COMPOSITIONS COMPRISING BACTERIAL STRAINS

• US 20190000892A1
• Filed: 07/10/2018
• Published: 01/03/2019
• Est. Priority Date: 11/20/2015
• Status: Active Grant

• Current Assignee: CJ Bioscience Incorporated
• Original Assignee: 4D Pharma Research Limited (4D Pharma PLC)
• Inventors: Mulder, Imke Elisabeth, Holt, Amy Beth, McCluskey, Seanin Marie, Lennon, Grainne Clare, Ahmed, Suaad
• Granted Patent: US 10,471,108 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 2039/52 Bacterial cells; Fungal cells; Protozoal cells
• CPC Class Codes: A61K 2039/585 wherein the target is cancer
• 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 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• 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: A61K 9/50 Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals A61K9/2081 takes precedence; particles with a single coating comprising drug A61K9/167
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 : Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

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

Claims

1. A pharmaceutical composition that comprises an amount of a bacteria strain of the species Enterococcus faecium;

wherein said Enterococcus faecium is the sole species present in the pharmaceutical composition in an amount that is greater than 1×

10⁶ CFU/g with respect to a total weight of the pharmaceutical composition;

wherein the Enterococcus faecium bacteria strain is live and lyophilized; and

wherein the Enterococcus faecium bacteria strain has an enzyme profile as determined by a Rapid ID 32A analysis that is;

positive for at least one of;

arginine dihydrolase, β

-glucosidase, mannose fermentation, glutamic acid decarboxylase, arginine arylamidase, phenylalanine arylamidase, leucine arylamidase, pyroglutamic acid arylamidase, tyrosine arylamidase, glycine arylamidase, histidine arylamidase and serine arylamidase; and

(ii) intermediate for N-acetyl-β

-glucosaminidase.

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

3. The pharmaceutical composition of claim 1, wherein the Enterococcus faecium bacteria strain comprises a polynucleotide sequence that is a 16s rRNA gene sequence with at least 95% sequence identity to the polynucleotide of SEQ ID NO:

2 as 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.

4. The pharmaceutical composition of claim 1, wherein the Enterococcus faecium bacteria strain that comprises a polynucleotide sequence that is the 16s rRNA gene sequence of SEQ ID NO:

2.

5. The pharmaceutical composition of claim 1, wherein said Enterococcus faecium bacterial strain is the Enterococcus faecium bacteria strain deposited under accession number NCIMB 42487.

7. The pharmaceutical composition of claim 1, wherein the amount is sufficient to decrease production of at least one cytokine when administered to a subject, wherein the at least one cytokine comprises an IL-17 cytokine selected from the group consisting of:

IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, and IL-17F.

8. The pharmaceutical composition of claim 1, wherein the amount is effective to treat a condition mediated by an increase in the at least one cytokine when administered to a subject.

9. The pharmaceutical composition of claim 1, wherein at least 50% of the Enterococcus faecium 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.

10. The pharmaceutical composition of claim 1, wherein the amount comprises from about 1×

10⁶ to about 1×

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

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

13. The pharmaceutical composition of claim 12, further comprising 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 galacto-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.

31. The pharmaceutical composition of claim 1, wherein the amount comprises from about 1×

10⁸ to about 1×

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

32. The pharmaceutical composition of claim 1, wherein the amount comprises from about 1×

10⁷ to about 1×

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

33. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is encapsulated.

34. The pharmaceutical composition of claim 1, in the form of a table, capsule, or powder.

35. The pharmaceutical composition of claim 1, wherein the enzyme profile is positive for arginine dihydrolase and phenylalanine arylamidase.

36. The pharmaceutical composition of claim 1, wherein the enzyme profile is positive for pyroglutamic acid arylamidase and histidine arylamidase.

37. The pharmaceutical composition of claim 1, wherein the Enterococcus faecium bacteria strain comprises a polynucleotide sequence that is a 16s rRNA gene sequence with at least 99% sequence identity to the polynucleotide of SEQ ID NO:

2 as 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.

6. (canceled)

11. (canceled)

15-30. -30. (canceled)

38. A pharmaceutical composition that comprises an amount of a bacteria strain of the species Enterococcus faecium;

wherein the Enterococcus faecium bacteria strain is the sole bacteria strain present in the pharmaceutical composition in an amount that is greater than 1×

10⁸ CFU/g with respect to a total weight of the pharmaceutical composition;

wherein the Enterococcus faecium bacteria strain is live and lyophilized; and

wherein the Enterococcus faecium bacteria strain has an enzyme profile as determined by a Rapid ID 32A analysis that is;

(i) positive for at least one of;

arginine dihydrolase, β

-glucosidase, mannose fermentation, glutamic acid decarboxylase, arginine arylamidase, phenylalanine arylamidase, leucine arylamidase, pyroglutamic acid arylamidase, tyrosine arylamidase, glycine arylamidase, histidine arylamidase and serine arylamidase; and

(ii) intermediate for N-acetyl-β

-glucosaminidase.