Site-specific in situ generation of allicin using a targeted alliinase delivery system for the treatment of cancers, tumors, infectious diseases and other allicin-senstive diseases

• US 20040115183A1
• Filed: 12/31/2003
• Published: 06/17/2004
• Est. Priority Date: 12/26/2000
• 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: Rabinkov, Aharon, Mirelman, David, Wilchek, Meir, Miron, Talia
• Granted Patent: US 7,445,802 B2
• Time in Patent Office: Days
• US Class Current: 424/94.4
• CPC Class Codes: A61K 38/51 Lyases (4)
• CPC Class Codes: A61K 47/6815 Enzymes
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C12N 9/88 Lyases (4.)

Abstract

Conjugates of the enzyme alliinase with a protein carrier that targets the alliinase to specific cells are used in combination with alliin to produce allicin at a desired target site. The enzyme converts alliin to allicin at the target site to kill cancer cells or pathogens.

Claims

1. A conjugate of the enzyme alliinase in an enzymatically active form with a targeting carrier that guides the enzyme to a cell or to a microorganism of interest in the body.

2. A conjugate according to claim 1, wherein the alliinase is a natural or recombinant alliinase or alliinase-like enzyme, a part thereof or a derivative thereof capable of exhibiting catalytic activity and ability to generate allicin or analogs thereof in a lyase reaction from alliin substrates or analogs thereof.

3. A conjugate according to claim 1 or 2, wherein the alliinase is a natural alliinase.

4. A conjugate according to claim 3, wherein the alliinase is onion or garlic alliinase.

5. A conjugate according to claim 4, wherein the alliinase is garlic alliinase.

6. A conjugate according to any one of claims 1 to 5, wherein the carrier is a cell- or tissue-specific monoclonal antibody or a derivative thereof.

7. A conjugate according to claim 6, wherein said cell- or tissue-specific monoclonal antibody or derivative thereof recognizes specific receptors on the cell surface.

8. A conjugate according to claim 7, wherein said monoclonal antibody is a natural antibody of human or animal origin.

9. A conjugate according to claim 7, wherein said monoclonal antibody is a recombinant or humanized antibody.

10. A conjugate according to claim 6, wherein said derivative of said monoclonal antibody is a F(ab)₂ dimer, F(ab) monomer, Fv or a single chain natural or recombinant Fv.

11. A conjugate according to any one of claims 1 to 5, wherein the carrier is a lectin, a carbohydrate-binding protein, a hormone, or a ligand which has specific receptor binding properties on specific cells.

12. A conjugate according to any one of claims 1 to 5, wherein the carrier is a polymer with tropism to particular tissues and cells.

13. A conjugate according to claim 6, wherein said monoclonal antibody or derivative thereof recognizes specific antigens on the surface of cancer cells.

14. A conjugate according to claim 13, wherein said monoclonal antibody recognizes the ErbB-2 receptor on the surface of cancer cells.

15. A conjugate according to claim 14, wherein alliinase is conjugated to the monoclonal antibody designated N28 that recognizes the ErbB-2 receptor.

16. A conjugate according to claim 14, wherein alliinase is conjugated with the F(ab)₂ dimer or F(ab) monomer of the monoclonal antibody designated N28 that recognizes the ErbB-2 receptor.

17. A conjugate according to any one of claims 1 to 16, wherein the alliinase molecule is pegylated.

18. A pharmaceutical composition comprising a conjugate according to any one of claims 1 to 17 and a pharmaceutically acceptable carrier.

19. A pharmaceutical kit comprising, in separate compartments, a pharmaceutical composition according to claim 18 and a composition of alliin.

20. A kit in accordance with claim 19, further including instructions for administration of the two compositions.

21. A method for treating a disorder or disease treatable with allicin that comprises administering to an individual in need thereof a conjugate of the enzyme alliinase with a targeting carrier that targets the conjugate to a desired tissue or organ in the body followed by administration of alliin, whereby allicin is generated at said tissue or organ, thus exerting its biological activity.

22. A method according to claim 21 for the treatment of cancer, wherein the targeting carrier of the conjugate is related to a cancer antigen 22. A method according to claim 21 for the treatment of infectious diseases, wherein the targeting carrier of the conjugate is related to an infectious disease.