Methods of populating a gastrointestinal tract

Patent metadata

Field	Value
Publication number	US-10064900-B2
Application number	US-201414765810-A
Country	US
Kind code	B2
Filing date	Feb 4, 2014
Priority date	Feb 4, 2013
Publication date	Sep 4, 2018
Grant date	Sep 4, 2018

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.

First claim

What is claimed is:

1. A method of treating or reducing the severity of at least one sign or symptom of a gastrointestinal disease in a human subject, the method comprising administering to the human subject an effective amount of a composition consisting essentially of a purified population of germinable bacterial spores,
wherein the population of germinable bacterial spores includes at least a first Operational Taxonomic Unit (OTU) and a second OTU, the first OTU comprising a first 16S rDNA comprising a first sequence having at least 97% identity to SEQ ID NO: 381 and the second OTU comprising a second 16S rDNA comprising a second sequence having at least 97% identity to SEQ ID NO: 556,
wherein the effective amount treats or reduces the severity of the at least one sign or symptom of the gastrointestinal disease in the human subject.

2. The method of claim 1 , wherein the first 16S rDNA comprises SEQ ID NO:381 and the second 16S rDNA comprises SEQ ID NO:556.

3. The method of claim 1 , wherein the composition comprises at least 1×10 4 colony forming units of germinable bacterial spores per dose of the composition.

4. The method of claim 1 , wherein the gastrointestinal disease is selected from the group consisting of Clostridium difficile -induced diarrhea, irritable bowel syndrome (IBS), infection or colonization with a pathogen or pathobiont including a drug resistant pathogen or pathobiont, colitis, a metabolic disorder, and Crohn's disease.

5. The method of claim 1 , wherein the purified population of germinable bacterial spores is produced by the steps of a) providing a fecal material comprising germinable bacterial spores and b) subjecting the fecal material to a treatment step resulting in purification of the germinable bacterial spores.

6. The method of claim 5 , wherein the treatment step comprises heat treatment or ethanol treatment.

7. The method of claim 5 , wherein the purified population is substantially depleted of a detectable level of a first pathogenic material.

8. The method of claim 7 , wherein the detectable level is detected by qPCR.

9. The method of claim 1 , wherein administering comprises oral administration.

10. The method of claim 1 , wherein the human subject has received one or more doses of an antibiotic therapy.

11. The method of claim 1 , wherein the composition is administered as a complement to an antibiotic therapy.

12. The method of claim 1 , wherein administration of the composition to the human subject reduces a colonization of Fusobacterium nucleatum ( Fusobacterium sp. 3_1_33) in the human subject.

13. The method of claim 12 , wherein the colonization of Fusobacterium nucleatum is reduced beyond detectable levels as detected by 16S-V4 sequencing.

14. The method of claim 1 , wherein a colonization of one or more species of Klebsiella in the human subject is detectably decreased as detected by 16S-V4 sequencing.

15. The method of claim 1 , wherein a colonization of one or more imipenem resistant Enterobacteriaceae species in the human subject is detectably decreased as detected by 16S-V4 sequencing.

16. The method of claim 1 , wherein a colonization of one or more non-pathogenic Bacteroides species in the human subject is detectably increased as detected by 16S-V4 sequencing.

17. The method of claim 1 , wherein at least one of the 16S rDNA sequences is a 16S-V4 rDNA sequence.

Assignees

• 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

Classifications

• A61P31/04

  Antibacterial agents · CPC title

• A61P1/04

  for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants · CPC title

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title

• A61P1/12

  Antidiarrhoeals · CPC title

• A61K9/0053 Primary

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title