastrointestinal tract of the subject.

28. The method according to any one of claims 1 to 27, wherein the composition is administered to the colon and / or rectum of the subject.

29. The method according to any one of claims 1 to 28, wherein the composition is administered by intraluminal injection.

30. The method according to any one of claims 1 to 29, wherein the composition is administered to the submucosal layer of the colon wall of the subject.

31. The method according to any one of claims 1 to 30, wherein the composition is administered to multiple sites on the wall of the gastrointestinal tract of the target.

32. The method according to any one of claims 1 to 24, wherein the composition is administered intravenously.

33. The method according to any one of claims 25 to 31, wherein the composition is also administered intravenously.

34. The method according to any one of claims 1 to 33, wherein the MLPSC is a mesenchymal stem cell (MSC).

35. The method according to any one of claims 1 to 34, wherein the MLPSCs are of the same type but different in structure.

36. The method according to any one of claims 9 to 35, wherein the Crohn's disease is moderate to severe.

37. The method according to any one of claims 1 to 36, wherein the CDAI of the target is greater than 300.

38. The method according to any one of claims 9 to 37, wherein the Crohn's disease is Crohn's disease accompanied by fistulas.

39. The method according to any one of claims 1 to 31 and 33 to 38, wherein the mesenchymal progenitor or stem cell (MLPSC) is administered by endoscopy.

40. 1 x 10 ７ ~2 x 10 ８ The method according to any one of claims 1 to 39, comprising administering individual cells.

41. 1 × 10 ７ ~2 x 10 ８ The method according to any one of claims 1 to 31 and 33 to 40, comprising administering individual cells.

42. The method according to any one of claims 1 to 41, wherein the composition further comprises Plasma-Lyte A, dimethyl sulfoxide (DMSO), and human serum albumin (HSA).

43. 7.5 x 10 ７ The method according to any one of claims 1 to 39 or 42, comprising administering individual cells.

44. 1.5 x 10 ８ The method according to any one of claims 1 to 39 or 42, comprising administering individual cells.

45. The method according to any one of claims 1 to 44, wherein the composition further comprises a solution of Plasma-Lyte A (70%), DMSO (10%), and HSA (25%), the HSA solution comprising 5% HSA and 15% buffering agent.

46. The above composition is 6.68 × 10 ６ The method according to any one of claims 1 to 45, comprising more than 1000 living cells / mL.

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