Device, method, and system for neural modulation as vaccine adjuvant in a vertebrate subject

• US 8,364,258 B2
• Filed: 06/14/2010
• Issued: 01/29/2013
• Est. Priority Date: 12/22/2009
• Status: Active Grant

• Current Assignee: Gearbox LLC (Intellectual Ventures LLC)
• Original Assignee: The Invention Science Fund I, L.L.C. (Intellectual Ventures LLC)
• Inventors: Della Rocca, Gregory J., Dowling, Joshua L., Goodall, Eleanor V., Hyde, Roderick A., Kare, Jordin T., Ishikawa, Muriel Y., Leuthardt, Eric C., Malaska, Stephen L., Myhrvold, Nathan P., Santiago, Paul, Stewart, Todd J., Sweeney, Elizabeth A., Tegreene, Clarence T., Wood, Lowell L. Jr., Wood, Victoria Y. H.
• Primary Examiner(s): Layno, Carl H
• Assistant Examiner(s): Stice, Paula J
• Application Number:
  US12/802,812
• Publication Number:
  US 20110152748A1
• Time in Patent Office: 960 Days
• Field of Search: 607 2- 3, 607/45
• US Class Current: 607/3
• CPC Class Codes: A61F 7/00 Heating or cooling appliances for medical or therapeutic treatment of the human body heating or cooling means in connection with bedsteads or mattresses A47C21/00 ; massage, therapeutic baths A61H; hyperthermia using electric or magnetic fields or ultrasound A61N; electric heating elements H05B
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61M 37/0092 using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
• CPC Class Codes: A61N 1/303 Constructional details electrodes for external use A61N1/0428
• CPC Class Codes: A61N 1/306 Arrangements where at least part of the apparatus is introduced into the body
• CPC Class Codes: A61N 1/32 alternating or intermittent currents applying electric fields by inductive or capacitive coupling A61N1/40; microwave apparatus A61N5/02
• CPC Class Codes: A61N 1/36121 Production of neurotransmitters; Modulation of genes expression
• CPC Class Codes: A61N 2/00 Magnetotherapy
• CPC Class Codes: A61N 2/002 in combination with another treatment
• CPC Class Codes: A61N 2/006 for magnetic stimulation of nerve tissue
• CPC Class Codes: A61N 2/02 using magnetic fields produced by coils, including single turn loops or electromagnets A61N2/12 takes precedence
• CPC Class Codes: A61N 5/0622 Optical stimulation for exciting neural tissue
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

An apparatus for enhancing an immune response in a vertebrate subject is described. The apparatus includes providing at least one energy stimulus configured to modulate one or more nervous system components of the vertebrate subject, and administering one or more immunogen to the vertebrate subject, wherein the at least one energy stimulus and the one or more immunogen are provided in a combination and in a temporal sequence sufficient to enhance an immune response in the vertebrate subject.

Claims

1. A device comprising:

an energy generator configured to provide at least one energy stimulus, one or more transducer configured to direct the at least one energy stimulus to one or more nervous system components in a tissue of a vertebrate subject, and an apparatus configured to deliver one or more immunogen to the vertebrate subject, wherein the at least one energy stimulus and the one or more immunogen are configured to elicit an enhanced immune response to a disease in the vertebrate subject.

2. The device of claim 1, wherein the energy generator provides the at least one energy stimulus and the apparatus is configured to deliver the one or more immunogen, wherein the at least one energy stimulus and the one or more immunogen are configured in a combination and in a temporal sequence sufficient to enhance the immune response to the disease in the vertebrate subject.

3. The device of claim 2, wherein the apparatus further includes one or more reservoirs including at least one of the one or more immunogen or one or more adjuvants.

4. The device of claim 1, wherein the at least one energy stimulus includes one or more of electrical energy, magnetic energy, electromagnetic energy, ultrasonic energy, acoustic energy, mechanical energy, or thermal energy.

5. The device of claim 4, wherein the at least one energy stimulus includes an electrical stimulus in combination with an ultrasonic stimulus.

6. The device of claim 4, wherein the at least one energy stimulus includes an electrical stimulus in combination with a magnetic stimulus.

7. The device of claim 4, wherein the at least one energy stimulus includes an electrical stimulus in combination with a mechanical stimulus.

8. The device of claim 1, wherein the at least one energy stimulus includes at least one energy characteristic having one or more of waveform, frequency, amplitude, or duration.

9. The device of claim 1, further including circuitry configured to provide the at least one energy stimulus in a temporal sequence configured to modulate one or more nervous system components in the vertebrate subject, and to provide the one or more immunogen to the vertebrate subject.

10. The device of claim 1, wherein the one or more immunogen includes one or more of a bacterial antigen, a viral antigen, a fungal antigen, or a parasital antigen.

11. The device of claim 1, wherein the one or more immunogen includes a tumor antigen.

12. The device of claim 1, wherein the one or more immunogen includes one or more of a polypeptide, a lipid, a carbohydrate, a lipopolysaccharide, a peptide mimetic, a viral antigen, a bacterial antigen, a carcinoembryonic antigen, a mucin, a glycosphingolipid, a genetically engineered antigen, an antigen designed in silico, or a synthetic antigen.

13. The device of claim 1, wherein the energy generator providing the at least one energy stimulus and the apparatus configured to deliver the one or more immunogen is provided simultaneously.

14. The device of claim 1, comprising one or more controllers configured to activate the energy generator to deliver the at least one energy stimulus prior to activating the apparatus to deliver the one or more immunogen.

15. The device of claim 1, comprising one or more controllers configured to activate the apparatus to deliver the one or more immunogen prior to activating the energy generator to deliver the at least one energy stimulus.

16. The device of claim 1, wherein the energy generator providing the at least one energy stimulus and the apparatus configured to deliver the one or more immunogen are provided at one administration site.

17. The device of claim 1, wherein the energy generator providing the at least one energy stimulus and the apparatus configured to deliver the one or more immunogen are provided at different administration sites.

18. The device of claim 1, wherein the energy generator providing the at least one energy stimulus and the apparatus configured to deliver the one or more immunogen are provided as multiple rounds of immunization with the at least one energy stimulus and the one or more immunogen.

19. The device of claim 1, wherein the energy generator and the apparatus are enclosed in a single unit.

20. The device of claim 1, wherein the energy generator and the apparatus are enclosed in two or more units, wherein the two or more units are configured to be substantially in communication.

21. The device of claim 1, wherein the energy generator includes one or more transducer configured to direct the at least one energy stimulus.

22. The device of claim 1, wherein the at least one energy stimulus includes an excitatory stimulus directed to the one or more nervous system components.

23. The device of claim 1, wherein the at least one energy stimulus includes an inhibitory stimulus directed to the one or more nervous system components.

24. The device of claim 1, wherein the at least one energy stimulus is configured to modulate release of a neurotransmitter.

25. The device of claim 24, wherein the neurotransmitter is configured to provoke an excitatory nerve impulse in the vertebrate subject.

26. The device of claim 24, wherein the neurotransmitter is configured to provoke an inhibitory nerve impulse in the vertebrate subject.

27. The device of claim 24, wherein the neurotransmitter includes a glucocorticoid, norepinephrine, noradrenalin, neuropeptide Y, substance P, CGRP, NGF or VIP.

28. The device of claim 24, wherein the at least one energy stimulus is provided to the vertebrate subject within a region of an immunogen administration site in the vertebrate subject.

29. The device of claim 28, wherein the at least one energy stimulus is provided to the vertebrate subject in a location configured to stimulate a lymph node within the region of the immunogen administration site.

30. The device of claim 28, wherein the at least one energy stimulus is configured to stimulate a lymphoid organ, thymus, spleen, bone marrow, peritoneum, mucosal tissue, or a portion of a digestive tract of the vertebrate subject.

31. The device of claim 1, wherein the at least one energy stimulus is configured to elicit a systemic neurogenic response in the vertebrate subject.

32. The device of claim 1, wherein the at least one energy stimulus is configured to elicit a local neurogenic response in the vertebrate subject.

33. The device of claim 32, wherein the at least one energy stimulus is provided in an application pattern including at least one energy characteristic having one or more of waveform, frequency, amplitude, or duration, to elicit the neurogenic response in the vertebrate subject.

34. The device of claim 33, wherein the application pattern includes a cyclical pattern, an intermittent pattern, a repetitive pattern, a random pattern, or a non-random pattern.

35. The device of claim 1, wherein the apparatus configured to deliver the one or more immunogen includes one or more of microneedles, microfine lances, microfine cannulas, microinjector, jet fluid injector, high pressure jet fluid injector, or tissue implant.

36. The device of claim 1, wherein the apparatus configured to deliver the one or more immunogen includes one or more of transdermal delivery devices, transcutaneous delivery devices, percutaneous delivery devices, intradermal delivery devices, or implantable delivery devices.

37. The device of claim 1, wherein at least a portion of the energy generator configured to deliver the at least one energy stimulus is implantable.

38. The device of claim 1, wherein the energy generator configured to deliver the at least one energy stimulus is configured to deliver the at least one energy stimulus to the one or more nervous system components of the vertebrate subject from a site external to the vertebrate subject.