MICROMOLDED OR 3-D PRINTED PULSATILE RELEASE VACCINE FORMULATIONS

• US 20190328871A1
• Filed: 05/02/2019
• Published: 10/31/2019
• Est. Priority Date: 12/16/2013
• Status: Active Grant

• Current Assignee: Tokitae LLC (Intellectual Ventures LLC), Massachusetts Institute of Technology
• Original Assignee: Tokitae LLC (Intellectual Ventures LLC), Massachusetts Institute of Technology
• Inventors: Jaklenec, Ana, Gates, William, Welkhoff, Philip A., Nikolic, Boris, Wood, JR., Lowell L., Langer, Robert S., Nguyen, Thanh Duc, Tzeng, Stephany Yi, Norman, James J., McHugh, Kevin
• Granted Patent: US 10,960,073 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 2039/55566 Emulsions, e.g. Freund's adjuvant, MF59
• CPC Class Codes: A61K 2039/6093 Synthetic polymers, e.g. polyethyleneglycol [PEG], Polymers or copolymers of (D) glutamate and (D) lysine
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C12N 2770/32634 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Emulsion-based and micromolded (“MM”) or three dimensional printed (“3DP”) polymeric formulations for single injection of antigen, preferably releasing at two or more time periods, have been developed. Formulations are preferably formed of biocompatible, biodegradable polymers. Discrete regions encapsulating antigen, alone or in combination with other antigens, adjuvants, stabilizers, and release modifiers, are present in the formulations. Antigen is preferably present in excipient at the time of administration, or on the surface of the formulation, for immediate release, and incorporated within the formulation for release at ten to 45 days after initial release of antigen, optionally at ten to 90 day intervals for release of antigen in one or more additional time periods. Antigen may be stabilized through the use of stabilizing agents such as trehalose glass. In a preferred embodiment for immunization against polio, antigen is released at the time of administration, and two, four and six months thereafter.

Claims

1-19. -19. (canceled)

20. A method of delivery of a therapeutic, prophylactic, nutraceutical or diagnostic agent to an individual in need thereof, comprising administering to the individual a polymeric device comprising a polymeric shell and at least one discrete region comprising a therapeutic, prophylactic, nutraceutical, or diagnostic agent, optionally in combination with a stabilizing excipient, wherein the shell and discrete regions are formed from successive layers of polymeric particles bonded together by solvent and/or temperature.

21. The method of claim 20 wherein the device is made by three dimensional printing and/or micromolding.

22. The method of claim 21 wherein the agent is encapsulated in polymeric particles in the form of microparticles, microcapsules, or microspheres.

23. The method of claim 20, wherein the device is injectable.

24. The method of claim 20, wherein the device is implantable.

25. The method of claim 20, wherein the device can be applied to a mucosal surface selected from the group consisting of nasal, pulmonary, oral, vaginal and rectal.

26. The method of claim 20 for delivering antigen comprising administering a device comprising a polymeric shell and one or more discrete regions comprising antigen, optionally in combination with a stabilizing excipient for the antigen, wherein an effective amount of the antigen is released in one or more time periods in an effective amount to elicit an immune response.

27. The method of claim 20, wherein the agent is released at two or more intervals.

28. The method of claim 27 wherein the agent is released at intervals of between 30 and 60 days.

29. The method of claim 27, wherein the agent is released in at least three time periods at intervals of between ten and ninety days.

30. The method of claim 26 providing release at intervals of between ten and ninety days.

31. The method of claim 26, wherein the antigen elicits an immune response to an infectious agent or to a tumor.

32. The method of claim 31, wherein the infectious agent is a virus, bacteria, fungus or protozoan.

33. The method of claim 32, wherein the virus is selected from the group consisting of polio, influenza, hepatitis, rotavirus, measles, mumps, rubella, and varicella.

34. The device of claim 33, wherein the bacteria is selected from the group consisting of Corynebacterium diphtheriae, Bordetella pertussis, Clostridium tetani, Streptococcus pneumonia (Pneumococcus), and Neisseria meningitidis (Meningococcus).

35. The method of claim 31, wherein the antigen is a tumor antigen selectively eliciting a T cell response to a tumor.

36. The method of claim 20 wherein the device comprises a stabilizing excipient on the surface of the device, or mixed with the polymer of the device.

37. The method of claim 36, wherein the stabilizing excipient is selected from the group consisting of sugars, oils, lipids, and carbohydrates.

38. The method of claim 36 wherein the stabilizing excipient comprises monosodium glutamate (MSG).

39. The method of claim 36, wherein the stabilizing excipient comprises magnesium chloride (MgCl₂).

40. The method of claim 37, wherein the sugar is selected from the group consisting of sucrose, trehalose, and combinations thereof.

41. The method of claim 20, wherein the device further comprises a buffering agent.

42. The method of claim 41, wherein the buffering agent is selected from the group consisting of magnesium hydroxide, aluminum hydroxide, and myristic acid.

43. The method of claim 20, wherein the polymer is biodegradable by hydrolysis.

44. A method of making a polymeric device comprising a polymeric shell and at least one discrete region, comprising

forming the shell and discrete regions comprising a therapeutic, prophylactic, nutraceutical, or diagnostic agent, optionally in combination with a stabilizing excipient, by bonding together successive layers of polymeric particles bonded using solvent and/or temperature.

45. The method of claim 44 wherein the device is made by three dimensional printing and/or micromolding.

46. The method of claim 44 wherein the agent is encapsulated in polymeric particles in the form of microparticles, microcapsules, or microspheres.

47. The method of claim 44 further comprising adding to the device a stabilizing agent and/or a buffering agent.