SYNERGISTIC BACTERIAL COMPOSITIONS AND METHODS OF PRODUCTION AND USE THEREOF

• US 20140147425A1
• Filed: 11/26/2013
• Published: 05/29/2014
• Est. Priority Date: 11/23/2012
• Status: Active Grant

• Current Assignee: Seres Therapeutics, Inc.
• Original Assignee: Seres Health Inc.
• Inventors: von Maltzahn, Geoffrey, Berry, David A., Afeyan, Noubar B., Henn, Matthew R., D'Onofrio, Anthony Mario, Litcofsky, Kevin Daniel, Cook, David N., Aunins, John Grant
• Granted Patent: US 8,906,668 B2
• Time in Patent Office: Days
• US Class Current: 424/93.41
• 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 therapeutic composition comprising a first purified bacterial population capable of forming spores consisting of Collinsella aerofaciens and a second purified bacterial population consisting of a species selected from Table 1 or Table 4, wherein at least one of the first type and the second type are cytotoxic or cytostatic to a pathogenic bacterium.

2. The composition of claim 1, wherein a synergistic combination of the first bacterial spore population and the second bacterial spore population are cytotoxic or cytostatic to the pathogenic bacterium.

3. The composition of claim 2, wherein the combination is capable of inhibiting proliferation of the pathogenic bacterial present at a concentration at least equal to the concentration of the combination of the first type and the second type.

4. The composition of claim 2, wherein the combination is capable of inhibiting proliferation of the pathogenic bacterial present at a concentration at least about twice the concentration of the combination of the first type and the second type.

5. The composition of claim 2, wherein the combination is capable of inhibiting proliferation of the pathogenic bacterial present at a concentration at least about ten times the concentration of the combination of the first type and the second type.

6. The composition of claim 2, wherein the pathogenic bacterium is selected from the group consisting of Yersinia, Vibrio, Treponema, Streptococcus, Staphylococcus, Shigella, Salmonella, Rickettsia, Pseudomonas, Neisseria, Mycoplasma, Mycobacterium, Listeria, Leptospira, Legionella, Helicobacter, Haemophilus, Francisella, Escherichia, Enterococcus, Corynebacterium, Clostridium, Chlamydia, Chlamydophila, Campylobacter, Brucella, Borrelia, and Bordetella.

7. The composition of claim 2, wherein the pathogenic bacterium is Clostridium difficile.

8. The composition of claim 2, wherein the first bacterial spore population and the second bacterial spore population synergistically interact to be cytotoxic to the pathogenic bacterium.

9. The composition of claim 2, wherein the first bacterial spore population and the second bacterial spore population synergistically interact to be cytostatic to the pathogenic bacterium.

10. The composition of claim 1, wherein the bacterial composition comprises at least about 3 types of isolated bacteria capable of forming spores.

11. The composition of claim 1, wherein the bacterial composition comprises at least about 5 types of isolated bacteria capable of forming spores.

12. The composition of claim 1, wherein the first bacterial spore population and the second bacterial spore population are present in the composition in approximately equal concentrations.

13. The composition of claim 1, consisting essentially of between two and about ten bacterial spore populations of isolated bacteria.

14. A therapeutic composition comprising a first purified bacterial population consisting of bacteria comprising 16S rRNA sequence at least about 97% identical to a 16S rRNA sequence present in a reference Collinsella aerofaciens OTU, and a second purified bacterial population consisting of bacteria comprising 16S rRNA sequence at least about 97% identical to a 16S rRNA sequence present in a reference bacterium listed in Table 1 or Table 4, wherein at least one of the first type and the second type are cytotoxic or cytostatic to a pathogenic bacterium.

15. The composition of claim 14, wherein a synergistic combination of the first type and the second type are cytotoxic or cytostatic to the pathogenic bacterium.

16. The composition of claim 14, wherein the combination is capable of inhibiting proliferation of the pathogenic bacterial present at a concentration at least equal to the concentration of the combination of the first type and the second type.

17. The composition of claim 14, wherein the first type and the second type synergistically interact to be cytotoxic or cytostatic to the pathogenic bacterium.

18. The composition of claim 14, wherein the first purified bacterial population and the second purified bacterial population are capable of functionally populating the gastrointestinal tract of a human subject to whom the composition is administered.

19. The composition of claim 18, wherein the functional populating of the gastrointestinal tract comprises preventing, treating, reducing the severity of or reducing a symptom of a dysbiosis of the gastrointestinal tract.

20. The composition of claim 18, wherein the functional populating of the gastrointestinal tract comprises i) reducing the number of one or more types of pathogenic bacteria in the gastrointestinal tract;

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

21. The composition of claim 14, further comprising an effective amount of an anti-bacterial agent, an anti-fungal agent, an anti-viral agent or an anti-parasitic agent.

22. A method of treating or preventing an occurrence or a recurrence of a Clostridium difficile infection, comprising administering to a human subject in need thereof an effective amount of the therapeutic composition of claim 14 under conditions such that the first purified bacterial population and the second purified bacterial population exert an inhibitory effect on a pathogenic bacterium present in or entering into the gastrointestinal tract of the human subject, such that the number of Clostridium difficile bacteria present in the gastrointestinal tract is not detectably increased or is detectably decreased over a period of time.

23. The method of claim 22, 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.

24. The method of claim 22, wherein the first purified bacterial population and the second purified bacterial population synergistically interact to be cytotoxic and/or cytostatic to the Clostridium difficile bacteria.

25. The method of claim 22, wherein the therapeutic composition is orally administered.

26. The method of claim 22, wherein the therapeutic composition comprises a medical food.

30. The composition of claim 14, wherein the first purified bacterial population and/or the second purified bacterial population comprise spores.

27. A kit comprising in one or more containers:

a first purified population of a first type of bacteria capable of forming spores; and

a second purified population of a second type of bacteria capable of forming spores, wherein the first type and the second type are not identical, and wherein the first type and the second type, when co-localized in a target region of a gastrointestinal tract of a human subject in need thereof, are capable of functionally populating the gastrointestinal tract.

28. The kit of claim 27, wherein the first purified population and the second purified population are present in a single container.

29. The kit of claim 27, formulated for use as a nutritional supplement and optionally comprising a prebiotic material.