GLYCAN THERAPEUTICS AND RELATED METHODS THEREOF

• US 20160213702A1
• Filed: 02/05/2016
• Published: 07/28/2016
• Est. Priority Date: 01/26/2015
• Status: Active Grant

• Current Assignee: DSM Nutritional Products Incorporated (DSM-Firmenich AG)
• Original Assignee: Kaleido Biosciences Inc
• Inventors: von Maltzahn, Geoffrey A., Yamanaka, Yvonne J., Milwid, John Miles, Silverman, Jared, Geremia, John M.
• Granted Patent: US 9,492,473 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2035/115 Probiotics
• CPC Class Codes: A61K 31/09 having two or more such linkages
• CPC Class Codes: A61K 31/11 Aldehydes
• CPC Class Codes: A61K 31/12 Ketones
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/34 having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61K 31/365 Lactones
• CPC Class Codes: A61K 31/366 having six-membered rings, e.g. delta-lactones
• CPC Class Codes: A61K 31/7034 attached to a carbocyclic compound, e.g. phloridzin
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 31/706 containing six-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61K 31/715 Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
• CPC Class Codes: A61K 31/716 Glucans

Abstract

Preparations of glycan therapeutics, pharmaceutical compositions and medical foods thereof, optionally comprising micronutrients, polyphenols, prebiotics, probiotics, or other agents are provided and methods of making same. Also provided are methods of using said glycan therapeutics, e.g. for the modulation of human gastrointestinal microbiota and to treat dysbioses.

Claims

1. A method of treating a human subject having diarrhea comprising administering to the subject a pharmaceutical composition comprising a glycan therapeutic preparation in an amount effective to treat the diarrhea, wherein

i) the glycan therapeutic preparation comprises branched glycans that comprise glucose, galactose, arabinose, mannose, fructose, xylose, fucose, or rhamnose glycan units,

ii) the average degree of branching (DB) of the branched glycans in the glycan therapeutic preparation is between 0.01 and 0.3,

iii) at least 50% of the glycans in the glycan therapeutic preparation have a degree of polymerization (DP) of at least 3 and less than 30 glycan units,

iv) the average DP of the glycan therapeutic preparation is between about DP6 and about DP10,

v) the ratio of alpha- to beta-glycosidic bonds present in the glycans of the glycan therapeutic preparation is between about 1:

1 to about 5;

1, and

vi) the glycan therapeutic preparation has a final solubility limit in water of at least about 60 Brix at 23°

C.

2. The method of claim 1, wherein at least two of the glycosidic bonds independently comprise a 1->

2 glycosidic bond, a 1->

3 glycosidic bond, a 1->

4 glycosidic bond, or a 1->

6 glycosidic bond.

3. The method of claim 1, wherein at least 60% of the glycan therapeutic preparation has an average molecular weight of less than 2000 g/mol.

4. The method of claim 1, wherein the average degree of branching (DB) of the branched glycans in the glycan therapeutic preparation is between 0.05 and 0.1.

5. The method of claim 1, wherein at least 60% of the glycans in the glycan therapeutic preparation have a degree of polymerization (DP) of at least 3 and less than 30 glycan units.

6. The method of claim 1, wherein at least 70% of the glycans in the glycan therapeutic preparation have a degree of polymerization (DP) of at least 3 and less than 30 glycan units.

7. The method of claim 1, wherein the glycan therapeutic preparation comprises branched glycans that comprise at least two of glucose, galactose, arabinose, mannose, fructose, xylose, fucose, or rhamnose glycan units.

8. The method of claim 1, wherein the glycan therapeutic preparation comprises branched glycans that comprise at least three of glucose, galactose, arabinose, mannose, fructose, xylose, fucose, or rhamnose glycan units.

9. The method of claim 1, wherein the glycan therapeutic preparation comprises branched glycans consisting of one or more of glucose, galactose, arabinose, mannose, fructose, xylose, fucose, or rhamnose glycan units.

10. The method of claim 1, wherein the glycan therapeutic preparation comprises branched glycans consisting of one or more of glucose, galactose, mannose, or fucose glycan units.

11. The method of claim 1, wherein the glycan therapeutic preparation comprises branched glycans consisting of one or both of arabinose or xylose glycan units.

12. The method of claim 1, wherein the glycan therapeutic preparation comprises branched glycans that comprise at least two of glucose, galactose, arabinose, mannose, fructose, xylose, fucose, or rhamnose glycan units, and at least 60% of the glycan therapeutic preparation has an average molecular weight of less than 2000 g/mol.

13. The method of claim 1, wherein the glycan therapeutic preparation comprises branched glycans consisting of one or more of glucose, galactose, arabinose, mannose, fructose, xylose, fucose, or rhamnose glycan units, and the glycan therapeutic preparation has a final solubility limit in water of at least about 70 Brix at 23°

C.

14. The method of claim 1, wherein the treating further comprises administering a second pharmaceutical composition to the subject.

15. The method of claim 14, wherein the second pharmaceutical composition comprises a probiotic microbe.

16. The method of claim 1, wherein the treating further comprises administering a polyphenol preparation.

17. The method of claim 1, wherein the pharmaceutical composition is provided as a unit-dosage form formulated as a liquid or solid for oral delivery.

18. The method of claim 1, wherein the pharmaceutical composition is administered each day for between about 1 day and about 30 days.

19. The method of claim 1, further comprising identifying the human subject as having diarrhea.

20. A method of treating a human subject having diarrhea comprising administering to the subject a pharmaceutical composition comprising a glycan therapeutic preparation in an amount effective to treat the diarrhea, wherein

i) the glycan therapeutic preparation comprises branched glycans that consist of one or more of glucose, galactose, arabinose, mannose, fructose, xylose, fucose, or rhamnose glycan units,

ii) the average degree of branching (DB) of the branched glycans in the glycan therapeutic preparation is between 0.05 and 0.1,

iii) at least 70% of the glycans in the glycan therapeutic preparation have a degree of polymerization (DP) of at least 3 and less than 30 glycan units,

iv) the average DP of the glycan therapeutic preparation is between about DP6 and DP10,

v) the ratio of alpha- to beta-glycosidic bonds present in the glycans of the glycan therapeutic preparation is between about 1:

1 to about 4;

1, and

vi) the glycan therapeutic preparation has a final solubility limit in water of at least about 75 Brix at 23°

C.