Methods and compositions relating to microbial treatment and diagnosis of disorders

• US 10,675,312 B2
• Filed: 10/12/2018
• Issued: 06/09/2020
• Est. Priority Date: 10/31/2014
• Status: Active Grant

• Current Assignee: Pendulum Therapeutics, Inc.
• Original Assignee: Pendulum Therapeutics, Inc.
• Inventors: Cutcliffe, Colleen, Eid, John S., Bullard, James H., Schicklberger, Marcus F.
• Primary Examiner(s): Davis, Ruth A
• Application Number:
  US16/159,536
• Publication Number:
  US 20190030095A1
• Time in Patent Office: 606 Days
• CPC Class Codes: A23L 33/135 Bacteria or derivatives thereof, e.g. probiotics
• CPC Class Codes: A23V 2002/00 Food compositions, function of food ingredients or processes for food or foodstuffs
• CPC Class Codes: A23V 2200/3202 Prebiotics, ingredients fermented in the gastrointestinal tract by beneficial microflora
• CPC Class Codes: A23V 2200/3204 Probiotics, living bacteria to be ingested for action in the digestive tract
• CPC Class Codes: A23V 2200/328 having effect on glycaemic control and diabetes
• CPC Class Codes: A23V 2200/332 Promoters of weight control and weight loss
• CPC Class Codes: A61K 2035/115 Probiotics
• 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 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/733 Fructosans, e.g. inulin
• 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 35/745 Bifidobacteria
• 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 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• CPC Class Codes: A61K 9/4816 Wall or shell material
• 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: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C12N 1/20 : Bacteria; Culture media therefor
• CPC Class Codes: C12Q 1/689 : for bacteria
• CPC Class Codes: G01N 2333/605 : Glucagons
• CPC Class Codes: G01N 2800/04 : Endocrine or metabolic disorders
• CPC Class Codes: G01N 33/66 : involving blood sugars, e.g. galactose

Abstract

The present disclosure provides methods, systems, compositions, and kits to address the need for microbiome-related treatment of health conditions and disease. The present disclosure provides for treatment of metabolic conditions using microbial compositions.

Claims

1. A method of treating a metabolic disorder in a subject, the method comprising:

administering to the subject a composition comprising;

a) a first microbe comprising a 16S rRNA sequence comprising at least about 97% sequence identity to a 16S rRNA sequence of Akkermansia muciniphila;

b) a second microbe comprising a 16S rRNA sequence comprising at least about 97% sequence identity to a 16S rRNA sequence of Eubacterium hallii;

and

c) a third microbe comprising a 16S rRNA sequence comprising at least 97% sequence identity to a 16S rRNA sequence of Clostridium beijerinckii;

thereby treating the metabolic disorder, wherein the metabolic disorder is selected from the group consisting of Type 2 Diabetes Mellitus, Type 1 Diabetes Mellitus, obesity, and insulin resistance.

2. The method of claim 1, wherein the first microbe is Akkermansia muciniphila.

3. The method of claim 1, wherein the composition further comprises a fourth microbe, wherein the fourth microbe comprises a 16S rRNA sequence that comprises at least about 97% sequence identity to a 16S rRNA sequence of a microbe selected from the group consisting of:

Bifidobacterium infantis, Clostridium butyricum, Clostridium indolis, and Faecalibacterium prausnitzii.

4. The method of claim 1, wherein the composition further comprises one or more of:

Bifidobacterium infantis, Clostridium butyricum, Clostridium indolis, or Faecalibacterium prausnitzii.

5. The method of claim 1, wherein the composition further comprises Bifidobacterium infantis.

6. The method of claim 1, wherein the composition does not contain dairy.

7. The method of claim 1, wherein the composition is administered daily.

8. The method of claim 1, wherein the composition is administered at least twice daily.

9. The method of claim 1, wherein the composition is in a form of a capsule.

10. The method of claim 1, wherein the composition is a food composition in a form of a bar.

11. The method of claim 1, wherein the metabolic disorder is Type 2 diabetes mellitus.

12. The method of claim 1, wherein the second microbe is Eubacterium hallii.

13. The method of claim 1, wherein the first microbe, the second microbe, or the third microbe has been grown substantially on plant-based media.

14. The method of claim 13, wherein the plant-based media comprises an amino acid source that is a plant-protein hydrolysate.

15. The method of claim 1, wherein the third microbe is Clostridium beijerinckii.

16. A method of treating a metabolic disorder in a subject, the method comprising:

administering to the subject a composition comprising;

a) a first microbe comprising a 16S rRNA sequence comprising at least about 85% sequence identity to a 16S rRNA sequence of Akkermansia muciniphila;

b) a second microbe comprising a 16S rRNA sequence comprising at least about 85% sequence identity to a 16S rRNA sequence of Eubacterium hallii;

and

c) a third microbe comprising a 16S rRNA sequence comprising at least about 85% sequence identity to a 16S rRNA sequence of Clostridium beijerinckii;

thereby treating the metabolic disorder, wherein the metabolic disorder is selected from the group consisting of Type 2 Diabetes Mellitus, Type 1 Diabetes Mellitus, obesity, and insulin resistance.

17. The method of claim 16, wherein the first microbe is Akkermansia muciniphila.

18. The method of claim 16, wherein the composition is administered daily.

19. The method of claim 16, wherein the composition is in a form of a capsule.

20. The method of claim 16, wherein the composition is a food composition in a form of a bar.

21. The method of claim 16, wherein the composition does not contain dairy.

22. The method of claim 16, wherein the composition further comprises a fourth microbe, wherein the fourth microbe comprises a 16S rRNA sequence that comprises at least about 85% sequence identity to a 16S rRNA sequence from a microbe selected from the group consisting of:

Bifidobacterium infantis, Clostridium butyricum, Clostridium indolis, and Faecalibacterium prausnitzii.

23. The method of claim 16, wherein the composition further comprises Bifidobacterium infantis.

24. The method of claim 16, wherein the metabolic disorder is Type 2 diabetes mellitus.

25. The method of claim 16, wherein the composition further comprises one or more of:

Bifidobacterium infantis, Clostridium butyricum, Clostridium indolis, or Faecalibacterium prausnitzii.

26. The method of claim 16, wherein the second microbe is Eubacterium hallii.

27. The method of claim 16, wherein the composition comprises at least 1×

10⁵ CFUs of the first microbe, the second microbe, the third microbe, or a combination thereof.

28. The method of claim 16, wherein the third microbe is Clostridium beijerinckii.

29. The method of claim 16, wherein the composition further comprises an excipient comprising a growth media, wherein the growth media is a substantially plant-based media.

30. The method of claim 29, wherein the substantially plant-based media is in a powdered form in the composition.

31. The method of claim 29, wherein the substantially plant-based media comprises an amino acid source that is a plant-protein hydrolysate.