Compositions and methods for therapeutic delivery with microorganisms

• US 20110184387A1
• Filed: 01/22/2010
• Published: 07/28/2011
• Est. Priority Date: 01/22/2010
• Status: Abandoned Application

• Current Assignee: Searete LLC (Intellectual Ventures LLC)
• Original Assignee: Searete LLC (Intellectual Ventures LLC)
• Inventors: Rinaldo, John D. JR., Lord, Robert W., Jung, Edward K.Y., Levien, Royce A., Wood, Lowell L. JR., Hyde, Roderick A., Malamud, Mark A.
• Application Number:
  US12/657,608
• Publication Number:
  US 20110184387A1
• Time in Patent Office: Days
• US Class Current: 604/890.1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/74 Bacteria therapeutic use of a bacterial protein A61K38/00
• CPC Class Codes: A61K 35/747 Lactobacilli, e.g. L. acidophilus or L. brevis
• CPC Class Codes: A61K 36/064 Saccharomycetales, e.g. baker's yeast
• CPC Class Codes: A61K 38/162 from virus
• CPC Class Codes: A61K 38/1841 Transforming growth factor [TGF]
• CPC Class Codes: A61K 38/2013 IL-2
• CPC Class Codes: A61K 38/2066 IL-10
• CPC Class Codes: A61K 38/208 IL-12
• CPC Class Codes: C12N 1/36 Adaptation or attenuation of cells
• CPC Class Codes: C12N 15/635 Externally inducible repressor mediated regulation of gene expression, e.g. tetR inducible by tetracyline
• 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

Certain embodiments disclosed relate to compositions, including therapeutic compositions, methods, devices, and systems that include modified microorganisms including at least one genetic element encoding at least one therapeutic agent or environmental treatment agent.

Claims

1. A delivery device, comprising:

a housing including at least one reservoir containing at least one composition, the at least one composition including at least one first constituent including at least one auxotrophic microorganism including at least one pH inducible promoter operably coupled to at least one heterologous genetic element encoding at least one therapeutic agent, and at least one genetic element inducible to initiate death of the at least one auxotrophic microorganism; and

at least one second constituent including at least one metabolite required by the at least one auxotrophic microorganism;

the reservoir configured to receive, retain, and dispense at least a portion of the at least one composition; and

at least one constituent configured to administer the at least one composition to at least one biological tissue.

2. The device of claim 1, wherein the at least one composition further includes at least one pharmaceutically-acceptable carrier or excipient.

3. The device of claim 1, wherein the at least one first constituent of the composition and the at least one second constituent of the composition are located in different reservoirs of the delivery device.

4. The device of claim 1, wherein the device is implantable.

6. The device of claim 1, wherein the device is external to a subject.

7. The device of claim 1, wherein at least one component configured to administer the at least one composition to at least one biological tissue includes one or more ports.

8. The device of claim 1, wherein at least one of the one or more ports includes at least one outlet port or at least one inlet port.

9. The device of claim 1, wherein each reservoir includes at least one separate port.

10. The device of claim 1, wherein the delivery device includes at least one reservoir including at least one inducer formulated to induce at least one promoter operably coupled to the at least one genetic element inducible to initiate death of the at least one auxotrophic microorganism.

11. The device of claim 1, further comprising one or more controllable output mechanisms operably linked to the one or more ports to control dispensing of at least a portion of the at least one composition from the at least one reservoir.

12. The device of claim 11, wherein the at least one controllable output mechanism includes at least one of a micropump, valve, or actuator.

13. The device of claim 12, wherein the valve includes at least one of a one-way valve, or pressure settable valve.

14. The device of claim 12, wherein the actuator includes at least one of a piezoelectric actuator, electrostatic actuator, thermal actuator, shape-memory alloy actuator, bioactuator, or magnetic actuator.

15. The device of claim 11, wherein the at least one controllable output mechanism includes at least one thermal or nonthermal gate in communication with the at least one outlet of the at least one reservoir.

16. The device of claim 11, further comprising at least one control circuitry configured to control the at least one controllable output mechanism.

17. The device of claim 16, wherein the at least one control circuitry is configured to control the release of the at least two constituents of the composition.

18. The device of claim 17, wherein at least one of the rate of release, amount of release, or time of release of the at least two constituents of the composition are different for each constituent.

19. The device of claim 16, wherein the at least one control circuitry is configured to generate and transmit an electromagnetic control signal configured to control the at least one controllable output mechanism.

20. The device of claim 16, wherein the at least one control circuitry is configured to control the at least one controllable output mechanism for time-release of at least a portion of the at least one composition from the at least one reservoir.

21. The device of claim 16, wherein the at least one control circuitry is configured for variable programming control of the at least one controllable output mechanism.

22. The device of claim 16, wherein the at least one control circuitry is configured to control release of the composition or a portion thereof in response to a signal from a sensor.

23. The device of claim 16, wherein the at least one control circuitry is configured to control release of at least one inducer formulated to activate at least one promoter operably coupled to the at least one genetic element inducible to initiate death of the at least one auxotrophic microorganism.

24. The device of claim 1, further comprising at least one transducer.

25. The device of claim 1, further comprising at least one receiver.

26. The device of claim 25, wherein the at least one receiver is configured to receive information from at least one distal or remote sensor.

27. The device of claim 25, wherein the receiver is configured to obtain release instructions or authorization to release the at least one composition.

28. The device of claim 25, wherein the receiver is configured to receive programming instructions or data for the controller.

29. The device of claim 1, further comprising at least one transmitter.

30. The device of claim 29, wherein the at least one transmitter is configured to transmit information regarding one or more of the date, time, presence or approximate quantity of one or more of at least a portion of the at least one composition, at least one constituent thereof, or at least one product thereof;

at least one cell or substance associated with the at least one biological tissue;

at least one metabolite associated with the at least one biological tissue;

or at least one microorganism associated with the at least one biological tissue.

31. The device of claim 1, further comprising at least one power source.

32. The device of claim 1, further comprising at least one detection material.

33. The device of claim 32, further comprising at least one reservoir for controlled release of the at least one detection material.

34. The device of claim 32, wherein the at least one detection material includes at least one of a radioactive, luminescent, colorimetric or odorous substance.

35. The device of claim 32, wherein the at least one detection material includes at least one of a taggant, contrast agent, sensor, or electronic identification device.

36. The device of claim 35, wherein the at least one electronic identification device includes at least one radio frequency identification device.

37. The device of claim 35, wherein the at least one sensor includes at least one biosensor.

38. The device of claim 37, wherein the at least one biosensor includes at least one modified microorganism.

39. The device of claim 35, wherein the at least one sensor receives information associated with at least one of temperature, pH, inflammation, presence of at least one inducer, amount of at least one inducer, presence of at least one repressor, amount of at least one repressor, or biological response to administration of the at least one composition.

40. The device of claim 32, wherein the at least one detection material includes at least one of a diamagnetic particle, ferromagnetic particle, paramagnetic particle, super paramagnetic particle, particle with altered isotope, or other magnetic particle.

41. The device of claim 32, wherein the at least one detection material is responsive to the presence of at least one of the at least one composition, at least one constituent thereof, or at least one product thereof;

at least one cell or substance associated with the at least one biological tissue;

the at least one metabolite, or at least one product thereof, or the at least one therapeutic agent, or a by-product thereof.

42. The device of claim 32, wherein the at least one detection material is responsive to the approximate quantity of at least one of the at least one composition, at least one constituent thereof, or at least one product thereof;

at least one cell or substance associated with the at least one biological tissue;

or the at least one metabolite, or at least one product thereof.

43. The device of claim 32, wherein the at least one detection material is responsive to the approximate number of microorganisms producing the at least one therapeutic agent.

46. The device of claim 1, further comprising at least one memory mechanism for storing instructions for generating and transmitting an electromagnetic control signal.

47. The device of claim 1, further comprising at least one imaging apparatus capable of imaging the approximate quantity within a treatment region of one or more of the at least one composition, at least one constituent thereof, or at least one product thereof;

at least one cell or substance associated with the at least one biological tissue;

or the at least one metabolite, or at least one product thereof.

48. The device of claim 1, further comprising at least one reservoir for controlled release of at least one inducer or repressor of the at least one heterologous genetic element encoding at least one therapeutic agent.

49. The device of claim 1, further comprising at least one reservoir for controlled release of at least one inducer or repressor of the at least one genetic element inducible to initiate death of the at least one modified microorganism.

50. The device of claim 1, further comprising at least one memory location for recording information.

51. The device of claim 50, wherein the at least one memory location is configured to record information regarding at least one sensor.

52. The device of claim 50, wherein the at least one memory location is configured to record information regarding at least one of a sensed condition, history, or performance of the device.

53. The device of claim 50, wherein the at least one memory location is configured to record information regarding one or more of the date, time, presence or approximate quantity of at least one of the administered composition, constituent thereof, or product thereof;

the at least one administered metabolite, or product thereof;

or at least one cell or substance associated with the at least one biological tissue.

55. The device of claim 50, further comprising at least one information transmission mechanism configured to transmit information recorded by the at least one electronic memory location.

56. The device of claim 1, wherein the device is located in or is substantially in the form of one or more of a spray apparatus, pump apparatus, bioreactor, or drilling apparatus.

57. The device of claim 1, further comprising a controller configured to respond to the at least one sensor.

59. The device of claim 1, further comprising at least one reservoir for controlled release of at least one inducer or repressor of the at least one heterologous genetic element encoding at least one environmental medium treatment agent.

5. (canceled)

44-45. -45. (canceled)

54. (canceled)

58. (canceled)