IP Library Granted Patent US 10,864,236
Granted Patent B2
US 10,864,236 · App. 16/248,857 · Granted Dec 15, 2020

Compositions comprising bacterial strains

Inventors: George Grant (Aberdeen, GB); Angela Margaret Patterson (Norwich, GB); Imke Mulder (Aberdeen, GB); Seanin McCluskey (Leeds, GB); Emma Raftis (Leeds, GB)
Assignee: 4D Pharma Research Limited
A61K35/745A61K9/0053A61K9/19A61K35/74C12R1/01
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Quick Facts
Patent No.
US 10,864,236
App. No.
16/248,857
Granted
Dec 15, 2020
Kind
B2
Abstract

The invention provides compositions comprising bacterial strains for treating and preventing inflammatory and autoimmune diseases.

Claims (29)

1. A method of treating asthma in a subject, comprising orally administering to the subject a pharmaceutical composition that comprises: at least 1×10 6 CFU/g of a dried bacteria strain of the genus Bifidobacterium , wherein the Bifidobacterium bacteria strain is positive for fermentation of raffinose, as determined by an Analytical Profile Index test comprising:

a) contacting a suspension of the Bifidobacterium bacteria strain with a Rapid ID 32A strip at 37° C. for at least 4 hours;

b) contacting the suspension with a development reagent comprising FastBlue for at least 5 minutes; and

c) measuring the color of the suspension,

wherein the Bifidobacterium bacteria strain comprises a polynucleotide sequence of a 16s rRNA gene having at least 95% sequence identity to the polynucleotide sequence of SEQ ID NO: 1 as determined by the Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 12 and a gap extension penalty of 2, and a BLOSUM matrix of 62,

wherein the administering results in a reduction of an amount of an eosinophil, neutrophil, or lymphocyte in the subject relative to a corresponding amount of the eosinophil, neutrophil, or lymphocyte prior to the administering, and

wherein the dried Bifidobacterium bacteria strain is live.

2. The method of claim 1 , wherein a bacterial cell of the Bifidobacterium bacteria strain binds to a human cell to a lesser extent than a bacterial cell of Bifidobacterium breve strain JCM 7017 binds to a corresponding cell, as determined by an in vitro assay comprising comparing a measurement of an optical density.

3. The method of claim 1 , wherein the Bifidobacterium bacteria strain is of species Bifidobacterium breve.

4. A method of treating asthma in a subject, comprising orally administering to the subject a pharmaceutical composition that comprises: at least 1×10 6 CFU/g of a dried Bifidobacterium bacteria strain, wherein the Bifidobacterium bacteria strain is the bacteria strain deposited under accession number NCIMB 42380, wherein the Bifidobacterium bacteria strain is positive for fermentation of raffinose, as determined by an Analytical Profile Index test comprising:

a) contacting a suspension of the Bifidobacterium bacteria strain with a Rapid ID 32A strip at 37° C. for at least 4 hours;

b) contacting the suspension with a development reagent comprising FastBlue for at least 5 minutes; and

c) measuring a color of the suspension,

wherein the Bifidobacterium bacteria strain comprises a polynucleotide sequence of a 16s rRNA gene having at least 95% sequence identity to the polynucleotide sequence of SEQ ID NO: 1 as determined by the Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 12 and a gap extension penalty of 2, and a BLOSUM matrix of 62,

wherein the administering results in a reduction of an amount of an eosinophil, neutrophil, or lymphocyte in the subject relative to a corresponding amount of the eosinophil, neutrophil, or lymphocyte prior to the administering, and wherein the Bifidobacterium bacteria strain is live.

5. The method of claim 1 , wherein the Bifidobacterium bacteria strain produces an amount of an exopolysaccharide on a surface of a bacterial cell of the Bifidobacterium bacteria strain that is greater than an amount of the same exopolysaccharide produced by a bacterial cell of Bifidobacterium breve strain JCM 7017 as determined by an in vitro assay comprising:

a) binding of the exopolysaccharide to Congo Red;

b) measuring a light absorbance of the Congo Red bound to the exopolysaccharide for the bacterial cell of the Bifidobacterium bacteria strain and the bacterial cell of the Bifidobacterium breve strain JCM 7017; and

c) comparing the light absorbance of the Congo Red bound to the bacterial cell of the Bifidobacterium bacteria strain and the bacterial cell of the Bifidobacterium breve strain JCM 7017.

6. The method of claim 1 , wherein the administering reduces an amount of a cytokine in a lung tissue of the subject, wherein the cytokine is selected from the group consisting of: IL-9, IL-la, IFNg, IL-17A, IL-4, IL-5, IL-1b, RANTES, MIP-1a, KC, and MIP-2.

7. The method of claim 1 , wherein the administering reduces an amount of a house dust mite (HDM) specific immunoglobulin in the subject, as determined by an ELISA assay.

8. The method of claim 7 , wherein the immunoglobulin is an IgG1 or an IgG2a.

9. The method of claim 1 , wherein the administering reduces peribronchiolar infiltration in the subject, as measured by a mean peribronchiolar infiltration score.

10. The method of claim 1 , wherein the administering reduces perivascular infiltration in the subject, as measured by a mean perivascular infiltration score.

11. The method of claim 1 , wherein the asthma is neutrophilic asthma or allergic asthma.

12. The method of claim 1 , wherein the Bifidobacterium bacteria strain ferments raffinose to an identical extent as the Bifidobacterium bacteria strain deposited under accession number NCIMB 42380, as determined by the Analytical Profile Index test.

13. The method of claim 1 , wherein the Bifidobacterium bacteria strain ferments raffinose to an identical extent as the Bifidobacterium bacteria strain deposited under accession number NCIMB 42380, as determined by the Analytical Profile Index test.

14. The method of claim 1 , wherein the Bifidobacterium bacteria strain is present in an amount of from 1×10 6 to 1×10 11 CFU/g.

15. The method of claim 4 , wherein the Bifidobacterium bacteria strain is present in an amount of from 1×10 6 to 1×10 11 CFU/g.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 14, 2023
From: 4D PHARMA PLC; 4D PHARMA RESEARCH LIMITED
To: CJ BIOSCIENCE, INC.
Reel/Frame 063992/0427 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 31, 2022
From: OXFORD FINANCE LUXEMBOURG S.A R.L.
To: ARMISTICE CAPITAL MASTER FUND LTD.
Reel/Frame 061806/0371 →
INTELECTUAL PROPERTY SECURITY AGREEMENT Recorded Jul 30, 2021
From: 4D PHARMA PLC; 4D PHARMA RESEARCH LIMITED; 4D PHARMA CORK LIMITED; 4D PHARMA DELAWARE INC.
To: OXFORD FINANCE LUXEMBOURG S.A R.L.
Reel/Frame 057042/0715 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 15, 2019
From: GRANT, GEORGE; PATTERSON, ANGELA MARGARET; MULDER, IMKE; RAFTIS, EMMA; MCCLUSKEY, SEANIN
To: 4D PHARMA RESEARCH LIMITED
Reel/Frame 048886/0106 →
Priority Claims (2)
GB 1510467.2 · Jun 15, 2015 · national
GB 1520501.6 · Nov 20, 2015 · national
Continuity (3)
Continuation 15700007 · Sep 8, 2017
Continuation PCTGB2016051776 · Jun 15, 2016
Related Publication 20190247448A1 · Aug 15, 2019