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Isis Pharmaceuticals’ Genetrove Division Signs Deal with Celera Genomics to Functionalize More than 200 Novel Human Genes

Rockville, MD and Carlsbad, CA - July 16, 2001

Celera Genomics (NYSE:CRA), an Applera Corporation business, and Isis Pharmaceuticals, Inc., (NASDAQ: ISIP) announced today that Celera will employ Isis’ GeneTrove expertise in antisense gene functionalization to identify the biological role of more than 200 novel genes. GeneTrove, Isis’ functional genomics division, will complete this work within 18 months using its proprietary High Throughput Gene Functionalization system.

Under the agreement, Celera will select the genes to be studied. Celera and GeneTrove will jointly prioritize the genes for functionalization studies to be performed by GeneTrove in its extensive set of pharmacological assays. Isis will maintain rights to develop antisense drugs to the genes. Celera has the right to select a limited number of functionalized genes as exclusive targets in developing therapeutic agents. GeneTrove will provide Celera antisense reagents for its exclusive functionalized genes. Isis will commercialize the data on the remaining genes through its GeneTrove Human Gene Function Database. Gene function intellectual property generated by the collaboration will be jointly owned by the companies and will be available to GeneTrove’s Human Gene Function Database subscribers. Celera and Isis will equally share revenue generated by the licensing of collaboration intellectual property. The financial terms of the agreement were not disclosed.

“We are impressed with the power and efficiency of the Isis antisense gene functionalization technology,” said J. Craig Venter, Ph.D., Celera's President and Chief Scientific Officer. “This agreement should provide Celera with valuable information on the function and potential medical implications of key genes, which we plan to use in our internal drug discovery program.”

“Our collaboration with Celera is highly synergistic, as it brings us together with a leader in genomic sequencing,” said Stanley T. Crooke, M.D., Ph.D., Isis Chairman and CEO. “The collaboration is strategically important for GeneTrove, as we gain access to new genes that will enrich our Human Gene Function Database. This transaction will help us achieve our goal of inhibiting 1,500-2,000 genes in total this year and functionalizing 10,000 genes in four years.”

GeneTrove is engaged in functional genomics collaborations with a growing number of pharmaceutical company partners. By year-end, the division will introduce its first subscription database product to Early Access Program partners. GeneTrove’s Human Gene Function Database will be populated with data on up to 10,000 genes studied in multiple phenotypic assays that are relevant to oncology, angiogenesis, and inflammatory and metabolic diseases. Subscribers will have access to biological data that documents cause-and-effect gene relationships in a powerful software platform. The data will enable empirically-based drug discovery decisions.

Isis and its GeneTrove division have pioneered antisense methods that rapidly, efficiently and precisely determine the role of particular genes within a biological system. GeneTrove’s antisense inhibitors are highly specific can be used in a broad variety of cell types. GeneTrove also has industry-leading expertise in the in vivo application of antisense inhibitors that allows evaluation in animal models of disease.

Isis will conduct a live webcast conference call to discuss this release on Monday, July 16, at 10:30 AM Eastern time. To participate over the Internet, go to A replay of the webcast will be available at this address for up to 90 days.

About Celera
Applera Corporation comprises two operating groups. The Celera Genomics Group, an integrated source of genomic and related medical information headquartered in Rockville, MD, is evolving to become a next generation diagnostic and therapeutic discovery company. Celera intends to leverage its industrialized approach to biology to develop platforms for enabling these new discoveries both for subscribers and for its own internal product development. The Applied Biosystems Group (NYSE: ABI) develops and markets instrument-based systems, reagents, software, and contract services to the life science industry and research community. Applied Biosystems is headquartered in Foster City, CA, and reported sales of $1.4 billion during fiscal 2000. Information about Applera Corporation, including reports and other information filed by the company with the Securities and Exchange Commission, is available on the World Wide Web at, or by telephoning (800) 762-6923.

About Isis
Isis Pharmaceuticals, Inc. is exploiting its expertise in RNA to discover and develop novel human therapeutic drugs. The company has commercialized its first product, Vitravene™ (fomivirsen), to treat CMV-induced retinitis in AIDS patients. In addition, Isis has 11 products in its development pipeline, with two in late-stage development and four in Phase II human clinical trials. ISIS 3521, an inhibitor of PKC-alpha, is in Phase III trials for non-small cell lung cancer. Isis is preparing to initiate a Phase III program for ISIS 2302 (alicaforsen) an ICAM-1 inhibitor, in Crohn's disease. Isis has a broad patent estate, as the owner or exclusive licensee of nearly 800 issued patents worldwide. Isis' Gene Trove™ division uses antisense to assist pharmaceutical industry partners in validating and prioritizing potential gene targets through customized services and access to an extensive gene function database. Ibis Therapeutics™ is a division focused on the discovery of small molecule drugs that bind to RNA.

This press release contains forward-looking statements concerning Isis Pharmaceuticals' functional genomics division, GeneTrove, and its product offerings, and the drug discovery activities of the company. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of conducting gene functionalization and target validation activities, in launching new products and services for or with collaborators, and in discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and financing such activities. Actual results could differ materially from those projected in this release. As a result, the reader is cautioned not to rely on these forward-looking statements. These and other risks concerning the company's research and development programs are described in additional detail in its Annual Report on Form 10K-A for the year ended December 31, 2000, which is on file with the U.S. Securities and Exchange Commission, copies of which are available from the company upon request.

Certain statements in this press release are forward-looking. These may be identified by the use of forward-looking words or phrases such as “believe,” “expect,” “anticipate,” and “potential,” among others. These forward-looking statements are based on Applera Corporation’s current expectations. The Private Securities Litigation Reform Act of 1995 provides a “safe harbor” for such forward-looking statements. In order to comply with the terms of the safe harbor, Applera Corporation notes that a variety of factors could cause actual results and experience to differ materially from the anticipated results or other expectations expressed in forward-looking statements within this press release. The risks and uncertainties include but are not limited to: (1) dependence on the final assembly and annotation of the human genome; (2) unproven use of genomics information to develop products; (3) dependence on computer hardware, software, and internet applications; (4) potential adverse effect on the Celera Genomics group’s intellectual property protection and the value of its products and services due to public disclosure of genomics sequence data; (5) government regulation of Celera’s products and services; and (6) other factors that might be described from time to time in Applera Corporation’s filings with the Securities and Exchange Commission.

Applera, Celera, Celera Genomics, and Celera Discovery System are trademarks and Applied Biosystems is a registered trademark of Applera Corporation or its subsidiaries in the US and certain other countries. Vitravene™ is a trademark of Novartis AG. Gene Trove™ and Ibis Therapeutics™ are trademarks of Isis Pharmaceuticals, Inc.

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