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Aventis Pharmaceuticals, Incyte Genomics, Amersham Biosciences

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Aventis Pharmaceuticals of Bridgewater, NJ, received US Patent No. 6,502,039, “Mathematical analysis for the estimation of changes in the level of gene expression.” The patent covers a highly accurate and reproducible mathematically-based methodology for quantifying the levels of differential gene expression from microassay protocols. Specifically, the technology provides a simple deductive approach, grounded in a Bayesian framework, to circumvent the heuristic-based limitation of previous methodologies. Rather than seeking a point-estimate of the fold-change of the level of gene expression, the system utilizes the derivation of a mathematical formula to determine the a posteriori distribution of all the fold-changes of differential gene expression that may be inferred from the given measurements. From this distribution the following may be obtained: (i) an estimator for the fold-change of the level of gene expression; (ii) confidence limits for the fold-change, at any given confidence level; and (iii) a P-value for assessing the statistical significance of change. The technology also possesses the advantage that fold-change estimates and confidence limits may even be assigned to signal pairs where both signals are zero or negative, without resorting to heur istic thresholds.

Incyte Genomics received US Patent No. 6,500,938, “Composition for the detection of signaling pathway gene expression.” The technology is a composition of polynucleotide probes that can be used as elements in a microarray. The technology also describes a method for selecting polynucleotide probes of the composition. The microarray of this invention is particularly useful in the diagnosis and treatment of cancer, immunopathology, and neuropathology.

Amersham Biosciences received US Patent No. 6,500,921, “Schiff base reductant co-dispense process.” The patent covers methods for producing a covalent linkage with chemical stability between an amine-containing biomolecule and a solid support or hydrogel surface containing an aldehyde moiety. The technology provides methods for stabilizing amine-derivatized oligonucleotides and nucleic acids to aldehyde-functionalized solid supports. The solid support comprises a microarray and a hydrogel matrix. The technology provides improved methods for forming a stable amine bond between an amine-containing biomolecules, most preferably an amino-terminal oligonucleotide or nucleic acid, and an aldehyde moiety comprising the polymeric component of the hydrogel. The invention provides improved methods involving two phases (solid and liquid) to reduce an unstable Schiff base formed by contacting a solution of the amino-terminal oligonucleotide or nucleic acid with a hydrogel comprising an aldehyde moiety. Sodium cyanoborohydride is used to reduce the Schiff base.

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