MHC-less cells

• US 20120022337A1
• Filed: 07/26/2010
• Published: 01/26/2012
• Est. Priority Date: 07/26/2010
• Status: Abandoned Application

• Current Assignee: Searete LLC (Intellectual Ventures LLC)
• Original Assignee: Searete LLC (Intellectual Ventures LLC)
• Inventors: Hyde, Roderick A., Ishikawa, Muriel Y., Jung, Edward K.Y., Kindsvogel, Wayne R., Leuthardt, Eric C., Malaska, Stephen L., McKnight, Gary L., Sweeney, Elizabeth A., Wood, Lowell L. Jr.
• Application Number:
  US12/804,649
• Publication Number:
  US 20120022337A1
• Time in Patent Office: Days
• US Class Current: 600/301
• CPC Class Codes: A61K 2035/122 for inducing tolerance or supression of immune responses
• CPC Class Codes: A61K 35/15 Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells presenting a specific antigen A61K39/00; therapeutic combinations of antibodies, or fragments thereof, and blood-derived cells A61K39/00
• CPC Class Codes: A61K 35/17 Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes when activated by a specific antigen A61K39/00
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 35/407 Liver; Hepatocytes
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present disclosure relates to compositions, methods, systems, computer-implemented methods, and computer program products thereof that relate to biological cells for delivery of at least one therapeutic agent to a biological tissue or subject.

Claims

1. A delivery device, comprising:

a housing including at least one first reservoir containing at least one composition,

the at least one composition including at least one histocompatibility antigen related gene modified eukaryotic cell; and

at least one port for dispensing a portion of the at least one composition to at least one biological tissue.

2. The device of claim 1, wherein the at least one histocompatiblity antigen gene-modified eukaryotic cell includes at least one modified eukaryotic cell including at least one regulatory nucleic acid construct including an operon with an inducible promoter and encoding a regulatory gene product that is sufficient to modulate the expression of at least one endogenous modified eukaryotic cell histocompatibility antigen related gene,

the modified eukaryotic cell further including at least one therapeutic nucleic acid construct including an operon and encoding at least one therapeutic agent.

3. The device of claim 1, wherein the at least one histocompatibility antigen related gene-modified eukaryotic cell includes at least one modified eukaryotic cell including at least one modification sufficient to reduce or eliminate expression of at least one endogenous histocompatibility antigen related gene,

the modified eukaryotic cell including at least one rescue nucleic acid construct including an operon with an inducible promoter and encoding at least a portion of one or more of an exogenous histocompatibility gene product, or a homologue thereof, or at least a portion of one or more superantigens;

and

the modified eukaryotic cell further including at least one therapeutic nucleic acid construct including an operon and encoding at least one therapeutic agent.

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

5. The device of claim 1, wherein the device is at least partially implantable.

6. The device of claim 1, wherein the device is implanted into a subject.

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

8. The device of claim 1, further including at least one regulatory element reservoir configured for holding at least one of an inducer, activator, repressor, or co-repressor formulated to interact with one or more nucleic acid constructs included in the at least one modified eukaryotic cell.

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

10. The device of claim 1, wherein the at least one controllable output mechanism includes at least one of a micropump, valve, or actuator.

11. The device of claim 1, wherein the valve includes at least one of a one-way valve, or pressure settable valve.

12. The device of claim 1, wherein the actuator includes at least one of a piezoelectric actuator, electrostatic actuator, thermal actuator, shape-memory alloy actuator, bioactuator, or magnetic actuator.

13. The device of claim 10, wherein the at least one controllable output mechanism includes at least one thermal or nonthermal gate in communication with the at least one port of the at least one reservoir.

14. The device of claim 10, further comprising at least one control circuitry configured to control the at least one controllable output mechanism.

15. The device of claim 14, wherein the at least one control circuitry is configured to control the dispensing of at least a portion of the at least one composition from the at least one reservoir.

16. The device of claim 14, 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.

17. The device of claim 14, 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.

18. The device of claim 14, wherein the at least one control circuitry is configured for variable programming control of the at least one controllable output mechanism.

19. The device of claim 14, wherein the at least one control circuitry is configured to control dispensing of at least a portion of the composition in response to a signal from a sensor.

20. The device of claim 19, further comprising a controller configured to respond to the at least one sensor.

21. The device of claim 14, wherein the at least one control circuitry is configured to control dispensing of at least a portion of the at least one inducer, activator, repressor, or co-repressor formulated to interact with the one or more nucleic acid constructs of the at least one modified eukaryotic cell.

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

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

24. The device of claim 23, wherein the at least one receiver is configured to receive information from at least one distal or remote sensor.

25. The device of claim 23, wherein the receiver is configured to obtain release instructions or authorization to dispense at least a portion of the at least one composition from the at least one first reservoir.

26. The device of claim 23, wherein the receiver is configured to receive programming instructions or data for the controller.

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

28. The device of claim 27, 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, or at least one product thereof;

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

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

30. The device of claim 29, wherein the at least one power source includes at least one of a battery, solar cell, fuel cell, photovoltaic cell, or PZT-silicone compound.

31. The device of claim 30, wherein the battery includes at least one of a thin film battery, or microbattery.

32. The device of claim 1, further comprising at least one detection material reservoir configured for holding at least one detection material.

33. The device of claim 32, wherein the at least one detection material includes at least one of a radioactive substance, luminescent substance, reporter gene construct, colorimetric substance, odorous substance, or a cell containing at least one thereof.

34. 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.

35. The device of claim 34, wherein the at least one electronic identification device includes at least one radio frequency identification device.

36. The device of claim 34, wherein the at least one sensor includes at least one biosensor.

37. The device of claim 34, 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.

38. 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.

39. The device of claim 32, wherein the at least one detection material is configured to detect at least one of the presence or the approximate quantity of at least one of the at least one composition, or at least one product thereof;

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

40. The device of claim 32, wherein the at least one detection material is configured to detect at least one of the presence or the approximate quantity of modified eukaryotic cells producing the at least one therapeutic agent.

41. The device of claim 32, wherein the at least one detection material is responsive to at least one of:

enzyme, acid, amino acid, peptide, polypeptide, protein, oligonucleotide, nucleic acid, ribonucleic acid, oligosaccharide, polysaccharide, glycopeptide, glycolipid, lipoprotein, sphingolipid, glycosphingolipid, glycoprotein, peptidoglycan, lipid, carbohydrate, metalloprotein, proteoglycan, chromosome, adhesion molecule, cytokine, chemokine, immunoglobulin, antibody, antigen, platelet, extracellular matrix, blood plasma, cell wall, hormone, organic compound, inorganic compound, salt, receptor, antigen, soluble antigen, or cell ligand.

42. The device of claim 32, wherein the at least one detection material is responsive to at least one of:

glucose, lactate, urea, uric acid, glycogen, oxygen, carbon dioxide, carbon monoxide, ketone, nitric oxide, nitrous oxide, alcohol, alkaloid, opioid, cannabinol, endorphin, epinephrine, dopamine, serotonin, nicotine, amphetamine, methamphetamine, anabolic steroid, hydrocodone, hemoglobin, heparin, clotting metabolite, cytokine, tumor antigen, pH, albumin, ATP, NADH, FADH₂, pyruvate, sulfur, mercury, lead, creatinine, cholesterol, lipoprotein, α

-fetoprotein, chorionic gonadotropin, estrogen, progesterone, testosterone, thyroxine, melatonin, calcitonin, antimullerian hormone, adiponectin, angiotensin, cholecystokinin, corticotrophin-releasing hormone, erythropoietin, bilirubin, creatine, follicle-stimulating hormone, gastrin, ghrelin, glucagon, gonadotropin-releasing hormone, inhibin, growth hormone, growth hormone-releasing hormone, insulin, human placental lactogen, oxytocin, orexin, luteinizing hormone, leptin, prolactin, somatostatin, thrombopoietin, cortisol, aldosterone, estradiol, estriol, estrone, leukotriene, brain natriuretic peptide, neuropeptide Y, histamine, vitamin, mineral, endothelin, renin, enkephalin, DHEA, DHT, alloisoleucine, toxic substance, illegal substance, therapeutic agent, or any metabolite thereof.

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

44. 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, or at least one product thereof;

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

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

46. The device of claim 45, wherein the at least one memory location is configured to record information relating to at least one sensor.

47. The device of claim 46, 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.

48. The device of claim 47, 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, or product thereof;

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

50. The device of claim 46, further comprising at least one information transmission mechanism configured to transmit information recorded by the at least one electronic memory location.

51. 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, iontophoretic apparatus, diffusible patch, stent, shunt, dentures or other oral implant, contact lens or other ocular implant, suture, surgical staple, bandage, or pump apparatus.

49. (canceled)