Methods of Populating a Gastrointestinal Tract

• US 20160158294A1
• Filed: 02/04/2014
• Published: 06/09/2016
• Est. Priority Date: 02/04/2013
• Status: Active Grant

• Current Assignee: Seres Therapeutics, Inc.
• Original Assignee: Seres Therapeutics, Inc.
• Inventors: von Maltzahn, Geoffrey, Henn, Matthew R., Cook, David N., Berry, David Arthur, Afeyan, Noubar B., Goodman, Brian, McKenzie, Mary-Jane Lombardo, Vulic, Marin
• Granted Patent: US 10,064,900 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 35/37 Digestive system
• CPC Class Codes: A61K 35/74 Bacteria therapeutic use of a bacterial protein A61K38/00
• CPC Class Codes: A61K 35/741 Probiotics probiotic yeast, e.g. saccharomyces A61K36/06
• CPC Class Codes: A61K 35/742 Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
• CPC Class Codes: A61K 35/744 Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
• CPC Class Codes: A61K 35/745 Bifidobacteria
• CPC Class Codes: A61K 35/747 Lactobacilli, e.g. L. acidophilus or L. brevis
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• CPC Class Codes: A61K 9/4816 Wall or shell material
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• 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 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C12N 1/20 Bacteria; Culture media therefor
• 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

Methods and compositions for populating the gastrointestinal tract of a subject are described. Methods include administering to a subject a therapeutic composition comprising a purified population of spore-forming bacteria produced by providing a fecal material and subjecting the material to a treatment step resulting in purification of spore forming bacteria. Methods include administering an amount effective to engraft and/or augment in the gastrointestinal tract in order to treat or prevent a dysbiosis in the mammalian subject.

Claims

1. A method of populating the gastrointestinal tract of a mammalian subject, comprising the step of orally administering to the mammalian subject an effective amount of a therapeutic composition comprising a purified population of spore-forming bacteria produced by the steps of a) providing a fecal material and b) subjecting the material to a treatment step resulting in purification of spore-forming bacteria, wherein the purified population is present in an amount effective to engraft and/or augment in the gastrointestinal tract in order to treat or prevent a dysbiosis in the mammalian subject.

15. The method of claim 1, wherein the dysbiosis comprises i) a gastrointestinal disease, disorder or condition selected from the group consisting of Clostridium difficile-induced diarrhea, irritable bowel syndrome (IBS), colonization with a pathogen or pathobiont, infection with a drug-resistant pathogen or pathobiont, colitis, and Crohn'"'"'s Disease, or ii) a non-gastrointestinal disease, disorder or condition.

2. A method of populating the gastrointestinal tract of a mammalian subject, comprising the step of orally administering to the subject an effective amount of a therapeutic composition comprising a purified population of spore-forming bacteria, in an amount effective to engraft and/or augment in the gastrointestinal tract in order to treat or prevent a dysbiosis in a mammalian subject.

3-14. -14. (canceled)

16-22. -22. (canceled)

23. A therapeutic composition comprising a purified population of spore-forming bacteria or bacteria having a substantial activity of spore-forming bacteria, in an amount effective to populate the gastrointestinal tract of a mammalian subject to whom the therapeutic composition is administered.

53. The therapeutic composition of claim 23, wherein the purified population is obtained by the steps of a) providing a fecal material comprising spore-forming bacteria and b) subjecting the spore-forming bacteria to a treatment step resulting in purification of the spore-forming bacteria.

71. A method for production of the therapeutic composition of claim 23, comprising the steps of:

(a) providing a fecal material obtained from a mammalian donor subject; and

(b) subjecting the fecal material to at least one purification step under conditions such that a purified population of spore-forming bacteria is produced from the fecal material.

75. A method of treating or preventing a dysbiosis in a human subject, comprising administering to the human subject the therapeutic composition of claim 23.

76. The method of claim 75, wherein the therapeutic administration comprises oral administration of a composition comprising at least about 1×

10⁴ colony forming units of bacterial spores per dose of the composition.

77. The method of claim 76, wherein the bacterial spores comprise bacteria from the genera provided in Table 1.

24-52. -52. (canceled)

54-70. -70. (canceled)

72-74. -74. (canceled)

78-120. -120. (canceled)