Compositions comprising bacterial strains

Patent metadata

Field	Value
Publication number	US-9987311-B2
Application number	US-201615359988-A
Country	US
Kind code	B2
Filing date	Nov 23, 2016
Priority date	Nov 23, 2015
Publication date	Jun 5, 2018
Grant date	Jun 5, 2018

Abstract

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

First claim

What is claimed is:

1. A pharmaceutical composition that reduces inflammation associated with Th17 differentiation in a subject in need thereof, that comprises a therapeutically effective amount of a single bacteria strain of the species Erysipelatoclostridium ramosum ; and
a pharmaceutically acceptable excipient, diluent, or carrier;
wherein the therapeutically effective amount comprises from about 1×10 3 to about 1×10 11 CFU of the bacteria strain;
wherein the bacterial strain is lyophilized; and

wherein the bacteria strain comprises a polynucleotide sequence of a 16s rRNA gene that has at least 95% sequence identity to the polynucleotide sequence of SEQ ID NO:3, 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.

2. The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient or carrier comprises a lyoprotectant.

3. The pharmaceutical composition of claim 1 , wherein the bacteria strain comprises the polynucleotide sequence of SEQ ID NO:3.

4. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition consists essentially of the bacteria strain of species Erysipelatoclostridium ramosum.

5. The pharmaceutical composition of claim 1 , further comprising at least one additional bacteria strain.

6. The pharmaceutical composition of claim 1 , wherein at least 50% of the 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.

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

8. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for oral delivery, and wherein the pharmaceutical composition comprises an enteric coating.

9. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises a prebiotic compound selected from the group consisting of: a fructo-oligosaccharide, a short-chain fructo-oligosaccharide, inulin, an isomalt-oligosaccharide, a transgalacto-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.

10. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises an adjuvant.

11. A method of treating a condition in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition that comprises a bacteria strain of the species Erysipelatoclostridium ramosum and a pharmaceutically acceptable excipient, diluent, or carrier;
wherein the bacteria strain is present in an amount sufficient for treating a condition mediated by the Th17 pathway or by an increase in the IL-17 cytokine in the subject;
wherein the therapeutically effective amount comprises from about 1×10 3 to about 1×10 11 CFU of the bacteria strain;
wherein the bacteria strain is lyophilized; and
wherein the bacteria strain comprises a polynucleotide sequence of a 16s rRNA gene that has at least 95% identity to the polynucleotide sequence of SEQ ID NO:3, 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.

12. The method of claim 11 , wherein the condition mediated by the Th17 pathway or by an increase in the IL-17 cytokine is uveitis, and wherein said treating or preventing comprises reducing or preventing retinal damage in uveitis.

13. The method of claim 11 , wherein the bacteria strain is present in an amount sufficient for treating the condition mediated by the Th17 pathway, wherein the condition mediated by the Th17 pathway is a cancer, and wherein the cancer is breast cancer, lung cancer, liver cancer, colon cancer, or ovarian cancer.

14. The method of claim 11 , wherein the bacteria strain comprises the polynucleotide sequence of SEQ ID NO:3.

15. The method of claim 11 , wherein the subject has the condition, or has been identified as being at risk of the condition.

16. The method of claim 11 , further comprising administering an additional therapeutic agent to the subject.

17. The method of claim 11 , wherein the bacteria strain comprises a polynucleotide sequence of a 16s rRNA gene that has at least 99.5% sequence identity to the polynucleotide of SEQ ID NO:3, 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 BLOSUM of 62.

18. The method of claim 11 , wherein the bacteria strain is the strain deposited under accession number NCIMB 42688.

19. The pharmaceutical composition of claim 1 , wherein the bacteria strain is the strain deposited under accession number NCIMB 42688.

20. The pharmaceutical composition of claim 1 , wherein the bacteria strain is strain JCM 1298.

21. The pharmaceutical composition of claim 1 , wherein the bacteria has a fermentation profile of a bacteria strain selected from the group consisting of ATCC 25582, JCM 1298, and MRX027.

22. The pharmaceutical composition of claim 1 , wherein the bacteria has a fermentation profile of a bacteria strain deposited under accession number NCIMB 42689.

23. The pharmaceutical composition of claim 1 , wherein the bacteria strain is not in sporulated form or comprises spores in a de minimis amount.

Assignees

• 4D Pharma Res Ltd

Inventors

• MULDER Imke Elisabeth
• HOLT Amy Beth
• Mccluskey Seanin Marie
• Lennon Grainne Clare
• Ahmed Suaad

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title