IP Library Granted Patent US 10,736,926
Granted Patent B2
US 10,736,926 · App. 16/219,667 · Granted Aug 11, 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 10,736,926
App. No.
16/219,667
Granted
Aug 11, 2020
Kind
B2
Abstract

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

Claims (21)

1. A method of treating cancer in a subject, comprising orally administering to the subject a pharmaceutical composition that comprises at least about 1×10 6 CFU/g of a bacteria strain of the genus Bifidobacterium , with respect to a total weight of the pharmaceutical composition, wherein the Bifidobacterium bacteria strain is positive for fermentation of raffinose as determined by an Analytical Profile Index test, wherein the cancer is a solid tumor cancer associated with Th17 cell differentiation, and wherein the cancer is treated.

2. The method of claim 1 , wherein the pharmaceutical composition comprises from about 1×10 6 to about 1×10 11 CFU/g of the Bifidobacterium Bifidobacterium bacteria strain with respect to a total weight of the pharmaceutical composition.

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

4. The method of claim 1 , 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.

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

6. A method of treating cancer in a subject, comprising orally administering to the subject a pharmaceutical composition that comprises at least about 1×10 6 CFU/g of the bacteria strain deposited under accession number NCIMB 42380, wherein the cancer is a solid tumor cancer associated with Th17 cell differentiation, and wherein the cancer is treated.

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

a. binding of the exopolysaccharide to Congo Red; and

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

8. The method of claim 1 , further comprising administering a therapeutic agent.

9. A method of treating a solid tumor in a subject, comprising orally administering to the subject a pharmaceutical composition that comprises at least about 1×10 6 CFU/g of a bacteria strain of the genus Bifidobacterium , with respect to a total weight of the pharmaceutical composition, wherein the Bifidobacterium bacteria strain is positive for fermentation of raffinose as determined by an Analytical Profile Index test, wherein the solid tumor is associated with Th17 cell differentiation, and wherein the administering of the pharmaceutical composition reduces the size or growth of the solid tumor.

10. The method of claim 9 , wherein a bacterial cell of the Bifidobacterium bacteria strain and a bacteria cell of the Bifidobacterium breve strain JCM 7017 when contacted with a human cell bind to the human cell, and wherein the Bifidobacterium bacterial cell binds to the human cell to a lesser extent than the bacterial cell of the Bifidobacterium breve strain JCM 7017 as determined by an in vitro assay comprising comparing a measurement of an optical density of the Bifidobacterium bacteria strain bacteria cell bound to the human cell and an optical density of the Bifidobacterium breve strain JCM 7017 bacteria cell bound to the human cell.

11. The method of claim 9 , 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.

12. The method of claim 9 , wherein the Bifidobacterium bacteria strain is of the species Bifidobacterium breve.

13. The method of claim 9 , wherein the Bifidobacterium bacteria strain produces an amount of an exopolysaccharide on the surface of a bacterial cell of the Bifidobacterium bacteria strain that is greater than an amount of the same exopolysaccharide produced by a bacteria cell of Bifidobacterium breve strain JCM 7017 as determined by an in vitro assay comprising:

a. binding of the exopolysaccharide to Congo Red; and

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

14. A method of treating cancer in a subject, comprising orally administering to the subject a pharmaceutical composition that comprises: at least about 1×10 6 CFU/g of a bacteria strain of the genus Bifidobacterium , with respect to a total weight of the pharmaceutical composition, and a therapeutic agent, wherein the Bifidobacterium bacteria strain is positive for fermentation of raffinose as determined by an Analytical Profile Index test, wherein the cancer is a solid tumor cancer associated with Th17 cell differentiation, and wherein the cancer is treated.

15. The method of claim 14 , wherein the therapeutic agent comprises pembrolizumab.

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 048885/0931 →
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 20190099458A1 · Apr 4, 2019