Method for the prediction of the risk potential for...

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid

Reexamination Certificate

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C435S091200, C536S023500

Reexamination Certificate

active

10250508

ABSTRACT:
The invention relates to a method for the prediction of the risk potential and/or diagnosis of cancerous diseases or inflammatory intestinal diseases, whereby a DNA sample is tested for the presence of polymorphic UGT1A7 allele. A positive result for a mutation is a positive indication of a sensitivity to cancerous diseases. A prediction of sensitivity to an inflammatory intestinal disease can similarly be made. A PCR amplification of the exon 1, using the DNA sample with subsequent sequence analysis is carried out in the method and the determined sequence compared with that of the wild type and the polymorphic allele. The presence or lack of mutations is monitored by sequencing the corresponding cDNA using automated fluorescent dye sequencing. The test arrangement for requires genetic detection reagents, namely the required primer or cDNAs, on a stationary support in a pre-prepared arrangement or sequence for reading off the results. The recombinant UGT1A7 enzymes are also used for therapeutic purposes.

REFERENCES:
patent: 5925566 (1999-07-01), Davis et al.
patent: WO99/57322 (1999-11-01), None
patent: WO 00/06776 (2000-02-01), None
Vogel, A et al. Genetic link of hepatocellular carcinoma with polymorphisms of the UDP-glucuronosyltransferase UGT1A7 gene. 2001. Gastroenterology. vol. 121 pp. 1136-1144.
Liu, Vincent et al. Quantitative Allele Specific PCR: Demonstration of Age Association Accumulation in Human Tissues of the A/G Muation at Nucleotide 3243 in Mitochondrial DNA. 1997. Human Mutation vol. 9 pp. 265-271.
Strassburg, C.P., et al., “Expression of the UDP-glucuronosyltransferase 1A Locus in Human Colon”, J.Biol.Chem., vol. 273. No. 15, pp. 8719-8726 (1998).
Strassburg, C.P., et al., “Differential Down-Regulation of the UDP-Glucuronosyltransferase 1A Locus is an Early Event in Human Liver and Biliary Cancer”, Cancer Research, pp. 2979-2985 (1997).
Guillemette, C., et al., “Structural heterogenelty at the UDP-glucuronosyltransferase I locus: functional consequences of three novel missense mutations in the human UGT1A7 gene”, Pharmacogenetics, 10:629-644 (2000).
Tukey, R.H., et al., “Human UDP-Glucuronosyltransferases: Metabolism, Expression, and Disease”, Ann.Rev.Pharmacol. Toxicol., 40:581-616 (2000).
Vogel, A., et al., “Genetic Link of Hepatocellular Carcinoma With Polymorphisms of the UDP-Glucuronosyltransferase UGT1A7 Gene”, Gastroenterology, vol. 121, No. 5, pp. 1136-1144 (2001).
Strassburg, C.P., et al., “Polymorphisms of the human UDP-glucuronosyltransferase (UGT) 1A7 gene in colorectal cancer”, GUT, pp. 851-856 (2002).
Strassburg, C.P., et al., Differential Expression of the UGT1A Locus in Human Liver, Biliary, and Gastric Tissue: Identification of UGT1A7 and UGT1A10 Transcripts in Extrahepatic Tissue, Molecular Pharmacology, 52:212-220 (1997).
Hirschhorn, J.N., et al., “SBE-TAGS: An array-based method for efficient single-nucleotide polymorphism genotyping”, PNAS, vol. 97, No. 22, pp. 12164-12169 (Oct. 14, 2000).
A. Vogel, et al., Polymorphisms of the Carcinogen Detoxifying UDP-Glucuronosyltransferase UGT1A7 in Proximal Digestive Tract Cancer, Gastroenterol, 40:497-502 (2002).
NCBI Sequence Viewer—U39570 (2pgs).
NCBI Sequence Viewer—U89507 (2pgs).

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