Liposomes comprising duramycin and anti-viral agents

• US 7,976,868 B2
• Filed: 03/04/2010
• Issued: 07/12/2011
• Est. Priority Date: 07/15/2002
• Status: Expired due to Fees

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Thorpe, Philip E.
• Primary Examiner(s): Goddard; Laura B
• Application Number:
  US12/717,295
• Publication Number:
  US 20100310638A1
• Time in Patent Office: 495 Days
• Field of Search: None
• US Class Current: 424/450
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 47/62 the modifying agent being a protein, peptide or polyamino acid
• CPC Class Codes: A61K 47/6811 the drug being a protein or peptide, e.g. transferrin or bleomycin
• CPC Class Codes: A61K 47/6835 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/2836 against CD106
• CPC Class Codes: C07K 16/44 against material not provided for elsewhere , e.g. haptens, metals, DNA, RNA, amino acids
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/77 Internalization into the cell

Abstract

Disclosed are surprising discoveries concerning the role of anionic phospholipids and aminophospholipids in tumor vasculature and in viral entry and spread, and compositions and methods for utilizing these findings in the treatment of cancer and viral infections. Also disclosed are advantageous antibody, immunoconjugate and duramycin-based compositions and combinations that bind and inhibit anionic phospholipids and aminophospholipids, for use in the safe and effective treatment of cancer, viral infections and related diseases.

Claims

1. A composition comprising a liposome or nanoparticle operatively associated with a targeting agent and at least a first anti-viral agent;

wherein said targeting agent is a duramycin peptide that binds to phosphatidylethanolamine.

2. The composition of claim 1, wherein said composition is a pharmaceutically acceptable composition.

3. A composition comprising a liposome or nanoparticle operatively associated with a duramycin peptide and at least a first anti-viral agent;

wherein said duramycin peptide binds to phosphatidylethanolamine at the cell surface of virally infected cells and delivers said anti-viral agent to said virally infected cells.

4. The composition of claim 3, wherein said composition comprises said liposome.

5. The composition of claim 4, wherein said liposome is a stealthed liposome.

6. The composition of claim 3, wherein said composition comprises said nanoparticle.

7. The composition of claim 3, wherein said liposome or nanoparticle comprises an outer membrane and a central core and wherein said outer membrane is coated with said duramycin peptide.

8. The composition of claim 3, wherein said liposome or nanoparticle comprises an outer membrane and a central core and wherein said at least a first anti-viral agent is maintained within said central core.

9. The composition of claim 3, wherein said liposome or nanoparticle comprises an outer membrane and a central core;

wherein said outer membrane is coated with said duramycin peptide and wherein said at least a first anti-viral agent is maintained within said central core.

10. The composition of claim 3, wherein said duramycin peptide is operatively attached to albumin.

11. The composition of claim 3, wherein said at least a first anti-viral agent is a nucleoside, a nucleoside reverse transcriptase inhibitor, a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor.

12. The composition of claim 3, wherein said at least a first anti-viral agent is ribavirin.

13. The composition of claim 3, wherein said composition is a pharmaceutically acceptable composition formulated for administration as an aerosol.