Compositions and methods for therapeutic delivery with microorganisms

• US 20110183319A1
• 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:
  US12/657,609
• Publication Number:
  US 20110183319A1
• Time in Patent Office: Days
• US Class Current: 435/6.1
• 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 system, comprising:

at least one computing device;

at least one delivery device configured to retain and dispense at least a portion of at least one composition to at least one biological tissue; and

a recordable medium including one or more instructions that when executed on the computing device cause the computing device to regulate dispensing of at least a portion of the at least one composition,

wherein the at least one composition includes 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 including 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.

2. The system of claim 1, wherein the at least one computing device includes at least one computing device located on or in the at least one delivery device.

3. The system of claim 1, wherein the at least one computing device includes at least one computing device located remotely from the at least one delivery device.

4. The system of claim 1, wherein the at least one computing device includes one or more of a desktop computer, workstation computer, or computing system.

5. The system of claim 1, wherein the at least one computing system includes one or more of a cluster of processors, a networked computer, a tablet personal computer, a laptop computer, a mobile device, a mobile telephone, or a personal digital assistant computer.

6. The system of claim 1, further comprising one or more instructions that when executed on the at least one computing device cause the at least one computing device to generate at least one output to a user.

7. The system of claim 6, wherein the at least one output includes at least one graphical illustration 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;

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

at least one property of the delivery device;

or at least one property of dispensing the at least one delivery device.

8. The system of claim 6, wherein the at least one output includes at least one protocol for generating the at least one auxotrophic microorganism.

9. The system of claim 6, wherein the at least one output includes at least one protocol for making the at least one composition.

10. The system of claim 6, wherein the at least one output includes at least one protocol for administering the at least one composition to the at least one biological tissue.

11. The system of claim 6, wherein the user includes at least one entity.

12. The system of claim 11, wherein the entity includes at least one person, or computer.

13. The system of claim 6, wherein the output includes output to a user readable display.

14. The system of claim 13, wherein the user readable display includes a human readable display.

18. The system of claim 1, further comprising one or more instructions for making the at least one composition.

19. The system of claim 1, further comprising one or more instructions for inducing the at least one pH inducible promoter operably coupled to at least one heterologous genetic element encoding at least one therapeutic agent.

20. The system of claim 1, further comprising one or more instructions for inducing the at least one genetic element inducible to initiate death of the at least one auxotrophic microorganism.

22. The system of claim 1, further comprising one or more instructions for selecting the composition, or a constituent thereof.

23. The system of claim 1, further comprising one or more instructions for administering the at least one composition or a constituent thereof to at least one biological tissue.

24. The system of claim 1, further comprising one or more instructions for receiving information related to one or more biological tissue indicators prior to, during, or subsequent to administering the at least one composition to the at least one biological tissue.

28. The system of claim 1, further comprising one or more instructions for receiving information related to one or more biological tissue indicators relate to one or more of:

administering the at least one composition, at least one constituent thereof, or at least one product thereof;

administering the at least one metabolite, cell or tissue formation, cell or tissue growth, cell or tissue apoptosis, cell or tissue necrosis, cell division, cytoskeletal rearrangement, cell or tissue secretion, cell or tissue differentiation, status of the at least one microorganism of the at least one composition, status of the at least one composition, status of the at least one therapeutic agent, status of the at least one metabolite, or depletion of the at least one metabolite.

35. The system of claim 1, further comprising one or more instructions for obtaining genetic sequence information from at least one microorganism isolated from the at least one biological tissue.

36. The system of claim 35, further comprising one or more instructions for modifying the at least one microorganism isolated from the at least one biological tissue.

37. The system of claim 35, further comprising one or more instructions for amplifying the at least one microorganism isolated from the at least one biological tissue.

38. The system of claim 35, further comprising one or more instructions for reinstating the at least one microorganism isolated from the at least one biological tissue subsequent to modification.

39. The system of claim 1, further comprising one or more instructions for predetermining at least one microorganism type for modifying to produce at least one therapeutic agent based on at least one feature of the at least one biological tissue.

40. The system of claim 39, wherein the at least one feature of the at least one biological tissue includes at least one property of one or more microorganism populations associated with the at least one biological tissue.

15-17. -17. (canceled)

21. (canceled)

25-27. -27. (canceled)

29-34. -34. (canceled)

41. A computer-implemented method comprising:

one or more instructions for regulating dispensing at least one composition from at least one delivery device to at least one biological tissue, the at least one composition including at least one auxotrophic microorganism including at least one pH inducible heterologous genetic element encoding at least one therapeutic agent formulated for at least one biological tissue, and including at least one genetic element inducible to initiate death of the at least one auxotrophic microorganism; and

at least one metabolite required by the at least one auxotrophic microorganism.

42. The computer-implemented method of claim 41, further comprising generating at least one output to a user.

43. The computer-implemented method of claim 42, wherein the at least one output includes at least one graphical illustration of one or more of the at least one composition, at least one constituent thereof, or at least one product thereof;

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

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

at least one property of the at least one delivery device;

or at least one property of dispensing the at least one delivery device.

44. The computer-implemented method of claim 42, wherein the at least one output includes at least one protocol for generating the at least one auxotrophic microorganism.

45. The computer-implemented method of claim 42, wherein the at least one output includes at least one protocol for making the at least one composition.

46. The computer-implemented method of claim 42, wherein the at least one output includes at least one protocol for administering the at least one composition to the at least one biological tissue.

47. The computer-implemented method of claim 42, wherein the user includes at least one entity.

48. The computer-implemented method of claim 47, wherein the entity includes at least one person, or computer.

49. The computer-implemented method of claim 42, wherein the at least one output includes at least one output to a user readable display.

50. The computer-implemented method of claim 49, wherein the user readable display includes a human readable display.

51. The computer-implemented method of claim 49, wherein the user readable display includes one or more active displays.

52. The computer-implemented method of claim 49, wherein the user readable display includes one or more passive displays.

53. The computer-implemented method of claim 49, wherein the user readable display includes one or more of a numeric format, graphical format, or audio format.

54. The computer-implemented method of claim 42, further comprising one or more instructions for making the at least one composition.

55. The computer-implemented method of claim 42, further comprising one or more instructions to dispense the at least one composition or a constituent thereof to at least one biological tissue.

57. The computer-implemented method of claim 42, further comprising receiving information related to one or more biological tissue indicators prior to, during, or subsequent to administering the at least one composition or a constituent thereof, to the at least one biological tissue.

58. The computer-implemented method of claim 42, further comprising one or more instructions for dispensing the at least one composition or a constituent thereof, to the at least one biological tissue in response to the one or more biological tissue indicators.

59. The computer-implemented method of claim 42, further comprising one or more instructions for dispensing at least one inducer formulated to induce the at least one genetic element inducible to initiate death of the at least one auxotrophic microorganism, to the at least one biological tissue in response to the one or more biological tissue indicators.

60. The computer-implemented method of claim 42, wherein the receiving information related to one or more biological tissue indicators includes information from at least one of an assay, image, or gross assessment of the at least one biological tissue prior to, during, or subsequent to administering the at least one composition.

63. The computer-implemented method of claim 42, wherein the one or more biological tissue indicators relate to one or more of:

administration of the at least one therapeutic agent, or a constituent thereof, or product thereof;

administration of the at least one composition, or constituent thereof, or product thereof;

administration of the at least one metabolite, administration of the at least one auxotrophic microorganism, cell or tissue formation, cell or tissue growth, cell or tissue apoptosis, cell or tissue necrosis, cell division, cytoskeletal rearrangement, cell or tissue secretion, cell or tissue differentiation, status of the at least one microorganism of the at least one composition, status of the at least one composition, status of the at least one therapeutic agent, status of the at least one metabolite, or depletion of the at least one metabolite.

70. The computer-implemented method of claim 42, further comprising obtaining genetic sequence information from at least one microorganism isolated from the at least one biological tissue.

71. The computer-implemented method of claim 70, further comprising one or more instructions for modifying the at least one microorganism isolated from the at least one biological tissue.

72. The computer-implemented method of claim 70, further comprising one or more instructions for amplifying the at least one microorganism isolated from the at least one biological tissue.

73. The computer-implemented method of claim 70, further comprising one or more instructions for reinstating the at least one microorganism isolated from the at least one biological tissue subsequent to modification.

74. The computer-implemented method of claim 70, further comprising one or more instructions for predetermining at least one microorganism type for modifying to produce at least one therapeutic agent based on at least one feature of the at least one biological tissue.

75. The computer-implemented method of claim 74, wherein the at least one feature of the at least one biological tissue includes at least one property of one or more microorganism populations associated with the at least one biological tissue.

56. (canceled)

61-62. -62. (canceled)

64-69. -69. (canceled)

76. A computer program product, comprising:

a recordable medium bearing one or more instructions for regulating dispensing of at least one delivery device,

wherein the delivery device includes at least one composition, wherein the at least one composition includes at least one auxotrophic microorganism including at least one pH inducible heterologous genetic element encoding at least one therapeutic agent formulated for at least one biological tissue, including at least one genetic element inducible to initiate death of the at least one auxotrophic microorganism; and

at least one metabolite required by the at least one auxotrophic microorganism; and

generating at least one output.

77-91. -91. (canceled)