Compounds and methods for targeted immune system delivery

Patent metadata

Field	Value
Publication number	US-9962448-B2
Application number	US-201314431685-A
Country	US
Kind code	B2
Filing date	Oct 4, 2013
Priority date	Oct 4, 2012
Publication date	May 8, 2018
Grant date	May 8, 2018

Abstract

Compounds and methods for targeted immune system delivery are disclosed. Pharmaceutical compositions including the disclosed compounds and a pharmaceutically acceptable excipient are also disclosed. Methods of targeted delivery to an antigen-presenting cell, and methods of treating or preventing a disease or condition susceptible to treatment by immunomodulation are disclosed.

First claim

We claim:

1. A compound having the structure of Formula (I),

or a pharmaceutically acceptable salt or hydrate thereof, wherein
R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are each independently H, OH, O-monosaccharide, NHAc, or Me;
n 1 and n z are each independently 0, 1, 2, 3, or 4, provided that the sum of n 1 and n z is 4;
R 7 and R 8 are each independently hydrogen, or R 7 and R 8 together form an oxo (═O); and
D 1 is a polymer selected from a group consisting of negative polymer, positive polymer, neutral polymer, linear or branched polymer, a lipid, hydrophobic carbon chain, nanoparticle organic molecule, nanoparticle inorganic molecule, drug, ribonucleic acids, peptide-nucleic acids (PNAs), and a mixture thereof.

2. The compound of claim 1 , wherein the D1 is a peptide or a protein.

3. The compound of claim 1 , wherein the D 1 is a polymer selected from the group consisting of a nylon, PVC, silicone, latex, polyvinyl butyral, polyacrylonitrile, polystyrene, polyethylene, polyethyleneglycol (PEG) or a PEG derivative, polyethyleneoxide (PEO), polyethyleneimine (PM), polyoxymethylene (POM), biodegradable polymers and a mixture thereof.

4. The compound of claim 3 , wherein the PEG derivative is selected from the group consisting of PEG-DSPE, PEGCer (PEG-ceramide), PEGCerC14 (PEGCer containing a 14-carbon fatty acyl chain), PEGCerCzo (PEGCer containing a 20-carbon fatty acyl chain), PEG-COOH (carboxylated PEG-derivative), PEG-PE (poly(ethylene glycol)phosphatidylethanolamine), PEG-DPPE, PEG-DOPE, PEG-DMPE, fluorescent PEG-DSPE derivative, Succinyl-PEG, Carboxylic Acid-PEG, Maleimide-PEG, PDP-PEG, Amine-PEG, Biotin-PEG, Cyanur-PEG, Folate-PEG, PEG-Osu (poly(ethylene glycol) hydroxysuccinimide ester) and a mixture thereof.

5. The compound of claim 4 , wherein the PEG derivative is PEG-DSPE, PEG-DPPE, PEG-DOPE, PEG-DMPE, PEG-ceramide, fluorescent PEG-DSPE derivative, Succinyl-PEG, Carboxylic Acid-PEG, Maleimide-PEG, PDP-PEG, Amine-PEG, Biotin-PEG, Cyanur-PEG, Folate-PEG, or a mixture thereof.

6. The compound of claim 5 , wherein the PEG-ceramide is octanoyl-sphingosine, palmitoyl-sphingosine, or a mixture thereof.

7. The compound of claim 5 , wherein the fluorescent PEG-DSPE derivative is carboxyfluorescein-PEG-DSPE.

8. The compound of any one of claims 1 and 3 - 7 , having a structure selected from the group consisting of:

9. A compound having the structure of Formula (II),

10. A pharmaceutical composition comprising the compound of any one of claims 1 , 3 , 4 and 9 and a pharmaceutically acceptable excipient.

11. The composition of claim 10 , further comprising a nanocarrier.

12. The composition of claim 11 , further comprising an active substance.

13. The composition of claim 12 , wherein the active substance is an immunomodulator.

14. The composition of claim 13 , wherein the immunomodulator is DNA, tRNA, siRNA, viral particle, protein, peptide, carbohydrate, glycoprotein, glycopeptides, proteoglycan, cell extract, hydrophilic drug, hydrophobic drug, B-cell antigen, T-cell antigen, antigen of a fungal, protozoan, parasitic organism, synthetic lipid, mineral, vegetal lipid, saponine, or mixtures thereof.

15. The composition of any one of claims 11 - 14 , wherein the nanocarrier is formed by a phospholipid.

16. The composition of claim 15 , wherein the nanocarrier is a liposome.

17. The composition of any one of claims 11 - 14 , wherein the nanocarrier is a micelle.

18. The composition of any one of claims 11 - 14 , wherein the nanocarrier is a synthetic nanocarrier.

19. The composition of any one of claims 11 - 14 , wherein the nanocarrier is niosome, lipoprotein, carbon nanotube, nanocapsule, nanocrystal, silicon nanoparticle, calcium phosphate, ciclodextrin, metallic nanoparticle, dendrimer, protein-core nanoparticle, fullerene, or a mixture thereof.

20. A method of targeted delivery to an antigen-presenting cell, comprising contacting the antigen-presenting cell with at least one compound of any one of claims 1 , 3 - 7 , and 9 .

21. A method of targeted delivery to an antigen-presenting cell, comprising contacting the antigen-presenting cell with the composition of claim 10 .

22. The method of claim 20 , wherein the antigen-presenting cell is a dendritic cell.

23. A method of treating a disease or condition susceptible to treatment by immunomodulation, the method comprising administering the composition of claim 10 to a subject, wherein the disease or condition is an infectious disease, cancer, an autoimmune disease, or transplant rejection.

24. The method of claim 21 , wherein the antigen-presenting cell is a dendritic cell.

25. The method of claim 3 , wherein the biodegradable polymer is one of polylactic acid (PLA) and polylactic co glycolic acid (PLGA).

Assignees

• Univ Northeastern
• National Institute Of Agricultural Tech
• Univ Of Padova

Inventors

• Pappalardo Juan Sebastian
• Toniutti Micaela
• Salmaso Stefano
• Levchenko Tatyana S
• Torchilin Vladimir

Classifications

• A61K39/0005

  Vertebrate antigens (from snakes A61K39/38) · CPC title

• A61K39/12

  Viral antigens · CPC title

• C07H15/20

  Carbocyclic rings · CPC title

• A61K39/002

  Protozoa antigens · CPC title

• A61K9/127

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title