Therapeutic transplantation using developing, human or porcine, renal or hepatic, grafts

• US 20050226854A1
• Filed: 01/19/2005
• Published: 10/13/2005
• Est. Priority Date: 09/07/2001
• Status: Active Grant

• Current Assignee: Yeda Research and Development Co. Ltd. (Weizmann Institute of Science)
• Original Assignee: Yeda Research and Development Co. Ltd. (Weizmann Institute of Science)
• Inventors: Dekel, Benjamin, Eventov-Friedman, Smadar, Aronovich, Anna, Reisner, Yair, Tchorsh, Dalit, Katchman, Helena, Shezen, Elias
• Granted Patent: US 7,780,993 B2
• Time in Patent Office: Days
• US Class Current: 424/93.700
• 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 35/22 Urine; Urinary tract, e.g. kidney or bladder; Intraglomerular mesangial cells; Renal mesenchymal cells; Adrenal gland
• CPC Class Codes: A61K 35/407 Liver; Hepatocytes
• CPC Class Codes: A61K 35/54 Ovaries; Ova; Ovules; Embryos; Foetal cells; Germ cells
• CPC Class Codes: A61K 39/39541 against normal tissues, cells
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61L 2430/28 for liver reconstruction
• CPC Class Codes: A61L 27/3604 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• CPC Class Codes: A61L 27/3641 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics

Abstract

A method of treating a renal, hepatic or enzyme-deficiency disorder in a subject in need thereof is disclosed. The method is effected by transplanting into the subject tissue derived from a human or porcine, kidney or liver, the kidney or liver being at a selected gestational stage.

Claims

1. A method of a renal disorder in a subject in need thereof, the method comprising transplanting renal issue into the subject, said renal tissue being derived from a human kidney being at a stage of development selected from a range of 48 to 57 days of gestation, thereby treating the renal disorder in the subject.

2. The method of claim 1, wherein said human kidney is at a stage of development selected from a range of 49 to 56 days of gestation.

3. The method of claim 1, further comprising the subject with an immunosuppressive region prior to, concomitantly with or following said transplanting said renal tissue into the subject, thereby promoting engraftment of said tissue in the subject.

4. The method of claim 3, wherein said treating the subject. with an immunosuppressive regimen is effected by administering at least one immunosuppressant drug to the subject.

5. The method of claim 4, wherein said at least one immunosuppressant drug is capable of blocking binding of a lymphocyte coreceptor with a ligand of said lymphocyte coreceptor.

6. The method of claim 5, wherein said at least one immunosuppressant drug is capable of blocking binding of a lymphocyte coreceptor with a ligand of said lymphocyte coreceptor, and wherein said administering said at least one immunosuppressant drug to the subject is effected during a time period selected from a range of 1 to 60 days.

7. The method of claim 5, wherein said lympbocyte coreceptor is selected from the group consisting of B7-1, CD40, and CD40L.

8. The method of claim 5, wherein said ligand of said lymphocyte coreceptor is selected from the group consisting of B7-1, CD40, and CD40L.

9. The method of claim 4, wherein said at least one immunosuppressant drug comprises CTLA-4-Ig.

10. The method of claim 4, wherein said at least one immunosuppressant drug comprises CTLA-4-Ig and anti-CD40L antibody.

11. The method of claim 4, wherein said at least one immunosuppressant drug comprises CTLA-4-Ig CD40L antibody and rapamycin.

12. The method of claim 1, said transplanting said renal tissue into the subject is effected by transplanting said renal tissue into an anatomical location of the subject selected from the group consisting of the renal capsule, the kidney, the omentum, the intra-abdominal space, and an intestmal loop.

13. The method of claim 1, wherein the subject is a mammal.

14. The method of claim 1, wherein the subject is a human.

15. The method of claim 1, said human kidney is non-syngeneic with the subject.

16. The method of claim 1, wherein said human kidney is allogeneic with the subject.

17. The method of claim 1, wherein said renal tissue is a whole metanephros.

18. The method of claim 1, wherein said renal tissue is a whole metanephros.

19. A method of treating a renal disorder in a subject in need thereof, the method comprising transplanting renal tissue into the subject, said renal tissue being derived from a porcine kidney being at a stage of development selected from a range of 26 to 29 days of gestation, thereby treating the renal disorder in the subject.

20. The method of claim 19, w in said porcine kidney is at a stage of development selected from a range of 27 to 28 days of gestation.

21. The method of claim 19, further comprising treating the subject with an immunosuppressive regimen prior to, concomitantly with or following said transplanting said renal tissue into the subject, thereby promoting engraftment of said tissue in the subject.

22. The method of claim 21, wherein said treating the subject with an immunosuppressive regimen is effected by administering at least one immunosuppressant drug to the subject.

23. The method of claim 22, wherein said at least one immunosuppressant drug is capable of blocking binding of a lymphocyte coreceptor with a ligand of said lymphocyte receptor.

24. The method of claim 23, wherein said at least one immunosuppressant drug is capable of blocking binding of a lymphocyte coreceptor with a ligand of said lymphocyte corecetor, and wherein said administering said at least one immunosuppressant drug to the subject is effected during a time period selected from a range of 1 to 60 days.

25. The method of claim 23, wherein said lymphocyte coreceptor is selected from the group consisting of B7-1, CD40, and CD40L.

26. The method of claim 23, wherein said ligand of said lymphocyte coreceptor is selected from the group consisting of B7-1, CD40, and CD40L.

27. The method of claim 22, wherein said at least one immunosuppressant drug cons CTLA4-Ig.

28. The method of claim 22, wherein said at least one immunosuppressant drug comprises CTLA4-Ig and anti CD40L antibody.

29. The method of claim 22, wherein said at least one immunosuppressant drug comprises CTLA4-Ig, anti CD40L antibody and rapamycin.

30. The method of claim 19, wherein said transplanting said renal tissue into the subject is effected by transplanting said renal tissue into an anatomical location of the subject selected from the group consisting of the renal capsule, the kidney, the omentum, the intra-abdominal space, and an intestinal loop.

31. The method of claim 19, wherein the subject is a mammal.

32. The method of claim 19, wherein the subject is a human.

33. The method of claim 19, wherein said porcine kidney is non-syngeneic with the subject.

34. The method of claim 19, wherein said porcine kidney is xenogeneic with the subject.

35. The method of claim 19, wherein said renal tissue is a whole metanephros.

36. The method of clam 19, wherein said renal tissue is a partial metanephros.

37. A method of treating a hepatic, or enzyme-deficiency disorder in a subject in need thereof, the method comprising transplanting hepatic tissue into the subject, said hepatic tissue being derived from a porcine liver being at a stage of development selected from 25 to 56 days of gestation.

38. The method of claims 37, wherein said porcine liver is at a stage of development selected from 26 to 56 days of gestation.

39. The method of claim 37, wherein said porcine liver is at a stage of development selected from 27 to 56 days of gestation.

40. The method of claim 37, wherein said porcine liver is at a stage of development selected from a range of 28 to 56 days of gestation.

41. The method of claim 37, wherein said porcine liver is at a stage of development selected from a range of 28 to 42 days of gestation.

42. The method of claim 37, said porcine liver is at a stage of development selected from a range of 27 to 29 days of gestation.

43. The method of claim 37, wherein said porcine liver is at a stage of development of 28 days of gestation.

44. The method of claim 37, further comprising treating the subject with an immunosuppressive regimen prior to, concomitantly with or following said transplanting said renal tissue into the subject, thereby promoting engraftment of said tissue in the subject.

45. The method of claim 44, wherein said treating the subject with an immunosuppressive regimen is effected by administering at least one immunosuppressant drug to the subject.

46. The method of claim 45, wherein said at least one immunosuppressant drug is capable of blocking binding of a lymphocyte coreceptor with a ligand of said lymphocyte coreceptor.

47. The method of claim 46, wherein said at least one immunosuppressant drug is capable. of blocking binding of a lymphocyte coreceptor with a ligand of said lymphocyte coreceptor, and wherein said administering said at least one immunosuppressant drug to the subject is effected during a time period selected from a range of 1 to 60 days.

48. The method of claim 46, wherein said lymphocyte coreceptor is selected from the group consisting of B7-1, CD40, and CD40L.

49. The method of claim 46, wherein said ligand of said lymphocyte coreceptor is selected fom the group consisting of B7-1, CD40, and CD40L.

50. The method of claim 45, wherein said at least one immunosuppressant drug comprises CTLA4-Ig.

51. The method of claim 45, wherein said at least one immunosuppressant drug comprises CTLA4-Ig and anti CD40L antibody.

52. The method of claim 45, wherein said. at least one immunosuppressant drug comprises CTLA4-Ig, anti-CD40L antibody and rapamycin.

53. The method of claim 37, wherein said transplanting said hepatic tissue into the subject is effected by transplanting said. hepatic tissue into an anatomical location of the subject selected from the group consisting of the portal vein, the liver, the renal capsule, the sub-cutis, the omentum, the spleen, and the intra-abdominal space.

54. The method of claim 37, wherein the subject is a mammal.

55. The method of claim 37, wherein said porcine liver is non-syngeneic with the subject.

56. The method of claim 37, wherein said porcine live is xenogeneic with the subjet.

57. A method of treating a hepatic or enzyme-deficienty disorder in a subject in need thereof, the method comprising planting hepatic tissue into the subject, said hepatic tissue being derived from a human liver being at a stage of development selected from a range of 6 to 14 weeks of gestation, thereby treating the hepatic or enzyme-deficiency disorder in the subject.

58. The method of claim 57, wherein said human liver is at a stage of development selected from a range of 6 to 12 weeks of gestation.

59. The method of claim 57, wherein said human liver is at a stage of development selected from a range of 6 to 10 weeks of gestation.

60. The method of claim 57, wherein said human liver is at a stage of development selected from a range of 6 to 9 weeks of gestation.

61. The method of claim 57, wherein said human liver is at a stage of development selected from a range of 6 to 1 weeks of gestation.

62. The method of claim 57, wherein said human liver is at a stage of development of 7 weeks of gestation.

63. The method of claim 57, further comprising treating the subject with an immunosuppressive regimen prior to, concomitantly with or following said transplanting said renal tissue into the subject, thereby promoting engraftment of said tissue in the subject.

64. The method of claim 63, wherein said treating the subject with an immunosuppressive regimen is effected by administering at least one immunosuppressant drug to the subject.

65. The method of claim 64, wherein said at least one immunosuppressant drug is capable of blooking binding of a lymphocyte coreceptor with a ligand of said lymphocyte coreceptor.

66. The method of claim 65, wherein said at least one immunosuppressant drug is capable of blocking binding of a lymphocyte coreceptor with a ligand of said lymphocyte coreceptor, and wherein said administering said at least one immunosuppressant drug to the subject is effected during a time period selected from a range of 1 to 60 days.

67. The method of claim 65, wherein said lymphocyte coreceptor is selected from the group consisting of B7-1, CD40, and CD40L.

68. The method of claim 65, wherein said ligand of said lymphocyte coreceptor is selected from the group consisting of B7-1, CD40, and CD40L.

69. The method of claim 64, wherein said at least one immunosuppressant drug comprises CTLA4-Ig.

70. The method of claim 64, wherein said at least one immunosuppressant drug comprises CTLA4-Ig and anti-CD40L antibody.

71. The method of claim 64, wherein said least one immunosuppressant drug comprises CTLA4-Ig, anti-CD40L antibody and rapamycin.

72. The method of claim 57, wherein said transplanting said hepatic tissue into the subject is effected by transplanting said hepatic tissue into an anatomical location of the subject selected from the group consisting of the portal vein, the liver, the renal capsule, the sub-cutis, the omentum, the spleen, and the intra-abdominal space.

73. The method of claim 57, wherein the subject is a mammal.

74. The method of claim 57, wherein said human liver is non-syngeneic with the subject.

75. The method of claim 57, wherein said human liver is allogenic with the subject.

76-97. -97. (canceled)