Compositions and methods comprising phosphatidylethanolamine-binding peptide derivatives

• US 8,653,034 B2
• Filed: 05/08/2008
• Issued: 02/18/2014
• 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., He, Jin
• Primary Examiner(s): Goddard, Laura B
• Application Number:
  US12/117,255
• Publication Number:
  US 20120164071A1
• Time in Patent Office: 2,112 Days
• Field of Search: None
• US Class Current: 514/19.3
• 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: A61K 49/00 Preparations for testing in vivo
• CPC Class Codes: A61K 49/14 Peptides, e.g. proteins
• CPC Class Codes: A61K 51/025 inorganic Tc complexes or compounds
• CPC Class Codes: A61K 51/08 Peptides, e.g. proteins , carriers being peptides, polyamino acids, proteins
• CPC Class Codes: A61K 51/088 conjugates with carriers being peptides, polyamino acids or proteins antibodies A61K51/10
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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 2/00 Peptides of undefined number of amino acids; Derivatives thereof
• 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
• CPC Class Codes: C07K 7/64 : Cyclic peptides containing only normal peptide links

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 method for treating an animal with cancer, comprising administering to said animal a pharmaceutical composition comprising a substantially cell-impermeant phosphatidylethanolamine (PE)-binding peptide, which comprises a PE-binding peptide operatively attached to a cell impermeant group, in an amount effective to treat cancer in said animal;

wherein said PE-binding peptide is a cinnamycin peptide or a duramycin peptide.

2. The method of claim 1, wherein said pharmaceutical composition is a liposome or nanoparticle composition.

3. The method of claim 1, wherein said PE-binding peptide is a cinnamycin peptide.

4. The method of claim 1, wherein said PE-binding peptide is a duramycin peptide.

5. The method of claim 1, wherein said PE-binding peptide is operatively attached to a group that has a positive charge at physiological pH.

6. The method of claim 1, wherein said PE-binding peptide is operatively attached to a group that has a negative charge at physiological pH.

7. The method of claim 1, wherein said PE-binding peptide is operatively attached to a sulfate, sulfonate, phosphate, carboxyl, phenolic, quaternary ammonium ion or amine group.

8. The method of claim 1, wherein said PE-binding peptide is operatively attached to biotin.

9. The method of claim 1, wherein said PE-binding peptide is operatively attached to a sugar, oligo- or polysaccharide, amino acid, peptide, polypeptide, protein or a polyalcohol group.

10. The method of claim 9, wherein said PE-binding peptide is operatively attached to an inert carrier protein.

11. The method of claim 10, wherein PE-binding peptide is operatively attached to neutravidin, streptavidin, albumin or an inert immunoglobulin carrier protein.

12. The method of claim 11, wherein PE-binding peptide is operatively attached to an inert human IgG carrier protein.

13. The method of claim 1, wherein said pharmaceutical composition is administered to said animal intravenously.

14. The method of claim 1, further comprising subjecting said animal to surgery.

15. The method of claim 1, further comprising subjecting said animal to radiotherapy.

16. The method of claim 1, wherein at least a second, distinct anti-cancer agent is administered to said animal.

17. The method of claim 16, wherein said at least a second, distinct anti-cancer agent is a chemotherapeutic agent, radiotherapeutic agent, cytokine or anti-angiogenic agent.

18. The method of claim 17, wherein said at least a second, distinct anti-cancer agent is a tyrosine kinase inhibitor, folic acid analog, anti-tubulin drug, topoisomerase inhibitor, taxane, combretastatin, antibiotic, platinum coordination complex or alkylating agent.

19. The method of claim 18, wherein said at least a second, distinct anti-cancer agent is docetaxel, paclitaxel, 5-fluorouracil, gemcitabine, irinotecan, cisplatin or carboplatin.

20. The method of claim 1, wherein said animal is a human patient.

21. A method for treating an animal with cancer, comprising administering to said animal a pharmaceutical composition comprising a substantially cell-impermeant PE-binding peptide in an amount effective to treat cancer in said animal;

wherein said substantially cell-impermeant PE-binding peptide comprises a cinnamycin peptide or a duramycin peptide operatively attached to a sulfate, sulfonate, phosphate, carboxyl, phenolic, quaternary ammonium ion, polyalcohol or amine group;

or to biotin, a sugar, an oligosaccharide, a polysaccharide, an amino acid, a peptide, a polypeptide, an inert carrier protein or an inert immunoglobulin carrier protein.

22. A method for treating an animal with cancer, comprising administering to said animal a pharmaceutical composition comprising a substantially cell-impermeant PE-binding peptide in an amount effective to treat cancer in said animal;

wherein said substantially cell-impermeant PE-binding peptide comprises a cinnamycin peptide or a duramycin peptide operatively attached to a sulfate or sulfonate group, or to biotin, neutravidin, streptavidin or an inert carrier protein.

23. A method for treating an animal with cancer, comprising administering to said animal a pharmaceutical composition comprising a substantially cell-impermeant PE-binding peptide in an amount effective to treat cancer in said animal;

wherein said substantially cell-impermeant PE-binding peptide comprises a cinnamycin peptide or a duramycin peptide operatively attached to biotin or an inert carrier protein.

24. The method of claim 23, wherein said inert carrier protein is an immunoglobulin carrier protein that does not impart a targeting function to said substantially cell-impermeant PE-binding peptide.

25. The method of claim 24, wherein said immunoglobulin carrier protein is a human IgG carrier protein that does not impart a targeting function to said substantially cell-impermeant PE-binding peptide.

26. A method for treating an animal with cancer, comprising administering to said animal a pharmaceutical composition comprising a substantially cell-impermeant PE-binding peptide in an amount effective to treat cancer in said animal;

wherein said substantially cell-impermeant PE-binding peptide is DLB, DIB, (DLB)₄NA, (DLB)₄NA-F, (DIM)_nHIgG, (DIM)_nHIgG-F, (DIM)_nHIgG-B, (DIB)₄NA, (DIB)₄NA-B, DS-1, DS-2, DS-3, DS-4, DS-5 or DC-1.

27. A method for treating an animal with cancer, comprising administering to said animal a pharmaceutical composition comprising a substantially cell-impermeant phosphatidylethanolamine (PE)-binding peptide, which comprises a PE-binding peptide covalently linked to a cell impermeant group, in an amount effective to treat cancer in said animal;

wherein said PE-binding peptide is a cinnamycin peptide or a duramycin peptide.

28. A method for treating an animal with cancer, comprising administering to said animal a pharmaceutical composition comprising a substantially cell-impermeant PE-binding peptide in an amount effective to treat cancer in said animal;

wherein said substantially cell-impermeant PE-binding peptide comprises a cinnamycin peptide or a duramycin peptide covalently linked to a sulfate, sulfonate, phosphate, carboxyl, phenolic, quaternary ammonium ion, polyalcohol or amine group;

or to biotin, a sugar, an oligosaccharide, a polysaccharide, an amino acid, a peptide, a polypeptide, an inert carrier protein or an inert immunoglobulin carrier protein.

29. A method for treating an animal with cancer, comprising administering to said animal a pharmaceutical composition comprising a substantially cell-impermeant PE-binding peptide in an amount effective to treat cancer in said animal;

wherein said substantially cell-impermeant PE-binding peptide comprises a cinnamycin peptide or a duramycin peptide covalently linked to a sulfate or sulfonate group, or to biotin, neutravidin, streptavidin or an inert carrier protein.