West Coast Editor

If there are "orphan proteins" as well as orphan drugs, then you might say ZymoGenetics Inc. has found a parent for several more of its interleukins - and once again the taker is Novo Nordisk A/S, under a recently extended option and licensing agreement.

Seattle-based ZymoGenetics (NASDAQ:ZGEN) rose 9 cents Tuesday to close at $19.29.

Under the terms of the latest arrangement, Novo gets exclusive development rights outside North America to patents that cover interleukin-28A, interleukin-29 and interleukin-31. The first two have shown potential in providing immunity to viral infection, and the third apparently stimulates cellular infiltration and inflammation.

"Nobody really knew about IL-31 until the publication came out in Nature Immunology," said Susan Specht, ZymoGenetics' public relations manager. That paper by the company's scientists in the July 2004 issue outlined the hypothesized role of IL-31 in atopic dermatitis (also called eczema) and respiratory disease, suggesting directions for more research.

Bagsvaerd, Denmark-based Novo will pay ZymoGenetics initial license fees along with potential milestone and royalty payments, but specific financial terms were not disclosed.

ZymoGenetics identified from the human genomic sequence the cytokine family containing IL-28A and IL-29. Distantly related to Type I interferons and the IL-10 family, those use a newly identified class II receptor, IL-28R, and - like the Type I interferons - they have antiviral activity and are induced by viral infection. So the newly identified cytokine family might serve as an alternative to the Type I approach.

IL-31 came from ZymoGenetics' genomics-based discovery platform. The company said analysis of the protein and its receptor levels in human and mouse disease tissues suggests that they are significantly more common in inflammatory bowel disease, asthma and psoriasis.

ZymoGenetics Inc. was spun out of Novo in October 2000 and entered the licensing-option deal the following month. In early January 2003, the pair signed a collaborative agreement for preclinical development of IL-21 worth up to $11 million. This spring, Novo licensed IL-20 for $4 million plus milestones and royalties. (See BioWorld Today, Jan. 10, 2003, and March 17, 2004.)

Last month, Novo opted to extend the fundamental deal into late 2006, paying ZymoGenetics $7.5 million each year, with all terms of the original agreement still in force.

"They can take up to eight proteins within the first four-year option and license agreement, and for the two-year extension that was just announced, they can take up to four, so that's 12 total," Specht said.

ZymoGenetics has more would-be drugs than it can handle with its resources. At least, "that is one way to put it," she told BioWorld Today. "The other way is, our patent estate is large due to the rigorous bioinformatics development we did in the 1990s" - and sharing the wealth with the likes of Novo is a way to get wealthier.

How many proteins ZymoGenetics can crank out with its discovery engine is difficult to say, Specht said.

"It's hard, slogging, detective work," she said. "Sometimes it's quite quick. With IL-28 and IL-29, it was fairly speedy, 12 to 18 months. But then at other times we take years and don't find the biology behind a protein that we've discovered."

No Comments