# US 10,245,287 B2 · Compositions comprising bacterial strains

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- Number: US 10,245,287 B2
- Document ID: US10245287B2
- Status: Granted
- Kind: B2
- Application number: 15/803,721
- Filed: 2017-11-03
- Published: 2018-03-22
- Granted: 2019-04-02
- Earliest claimed: 2015-11-20
- Assignees: 4D Pharma Research Limited
- Applicants: 4D Pharma Research Limited
- Inventors: Imke Elisabeth Mulder; Amy Beth Holt; Domenico Panzica; Seanin Marie McCluskey
- Web page: https://patentgrep.com/patent/US10245287B2

## CPC

- A61K 35/74: Bacteria (therapeutic use of a bacterial protein A61K38/00)
- A23C 9/1585: {Antibiotics; Bacteriocins; Fungicides from microorganisms}
- A23L 33/135: Bacteria or derivatives thereof, e.g. probiotics
- 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)}
- A61K 31/739: Lipopolysaccharides
- A61K 35/744: Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K 39/09: {Lactobacillales, e.g. aerococcus, enterococcus, lactobacillus, lactococcus}, streptococcus
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C12N 1/20: Bacteria; Culture media therefor
- C12R 1/46
- A23V 2002/00: Food compositions, function of food ingredients or processes for food or foodstuffs
- A61K 2035/11: {Medicinal preparations comprising living procariotic cells}
- A61K 2039/585: {wherein the target is cancer}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A23C: DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; PREPARATION THEREOF (preservation thereof A23B11/00)
- A23L: FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF (preservation thereof A23B)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12R: INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- A23V: INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION

## Abstract

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

## Claims

### Claim 1

A pharmaceutical composition that comprises:
a bacteria strain that comprises a 16s rRNA gene sequence with at least 99.5% sequence identity to the polynucleotide of SEQ ID NO:2, wherein the sequence identity is 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; and
a pharmaceutically acceptable excipient, diluent, or carrier;
wherein said bacteria strain has a carbohydrate fermentation profile that comprises:
(i) a positive fermentation of at least one of: L-arabinose and D-xylose; and
(ii) an intermediate fermentation of Methyl-αD-glycopyranoside;
and wherein said bacteria strain is lyophilized.

### Claim 2 (depends on 1)

The pharmaceutical composition of claim 1, wherein said carbohydrate profile further comprises a positive fermentation of at least one of: D-tagatose, D-ribose, potassium gluconate, D-galactose, D-glucose, D-fructose, D-mannose, N-acetylglucosamine, amygdalin, arbutin, salicin, D-cellobiose, D-maltose, sucrose, D-trehalose, and gentiobiose.

### Claim 3 (depends on 1)

The pharmaceutical composition of claim 1, wherein said carbohydrate profile further comprises an intermediate fermentation of at least one of: D-mannitol, D-lactose, and starch.

### Claim 4 (depends on 1)

The pharmaceutical composition of claim 1, wherein said carbohydrate profile further comprises:
i. a positive fermentation of at least one of: D-tagatose, D-ribose, potassium gluconate, D-galactose, D-glucose, D-fructose, D-mannose, N-acetylglucosamine, amygdalin, arbutin, salicin, D-cellobiose, D-maltose, sucrose, D-trehalose, and gentiobiose; and
ii. an intermediate fermentation of at least one of: D-mannitol, D-lactose, and starch.

### Claim 5 (depends on 4)

The pharmaceutical composition of claim 4, wherein said carbohydrate profile comprises a positive fermentation of L-arabinose, D-xylose, and gentiobiose.

### Claim 6 (depends on 4)

The pharmaceutical composition of claim 4, wherein said carbohydrate profile comprises a positive fermentation of L-arabinose and D-xylose and an intermediate fermentation of Methyl-αD-glycopyranoside.

### Claim 7 (depends on 1)

The pharmaceutical composition of claim 1, wherein said acceptable excipient, diluent, or carrier further comprises a lyoprotectant.

### Claim 8 (depends on 1)

The pharmaceutical composition of claim 1, wherein said pharmaceutical composition further comprises at least one additional bacteria strain.

### Claim 9 (depends on 1)

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

### Claim 10 (depends on 1)

The pharmaceutical composition of claim 1, wherein said bacteria strain is present in an amount that 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.

### Claim 11 (depends on 1)

The pharmaceutical composition of claim 1, wherein said pharmaceutical composition further comprises a lipopolysaccharide.

### Claim 12 (depends on 1)

The pharmaceutical composition of claim 1, wherein said bacteria strain is effective to increase production of at least one cytokine selected from the group consisting of IL-6, TNF-α, and IL-1β.

### Claim 13 (depends on 1)

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

### Claim 14 (depends on 13)

The pharmaceutical composition of claim 13, wherein said pharmaceutical composition comprises an enteric coating.

### Claim 15 (depends on 1)

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

### Claim 16 (depends on 1)

The pharmaceutical composition of claim 1, wherein said bacteria strain comprises a 16s rRNA gene sequence with at least 99.9% sequence identity to the polynucleotide of SEQ ID NO:2, wherein the sequence identity is 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.

### Claim 17 (depends on 1)

The pharmaceutical composition of claim 1, wherein said bacteria strain comprises the 16s rRNA gene sequence of SEQ ID NO: 2.

### Claim 18 (depends on 1)

The pharmaceutical composition of claim 1, wherein said bacteria strain is of the species Enterococcus gallinarum.