Methods and compositions relating to microbial treatment and diagnosis of disorders

• US 10,668,116 B2
• Filed: 09/21/2016
• Issued: 06/02/2020
• 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:
  US15/271,672
• Publication Number:
  US 20170027996A1
• Time in Patent Office: 1,350 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 composition comprising:

(a) a first microbe with a 16S ribosomal RNA (rRNA) sequence comprising at least about 97% sequence identity to a 16S rRNA sequence from Clostridium beijerinckii;

(b) a second microbe with a 16S rRNA sequence comprising at least about 97% sequence identity to a 16S rRNA sequence from Akkermansia muciniphila;

(c) a third microbe with a 16S rRNA sequence comprising at least about 97% sequence identity to a 16S rRNA sequence from Clostridium butyricum;

(d) a fourth microbe with a 16S rRNA sequence comprising at least about 97% sequence identity to a 16S rRNA sequence from Eubacterium hallii; and

(e) an enteric coating.

2. The composition of claim 1, wherein said composition is suitable for oral delivery.

3. The composition of claim 1, wherein said enteric-coating dissolves at a pH greater than at least about pH 6.5.

4. The composition of claim 1, wherein said composition is suitable for administration to a human subject.

5. The composition of claim 1, wherein said composition further comprises a prebiotic.

6. The composition of claim 5, wherein said prebiotic is selected from the group consisting of:

a complex carbohydrate, a complex sugar, a resistant dextrin, a resistant starch, an amino acid, a peptide, biotin, polydextrose, a fructooligosaccharide (FOS), a galactooligosaccharide (GOS), inulin, a starch, lignin, psyllium, chitin, chitosan, gum, guar gum, high amylose cornstarch (HAS), cellulose, β

-glucan, hemi-cellulose, lactulose, mannooligosaccharide, mannan oligosaccharide (MOS), oligofructose-enriched inulin, an oligofructose, an oligodextrose, a tagatose, a trans-galactooligosaccharide, pectin, a resistant starch, xylooligosaccharide (XOS), and any combination thereof.

7. The composition of claim 5, wherein said prebiotic comprises inulin.

8. The composition of claim 5, wherein said prebiotic comprises fructooligosaccharide.

9. The composition of claim 5, wherein said prebiotic comprises fructooligosaccharide and inulin.

10. The composition of claim 1, wherein said composition comprises at least about 10⁵ colony forming units (CFU) of each of said first, second, third, and fourth microbes.

11. The composition of claim 1, wherein said composition comprises at least about 10⁷ CFUs of said first microbe, said second microbe, said third microbe, said fourth microbe, or a combination thereof.

12. The composition of claim 1, wherein said composition further comprises a microbe with a 16S rRNA sequence comprising at least about 85% sequence identity to a 16S rRNA sequence of a microbe selected from the group consisting of:

Anaerostipes caccae, Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum, Clostridium aminophilum, Clostridium colinum, Clostridium indolis, Clostridium orbiscindens, Enterococcus faecium, Eubacterium rectale, Faecalibacterium prausnitzii, Fibrobacter succinogenes, Oscillospira guilliermondii, Roseburia cecicola, Roseburia inulinivorans, Ruminococcus flavefaciens, Ruminococcus gnavus, Ruminococcus obeum, Streptococcus cremoris, Streptococcus faecium, Streptococcus infantis, Streptococcus mutans, Streptococcus thermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus, Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani, Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacterium dolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis, and Roseburia intestinalis.

13. The composition of claim 1, wherein said composition is suitable for delivery to a small intestine, a large intestine, an ileum, or a combination thereof of a subject.

14. The composition of claim 1, wherein said first microbe is Clostridium beijerinckii.

15. The composition of claim 1, wherein said second microbe is Akkermansia muciniphila.

16. The composition of claim 1, wherein said third microbe is Clostridium butyricum.

17. The composition of claim 1, wherein said fourth microbe is Eubacterium hallii.

18. The composition of claim 1, wherein said composition further comprises a microbe with a 16S rRNA sequence comprising at least about 97% sequence identity to a 16S rRNA sequence from Bifidobacterium infantis.

19. The composition of claim 1, wherein said composition further comprises Bifidobacterium infantis.

20. A composition comprising:

Clostridium beijerinckii, Akkermansia muciniphila, Clostridium butyricum, Eubacterium hallii, and an enteric coating.

21. The composition of claim 20, wherein said composition is suitable for oral delivery to a subject.

22. The composition of claim 20, wherein said enteric-coating dissolves at a pH greater than at least about pH 6.5.

23. The composition of claim 20, wherein said composition is suitable for administration to a human subject.

24. The composition of claim 20, wherein said composition further comprises a prebiotic.

25. The composition of claim 24, wherein said prebiotic is selected from the group consisting of:

a complex carbohydrate, a complex sugar, a resistant dextrin, a resistant starch, an amino acid, a peptide, biotin, polydextrose, a fructooligosaccharide (FOS), a galactooligosaccharide (GOS), inulin, a starch, lignin, psyllium, chitin, chitosan, gum, guar gum, high amylose cornstarch (HAS), cellulose, β

-glucan, hemi-cellulose, lactulose, mannooligosaccharide, mannan oligosaccharide (MOS), oligofructose-enriched inulin, an oligofructose, an oligodextrose, a tagatose, a trans-galactooligosaccharide, pectin, a resistant starch, xylooligosaccharide (XOS), and any combination thereof.

26. The composition of claim 24, wherein said prebiotic comprises inulin.

27. The composition of claim 24, wherein said prebiotic comprises fructooligosaccharide.

28. The composition of claim 24, wherein said prebiotic comprises inulin and fructooligosaccharide.

29. The composition of claim 20, wherein said composition comprises at least about 10⁵ colony forming units (CFU) of each of said Clostridium beijerinckii, said Akkermansia muciniphila, said Clostridium butyricum, and said Eubacterium hallii.

30. The composition of claim 20, wherein said composition comprises at least about 10⁷ colony forming units (CFU) of each of said Clostridium beijerinckii, said Akkermansia muciniphila, said Clostridium butyricum, and said Eubacterium hallii.

31. The composition of claim 20, wherein said composition further comprises a microbe with a 16S rRNA sequence comprising at least about 85% sequence identity to a 16S rRNA sequence of a microbe selected from the group consisting of:

Anaerostipes caccae, Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum, Clostridium aminophilum, Clostridium colinum, Clostridium indolis, Clostridium orbiscindens, Enterococcus faecium, Eubacterium rectale, Faecalibacterium prausnitzii, Fibrobacter succinogenes, Oscillospira guilliermondii, Roseburia cecicola, Roseburia inulinivorans, Ruminococcus flavefaciens, Ruminococcus gnavus, Ruminococcus obeum, Streptococcus cremoris, Streptococcus faecium, Streptococcus infantis, Streptococcus mutans, Streptococcus thermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus, Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani, Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacterium dolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis, and Roseburia intestinalis.

32. The composition of claim 20, wherein said composition is suitable for delivery to a small intestine, a large intestine, an ileum, or a combination thereof of a subject.

33. The composition of claim 20, wherein said composition further comprises a microbe with a 16S rRNA sequence comprising at least about 97% sequence identity to a 16S rRNA sequence from Bifidobacterium infantis.

34. The composition of claim 20, wherein said composition further comprises Bifidobacterium infantis.