MICROBIOTA RESTORATION THERAPY (MRT), COMPOSITIONS AND METHODS OF MANUFACTURE

• US 20160058804A1
• Filed: 11/12/2015
• Published: 03/03/2016
• Est. Priority Date: 06/05/2013
• Status: Active Grant

• Current Assignee: Rebiotix Inc. (Ferring Holding SA)
• Original Assignee: Rebiotix Inc. (Ferring Holding SA)
• Inventors: Jones, Lee A., Jones, Courtney R., Hlavka, Edwin J., Gordon, Ryan D.
• Granted Patent: US 9,642,880 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A01N 1/021 Preservation or perfusion media, liquids, solids or gases used in the preservation of cells, tissue, organs or bodily fluids
• CPC Class Codes: A01N 1/0284 Temperature processes, i.e. using a designated change in temperature over time
• CPC Class Codes: A61K 35/38 Stomach; Intestine; Goblet cells; Oral mucosa; Saliva
• 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 35/747 Lactobacilli, e.g. L. acidophilus or L. brevis
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 9/0031 Rectum, anus
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: B65B 25/00 Packaging other articles presenting special problems bundling B65B27/00
• CPC Class Codes: B65B 7/02 Closing containers or receptacles deformed by, or taking-up shape, of, contents, e.g. bags, sacks
• CPC Class Codes: C12N 1/20 Bacteria; Culture media therefor
• CPC Class Codes: C12Q 1/04 Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor C12Q1/6897 takes precedence
• 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

Microbiota restoration therapy compositions and methods for manufacturing, processing, and/or delivering microbiota restoration therapy compositions are disclosed. An example method for manufacturing a microbiota restoration therapy composition may include collecting a human fecal sample and adding a diluent to the human fecal sample to form a diluted sample. The diluent may include a cryoprotectant. The method may also include mixing the diluted sample with a mixing apparatus and filtering the diluted sample. Filtering may form a filtrate. The method may also include transferring the filtrate to a sample bag and sealing the sample bag.

Claims

1. A method for treating ulcerative colitis, the method comprising:

administering a microbiota restoration therapy composition to a patient with ulcerative colitis;

wherein the microbiota restoration therapy composition is pre-screened for bacterial diversity;

wherein the pre-screened microbiota restoration therapy composition includes bacteria from at least seven different families and has a Shannon Diversity Index of 0.4-2.5 when calculated at the family level; and

wherein the microbiota restoration therapy composition comprises a mixture of an effective amount of fecal microbiota and an effective amount of polyethylene glycol.

2. The method of claim 1, further comprising administering a pre-treatment antibiotic to the patient, wherein the pre-treatment antibiotic includes vancomycin, fidaxomicin, rifaximimin, linezolid, daptomycin, quinupristin-dalfopristin, tigecycline, ceftaroline, ceftobiprole, televancin, teicoplanin, dalbavancin, metronidazole, ortivancin, or a combination thereof.

3. The method of claim 2, wherein the pre-treatment antibiotic is administered at a dose of 0.01 mg per day to 5000 mg per day.

4. The method of claim 2, wherein the pre-treatment antibiotic is administered orally, by enema, or by suppository.

5. The method of claim 2, wherein administering a pre-treatment antibiotic to the patient includes administering a single dose of the pre-treatment antibiotic to the patient.

6. The method of claim 2, wherein administering a pre-treatment antibiotic to the patient includes administering two or more doses of the pre-treatment antibiotic to the patient.

7. The method of claim 1, further comprising administering a post-treatment antibiotic to the patient after administering the microbiota restoration therapy composition to the patient.

8. The method of claim 1, further comprising administering a second dose of the microbiota restoration therapy composition to the patient.

9. The method of claim 1, wherein administering a microbiota restoration therapy composition to a patient with ulcerative colitis includes manufacturing the microbiota restoration therapy composition and wherein manufacturing the microbiota restoration therapy composition comprises:

collecting a human fecal sample;

adding polyethylene glycol to the human fecal sample to form a diluted sample;

mixing the diluted sample with a mixing apparatus;

filtering the diluted sample;

wherein filtering forms a filtrate;

transferring the filtrate to a sample bag; and

sealing the sample bag.

10. The method of claim 1, wherein administering a microbiota restoration therapy composition to a patient with ulcerative colitis includes administering a microbiota restoration therapy composition with an enema tube.

11. The method of claim 1, wherein administering a microbiota restoration therapy composition to a patient with ulcerative colitis includes administering a microbiota restoration therapy composition orally.

12. The method of claim 1, wherein the microbiota restoration therapy composition includes bacteria and wherein in the range of 40-60% of the bacteria is from the order Bacteroidales, in the range of 30-40% of the bacteria is from the order Clostridiales, and in the range of 36-48% of the bacteria is from the family Bacteroidaceae.

13. A method of treating ulcerative colitis, the method comprising:

administering a primary dose of a microbiota restoration therapy composition to a patient with ulcerative colitis, wherein the microbiota restoration therapy composition has been manufactured using the following method;

collecting a human fecal sample;

placing the human fecal sample into a filter bag;

adding a mixture of polyethylene glycol and saline to the human fecal sample to form a diluted sample at a concentration of 2-4 milliliters of the mixture of polyethylene glycol and saline per gram of the human fecal sample;

mixing the diluted sample with a paddle mixer at 230 rpm for two minutes;

filtering the diluted sample;

wherein filtering forms a filtrate;

transferring the filtrate to a sample bag; and

sealing the sample bag;

wherein the microbiota restoration therapy composition is pre-screened for bacterial diversity;

wherein the pre-screened microbiota restoration therapy composition includes bacteria from at least seven different families; and

administering a secondary dose of the pre-screened microbiota restoration therapy composition to the patient with ulcerative colitis.

14. The method of claim 13, further comprising administering a pre-treatment antibiotic to the patient, wherein the pre-treatment antibiotic includes vancomycin, fidaxomicin, rifaximimin, linezolid, daptomycin, quinupristin-dalfopristin, tigecycline, ceftaroline, ceftobiprole, televancin, teicoplanin, dalbavancin, metronidazole, ortivancin, or a combination thereof.

15. The method of claim 13, wherein the pre-treatment antibiotic is administered at a dose of 0.01 mg per day to 5000 mg per day.

16. The method of claim 13, wherein the pre-treatment antibiotic is administered orally, by enema, or by suppository.

17. The method of claim 13, further comprising administering a post-treatment antibiotic to the patient after administering the microbiota restoration therapy composition to the patient.

18. The method of claim 13, wherein administering a microbiota restoration therapy composition to a patient with ulcerative colitis includes administering a microbiota restoration therapy composition with an enema tube.

19. The method of claim 13, wherein administering a microbiota restoration therapy composition to a patient with ulcerative colitis includes administering a microbiota restoration therapy composition orally.

20. A method of treating ulcerative colitis, the method comprising:

administering one or more doses of a microbiota restoration therapy composition to a patient with a ulcerative colitis, wherein the microbiota restoration therapy composition has been manufactured using the following method;

collecting a human fecal sample;

placing the human fecal sample into a filter bag;

adding a diluent to the human fecal sample to form a diluted sample at a concentration of 2-4 milliliters of the diluent per gram of the human fecal sample, wherein the diluent is a mixture of saline and polyethylene glycol and the concentration of polyethylene glycol in the diluent is about 30-90 grams/liter;

mixing the diluted sample with a paddle mixer at 230 rpm for two minutes;

filtering the diluted sample;

wherein filtering forms a filtrate;

transferring the filtrate to a sample bag; and

sealing the sample bag;

wherein the microbiota restoration therapy composition is pre-screened for bacterial diversity and the pre-screened microbiota restoration therapy composition includes bacteria from at least two orders and at least seven different families and has a Shannon Diversity Index of 0.4-2.5 when calculated at the family level, wherein in the range of 40-60% of the bacteria is from the order Bacteroidales, in the range of 30-40% of the bacteria is from the order Clostridiales, and in the range of 36-48% of the bacteria is from the family Bacteroidaceae.