Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
2002-01-10
2004-09-21
Nguyen, Dave T. (Department: 1635)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C424S093100, C424S197110
Reexamination Certificate
active
06794368
ABSTRACT:
FIELD OF INVENTION
The present invention relates to a method for treating prostate cancer.
BACKGROUND OF THE INVENTION
Cancer is an aberrant net accumulation of atypical cells, which can result from an excess of proliferation, an insufficiency of apoptosis, or a combination of the two. Apoptosis is an active cellular death process characterized by distinctive morphological changes that include condensation of nuclear chromatin, cell shrinkage, nuclear disintegration, plasma membrane blebbing, and the formation of membrane-bound apoptotic bodies (Wyllie et al. Int. Rev. Cytol. 68:251, 1980). A molecular hallmark of apoptosis is degradation of the cell's nuclear DNA into oligonucleosomal-length fragments as the result of activation of endogenous endonucleases (Wyllie A. H. Nature 284:555, 1981).
Prostate cancer is a major cause of cancer deaths among the male population. For patients with capsule confined prostate cancer, radical prostatectomy, radiotherapy, a combination of the two, and brachytherapy with radiolabeled seed implants are the most common treatments. Radical prostatectomy can result in impotence and incontinence. Radiotherapy is associated with prostate specific antigen (PSA) recurrence. Brachytherapy can be used only in carefully selected patients.
For patients with extracapsular tumors and metastases, androgen ablation and chemotherapy are the most common treatments. Androgen ablation, for use in patients with androgen-dependent prostate cancer, includes surgical castration (bilateral orchiectomy) and chemical castration using anti-androgens and leutinizing hormone production suppressors. Many patients refuse orchiectomy. Anti-androgens and leutinizing hormone production suppressors, used together to effect total androgen blockade, result in androgen withdrawal symptoms and, also, are very expensive. Moreover, the response to androgen ablation therapy is finite and lasts a medium of 12 to 16 months (Crawford et al. New Eng. J. Med. 321:419, 1989). Enhanced programmed cell death or apoptosis has been identified as a desirable therapeutic outcome in the treatment of prostate cancer (Kyprianou et al., Cancer Surv. 11:265, 1991). Mutations in p53, a protein that is implicated in the control and induction of apoptosis, are associated with poor clinical prognosis and decreased efficacy of a wide range of therapeutic agents used in the treatment of cancer (Chang et al., J. Clin. Oncol. 13:1009, 1995). p53 gene mutation, which results in the accumulation of non-functional p53 protein, is known to be associated with a lack of responsiveness to androgen ablation therapy in the treatment of prostate cancer (Navone et al., J. Natl. Cancer Inst. 85:1657, 1993).
Therapeutic agents that are effective in inhibiting the proliferation of and inducing apoptosis in cancer cells in vitro are recognized as having therapeutic utility for the in vivo treatment of cancer (Furukawa et al., J. Surg. Oncol. 48:188, 1991). For example, the anti-proliferative activity in vitro of chemotherapeutic agents towards prostate adenocarcinoma cancer cells has been shown to positively correlate with their in vivo anti-cancer activity (Pienta et al., Prostate 26:270, 1995). The activity of many of these therapeutic agents is however influenced by p53 mutation status, and those agents whose mechanism of action appears to be independent of p53 are non-selective and highly toxic. Chemotherapy, for use in patients with androgen-independent (hormone refractory) prostate cancer, has palliation as its primary goal. However, the toxic side effects of chemotherapy are debilitating, often dose limiting, and compromise the quality of the patient's life.
Castration or androgen ablation therapy (either alone or in combination) induces apoptosis in prostate tumors. The amount of apoptosis occurring in prostate tumors after androgen ablation has been correlated with p53 status (Westin et al., Am. J. Pathol. 146:1368, 1995). However, almost all patients with metastatic prostate cancer will escape first-line androgen ablation therapy. The induction of apoptosis in prostatic adenocarcinoma following androgen ablation is associated with infiltrating immune effector cells such as cytotoxic T cells and activated macrophages (Landstrom and Funa, Int. J. Cancer 71:451, 1997). The activation of the innate and acquired immune systems, in addition to inhibition of prostate cancer cell proliferation, would be beneficial for the treatment of prostate cancer.
Therefore, there is a need for a novel therapeutic agent for treating prostate cancer that is simple and relatively inexpensive to prepare, that remains therapeutically stable over time, that is effective in the presence of mutated p53, that is capable of stimulating the innate and or the acquired immune system and that is effective at dose regimens that are associated with minimal toxicity even upon repeated administration.
SUMMARY OF THE INVENTION
The present invention satisfies the above need by providing a method for treating prostate cancer in an animal, including a human, wherein a composition comprising
Mycobacterium phlei
(
M. phlei
) DNA (M-DNA) and M-DNA, wherein the M-DNA is preserved and is complexed with the
M. phlei
cell wall (MCC), is administered to the animal in need of such treatment in an amount effective to have an anti-neoplastic effect on cancer cells in the prostate of the animal.
M-DNA and MCC are simple and relatively inexpensive to prepare, their activities are reproducible among preparations, they remain therapeutically stable over time, and they are effective at dose regimens that are associated with minimal toxicity even upon repeated administration.
To prepare MCC,
M.phlei
are grown in liquid medium and harvested. The
M. phlei
are disrupted, and the solid components of the disrupted
M. phlei
are collected by centrifugal sedimentation. The solid components are deproteinized, delipidated, and washed. M-DNA is purified from MCC or is purified directly from
M. phlei.
DNase-free reagents are used to minimize DNA degradation (preserve DNA) during preparation of MCC and M-DNA.
A composition comprising M-DNA or MCC and a pharmaceutically acceptable carrier is administered to an animal, including a human, having prostate cancer in an amount effective to prevent, treat or eliminate prostate cancer cells in the animal, including the human, having prostate cancer. Optionally, additional therapeutic agents including, but not limited to, anti-androgens, chemotherapeutic agents, immunomodulatory agents and steroids can be administered with the M-DNA and MCC. The unexpected and surprising ability of M-DNA and of MCC to prevent, treat or eliminate prostate cancer cells addresses a long felt unfulfilled need in the medical arts and provides an important benefit for animals, including humans.
Accordingly, it is an object of the present invention is to provide a composition and method effective to prevent prostate cancer.
Another object of the present invention is to provide a composition and method effective to prevent hormone sensitive prostate cancer.
Another object of the present invention is to provide a composition and method effective to prevent hormone insensitive prostate cancer.
Another object of the present invention is to provide a method effective to treat prostate cancer.
Another object of the present invention is to provide a method effective to treat hormone sensitive prostate cancer.
Another object of the present invention is to provide a method effective to treat hormone insensitive prostate cancer.
Another object of the present invention is to provide a method effective to eliminate prostate cancer.
Another object of the present invention is to provide a method effective to eliminate hormone sensitive prostate cancer.
Another object of the present invention is to provide a method effective to eliminate hormone insensitive prostate cancer.
Another object of the present invention is to provide a method that has an anti-neoplastic effect on prostate cancer cells.
Another object of the present invention is to provide a method th
Filion Mario C.
Phillips Nigel C.
Angell Jon Eric
Bioniche Life Sciences Inc.
Kilpatrick & Stockton LLP
Nguyen Dave T.
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