Prosthesis (i.e. – artificial body members) – parts thereof – or ai – Arterial prosthesis – Drug delivery
Reexamination Certificate
1997-12-12
2002-11-26
Casler, Brian L. (Department: 3734)
Prosthesis (i.e., artificial body members), parts thereof, or ai
Arterial prosthesis
Drug delivery
C604S500000, C604S104000, C604S265000, C128S898000
Reexamination Certificate
active
06485514
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to the local delivery of therapeutic agents that are preferentially cytotoxic or cytostatic with regards to proliferating cells.
2. Description of Related Art
Uncontrolled cell proliferation can be a serious problem. For example, one form of uncontrolled cell proliferation is cancer, which is second only to cardiac disease as a cause of death in the United States. Another form of uncontrolled cell proliferation is restenosis, which can be life threatening if not treated.
Researchers have developed a series of therapeutic agents for systemic treatment of cancer. Two therapeutic agents of interest are camptothecin and taxol.
20(S)-camptothecin (CPT), a plant alkaloid, was found to have anticancer activity in 1966 (Wall, M., Wani, M. C., Cooke, C. E., Palmer, K. H., McPhail, A. T. and Slim, G. A. “Plant antitumor agents. I. The isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibitor from
Camptotheca acuminata”, J. Am. Chem. Soc.
88: 3888-3890, 1966).
During the sixties and seventies the sodium salt of CPT was derived from CPT, and clinical trials of this chemically altered CPT were carried out and then abandoned because of the high toxicity and low potency of this compound (Gottlieb, J. A., Guarino, A. M., Call, J. B., Oliverio, V. T. and Block, J. B. “Preliminary pharmacological and clinical evaluation of camptothecin sodium salt (NSC 100880)”,
Cancer Chemother. Rep.
54: 461-470; 1979; Muggia, F. M., Creaven, P. J., Hansen, H. H., Cohen, M. N. and Selawry, D. S. “Phase I clinical trials of weekly and daily treatment with camptothecin (NSC 100880). Correlation with clinical studies.”
Cancer Chemother. Rep.
56: 515-521; 1972; Gottlieb, J. A. and Luce, J. K. “Treatment of malignant melanoma with camptothecin (NSC 100880).”
Cancer Chemother. Rep.
56: 103-105; 1972; and Moertel, C. G., Schutt, A. J., Reitemeier, R. J. and Hahn, R. G. “Phase II study of camptothecin (NSC 100880) in the treatment of advanced gastrointestinal cancer.”
Cancer Chemother Rep.
56: 95-101; 1972.
All these trials were conducted using the hydrosoluble, sodium salt derivative of CPT (CPT Na+), which was administered intravenously. The net result of this research established the ineffectiveness and the toxicity of CPT Na+.
Drug therapies have been evaluated with respect to treating human cancer, e.g., human cancer xenograft lines. Human tumors are serially heterotransplanted into immunodeficient, so-called “nude” mice, and the mice then tested for their responsiveness to a specific drug. (Giovanella, B. C., et al.,
Cancer
52(7): 1146(1983)). The data obtained in these studies strongly support the validity of heterotransplanted human tumors into immunodeficient mammals, such as nude mice, as a predictive model for testing the effectiveness of anticancer agents.
It was determined that 9-Amino-20(S)-Camptothecin (9AC) and 10,11-Methylendioxy-20(S)-Camptothecin (10,11 MD) are capable of having high anticancer activity against human colon cancer xenografts (Giovanella, B. C., Wall, M. E., Wani, M. C. Nicholas, A. W., Liu, L. F., Silber, R. and Potmesil, M. “Highly effective topoisomerase-I targeted chemotherapy of human colon cancer in xenografts.”
Science
246: 1046-1048; 1989).
U.S. Pat. No. 5,552,154 to Giovanella et al. disclosed methods of treating specific forms of cancer with water-insoluble 20(S)-camptothecin and derivatives thereof, having the closed-lactone ring intact. In particular, transdermal, oral and intramuscular methods of administration using solutions of water-insoluble 20(S)-camptothecin were disclosed.
However, these methods of administration are all systemic, and therefore can create undesirable systemic side-effects.
Taxol is a naturally occurring compound which has shown promise as an anti-cancer drug. For example, taxol has been found to be an active agent against drug-refractory ovarian cancer by McGuire et al. See “Taxol: A Unique Anti-Neoplastic Agent With Significant Activity Against Advanced Ovarian Epithelial Neoplasms.”
Ann. Int. Med.,
111. 273-279 (1989).
Unfortunately, taxol has extremely low solubility in water, which makes it difficult to provide a suitable dosage form. In fact, in Phase I clinical trials, severe allergic reactions were caused by the emulsifiers administered in conjunction with taxol to compensate for taxol's low water solubility; at least one patient's death was caused by an allergic reaction induced by the emulsifiers. Dose limiting toxicities include neutropenia, peripheral neuropathy, and hypersensitivity reactions.
These investigations showed that systemic administration of taxol can result in severe systemic side-effects, which limits the usefulness of taxol in a clinical setting.
Furthermore, the investigations into CPT and taxol, as discussed above, focused primarily on the use of these materials as anti-cancer agents. By way of comparison, fairly little work has been done with these materials in the area of restenotic lesions.
Restenosis may be defined as the reclosure of a previously stenosed and subsequently dilated peripheral or coronary vessel. It may occur at a rate of 20-50% for these procedures and is dependent on a number of clinical and morphological variables. Restenosis may begin shortly after a stenosing procedure, and tends to cease after about 4-12 months thereafter. Several hypotheses exist on why and how restenosis occurs. Some researchers believe that restenosis is a natural healing process in response to the injury that occurs during a stenosing procedure. The problem associated with this healing process is that, in some instances, it does not shut off. the artery continues to “heal” until it becomes occluded by proliferating cells.
Unfortunately, there has been only marginal success in the treatment of restenosis, particularly in the area of restenosis of coronary arteries.
There is therefore a need for apparatus, methods and kits for the treatment of proliferating cells, such as cancerous or restenotic cells, to resolve the aforementioned problems.
SUMMARY OF THE INVENTION
This invention relates to implants for administering at least one therapeutic agent that is preferentially cytotoxic or cytostatic with regards to proliferating cells comprising an implant structure and at least one therapeutic agent that is preferentially cytotoxic or cytostatic with regards to proliferating cells.
In another aspect, this invention relates to stents comprising at least one therapeutic agent that is preferentially cytotoxic or cytostatic with regards to proliferating cells. Additionally, this invention relates to a method of treatment comprising inserting a stent into a lumen of a body, wherein the stent comprises at least one therapeutic agent that is preferentially cytotoxic or cytostatic with regards to proliferating cells.
In still another aspect, the invention relates to an apparatus comprising an intraluminal catheter and a supply of at least one therapeutic agent that is preferentially cytotoxic or cytostatic with regards to proliferating cells. Additionally, the invention relates to an apparatus comprising a container adaptable for connection to an intraluminal catheter, wherein the container contains at least one therapeutic agent that is preferentially cytotoxic or cytostatic with regards to proliferating cells.
Furthermore, the invention relates to a method of treatment comprising administering at least one therapeutic agent that is preferentially cytotoxic or cytostatic with regards to proliferating cells through an intraluminal catheter. In addition, the invention relates to a kit comprising a container adaptable for connection to an intraluminal catheter, wherein the container contains at least one therapeutic agent that is preferentially cytotoxic or cytostatic with regards to proliferating cells.
DETAILED DESCRIPTION OF THE INVENTION
In one aspect, the invention relates to an implant for administering at least one therapeutic agent that is preferentially cytotoxic or cytostatic with r
Chen Shirley
Rodriguez Cris L.
SuperGen, Inc.
Wilson Sonsini Goodrich & Rosati
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