CAMBRIDGE, Mass. -- As of this morning, the watchword atProtein Engineering Corp. (PEC) is "Have patent, will license."
On Tuesday, the U.S. Patent and Trademark Office notified PECthat U.S. Patent No. 5,223,409, "Directed Evolution of NovelBinding Proteins," had officially issued. It is dated June 29,1993, nearly five years after the Cambridge-based companyfiled its application in September 1988.
The patent's 66 claims cover "I a method of obtaining a nucleicacid encoding a binding protein I that binds a predeterminedtarget material I other than an antibody, with an exposedantigen-combining site."
While this is not the first U.S. patent awarded to PEC, it "hasvery broad claims and provides PEC with a dominantproprietary position for our core technology," said WilliamWardell, company president.
"The method PEC has pioneered accelerates the way natureevolves proteins," added scientific director Robert Ladner, "bydriving selection toward newly evolved proteins that bind totarget molecules of pharmaceutical significance."
As originally filed, the patent application enumerated severalspecific products -- protease inhibitors -- in addition to itsprocess claims, Ladner told BioWorld. The patent examinerssplit these off into a separate composition-of-matter patent,which is still pending.
Asked by BioWorld whether he contemplates that any of PEC'scompetitors may be infringing the newly issued methodspatent, John Freeman, the company's chairman and chiefexecutive, said yes. But, he added, "we certainly are not in aposition to indicate who may or may not be infringing. ... PEC'spurpose is not to sue, but to make products and create values."
Citing only the public record, Freeman noted that "Affymax,Genentech and Cetus (now merged with Chiron) have publishedin this field." Affymax is also known to be working in a relatedarea.
Of the products in PEC's pipeline, the furthest along towardeventual pharmaceutical application is a potent proteaseinhibitor that targets human neutrophil elastase. This is theenzyme that attacks elastin in the walls of cigarette smokers'lung alveoli, causing emphysema. Elastase also plays adestructive role in cystic fibrosis, bronchitis and otherrespiratory diseases.
To create its inhibitor, PEC scientists remodeled the amino acidstructure of the native anti-trypsin protein, protinin, increasingits affinity for elastin some 4 million-fold and essentiallyeliminating its trypsin affinity.
To do this, by their now-patented "directed evolution," theycaused a workhorse bacterial virus, phage M13, to express onits surface variants of protinin engineered to vary at key aminoacids that determine binding affinities. The viruses thenmultiplied, and elastase-coated microbeads selected thevariants that bound best.
Finally, the viral clones of choice, carrying the high-bindingprotinin gene, were allowed to multiply in yeast host cells.
"We are really at the preclinical stage," Freeman told BioWorld."So far, we have conducted tests in vitro, measuring theprotection of elastin from degradation by elastase." For clinicaltrials, PEC is inviting pharmaceutical alliances. Meanwhile, thecompany plans early toxicity studies in a rat model ofemphysema.
For a small drug-discovery company such as PEC (which hasonly14 R&D personnel), industrial allies are essential todeveloping and commercializing new products. This week,Ladner, Wardell and L. Edward Cannon, vice-president of R&D,are visiting pharmaceutical companies around the countryseeking licensees and partners.
"Several major companies have expressed a great deal ofinterest in collaborating with us, using our core technology tocreate new kinds of diagnostics," said Freeman." Specifically, heexplained, "one of the 'holy grails' of in vitro diagnostics ishomogeneous assays, and we are filing patent applications inthat field pretty much as we speak."
Homogeneous assay, Ladner explains, gets rid of the separationstep in current in vitro diagnostics. It acts in solution, ratherthan binding the agent to a matrix.
Is there an initial public offering in PEC's future?
"We certainly hope so," Freeman replied fervently. When?"That depends on market conditions. We feel we will soon beready."
-- David N. Leff Science editor
(c) 1997 American Health Consultants. All rights reserved.