Companies Rely on RCT Protein Expression Technology to Make Therapeutic Products.

TUCSON, Ariz. -- A genetically active DNA sequence that enables high levels of protein expression in mammalian cells is in use worldwide for making products ranging from reagents to therapeutics.

The bovine growth hormone polyadenylation (bgh-polyA) signal is a specialized termination sequence useful for producing pharmaceutical proteins and peptides in mammalian cells, increasing gene expression in gene therapy, and producing recombinant proteins in transgenic animals. Research Corporation Technologies' Gene eXpression Technologies (GXT) licensing program has licensed the bgh-polyA signal sequence to more than 130 companies in the United States, Canada, Japan, Europe and Australia.

Three currently available therapeutics that are produced using the bgh-polyA signal include Bristol-Myers Squibb's ORENCIA([R]) (abatacept), a receptor fusion protein therapy for rheumatoid arthritis, and Aldurazyme([R]) (laronidase), an enzyme-replacement therapy developed and commercialized through a collaboration between BioMarin Pharmaceutical Inc. and Genzyme Corporation for a rare inherited disorder known as MPS I. Additionally, the bgh-polyA signal is used to produce therapeutic monoclonal-antibody products that have become a standard of care in treating non-Hodgkin's lymphoma and rheumatoid arthritis.

For protein expression to occur in mammalian cells, messenger RNA (mRNA) must be transported from the cell nucleus, where transcription occurs, to the cytoplasm for translation into protein. The bgh-polyA sequence signals the addition of a "tail" of adenines to the end of the mRNA that enables export to the cytoplasm. Upon reaching the cytoplasm, the polyA tail is maintained during protein translation and stabilizes the mRNA during protein expression.

Fritz Rottman, Ph.D., professor emeritus at Case Western Reserve University in Cleveland, and colleagues discovered this specialized sequence.

"In early studies on the cloned bgh gene we saw a short sequence was responsible for the addition of poly A to the protein-encoding region," Rottman said. "The high efficiency of protein expression obtained with this particular bgh-polyA signal became apparent as we subsequently documented its efficiency in a wide range of chimeric protein expression systems, both in vivo and in vitro."

RCT manages commercialization of the bgh-polyA signal sequence for Case Western Reserve University in Cleveland, which assigned RCT the rights to its U.S., European and Japanese patents in 1997.

The GXT program is gathering many of the world's most widely used gene expression systems, tools and genes into one convenient and affordable licensing program. GXT licenses are flexible and nonexclusive, with manageable fees and royalties based on fields of use. For more information about the GXT program, visit http://www.rctech.com/licensing/gene-expression.php.

For information about licensing the bgh-polyA signal sequence, contact Bennett N. Cohen, Ph.D., RCT Managing Director, at [phone].

Research Corporation Technologies (www/rctech.com) is a technology investment and management company that provides early-stage funding and development for promising biomedical companies and technologies.