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Last Updated: April 26, 2024

Claims for Patent: 8,591,890


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Summary for Patent: 8,591,890
Title:Using heat shock proteins to improve the therapeutic benefit of a non-vaccine treatment modality
Abstract: The present invention relates to methods of improving a treatment outcome comprising administering a heat shock protein (HSP) preparation or an .alpha.-2-macroglobulin (.alpha.2M) preparation with a non-vaccine treatment modality. In particular, an HSP preparation or an .alpha.2M preparation is administered in conjunction with a non-vaccine treatment modality for the treatment of cancer or infectious diseases. In the practice of the invention, a preparation comprising HSPs such as but not limited to, hsp70, hsp90 and gp96 alone or in combination with each other, noncovalently or covalently bound to antigenic molecules or .alpha.2M, noncovalently or covalently bound to antigenic molecules is administered in conjunction with a non-vaccine treatment modality.
Inventor(s): Srivastava; Pramod K. (Avon, CT), Li; Zihai (Mount Pleasant, SC)
Assignee: University of Connecticut Health Center (N/A)
Application Number:13/250,141
Patent Claims:1. A method of treating a cancer in a subject in need thereof comprising: administering to the subject a purified heat shock protein preparation comprising a heat shock protein-peptide complex comprising a heat shock protein covalently or noncovalently attached to an antigenic peptide, wherein the antigenic peptide displays antigenicity of an antigen of the cancer, and wherein the subject has been administered Bevacizumab to treat the cancer.

2. The method of claim 1, wherein the purified heat shock protein preparation comprises heat shock protein-peptide complexes that comprise one or more of hsp70, hsp90, hsp110, gp96, grp170, and calreticulin.

3. The method of claim 2, wherein the purified heat shock protein preparation comprises heat shock protein-peptide complexes that comprise gp96.

4. The method of claim 1, wherein the subject receives further administrations of Bevacizumab and the purified heat shock protein preparation, wherein the administrations are repeated for up to 12 cycles.

5. The method of claim 1, comprising administering the purified heat shock protein preparation once a week for the first 4 weeks.

6. The method of claim 5, comprising administering the purified heat shock protein once every other week after the first 4 weeks of administration.

7. The method of claim 1, wherein the purified heat shock protein preparation and the Bevacizumab are administered 2 to 4 days apart, 4 to 6 days apart, 1 week apart, 1 to 2 weeks apart, or 2 to 4 weeks apart.

8. The method of claim 1, which further comprises the step of administering to the subject radiation therapy.

9. The method of claim 1, wherein the purified heat shock protein preparation is administered for a first period of time, followed by administration of Bevacizumab for a second period of time, wherein this sequential administration is repeated.

10. The method of claim 1, wherein the Bevacizumab is administered prior to an initial administration of the purified heat shock protein preparation.

11. The method of claim 1, wherein Bevacizumab is administered concurrently with the administration of the purified heat shock protein preparation.

12. The method of claim 1, wherein the Bevacizumab is administered subsequent to an initial administration of the purified heat shock protein preparation.

13. The method of claim 1, wherein the purified heat shock protein preparation is cyclically administered with Bevacizumab.

14. The method of claim 1, wherein the purified heat shock protein preparation is autologous to the subject.

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

16. The method of claim 15, wherein the purified heat shock protein preparation comprises heat shock protein-peptide complexes isolated from cells of the cancer of the subject.

17. The method of claim 1, wherein the purified heat shock protein preparation comprises heat shock protein-peptide complexes comprising heat shock proteins non-covalently attached to antigenic peptides.

18. The method of claim 1, wherein the purified heat shock protein preparation comprises heat shock protein-peptide complexes isolated from cells of the cancer.

19. The method of claim 1, wherein the antigenic peptide displays antigenicity of a tumor-specific antigen or a tumor-associated antigen of the cancer in the subject.

20. The method of claim 1, wherein the cancer is a relapse form of cancer.

21. The method of claim 12, wherein the subsequent Bevacizumab administration is administered no more than 24 hours after the initial administration of the purified heat shock protein preparation.

22. The method of claim 1, wherein the purified heat shock protein preparation is administered intradermally.

23. The method of claim 22, wherein the Bevacizumab is administered intravenously.

24. A method of treating a cancer in a subject in need thereof, wherein the subject is a candidate for receiving Bevacizumab to treat the cancer, comprising: (a) administering to the subject Bevacizumab; and (b) administering to the subject a purified heat shock protein preparation comprising a heat shock protein-peptide complex comprising a heat shock protein covalently or noncovalently attached to an antigenic peptide, wherein the antigenic peptide displays antigenicity of an antigen of the cancer.

25. The method of claim 24, wherein the purified heat shock protein preparation comprises heat shock protein-peptide complexes that comprise one or more of hsp70, hsp90, hsp110, gp96, grp170, and calreticulin.

26. The method of claim 25, wherein the purified heat shock protein preparation comprises heat shock protein-peptide complexes that comprise gp96.

27. The method of claim 24, wherein steps (a) and (b) are repeated for 1 to 12 cycles.

28. The method of claim 24, comprising administering the purified heat shock protein preparation once a week for the first 4 weeks.

29. The method of claim 28, comprising administering the purified heat shock protein once every other week after the first 4 weeks of administration.

30. The method of claim 24, wherein the purified heat shock protein preparation and the Bevacizumab are administered 2 to 4 days apart, 4 to 6 days apart, 1 week apart, 1 to 2 weeks apart, or 2 to 4 weeks apart.

31. The method of claim 24, which further comprises the step of administering to the subject radiation therapy.

32. The method of claim 24, comprising administering the purified heat shock protein preparation for a first period of time, followed by administering the Bevacizumab for a second period of time, and repeating this sequential administration.

33. The method of claim 24, wherein the Bevacizumab is administered prior to an initial administration of the purified heat shock protein preparation.

34. The method of claim 24, wherein the Bevacizumab is administered concurrently with the administration of the purified heat shock protein preparation.

35. The method of claim 24, wherein the Bevacizumab is administered subsequent to an initial administration of the purified heat shock protein preparation.

36. The method of claim 24, wherein the Bevacizumab and the purified heat shock protein preparation are cyclically administered.

37. The method of claim 24, wherein the purified heat shock protein preparation is autologous to the subject.

38. The method of claim 24, wherein the subject is human.

39. The method of claim 38, wherein the purified heat shock protein preparation comprises heat shock protein-peptide complexes isolated from cells of the cancer of the subject.

40. The method of claim 24, wherein the purified heat shock protein preparation comprises heat shock protein-peptide complexes comprising heat shock proteins non-covalently attached to antigenic peptides.

41. The method of claim 24, wherein the purified heat shock protein preparation comprises heat shock protein-peptide complexes isolated from cells of the cancer.

42. The method of claim 24, wherein the antigenic peptide displays antigenicity of a tumor-specific antigen or a tumor-associated antigen of the cancer in the subject.

43. The method of claim 24, wherein the cancer is a relapse form of cancer.

44. The method of claim 24, wherein the Bevacizumab is administered no more than 24 hours after the purified heat shock protein preparation.

45. The method of claim 24, wherein the purified heat shock protein preparation is administered intradermally.

46. The method of claim 45, wherein the Bevacizumab is administered intravenously.

47. A method of treating a cancer in a subject in need thereof, the method comprising: administering to the subject a purified heat shock protein preparation comprising a heat shock protein-peptide complex comprising a heat shock protein covalently or noncovalently attached to an antigenic peptide, wherein the antigenic peptide displays antigenicity of an antigen of the cancer, wherein the subject is a candidate for receiving Bevacizumab to treat the cancer and wherein the subject is administered Bevacizumab within 2 weeks or one month from being administered the purified heat shock protein preparation.

48. The method of claim 47, wherein the Bevacizumab is administered subsequent to the administration of the purified heat shock protein preparation.

49. The method of claim 47, wherein the Bevacizumab is administered prior to the administration of the purified heat shock protein preparation.

50. The method of claim 48, wherein the cancer is a relapse form of cancer.

51. The method of claim 49, wherein the cancer is a relapse form of cancer.

52. The method of claim 47, wherein the purified heat shock protein preparation comprises heat shock protein-peptide complexes that comprise gp96.

53. The method of claim 47, wherein the purified heat shock protein preparation is autologous to the subject.

54. The method of claim 47, wherein the subject is human.

55. The method of claim 47, wherein the purified heat shock protein preparation comprises heat shock protein-peptide complexes comprising heat shock proteins non-covalently attached to antigenic peptides.

56. The method of claim 47, wherein the antigenic peptide displays antigenicity of a tumor-specific antigen or a tumor-associated antigen of the cancer in the subject.

57. The method of claim 47, wherein the subject is administered Bevacizumab no more than 24 hours after the purified heat shock protein preparation.

58. The method of claim 47, wherein the purified heat shock protein preparation is administered intradermally.

59. The method of claim 58, wherein the Bevacizumab is administered intravenously.

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