Synergistic bacterial compositions and methods of production and use thereof

• US 9,533,014 B2
• Filed: 01/08/2015
• Issued: 01/03/2017
• Est. Priority Date: 11/23/2012
• Status: Active Grant

• Current Assignee: Seres Therapeutics, Inc.
• Original Assignee: Seres Therapeutics, Inc.
• Inventors: Henn, Matthew R., von Maltzahn, Geoffrey, D'Onofrio, Anthony Mario, Litcofsky, Kevin Daniel, Berry, David Arthur, Cook, David N., Afeyan, Noubar B., Aunins, John Grant
• Primary Examiner(s): GRASER, JENNIFER E
• Application Number:
  US14/592,481
• Publication Number:
  US 20150190435A1
• Time in Patent Office: 726 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A23L 33/127 Antibiotics
• CPC Class Codes: A23L 33/135 Bacteria or derivatives thereof, e.g. probiotics
• CPC Class Codes: A23P 10/30 Encapsulation of particles, e.g. foodstuff additives
• CPC Class Codes: A23V 2002/00 Food compositions, function of food ingredients or processes for food or foodstuffs
• 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 35/74 Bacteria therapeutic use of a bacterial protein A61K38/00
• CPC Class Codes: A61K 35/742 Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
• CPC Class Codes: A61K 38/13 Cyclosporins
• 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 9/4891 Coated capsules; Multilayered drug free capsule shells with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004
• 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

Provided are therapeutic compositions containing Ecobiotic™ populations for prevention, treatment and reduction of symptoms associated with a dysbiosis of a mammalian subject such as a human.

Claims

1. A method of treating an occurrence or a recurrence of a Clostridium difficile infection, comprising administering to a human subject in need thereof an effective amount of a therapeutic composition comprising a first purified bacterial population consisting of a first bacteria comprising a 16S rDNA sequence at least about 97% identical to a 16S rDNA sequence present in a reference Collinsella aerofaciens OTU, and a second purified bacterial population consisting of a second bacteria comprising a 16S rDNA sequence at least about 97% identical to a 16S rDNA sequence present in a reference bacterium of the family Clostridiaceae listed in Table 1, wherein a synergistic combination of the first bacteria and the second bacteria is cytotoxic or cytostatic to a Clostridium difficile.

2. The method of claim 1, wherein the number of Clostridium difficile bacteria present in or excreted from the gastrointestinal tract of the human subject is detectably reduced within one month of administration of the bacterial composition.

3. The method of claim 1, wherein the synergistic combination of the first bacteria and the second bacteria is cytotoxic or cytostatic to Clostridium difficile as demonstrated by a CivSim assay.

4. The method of claim 1, wherein the therapeutic composition is orally administered.

5. The method of claim 1, wherein the therapeutic composition comprises a medical food.

6. The method of claim 1, further comprising administering an effective amount of an anti-bacterial agent, an anti-fungal agent, an anti-viral agent, or an anti-parasitic agent.

7. The method of claim 1, wherein the synergistic combination is capable of inhibiting proliferation of Clostridium difficile bacterium present at a concentration at least equal to the concentration of the combination of the first bacterial population and the second bacterial population.

8. The method of claim 1, wherein the first purified bacterial population and the second purified bacterial population are capable of functionally populating the gastrointestinal tract of the human subject to whom the composition is administered.

9. The method of claim 8, wherein the functional populating of the gastrointestinal tract comprises treating or reducing the severity of or reducing a symptom of a Clostridium difficile infection of the gastrointestinal tract.

10. The method of claim 8, wherein the functional populating of the gastrointestinal tract comprises i) reducing the number of Clostridium difficile bacteria in the gastrointestinal tract;

or ii) increasing the number of one or more non-pathogenic bacteria in the gastrointestinal tract.

11. The method of claim 1, wherein the second purified bacterial population comprise spores.