Compositions comprising bacterial strains

Patent metadata

Field	Value
Publication number	US-11419931-B2
Application number	US-202017024628-A
Country	US
Kind code	B2
Filing date	Sep 17, 2020
Priority date	Mar 19, 2018
Publication date	Aug 23, 2022
Grant date	Aug 23, 2022

Abstract

The invention provides compositions comprising bacterial strains for stimulating the immune system and treating and preventing diseases.

First claim

The invention claimed is:

1. A method of increasing differentiation of cytotoxic T cells in a subject in need thereof, comprising
administering to the subject a pharmaceutical composition that comprises a bacteria strain of the genus Enterococcus , wherein the bacteria strain comprises a 16S rRNA gene sequence that has at least 95% sequence identity to the polynucleotide sequence of SEQ ID NO: 2, as determined by a Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 12 and a gap extension penalty of 2,
wherein the subject has been diagnosed with deficient immune activity, and
wherein the administering is sufficient to increase differentiation of cytotoxic T cells in the subject, relative to a level of differentiation of cytotoxic T cells in the subject prior to the administering.

2. The method of claim 1 , wherein the cytotoxic T cells are CD8 cells, and wherein the administering is sufficient to increase a level of CD8 cells in a serum of the subject, relative to a level of CD8 cells in the serum of the subject prior to the administering.

3. The method of claim 1 , wherein the administering increases differentiation of T helper cells, relative to a level of differentiation of T helper cells in the subject prior to the administering.

4. The method of claim 1 , wherein the administering activates a toll-like receptor (TLR) signaling pathway in the subject.

5. The method of claim 4 , wherein the TLR is TLR5 or TLR9.

6. The method of claim 1 , wherein the administering increases a level of a cytokine in a serum of the subject, relative to a level of the cytokine in the serum of the subject prior to the administering.

7. The method of claim 6 , wherein the cytokine is IL-6 or IL-23.

8. The method of claim 1 , wherein the administering increases a level of NFκBIA in the subject, relative to a level of NFκBIA in the subject prior to the administering.

9. The method of claim 1 , wherein the administering comprises oral, rectal, nasal, buccal, sublingual, or subcutaneous administration.

10. The method of claim 1 , wherein the bacterial strain is dried.

11. The method of claim 1 , wherein the pharmaceutical composition comprises from about 1×10 3 to about 1×10 11 colony forming units (CFU)/g of the bacteria strain with respect to the total weight of the pharmaceutical composition.

12. The method of claim 1 , wherein the bacteria strain at least partially colonizes an intestine of the subject.

13. The method of claim 1 , wherein the pharmaceutical composition is formulated for delivery to an intestine of the subject.

14. The method of claim 1 , wherein the bacteria strain comprises a 16S rRNA gene sequence that has at least 99% sequence identity to the polynucleotide sequence of SEQ ID NO: 2, as determined by a Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 12 and a gap extension penalty of 2.

15. The method of claim 1 , wherein the bacteria strain comprises a 16S rRNA gene sequence that is the polynucleotide sequence of SEQ ID NO: 2 or SEQ ID NO: 3.

16. The method of claim 1 , wherein the bacterial strain is of the species Enterococcus gallinarum.

17. The method of claim 1 , wherein the bacterial strain is the strain deposited under accession number NCIMB 42488 or the strain deposited under accession number NCIMB 42761.

18. The method of claim 1 , wherein the pharmaceutical composition further comprises one or more pharmaceutically acceptable excipients, carriers, or diluents.

19. The method of claim 1 , further comprising administering a cell therapy to the subject.

20. The method of claim 19 , the cell therapy is chimeric antigen receptor T cell (CAR-T) therapy, mesenchymal stem cell (MSC) therapy, stem cell transplantation therapy, or hematopoietic stem cell transplantation.

Assignees

• 4D Pharma Res Ltd

Inventors

• Panzica Domenico
• HOLT Amy Beth
• Ahmed Suaad
• Ettorre Anna
• MULDER Imke Elisabeth
• Cowie Philip
• Raftis Emma
• Hennessy Emma Elizabeth Clare
• Laute-Caly Delphine Louise Claudette
• Couturier-Maillard Aurélie Pascale Patricia
• Delday Margaret Inkster
• Adriani Marsilio
• Christofi Maria

Classifications

• A61K38/164 Primary

  from bacteria · CPC title

• C12R2001/46

  Streptococcus {; Enterococcus; Lactococcus} · CPC title

• A61K35/744

  Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs · CPC title

• A61K2039/585

  wherein the target is cancer · CPC title

• A23L33/135

  Bacteria or derivatives thereof, e.g. probiotics · CPC title