Immunomodulating compositions and methods of use thereof

• US 9,457,047 B2
• Filed: 09/26/2013
• Issued: 10/04/2016
• Est. Priority Date: 11/06/2006
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology, The General Hospital Corporation (Mass General Brigham, Inc.), Trustees of Boston University, Whitehead Institute
• Original Assignee: Massachusetts Institute of Technology, The General Hospital Corporation (Mass General Brigham, Inc.), Trustees of Boston University, Whitehead Institute
• Inventors: Fuller, Jason E, Rubin-Bejerano, Ifat, Fink, Gerald R., Abeijon, Claudia, Kohane, Daniel S., Langer, Robert S.
• Primary Examiner(s): Kim, Yunsoo
• Application Number:
  US14/037,420
• Publication Number:
  US 20140030277A1
• Time in Patent Office: 1,104 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/55583 Polysaccharides
• CPC Class Codes: A61K 2039/572 cytotoxic response
• CPC Class Codes: A61K 31/716 Glucans
• CPC Class Codes: A61K 36/064 Saccharomycetales, e.g. baker's yeast
• CPC Class Codes: A61K 36/09 Lichens
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/385 Haptens or antigens, bound to carriers
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 47/6843 the antibody targeting a material from animals or humans
• CPC Class Codes: A61K 47/6921 the form being a particulate, a powder, an adsorbate, a bead or a sphere
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: C08B 37/0024 beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
• CPC Class Codes: C08J 2300/16 Biodegradable polymers
• CPC Class Codes: C08J 2325/06 Polystyrene
• CPC Class Codes: C08J 2367/04 Polyesters derived from hydroxy carboxylic acids, e.g. lactones C08J2367/06 takes precedence
• CPC Class Codes: C08J 2400/16 Biodegradable polymers
• CPC Class Codes: C08J 2405/00 Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2401/00 or C08J2403/00
• CPC Class Codes: C08J 3/126 Polymer particles coated by polymer, e.g. core shell structures
• CPC Class Codes: C08J 3/128 : Polymer particles coated by inorganic and non-macromolecular organic compounds

Abstract

This invention is directed to β-1-6-glucans, compositions and devices comprising the same, and methods of use thereof in modulating immune responses. The β-1-6-glucans of certain embodiments of the invention are enriched for O-acetylated groups and/or conjugated to a solid support or linked to a targeting moiety.

Claims

1. A composition comprising β

-1-6-glucan linked to a targeting moiety, wherein the targeting moiety is selected from the group consisting of an engineered binding protein, an antibody, an antibody fragment, a nucleic acid, a peptide, and a small molecule, and wherein the targeting moiety specifically interacts with a neoplastic cell, a pre-neoplastic cell, a pathogen, or a component thereof.

2. The composition of claim 1, wherein the targeting moiety specifically interacts with a pathogen or a component thereof.

3. The composition of claim 2, wherein the composition enhances phagocytosis and/or cytotoxic responses to the pathogen.

4. The composition of claim 2, wherein the composition enhances complement-mediated lysis of the pathogen.

5. The composition of claim 2, wherein the composition enhances the immune response to the pathogen.

6. The composition of claim 2, wherein the pathogen is a bacterium, virus, or parasite.

7. The composition of claim 1, wherein the targeting moiety is a small molecule.

8. The composition of claim 1, wherein the targeting moiety is a peptide.

9. The composition of claim 8, wherein the peptide is a peptide which binds to a transmembrane molecule.

10. The composition of claim 8, wherein the peptide is a naturally occurring peptide ligand for a receptor, or a modified form thereof.

11. The composition of claim 1, wherein the targeting moiety is a nucleic acid.

12. The composition of claim 11, wherein the nucleic acid is an aptamer.

14. The composition of claim 1, wherein the β

-1-6-glucan is derived from a fungal glucan.

15. The composition of claim 1, wherein the β

-1-6-glucan is derived from pustulan.

16. The composition of claim 1, wherein the β

-1-6-glucan is derived from a fungal glucan via one or more processing steps that include hydrolysis and/or enzymatic digestion.

17. The composition of claim 1, wherein the β

-1-6-glucan is chemically synthesized.

18. The composition of claim 1, wherein the β

-1-6-glucan is genetically engineered.

19. The composition of claim 18, wherein the β

-1-6-glucan is synthesized in a bacteria, yeast, or mammalian cell.

20. The composition of claim 1, wherein the β

-1-6-glucan is soluble.

21. The composition of claim 1, wherein the β

-1-6-glucan comprises a structural modification selected from the group consisting of O-acetylation, methylation, alkylation, esterification, a tkoy iation, sulfation, phosphorylation, lipid conjugation and combinations thereof.

22. The composition of claim 1, wherein the β

-1-6-glucan has a molecular weight less than 100 kDa.

23. The composition of claim 1, wherein the β

-1-6-glucan contains fewer than 85 glucose monosaccharide units.

24. The composition of claim 1, wherein the β

-1-6-glucan contains 85, 84, 83, 82, 81, 80, 79, 78, 77, 76, 75, 74, 73, 72, 71, 70, 69, 68, 67, 66, or 65 glucose monosaccharide units.

25. The composition of claim 1, wherein the β

-1-6-glucan contains 64, 63, 62, 61, 60, 59, 58, 57, 56, 55, 54, 53, 52, 51, 50, 49, 48, 47, 46, 45, or 44 glucose monosaccharide units.

26. The composition of claim 1, wherein the β

-1-6-glucan contains 43, 42, 41, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, or 23 glucose monosaccharide units.

27. The composition of claim 1, wherein the β

-1-6-glucan contains 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, or 4 glucose monosaccharide units.

28. The composition of claim 1, wherein at least 90% of the dry weight of glucan contained in the composition is β

-1-6-glucan.

29. The composition of claim 1, wherein less than 10% of the total glucan in the composition, by weight, is β

-1-3-glucan.

30. The composition of claim 1, wherein the composition is substantially free of β

-1-3-glucan.

31. The composition of claim 1, wherein the β

-1-6-glucan is directly linked to the targeting moiety.

32. The composition of claim 1, wherein the β

-1-6-glucan is linked to the targeting moiety via a linker molecule.

33. The composition of claim 1, wherein the β

-1-6-glucan is linked to the targeting moiety via amide, urethane, imine or disulfide formation between the respective molecules, or between a linker molecule and the respective molecules.

34. The composition of claim 1, wherein the targeting moiety targets a neoplastic cell, a pre-neoplastic cell or a component thereof.

35. The composition of claim 34, wherein the targeting moiety targets a tumor antigen.

13. The composition of claim wherein e targeting moiety is an engineered binding protein.

36. A composition comprising β

-1-6-glucan comprising at least 4 and fewer than 50 glucose monosaccharide units linked to a targeting moiety, wherein the targeting moiety is selected from the group consisting of an engineered binding protein, an antibody, an antibody fragment, a nucleic acid, a peptide, and a small molecule, and wherein at least 95% of the dry weight of glucan contained in the composition is β

-1-6-glucan.

37. A composition comprising soluble β

-1-6-glucan linked to a targeting moiety, wherein the targeting moiety is selected from the group consisting of an engineered binding protein, an antibody, an antibody fragment, a nucleic acid, a peptide, and a small molecule, and wherein at least 95% of the dry weight of glucan contained in the composition is soluble β

-1-6-glucan.

38. A composition comprising β

-1-6-glucan comprising at least 4 and fewer than 50 glucose monosaccharide units linked to a targeting moiety, wherein the targeting moiety is selected from the group consisting of an engineered binding protein, an antibody, an antibody fragment, a nucleic acid, a peptide, and a small molecule, and wherein less than 5% of the total glucan in the composition, by weight, is β

-1,3-glucan.

39. A composition comprising soluble β

-1-6-glucan linked to a targeting moiety, wherein the targeting moiety is selected from the group consisting of an engineered binding protein, an antibody, an antibody fragment, a nucleic acid, a peptide, and a small molecule, and wherein less than 5% of the total glucan in the composition, by weight, is β

-1,3-glucan.