During the 1970s, when he was at the University of Chicago, Dr. Robert Hunter, now a pathology professor at Emory, was working on a test to diagnose cancer with use of a tumor marker. He published papers about the test, received an NIH grant to pursue clinical trials, and after getting promising results, decided to approach a company about the feasibility of marketing his discovery.
Emory pathologist Robert Hunter is the scientific founder of CytRx, a biopharmaceutical company developing products for use in vascular, infectious, and immune system disease and in burns. The company currently markets TiterMax, a vaccine adjuvant used in basic research.
"Unfortunately, when I went to visit companies, they told me they wanted patents, not publications," says Dr. Hunter, who subsequently started a company focusing on a drug to treat hematologic problems. "My test never got developed, as was the fate of many good innovations developed without a patent."
Dr. Hunter's idea never got a chance to be brought to market because US laws at that time prohibited universities from obtaining patents on research projects funded by the federal government. This embargo was lifted with passage of the Bayh-Dole Act in 1980, when lawmakers on both sides of the aisle acknowledged that allowing universities to patent their discoveries would increase the number of new technologies entering the market, thereby strengthening the economy as well as decreasing universities' dependence on taxpayer support.
Universities now actively encourage their researchers to patent their ideas and pursue marketing opportunities. Examples include tools for gene splicing and magnetic resonance imaging-unarguable moneymakers for their institutions but, more important, also valuable technologies in the fight against disease.
"Emory's research funding has more than doubled over the past decade, and the more research funding you have, the more opportunity there is for development of marketable products," he says. "What most universities experience is that for every million to $2 million in research funding they receive, their investigators make what we call one invention disclosure."
An invention disclosure is a broad term covering biologic materials, software programs, and medical devices. A researcher making a disclosure to the technology transfer office is merely notifying the university of what he or she thinks is a patentable idea. The university can then match this idea with funding sources, help the researcher apply for a patent, and counsel the researcher on how best to proceed with marketing the idea.
Emory averaged 32 disclosures per year from 1991 to 1993, which have resulted in six exclusive licenses, 16 nonexclusive licenses, and five option agreements with companies such as General Electric and Sandoz Pharmaceuticals. Indeed, the number of patents issued annually to Emory has risen steadily since the 1980s, from one to six, with the number of patents pending reaching 15 per year in 1993. The disclosure rate, says Mr. La Terza, is now mushrooming. "Our office has received more than 50 in the first three quarters of this fiscal year."
Emory's success to date has been in three areas-therapeutic compositions and their methods of synthesis, diagnostic and research tools, and therapeutic devices. In 1992, Emory ranked 19th among all US universities in the amount of royalties received annually, with an income of $1.5 million. Last year's revenues were $2.6 million.
When Emory receives a royalty for a product, 40% goes to the inventor(s), and the remaining 60% is divided among the inventor(s)' laboratory, department chair, and dean and the university president, for continued research and support. "This division of funds provides incentives for researchers to pursue patenting opportunities and for the institution to allow the researchers the latitude to follow a good idea," says Mr. La Terza. "In addition, Emory may help support the start-up of a company by accepting its stock instead of cash payment for patent rights."
In addition to its internal operations of assisting Emory researchers, the technology transfer office has a strong external component, providing companies a port of entry into the university where they can inquire about investment opportunities. "We've seen more venture capitalists coming to Emory because they understand that the technology is here, and there are a lot of opportunities to invest," says Mr. La Terza.
The highest-profile products brought to market thus far because of technology transfer are those which have made the most money-Gatorade, for example, from the University of Florida. Dr. Hendricks notes, however, that the challenge in technology transfer is to develop the middle tier of projects-that gray area that has the potential to provide solid, if not spectacular, returns. This middle tier is where the promise to develop the greatest number of new technologies lies.
"If our goal were simply to make money, then we would focus all of our energies on one or two big 'hits,'" she says "But the real goal of technology transfer is to further important research that otherwise might go unfunded. Some of this research will pay off in the short run in terms of dollars, but a lot of it will more likely pay off in the long run in terms of tiny pieces of knowledge added to the overall puzzle in understanding disease. So we need to balance the obvious needs of any university to fund operations, with the priority of finding answers to as many health problems as possible."
According to Dr. Hendricks, even the most seemingly esoteric research may have market potential. "Some basic science research involves development of useful new tools and techniques that can be commercialized. For example, new cell lines developed to study specific types of cancer are marketable because other researchers would gladly purchase them rather than spend a vast amount of time and money developing their own."
Mr. La Terza notes that his office is sensitive to keeping the mission of the university at the level of basic science research. He stresses that the process of technology transfer includes helping researchers find additional funding, which, in turn, will enable them to continue and expand their original research. "Generally, the investigators who come to our office are not looking for a personal return on their work, but rather, for further funding," he notes.
"The process of gaining new knowledge doesn't follow a neat, linear path," he adds. "It takes time for scientists, health care providers, and investors to understand innovative products and their risks, benefits, and optimal uses. Having a third party examine a research project helps ensure that the business end of science won't be overlooked."
After obtaining the initial boost of funds from the venture capitalist, CytRx held a public offering to raise additional capital. The public offering was successful, and the researchers began to study a specific drug named RheothRx, which facilitates blood flow.
"The old heart-lung bypass machines tested on animal models damaged blood cells so severely that the animals died. A crude form of RheothRx was used to prevent such damage and made the application of open heart surgery possible in humans," says Dr. Hunter. "We starting looking at RheothRx's unique properties and saw more opportunities for a drug of this nature."
The researcher spent the next few years learning more about RheothRx and filing a series of use claims, including prevention of damage to tissue and treatment of heart attack and stroke. CytRx performed two Phase I clinical studies, then licensed the drug to Burroughs Wellcome (now Glaxo Wellcome), which repeated the studies and continued the research process with several Phase II clinical trials, testing the drug in cases of heart attack and sickle cell anemia. The heart attack study was promising enough to continue to a Phase III trial, in which high doses of the drug were associated with renal toxicity in elderly people with preexisting renal damage. However, the sickle cell anemia trial had good results. Even so, Glaxo Wellcome dropped the drug and returned the license to CytRx in the fall of 1995. "Sickle cell crisis is a small indication for a large company like Glaxo," notes Dr. Hunter, "but a big indication for a little comapny like CytRx." In other words, pursuing research into this application of RheothRx remains worthwhile for CytRx, if not for Glaxo.
Research continues on use of RheothRx for treatment of stroke, and further study has unearthed additional applications, including therapy for adult respiratory distress syndrome. Dr. Hunter is philosophical about the failure of RheothRx in the heart attack study. "Working in research gives you the understanding that avenues that seem promising can go nowhere while others unexpectedly can turn out to be important. If the science is good and you persevere, things may work out."
After signing a license agreement with Emory, Burroughs repeated the testing already done here and examined FTC further in a Phase I trial. Then Burroughs Wellcome merged with Glaxo. The new company, Glaxo Wellcome, decided to pursue only one drug of this type and chose 3TC, which was ahead of FTC in development and recently received FDA approval. The license for FTC was returned to Emory in December 1995.
In April, Emory licensed FTC to another company, Triangle Pharmaceuticals, in Durham, North Carolina, which was founded in July 1995 by key members of the former antiviral drug team at Burroughs Wellcome. "Tri-angle recently raised $18 million in a second round of private financing and is well positioned to resume clinical development of FTC," says Mr. La Terza, who expects this drug to have a substantial market presence as therapy for HIV and hepatitis B by the year 2000.
"We kept asking the question-how can we provide the anticoagulant necessary to prevent blood clots from developing at the site of the stent without poisoning the entire patient?" says Emory cardiologist Neal Scott.
To answer that question, he and Emory cardiologist Spencer King worked with hematologists Stephen Hanson and Laurence Harker to develop a drug-impregnated sheath to be wrapped around the stent. Release of tiny amounts of the anticoagulant in the area around the stent results in a high local concentration of the blood thinner and a low systemic concentration. The drug supply is temporary, intended only to get the patient through the critical first week after angioplasty. "Once we developed the sheath, a new technique hit the market, that of using high-pressure balloons to keep coronary arteries open," says Dr. Scott. "So we switched our research to focus on restenosis, asking the same question-is there a way to deliver a small dose of anticoagulant to a small section of an artery, rather than administering large doses of the drug systemically?"
The group capitalized on the dynamics of blood flow through the vessel. Flow is slowest against the arterial wall and fastest in the middle of the stream. ("Think about a trout stream," says Dr. King. "Trout swimming against the current don't have to swim as hard along the edge because the water is moving slowly.") Dr. Hanson and the other researchers developed a catheter that can be positioned against the arterial wall, a little upstream of the area that needs to be treated. Tiny holes in the catheter allow the drug to seep out, where it is caught in the slower-moving part of the bloodstream and carried to the angioplasty site, where it reaches its highest concentration and can do the most good.
The researchers have a patent pending on this device and have already licensed its development to Minneapolis-based Interventional Innovations Corporation. Another company, Miami Lakes, Florida-based Cordis Corporation, which was recently acquired by Johnson & Johnson, has an agreement to distribute and market the product.
A third technology currently being developed to prevent restenosis uses low-dose radiation to inhibit formation of scar tissue. Emory investigators Ron Waksman, Ian Crocker, Keith Robinson, and Spencer King have collaborated to develop a technique to deliver low-dose radiation to the angioplasty site. This technology is licensed to Novoste Corporation, in Norcross, Georgia, which recently raised more than $20 million in an initial public offering of its stock.
CEqual, developed in collaboration with Cedars Sinai Medical Center in Los Angeles, is sold by a number of large companies and is currently in use in several hundred medical centers. PerfSPECTive, developed in collaboration with Georgia Tech, is currently being marketed by Siemens.
"The products we've developed assist physicians in interpreting myocardial perfusions scans," says Dr. Garcia. "We've developed what we call the Emory cardiac toolbox that has software to quantify information and create a picture of the distribution of blood flow."
Ultimately, Dr. Garcia would like to develop other toolboxes, such as one for angiography. "If you work in an applied science, you need to take on the responsibility of seeing a good idea through the process of commercialization," he says. "That is the only way that medicine will move forward, if you develop your product to the point where others can use it."
Dr. Garcia's CEqual program retails for $6,500, and the royalties on each sale are $2,500. "All the royalties do is enable me to do more research," says Dr. Garcia. "I've looked into starting a business at times, but it is more rewarding for me to work at a research institution. I don't have a board of directors to please, and I can follow my research in the direction I find most interesting, regardless of the financial opportunities. In terms of quality of life, it is tough to beat this arrangement-I have the best of both worlds."
For more general information on The Robert W. Woodruff Health Sciences Center, call Health Sciences News and Information at 404-727-5686.