Energy-activated targeted cancer therapy

• US 20050196401A1
• Filed: 04/26/2005
• Published: 09/08/2005
• Est. Priority Date: 01/15/1999
• Status: Abandoned Application

• Current Assignee: Light Sciences Oncology, Inc.
• Original Assignee: Light Sciences Oncology, Inc.
• Inventors: Chen, James
• Application Number:
  US11/115,740
• Publication Number:
  US 20050196401A1
• Time in Patent Office: Days
• US Class Current: 424/155.1
• CPC Class Codes: A61K 41/0057 Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
• CPC Class Codes: A61K 41/0061 5-aminolevulinic acid-based PDT: 5-ALA-PDT involving porphyrins or precursors of protoporphyrins generated in vivo from 5-ALA
• CPC Class Codes: A61K 41/0071 PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
• CPC Class Codes: A61K 47/6817 Toxins
• 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 47/6867 the tumour determinant being from a cell of a blood cancer
• CPC Class Codes: A61N 5/062 Photodynamic therapy, i.e. excitation of an agent
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Abstract

The present invention is drawn to delivery systems for administering a therapy to a target tissue or target composition in a mammalian subject, using an ultrasonic energy-activated targeted agent. The claimed energy-activated targeted therapy is useful in the treatment of specifically selected target tissues, such as vascular endothelial tissue, the abnormal vascular walls of tumors, solid tumors of the head and neck, tumors of the gastrointestinal tract, tumors of the liver, tumors of the breast, tumors of the prostate, tumors of the lung, nonsolid tumors, malignant cells of the hematopoietic and lymphoid tissue and other lesions in the vascular system or bone marrow, and tissue or cells related to autoimmune and inflammatory disease.

Claims

1. An ultrasonic energy-activated targeted delivery system that is selectively targeted to a target tissue, comprising:

(a) an ultrasonic energy-activated agent that absorbs energy and destroys a target tissue to which it is bound; and

(b) a ligand conjugated to the ultrasonic energy-activated agent, the ligand binding to a receptor on the target tissue with specificity, so that binding of the ligand to a non-target tissue is minimized.

2. The delivery system of claim 1, wherein the energy-activated agent comprises a prodrug.

3. The delivery system of claim 1, wherein the ligand comprises an antibody that binds to the receptor.

4. The delivery system of claim 1, wherein the receptor is selected from the group consisting of a vascular endothelium antigen, an antigen that is specific for an abnormal vascular wall of a tumor and an antigen that is specific for a non-vascular tumor tissue.

5. The delivery system of claim 1, wherein the ligand is selected from the group consisting of a target-specific antibody, a target-specific antibody fragment, a target-specific peptide and a target-specific polymer.

6. The delivery system of claim 1, wherein the ligand and the receptor comprise a binding pair selected from the group consisting of a biotin-streptavidin, a chemokine-chemokine receptor, a growth factor-growth factor receptor and an antigen-antibody.

7. The delivery system of claim 1, wherein the ligand is a target-specific antibody specific to an antigen selected from the group consisting of tumor surface antigen, tumor endothelial antigen, non-tumor endothelial antigen and tumor vessel wall antigen.

8. The delivery system of claim 1, wherein the target tissue is selected from the group consisting of a vascular endothelial tissue, an abnormal vascular wall of a tumor, a solid tumor in one of the head, the neck, the gastrointestinal tract, the liver, the breast, the prostate, and the lung, a nonsolid tumor, malignant cells in hematopoietic tissue, malignant cells in lymphoid tissue, lesions in a vascular system, diseased bone marrow, cells afflicted by an autoimmune disease and cells afflicted with an inflammatory disease.

9. The delivery system of claim 1, wherein the agent is selected from the group consisting of indocyanine green, methylene blue, toluidine blue, aminolevulinic acid, phthalocyanines, porphyrins, purpurins, texaphyrins, chlorins, bacteriochlorins, merocyanines, psoralens, benzoporphyrin derivatives (BPD), porfimer sodium and protoporphyrin IX.

10. The delivery system of claim 1, wherein the agent is selected from the group consisting of a gallium-porphyrin complex, protoporphyrin, hematoporphyrin, daunorubicin and adriamycin.

11. An ultrasonic energy-activated targeted delivery system, comprising:

(a) an ultrasonic energy-activated agent that absorbs energy and destroys a target tissue to which it is bound;

(b) a liposome delivery system; and

(b) a ligand that binds to a receptor on a target tissue with specificity;

wherein the ligand is separately conjugated to the ultrasonic energy-activated agent and to the liposomes of the liposome delivery system to provide dual targeting of the agent to the target tissue.

12. The delivery system of claim 11, wherein the energy-activated agent comprises a prodrug.

13. The delivery system of claim 11, wherein the ligand comprises an antibody that binds to the receptor.

14. The delivery system of claim 11, wherein the receptor is selected from the group consisting of a vascular endothelium antigen, an antigen that is specific for an abnormal vascular wall of a tumor and an antigen that is specific for a non-vascular tumor tissue.

15. The delivery system of claim 11, wherein the ligand is selected from the group consisting of a target-specific antibody, a target-specific antibody fragment, a target-specific peptide and a target-specific polymer.

16. The delivery system of claim 11, wherein the ligand and the receptor comprise a binding pair selected from the group consisting of a biotin-streptavidin, a chemokine-chemokine receptor, a growth factor-growth factor receptor and an antigen-antibody.

17. The delivery system of claim 11, wherein the ligand is a target-specific antibody specific to an antigen selected from the group consisting of tumor surface antigen, tumor endothelial antigen, non-tumor endothelial antigen and tumor vessel wall antigen.

18. The delivery system of claim 11, wherein the target tissue is selected from the group consisting of a vascular endothelial tissue, an abnormal vascular wall of a tumor, a solid tumor in one of the head, the neck, the gastrointestinal tract, the liver, the breast, the prostate, and the lung, a nonsolid tumor, malignant cells in hematopoietic tissue, malignant cells in lymphoid tissue, lesions in a vascular system, diseased bone marrow, cells afflicted by an autoimmune disease and cells afflicted with an inflammatory disease.

19. The delivery system of claim 11, wherein the agent is selected from the group consisting of indocyanine green, methylene blue, toluidine blue, aminolevulinic acid, phthalocyanines, porphyrins, purpurins, texaphyrins, chlorins, bacteriochlorins, merocyanines, psoralens, benzoporphyrin derivatives (BPD), porfimer sodium and protoporphyrin IX.

20. The delivery system of claim 11, wherein the agent is selected from the group consisting of a gallium-porphyrin complex, protoporphyrin, hematoporphyrin, daunorubicin and adriamycin.