Compositions comprising bacterial strains

• US 9,987,311 B2
• Filed: 11/23/2016
• Issued: 06/05/2018
• Est. Priority Date: 11/23/2015
• Status: Active Grant

• Current Assignee: Armistice Capital Master Fund Ltd. (Armistice Capital LLC), 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
• Primary Examiner(s): Berke-Schlessel, David W
• Application Number:
  US15/359,988
• Publication Number:
  US 20170143775A1
• Time in Patent Office: 559 Days
• Field of Search: None
• CPC Class Codes: A23C 9/152 containing additives fermented milk preparations containing additives A23C9/13
• 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 2039/542 oral/gastrointestinal
• CPC Class Codes: A61K 2039/55594 from bacteria
• CPC Class Codes: A61K 2039/577 tolerising response
• CPC Class Codes: A61K 2039/58 raising an immune response against a target which is not the antigen used for immunisation
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 35/74 Bacteria therapeutic use of a bacterial protein A61K38/00
• CPC Class Codes: A61K 39/08 Clostridium, e.g. Clostridium tetani
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• 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 1/00 Drugs for disorders of the alimentary tract or the digestive system
• 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 11/08 : Bronchodilators
• CPC Class Codes: A61P 17/00 : Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 : for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/04 : Antipruritics
• CPC Class Codes: A61P 17/06 : Antipsoriatics
• CPC Class Codes: A61P 19/00 : Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 : for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 : for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• 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 35/04 : specific for metastasis
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• 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 7/00 : Drugs for disorders of the blood or the extracellular fluid
• 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 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×

10³ to about 1×

10¹¹ 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×

10⁶ to about 1×

10¹¹ 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.

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.

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×

10³ to about 1×

10¹¹ 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.