Nine years after his "Eureka! moment," John Kopchick's invention has taken the form of a drug that one day may be used to treat such diseases as gigantism, acromegaly, diabe tic eye and kidney disease, and some forms of cancer.

Photo: Rick Fatica

By Kelli Whitlock

The path to discovery is rarely obvious and hardly ever glamorous. A key, a kite and a wayward bolt of lightning helped identify electrical currents. Moldy bread led to penicillin. A falling apple explained gravity.

Still, an invention is a thing of wonder. We marvel at the creation of the transistor, welcome the identification of genes that cause disease and are in awe at the speed of a Pentium processor. If the inventive process itself is sometimes fortuitous, it only adds to the mystique.

For researchers in the lab of Ohio University's John Kopchick, the route was marked by tiny mice that were supposed to be big. In the late 1980s, Kopchick's group set out to study growth hormone, a product of the pituitary gland involved in many bodily processes. But like many creators before them, they soon became accidental tourists on the road to discovery.

"Sometimes in science, what you're looking for isn't exactly what you find," says Kopchick, Goll-Ohio professor of molecular biology. The researchers weren't looking for a protein antagonist in their studies at Ohio University's Edison Biotechnology Institute. But that's what they found. The invention, a manipulation of one amino acid in a growth hormone protein chain, inhibits the action of the hormone at the cellular level.

Nine years after Kopchick and co-inventor Wen Chen, a senior scientist at EBI, experienced their "Eureka! moment," their discovery has become the basis of a drug that one day may be used to treat diseases characterized by an overproduction of growth hormone, including gigantism, acromegaly, diabetic eye and kidney disease, and some forms of cancer. The drug, called TrovertŪ, has been developed by Sensus Drug Development Corp., a pharmaceutical firm in A ustin, Texas, started by Ohio University alumnus Richard Hawkins, BS '72.

Sensus is conducting clinical trials of the drug for use in some 40,000 people worldwide with acromegaly, a disease caused by a brain tumor that affects pituitary gland cells. People with acromegaly have elevated growth hormone levels; display abnormal growth of the hands, feet, and bone and cartilage in the face and other parts of the body; and enlargement of the liver, spleen, kidneys and heart. Phase III human clinical trials are under way at nine sites in the United States and Europe. If all goes well, TrovertŪ could be up for Food and Drug Administration approval for the treatment of acromegaly by the end of 1999.

Meanwhile, studies by Kopchick's research team suggest diabetic mice transgenically altered to express the growth hormone antagonists do not develop diabetes-related eye or kidney disease. The studies were convincing enough to send TrovertŪ to human clinical trials for diabetic eye disease, the leading cause of blindness in the U.S. Results from Phase II human trials now being conducted at four sites are expected next spring. Phase II human trials for the treatment of diabetic kidney disease could begin next spring as well.

"We're really proud that our research could actually help people with a variety of disease states," says Kopchick, who with Chen was credited at an Ohio University ceremony this fall for developing the Invention of the Year.

Until 20 years ago, universities weren't allowed to own their inventions. The 1980 Bayh-Dole Act, sponsored by former Sens. Birch Bayh and Robert Dole, enabled universities, nonprofit research institutions and small businesses to own and patent inventions developed under federally funded research programs. Since its passage, the number of patents granted for university inventions has risen from about 250 to 1,500 a year, according to the Association of University Technology Managers. The group also reports that the licensing of university inventions -- called technology transfer -- adds more than $21 billion to the economy and supports 180,000 jobs annually.

Ohio University has received 34 U.S. patents since 1973 and $1.6 million in revenue from licensing agreements. Technology developed on campus has led to the creation of five new companies, three of which got their start in the university's Innovation Center. (See Related Story). A 1996 survey by the As sociation of University and Technology Managers ranked the university among the top 50 in the nation for technology transfer, a listing based on business start-ups attributed to university-created technology, licenses executed, new patents applied for, research funding related to a license, total industrial funding and licensing income.

"Moving something from the lab to the marketplace is a huge step," says Gary Meyer, assistant vice president for economic and technology development and director of Ohio University's Technology Transfer Office.

The venture begins with a marketable idea, such as a protein antagonist with implications for drug development. Patent protection of the invention, also called intellectual property, is a critical part of the process. The university, Kopchick and Chen received the first patent for growth hormone antagonists in 1994 and a second in 1997. More patents are pending.

Once domestic and foreign patent applications have been filed, the intellectual property rights are established and the search begins for a commercial partner. In Kopchick's case, that search resulted in a partnership with Sensus' Hawkins, a Baltimore, Ohio, native who began a career in the pharmaceutical industry after earning a degree in secondary education with a focus on biology.

"The wisdom of leaders in Ohio and at the university who developed the Edison Biotechnology Institute and attracted such capable researchers to run it is impress ive," Hawkins says. "It's all a part of the growing-up process of any university."

Other university faculty are learning to negotiate the technology transfer process, among them Marcia Kieliszewski, an assistant professor of chemistry and inventor of a designer gene that could pique the interest of soft drink manufacturers. A component of many soft drinks is gum arabic, which is found in trees in Sudan. The Sudanese cut the bark of the trees, prompting the production of gum arabic, a thi ck, sticky gum that plugs the trees' wounds. The gum arabic is harvested, processed and sold to companies that use it in confections, soft drinks and other products. A trading ban with Sudan presents a problem for industry and an opportunity for Kieliszewski.

"The important part of gum arabic is glycoprotein, a protein that's covered with sugar, Kieliszewski says. "We identified the protein sequence of that glycoprotein and used it to design our own gene, one that could be made to work in plants commonly found here, such as tomato plants or tobacco plants."

It could take two to five years for Kieliszewski to receive the domestic and foreign patents she has applied for in the past year. Meanwhile, she continues her work safe in the knowledge that her intellectual property is protected.

Faculty inventors on campus are at different stages of the technology transfer process. Some are completing the necessary paperwork to obtain patent protection, while others, like Kieliszewski, are awaiting word on their patent applications. Several are in collaboration with industry partners on their way to taking Ohio University technology to the public. Still more technologies are awaiting a match with a commercial partner: Inventions designed to do everything from control zebra mussels in water systems to recycle plastic materials in a new way are available for licensing.

Technology transfer is a burgeoning area at Ohio University and on campuses across the nation: A survey of technology transfer at national universities from 1991 to 1995 by the Association of University Technology Managers found a 120 percent increase in U.S. patent applications and a 68 percent rise in licensing activity during that time. That, the group says, is a sign technology transfer in higher education will continue to grow into the next decade.

Kopchick agrees such growth is assured. Higher education promotes the creative exploration of why things are; creativ ity leads to invention. If necessity is the mother of invention, curiosity is a next-of-kin. Kopchick got started in his line of work because he was curious about a specific biological process. In his case, the wonder of living organisms and how they grow laid out a rather circuitous path that led to a patented invention carrying his name and that of Ohio University. But as with all discoveries supported by technology transfer, the benefits belong to everyone.

< td>THE SEQUENCE OF PROGRESS1998: A drug based on their discovery is in human clinical trials for the treatment of acromegaly and diabetic eye disease. While they await results, the group returns to the drawing board to find more uses for the technology.

1989: Researchers in John Kopchick's lab take their first step toward discovery when they manipulate the structure of the growth hormone protein chain. This allowed the scientists to inhibit growth in mice.

1994: Kopchick, Wen Chen and Ohio University receive the first U.S. patent on growth hormone antagonist. A second patent is issued in 1997 and more are pending.

Kelli Whitlock is the research communications editor and a science writer for University News Services and Periodicals.

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