Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Patent
1998-09-23
2000-11-14
Zitomer, Stephanie
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
435 29, 435 71, 435 4, 436501, C12Q 168, C12Q 102, G01N 3353
Patent
active
061468304
ABSTRACT:
This invention relates to methods and systems for characterizing the actions of drugs in cells. In particular, the invention provides methods for determining the presence of a number of primary targets through which a drug, drug candidate, or other compound of interest acts on a cell. Thus, the invention also relates to methods for drug development based on the disclosed methods for determining the presence of a number of primary targets of a drug. The methods of the invention involve: (i) measuring responses of cellular constituents to graded exposures of the cell to a drug of interest; (ii) identifying an "inflection concentration" of the drug for each cellular constituent measured; and (iii) identifying "expression sets" of cellular constituents from the distribution of the inflection drug concentrations. Each expression set corresponds to a particular primary target of the drug. The invention also provides computer systems which determine the presence of a number of targets of a drug by executing the disclosed methods.
REFERENCES:
patent: 5510270 (1996-04-01), Fodor et al.
patent: 5539083 (1996-07-01), Cook et al.
patent: 5556752 (1996-09-01), Lockhart et al.
patent: 5569588 (1996-10-01), Ashby et al.
patent: 5578832 (1996-11-01), Trulson et al.
patent: 5965352 (1999-10-01), Stoughton et al.
Shupnik, M.A. et al. "Triiodothyronine regulation of thyrotropin subunit . . . " Endocrinology 118(1):367-371 1986.
DeRisi, J.L., et al. "Exploring metabolic and genetic control of gene exp . . . "Science 278:680-686 1997.
Lockhart, D.J., et al. "Expression monitoring by hybridization . . . "Nature Biotech 14 (13):1675-1680 1996.
Phillips, T.Y., et al. "O(log n) Bimodality analysis" Pattern Recognition 22(6):741-746 1989.
Blanchard AP and Hood L, "Sequence to array: probing the genome's secrets", Nat Biotechnol. Dec. 1996;14(13):1649.
Blanchard AP and Hood L, 1996, "High-density oligonucleotide arrays", Biosensors and Bioelectronics 11:687-690.
Brachmann CB et al., "Designer deletion strains derived fromSaccharomyces cerevisiae S288C: a useful set of strains and plasmids for PCR-mediated gene disruption and other applications", Yeast. Jan. 30,; 1998 14(2):115-32.
Chirgwin et al., 1979, "Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease", Biochemistry 18:5294-5299.
DeRisi et al., 1996, "Use of a cDNA microarray to analyse gene expression patterns in human cancer", Nat Genet 14:457-460.
Egholm et al., 1993, "PNA hybridizes to complementary oligonucleotides obeying the Watson-Crick hydrogen-bonding rules", Nature 365:566-568.
Ferguson et al., 1996, "A fiber-optic DNA biosensor microarray for the analysis of gene expression", Nature Biotechnol 14:1681-1684.
Fodor et al., 1991, "Light-directed. spatially addressable parallel chemical synthesis", Science 251:767-773.
Froehler et al., 1986, "Synthesis of DNA via deoxynucleoside H-phosphonate intermediates", Nucleic Acids Res 14:5399-5407.
Gari et al., 1997, "A set of vectors with a tetracycline-regulatable promoter system for modulated gene expression in Saccharomyces cerevisiae", Yeast 13:837-848.
Goffeau et al., 1996, "Life with 6000 genes", Science 274:546, 563-567.
Jones JS et al., "Yeast Saccharomyces cerevisiae selectable markers in pUC18 polylinkers", Yeast. 1990 Sep.-Oct.;6(5):363-6.
Lander, 1996, "The new genomics: global views of biology", Science 274:536-539.
Lockhart et al., 1996, "Expression monitoring by hybridization to high-density oligonucleotide arrays", Nat Biotechnol 14:1675-1680.
Maskos and Southern, 1992, "Oligonucleotide hybridizations on glass supports: a novel linker for oligonucleotide synthesis and hybridization properties of oligonucleotides synthesised in situ", Nucleic Acids Res 20:1679-1684.
McBride and Caruthers, 1983, "An investigation of several deoxynucleoside phosphoramidites useful for synthesizing deoxyoligonucleotides", Tetrahedron Lett 24:245-248.
Nguyen et al., 1995, "Differential gene expression in the murine thymus assayed by quantitative hybridization of arrayed cDNA clones", Genomics 29:207-216.
Oliff et al., 1997, "Molecular Targets for Drug Development" in Cancer: Principles and Practice of Oncology, Fifth Edition, DeVita et al. (eds.), Lippincott-Raven Publishers, Philadelphia, Pa.
Pease et al., 1994, "Light-generated oligonucleotide arrays for rapid DNA sequence analysis", Proc Natl Acad Sci USA 91:5022-5026.
Phillips TY et al., "O(log n) Bimodality Analysis", Pattern Recognition 22:741-746. 1989.
Prashar and Weissman, 1996, "Analysis of differential gene expression by display of 3' end restriction fragments of cDNAs", Proc Natl Acad Sci USA 93:659-663.
Sagliocco et al., 1996, "Identification of proteins of the yeast protein map using genetically manipulated strains and peptide-mass fingerprinting", Yeast 12:1519-1533.
Schena et al., 1996, "Parallel human genome analysis: microarray-based expression monitoring of 1000 genes", Proc Natl Acad Sci USA 93:10614-10619.
Schena et al., 1995, "Quantitative monitoring of gene expression patterns with a complementary DNA microarray", Science 270:467-470.
Shalon et al., 1996, "A DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization", Genome Res 6:639-645.
Shevchenko et al., 1996, "Linking genome and proteome by mass spectrometry: large-scale identification of yeast proteins from two dimensional gels", Proc Natl Acad Sci USA 93:14440-14445.
Velculescu, 1995, "Serial analysis of gene expression", Science 270:484-487.
Wach et al., 1994, "New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae, " Yeast, 10:1793-808.
Heller et al., 1997, "Discovery and Analysis of Inflammatory Disease-Related Genes Using cDNA Microarrays," Proc. Natl. Acad. Sci. USA 94:2150-2155.
Friend Stephen H.
Stoughton Roland
Forman B.J.
Rosetta Inpharmatics, Inc.
Zitomer Stephanie
LandOfFree
Method for determining the presence of a number of primary targe does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for determining the presence of a number of primary targe, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for determining the presence of a number of primary targe will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2063721