Covalent polymer-antigen conjugated particles

Patent metadata

Field	Value
Publication number	US-11510996-B2
Application number	US-201616064528-A
Country	US
Kind code	B2
Filing date	Dec 22, 2016
Priority date	Dec 23, 2015
Publication date	Nov 29, 2022
Grant date	Nov 29, 2022

Abstract

The present invention provides compositions comprising tolerizing immune modified particles (TIMPs) and methods for using and making said TIMPs. In particular, carrier polymer is covalently conjugated with antigenic peptide before particle formation, which allows for exquisite control of particle size and antigen encapsulation (e.g., for use in eliciting induction of immunological tolerance).

First claim

What is claimed is:

1. A composition comprising one or more antigens covalently attached to a polymeric carrier particle comprising a poly(lactide-co-glycolide) (PLG) particle, a polylactic acid (PLA) particle or a poly(lactic-co-glycolic acid) particle, wherein said one or more antigens are encapsulated in said particle by covalent attachment to the internal particle surfaces, and, optionally wherein said antigens are further attached to the surface of the polymeric particle, and wherein the zeta potential of the particle is from −80 to −30 mV and the particle has an average diameter between about 0.3 μm to about 5 μm.

2. The composition of claim 1 , wherein the composition further comprises an unconjugated carrier polymer.

3. The composition of claim 1 , wherein the particle comprises a co-polymer having a molar ratio from about 50:50, 80:20 to about 100:0.

4. The composition of claim 1 , wherein the particle comprises poly(lactic-co-glycolic acid).

5. The composition of claim 1 , wherein the particle has an average diameter of between about 400 to about 800 nanometers.

6. The composition of claim 1 , wherein said one or more antigens comprises an autoimmune antigen, an antigen expressed on a tissue to be transplanted into a subject, an enzyme for enzyme and/or protein replacement therapy, or an allergen.

7. The composition of claim 1 , wherein said one or more antigens comprises one or more epitopes.

8. The composition of claim 7 , wherein the one or more epitopes is associated with an allergy, an autoimmune disease, an enzyme used in enzyme and/or protein replacement therapy, lysosomal storage disease, or an inflammatory disease or disorder.

9. The composition of claim 1 , wherein said one or more antigens is directly covalently bound to said carrier particle.

10. A method of inducing antigen-specific tolerance in a subject comprising: administering to said subject an effective amount of a composition of claim 1 .

11. The method of claim 10 , wherein said administering is performed to treat or prevent a disease or condition.

12. The method of claim 11 , wherein said disease or condition is selected from the group consisting of: an autoimmune disease, a lysosomal storage disease, an enzyme deficiency, a protein deficiency, inflammatory disease, an allergy, transplantation rejection, and a hyperimmune response.

13. The method of claim 10 , wherein the carrier particle comprises a polystyrene particle, a carboxylated polystyrene particle, a polaxamer stabilized polypropylene sulfide particle, a poly(lactide-co-glycolide) (PLG) particle, a polylactic acid (PLA) particle, or a poly(lactic-co-glycolic acid) particle.

14. The method of claim 10 , wherein the carrier particle comprises a poly(lactic-co-glycolic acid) particle.

15. The method of claim 10 , wherein said composition is administered intravenously.

16. A method of inducing regulatory T cells comprising treating said T cells with an effective amount of a composition of claim 1 , wherein the particle size is greater than 80 nm.

17. A process for the preparation of the composition of claim 1 which forms a tolerizing immune modifying particle (TIMP) having one or more antigens encapsulated within said particle by covalent attachment to the internal particle surfaces, said process comprising:
a) covalently linking one or more carrier polymers with one or more antigens to form carrier polymer-antigen conjugates; and
b) contacting the carrier polymer-antigen conjugates with a solution under conditions effective to form the TIMP,
wherein the TIMP having one or more antigens encapsulated in the TIMP by covalent attachment to the internal particle surfaces, is formed.

18. The process of claim 17 , wherein the particle comprises a poly(lactide-co-glycolide) (PLG) particle, a polylactic acid (PLA) particle or a poly(lactic-co-glycolic acid) particles.

Assignees

• Cour Pharmaceuticals Dev Company Inc
• Univ Michigan Regents

Inventors

• Pearson Ryan
• Getts Daniel
• Puisis John
• Herrmann James
• Shea Lonnie D

Classifications

• A61K39/0008

  Antigens related to auto-immune diseases; Preparations to induce self-tolerance · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61P5/00

  Drugs for disorders of the endocrine system · CPC title

• A61K2039/577

  tolerising response · CPC title

• A61P19/06

  Antigout agents, e.g. antihyperuricemic or uricosuric agents · CPC title