Polymeric arrays and methods for their use in binding assays

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

Reexamination Certificate

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C435S091100, C435S091210, C435S283100, C435S285200, C435S287200, C435S287700, C536S023100, C536S024300, C536S024310, C536S024320, C536S024330, C422S068100, C204S600000, C210S635000

Reexamination Certificate

active

06287768

ABSTRACT:

INTRODUCTION
1. Technical Field
The field of this invention is biopolymeric micro arrays.
2. Background of the Invention
“Biochips” or micro arrays of binding agents, such as oligonucleotides, have become an increasingly important tool in the biotechnology industry and related fields. These binding agent micro arrays, in which a plurality of binding agents are deposited onto a solid support surface in the form of an array or pattern, find use in a variety of applications, including drug screening, oligonucleotide sequencing, and the like. One important use of biochips is in the analysis of differential gene expression, where the expression of genes in different cells, normally a cell of interest and a control, is compared and any discrepancies in expression are identified. In such assays, the presence of discrepancies indicates a difference in the classes of genes expressed in the cells being compared. While such information is useful for the identification of the types of genes expressed in a particular cell or tissue type, it does not provide information regarding the size of specific gene products expressed by the cell.
To obtain such information, one has to rely on the standard blotting protocols, e.g. Northern blotting and analogous procedures. In such procedures, a complex mixture of potential target compounds is first size separated and then transferred to a flexible support. A probe capable of detecting the compound of interest in then contacted with the size separated targets. Following a positive probe/target binding event, detection of the bound probe yields information regarding the expression level (or abundance) and size of the target. While such blotting procedures are capable of providing size information, formats being used to date are not suitable for use in high throughput analysis.
Because information concerning types of genes expressed, level of expression and the size of the expressed products in a particular cell or tissue type are of interest in many applications, there is interest in the development of an array type device which can provide both types of information in a high throughput format.
Relevant Literature
Patents and patent applications describing arrays of biopolymeric compounds and methods for their fabrication include: U.S. Pat. Nos. 5,242,974; 5,384,261; 5,405,783; 5,412,087; 5,424,186; 5,429,807; 5,436,327; 5,445,934; 5,472,672; 5,527,681; 5,529,756; 5,545,531; 5,554,501; 5,556,752; 5,561,071; 5,599,895; 5,624,711; 5,639,603; 5,658,734; WO 93/17126; WO 95/11995; WO 95/35505; EP 742 287; and EP-799 897.
Patents and patent application describing methods of using arrays in various applications include: U.S. Pat. Nos. 5,143,854; 5,288,644; 5,324,633; 5,432,049; 5,470,710; 5,492,806; 5,503,980; 5,510,270; 5,525,464; 5,547,839; 5,580,732; 5,661,028; WO 95/21265; WO 96/31622; WO 97/10365; WO 97/27317; EP 373 203; and EP 785 280.
Other references providing of micro array technology, including formats for arrays and methods of their use include: Lockhart et al., Nature Biotechnology (Dec. 1996)14: 1675.
Clontech Catalogue, 97/98, (Clontech Laboratories, Inc. 1020 East Meadow Circle, Palo Alto, Calif. 94303) p. 81 describes premade Northern blots.
SUMMARY OF THE INVENTION
Arrays of polymeric targets stably associated with the surface of a rigid support are provided. In the subject arrays, the polymeric targets are arranged at least according to size of the targets. The polymeric targets are generally biopolymeric compounds, e.g. nucleic acids or proteins, and are preferably ribonucleic acids or proteins. The subject arrays find use in a variety of applications, and are particularly suited for use in high throughput gene expression analysis applications.


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