Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2002-10-01
2004-06-22
Krass, Frederick (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S893000, C604S890100, C604S891100, C604S892100, C604S506000, C604S507000, C604S508000, C604S510000, C604S093010, C604S264000, C604S272000, C604S006160
Reexamination Certificate
active
06753328
ABSTRACT:
BACKGROUND OF THE INVENTION
The invention relates to cancer therapy.
Colorectal cancer is the third most common malignancy in men and women in the United States and is the second leading cause of cancer deaths. It is responsible for an estimated 56,700 deaths in 2001. Approximately 60 percent of those patients diagnosed with colorectal cancer will develop hepatic metastases for which the therapeutic gold standard remains hepatic resection. Despite surgical treatment, the majority of patients after liver resection will develop recurrences and of these recurrences, approximately fifty percent will be within the liver.
SUMMARY OF THE INVENTION
The invention features methods for preventing and inhibiting the spread of disseminating cancers. For example, a method of inhibiting metastases of a primary tumor to a liver tissue is carried out by directly contacting a liver tissue with Taurolidine. Preferably, the primary tumor is not a liver tumor. The primary tumor is in an organ of the peritoneal cavity. Advantages of the invention include reduction in the need for hepatic resection.
The method also includes a step of identifying an individual who is at risk of developing a metastatic liver tumor. For example, the individual is identified as suffering from a colorectal tumor or another tumor such as a lung tumor, breast tumor, kidney tumor, colon tumor, esophageal tumor, testicular tumor, pancreatic tumor, melanoma, or choriocarcinoma. Patients, who have been diagnosed with a class of tumors which commonly metastasize to the liver, are treated with Taurolidine.
The individual to be treated is a mammal such as a human patient. However, the methods are applicable to veterinary use, e.g., for the treatment of tumor metastases in pets such as dogs or cats or in livestock.
To treat or prevent metastatic disease of the liver, liver tissue is isolated from systemic circulation prior to contacting it with Taurolidine. For example, the liver is perfused with Taurolidine in situ. Liver blood circulation is essentially isolated from systemic blood circulation while liver tissue is contacted with the drug. Perfusion is performed prior to or after excision of a primary tumor. Perfusion is also carried out in conjunction with an abdominal surgery, e.g., when the abdominal cavity is surgically accessible during removal of a tumor. Other methods of administration include contacting the liver over time using in-dwelling catheter. The therapeutic methods includes peritoneal or intravenous (or other systemic) administration. Alternatively, the method does not include peritoneal or intravenous administration of Taurolidine. Drug is infused into the liver directly via the hepatic artery (pre-op; post-op; and/or during an operation to surgically remove a tumor).
Drug is administered intraperitoneally and/or intravenously before, during or after surgical removal of a tumor mass. For example, Taurolidine is administered 1, 2, 3, 4, 5, 10 or more days prior surgery. Local tissues in the area of resection are optionally bathed in a Taurolidine solution following removal of a tumor mass. Following surgery and to inhibit secondary tumor formation, drug is administered for several days (1-7 days), to weeks, and months after removal of a tumor.
Taurolidine compositions are administered at a dose that is therapeutically effective to prevent or inhibit tumor cell adherence. The term “therapeutically effective amount” as used herein means that the amount of a compound(s) or pharmaceutical composition elicits a beneficial biological or medicinal response in a tissue, system, animal or human. For example, a therapeutically effective amount of a Taurolidine reduces the number of metastatic foci in the liver tissue. Therapeutic effectiveness is also indicated by a reduction in the amount of a tumor associated antigen, e.g., carcinoembryonic antigen (CEA) or prostate specific antigen (PSA), following treatment. Taurolidine is administered alone or in combination with one or more other anti-cancer compositions. Preferably, the drug is administered at a dose that inhibits cell adherence but is not cytotoxic. The drug is administered at a doses that increase caspase (e.g., caspase-3) activity in a cell. For example, the dose induces caspase-mediated apoptosis of a cell which has been contacted with Taurolidine.
Therapeutic compositions are isolated or purified. An “isolated” or “purified” protein or biologically active portion thereof is substantially free of cellular material or other contaminating proteins from the cell or tissue source from which it is derived, or substantially free from chemical precursors or other chemicals when chemically synthesized. Preferably, a preparation of a therapeutic compound, e.g, Taurolidine, is at least 75%, more preferably 80%, more preferably 85%, more preferably 90%, more preferably 95%, more preferably 98%, and most preferably 99 or 100% of the dry weight of the preparation.
Other features, objects, and advantages of the invention will be apparent from the description and from the claims. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All patents and publications cited in this specification are incorporated by reference.
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Carlson Rolf I.
Maggio Paul
Wands Jack R.
Beattie Ingrid A.
Krass Frederick
Mintz Levin Cohn Ferris Glovsky and Popeo P.C.
Rhode Island Hospital
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