Zymogenetics In Race For Patent -- Protein Discovery Puts Firm In The Limelight

If ZymoGenetics Inc. could have picked its timing for announcing an important discovery, it probably wouldn't have been this week.

Files cover Don Foster's desk. Stacks of loose glossy pages sit on the floor of his office. A jumble of notebooks litter a table near the window. Other offices are in similar disarray.

ZymoGenetics, a Seattle biotechnology company, is preparing to move next week from the University District to the old Lake Union steam plant.

And suddenly, all eyes are upon them.

"It's a little chaotic," said Foster, who heads up a research team currently in the limelight. "I'm getting nothing done except for talking to press people."

Yesterday, the company and collaborators at the University of Washington reported success in discovering, isolating and cloning thrombopoietin (TPO), a protein that stimulates the production of cells critical to blood clotting.

Today, it is racing to push TPO through clinical trials and toward Food and Drug Administration approval.

And it truly is a race: San Francisco-based Genentech Inc. published news of a similar discovery yesterday. It will compete with ZymoGenetics for the patent on TPO.

TPO is a protein found naturally in the body that stimulates growth of tiny blood cells called platelets, which in turn induce blood clotting. ZymoGenetics hopes use of the protein will one day replace platelet transfusions as a treatment for those undergoing chemotherapy and others with low platelet counts.

The present treatment method isn't flawless: Often foreign platelets from transfusions are attacked by the patient's own nervous system.

If TPO works for people as it does in the laboratory, the protein has the potential to help as many as 300,000 cancer patients worldwide.

Because of the news, several cancer patients and their relatives and friends called ZymoGenetics yesterday, asking when the drug would be available. Foster said the process to get it approved and out on the market could take as long as five years.

TPO has been a long time coming already, Foster said. Scientists started searching for the protein more than 30 years ago, when they first theorized its existence. Finding it is "clearly the most exciting thing that's happened to me in 15 years in biotech," said Foster. "It's the most exciting thing that's happened to the company."

A team of 25 scientists in their late 20s to early 40s worked full-time and sometimes around the clock in laboratories cluttered with petri dishes.

"It's been a bit of the Holy Grail," said Si Lok, one of the chief scientists on the project who has been with it from the beginning.

Scientists rarely get to work on a project where the end result is so clear, said Anne Bell, a molecular scientist with ZymoGenetics for a decade.

In addition to emotional satisfaction, TPO promises monetary rewards. Analysts have estimated the market for a drug like TPO may exceed $1 billion a year, although Foster said that seems high.

Research on TPO has cost ZymoGenetics between $5 million and $15 million so far, said Mark Murray, director of new-business development. He expects costs to soar to well over $100 million by the time clinical trials are completed.

The research and development budget of ZymoGenetics's parent company was $300 million for fiscal year 1993. ZymoGenetics is a wholly owned subsidiary of Novo Nordisk A/S, in Denmark.

The company may lose part or all of its investment in TPO if the U.S. Patent Office grants the patent to Genentech, Murray said.

ZymoGenetics is actively pursuing a patent, he said.

ZymoGenetics refuses to reveal when the company started work on the project. The amount of time it has pursued TPO may have a bearing on whether ZymoGenetics receives the patent, Murray said.

With the discovery of TPO so long in the making, other companies have done work on substitutes for the protein. Immunex Corp. of Seattle is one of those companies. Its drug, Pixykine, is in the final stages of clinical testing and is expected to be on the market in two years, said Doug Williams, director of biological services. The drug stimulates both white blood cell and platelet production.