IP Library › Granted Patent US 12,186,384
Granted Patent B2
US 12,186,384 · App. 17/741,894 · Granted Jan 7, 2025

Compositions and methods for making and using thermostable immunogenic formulations with increased compatibility of use as vaccines against one or more pathogens

Inventors: Theodore W. Randolph (Niwot, CO); Robert Garcea (Boulder, CO); Alan W. Weimer (Niwot, CO)
Assignee: The Regents of the University of Colorado, a body corporate
A61K39/12A61K9/5015A61K39/02A61K39/39A61K2039/55505A61K2039/55555A61K2039/60C12N2710/20034C12N2770/24134
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Quick Facts
Patent No.
US 12,186,384
App. No.
17/741,894
Granted
Jan 7, 2025
Kind
B2
Abstract

Embodiments of the present disclosure provide novel compositions, methods of use and methods for single composition, multi-dose, thermostable vaccine formulations. In certain embodiments, the present disclosure provides compositions and methods for dehydrating immunogenic agents in the presence of glass-forming agents, and coating the particles formed by the glass-forming agents. In other embodiments, the present disclosure provides for generating compositions for administering an immunogenic composition to a subject multiple times using a single immunogenic composition capable of time-release administration. In other embodiments, single-dose immunogenic agent-containing particles can be directed to two or more pathogens. In other embodiments, incompatible immunogenic agents against two or more different pathogens of immunogenic agent-containing particles disclosed herein can be mixed together and coated for timed-release administration to produce single-administration formulations capable of eliciting an immune response to the two or more pathogens in a subject.

Claims (49)

1. An immunogenic agent-containing particle comprising:

a central or innermost immunogenic agent-containing glassy microparticle comprising at least one immunogenic agent and at least one glass-forming agent; and

one or more atomic layer deposition (ALD) coating layers completely encasing the central or innermost immunogenic agent-containing glassy microparticle.

2. The immunogenic agent-containing particle according to claim 1 , wherein the central or innermost immunogenic agent-containing glassy microparticle further comprises at least one smoothing excipient.

3. The immunogenic agent-containing particle according to claim 1 , wherein the at least one immunogenic agent comprises one or more antigens from a pathogenic virus, a pathogenic bacteria, a fungal pathogen; a peptide or polypeptide derived from a pathogenic virus, a pathogenic bacteria or fungal pathogen; a recombinant molecule derived from a pathogenic virus, bacterial pathogen or fungal pathogen; an inactivated pathogenic virus, pathogenic bacteria, or fungal pathogen; a chimera, or a toxoid agent.

4. The immunogenic agent-containing particle according to claim 1 , wherein the at least one immunogenic agent comprises a recombinant viral protein; a virus-like particle; a live virus; a live, attenuated virus; an inactivated virus; one or more viral proteins or a combination thereof.

5. The immunogenic agent-containing particle according to claim 1 , wherein the at least one glass-forming agent comprises at least one of trehalose, sucrose, ficoll, dextran, sucrose, maltotriose, lactose, mannitol, hydroxyethyl starch, glycine, cyclodextrin, povidone and a combination thereof.

6. The immunogenic agent-containing particle according to claim 2 , wherein the at least one smoothing excipient comprises at least one of hydroxyethyl starch, serum albumin, human serum albumin, dextran, hetastarch, plasma protein factor, or a combination thereof.

7. The immunogenic agent-containing particle according to claim 1 , wherein each layer of the one or more coating layers comprises one or more of aluminum oxide (Al 2 O 3 ), an aluminum alkoxide, silicon dioxide (SiO 2 ), titanium dioxide (TiO 2 ), and silicon nitride (Si 3 N 4 ).

8. A method of making immunogenic agent-containing particles, the method comprising:

combining at least one immunogenic agent with at least one glass-forming agent to form a primary liquid immunogenic composition;

dehydrating the primary liquid immunogenic composition to form immunogenic agent-containing glassy microparticles; and

coating the immunogenic agent-containing glassy microparticles with one or more coating layers by atomic layer deposition (ALD) to form coated immunogenic agent-containing glassy microparticles.

9. The method according to claim 8 , wherein the primary liquid immunogenic composition further comprises at least one smoothing excipient.

10. The method according to claim 8 , wherein the primary liquid immunogenic composition is dehydrated by lyophilization, vacuum drying, spray drying, or spray-freeze-drying.

11. An immunogenic composition comprising a plurality of immunogenic agent-containing glassy microparticles according to claim 1 .

12. The immunogenic composition according to claim 11 , further comprising a pharmaceutically acceptable excipient.

13. An immunogenic composition comprising a standard immunogenic composition against a pathogen and a plurality of immunogenic agent-containing glassy microparticles according to claim 1 , wherein the at least one immunogenic agent of immunogenic agent-containing glassy microparticles contains at least one immunogenic agent against the pathogen and is capable of eliciting a boost immune response to the standard immunogenic composition against the pathogen.

14. A method for eliciting an immune response in a subject, the method comprising administering to the subject a pharmaceutically acceptable immunogenic agent-containing glassy microparticle composition according to claim 1 .

15. The method according to claim 14 , wherein the immune response is prophylactic or therapeutic.

16. The method according to claim 14 , wherein a primary response and a boost response are elicited in the subject.

17. The method according to claim 14 , wherein an immune response is elicited against the at least one immunogenic agent when the at least one immunogenic agent is released in the subject at a predetermined period after administering the immunogenic agent-containing glassy microparticle composition to the subject.

18. A kit comprising at least one ALD-coated immunogenic agent-containing glassy microparticle composition according to claim 1 and at least one container.

19. The method according to claim 17 , wherein releasing of the at least one immunogenic agent of the central or innermost immunogenic agent-containing glassy microparticle in the subject depends on number of ALD coating layers applied to the central or innermost immunogenic agent-containing glassy microparticle.

20. The immunogenic agent-containing particle according to claim 1 , wherein at least a second composition of immunogenic agent-containing glassy microparticles encases an outer layer of the ALD-coated immunogenic agent-containing glassy microparticle comprising the central or innermost immunogenic agent-containing glassy microparticle wherein the at least second composition comprises the same or different immunogenic agent compared to the at least one immunogenic agent of the central or innermost immunogenic agent-containing glassy microparticle.

21. The immunogenic agent-containing particle according to claim 3 , wherein at least a second composition of immunogenic agent-containing glassy microparticles encases an outer layer of the ALD-coated immunogenic agent-containing glassy microparticle comprising the central or innermost immunogenic agent-containing glassy microparticle wherein the at least second composition of immunogenic agent-containing glassy microparticles comprises the same or a different immunogenic agent compared to the at least one immunogenic agent of the central or innermost immunogenic agent-containing glassy microparticle.

22. The immunogenic composition according to claim 1 , wherein the one or more atomic layer deposition (ALD) coating layers completely encasing the central or innermost immunogenic agent-containing glassy microparticle comprises one or more nanometer-thick coating layers completely encasing the central or innermost immunogenic agent-containing glassy microparticle.

23. The immunogenic composition according to claim 1 , wherein the one or more atomic layer deposition (ALD) coating layers completely encasing the central or innermost immunogenic agent-containing glassy microparticle comprise one or more coating layers of an inorganic material completely encasing the central or innermost immunogenic agent-containing glassy microparticle.

24. The immunogenic composition according to claim 12 , wherein the at least one immunogenic agent comprises one or more antigens from a pathogenic virus, a pathogenic bacteria, a fungal pathogen; a peptide or polypeptide derived from a pathogenic virus, a pathogenic bacteria or fungal pathogen; a recombinant molecule derived from a pathogenic virus, bacterial pathogen or fungal pathogen; an inactivated pathogenic virus, pathogenic bacteria, or fungal pathogen; a chimera or a toxoid agent.

25. The immunogenic composition according to claim 12 , wherein the at least one immunogenic agent comprises a recombinant viral protein; a virus-like particle; a live virus; a live, attenuated virus; an inactivated virus; one or more viral proteins or a combination thereof.

26. The immunogenic composition according to claim 12 , wherein each layer of the one or more coating layers comprises one or more of aluminum oxide (Al 2 O 3 ), an aluminum alkoxide, silicon dioxide (SiO 2 ), titanium dioxide (TiO 2 ), and silicon nitride (Si 3 N 4 ).

27. The immunogenic composition according to claim 1 , wherein the at least one immunogenic agent comprises at least one pathogenic bacteria.

28. The immunogenic composition according to claim 27 , wherein the at least one pathogenic bacteria comprise at least one of Pneumococcus, and Streptococcus.

29. The immunogenic composition according to claim 1 , wherein the at least one immunogenic agent comprises at least one pathogenic virus.

30. The immunogenic composition according to claim 29 , wherein the at least one pathogenic virus comprises at least one of influenza, respiratory syncytial virus (RSV), and human papilloma virus (HPV).

31. The immunogenic composition according to claim 1 , wherein the at least one immunogenic agent comprises at least one pathogenic virus and the at least one pathogenic virus comprises at least one species of HPV.

32. The method according to claim 14 , wherein a second immune response is elicited in the subject against the same or a different immunogenic agent of at least a second composition of immunogenic agent-containing glassy microparticles administered to the subject.

33. An immunogenic agent-containing particle comprising:

a central or innermost immunogenic agent-containing glassy microparticle comprising at least one immunogenic agent and at least one glass-forming agent; and

one or more coating layers completely encasing the central or innermost immunogenic agent-containing glassy microparticle wherein each layer of the one or more coating layers comprises one or more of aluminum oxide (Al 2 O 3 ), an aluminum alkoxide, silicon dioxide (SiO 2 ), titanium dioxide (TiO 2 ), and silicon nitride (Si 3 N 4 ).

34. The immunogenic agent-containing particle according to claim 33 , wherein the at least one immunogenic agent comprises one or more antigens from a pathogenic virus, a pathogenic bacteria, a fungal pathogen; a peptide or polypeptide derived from a pathogenic virus, a pathogenic bacteria or fungal pathogen; a recombinant molecule derived from a pathogenic virus, bacterial pathogen or fungal pathogen; an inactivated pathogenic virus, pathogenic bacteria, or fungal pathogen; a chimera, or a toxoid agent.

35. The immunogenic agent-containing particle according to claim 33 , wherein the at least one immunogenic agent comprises a recombinant viral protein; a virus-like particle; a live virus; a live, attenuated virus; an inactivated virus; one or more viral proteins or a combination thereof.

36. The immunogenic agent-containing particle according to claim 33 , wherein the at least one glass-forming agent comprises at least one of trehalose, sucrose, ficoll, dextran, sucrose, maltotriose, lactose, mannitol, hydroxyethyl starch, glycine, cyclodextrin, povidone and a combination thereof.

37. The immunogenic agent-containing particle according to claim 33 , further comprising at least one smoothing excipient, wherein the at least one smoothing excipient comprises at least one of hydroxyethyl starch, serum albumin, human serum albumin, dextran, hetastarch, plasma protein factor, or a combination thereof.

38. The immunogenic composition according to claim 33 , wherein the at least one immunogenic agent comprises a pathogenic bacteria.

39. The immunogenic composition according to claim 38 , wherein the at least one pathogenic bacteria comprise at least one of Pneumococcus, and Streptococcus.

40. The immunogenic composition according to claim 33 , wherein the at least one immunogenic agent comprises at least one pathogenic virus.

41. The immunogenic composition according to claim 40 , wherein the at least one pathogenic virus comprises at least one of influenza, respiratory syncytial virus (RSV), and human papilloma virus (HPV).

42. The immunogenic composition according to claim 33 , wherein the at least one immunogenic agent comprises at least one pathogenic virus and the at least one pathogenic virus comprises at least one species of HPV.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 13, 2025
From: RANDOLPH, THEODORE W.; GARCEA, ROBERT; WEIMER, ALAN W.
To: THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE
Reel/Frame 071102/0319 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 10, 2022
From: RANDOLPH, THEODORE; WEIMER, ALAN W.; GARCEA, ROBERT L.
To: THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE
Reel/Frame 060768/0831 →
Continuity (6)
Continuation 16909689 · Jun 23, 2020
Continuation 16079507
Provisional Application 62404408 · Oct 5, 2016
Provisional Application 62381558 · Aug 30, 2016
Provisional Application 62298912 · Feb 23, 2016
Related Publication 20220265810A1 · Aug 25, 2022
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