IP Library Granted Patent US 10,543,238
Granted Patent B2
US 10,543,238 · App. 16/147,551 · Granted Jan 28, 2020

Compositions comprising bacterial strains

Inventors: Ian Jeffery (Cork, IE); Fergus Shanahan (Kinsale, IE); Paul O'Toole (Cork, IE); Alex Stevenson (Leeds, GB); Imke Mulder (Aberdeen, GB); Helene Savignac (Leeds, GB)
Assignee: 4D PHARMA PLC
A61K35/74A61K9/19A61K9/48A61P1/00A61P1/14A61P29/00A61K2035/11
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Quick Facts
Patent No.
US 10,543,238
App. No.
16/147,551
Granted
Jan 28, 2020
Kind
B2
Abstract

Provided are compositions comprising a bacterial strain of the genus Blautia , for use in a method of increasing the microbiota diversity and/or inducing stability of the microbiota of a subject.

Claims (15)

1. A method of increasing microbiome diversity in a gastrointestinal flora of a subject, comprising administering to the subject a pharmaceutical composition containing an effective amount of a Blautia hydrogenotrophica bacteria strain comprising a 16s rRNA gene sequence with 95% sequence identity to SEQ ID NO:5, as determined by a Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 12, a gap extension penalty of 2, and a Blocks Substitution Matrix (BLOSUM) of 62, wherein said the administering is sufficient to increase microbiome diversity in a gastrointestinal flora of a subject, as determined by an increase in a Shannon Diversity Index of at least about 0.1 from a fecal sample obtained from the subject about 4 weeks after the administering, relative to a fecal sample obtained from the subject prior to the administering, and wherein the administration produces an increase in bacteria strains of Clostridium cluster IV, Bifidobacterium and Prevotella.

2. The method of claim 1 , wherein the subject has or is at risk of having an inflammatory condition.

3. The method of claim 2 , wherein the inflammatory condition is a neuroinflammatory condition.

4. The method of claim 3 , wherein the neuroinflammatory condition is multiple sclerosis.

5. The method of claim 2 , wherein the inflammatory condition is a gastrointestinal condition.

6. The method of claim 5 , wherein the gastrointestinal disorder is irritable bowel disease or irritable bowel syndrome.

7. The method of claim 1 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable excipient, diluent, or carrier.

8. The method of claim 1 , wherein the Blautia hydrogenotrophica bacteria strain is lyophilized.

9. The method of claim 1 , wherein the pharmaceutical composition comprises at least 1×10 3 colony forming units (CFU)/g of the Blautia hydrogenotrophica bacteria strain with respect to a total weight of the pharmaceutical composition.

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

11. The method of claim 1 , wherein the pharmaceutical composition is enterically formulated.

12. The method of claim 1 , wherein the Blautia hydrogenotrophica bacteria strain comprises a 16s rRNA gene sequence with at least 95% sequence identity to the 16s rRNA gene sequence of SEQ ID NO:5.

13. The method of claim 1 , further comprising administering an additional agent to the subject.

14. A method of increasing microbiome diversity in a gastrointestinal flora of a subject, comprising administering to the subject a pharmaceutical composition containing an effective amount of single bacteria strain, wherein the single bacteria strain is of the species a Blautia hydrogenotrophica bacteria strain comprising a 16s rRNA gene sequence with 95% sequence identity to SEQ ID NO:5, as determined by a Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 12, a gap extension penalty of 2, and a Blocks Substitution Matrix (BLOSUM) of 62, wherein said the administering is sufficient to increase microbiome diversity in a gastrointestinal flora of a subject, as determined by an increase in a Shannon Diversity Index of at least about 0.1 from a fecal sample obtained from the subject about 4 weeks after the administering, relative to a fecal sample obtained from the subject prior to the administering, and wherein the administration produces an increase in bacteria strains of Clostridium cluster IV, Bifidobacterium and Prevotella.

15. A method of increasing microbiome diversity in a gastrointestinal flora of a subject, comprising administering to the subject a pharmaceutical composition containing an effective amount of a Blautia hydrogenotrophica bacteria strain comprising a 16s rRNA gene sequence with 95% sequence identity to SEQ ID NO:5, as determined by a Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 12, a gap extension penalty of 2, and a Blocks Substitution Matrix (BLOSUM) of 62, wherein the pharmaceutical composition comprises at least 1×10 6 colony forming units (CFU)/g of the Blautia hydrogenotrophica bacteria strain with respect to a total weight of the pharmaceutical composition, wherein said the administering is sufficient to increase microbiome diversity in a gastrointestinal flora of a subject, as determined by an increase in a Shannon Diversity Index of at least about 0.1 from a fecal sample obtained from the subject about 4 weeks after the administering, relative to a fecal sample obtained from the subject prior to the administering, and wherein the administration produces an increase in bacteria strains of Clostridium cluster IV, Bifidobacterium and Prevotella.

Assignments (3)
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 Mar 29, 2019
From: JEFFERY, IAN; SHANAHAN, FERGUS; O'TOOLE, PAUL; STEVENSON, ALEX; MULDER, IMKE; SAVIGNAC, HELENE
To: 4D PHARMA PLC
Reel/Frame 048735/0451 →
Priority Claims (1)
GB 1621123.7 · Dec 12, 2016 · national
Continuity (3)
Continuation 15915889 · Mar 8, 2018
Continuation PCTGB2017053722 · Dec 12, 2017
Related Publication 20190255123A1 · Aug 22, 2019