IP Library Granted Patent US 11,331,352
Granted Patent B2
US 11,331,352 · App. 17/006,356 · Granted May 17, 2022

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
A61K35/745A61K9/0053A61K9/19A61K35/74C12N1/205C12R2001/01
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Quick Facts
Patent No.
US 11,331,352
App. No.
17/006,356
Granted
May 17, 2022
Kind
B2
Abstract

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

Claims (34)

1. A pharmaceutical composition in the form of a tablet, capsule, or microcapsule that comprises at least 1×10 3 colony forming units (CFU) per gram of a dried bacteria strain, with respect to a total weight of the pharmaceutical composition and a pharmaceutically acceptable excipient, diluent, or carrier; wherein the bacteria strain comprises a biochemical profile that is:

(a) positive for raffinose fermentation;

(b) positive for at least three of: mannose fermentation, β-galactosidase, arginine arylamidase, proline arylamidase, phenylalanine arylamidase, leucine arylamidase, tyrosine arylamidase, glycine arylamidase, and histidine arylamidase;

(c) intermediate for at least one of: α-galactosidase, α-glucosidase, β-glucosidase, and α-arabinose; and

(d) negative for at least five of: urease, arginine dihydrolase, β-galactosidase-6-phosphate, β-glucoronidase, N-acetyl-β-glucosaminidase, glutamic acid decarboxylase, α-fucosidase, nitrate reduction, indole production, alkaline phosphatase, leucyl glycine arylamidase, pyroglutamic acid arylamidase, alanine arylamidase, glutamyl glutamic acid arylamidase, and serine arylamidase;

as determined by an Analytical Profile Index test comprising:

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

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

(iii) measuring a color of the suspension.

2. The pharmaceutical composition of claim 1 , wherein the bacteria strain comprises a biochemical profile that is:

(a) positive for raffinose fermentation;

(b) positive for arginine arylamidase, proline arylamidase, and phenylalanine arylamidase;

(c) intermediate for α-galactosidase; and

(d) negative for β-galactosidase-6-phosphate, β-glucoronidase, N-acetyl-β-glucosaminidase, nitrate reduction, and serine arylamidase.

3. The pharmaceutical composition of claim 1 , wherein the bacteria strain comprises a biochemical profile that is:

(a) positive for raffinose fermentation;

(b) positive for at least five of: mannose fermentation, β-galactosidase, arginine arylamidase, proline arylamidase, phenylalanine arylamidase, leucine arylamidase, tyrosine arylamidase, glycine arylamidase, and histidine arylamidase;

(c) intermediate for α-galactosidase; and

(d) negative for at least ten of: urease, arginine dihydrolase, β-galactosidase-6-phosphate, glucoronidase, N-acetyl-β-glucosaminidase, glutamic acid decarboxylase, α-fucosidase, nitrate reduction, indole production, alkaline phosphatase, leucyl glycine arylamidase, pyroglutamic acid arylamidase, alanine arylamidase, glutamyl glutamic acid arylamidase, and serine arylamidase.

4. The pharmaceutical composition of claim 1 , wherein the bacteria strain is a butyrate-producing bacteria strain.

5. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is in the form of a capsule.

6. The pharmaceutical composition of claim 1 , wherein a bacterial cell of the 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 human cell, as determined by an in vitro assay comprising comparing a measurement of an optical density.

7. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises from about 1×10 6 to about 1×10 11 CFU per gram, with respect to the total weight of the pharmaceutical composition.

8. The pharmaceutical composition of claim 1 , further comprising a prebiotic compound.

9. The pharmaceutical composition of claim 8 , wherein the prebiotic compound is selected from the group consisting of: fructo-oligosaccharides (or FOS), short-chain fructo-oligosaccharides, inulin, isomalt-oligosaccharides, pectins, xylo-oligosaccharides (or XOS), chitosan-oligosaccharides (or COS), beta-glucans, arable gum modified and resistant starches, polydextrose, D-tagatose, acacia fibers, carob, oats, and citrus fiber.

10. The pharmaceutical composition of claim 1 , comprising the pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier is selected from the group consisting of: lactose, starch, glucose, methyl cellulose, magnesium stearate, mannitol and sorbitol.

11. The pharmaceutical composition of claim 1 , further comprising an antioxidant.

12. The pharmaceutical composition of claim 11 , wherein the antioxidant is ascorbic acid.

13. The pharmaceutical composition of claim 1 , wherein the bacteria strain is an anaerobic bacteria strain.

14. The pharmaceutical composition of claim 1 , wherein the bacteria strain is a live bacteria strain.

15. The pharmaceutical composition of claim 1 , further comprising an anticancer agent.

16. The pharmaceutical composition of claim 15 , wherein the anticancer agent is selected from the group consisting of: an immune checkpoint inhibitor, a targeted antibody immunotherapy, a CAR-T cell therapy, an oncolytic virus, and a cytostatic drug.

17. The pharmaceutical composition of claim 1 , wherein the bacteria strain is positive for methyl α-D-glucopyranoside fermentation, as determined by an API 50 CH analytical profile test.

18. The pharmaceutical composition of claim 1 , wherein the bacteria strain is positive for methyl D-melibiose fermentation, as determined by an API 50 CH analytical profile test.

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 Dec 10, 2020
From: GRANT, GEORGE; PATTERSON, ANGELA MARGARET; MULDER, IMKE; RAFTIS, EMMA; MCCLUSKEY, SEANIN
To: 4D PHARMA RESEARCH LIMITED
Reel/Frame 054601/0257 →
Priority Claims (2)
GB 1510467 · Jun 15, 2015 · national
GB 1520501 · Nov 20, 2015 · national
Continuity (4)
Continuation 16248857 · Jan 16, 2019
Continuation 15700007 · Sep 8, 2017
Continuation PCTGB2016051776 · Jun 15, 2016
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