Aurora Biosciences, Warner-Lambert Collaborate on Functional Genomics

Aurora Biosciences Corp. (San Diego, CA) and the Parke-Davis Pharmaceutical Research Division of Warner-Lambert Co. (Morris Plains, NJ) have entered a new collaboration on functional genomics which expands their earlier agreement. Under the new terms the companies will use Aurora's GenomeScreen program to characterize and profile effects of a number of compounds on gene expression in a human cell line. Aurora will receive research funding, payment upon isolation and delivery of cell clones with identified genes, and, potentially, milestones and royalty payments if compounds for development are discovered as a result of this work.

In Aurora's GenomeScreen system, genes that are induced or repressed in response to a given stimulus are identified using Aurora's beta-lactamase fluorescent reporter gene randomly integrated across the genome. Clonal cell lines of such responsive genes can be rapidly selected by cell sorting, grown and used directly in high throughput screening, and ultimately in miniaturized assays in Aurora's UHTS (Ultra High Throughput Screening) system, to identify and profile compounds that modulate the expression of these genes. Some aspects of this technology were described in a recent cover article in Nature Biotechnology, Vol. 16, No. 13, December 1998.

Aurora designs and develops proprietary drug discovery systems, services and technologies to accelerate and enhance the discovery of new medicines. Aurora is developing an integrated technology platform comprised of a portfolio of proprietary fluorescent assay technologies and an UHTSS platform designed to allow assay miniaturization and to overcome many of the limitations associated with the traditional drug discovery process. According to Aurora, the UHTSS platform will enable it and its collaborators to take advantage of the opportunities created by recent advances in genomics and combinatorial chemistry that have generated many new therapeutic targets and an abundance of new, small molecule compounds. Current collaborators include Merck & Co., Inc., Warner-Lambert, Bristol-Myers Squibb Co., Eli Lilly and Co., Roche Bioscience, Allelix Biopharmaceuticals, Inc., and Cytovia, Inc.

Core Technology: Ultra High Throughput Screening

Aurora's Ultra-high Throughput Screening System (UHTSS) will have the capability of screening over 100,000 compounds per day with over 2400 re-tests, accessed from a store of over one million compounds bringing drug discovery to a truly industrialized level. Completion of the UHTSS is expected by year 2000.

Because most current high throughput screening (HTS) systems have been developed without an adequately integrated design concept, improving performance at certain rate-limiting steps—without creating almost equally limiting bottlenecks—is a major challenge. In addition, many HTS systems are designed to screen only one class of target or one type of assay. To overcome these limitations and to exploit the power of its fluorescent assay technologies, Aurora is developing its fully-automated Ultra-high Throughput Screening System (UHTSS) technology, which is expected to be operational at Aurora in the second half of 1999.

The automated storage and retrieval system used with UHTSS.

The UHTSS automated storage and retrieval module houses over 1,000,000 compounds in solution for rapid access. The robotic systems for storage and retrieval of compounds have been adapted from other industrial settings where automated, rapid access to very large stores of small items has been reliably deployed. Aurora's own proprietary innovations have been added to adapt these advanced technologies to this UHTSS module. The system is designed to deliver and return over 100,000 selected compounds per day for primary screening and over 2,000 hits for re-test and potency determination as well as allow ready replenishment of the compound store from libraries in the master store. The ability to deliver selected compounds to the screen at ultra-high rates under computer control is a key advance offered by the Aurora platform. The automated storage and retrieval system can facilitate high throughput screening in conventional 96-well and 384-well plates today, and is in use at Bristol-Myers Squibb, Eli Lilly & Co. and Parke Davis.

Nanoplates, a key enabling technology for UHTSS, are used by several of Aurora's pharmaceutical company customers.

Another key component of Aurora's UHTSS is the NanoPlate screening platform for performing fluorescent assay screens in 3,456 miniaturized wells. Aurora has developed a manufacturing system for disposable NanoPlates with external collaborators. A key feature is the small assay volume, approximately 100 times smaller than most conventional screening assays. This volume reduction is critical for reducing the cost per test and conserving compound libraries that often consist of only very small amounts of each test compound. Aurora has thus far successfully addressed most of the problems inherent in such small assay volumes. NanoPlates are developed to be compatible with most of Aurora's fluorescent assay technologies and other sensitive fluorescent assays. Several cell-based and biochemical assays, based on Aurora's fluorescent reporters, have already been shown to work in NanoPlates.

For more information: Timothy Rink, CEO, Aurora Biosciences Corp., 11010 Torreyana Road, San Diego, CA 92121. Tel: 619-452-5000.