Serpin drugs for treatment of HIV infection and method of use thereof

• US 20050058637A1
• Filed: 07/15/2004
• Published: 03/17/2005
• Est. Priority Date: 01/26/2001
• Status: Active Grant

• Current Assignee: Bruce D. Walker, Ralf Geiben Lynn
• Original Assignee: Bruce D. Walker, Ralf Geiben Lynn
• Inventors: Lynn, Ralf Geiben, Walker, Bruce D.
• Granted Patent: US 7,510,828 B2
• Time in Patent Office: Days
• US Class Current: 424/94.640
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/4873 Cysteine endopeptidases (3.4.22), e.g. stem bromelain, papain, ficin, cathepsin H
• CPC Class Codes: C07K 14/8121 Serpins

Abstract

The invention includes compositions comprising substantially purified serpin that are useful in methods for the treatment and prevention of HIV infection. The invention also includes methods for the treatment and prevention of HIV infection comprising contacting a composition of the invention with a human patient or treating HIV infection by introducing into a cell susceptible to HIV infection a DNA molecule encoding a serpin. Additionally, the invention includes antibodies and kits useful in the detection, treatment, and prevention of HIV infection.

Claims

1. A method of inhibiting the infectivity of HIV, said method comprising the steps of:

(a) contacting an HIV virion with an antithrombin selected from the group consisting of 43 kDa modified antithrombin, R-antithrombin, S-antithrombin, pre-latent antithrombin, and combinations thereof; and

(b) incubating said virion with said antithrombin for a period of time sufficient to inhibit the infectivity of HIV.

2. The method of claim 1, wherein said antithrombin is bovine-originated or human-originated.

3. The method of claim 1, wherein said antithrombin is 43 kDa modified antithrombin.

4. The method of claim 1, wherein said antithrombin is R-antithrombin.

5. The method of claim 1, wherein said antithrombin is S-antithrombin.

6. The method of claim 1, wherein said antithrombin is pre-latent antithrombin.

7. A method of decreasing the infectivity of HIV, if any is present, in a biological sample, the method comprising the steps of:

(a) identifying a biological sample in which a decrease or elimination of HIV infectivity is desirable; and

(b) contacting the biological sample with an amount of an antithrombin selected from the group consisting of 43 kDa modified antithrombin, R-antithrombin, S-antithrombin, pre-latent antithrombin, a variant thereof, and combinations thereof, sufficient to decrease the infectivity of HIV in the biological sample.

8. The method of claim 7, wherein said biological sample is selected from a group consisting of blood, plasma, serum, saliva, semen, cervical secretions, urine, breast milk, and amniotic fluids.

9. The method of claim 7, wherein said antithrombin is bovine-originated or human-originated.

10. The method of claim 7, wherein said antithrombin is 43 kDa modified antithrombin.

11. The method of claim 7, wherein said antithrombin is R-antithrombin.

12. The method of claim 7, wherein said antithrombin is S-antithrombin.

13. The method of claim 7, wherein said antithrombin is pre-latent antithrombin.

14. The method of claim 7, wherein the amount of said antithrombin is at least about 2 units per milliliter of the biological sample volume.

15. The method of claim 7, wherein the amount of said antithrombin is at least about 5 units per milliliter of the biological sample volume.

16. The method of claim 7, wherein the amount of said antithrombin is at least about 10 units per milliliter of the biological sample volume.

17. A method of treating HIV infection, the method comprising introducing into a cell susceptible to HIV infection a DNA molecule encoding an antithrombin, expressing said antithrombin selected from the group consisting of 43 kDa modified antithrombin, R-antithrombin, S-antithrombin, pre-latent antithrombin, and combinations thereof, and in an amount sufficient to inhibit infection of the cell by the HIV.

18. The method of claim 17, wherein said DNA encodes an antithrombin that is bovine-originated or human-originated.

19. The method of claim 17, wherein said antithrombin is 43 kDa modified antithrombin.

20. The method of claim 17, wherein said antithrombin is R-antithrombin.

21. The method of claim 17, wherein said antithrombin is S-antithrombin.

22. The method of claim 17, wherein said antithrombin is pre-latent antithrombin.

24. A method of treating HIV infection in a subject, the method comprising introducing into the subject a producer cell that expresses an antithrombin selected from the group consisting of 43 kDa modified antithrombin, R-antithrombin, S-antithrombin, pre-latent antithrombin, and combinations thereof, in an amount sufficient to inhibit infection of an endogenous cell of the subject, the endogenous cell being susceptible to HIV infection.

25. The method of claim 24, wherein said antithrombin is bovine-originated or human-originated.

26. The method of claim 24, wherein said antithrombin is 43 kDa modified antithrombin.

27. The method of claim 24, wherein said antithrombin is R-antithrombin.

28. The method of claim 24, wherein said antithrombin is S-antithrombin.

29. The method of claim 24, wherein said antithrombin is pre-latent antithrombin.

30. A method of inhibiting the infectivity of HIV, said method comprising the steps of:

(a) contacting an HIV virion with a composition having a surface which comprises an antithrombin selected from the group consisting of 43 kDa modified antithrombin, R-antithrombin, S-antithrombin, pre-latent antithrombin, and combinations thereof, associated with said surface; and

(b) incubating said HIV virion with said antithrombin for a period of time sufficient to inhibit the infectivity of HIV.

31. The method of claim 30, wherein said antithrombin is bovine-originated or human-originated.

32. The method of claim 30, wherein said antithrombin is 43 kDa modified antithrombin.

33. The method of claim 30, wherein said antithrombin is R-antithrombin.

34. The method of claim 30, wherein said antithrombin is S-antithrombin.

35. The method of claim 30, wherein said antithrombin is pre-latent antithrombin.

36. A method of inhibiting the infectivity of HIV, said method comprising the steps of:

(a) contacting an HIV virion with antithrombin III bound to heparin; and

(b) incubating said virion with said antithrombin for a period of time sufficient to inhibit the infectivity of HIV.