HIV Viral Replication In Living Cells Blocked Using Eukarion Antibody Lipidation Technology

April 14, 1997

(Bedford, MA, April 14, 1997) -- Eukarion, Inc. today announced that it has successfully blocked HIV-1 viral replication in living cells using a monoclonal antibody chemically modified to permit passage across cell membranes. A paper describing these results was published in the March issue of the Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology.

"These findings are important for two reasons," said Bernard Malfroy, Ph.D., Eukarion's chief executive officer. "First, since HIV multiplies rapidly within cells, an approach to halting viral replication could contribute to the development of cell-specific AIDS immunotherapies." The Eukarion antibody targets the HIV-1 "Tat" protein that is required for HIV viral replication. In laboratory experiments using a human lymphocytic cell line, the modified (lipidated) anti-Tat antibody accumulated in HIV-1 infected cells. Once entering the infected cells, the lipidated anti-Tat antibody bound to the Tat protein and blocked its function, leading to suppressed viral replication and, concomitantly, to greatly improved cell survival. The lipidated anti-Tat antibody was found to be effective not only against a laboratory strain of HIV-1, but also against three strains of virus isolated from patients.

"Second and more broadly, we have demonstrated that Eukarion's lipidation technology can facilitate the delivery of antibodies to intracellular targets and that the antibodies retain their binding specificity and activity," Dr. Malfroy said. "Most monoclonal antibody-based products in development today bind to sites on cell surfaces. With lipidation, we can now use antibodies to target disease-causing substances inside cells and significantly expand the use of monoclonal antibodies for the treatment of human diseases." Eukarion is also evaluating the use of its lipidation technology for other therapeutic applications, and for use with proteins other than antibodies.

The journal article was authored by William W. Cruikshank, Susan R. Doctrow, Melissa S. Falvo, Hardy Kornfeld, Karl Huffmann, Jay Raina and Dr. Malfroy. It represents a collaborative effort between researchers at Eukarion and the Boston University School of Medicine. Dr. Cruikshank, who is Associate Professor of Medicine, directed the principal studies in his laboratory at the B.U. Pulmonary Center.

In addition to its lipidation program, Eukarion has a separate effort underway to develop synthetic catalytic scavenger (SCS) compounds to target reactive oxygen intermediates (ROIs), toxic by-products of tissue stress. ROIs have been implicated in the irreversible damage that occurs in patients suffering from many chronic disorders including asthma, atherosclerosis, lupus, multiple sclerosis, neurodegenerative diseases of the central nervous system, ischemia-induced organ damage, allergy and adult respiratory distress syndrome. These seemingly diverse conditions appear to have ROI involvement as a common link, creating the potential for a small number of SCS compounds to address huge unmet medical needs.

In February 1997, Eukarion signed an agreement with Glaxo Wellcome plc, the world's largest research based pharmaceutical company, for a three year collaborative research and development program for the Eukarion SCS program. The agreement will provide Eukarion scientists with access to Glaxo Wellcome's substantial R&D and screening capabilities and will allow Eukarion to operate at break-even financial levels for the foreseeable future.

Eukarion, Inc., located in Bedford, MA, is a privately held company formed in 1991 to develop proprietary compounds directed against intracellular targets for the treatment of human disease. Eukarion's technologies are protected by issued and pending patent applications owned by the company.
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Eukarion, Inc

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