Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
1998-04-02
2001-08-14
Saunders, David (Department: 1644)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C424S001490, C424S178100, C435S007100, C435S007720, C435S007940, C435S007950, C435S007920, C436S094000, C436S063000, C436S064000, C436S518000, C436S538000, C436S541000, C436S542000
Reexamination Certificate
active
06274314
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to an assay for the detection of modified nucleoside levels in a patient. Detection of the modified nucleoside levels in a patient having a disease such as cancer allows for the progression of the disease to be followed and therapeutic regimens to be altered. Such an assay is particularly useful in following the response of cancer patients to chemotherapeutic treatment.
BACKGROUND OF THE INVENTION
Ribonucleic acids (RNA) have central roles in all aspects of cellular metabolism. Protein synthesis is dependent upon the coordinated interactions of transfer RNA (tRNA), ribosomal RNA (rRNA), and messenger RNA (mRNA). The cellular roles of RNA are complex, as they function as structural elements (rRNA), catalytic components (in RNA processing), informational molecules (mRNA), and as a direct link between information contained in DNA and in proteins (tRNA). Gene activation is dependent not only on specific mRNA transcription but also on its correct splicing, capping and processing to create a functional mRNA. Consequently, in disease states such as cancer, where abnormal cell growth occurs, it is not unexpected that perturbations are indicative of metabolic alterations that can be exploited for cancer diagnosis or therapy.
RNA contains a variety of modified nucleosides, which are enzymatically modified post-transcriptionally by a variety of modification enzymes. Over 50 chemically distinct modifications have been described, each requiring a different enzyme. In humans and other animals normal RNA turnover and breakdown creates free modified nucleosides. These modified nucleosides collect in the circulation from which they are filtered and concentrated by the kidneys into the urine for excretion. Consequently, all urine contains levels of modified nucleosides that reflect RNA degradation in the organism.
Numerous reports have correlated increased rates of modified nucleoside urinary excretion with cancer and other disease states. Examples of such cancers include leukemias (Trweyn and Grever, 1986.
CRC Crit. Rev. Clin. Lab. Sci.,
24:71-93), chronic myelogenous leukemia (Heldman, et al. 1983.
J. Lab. Clin. Med.,
101:783-792), adult acute leukemia (Heldman, et al. 1983.
Blood,
61:291-296), childhood acute lymphoblastic leukemia (Heldman, et al. 1983.
J. Nat. Can. Inst.,
71:269-273), bronchogenic carcinoma (Rasmuson, et al. 1983.
Acta Radiolog. Oncology,
22:209-214), mammary and colorectal carcinoma (Rasmusen and Bjork, 1985.
Bull. Mol. Biol. Med.,
10:143-154), hepatocellular carcinoma (Tamura, 1986.
Cancer,
57:1571-1575), small cell lung cancer (Tamura, 1986.
Clin. Chem. Acta,
154:125-132) ovarian cancer (Oerlemans and Lange, 1986.), malignant lymphomas Rasmuson and Bjork, 1983.), nasopharyngeal carcinoma (Trewyn, 1982.
Cancer
49: 2513-2517), and malignant mesothelioma (Fishbein, et al, 1983.
Cancer Res.
43:2971-2974).
The monitoring of urinary modified nucleoside levels has not been demonstrated to be useful for cancer diagnosis, to stage disease, to determine the efficacy of a treatment a protocol or to monitor recurrence of cancers in remission. The present application provides one skilled in the art with the reagents and methodologies required to efficiently measure levels of modified nucleosides in a patient as a diagnostic or predictive assay useful in designing treatment protocols.
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Trweyn and Grever, (1986),CRC Crit. Rev. Clin. Lab. Sci.24:71-93.
Heldman, et al., (1983),J. Lab. Clin. Med., 101:783-792.
Heldman, et al., (1983),Blood., 61:291-296.
Heldman, et al., (1983),J. Nat. Can. Inst., 71:269-273.
Rasmuson, et al., (1983),Acta Radiolog. Oncology., 22:209-214.
Rasmusen and Bjork., (1985),Bull Mol. Biol. Med., 10:143-154.
Tamura., (1986),Cancer., 57:1571-1575.
Tamura., (1986),Clin. Chem. Acta., 154:125-132.
Trewyn., (1983),Cancer Res., 49:2513-2517.
Fishbein, et al., (1983),Cancer Res., 43:2971-2974.
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Gerrits, GPJM, et al., Arginosuccinic aciduria: clinical and biochemical findings in three children with the late onset form, with special emphasis on cerebrospinal fluid findings of amino acids and pyrimidines. Neuropediatrics 24:15-18, 1993.*
Manjula, S, et al., Urinary excretion of pseudouridine in patients with brain tumours. Acta Oncologica. 32(3):311-314, 1993.
Grutsch James F.
Moskal Joseph R.
McDonnell & Boehnen Hulbert & Berghoff
Nyxis NeuroTherapies, Inc.
Saunders David
Tung Mary Beth
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