IP Library Granted Patent US 9,585,921
Granted Patent B2
US 9,585,921 · App. 14/884,655 · Granted Mar 7, 2017

Compositions and methods

Inventors: Gregory McKenzie (Arlington, MA); Mary-Jane Lombardo McKenzie (Arlington, MA); David N. Cook (Brooklyn, NY); Marin Vulic (Boston, MA); Geoffrey von Maltzahn (Boston, MA); Brian Goodman (Boston, MA); John Grant Aunins (Doylestown, PA); Matthew R. Henn (Somerville, MA); David Arthur Berry (Brookline, MA); Jonathan Winkler (Boston, MA)
Assignee: SERES THERAPEUTICS, INC.
A61K35/741A61K9/0053A61K9/4816A61K35/74A61K35/742A61K35/744A61K35/745A61K35/747A61K45/06C12N1/20
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Quick Facts
Patent No.
US 9,585,921
App. No.
14/884,655
Granted
Mar 7, 2017
Kind
B2
Abstract

Disclosed herein are therapeutic compositions containing non-pathogenic, germination-competent bacterial spores, for the prevention, control, and treatment of gastrointestinal diseases, disorders and conditions and for general nutritional health.

Claims (37)

1. A composition for treating or reducing a severity of at least one symptom of a gastrointestinal disease, disorder or condition associated with a dysbiosis in a subject, the composition comprising a purified population of Acetivibrio ethanolgignens spores in an amount effective to populate a gastrointestinal tract in the subject and a capsule, wherein

the composition is derived from fecal material subjected to ethanol treatment or heat treatment; and

the composition is substantially depleted of a residual habitat product of the fecal material; and

the Acetivibrio ethanolgignens is not detectable in the fecal material before the ethanol treatment or the heat treatment.

2. The composition of claim 1 , wherein the Acetivibrio ethanolgignens is not detectable in the fecal material before the ethanol treatment or the heat treatment as assayed by full-length 16S sequencing of bacterial colonies grown and isolated from the fecal material before the ethanol treatment or the heat treatment.

3. The composition of claim 1 , wherein the Acetivibrio ethanolgignens is not detectable in the fecal material before the ethanol treatment or the heat treatment using an assay with a detectable limit of 20 cfu/ml.

4. The composition_of claim 3 , wherein the fecal material is a 10 to 20% fecal suspension.

5. The composition of claim 1 , further comprising at least one species of germinable bacterial spores selected from the group consisting of, Bacillus licheniformis, Bacillus pumilus, Clostridium hylemonae, Clostridium methypentosum, Clostridium sp YIT 12069, Anaerofustis stercorihominis, Bacillus anthracis, Bacillus horti, Bacillus nealsonii, Bacillus sp. BT1B_CT2, Bacillus thuringiensis, Bacteroides galacturonicus, Bacteroides pectinophilus, Brachyspira pilosicoli, Clostridium aldenense, Clostridium beijerinckii, Clostridium carnis, Clostridium celatum, Clostridium favososporum, Clostridium irregulare, Clostridium sp. L2-50, Clostridium sp. MT4 E, Clostridium sp. NML 04A032, Clostridium sp. SS2/1, Clostridium stercorarium, Clostridium xylanolyticum, Coprococcus sp. ART55/1, Deferribacteres sp. oral clone JV006, Desulfitobacterium frappieri, Eubacterium callanderi, Eubacterium siraeum, Exiguobacterium acetylicum, Gemmiger formicilis, Lachnospira multipara, Lachnospira pectinoschiza, Roseburia faecalis , and Ruminococcus albus.

6. The composition of claim 1 , wherein the composition comprises an amount of bacteria effective to augment growth in the subject's gastrointestinal tract of at least one bacteria not detectable in the composition or to modulate microbiota diversity after administration of the composition compared to the microbiota diversity present in the subject's gastrointestinal tract prior to administration of the composition.

7. The composition of claim 1 , wherein the subject is a human.

8. The composition of claim 1 , wherein the gastrointestinal disease, disorder or condition 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.

9. The composition of claim 1 , wherein the gastrointestinal disease, disorder or condition is Clostridium difficile -induced diarrhea.

10. The composition of claim 1 , wherein the composition comprises at least 1×10 4 colony forming units of the Acetivibrio ethanolgignens per dose of the composition.

11. The composition of claim 1 , wherein the fecal material is obtained from a validated mammalian donor subject not having a detectable level of a pathogen or a pathobiont prior to production of the fecal material.

12. The composition of claim 1 , wherein the fecal material is obtained from a validated mammalian donor subject not having a detectable level of a pathogen or a pathobiont prior to production of the fecal material and the pathogen or a pathobiont is selected from the group consisting of blood-borne pathogens (HIV, HTLV, HCV, HBV, CMV, HAV and Treponema pallidum ) and fecal bacterial pathogens ( Salmonella, Shigella, Yersinia, Campylobacter, E. coli 0157), ova and parasites, and other infectious agents ( Giardia, Cryptosporidium Cyclospora, Isospora ).

13. The composition of claim 1 , wherein the composition is derived from fecal material subjected to ethanol treatment and the ethanol treatment comprises

a. forming a 10% w/v suspension of human fecal material;

b. mixing the suspension with absolute ethanol in a 1:1 ratio;

c. incubating the suspension of (b);

d. collecting the bacterial spores in the suspension;

e. adding glycerol to the bacterial spores of (d); and

f. storing the composition at −80 degrees Celsius.

14. The composition of claim 1 , wherein the composition is derived from fecal material subjected to heat treatment and the heat treatment comprises

a. forming a 10% w/v suspension of human fecal material in PBS;

b. incubating the suspension of (a) at 80 degrees Celsius for 30 minutes, thereby forming a heat treated suspension;

c. adding glycerol to the heat treated suspension; and

d. storing the composition at −80 degrees Celsius.

15. The composition of claim 1 , wherein the residual habitat product is an abiotic material, a human or animal cell, a virus, a fungus, or a mycoplasma.

16. The composition of claim 1 , wherein the Acetivibrio ethanolgignens is not detectable in the fecal material before treatment by genomic and/or microbiological assay methods.

17. The composition of claim 1 , wherein, using qPCR, the Acetivibrio ethanolgignens is not detectable in the fecal material before treatment.

18. The composition of claim 1 , comprising a delayed release capsule.

19. The composition of claim 1 , formulated for oral administration.

20. The composition of claim 1 , further comprising an antibiotic.

21. The composition of claim 1 , wherein the composition is derived from fecal material subjected to ethanol treatment.

22. The composition of claim 21 , wherein the ethanol treatment comprises treatment with 30-90% ethanol.

23. The composition of claim 21 , wherein the ethanol treatment comprises treatment with 50-70% ethanol.

24. The composition of claim 21 , wherein the ethanol treatment comprises treatment with 50% ethanol.

Assignments (4)
RELEASE OF SECURITY INTEREST Recorded Sep 30, 2024
From: OAKTREE FUND ADMINISTRATION, LLC, AS ADMINISTRATIVE AGENT
To: SERES THERAPEUTICS, INC.
Reel/Frame 069082/0849 →
SECURITY INTEREST Recorded Apr 27, 2023
From: SERES THERAPEUTICS, INC.
To: OAKTREE FUND ADMINISTRATION, LLC
Reel/Frame 063485/0542 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 18, 2016
From: MCKENZIE, GREGORY; LOMBARDO-MCKENZIE, MARY-JANE; COOK, DAVID N.; VULIC, MARIN; GOODMAN, BRIAN; AUNINS, JOHN GRANT; HENN, MATTHEW R.; WINKLER, JONATHAN; VON MALTZHAN, GEOFFREY; BERRY, DAVID ARTHUR
To: SERES HEALTH, INC.
Reel/Frame 038037/0614 →
CHANGE OF NAME Recorded Mar 18, 2016
From: SERES HEALTH, INC.
To: SERES THERAPEUTICS, INC.
Reel/Frame 038177/0976 →
Continuity (9)
Continuation 14313828 · Jun 24, 2014
Division 14197044 · Mar 4, 2014
Continuation PCTUS2014014745 · Feb 4, 2014
Provisional Application 61760584 · Feb 4, 2013
Provisional Application 61760585 · Feb 4, 2013
Provisional Application 61760574 · Feb 4, 2013
Provisional Application 61760606 · Feb 4, 2013
Provisional Application 61926918 · Jan 13, 2014
Related Publication 20160199423A1 · Jul 14, 2016