Compositions containing combinations of bioactive molecules derived from microbiota for treatment of disease

Patent metadata

Field	Value
Publication number	US-2016144014-A1
Application number	US-201414903377-A
Country	US
Kind code	A1
Filing date	Jul 8, 2014
Priority date	Jul 9, 2013
Publication date	May 26, 2016
Grant date	—

Abstract

Compositions consisting of bioactive molecules derived from the microbiota of a mammal are provided herein. When administered orally with a colonic delivery system, the compositions are useful for the prophylaxis and treatment of diseases, in particular inflammatory, autoimmune and infectious diseases. The compositions comprise combinations of small molecules and bacterial antigens formulated in colonic delivery systems. Use of the compositions results in any or all of: induction of immune tolerance; strengthening of the gut mucosal barrier integrity; reduction of inflammation; and amelioration of a disease state caused by inflammation, an autoimmune reaction or an infectious agent.

First claim

1 . A composition having an effect of inducing tolerance, strengthening gut barrier integrity, and reducing inflammation, the composition comprising: (a) one or more short-chain fatty acid or short-chain fatty acid derivative; (b) at least one GPR109 ligand; (c) at least one GPR43 ligand; (d) at least one histone-deacetylase (HDAC) inhibitor; (e) one or more antigen derived from bacteria belonging to Clostridium Cluster IV, Clostridium Cluster XIVa, or Clostridium Cluster XVIII; (f) a flagellin polypeptide; or (g) a combination of at least one of (a)-(d) and one of (e)-(f).

2 . The composition of claim 1 , wherein (a) is selected from the group consisting of butyrate, isobutyrate, proprionate, acetate, tributyrin, pivaloyloxymethyl butyrate, and monoacetone glucose 3-butyrate.

3 . The composition of claim 1 , wherein (a) is butyrate.

4 . The composition of claim 1 , wherein (a) is a mixture of salts of butyrate, isobutyrate, propionate, and acetate.

5 . The composition of claim 1 , wherein (f) is selected from the group consisting of flagellin, a flagellin-like sequence, a flagellin component, CBir1, Fla-X, FliC, FliD, FlgK, FlgC and FlgE.

6 . The composition of claim 1 , wherein (f) is flagellin.

7 . The composition of claim 1 , wherein the bacteria of (e) comprise a combination of bacteria from Clostridium Cluster IV and bacteria from Clostridium Cluster XIVa, or bacteria from Clostridium Cluster IV and bacteria from Clostridium Cluster XVIII, or bacteria from Clostridium Cluster XIVa and bacteria from Clostridium Cluster XVIII, or bacteria from Clostridium Cluster IV, bacteria from Clostridium Cluster XIVa, and bacteria from Clostridium Cluster XVIII.

8 . A composition having an effect of inducing tolerance, strengthening gut barrier integrity, and reducing inflammation, the composition comprising butyrate and flagellin.

9 . A composition having an effect of inducing tolerance, strengthening gut barrier integrity, and reducing inflammation, the composition comprising a mixture of salts of butyrate, isobutyrate, propionate, and acetate, and flagellin.

10 . A composition of claim 1 , further comprising a delivery system that directs the composition preferentially to the colonic mucosa.

11 . A pharmaceutical composition comprising a composition according to claim 1 and a pharmaceutically acceptable component.

12 . A method of inducing tolerance, strengthening gut barrier integrity, and reducing inflammation in an individual in need thereof, comprising administering, to the individual, a composition of claim 1 .

13 . A method of treating, aiding in treating, reducing the severity of, or preventing at least one disease selected from an autoimmune disease, an inflammatory disease, an allergic disease, and an infectious disease in an individual in need thereof, the method comprising administering the composition of claim 1 to the individual.

14 . The method of claim 13 , wherein the administration is with a colonic delivery system.

15 . (canceled)

16 . A method of determining activation of a T-cell specific to an antigen expressed by bacteria belonging to Clostridium Cluster IV, Clostridium Cluster XIVa, or Clostridium Cluster XVIII, said method comprising the steps of (a) providing a sample from a subject suspected of comprising cells that recognize said antigen; (b) contacting the sample with complexes of MHC Class II tetramers containing an epitope of said antigen; and (c) determining if binding occurs between the cells of the sample and the MHC Class II tetramers containing the epitope.

Assignees

• Vedanta Biosciences
• Riken

Inventors

• Honda Kenya
• Olle Bernat
• Atarashi Koji
• Tanoue Takeshi
• Ohno Hiroshi
• Fukuda Shinji
• Hase Koji

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/08

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

• A61P43/00

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

• A61P31/04

  Antibacterial agents · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title