Methods and formulations for targeting infectious agents bearing host cell proteins

• US 7,357,930 B1
• Filed: 05/03/2000
• Issued: 04/15/2008
• Est. Priority Date: 05/03/1999
• Status: Expired due to Fees

• Current Assignee: Infectio Recherche Inc.
• Original Assignee: Infectio Recherche Inc.
• Inventors: Tremblay, Michel J., Desormeaux, Andre, Bergeron, Michel G.
• Primary Examiner(s): Chan; Christina
• Assistant Examiner(s): HUYNH, PHUONG N
• Application Number:
  US09/980,516
• Time in Patent Office: 2,904 Days
• Field of Search: 424/450, 424/9.321, 424/9.34, 424/9.51, 424/178.1, 514/394, 514/934, 514/45, 514/49, 514/50
• US Class Current: 424/178.1
• CPC Class Codes: A61K 47/6913 the liposome being modified on its surface by an antibody
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

A formulation is disclosed for the treatment of diseases caused by an infectious agent which acquires host membranes protein during its life cycle. The formulation is a targeting pharmaceutical composition. It comprises a ligand capable of binding the host membrane proteins coupled to a lipid-comprising vesicle, which may comprise or not a drug effective in the treatment of the disease. Specific liposomes bearing anti-HLA-DR or anti-CD4 antibodies comprising or not antiviral drugs, namely anti-HIV drugs, are disclosed and claimed. A method of formulation as well as a method of using the formulation in the treatment of a disease are also disclosed.

Claims

1. A formulation which comprises an anti-HLA-DR antibody molecule coupled to a liposome, said antibody molecule being selected from the group consisting of a whole antibody and an antigen binding fragment thereof, said formulation capable of binding to an HLA-DR protein present at both the surface of an infectious agent and at the membrane surface of a cell, wherein said liposome comprises a mixture of dipalmitoylphosphatidylcholine:

dipalmitoylphosphatidylglycerol;

dipalmitoylphosphatidylethanolamine-polyethyleneglycol in a molar ratio of 10;

3;

0.33 or dipalmitoylphosphatidylcholine;

dipalmitoylphosphatidylglycerol;

distearoylphosphatidylethanolamine-polyethyleneglycol in a molar ratio of 10;

3;

0.83.

2. The formulation according to claim 1, further comprising an additional antibody molecule to one or more proteins selected from the group consisting of a histocompatibility complex protein, a membrane ATPase, thy-1, an interleukin receptor, annexin II, CD3 (T3), CD4 (T4), CD5 (Ti), CD6 (T12), CD8 (T8), CD11a (LFA-1), CD11b (Mac-1), CD11c (gp150,95), CD1 (Lewis X), CD18, CD19, CD25 (Tac), CD30 (Ki-1), CD43 (leukosialin, sialophorin), CD44 (Pgp-1), CD48 (Blast-1), CD54 (ICAM-1), CD55 (DAF), CD59 (protectin, Mac inhibitor), CD63, CD71 (transferrin receptor), CDw108 (GR2), cyclophilin A, cytoskeletal proteins and β

2-microglobulin.

3. The formulation according to claim 1, which further comprises a drug encapsulated within the liposome, said drug effective against a disease or against the symptoms of a disease caused by said infectious agent.

4. The formulation according to claim 1, wherein said HLA-DR protein is present at the membrane surface of a lymphoid cell or a cell of the reticuloendothelial system.

5. The formulation according to claim 3, wherein said HLA-DR protein is present at the membrane surface of a lymphoid cell or a cell of the reticuloendothelial system.

6. The formulation according to claim 4, wherein said HLA-DR protein is acquired by HIV.

7. The formulation according to claim 5, wherein said HLA-DR protein is acquired by HIV.

8. The formulation according to claim 4, further comprising an additional antibody molecule to one or more of CD4, MHC-I and CD54 proteins.

9. The formulation according to claim 5, further comprising an additional antibody molecule to one or more of CD4, MHC-I and CD54 proteins.

10. The formulation according to claim 3, wherein said drug is selected from AZT, ddI, ddC, 3TC, indinavir, saquinavir, ritonavir, nelfinavir, ganciclovir, foscarnet, ribavirin, amphotericin B and nystatin A.

11. The formulation according to claim 1, wherein said antibody molecule is an anti-Fab′

antibody fragment directed against a HLA-DR protein.

12. The formulation according to claim 1, wherein said infectious agent is HIV.

13. The formulation according to claim 2, which further comprises a drug encapsulated within the liposome, said drug effective against a disease or against symptoms of a disease caused by said infectious agent.

14. The formulation according to claim 13, wherein said drug is selected from AZT, ddI, ddC, 3TC, indinavir, saquinavir, ritonavir, nelfinavir, ganciclovir, foscarnet, ribavirin, amphotericin B and nystatin A.

15. A formulation which comprises an anti HLA-DR antibody molecule coupled to a liposome, said antibody molecule being selected from the group consisting of a whole antibody and an antigen binding fragment thereof, and the liposome containing a drug, said formulation capable of binding to an HLA-DR protein present at both the surface of an infectious agent and at the membrane surface of a cell and of delivering said drug to said cell and infectious agent, wherein said liposome comprises a mixture of dipalmitoylphosphatidylcholine:

dipalmitoylphosphatidylglycerol;

dipalmitoylphosphatidylethanolamine-polyethyleneglycol in a molar ratio of 10;

3;

0.33 or dipalmitoylphosphatidylcholine;

dipalmitoylphosphatidylglycerol;

distearoylphosphatidylethanolamine-polyethyleneglycol in a molar ratio of 10;

3;

0.83.

16. The formulation of claim 15, wherein said infectious agent is HIV.