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

• US 7,445,802 B2
• Filed: 12/26/2001
• Issued: 11/04/2008
• Est. Priority Date: 12/26/2000
• Status: Expired due to Fees

• 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
• Primary Examiner(s): Helms; Larry
• Assistant Examiner(s): Goddard; Laura B
• Application Number:
  US10/451,849
• Publication Number:
  US 20040115183A1
• Time in Patent Office: 2,505 Days
• Field of Search: 530/387.1, 514/2
• US Class Current: 424/754
• 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 alliinase, in an enzymatically active form, with an antibody, wherein said conjugate binds to a cell or to a microorganism of interest in the body of a mammal.

2. A conjugate according to claim 1, wherein the alliinase is recombinant.

3. A conjugate according to claim 1, wherein the alliinase is onion or garlic alliinase.

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

5. A conjugate according to claim 1, wherein the antibody is a cell- or tissue-specific monoclonal antibody or an antigen-binding fraction thereof.

6. A conjugate according to claim 5, wherein said cell- or tissue-specific monoclonal antibody or antigen-binding fraction thereof recognizes a specific receptor on the cell surface.

7. A conjugate according to claim 6, wherein said monoclonal antibody is of human or animal origin.

8. A conjugate according to claim 6, wherein said monoclonal antibody is a recombinant or humanized antibody.

9. A conjugate according to claim 5, wherein said antibody comprises an antigen-binding fraction of a cell- or tissue-specific monoclonal antibody, said fraction being a F(ab)₂ dimer, F(ab) monomer, FV, or a single chain.

10. A conjugate according to claim 5, wherein said monoclonal antibody or antigen-binding fraction thereof recognizes a specific antigen on the surface of cancer cells.

11. A conjugate according to claim 10, wherein said monoclonal antibody recognizes the ErbB-2 receptor on the surface of cancer cells.

12. A conjugate according to claim 1, wherein the alliinase is pegylated.

13. A pharmaceutical composition comprising a conjugate according to claim 1 and a pharmaceutically acceptable carrier.

14. A pharmaceutical kit comprising, in separate compartments, a pharmaceutical composition according to claim 13 and a composition of alliin.

15. A kit in accordance with claim 14, further including instructions for administration of the two compositions.

16. A method for killing or inhibiting the growth of mammalian cells that express a cell-type specific protein or cancer antigen, comprising administering a conjugate of alliinase and an antibody that binds to said cell-type specific protein or cancer antigen, followed by administration of alliin, whereby the alliinase of the conjugate converts alliin to allicin and the allicin kills the cells or inhibits cell growth.

17. A method according to claim 16, wherein the mammalian cells are cancer cells.