Peptide conjugated particles

• US 10,617,747 B2
• Filed: 03/15/2018
• Issued: 04/14/2020
• Est. Priority Date: 08/13/2013
• Status: Active Grant

• Current Assignee: Northwestern University
• Original Assignee: Northwestern University
• Inventors: Shea, Lonnie D., Miller, Stephen D., Yap, Jonathan Woon Teck, Getts, Daniel R., McCarthy, Derrick
• Primary Examiner(s): Navarro, Albert M
• Application Number:
  US15/922,241
• Publication Number:
  US 20180271962A1
• Time in Patent Office: 761 Days
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 2039/577 tolerising response
• CPC Class Codes: A61K 2039/622 non-covalent binding
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/0008 Antigens related to auto-immune diseases; Preparations to induce self-tolerance
• CPC Class Codes: A61K 47/58 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
• CPC Class Codes: A61K 47/6911 the form being a liposome
• CPC Class Codes: A61K 47/6935 the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol
• CPC Class Codes: A61K 47/6937 the polymer being PLGA, PLA or polyglycolic acid
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61K 9/5153 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 5/06 : of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 : Antianaemics

Abstract

The present invention provides compositions comprising peptide-coupled biodegradable poly(lactide-co-glycolide) (PLG) particles. In particular, PLG particles are surface-functionalized to allow for coupling of peptide molecules to the surface of the particles (e.g., for use in eliciting induction of immunological tolerance).

Claims

1. A composition comprising surface functionalized biodegradable poly(lactide-co-glycolide) (PLG) particles comprising encapsulated antigen or one or more antigenic epitopes, wherein the particle has a negative zeta potential of from about −

30 mV to −

80 mV.

2. The composition of claim 1, wherein said antigen comprises an autoimmune antigen, an antigen expressed on a tissue to be transplanted into a subject, or an enzyme for enzyme replacement therapy.

3. The composition of claim 1, wherein the antigen is one or more antigenic gliadin epitopes.

4. The composition of claim 1, wherein the PLG comprises a copolymer ratio of about 50:

50 of polylactic acid;

polyglycolic acid.

5. The composition of claim 1, wherein the negative zeta potential is achieved by surface functionalization.

6. The composition of claim 1, wherein the is surface functionalization is carboxylation.

7. The composition of claim 6, wherein the carboxylation is achieved by using poly(ethylene-maleic anhydride) (PEMA).

8. The composition of claim 1, wherein the particles have a zeta potential of about −

50 mV to about −

40 mV.

9. The composition of claim 1, wherein the particles have a zeta potential of about −

60 mV to about −

30 mV.

10. The composition of claim 1, wherein the particle has a diameter of between about 200 nm to about 2000 nm.

11. The composition of claim 1, wherein the particle has a diameter of about 400 to about 800 nm.

12. The composition of claim 1, wherein the particle has a diameter of about 600 nm.

13. The composition of claim 1, further comprising a pharmaceutically acceptable excipient.

26. A method of inducing antigen-specific tolerance in a subject comprising:

administering to said subject an effective amount of a composition of claim 1.

27. The method of claim 26, wherein the subject is suffering from a disease or condition selected from the group consisting of:

an autoimmune disease, a lysosomal storage disease, an enzyme deficiency, an inflammatory disease, transplantation rejection, and a hyperimmune response.

28. The method of claim 27 wherein the autoimmune disease is selected from the group consisting of multiple sclerosis, scleroderma, type-I diabetes, rheumatoid arthritis, thyroiditis, systemic lupus erythmatosis, Reynaud'"'"'s syndrome, Sjorgen'"'"'s syndrome, autoimmune uveitis, autoimmune myocarditis, inflammatory bowel disease, Amyotrophic Lateral Sclerosis (ALS), Systemic Lupus, Neuromyelitis Optica, Idiopathic Thrombocytopenic Purpura, Thrombotic Thrombocytopenic Purpura, Membranous Nephropathy, Bullous Phemphigoid, Phemphigus Vulgaris, Myasthenia Gravis, ulcerative colitis, and Crohn'"'"'s disease.

29. The method of claim 26, wherein said composition is administered intravenously.

30. A method for the treatment of celiac disease in a subject in need thereof comprising administering a pharmaceutical composition comprising the surface functionalized particle of claim 1.

31. The method of claim 30, wherein the composition comprises one or more gliadin epitopes.

32. The method of claim 31, wherein the one or more gliadin epitopes comprises one or more of the sequences set forth in SEQ ID NOS:

1295-1724, 1726-1766, and 4986-5440.

33. The method of claim 30, wherein said composition is administered intravenously.

14. A composition comprising surface functionalized biodegradable poly(lactide-co-glycolide) (PLG) particles comprising encapsulated gliadin or one or more antigenic epitopes thereof wherein said PLG particles have a copolymer ratio of about 50:

50 poly(lactide-co-glycolide), a diameter of about 200 nm to about 2000 nm and a zeta potential of about −

30 my to about −

80 my.

15. The particles of claim 14 wherein the surface functionalization is carboxylation.

16. The composition of claim 15 wherein the carboxylation is achieved by using poly(ethylene-maleic anhydride) (PEMA).

17. A lyophilized composition comprising surface functionalized biodegradable poly(lactide-co-glycolide) (PLG) particles comprising encapsulated gliadin or one or more antigenic gliadin epitopes, wherein the particle has a zeta potential of about −

30 my to about −

80 my.

18. The lyophilized composition of claim 17, wherein the PLG comprises a copolymer ratio of about 50:

50 of polylactic acid;

polyglycolic acid.

19. The lyophilized composition of claim 18, wherein the surface functionalization is carboxylation.

20. The lyophilized composition of claim 19 wherein the carboxylation is achieved by using poly(ethylene-maleic anhydride) (PEMA).

21. The lyophilized composition of claim 19, wherein the particles have a zeta potential of about −

50 mV to about −

40 mV.

22. The composition of claim 20, wherein the particles have a zeta potential of about −

60 mV to about −

30 mV.

23. The lyophilized composition of claim 21, wherein the particle has a diameter of between about 200 nm to about 2000 nm.

24. The lyophilized composition of claim 22, wherein the particle has a diameter of about 1100 nm.

34. A method of treating celiac disease in a subject in need thereof comprising reconstituting the lyophilized particles of claim 17 to obtain a reconstituted pharmaceutical composition comprising surface functionalized particles and administering the reconstituted pharmaceutical composition to said subject thereby treating celiac disease.

35. The method of claim 34 wherein said composition is administered intravenously.

36. The method of claim 34, wherein the particles have a zeta potential of about −

50 mV to about −

40 mV.

37. The method of claim 34, wherein the particles have a zeta potential of about −

60 mV to about −

30 mV.

38. The method of claim 34, wherein the one or more antigenic gliadin epitopes comprises one or more of the sequences set forth in SEQ ID NOS:

1295-4724, 1726-1766, and 4986-5440.

39. The method of claim 34, wherein the PLG comprises a copolymer ratio of about 50:

50 of polylactic acid;

polyglycolic acid.

40. The method of claim 34, wherein the surface functionalization is carboxylation.

41. The method of claim 34, wherein the particle has a diameter of between about 200 nm to about 2000 nm.

42. The method of claim 34, wherein the particle has a diameter of about 400 to about 800 nm.

25. A lyophilized composition comprising surface functionalized biodegradable poly(lactide-co-glycolide) (PLG) particles comprising encapsulated gliadin or one or more antigenic epitopes thereof wherein said PLG particles have a copolymer ratio of about 50:

50 poly(lactide-co-glycolide, a diameter of about 200 nm to about 2000 nm and a zeta potential of about −

30 my to about −

80 my.