A trade-secrets lawsuit and counter-suit, fought for nearly a decade,has ended with the winning company licensing some of its embattledtechnology to the vanquished firm.

Since February 1988, Tropix Inc., of Bedford, Mass., has beendefending its chemiluminescent detection know-how against allegedmisappropriation of confidentiality by Lumigen Inc., of Southfield,Mich. Following years of litigation in both states, the Wayne CountyMichigan Circuit Court on Aug. 5, 1994, held in favor ofphotochemist Irena Bronstein, inventor of Tropix' enzyme-triggereddioxetane-based immunoassay and DNA-probe systems.

The court decreed that rights to the technology, embodied in nearlythree dozen issued and pending U.S. patents, be reassigned solely toTropix, and ordered a separate trial to determine the damages thatLumigen must pay that aggrieved company.

Those proceedings began in January, but ended on March 31, whenthe litigants reached agreement to settle their litigation out of court.Lumigen will make payments to Tropix, but neither company hasdisclosed the financial terms of their accord.

"Damages in the case, could reach into the millions of dollars," saidTropix' general counsel and vice president of business development,Nancy Watters last August, "based on the amount of revenueLumigen derived from its misappropriated technology since 1986."

Under the settlement, Lumigen and its founder, chemistry professorA. Paul Schaap, as well as Wayne State University, in Detroit, whereSchaap teaches, are permanently forbidden to file any patentapplication anywhere in the world covering the subject matter ofTropix' chemiluminescent reagents.

For its part, Tropix now has granted certain licenses to Lumigenunder the three dozen patents involved in their lawsuit, "in order toavoid any disruption to the industry's current users of thetechnology," said Watters.

These licenses, she added, "are on a limited basis, subject totermination under certain circumstances."

In its ruling last August, the court found that Schaap was acting forand on behalf of the university when he signed a confidentiality andnon-compete agreement with Tropix' predecessor company inNovember 1985. At the time, the company's founder, and inventor ofthe technology, Irena Bronstein, was negotiating with Schaap to havehis university laboratory synthesize for Tropix, under contract,chemiluminescent chemicals, dioxetanes, to be used in diagnosticproducts.

BioWorld Today was unable to reach Schaap for comment.

In a press release announcing the final settlement, Wayne StateUniversity stated: "Schaap pioneered the development ofchemiluminescent dioxetanes _ light-emitting substances _ that canbe used in clinical assays as a diagnostic tool for cancer, AIDS andother diseases. He formed a company, Lumigen Inc. in 1987 tomarket the discovery under license from Wayne State University."

Inventor Bronstein, who is Tropix' chairman and CEO, toldBioWorld Today, "The court's ruling puts an end once and for all toany lingering misconceptions among our 2,500 customers aboutownership of this important technology _ who is going to own it atthe end of the day."

Compound Makes Light Of Its Own Fragmentation

Dioxetanes, Bronstein explained, "are chemical compounds thatcontain a four-member ring with two oxygen atoms in it. To this ringare appended other groups, enzyme recognition sites, that are veryspecific. A given enzyme basically cleaves off a very specific group.

"The dioxetane itself then becomes unstable," she continued, "anddecomposes. One of its fragments gets into an excited state andcontains a lot of energy. That energy dissipates in the form of light."

The amount of light emitted is directly proportional to the amount oftarget substance bound to the enzyme that triggers thechemiluminescent dioxetane reagent. That light emission can bedetected and measured by any of several devices, from X-ray orblack/white film to luminometer to image or video cameras,Bronstein added.

She emphasized that "The technology is non-isotopic, and that meansa lot to a lot of people. It basically eliminates all of the hazards ofradioactive waste disposal, and licenses that institutions have to haveif they use radioisotopes."

To this she adds another claimed advantage: "For DNA probe tests,the ability to avoid PCR technology."

Describing a typical application of the assay method, she said, "Onecompany, which is in a hospital, uses our reagents in random access,very high through-put clinical analyzers, to detect thyroid conditions,for example, thyroid-stimulating hormone, and various types of tumormarkers, such as CA-125 for early detection of cancer. It detectsproteins that are generated in the presence, say, of breast cancer."

"The newest area that we have developed," Bronstein said, "is awhole range of reporter-gene assays. We now have three of thesecommercialized: One is for secreted placental alkaline phosphatase; asecond for beta-galactosidase; the third, for beta-glucuronidase, agene primarily used in transgenic plants."

Tropix sells its dioxetane reagents to other companies thatmanufacture clinical diagnostic products.

Tropix has a licensing agreement with Fujirebio Inc., of Tokyo, oneof Japan's leading medical diagnostics firms. Boehringer-MannheimGmbH of Mannheim, Germany, is worldwide distributor and re-sellerof Tropix's light-detection clinical diagnosis and biochemical research systems.Boehringer has also been marketing Lumigen's competing products.n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.