College signs deal with biotech firm

The US drugs giant, American Home Products, has signed a research contract with biotechnology specialists at Trinity College Dublin. The deal will open up opportunities for commercial development of discoveries made at the college.

The contract was finalised last week, according to Prof Luke O'Neill of Trinity's Department of Biochemistry and director of the college's Biotechnology Institute.

The project will be run by Trinity and will also involve scientists at Cambridge University in Britain.

The deal is with AHP subsidiary, Immunex Corporation. Based in Seattle, Washington, and established in 1982, the company employs 700 and was bought by AHP three years ago.

The firm is in the financial news because of its anti-arthritis drug, Enbrel. "It is one of the most successful biotechnology companies because of its anti-arthritis drug," Prof O'Neill said.

Enbrel is a genetically engineered human protein that works to reduce the joint inflammation associated with arthritis. The drug achieved sales of $650 million in 2000, the bulk of Immunex's $828 million turnover for that year. The fourth-quarter sales reached $191 million, leading analysts to suggest that the drug could yield sales of up to $1 billion during the current year.

Immunex is also important to Ireland given the company's decision to locate in Dublin what will be one of the largest, if not the largest, bulk drug fermenters in the world. AHP expects to employ 1,300 over the next five years at its Clondalkin plant. Building work is under way and production should begin by 2002, Prof O'Neill said. "The main product it will produce is Enbrel."

The Seattle company specialises in cloning human genes known to be associated with the immune system.

Genes produce biochemicals called proteins. Drug companies such as Immunex try to identify proteins associated with diseases with a view to developing drugs that either enhance or block the action of these proteins. "Most of their drugs are engineered drugs based on a human protein."

Enbrel is just such a drug. Immunex succeeded in cloning a "receptor", the place on a cell that connects with immune system messengers called cytokines. Cytokines encourage inflammation, the body's normal immune response when it seeks to respond to damage caused by bacterial or viral attack.

Cytokines are an essential and necessary part of the immune system, but they can also go out of balance, as in arthritis. In this case the immune system becomes too active, causing unwanted inflammation in the joints, causing pain and making movement difficult.

Enbrel interferes with a particular cytokine called TNF, which occurs in elevated levels in arthritic joints. Cells have TNF receptors, but the Enbrel clone acts like a receptor detached from the cell. It serves to mop up TNF, in the process stopping it from reaching the cell and reducing the inflammatory response in the joint.

"TNF in the joints turns them wild," said Prof O'Neill. The drug actually "modifies the disease" and is the first truly new response to arthritis in 50 years, he added. The drug is produced by engineering the cloned gene into bacteria and then getting the bacteria to "grow" the protein in a fermenter.

The US Food and Drug Administration approved Enbrel for use in the treatment of arthritis last July. It is effective in blocking the action of TNF, but because it also interferes with the immune response it can increase the risks associated with infections.

The Trinity research group will work in the general area of immunity and anti-arthritic drugs, said Prof O'Neill. "In particular we are interested to see what happens inside cells when they have seen cytokines. We will be looking for a royalty on any product that comes out of the research."

There will be three or four researchers working at Trinity and two or three in Cambridge. Initial employment at the plant will be about 400 people, divided evenly between production and research, said Prof O'Neill. The connection with Trinity arose because the company wanted to satisfy itself that it would be able to find the specialists needed to get the Clondalkin plant up and running.

"They wanted to see if we had the training procedures to produce research graduates," Prof O'Neill explained."