IP Library › Granted Patent US 10,898,436
Granted Patent B2
US 10,898,436 · App. 15/988,501 · Granted Jan 26, 2021

Nanoparticle compositions for generation of regulatory T cells and treatment of autoimmune diseases and other chronic inflammatory conditions

Inventors: Barbara Freund (Hamburg, DE); Jörg Heeren (Hamburg, DE); Peter Nielsen (Besitz, DE); Antonella Carambia (Hamburg, DE); Johannes Herkel (Hamburg, DE); Oliver Bruns (Boston, MA); Ansgar Lohse (Hamburg, DE); Stefan Lüth (Hamburg, DE); Horst Weller (Hamburg, DE); Sunhild Salmen (Hamburg, DE)
Assignee: Topas Therapeutics GmbH
A61K9/146A61K9/1075A61K39/0008A61K39/39A61K47/6907A61K49/0067A61K49/1809A61K49/1857A61K51/1227C12N5/0637A61K9/0019A61K2039/55555C12N2502/14
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 10,898,436
App. No.
15/988,501
Granted
Jan 26, 2021
Kind
B2
Abstract

The present invention relates to nanoparticles for the targeted delivery of antigen to liver cells, in particular, liver sinusoidal endothelial cells (LSEC) and/or Kupffer cells, and for the in vivo generation of regulatory T cells, notably CD4+CD25+FOXP3+ regulatory T cells (Treg). The invention provides pharmaceutical compositions and methods for the prevention and treatment of autoimmune diseases, allergies or other chronic inflammatory conditions, and for generation of regulatory T cells. The nanoparticles used in the invention comprise a) a micelle comprising an amphiphilic polymer rendering the nanoparticle water-soluble, and b) a peptide comprising at least one T cell epitope associated with the outside of the micelle. The micelle may or may not comprise a solid hydrophobic core.

Claims (26)

1. A method comprising administering a composition comprising a nanoparticle to a subject in need thereof, wherein said nanoparticle comprises

a) a micelle comprising an amphiphilic polymer rendering the nanoparticle water-soluble, and

b) a peptide comprising at least one T cell epitope associated with the outside of the micelle, and

wherein the composition generates regulatory T cells specific to said at least one T cell epitope in said subject.

2. The method of claim 1 , wherein the micelle does not comprise a solid core.

3. The method of claim 1 , wherein micelle coats a solid hydrophobic core.

4. The method of claim 3 , wherein the core comprises a traceable inorganic material selected from the group comprising iron oxide, CdSe/CdS/ZnS, silver and gold.

5. The method of claim 3 , wherein the diameter of the core is 5 to 30 nm.

6. The method of claim 1 , wherein the polymer is a synthetic polymer selected from the group consisting of poly(maleic anhydride-alt-1-octadecene), poly(maleic anhydride-alt-1-tetradecene) and polyisoprene-block polyethyleneoxide block copolymer.

7. The method of claim 1 , wherein the nanoparticle is negatively charged.

8. The method of claim 1 , wherein the peptide is covalently linked to the micelle or non-covalently associated.

9. The method of claim 1 , wherein the nanoparticle comprises a solid core comprising iron oxide having a diameter of about 9 to about 12 nm, which is encapsulated by a coating of poly(maleic anhydride-alt-1-octadecene) to which a peptide comprising a T cell epitope is covalently linked.

10. The method of claim 1 , wherein the nanoparticles are suitable for transferring the peptide to liver sinusoidal endothelial cells of said subject in vivo.

11. The method of claim 1 , wherein the pharmaceutical composition is suitable for inducing generation of regulatory T cells specific for the at least one epitope via presentation of said epitope by liver sinusoidal endothelial cells and/or Kupffer cells of said subject.

12. The method of claim 1 , wherein the nanoparticles are formulated for administration to said subject having a disease wherein suppression of a specific immune response is beneficial.

13. The method of claim 12 , wherein said disease is an autoimmune disease, or an allergy or a disease wherein inflammation is excessive, chronic or adverse.

14. The method of claim 12 , wherein the disease is selected from the group consisting of multiple sclerosis, type I diabetes, rheumatoid arthritis, systemic lupus erythematosus, degeneration after trauma or stroke, graft versus host disease, transplant rejection, inflammatory bowel disease (IBD), asthma and allergy.

15. A method of generating regulatory T cells, comprising isolating regulatory T cells from a sample taken from a subject, wherein said subject has been administered a nanoparticle comprising:

a) a micelle comprising an amphiphilic polymer rendering the nanoparticle water-soluble, and

b) a peptide comprising at least one T cell epitope associated with the outside of the micelle.

16. The method of claim 15 , further comprising:

administering to said subject said nanoparticle; and

taking said sample comprising T cells from said subject, prior to said isolating.

17. The method of claim 3 , wherein the diameter of the core is 9 to 12 nm.

18. The method of claim 1 , wherein the polymer is poly(maleic anhydride-alt-1-octadecene).

19. The method of claim 1 , wherein the peptide consists of 9 to 60 amino acids.

Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 30, 2018
From: HEINRICH PETTE INSTITUTE; UNIVERSITAT HAMBURG
To: UNIVERSITATSKLINIKUM HAMBURG-EPPENDORF
Reel/Frame 045932/0522 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 30, 2018
From: UNIVERSITATSKLINIKUM HAMBURG-EPPENDORF
To: TOPAS THERAPEUTICS GMBH
Reel/Frame 045932/0588 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 25, 2018
From: BRUNS, OLIVER
To: HEINRICH PETTE INSTITUTE
Reel/Frame 045904/0212 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 25, 2018
From: WELLER, HORST; SALMEN, SUNHILD
To: UNIVERSITAT HAMBURG
Reel/Frame 045904/0276 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 25, 2018
From: FREUND, BARBARA; HEEREN, JORG; NIELSEN, PETER; CARAMBIA, ANTONELLA; HERKEL, JOHANNES; LOHSE, ANSGAR; LUTH, STEFAN
To: UNIVERSITAT HAMBURG-EPPENDORF
Reel/Frame 045904/0453 →
Priority Claims (1)
EP 11009032 · Nov 14, 2011 · regional
Continuity (2)
Division 13261883
Related Publication 20180325821A1 · Nov 15, 2018