IP Library Granted Patent US 10,471,108
Granted Patent B2
US 10,471,108 · App. 16/031,024 · Granted Nov 12, 2019

Compositions comprising bacterial strains

Inventors: Imke Elisabeth Mulder (Aberdeen, GB); Amy Beth Holt (Aberdeen, GB); Seanin Marie McCluskey (Aberdeen, GB); Grainne Clare Lennon (Aberdeen, GB); Suaad Ahmed (Aberdeen, GB)
Assignee: 4D PHARMA RESEARCH LIMITED
A61K35/74A23C9/1585A23L33/135A61K9/0053A61K9/19A61K9/50A61K35/744A61K39/09A23V2002/00A61K2035/11A61K2039/52A61K2039/585
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Quick Facts
Patent No.
US 10,471,108
App. No.
16/031,024
Granted
Nov 12, 2019
Kind
B2
Abstract

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

Claims (26)

1. A pharmaceutical composition that comprises an amount of a bacteria strain of the species Enterococcus faecium ; wherein said Enterococcus faecium is the sole species present in the pharmaceutical composition in an amount that is greater than 1×10 6 CFU/g with respect to a total weight of the pharmaceutical composition;

wherein the Enterococcus faecium bacteria strain is live and lyophilized; and wherein the Enterococcus faecium bacteria strain has an enzyme profile as determined by a Rapid ID 32A analysis that is:

(i) positive for at least one of: arginine dihydrolase, β-glucosidase, mannose fermentation, glutamic acid decarboxylase, arginine arylamidase, phenylalanine arylamidase, leucine arylamidase, pyroglutamic acid arylamidase, tyrosine arylamidase, glycine arylamidase, histidine arylamidase and serine arylamidase; and

(ii) intermediate for N-acetyl-β-glucosaminidase.

2. The pharmaceutical composition of claim 1 , further comprising a lyoprotectant which is a pharmaceutically acceptable excipient, diluent, or carrier.

3. The pharmaceutical composition of claim 1 , wherein the Enterococcus faecium bacteria strain comprises a polynucleotide sequence that is a 16s rRNA gene sequence with at least 95% sequence identity to the polynucleotide of SEQ ID NO:2 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.

4. The pharmaceutical composition of claim 1 , wherein the Enterococcus faecium bacteria strain comprises a polynucleotide sequence that is the 16s rRNA gene sequence of SEQ ID NO:2.

5. The pharmaceutical composition of claim 1 , wherein said Enterococcus faecium bacterial strain is the Enterococcus faecium bacteria strain deposited under accession number NCIMB 42487.

6. The pharmaceutical composition of claim 1 , wherein the amount is sufficient to decrease production of at least one cytokine when administered to a subject, wherein the at least one cytokine comprises an IL-17 cytokine selected from the group consisting of: IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, and IL-17F.

7. The pharmaceutical composition of claim 1 , wherein the amount is effective to treat a condition mediated by an increase in at least one cytokine when administered to a subject.

8. The pharmaceutical composition of claim 1 , wherein at least 50% of the Enterococcus faecium bacteria strain as measured by an amount of colony forming units (CFU), remains viable after about 1 year of storage when the pharmaceutical composition is stored in a closed container at 25° C. at 95% relative humidity.

9. The pharmaceutical composition of claim 1 , wherein the amount comprises from about 1×10 6 to about 1×10 11 CFU/g of said Enterococcus faecium bacteria strain with respect to a total weight of the pharmaceutical composition.

10. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for oral delivery.

11. The pharmaceutical composition of claim 10 , further comprising an enteric coating.

12. The pharmaceutical composition of claim 1 , further comprising a prebiotic compound selected from the group consisting of: a fructo-oligosaccharide, a short-chain fructo-oligosaccharide, inulin, an isomalt-oligosaccharide, a galacto-oligosaccharide, a pectin, a xylo-oligosaccharide, a chitosan-oligosaccharide, a beta-glucan, an arable gum modified starch, a polydextrose, a D-tagatose, an acacia fiber, carob, an oat, and a citrus fiber.

13. The pharmaceutical composition of claim 1 , wherein the amount comprises from about 1×10 8 to about 1×10 11 CFU/g of said Enterococcus faecium bacteria strain with respect to a total weight of the pharmaceutical composition.

14. The pharmaceutical composition of claim 1 , wherein the amount comprises from about 1×10 7 to about 1×10 10 CFU/g of said Enterococcus faecium bacteria strain with respect to a total weight of the pharmaceutical composition.

15. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is encapsulated.

16. The pharmaceutical composition of claim 1 , in the form of a table, capsule, or powder.

17. The pharmaceutical composition of claim 1 , wherein the enzyme profile is positive for arginine dihydrolase and phenylalanine arylamidase.

18. The pharmaceutical composition of claim 1 , wherein the enzyme profile is positive for pyroglutamic acid arylamidase and histidine arylamidase.

19. The pharmaceutical composition of claim 1 , wherein the Enterococcus faecium bacteria strain comprises a polynucleotide sequence that is a 16s rRNA gene sequence with at least 99% sequence identity to the polynucleotide of SEQ ID NO:2 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.

20. A pharmaceutical composition that comprises an amount of a bacteria strain of the species Enterococcus faecium ; wherein the Enterococcus faecium bacteria strain is the sole bacteria strain present in the pharmaceutical composition in an amount that is greater than 1×10 8 CFU/g with respect to a total weight of the pharmaceutical composition;

wherein the Enterococcus faecium bacteria strain is live and lyophilized; and wherein the Enterococcus faecium bacteria strain has an enzyme profile as determined by a Rapid ID 32A analysis that is:

(i) positive for at least one of: arginine dihydrolase, β-glucosidase, mannose fermentation, glutamic acid decarboxylase, arginine arylamidase, phenylalanine arylamidase, leucine arylamidase, pyroglutamic acid arylamidase, tyrosine arylamidase, glycine arylamidase, histidine arylamidase and serine arylamidase; and

(ii) intermediate for N-acetyl-β-glucosaminidase.

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 Jul 11, 2018
From: MULDER, IMKE ELISABETH; HOLT, AMY BETH; MCCLUSKEY, SEANIN MARIE; AHMED, SUAAD; LENNON, GRAINNE CLARE
To: 4D PHARMA RESEARCH LIMITED
Reel/Frame 046322/0144 →
Priority Claims (1)
GB 1520497.7 · Nov 20, 2015 · national
Continuity (2)
Division 15357936 · Nov 21, 2016
Related Publication 20190000892A1 · Jan 3, 2019