Inhibition of colonic group 3 innate lymphoid cells

Patent metadata

Field	Value
Publication number	US-2021198619-A1
Application number	US-201816625217-A
Country	US
Kind code	A1
Filing date	Jun 22, 2018
Priority date	Jun 22, 2017
Publication date	Jul 1, 2021
Grant date	—

Abstract

In certain aspects, described herein are methods, bacteria, and compositions for the reduction of the amount, activity and/or proliferation of colonic group 3 innate lymphoid cells (ILC3s) and for the treatment and/or prevention of diseases associated with pathological immune responses, such as inflammatory bowel diseases.

First claim

What is claimed is:

1 . A bacterium comprising 16s DNA having a sequence that is at least 95% identical to SEQ ID NO: 1.

2 . The bacterium of claim 1 , wherein the 16s DNA sequence is at least 99% identical to SEQ ID NO: 1.

3 . The bacterium of claim 1 , wherein the 16s DNA sequence is at least 99.5% identical to SEQ ID NO: 1.

4 . The bacterium of claim 1 , wherein the 16s DNA sequence is at least 99.9% identical to SEQ ID NO: 1.

5 . The bacterium of claim 1 , wherein the 16s DNA sequence is identical to SEQ ID NO: 1.

6 . A bacterium having a genome comprising a sequence that is at least 90% identical to SEQ ID NO: 2.

7 . The bacterium of claim 6 , wherein the genome sequence is at least 95% identical to SEQ ID NO: 2.

8 . The bacterium of claim 6 , wherein the genome sequence is at least 99% identical to SEQ ID NO: 2.

9 . The bacterium of claim 6 , wherein the genome sequence is at least 99.5% identical to SEQ ID NO: 2.

10 . The bacterium of claim 6 , wherein the genome sequence is at least 99.9% identical to SEQ ID NO: 2.

11 . The bacterium of claim 6 , wherein the genome sequence is identical to SEQ ID NO: 2.

12 . A composition comprising the bacterium of any one of claims 1 to 11 .

13 . The composition of claim 12 , further comprising a pharmaceutically acceptable carrier.

14 . The composition of claim 11 or 12 , wherein at least 50% of the bacteria in the composition are bacteria of any one of claims 1 to 11 .

15 . The composition of claim 14 , wherein at least 75% of the bacteria in the composition are bacteria of any one of claims 1 to 11 .

16 . The composition of claim 14 wherein at least 90% of the bacteria in the composition are bacteria of any one of claims 1 to 11 .

17 . The composition of claim 14 , wherein at least 99% of the bacteria in the composition are bacteria of any one of claims 1 to 11 .

18 . The composition of any one of claims 12 to 17 , wherein the composition is formulated for oral administration.

19 . The composition of claim 18 , wherein the composition is a food product.

20 . The composition of any one of claims 12 to 17 , wherein the composition is formulated for rectal administration.

21 . The composition of any one of claims 12 to 20 , wherein the bacteria are live, replication competent bacteria.

22 . The composition of any one of claims 12 to 21 , further comprising a pre-biotic.

23 . A method of treating or preventing a condition in a subject comprising administering to the subject a bacterium of any one of claims 1 to 11 .

24 . A method of treating or preventing a condition in a subject comprising administering to the subject a composition of any one of claims 12 to 22 .

25 . The method of claim 23 or 24 , wherein the condition is colitis, inflammatory bowel disease, psoriasis, multiple sclerosis, or asthma.

26 . The method of claim 25 , wherein the condition is inflammatory bowel disease.

27 . The method of claim 26 , wherein the inflammatory bowel disease is Crohn's disease, ulcerative colitis, irritable bowel syndrome, microscopic colitis, lymphocytic-plasmocytic enteritis, coeliac disease, collagenous colitis, lymphocytic colitis and eosinophilic enterocolitis, indeterminate colitis, infectious colitis, ischemic colitis, pseudomembranous colitis, ischemic inflammatory bowel disease, microscoptic colitis, or Behcet's disease.

28 . The method of claim 27 , wherein the inflammatory bowel disease is ulcerative colitis.

29 . The method of claim 26 , wherein the multiple sclerosis (MS) is relapsing-remitting MS, secondary-progressive MS, primary-progressive MS, or progressive-relapsing MS.

30 . The method of any one of claims 23 to 29 , wherein the composition or bacterium is administered orally.

31 . The method of any one of claims 23 to 29 , wherein the composition or bacterium is administered rectally.

32 . The method of any one of claims 23 to 31 , wherein the administration reduces the number of IL-17 expressing colonic ILC3s in the subject.

33 . The method of any one of claims 23 to 32 , further comprising administering a pre-biotic to the subject.

34 . The method of any one of claims 23 to 33 , further comprising administering an antibiotic to the subject prior to the administration of the composition.

35 . A method of reducing the amount, activity and/or proliferation of colonic group 3 innate lymphoid cells (ILC3s) in a subject comprising administering to the subject a bacterium of any one of claims 1 to 11 .

36 . A method of reducing the amount, activity and/or proliferation of colonic group 3 innate lymphoid cells (ILC3s) in a subject comprising a composition of any one of claims 12 to 22 .

37 . The method of claim 35 or 36 , wherein the subject suffers from or is predisposed to an inflammatory bowel disease, colitis, multiple sclerosis, psoriasis, or asthma.

38 . The method of claim 37 , wherein the inflammatory bowel disease is Crohn's disease, ulcerative colitis, irritable bowel syndrome, microscopic colitis, lymphocytic-plasmocytic enteritis, coeliac disease, collagenous colitis, lymphocytic colitis and eosinophilic enterocolitis, indeterminate colitis, infectious colitis, pseudomembranous colitis, ischemic inflammatory bowel disease or Behcet's disease.

39 . The method of claim 37 , wherein the multiple sclerosis is relapsing-remitting MS, secondary-progressive MS, primary-progressive MS, or progressive-relapsing MS.

40 . The method of any one of claims 35 to 39 , wherein the bacterium or composition is administered orally.

41 . The method of any one of claims 35 to 39 , wherein the bacterium or composition is administered rectally.

42 . The method of any one of claims 35 to 41 , further comprising administering a pre-biotic to the subject.

43 . The method of any one of claims 35 to 41 , further comprising administering an antibiotic to the subject prior to the administration of the composition.

44 . A method of identifying bacteria that convey disease resistance comprising:
(a) determining a first microbiome profile for a disease-susceptible subject; (b) co-housing the disease-susceptible subject with a disease-resistant subject for a period of time sufficient for the disease-susceptible subject to acquire disease resistance; (c) after step (b), determining a second microbiome profile for the disease-susceptible subject; and (d) comparing the first microbiome profile with the second microbiome profile to identify operational taxonomic units (OTUs) of bacteria that are more prevalent in the second microbiome profile than the first microbiome profile.

45 . The method of claim 44 , further comprising determining a first microbiome profile in a disease-resistant subject in step (a) and a second microbiome profile in the disease-resistant subject in step (c).

46 . The method of claim 45 , further comprising comparing the first microbiome profile of the disease-resistant subject and the second microbiome profile

Assignees

• Harvard College
• Childrens Medical Center

Inventors

• Surana Neeraj K
• Kasper Dennis

Classifications

• A61K35/741

  Probiotics (probiotic yeast, e.g. saccharomyces A61K36/06) · CPC title

• A61K35/74

  Bacteria (therapeutic use of a bacterial protein A61K38/00) · CPC title

• C12Q1/04

  Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor {(C12Q1/6897 takes precedence)} · CPC title

• G01N2800/065

  Bowel diseases, e.g. Crohn, ulcerative colitis, IBS · CPC title

• C12N1/205

  Bacterial isolates · CPC title