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PROTEIN DESIGN LABS ANTIBODY AGAINST CELL ADHESION EFFECTIVE IN REPERFUSION INJURY MODEL

 MOUNTAIN VIEW, Calif., Dec. 8 /PRNewswire/ -- The SMART(TM) Anti-L- Selectin Antibody developed by Protein Design Labs Inc. (PDL) (NASDAQ: PDLI) was effective at reducing heart tissue damage in a cat model of reperfusion injury following myocardial infarction (heart attack), a collaborator of the company said today at a conference on cell adhesion molecules.
 Reperfusion is the restoration of blood flow after oxygen deprivation. Reperfusion injury is the damage caused by the migration of neutrophils, a type of white blood cell, into tissues after blood flow is restored. Reperfusion is believed to cause a significant part of the injury suffered in a heart attack. Approximately 800,000 heart attacks occur annually in the United States.
 Allan M. Lefer, Ph.D., professor and chairman of the department of physiology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, presented data from his study at a San Diego conference, "Commercial Prospects of Cell Adhesion Molecules," sponsored by Cambridge Healthtech Institute. The complete study is expected to be published in 1994.
 Lefer said that a single 2.0 mg/kg injection of the SMART Anti-L- Selectin Antibody reduced tissue death (necrosis) by 50-60 percent in cats after myocardial ischemia (oxygen deprivation) and reperfusion. Cats treated with the antibody also showed normal cardiac function within 90 minutes following reperfusion, as measured by the heart's ability to contract and pump blood. Cats treated with a control antibody exhibited no such restoration of cardiac function. The SMART Anti-L-Selectin Antibody was administered 80 minutes after ischemia was induced and 10 minutes before reperfusion was induced.
 "To my knowledge, this is the first report that a humanized antibody to a leukocyte adhesion molecule is effective in alleviating reperfusion injury," said Lefer.
 SMART Anti-L-Selectin has the potential to treat a broad range of inflammatory diseases that result when neutrophils migrate from the blood stream into tissues and release destructive enzymes and other substances. The humanized antibody works by binding to the L-Selectin adhesion molecule on neutrophils and blocking neutrophils from sticking to the inner linings of blood vessels (endothelium). This sticking process is the initial step in the passage of neutrophils into tissues.
 PDL senior scientist Nicholas Landolfi, Ph.D., speaking at the same conference, separately reported that in laboratory experiments SMART Anti-L-Selectin blocks the binding of human neutrophils to human endothelial cells as effectively as the mouse antibody from which it was derived. SMART Anti-L-Selectin was derived from a murine antibody that PDL licensed from Stanford University, where it was developed by Eugene Butcher, M.D.
 Dr. Cary Queen, senior vice president and vice president, research at PDL, said PDL's laboratory results and Lefer's animal studies advance PDL's position in the highly competitive adhesion molecule field. Queen added that these findings represent key steps required for human clinical trials of the SMART Anti-L-Selectin Antibody, although results of preclinical studies may not be repeated in human clinical trials. PDL will continue preclinical development of the antibody in 1994, with the intent to file an Investigational New Drug (IND) application for a Phase I trial in 1994 or 1995.
 Protein Design Labs, founded in 1986, is developing next-generation antibodies and other novel proteins to treat various disease conditions. PDL has four potential products in clinical trials. They are a human antibody against cytomegalovirus (CMV), which is being investigated for CMV retinitis in AIDS patients and for other CMV infections; a human antibody against the hepatitis B virus; the SMART Anti-Tac Antibody for graft-versus-host disease, certain leukemias and lymphomas, and organ transplant rejection; and the SMART M195 Antibody for myeloid leukemia. PDL believes its human and computer-designed SMART (humanized) monoclonal antibodies will have a longer half-life and will be less immunogenic than traditional mouse antibodies and therefore will be more useful as human therapeutics.
 -0- 12/8/93
 /CONTACT: Peter Dworkin, director of corporate communications, of Protein Design Labs, 415-903-3721/
 (PDLI)


CO: Protein Design Labs Inc. ST: California IN: MTC SU: PDT

TM-LW -- SJ003 -- 1623 12/08/93 09:01 EST
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