ZymoGenetics researchers identify novel Interleukin that plays key role in immune system regulation

November 01, 2000

Results published in Nature demonstrate power of integrated genomics approach

Seattle, WA, November 2, 2000 - Building on a rapidly growing body of research in the field of immunology, scientists at ZymoGenetics, Inc. have identified the interaction of two proteins that appear to play a key role in the human body's ability to fight disease. These proteins, designated Interleukin 21 (IL-21) and Interleukin 21 receptor (IL-21R), are members of an important class of naturally-occurring cytokine ligand-receptor pairs that are involved in the growth and activation of red blood cells, white blood cells, antibody-producing cells and other components critical for a strong immune response.

The discovery, reported in today's issue of the journal Nature, demonstrates the power of an integrated genomics approach for therapeutic protein discovery and validation. Researchers at ZymoGenetics employed the company's broad expertise in molecular genetics, bioinformatics, protein engineering and functional cloning to rapidly identify both components of the IL-21 ligand-receptor pair. ZymoGenetics' immunologists and stem cell biologists subsequently demonstrated key biological roles of IL-21 and IL-21R in regulating the immune system.

"ZymoGenetics was early to recognize the value of mining the human genome for the discovery of novel therapeutic proteins," said Bruce L. A. Carter, Ph.D., President and Chief Executive Officer of ZymoGenetics. "In addition to our bioinformatics expertise, our protein discovery engine also combines the power of protein chemistry and functional biology. This paper illustrates the value of such an integrated approach, where our research team was able to identify the IL-21 ligand, and subsequently characterize the previously unknown IL-21/IL-21R interaction as an important component of immune system regulation. Based on these exciting initial results, we are moving forward with advanced biological and preclinical studies."

ZymoGenetics recently announced its establishment as an independent private company in conjunction with the signing of a $150 million private placement. The proceeds from this financing will be used to further accelerate ZymoGenetics' targeted bioinformatics-driven programs for the discovery and development of novel therapeutic proteins.

Study Findings

ZymoGenetics researchers describe for the first time the identification of IL-21 ligand, and the interaction of IL-21 and its receptor, IL-21R, two proteins that are members of the family of molecules known as Class I cytokines and Class I cytokine receptors. Similar to other Class I cytokines such as erythropoietin (Epogen®) and G-CSF (Neupogen®), two potent stimulators of cell proliferation, initial biological studies indicate that IL-21 promotes rapid activation of immune system cells that are critical for defending the body against invading bacteria, viruses and cancer cells. Specifically, IL-21 has been shown to:

-Promote production of natural killer (NK) immune cells from bone marrow

-Improve the ability of mature NK cells to lyse (destroy)"non-self" target cells

-Stimulate expansion of select B and T cell populations.

"Critical to our ability to more fully understand the biological functions of IL-21 was our identification of the novel IL-21 protein itself as well as its corresponding receptor. We believe that these proteins work together to activate components of both the innate and acquired arms of the immune system," noted Frank Collins, Senior Vice President of Research at ZymoGenetics. "Because IL-21 promotes the proliferation and expansion of cells needed to defend against invaders, the molecules may have broad utility in therapeutic applications such as protecting against viral infection, enhancing vaccines, boosting the efficacy of chemotherapy or treating autoimmune disease. Our continued biological studies of IL-21 will clarify which activities will have primary therapeutic value."
-end-
Authors on the paper, titled"Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function," include researchers from both ZymoGenetics and the University of Washington. Multiple scientists representing the departments of Functional Cloning, Immunology, Protein Biochemistry, Biomolecular Informatics and Genetics at ZymoGenetics are included as authors. Senior authors on the paper are Don Foster, Ph.D., Director of Stem Cell Biology, and Julia Parrish-Novak, Ph.D., Senior Scientist, both of ZymoGenetics.

About ZymoGenetics

ZymoGenetics is a leading biopharmaceutical company focused on the discovery and development of protein therapeutics that prevent or treat significant human diseases. Building on a successful track record of marketed products derived from its work, ZymoGenetics is currently leveraging its expertise in genomics and bioinformatics to generate a broad pipeline of proprietary product candidates. The company has also established one of the strongest patent portfolios in protein therapeutics, which it plans to commercialize through internal development and pharmaceutical collaborations. ZymoGenetics, headquartered in Seattle, Washington, recently announced that it has been established at an independent company. For further information please visit www.zymogenetics.com

Contact:
Charles E. Hart, Ph.D.
Sr. Director, Business Development
ZymoGenetics, Inc.
www.zymogenetics.com
206-442-6744

Sharon Karlsberg
Director
Feinstein Kean Healthcare
617-577-8110, x267
www.fkhealth.com

Feinstein Kean Healthcare

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