COMPOSITIONS COMPRISING BACTERIAL STRAINS

• US 20170354695A1
• Filed: 08/17/2017
• Published: 12/14/2017
• Est. Priority Date: 06/15/2015
• Status: Active Grant

• Current Assignee: CJ Bioscience Incorporated
• Original Assignee: 4D Pharma Research Limited (4D Pharma PLC)
• Inventors: GRANT, George, PATTERSON, Angela Margaret, MULDER, Imke, MCCLUSKEY, Seanin, RAFTIS, Emma
• Granted Patent: US 10,493,112 B2
• Time in Patent Office: Days
• CPC Class Codes: A23L 33/135 Bacteria or derivatives thereof, e.g. probiotics
• CPC Class Codes: A23L 33/30 Dietetic or nutritional methods, e.g. for losing weight A23L33/10 takes precedence
• 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 35/74 Bacteria therapeutic use of a bacterial protein A61K38/00
• CPC Class Codes: A61K 35/747 Lactobacilli, e.g. L. acidophilus or L. brevis
• 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 17/00 Drugs for dermatological disorders
• 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 25/02 : for peripheral neuropathies
• 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 27/00 : Drugs for disorders of the senses
• 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 37/02 : 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: C12N 1/205 : Bacterial isolates
• CPC Class Codes: C12R 2001/01 : Bacteria or Actinomycetales ; using bacteria or Actinomycetales
• 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

1-35. -35. (canceled)

36. A method of treating a condition mediated by the Th17 pathway in a subject, comprising:

administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a bacterial strain, wherein said bacterial strain comprises a 16s rRNA sequence with at least 95% homology to the sequence shown in SEQ ID NO;

9;

wherein said bacterial strain is live and viable; and

wherein said administering is effective to reduce the level a one cytokine of the Th17 pathway in the subject relative to the level of said cytokine prior to the administering, thereby treating said condition.

37. The method of claim 36, wherein the treating comprises alleviating a Th17 inflammatory response.

38. The method of claim 36, wherein the condition is a Th17-mediated inflammatory disease or a Th17-mediated autoimmune disease.

39. The method of claim 36, wherein the bacterial strain comprises a 16s rRNA sequence with at least 99.9% homology to the sequence shown in SEQ ID NO:

9.

40. The method of claim 36, wherein the bacterial strain is of the species Parabacteroides distasonis.

41. The method of claim 36, wherein the bacterial strain is lyophilised and the pharmaceutical composition further comprises a pharmaceutically acceptable excipient, diluent, or carrier.

42. The method of claim 36, wherein the cytokine of the Th17 pathway comprises IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, IL-17F, IFN-γ

, IL-10, IL-6, or TNFα

.

43. The method of claim 36, wherein the condition comprises uveitis, a cancer, multiple sclerosis, an arthritis, neuromyelitis optica, psoriasis, systemic lupus erythematosus, celiac disease, an asthma, allergic asthma, neutrophilic asthma, chronic obstructive pulmonary disease (COPD), scleritis, vasculitis, Behcet'"'"'s disease, atherosclerosis, atopic dermatitis, emphysema, periodontitis, allergic rhinitis, and allograft rejection.

44. The method of claim 43, wherein the condition is uveitis;

and wherein the treating comprises reducing retinal damage in uveitis.

45. The method of claim 43, wherein the condition is asthma;

and wherein the treating comprises reducing neutrophilia or eosinophilia.

46. The method of claim 43, wherein the condition is cancer, wherein the cancer comprises breast cancer, lung cancer, liver cancer, colon cancer, or ovarian cancer.

47. The method of claim 43, wherein the condition is arthritis, wherein the arthritis comprises osteoarthritis, psoriatic arthritis, spondyloarthritis, ankylosing spondylitis, and juvenile idiopathic arthritis.

48. The method of claim 43, wherein the condition mediated is not ulcerative colitis, colitis, Crohn'"'"'s disease, irritable bowel disease, or rheumatoid arthritis.

49. A method of treating a condition mediated by the Th17 pathway in a subject, comprising:

administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising from about 1×

10⁶ to about 1×

10¹¹ colony forming units (CFU)/g of a bacterial strain of the species Parabacteroides distasonis;

wherein the administering of the pharmaceutical composition to the subject reduces a level of a cytokine of the Th17 pathway in the subject relative to the level of said cytokine prior to the administering;

thereby treating said condition.

50. The method of claim 49, wherein the condition comprises uveitis, a cancer, multiple sclerosis, an arthritis, neuromyelitis optica, psoriasis, systemic lupus erythematosus, celiac disease, an asthma, allergic asthma, neutrophilic asthma, chronic obstructive pulmonary disease (COPD), scleritis, vasculitis, Behcet'"'"'s disease, atherosclerosis, atopic dermatitis, emphysema, periodontitis, allergic rhinitis, and allograft rejection.

51. The method of claim 50, wherein the condition is uveitis;

and wherein the treating comprises reducing retinal damage in uveitis.

52. The method of claim 50, wherein the condition is asthma;

and wherein the treating comprises reducing neutrophilia or eosinophilia.

53. The method of claim 50, wherein the condition is cancer, and wherein the cancer comprises breast cancer, lung cancer, liver cancer, colon cancer, or ovarian cancer.

54. The method of claim 50, wherein the condition is arthritis, and wherein the arthritis comprises rheumatoid arthritis, osteoarthritis, psoriatic arthritis, spondyloarthritis, ankylosing spondylitis, and juvenile idiopathic arthritis.

55. The method of claim 49, wherein the bacterial strain is lyophilised and/or the pharmaceutical composition further comprises a pharmaceutically acceptable excipient, diluent, or carrier.

56. A pharmaceutical composition that contains:

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

9, wherein said bacterial strain is live and viable; and

a pharmaceutically acceptable excipient, diluent, or carrier;

wherein said bacterial strain is lyophilized.

57. The pharmaceutical composition of claim 56, wherein the bacterial strain comprises a 16s rRNA sequence with at least 99.9% homology to the sequence shown in SEQ ID NO:

9.

58. The pharmaceutical composition of claim 56, wherein the bacterial strain is of the genus Parabacteroides.

59. The pharmaceutical composition of claim 58, wherein the bacteria strain has a Sau3AI DNA restriction pattern that is the same as a Sau3AI DNA restriction pattern for a biotype of the Parabacteroides distasonis strain MRX005 deposited as NCIMB 42382 as determined by amplified ribosomal DNA restriction analysis;

and

wherein administration of said bacteria strain in a Collagen II stimulated mouse model results in a reduction in a level of IL-6, IL-10, IL-17A, IFN-γ

, or TNF-α

.

60. The pharmaceutical composition of claim 56, wherein the bacterial strain is of the species Parabacteroides distasonis.

61. The pharmaceutical composition of claim 56, wherein the bacterial strain is the Parabacteroides distasonis strain MRX005 deposited as NCIMB 42382.

62. The pharmaceutical composition of claim 56, wherein at least 50% of the bacterial strain as measured by an amount of 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.

63. The pharmaceutical composition of claim 56, wherein the therapeutically effective amount comprises from about 1×

10⁶ to about 1×

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

64. The pharmaceutical composition of claim 56, wherein the bacterial strain totally or partially colonises the intestine when administered to a subject.

65. A food product containing a single bacterial strain that comprises a polynucleotide sequence that is a 16s rRNA sequence with at least 99.9% homology to the polynucleotide of SEQ ID NO:

9.