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Celera Diagnostics Identifies Gene Variant Associated With Increased Risk For Rheumatoid Arthritis
Link Between RA Risk and PTPN22 Described at EULAR Meeting

ALAMEDA, CA and BERLIN, GERMANY - June 10, 2004

Celera Diagnostics today presented data linking variation in the gene PTPN22 to a two-fold increase in risk for rheumatoid arthritis (RA). In a scientific session at the Annual European Congress of Rheumatology (EULAR) in Berlin, Ann Begovich, Ph.D., Director, Inflammation at Celera Diagnostics, described the study, in which Celera Diagnostics and it collaborators at the North American Rheumatoid Arthritis Consortium (NARAC) and Genomics Collaborative, Inc. discovered and replicated the role of this genetic variation in RA. Celera Diagnostics is a joint venture between the Applied Biosystems Group (NYSE:ABI) and Celera Genomics Group (NYSE:CRA) of Applera Corporation.

“Rheumatoid arthritis clearly has a genetic component, but the role of genes in disease risk and progression is not well understood. Information from this disease association study may have broad implications for RA and other autoimmune disorders,” said Peter K. Gregersen, M.D., Principal Investigator of NARAC and Director of the Robert S. Boas Center for Genomics and Human Genetics at the North Shore-Long Island Jewish Research Institute, and a co-author of this study. “These exciting discoveries open a new window for studying the causes of autoimmune diseases. The role of certain immune cells in the development of rheumatoid arthritis is not fully understood. This genetic variant may affect other immune functions as well. We now have a way to pursue these questions.”

“Celera Diagnostics is determining the clinical utility of this gene variant and other genetic markers for early diagnosis as well as prediction of both disease severity and a patient’s response to various therapies in rheumatoid arthritis,” said Thomas White, Ph.D., Chief Scientific Officer, Celera Diagnostics. “Our goal at Celera Diagnostics is to incorporate these discoveries into new diagnostic tests. In addition, we have discovery efforts underway related to other autoimmune diseases, including two studies undertaken on behalf of Celera Genomics.”

Robert F. Booth, Ph.D., Chief Scientific Officer, Celera Genomics added, “The discovery of this gene variant provides new insights concerning the pathogenesis of rheumatoid arthritis. Celera Genomics is currently evaluating the biology surrounding these findings in the search for new drug targets that address the cause rather than the symptoms of the disease. Combining a diagnostic with an appropriate therapeutic could provide the first targeted medicine for rheumatoid arthritis.”

Summary of Scientific Findings
The genetic markers, or single nucleotide polymorphisms (SNPs), were discovered in a study that compared samples from 475 people diagnosed with RA to 475 individually matched controls. Potential genetic markers were replicated in a second sample collection from 840 RA patients, including siblings from 463 families, and control samples from 926 individuals. DNA samples analyzed in this study include those collected from families with RA collected by NARAC. Details of the research are scheduled for publication in the August issue of the American Journal of Human Genetics. In a related study with investigators at the University of Minnesota School of Medicine, the variant in PTPN22 was also shown to be involved in other autoimmune diseases. A study published earlier this year by other researchers in Nature Genetics associated the same SNP with type 1 diabetes.¹

PTPN22 is a gene that codes for a phosphatase enzyme that is known to be involved in regulating the immune system. Under normal conditions, the enzyme works as a “negative regulator” by keeping immune cells, specifically T cells, from becoming overactive. In cases where the SNP is present in one or both copies of an individual’s genes, the negative regulation by this enzyme appears to be inefficient, so that immune cells are hyper responsive.

About Rheumatoid Arthritis (RA)
Rheumatoid arthritis is an inflammatory disease in which the body’s natural immune system does not function properly and attacks healthy joint tissues, including the lining of the joints, or synovium. This can lead to joint destruction and results in pain, stiffness, swelling and loss of motion in the joints. The age of onset for RA is usually between 30 and 50 and the disease is two to three times more common in women than men. It is one of the most common autoimmune diseases, affecting approximately 1% of the population worldwide and its prevalence is expected to increase as the population ages. The exact cause of RA is not yet fully understood.

Physicians currently diagnose RA based on the overall pattern of symptoms, medical history, physical exam, X-rays and lab tests including a test for rheumatoid factor. Rheumatoid factor is an antibody found in the blood of approximately 70-80% of adults with RA. However, it is also seen in other conditions besides RA and in many healthy individuals. Diagnosis is not always certain and there are patients who have normal tests yet progressive disease.

About NARAC
The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute of Allergy and Infectious Diseases (NIAID) and the Arthritis Foundation joined in 1997 to support a national consortium of 12 research centers known as the North American Rheumatoid Arthritis Consortium (NARAC) in the search for genes that determine susceptibility to rheumatoid arthritis. The NARAC project has collected, analyzed and made available for use (by qualified members of the scientific community) the clinical and genetic data on nearly 1,000 sibling pairs with rheumatoid arthritis.

About Celera Diagnostics and Applera Corporation
Celera Diagnostics is a 50/50 joint venture between two Applera Corporation businesses, Applied Biosystems and Celera Genomics. Headquartered in Alameda, CA, Celera Diagnostics focuses on discovering novel genetic markers for disease and configuring these into new diagnostic tests to predict, characterize, monitor and select therapy for cardiovascular disease, auto-immunity, central nervous system disorders, and cancer. The Celera Genomics Group, located in Rockville, MD, and South San Francisco, CA, is engaged principally in integrating advanced technologies to discover and develop new therapeutics. Celera intends to leverage its proteomics, bioinformatics, and genomics capabilities to identify and validate drug targets, and to discover and develop novel therapeutic candidates. Its Celera Discovery System™ online platform, marketed exclusively by Applied Biosystems, is an integrated source of information based on the human genome and other biological and medical sources. The Applied Biosystems Group serves the life science industry and research community by developing and marketing instrument-based systems, consumables, software, and services. Customers use these tools to analyze nucleic acids (DNA and RNA), small molecules, and proteins to make scientific discoveries, develop new pharmaceuticals, and conduct standardized testing. Applied Biosystems is headquartered in Foster City, CA, and reported sales of $1.7 billion during fiscal 2003. Information about Applera Corporation, including reports and other information filed by the company with the Securities and Exchange Commission, is available at www.applera.com, or by telephoning 800.762.6923.

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," "plan," and "should," 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 notes that a variety of factors could cause actual results and experience to differ materially from the anticipated results or other expectations expressed in such forward-looking statements. These factors include but are not limited to (1) uncertainty as to whether Celera Diagnostics or Celera Genomics will be able to generate products, or therapeutic or diagnostic value from disease association studies conducted by Celera Diagnostics; and (2) other factors that might be described from time to time in Applera’s filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Applera does not undertake any duty to update this information, including any forward-looking statements, unless required by law.

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