Aptein Receives Basic Diversity Patents.

SEATTLE--(BW HealthWire)--Sept. 3, 1997--

Allows cell-free display of trillions of random peptides

Aptein Inc., announced today that it had been issued two United States patents, entitled "Cell-Free Synthesis and Isolation of Novel Genes and Polypeptides," that broadly cover methods to screen over 10(12) random polypeptides in small volumes.

U.S. Patent Numbers 5,643,768 and 5,658,754 describe a technology that utilizes in vitro translation to produce large libraries of "polysomes" that allow for the recovery of high-affinity binders against receptors and other targets.

"Dr. Kawasaki has, we believe, literally turned back the evolutionary clock with this pioneering technology," said Paul Abrams, M.D., J.D., chairman of Aptein. "Once certain patterns of amino acid sequences evolved in biological systems, they tended to be carried forward by nature with minor modifications. Aptein's technology, invented by Dr. Glenn Kawasaki, re-opens peptide and nucleic acid sequences to their initial statistically possible randomness and allows us to choose those with the most desirable characteristics."

This cell-free process involves polysome particles that contain a randomly generated polypeptide plus the genetic material coding for the peptide (mRNA), and one or more ribosomes engaged in protein synthesis. The polysomes bind via the peptides or proteins to targets of pharmaceutical interest and the associated genes can be rescued by gene amplification. A single polypeptide binding event may be detected and the sequence may be recovered with this invention. Typically, three or four rounds of polysome selection are serially performed to enrich for the highest affinity molecules, which are identified by DNA sequencing and binding assays. The terms, "polysome display" and "ribosome display," have been used to describe the same process.

"The polysome system is thousands of times more efficient than phage or bacterial display in creating and screening random libraries and has a wide variety of applications to pharmaceutical research and development," according to Kawasaki, Ph.D., president and CEO of Aptein. "As a result of larger genetic diversities, higher affinity binders are found with polysomes than with phage display. Trillions of peptides can be generated, screened and selected with one milliliter of fluid thereby using a small fraction of the reagents and space needed for peptides displayed on organisms. Moreover, because of the lack of limitation on sequence length, the polysomes have been used to display and select large polypeptide proteins such as globin and antibodies."

Aptein is applying the company's technology to Alzheimer's disease and has generated high-affinity binding peptides to molecules such as prostate-specific antigen (PSA). From the literature, it appears that a peptide binding the thrombopoietin (TPO) receptor has been produced by this method, and at least two other research organizations are displaying and selecting antibodies from polysomes made in vitro. Aptein is also developing techniques for producing and screening large cDNA libraries for genomic work.

Aptein Inc., is a privately-held company in Seattle. The biotechnology firm is focused on the use of polysome methods to isolate molecules that bind specific targets and to engineer proteins for improved or novel activities. Dr. Kawasaki, who founded Aptein in 1989, has a Ph.D. in genetics from the University of Washington in Seattle and was a research fellow at Harvard Medical School in Boston. The company will consider licensing the technology for defined fields of use. For additional information the firm's e-mail address is [e-mail] .

CONTACT: Aptein Inc.

Glenn Kawasaki, 206/283-6369