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  Taxol immunoassayUSPTO Application #: 20070092922Title: Taxol immunoassay Abstract: Novel conjugates of taxol and novel taxol immunogens derived from the 9 and 7 positions of taxol and monoclonal antibodies generated by these taxol linked immunogens are useful in immunoassays for the quantification and monitoring of taxol in biological fluids. (end of abstract) Agent: Gibbons P.C. - Newark, NJ, US Inventors: Salvatore J. Salamone, Jodi Blake Courtney, Dennis Stocker, Mahmoud Ahmed ElSohly, Waseem Gul USPTO Applicaton #: 20070092922 - Class: 435007920 (USPTO) Related Patent Categories: Chemistry: Molecular Biology And Microbiology, Measuring Or Testing Process Involving Enzymes Or Micro-organisms; Composition Or Test Strip Therefore; Processes Of Forming Such Composition Or Test Strip, Involving Antigen-antibody Binding, Specific Binding Protein Assay Or Specific Ligand-receptor Binding Assay, Assay In Which An Enzyme Present Is A Label, Heterogeneous Or Solid Phase Assay System (e.g., Elisa, Etc.) The Patent Description & Claims data below is from USPTO Patent Application 20070092922. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS-REFERENCE TO RELATED APPLICATION [0001] This Application is a Divisional of application Ser. No. 11/301,101, filed Dec. 12, 2005 which is a Continuation of application Ser. No. 11/191,497, filed Jul. 28, 2005 which is a Continuation-In-Part of application Ser. No. 11/044,667, filed Jan. 27, 2005 which also claims the benefit of Provisional Application Ser. No. 60/592,017, filed Jul. 29, 2004. FIELD OF THE INVENTION [0002] This invention relates to the field of immunological assays for determining the presence and/or quantifying the amount of taxol in human biological fluids in order to rapidly determine optimal drug concentrations during chemotherapy. BACKGROUND OF THE INVENTION [0003] Cancer is a term used to describe a group of malignancies that all share the common trait of developing when cells in a part of the body begin to grow out of control. Most cancers form as tumors, but can also manifest in the blood and circulate through other tissues where they grow. Cancer malignancies are most commonly treated with a combination of surgery, chemotherapy, and/or radiation therapy. The type of treatment used to treat a specific cancer depends upon several factors including the type of cancer malignancy and the stage during which it was diagnosed. [0004] Taxol, also known as paclitaxel, is one of the more common cytotoxic agents used for the treatment of Breast (Holmes et. al. Proc. Am. Soc. Clin. Oncol., 10, 60, 1991), Ovarian (Einzig et. al. Proc. Am. Assoc. Cancer Res., 31, 1114, 1990) and non-small cell lung cancer. Taxol has the formula: [0005] This compound has been associated with debilitating side effects such as bone marrow density loss, allergic reaction, neutropenia, hypotension, bardycardia, nausea and vomiting. By monitoring the levels of taxol in the body and adjusting the dose these side effects can be better controlled and limited in patients. [0006] At the same time, there is often highly variable relationship between the dose of taxol and the resulting serum drug concentration that affects therapeutic effect. The degree of intra- and inter-individual pharmacokinetic variability of taxol can be as high as 5-fold (Gurney et. al., J. Clin. Oncol. 14, pp 2590-2611, 1996) and is impacted by many factors, including: [0007] Organ function [0008] Genetic regulation [0009] Disease state [0010] Age [0011] Drug-drug interaction [0012] Time of drug ingestion, [0013] Mode of drug administration, and [0014] Technique-related administration. [0015] As a result of this variability, equal doses of the same drug in different individuals can result in dramatically different clinical outcomes (Hon et. al. Clinical Chemistry 44, pp 388-400, 1998). The effectiveness of the same taxol dosage varies significantly based upon individual drug clearance and the ultimate serum drug concentration in the patient. Therapeutic drug management would provide the clinician with insight on patient variation in both oral and intravenous drug administration. With therapeutic drug management, drug dosages could be individualized to the patient, and the chances of effectively treating the cancer, without the unwanted side effects, would be much higher. [0016] In addition, therapeutic drug management of taxol would serve as an excellent tool to ensure compliance in administering chemotherapy with the actual prescribed dosage and achievement of the effective serum concentration levels. It has been found that variability in serum concentration is not only due to physiological factors, but can also result from variation in administration technique. [0017] Routine therapeutic drug management of taxol would require the availability of simple automated tests adaptable to general laboratory equipment. Tests that best fit these criteria are immunoassays. A radioimmunoassay and an enzyme-linked immunosorbent assay) ELISA assay have been reported for taxol (Erlanger et. al. U.S. Pat. No. 5,756,301, May 26, 1998). However the derivatives and immunogens used in this assay impart to the corresponding antibodies a broad cross-reactivity to taxol, and taxol metabolites, particularly, 6-.alpha.-hydroxypaclitaxel. In order to be most effective in monitoring drug levels the antibody should be most specific to the active compound and display very low cross-reactivity to no cross-reactivity to the non-active metabolites. SUMMARY OF INVENTION [0018] In accordance with this invention, a new class of antibodies have been produced which are substantially selectively reactive to taxol so as to bind to taxol without any substantial cross reactivity to taxol metabolites, particularly 6-.alpha.-hydroxypaclitaxel and 3'-p-hydroxypaclitaxel. By selectively reactive it is meant that this antibody only reacts with the taxol molecule and does not substantially react with other compounds such as taxol metabolites the most important blocking metabolites being 6-.alpha.-hydroxypaclitaxel and 3'-p-hydroxypaclitaxel. [0019] It has been found that by using immunogens which are conjugates of an immunogenic polyamine polymer with a compound of the formula: [0020] Y is an organic spacing group; [0021] X is a terminal functional group capable of binding to a polyamine polymer; [0022] p is an integer from 0 to 1; and [0023] Ph is phenyl or compounds of the formula: [0024] wherein Ph, p, Y and X are as above and B is --CH.sub.2-- or or mixtures thereof; produce antibodies which are specific for taxol and do not substantially react with or bind to other compounds such as metabolites or related compounds of taxol, such as Baccatin III, 3'-p-hydroxypaclitaxel, and 6-.alpha.-hydroxypaclitaxel. The provision of these antibodies which substantially selectively react with taxol and do not cross react with 6-.alpha.-hydroxypaclitaxel and 3'-p-hydroxypaclitaxel allows one to produce an immunoassay which can specifically detect and monitor taxol in the fluid samples of patients being treated with taxol. Also included within this invention are reagents and kits for said immunoassay. The presence of 6-.alpha.-hydroxypaclitaxel and 3'-p-hydroxypaclitaxel as metabolites of taxol is the major cause for false positive readings in past immunoassays for taxol. DETAILED DESCRIPTION [0025] In accordance with this invention, a new class of antibodies is provided which substantially selectively reacts with taxol and do not substantially react or cross react with taxol metabolites mentioned hereinabove. It has been discovered that through the use of these derivatives of 9-carbonyl taxol of formula II-A and/or of the 7-hydroxy taxol of formula II-B or mixtures thereof; as immunogens, this new class of antibodies of this invention are provided. It is through the use of these antibodies that an immunoassay, including reagents and kits for such immunoassay for detecting and/or quantifying taxol in blood, plasma or other body fluid samples has been developed. By use of this immunoassay, the presence and amount of taxol in body fluid samples, preferable a blood or plasma sample, can be detected and/or quantified. In this manner, a patient being treated with taxol can be monitored during therapy and his treatment adjusted in accordance with said monitoring. By means of this invention one achieves the therapeutic drug management of taxol in cancer patients being treated with taxol as a chemotherapeutic agent. [0026] The reagents utilized in the assay of this invention are conjugates of a polymeric carrier with the compounds of formula II-A and II-B or mixtures thereof. These conjugates are competitive binding partners with the taxol present in the sample for the binding with the antibodies of this invention. Therefore, the amount of conjugate reagent which binds to the antibody will be inversely proportional to the amount of taxol in the sample. In accordance with this invention, the assay utilizes any conventional measuring means for detecting and measuring the amount of said conjugate which is bound or unbound to the antibody. Through the use of said means, the amount of the bound or unbound conjugate can be determined. Generally, the amount of taxol in a sample is determined by correlating the measured amount of the bound or unbound conjugate produced by the taxol in the sample with values of the bound or unbound conjugate determined from standard or calibration curve samples containing known amounts of taxol, which known amounts are in the range expected for the sample to be tested. These studies for producing calibration curves are determined using the same immunoassay procedure as used for the sample. [0027] The conjugates, as well as the immunogens, are prepared from compounds of the formula II-A or II-B or mixtures thereof. The conjugates or immunogens of the carrier are linked to the polyamine polymer ligand portions which have the formula: [0028] wherein Y, A and p are as above; and [0029] x' is --CH.sub.2-- or a functional linking group; compounds of the formula: [0030] wherein .chi.', A, B and p are as above. [0031] These ligand portions may be linked to one or more active sites on the carrier or polyamine polymer of the immunogen. Definitions [0032] Throughout this description the following definitions are to be understood: [0033] The term "Ph" as used throughout this application designates a phenyl radical. The term "alkylene" designates a divalent saturated straight or branch chain hydrocarbon substituent containing from one to ten carbon atoms [0034] The terms "immunogen" and "immunogenic" refer to substances capable of eliciting, producing, or generating an immune response in an organism. Continue reading... Full patent description for Taxol immunoassay Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Taxol immunoassay patent application. 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