COMPOSITIONS COMPRISING BACTERIAL STRAINS

• US 20170143772A1
• Filed: 11/21/2016
• Published: 05/25/2017
• Est. Priority Date: 11/20/2015
• Status: Active Grant

• Current Assignee: CJ Bioscience Incorporated
• Original Assignee: 4D Pharma Research Limited (4D Pharma PLC)
• Inventors: MCCLUSKEY, Seanin Marie, MULDER, Imke Elisabeth, HOLT, Amy Beth, PANZICA, Domenico
• Granted Patent: US 9,839,655 B2
• Time in Patent Office: Days
• CPC Class Codes: A23C 9/1585 Antibiotics; Bacteriocins; Fungicides from microorganisms
• CPC Class Codes: A23L 33/135 Bacteria or derivatives thereof, e.g. probiotics
• CPC Class Codes: A23V 2002/00 Food compositions, function of food ingredients or processes for food or foodstuffs
• CPC Class Codes: A61K 2035/11 Medicinal preparations comprising living procariotic cells
• CPC Class Codes: A61K 2039/585 wherein the target is cancer
• CPC Class Codes: A61K 31/739 Lipopolysaccharides
• CPC Class Codes: A61K 35/74 Bacteria therapeutic use of a bacterial protein A61K38/00
• CPC Class Codes: A61K 35/744 Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
• CPC Class Codes: A61K 39/09 Lactobacillales, e.g. aerococcus, enterococcus, lactobacillus, lactococcus, streptococcus
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C12N 1/20 Bacteria; Culture media therefor
• CPC Class Codes: C12N 1/205 Bacterial isolates
• CPC Class Codes: C12R 2001/46 Streptococcus ; Enterococcus; Lactococcus

Abstract

The invention provides compositions comprising bacterial strains for treating and preventing cancer.

Claims

1. A pharmaceutical composition comprising:

a therapeutically effective amount of a bacteria strain that comprises a 16s rRNA sequence with at least 95% homology to the polynucleotide of SEQ ID NO;

2;

wherein said therapeutically effective amount of said bacteria strain is an amount sufficient for treating or preventing cancer in a subject; and

wherein said bacteria strain is lyophilized and/or the pharmaceutical composition further comprises a pharmaceutically acceptable excipient, diluent, or carrier.

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

4. The pharmaceutical composition of claim 1, comprising a bacteria strain that comprises the 16s rRNA sequence of SEQ ID NO:

2.

5. The pharmaceutical composition of claim 1, comprising a bacteria strain of the species Enterococcus gallinarum.

6. The pharmaceutical composition of claim 1, said bacteria strain consisting essentially of the species Enterococcus gallinarum.

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

8. 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.

9. The pharmaceutical composition of claim 1, wherein the therapeutically effective amount of the bacteria strain comprises from about 1×

10⁶ to about 1×

10¹¹ CFU/g of said bacteria strain with respect to a total weight of the pharmaceutical composition.

10. The pharmaceutical composition of claim 1, wherein the composition is a lyophilized composition.

11. The pharmaceutical composition of claim 1, further comprising a lipopolysaccharide.

12. The pharmaceutical composition of claim 1, wherein the therapeutically effective amount is an amount effective to increase production of at least one cytokine selected from the group consisting of IL-6, TNF-α

, and IL-1B.

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

and wherein the pharmaceutical composition comprises an enteric coating.

14. 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 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.

15. A vaccine comprising the pharmaceutical composition of claim 1.

2. A pharmaceutical composition comprising:

a therapeutically effective amount of a bacteria strain of the species Enterococcus gallinarum;

wherein said therapeutically effective amount of said bacteria strain is an amount sufficient for treating or preventing cancer in a subject; and

wherein said bacteria strain is lyophilized and/or the pharmaceutical composition further comprises a pharmaceutically acceptable excipient, diluent, or carrier.

16. A food product that comprises:

a therapeutically effective amount of a bacteria strain that comprises a polynucleotide sequence with at least 95% homology to the polynucleotide of SEQ ID NO;

2; and

a nutritious product.

17. The food product of claim 16, wherein the nutritious product is a milk-food product, or a milk-based product selected from the group consisting of:

a cow'"'"'s milk, a goat'"'"'s milk, a sheep'"'"'s milk, skimmed milk, whole milk, milk recombined from powdered milk, yogurt, curdled milk, curd, sour milk, sour whole milk, butter milk, a whey beverage, a fermented milk, a condensed milk, an infant milk, a flavored milk, and an ice cream.

18. A method of treating or preventing cancer in a subject in need thereof, comprising:

administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising;

a bacteria strain with a 16s rRNA sequence with at least 95% homology to the polynucleotide of SEQ ID NO;

2;

wherein said bacteria strain is present in an amount sufficient for treating or preventing a cancer in the subject.

19. The method of claim 18, wherein the bacteria strain is lyophilized and/or the pharmaceutical composition further comprises a pharmaceutically acceptable excipient, diluent, or carrier.

20. The method of claim 18, wherein the bacteria strain is of the species Enterococcus gallinarum.

21. The method of claim 18, wherein the cancer is a lung cancer, and wherein the lung cancer is non-small-cell lung carcinoma or small-cell lung carcinoma.

22. The method of claim 18, wherein the cancer is a breast cancer, and wherein the breast cancer is mammary carcinoma or stage IV breast cancer.

23. The method of claim 18, wherein the cancer is a liver cancer, and wherein the liver cancer is hepatocellular carcinoma.

24. The method of claim 18, wherein the cancer is a colon cancer, and wherein the colon cancer is colorectal adenocarcinoma.

25. The method of claim 18, wherein the treating or preventing comprises a prevention of metastasis, a prevention of angiogenesis, a reduction of tumor size or a reduction of a tumor growth.

26. The method of claim 18, wherein the subject has cancer, or has been identified as being at risk of cancer.

27. The method of claim 18, wherein the subject has previously received treatment for cancer.

28. The method of claim 18, further comprising administering an additional therapeutic agent to the subject.

29. The method of claim 28, wherein the additional therapeutic 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.

30. The method of claim 18, wherein said administering comprises providing one or more doses of 1 g, 3 g, 5 g or 10 g of said pharmaceutical composition.