Compositions and methods for therapeutic use

• US 20030211598A1
• Filed: 06/03/2003
• Published: 11/13/2003
• Est. Priority Date: 01/08/1996
• Status: Abandoned Application

• Current Assignee: Canji Inc. (Merck & Co., Inc.)
• Original Assignee: Canji Inc. (Merck & Co., Inc.)
• Inventors: Shabram, Paul, Maneval, Daniel C., Engler, Heidrun, Huyghe, Bernard G.
• Application Number:
  US10/454,662
• Publication Number:
  US 20030211598A1
• Time in Patent Office: Days
• US Class Current: 435/320.1
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/186 Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/4736 Retinoblastoma protein
• CPC Class Codes: C07K 14/4746 p53
• CPC Class Codes: C12N 15/87 Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
• CPC Class Codes: C12N 2799/022 where the vector is derived from an adenovirus

Abstract

A method and pharmaceutical composition for the treatment of cancer using a gene delivery system, such as a viral vector delivery system, comprising a therapeutic gene such as p53 or a retinoblastoma tumor suppressor gene wherein the gene delivery system is formulated in a buffer comprising a delivery-enhancing agent such as ethanol or a detergent.

Claims

1. A method of administering a therapeutic agent to a tissue having an epithelial membrane, comprising administering a therapeutically effective amount of the therapeutic agent formulated in a buffer comprising a detergent.

2. The method of claim 1, wherein the therapeutic agent is a protein.

3. The method of claim 1, wherein the therapeutic agent is a nucleic acid.

4. The method of claim 3, wherein the nucleic acid is a tumor suppressor gene.

5. The method of claim 1, wherein the detergent is Big CHAP.

6. The method of claim 1, wherein the detergent is TRITON®

X-100.

7. The method of claim 1, wherein the therapeutic agent is a tumor suppressor gene.

8. The method of claim 7, wherein the tumor suppressor gene is p53.

9. The method of claim 7, wherein the tumor suppressor gene is a retinoblastoma gene.

10. The method of claim 1, wherein the concentration of the detergent is about 0.5-2×

the critical micellization concentration.

11. A pharmaceutical composition comprising a therapeutically effective amount of a therapeutic agent formulated in a buffer comprising a detergent.

12. The pharmaceutical composition of claim 11, wherein the therapeutic agent is a protein.

13. The pharmaceutical composition of claim 11, wherein the therapeutic agent is a nucleic acid.

14. The pharmaceutical composition of claim 13, wherein the nucleic acid is a tumor suppressor gene.

15. The pharmaceutical composition of claim 14, wherein the tumor suppressor gene is p53.

16. The pharmaceutical composition of claim 14, wherein the tumor suppressor gene is a retinoblastoma gene.

17. The pharmaceutical composition of claim 11, wherein the detergent is Big CHAP.

18. The pharmaceutical composition of claim 11, wherein the detergent is TRITON®

X-100 detergent.

19. The pharmaceutical composition of claim 11, wherein the concentration of the detergent is about 0.5-2×

the critical micellization concentration.

20. A method of treating bladder cancer comprising administration of a therapeutically effective amount of a therapeutic gene contained within a gene delivery system that is formulated in a buffer comprising a delivery-enhancing agent.

21. The method of claim 20 wherein the gene delivery system is a viral vector delivery system.

22. The method of claim 20 wherein the gene delivery system is a recombinant adenoviral vector delivery system.

23. The method of claim 20 wherein the therapeutic gene is a tumor suppressor gene.

24. The method of claim 23 wherein the tumor suppressor gene is a retinoblastoma tumor suppressor gene.

25. The method of claim 23 wherein the tumor suppressor gene is p53.

26. The method of claim 20 wherein the delivery-enhancing agent is an alcohol.

27. The method of claim 26 wherein the alcohol is ethanol.

28. The method of claim 20 wherein the delivery-enhancing agent is a detergent.

29. The method of claim 28, wherein the detergent is Big CHAP.

30. The method of claim 28, wherein the detergent is TRITON®

X-100.

31. The method of claim 20 wherein the administration is by intravesical administration.

32. The method of claim 20 wherein the therapeutically effective amount of a therapeutic gene contained within a gene delivery system is in the range of about from 1×

10⁸ particles/ml to 5×

10¹¹ particles/ml of a recombinant adenovirus in which the therapeutic gene is inserted.

33. The method of claim 20 wherein the therapeutically effective amount of a therapeutic gene contained within a gene delivery system is in the range of about from 1×

10⁹ particles/ml to 1×

10¹¹ particles/ml of a recombinant adenovirus in which the therapeutic gene is inserted.

34. The method of claim 24 wherein the retinoblastoma tumor suppressor gene encodes full length RB protein.

35. The method of claim 24 wherein the retinoblastoma tumor suppressor gene encodes p56^RB.

36. The method of claim 22 wherein the delivery-enhancing agent is administered prior to administration of the recombinant viral vector delivery system comprising the therapeutic gene.

37. The method of claim 22 wherein the delivery-enhancing agent is administered with the recombinant viral vector delivery system comprising the therapeutic gene.

38. The method of claim 28 wherein the concentration of the detergent is 0.5-2×

the critical micellization concentration.

39. A pharmaceutical formulation for administration of a recombinant adenovirus, comprising about 10⁹-10¹¹ PN/ml recombinant adenovirus, about 2-10 mM Big CHAP or about 0.1-1.0 mM TRITON®

-X-100 detergent, phosphate buffered saline (PBS), about 2-3% sucrose (w/v) and about 1-3 mM MgCl₂, about pH 6.4-8.4.