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Aplidine for multiple myeloma treatmentRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Peptide Containing (e.g., Protein, Peptones, Fibrinogen, Etc.) Doai, Cyclopeptides, BicyclicAplidine for multiple myeloma treatment description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070149445, Aplidine for multiple myeloma treatment. Brief Patent Description - Full Patent Description - Patent Application Claims
FIELD OF THE INVENTION [0001] The present invention relates to the use of aplidine and analogues in the treatment of cancer, in particular in the treatment of multiple myeloma. BACKGROUND OF THE INVENTION [0002] Multiple myeloma represents a malignant proliferation of plasma cells derived from a single clone. The terms multiple myeloma and myeloma may be used interchangeably. [0003] Plasma cells produce antibodies, proteins that move through the bloodstream to help the body get rid of harmful substances. Each type of plasma cell responds to only one specific substance by making a large amount of one kind of antibody. These antibodies find and act against that one substance. Because the body has many types of plasma cells, it can respond to many substances. When cancer involves plasma cells, the body keeps producing more and more of these cells. The unneeded plasma cells--all abnormal and all exactly alike--are called myeloma cells. Myeloma cells tend to collect in the bone marrow and in the hard outer part of bones. Sometimes they collect in only one bone and form a single mass, or tumor, called a plasmacytoma. In most cases, however, the myeloma cells collect in many bones, often forming many tumors and causing other problems. When this happens, the disease is called multiple myeloma (MM). [0004] Because people with MM have an abnormally large number of identical plasma cells, they also have too much of one type of antibody. The tumor, its products, and the host response to it result in a number of organ dysfunctions and symptoms of bone pain or fracture, renal failure, susceptibility to infection, anemia, hypercalcemia, and occasionally clotting abnormalities, neurologic symptoms, and vascular manifestations of hyperviscosity. [0005] MM is the 2nd most commonly diagnosed hematologic malignancy in the Western World, with an annual incidence of .about.15,000 new cases in the U.S. alone. Unfortunately, MM is presently considered an incurable disease and the overall survival of MM patients has remained essentially unchanged at a median of 3-4 years, despite intense efforts over the last .about.3 decades to improve on the activity of cytotoxic chemotherapy-based therapies for this disease. Importantly, the median age of diagnosis of MM in <65 years old and >1/3 of MM patients are <55 years old at diagnosis: for this substantial proportion of relatively young MM patients, the diagnosis of MM signifies, even in the absence of other co-morbidities, a high probability that their overall survival will be significantly shorter than the average life-expectancy of age-matched non-MM patients. [0006] Recently, there have been a series of important advances in the therapeutic management of MM, namely the documentation of anti-MM activity of 2 new classes of anti-cancer agents, thalidomide (and its immunomodulatory derivatives) and the proteasome inhibitors. Although these classes of agents have been shown to be active in the setting of MM patients who were relapsed/refractory to conventional or high-dose cytotoxic chemotherapy-based regimens, a significant proportion of MM patients has de novo resistance to those novel agents, while initial responders (even those achieving durable complete remissions) can eventually relapse. Therefore the development of novel classes of anti-MM agents is urgently needed, in order to further improve the outcome of MM patients and, hopefully, to achieve high cure rates for this presently incurable neoplasia. SUMMARY OF THE INVENTION [0007] We have established for the first time that aplidine has very potent anti-multiple myeloma activity. [0008] Aplidine (Dehydrodidemnin B) is a cyclic depsipeptide isolated from the Mediterranean tunicate Aplidium albicans. [0009] As used herein, the term aplidine also covers any pharmaceutically acceptable salt, ester, solvate, hydrate or a prodrug compound which, upon administration to the recipient is capable of providing (directly or indirectly) the compound aplidine. The preparation of salts and other derivatives, and prodrugs, can be carried out by methods known in the art. [0010] Aplidine analogues include the compounds disclosed in WO 02/2596. [0011] More information on aplidine, aplidine analogues, their uses, formulations and synthesis can be found in patent applications: WO 91/9485, WO 98/1352, WO 99/42125, WO 01 76616, WO 01/35974, WO 02/30441 and WO 02/2596. We incorporate by specific reference the content of each of these PCT texts. [0012] Aplidine has been shown, both in vitro and in clinical phase I and II trials to have potential of being useful as an anticancer agent. Aplidine has several modes of action, including the blockade of VEGF secretion, inhibition of protein synthesis and signal transduction, and inducing G1 cell cycle arrest. The dose-limiting toxicity in phase I/II trials was muscular toxicity, with a remarkable lack of severe myelosuppression. [0013] Aplidine shows potent in vitro activity against human tumor solid cell lines, especially non-small-cell lung and colon tumor cells with IC.sub.50 values at 0.18 nM and 0.45 nM respectively (Faircloth et al., 1995, Proceedings 8.sup.th ECCO Congress, Paris, Abstract no. 122, 529; Lobo et al., 1997, Anticancer Res, 17, 333-336). The National Cancer Institute's (NCI) human in vitro panel has confirmed selectivity for non-small-cell lung cancer (NSCLC), melanoma, ovarian and colorectal cancer cell lines (Faircloth et al., 1996, Ann Oncol., 7, 34). [0014] Initial studies with this marine depsipeptide suggested in vivo activity against murine tumors such as B16 melanoma (Fairclotll et al., 1995, Proceedings 8.sup.th ECCO Congress, Paris, Abstract no. 122, 529). Moreover, additional in vivo studies performed in mice bearing human xenografted tumors confirm activity against breast MX-1 and colon CX-1 (Faircloth et al., 1996, Ann Oncol., 7, 34). A phase I trial in pediatric leukemia is under implementation (Jimeno J. et al., 2002, Ann Oncol., 13 (suppl. 5), Abst. 65P). Finally, it has been shown that aplidine also demonstrated in vivo antitumor activity against subcutaneous implanted gastric, prostate and Burkitts lymphoma human xenografts as well as bladder carcinoma in the hollow fiber (Faircloth et al., 1999, Proc. Am. Assoc. Cancer Res., 40, Abstract 2612; Faircloth et al., 1998, Proc. Am. Assoc. Cancer Res., 39, Abstract 227). [0015] The present invention is directed to the use of aplidine and analogues in the treatment of multiple myeloma. [0016] The present invention is also directed to a pharmaceutical composition comprising aplidine or an analogue and a pharmaceutically acceptable carrier, vehicle or diluent, to be used in the treatment of multiple myeloma. [0017] The present invention further provides a method of treating any mammal, notably a human, affected by multiple myeloma which comprises administering to the affected individual a therapeutically effective amount of aplidine or an analogue. [0018] In another aspect the present invention is directed to the use of aplidine or an analogue in the manufacture of a medicament for the treatment of multiple myeloma. [0019] The invention additionally provides kits comprising separate containers containing a pharmaceutical composition comprising aplidine or an analogue, and a reconstituting agent. Methods of reconstitution are also provided. BRIEF DESCRIPTION OF THE FIGURES [0020] FIG. 1. Results of MTT colorimetric survival assays of a panel of aplidine-treated MM cell lines Continue reading about Aplidine for multiple myeloma treatment... Full patent description for Aplidine for multiple myeloma treatment Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Aplidine for multiple myeloma treatment patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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