Extracorporeal affinity adsorption treatments which are aimed at the substantial removal of two or more compounds that are etiological in the pathogenesis of diseases in man provide effective therapeutic intervention means for these diseases. The methods are particularly suitable for the treatment of atherosclerosis, cancer, degenerative and autoimmune diseases. Extracorporeal chelation and immunotherapy for atherosclerosis, extracorporeal chelation treatment with on-line regeneration or replacement of chelant, extracorporeal immunotherapy with antibody fragments, and extracorporeal immunoadsorption utilizing antibodies bound to Protein A are also disclosed.

Claims

I claim:

1. An extracorporeal device including means for drawing fluid from a mammal, means in said device for exposing said fluid to a chelating agent which is chemically bound to a matrix in said device, and means for returning to the mammal 5 at least a fraction of said fluid.

2. The device of claim 1 wherein said fluid is blood

3. The device of claim 1 wherein said fluid is plasma

4. The device of claim 1 wherein said chelating agent binds oxidants in said fluid.

5. The device of claim 4 wherein at least one of said oxidants is a metal ion.

6. The device of claim 5 wherein said metal ion is chosen from the group consisting of iron and copper.

7. The device of claim 1 including at least one semipermeable membrane.

8. The device of claim 7 wherein the device is an affinity filtration device, the device including means for filtration of said treated fluid through said at least one semipermeable membrane.

9. The device of claim 8 including pump means to generate a pressure gradient across said at least one semipermeable membrane.

10. The device of claim 7 wherein the device is an affinity dialysis device which enables dialyzable constituents of the treated fluid to dialyze through said at least one semipermeable membrane.

11. The device of claim 7 in which both dialysis and filtration processes take place through said at least one semipermeable membrane in said device.

12. The device of claim 7 wherein the semipermeable membrane comprises a hollow fiber.

13. The device of claim 12 wherein the semipermeable membrane is composed of a plurality of hollow fibers.

14. An extracorporeal device, including means for drawing from a mammal a fluid, means in said device for exposing at least a portion of the fluid to at least a first and a second specific affinity binding means for chemically binding at least one chemical species in said fluid to the first binding means and for binding at least a second chemical species in said fluid to a second binding means, and means for returning to the mammal at least a fraction of said fluid.

15. The device of claim 15 including a semipermeable membrane for preventing the specific affinity adsorbents from entering the body of the mammal.

16. The device of claim 15 wherein said fluid is blood.

17. The device of claim 16 including means for attaching the device into the blood circulatory system of the mammal.

18. The device of claim 15 wherein said fluid is plasma.

19. The device of claim 14 including means for exposing the fluid simultaneously to the first specific affinity binding means and the second specific affinity binding means.

20. The device of claim 14 including means for exposing said fluid sequentially to the first specific affinity binding means and the second specific affinity binding means.

21. The device of claim 14 wherein at least the first specific affinity binding means is a chelant.

22. The device of 21 wherein at least the second specific affinity binding means binds immunologically.

23. The device of claim 21 wherein said chelant binds heavy metals.

24. The device of claim 21 wherein the other specific affinity binding means binds a species, chosen from the group consisting of cholesterol, LDL, oxidized LDL and antibodies to oxidized LDL.

25. The device of claim 21 wherein the second specific affinity binding means binds a chemical species chosen from the group consisting of autoantibodies and immune complexes.

26. The device of claim 14 wherein at least one of the specific affinity binding means binds immunologically.

27. The device of claim 26 wherein at least one of the specific affinity binding means is chosen from the group consisting of Protein A, Protein G, and Clq bound to anti-Clq antibody.

28. The device of claim 14 wherein at least the first said affinity binding means is a non-immunological chemical affinity adsorbent.

29. The device of claim 14 wherein one of said specific affinity binding means is an antibody to an anticancer drug or a fragment of such antibody.

30. The device of claim 14 wherein at least one of said specific affinity binding means binds to a moiety consisting of an anticancer drug and a targeting antibody chemically bound to said anticancer drug directly or through a spacer, said targeting antibody being an intact antibody or a fragment of an antibody.

31. The device of claim 30 in which said specific affinity binding means is an antibody specific to said drug in the drug-targeting antibody moiety or a fragment of such antibody.

32. The device of claim 30 wherein said specific affinity binding means is an antibody specific to the tumor or tissue targeting antibody of the drug targeting antibody moiety, or a fragment of such antibody.

33. The device of claim 30 wherein said specific affinity binding means is tumor antigen, or tissue antigen, or fetal antigen to which the targeting antibody is directed.

34. The device of claim 33 wherein said specific affinity binding means is human-alpha-fetoprotein.

35. The device of claim 29 wherein said drug is adriamycin.

36. The device of claim 30 wherein said drug in the anticancer drug targeting antibody moiety is adriamycin.

37. The device of claim 29 or 30 wherein said drug is radioactive.

38. An extracorporeal device, including means for drawing fluid from a mammal, means in said device for exposing said fluid to a specific affinity binding means, said binding means being chemically bound to a matrix in said device, said binding means being selected from the group consisting of an antibody to an anticancer drug constituent of a moiety consisting of an anticancer drug bound to a targeting antibody, an antibody specific to targeting antibody constituent of said moiety, a "mirror image" antibody to said anticancer drug, said "mirror image" antibody binding to said anticancer drug on a site of said anticancer drug which is different from the site on the anticancer drug to which the targeting antibody constituent of the targeting antibody-anticancer drug moiety is bound, an antibody to a radioactive antigen or radioactive hapten constituent of a radioactive species bound to a targeting antibody, or fragment of a targeting antibody, and an antibody specific to a fragment of the targeting antibody constituent of an anticancer drug-targeting antibody moiety.

39. The device of claim 38, wherein the specific affinity binding means is a fragment of an intact antibody.

40. The device of claim 38 wherein said fluid is blood.

41. The device of claim 38 wherein said fluid is plasma.

42. The device of claim 38 wherein said anticancer drug is Adriamycin.

43. The device of claim 38 wherein said anticancer drug is a radioactive compound.

44. The device in claim 38 wherein said antibody or said antibody-fragment specific affinity binding means in said device is bound to the matrix through a spacer.

45. An extracorporeal device including means for drawing fluid from a mammal, means in said device for exposing said fluid to a specific affinity binding means, said binding means comprising Protein G or Clq bound to anti-Clq antibody, means for returning to the mammal at least portion of said fluid, and means for preventing said specific affinity binding means from entering into the mammal.

46. An extracorporeal device including means for drawing fluid from a mammal, means in said device for exposing said fluid to at least one specific affinity binding means, means for returning at least a portion of said fluid to the mammal, and means preventing said specific affinity binding means from entering into the mammal, the specific affinity adsorbent being characterized by being composed of at least one fragment of at least one antibody.

47. The device of claim 46 wherein said fluid is blood.

48. The device of claim 46 wherein said fluid is plasma.

49. The device of claim 46 wherein said fragment is a fragment of an antibody specific to a group consisting of LDL, oxidized LDL, antibody to oxidized LDL, immune complex, human anti-IgG antibody (rheumatoid factor), a moiety composed of an anticancer drug bound to a targeting antibody, and a moiety composed of anticancer drug bound to a fragment of targeting antibody.

50. An extracorporeal device, including means for drawing fluid from a mammal, means in said device for exposing said fluid to an antibody specific to at least one antigen or hapten, said antibody being bound in said device by non-covalent chemical binding to a substance chosen from the group consisting of Protein A and Protein G through an Fc portion of said antibody, the Protein A or Protein G in said device being bound to a matrix in said device by covalent chemical binding, means in said device for preventing the matrix-bound antibody from entering the body of the mammal, means for returning to the mammal at least a fraction of said fluid and a semipermeable membrane in said device for preventing IgG in the fluid from reaching the Protein A or Protein G in said device.

51. The device of claim 50 further including pressure means in said device for enabling said mammal's fluid to filtrate through said semipermeable membrane.

52. The device of claim 50 wherein said fluid is blood.

53. The device of claim 50 including means for attaching the device into the blood circulatory system of the mammal.

54. The device of claim 50 wherein said fluid is plasma.

55. The device of claim 50 wherein said specific antibody is chosen from the group consisting of antibody to LDL, antibody to oxidized LDL, antibody to free cholesterol.

56. An affinity adsorption device comprising a vessel having an inlet and an outlet, a moiety in said vessel comprising an antibody bound to a species chosen from the group consisting of Protein A and Protein G, and semipermeable membrane means in said vessel for preventing said moiety from passing through said outlet.

57. An extracorporeal affinity adsorption device containing an affinity adsorbent comprising an antibody to at least one drug wherein said drug is a constituent of a targeting antibody-drug moiety and means for connecting the device into the circulatory system of a mammal.

58. The device of claim 57 wherein the affinity adsorbent antibody is a mirror image antibody which binds to a site on the drug different from the site to which the targeting antibody or the fragment of the targeting antibody part of the moiety is bound.

59. The device of claim 57 wherein the specific affinity adsorbent is a fragment of a complete antibody.

60. The device of claim 57 wherein the antibody is bound to a matrix.

61. The device of claim 59 wherein the antibody is bound to the matrix.

62. An extracorporeal affinity adsorption device that includes as an affinity adsorbent at least one chelant, means in said device to connect the device in a fluid circulatory system of a mammal to expose at least a portion of the fluid of the mammal to said chelant, and means for replacing or regenerating said chelant without removing said device from said fluid circulatory system.

63. An extracorporeal affinity adsorption device including a specific affinity binding means, the affinity binding means being an antibody to a radioactive antigen or radioactive hapten when said radioactive hapten or antigen is a constituent in a moiety comprising said radioactive hapten or radioactive antigen bound to a targeting antibody directed to a target site.

64. The device of claim 63 wherein the targeting antibody is a fragment of an intact targeting antibody.

65. The device of claim 64 wherein the targeting antibody fragment is produced by synthesis.

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