Drug – bio-affecting and body treating compositions – Inorganic active ingredient containing – Heavy metal or compound thereof
Reexamination Certificate
2001-04-12
2003-10-07
Goldberg, Jerome D. (Department: 1614)
Drug, bio-affecting and body treating compositions
Inorganic active ingredient containing
Heavy metal or compound thereof
C514S296000
Reexamination Certificate
active
06630173
ABSTRACT:
FIELD OF THE INVENTION
The technical field of the invention is the use of naphthalimides with antiproliferative agents to treat a host with a cellular proliferative disease.
BACKGROUND OF THE INVENTION
There is considerable interest in modulating the efficacy of currently used antiproliferative agents to increase the rates and duration of antitumor effects associated with conventional antineoplastic agents.
Conventional antiproliferative agents used in the treatment of cancer are broadly grouped as (1) chemical compounds which affect the integrity of nucleic acid polymers by binding, alkylating, inducing strand breaks, intercalating between base pairs or affecting enzymes which maintain the integrity and function of DNA and RNA; (2) chemical agents that bind to proteins to inhibit enzymatic action (e.g., antimetabolites) or the function of structural proteins necessary for cellular integrity (e.g., antitubulin agents). Other chemical compounds that have been identified to be useful in the treatment of some cancers include drugs which block steroid hormone action for the treatment of breast and prostate cancer, photochemically activated agents, radiation sensitizers, and protectors.
Of special interest to this invention are those compounds that directly affect the integrity of the genetic structure of the cancer cells. Nucleic acid polymers such as DNA and RNA are prime targets for anticancer drugs. Alkylating agents such as nitrogen mustards, nitrosoureas, aziridine containing compounds directly attack DNA. Metal coordination compounds such as cisplatin and carboplatin similarly directly attack the nucleic acid structure resulting in lesions that are difficult for the cells to repair which, in turn, can result in cell death. Other nucleic acid affecting compounds include anthracycline molecules such as doxorubicin, which intercalates between the nucleic acid base pairs of DNA polymers, bleomycin, which causes nucleic acid strand breaks, fraudulent nucleosides such as pyrimidine and purine nucleoside analogs, which are inappropriately incorporated into nucleic polymer structures and ultimately cause premature DNA chain termination. Certain enzymes that affect the integrity and functionality of the genome can also be inhibited in cancer cells by specific chemical agents and result in cancer cell death. These include enzymes that affect ribonucleotide reductase (e.g., hydroxyurea, gemcitabine), topoisomerase I (e.g., camptothecin) and topoisomerase II (e.g., etoposide).
One of the most broadly used of these DNA targeted anticancer drugs is cisplatin (cis-diamminedichloroplatinum II, CDDP). This compound is active against several human cancers including testicular, small-cell lung, bladder, cervical and head and neck cancer.
Although the clinical activity of currently approved antiproliferative agents against many forms of cancers can be shown, improvements in tumor response rates, duration of response and ultimately patient survival are still sought. The invention described herein demonstrates the novel use of the naphthalimides and analogs thereof, including amonafide, which can potentiate the antitumor effects of chemotherapeutic drugs, in particular, agents affecting the integrity of nucleic polymers such as DNA.
SUMMARY OF THE INVENTION
Methods and compositions are provided for the treatment of a host having a cellular proliferative disease, particularly a neoplasia. In the subject methods, pharmaceutically acceptable naphthalimide and an antiproliferative agent are administered in an amount sufficient to modulate the cellular proliferative disease.
REFERENCES:
patent: 5420137 (1995-05-01), Brana et al.
patent: WO 01/68098 (2001-09-01), None
Ajani, J.A. et al., “In vitro activity of amonafide against primary human tumors compared with the activity of standard agents.” Invest New Drugs. 1988 Jun.;6(2):79-85.
Asbury, R.F. et al., “A Gynecologic Oncology Group phase II study of amonafide (NSC #308847) in squamous cell carcinoma of the cervix.” Am J Clin Oncol. 1994 Apr.;17(2):125-8.
Bernges, F. and Zeller, W.J. “Combination effects of poly(ADP-ribose) polymerase inhibitors and DNA-damaging agents in ovarian tumor cell lines—with special reference to cisplatin.” J Cancer Res Clin Oncol. 1996;122(11):665-70.
Cobb, P.W., et al., “Activity of DMP 840, a new bis-naphthalimide, on primary human tumor colony-forming units,” J Natl Cancer Inst. 1994 Oct. 5;86(19):1462-5.
Costanza, M.E. et al., “Safety and efficacy of using a single agent or a phase II agent before instituting standard combination chemotherapy in previously untreated metastatic breast cancer patients: report of a randomized study—Cancer and Leukemia Group B 8642.” J Clin Oncol. 1999 May;17(5):1397-406.
Costanza, M.E. et al., “Amonafide: An active agent in the treatment of previously untreated advanced breast cancer—a cancer and leukemia group B study (CALGB 8642).” Clin Cancer Res. 1995 Jul.;1(7):699-704.
Evans. W.K. et al., “Phase II study of amonafide: results of treatment and lessons learned from the study of an investigational agent in previously untreated patients with extensive small-cell lung cancer.” J Clin Oncol. 1990 Mar.;8(3):390-5.
Gallion, H.H. et al., “Phase II trial of amonafide in previously treated patients with advanced ovarian cancer: a Southwest Oncology Group study.” Gynecol Oncol. 1992 Aug.;46(2):230-2.
Hayes, D.F. et al., “Treatment of metastatic breast cancer: present and future prospects.”Semin Oncol. 1995 Apr.;22(2 Suppl 5):5-19; discussion 19-21.
Innocenti, F., “Pharmacogenetics: a tool for individualizing antineoplastic therapy.” Clin Pharmacokinet. 2000 Nov.;39(5):315-25.
Pérez, J.M., et al., “Combined effect of platination and intercalation upon DNA binding of novel cytotoxic Pt-bis(naphthalimide) complexes.” J Med Chem. 1999 Dec. 30;42(26):5482-6.
Wong, K. and Henderson, I.C. “Management of metastatic breast cancer.” World J Surg. 1994 Jan.-Feb.; 18(1):98-111.
Chemgenex Therapeutics, Inc.
Dorsey & Whitney LLP
Goldberg Jerome D.
Trecartin Richard F.
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