The Charlottesville biotechnology firm that developed this sperm antigen could begin the first human trials later this year. "If this works, it will be revolutionary," says John Herr, president of ContraVac Inc. and a professor of cell biology at the University of Virginia. Herr began his research more than 10 years ago, and now he's trying to raise $7.5 million to convert the technology into home sperm-count tests and a birth-control vaccine.

Another sensitive area in biotech is the fertility business. The Genetics & IVF Institute in Fairfax lets couples pick the sex of their babies through artificial insemination, using a technique that sorts the X and Y chromosomes. The institute did not respond to repeated inquiries from Virginia Business, but it recently told Time magazine that it can give couples an 85 percent chance of having a girl and a 65 percent chance of having a boy. The procedure costs $2,500 for each attempt.

Despite the ethical and financial challenges, the biotech industry is growing quickly in Virginia. Today there are more than 80 biotech firms in the state -- up from a handful in 1995. Exciting developments are under way, and many more are in the works. Here are 10 breakthroughs that could put Virginia on the biotech map.

In the early 1980s at U.Va., Herr helped the FBI develop antibody "probes" for identifying semen in sexual assaults. "This got us started on [developing] antibodies to sperm," says ContraVac's Herr. Now Herr is trying to find financing for clinical trials of SpermCheck I, a home sperm-count kit "for vasectomized men or ones taking male contraceptives." Herr estimates that the market for the kit would be around $25 million a year.

There will be a much bigger market, he predicts, for SpermCheck II, which is designed to help infertile couples. In the United States alone, between 3 million and 6 million couples suffer infertility problems each year. In many cases only women are tested, says Herr, but men are at least part of the problem in half of all cases. ContraVac plans to market its male fertility test through physicians, a potential $49 million market in the United States, and over the counter, a potential $147 million market.

ContraVac's long-term project, a sperm-based antigen, isn't just for women, either. It eventually could help regulate sperm production so that men, too, could have a similar birth-control method.

Researchers at the Jones Institute for Reproductive Medicine in Norfolk have invented a birth-control pill that women can take for 84 straight days, so that they menstruate only four times a year.

"Besides the lifestyle advantages, this new pill has medical advantages for women with anemia," says Gary Hodgen, professor of obstetrics and gynecology. "And it helps with compliance. The biggest failure of oral contraceptives is patients forgetting to start and stop their pills. Compliance is higher when they only have to remember four times a year vs. 13."

Barr Laboratories Inc. has licensed the new pill in a unique partnership that could give Eastern Virginia Medical School (home of the Jones Institute) a bigger cut of royalties from future sales. "This is our first licensing arrangement of this kind: The university is more of an equity partner," says Bruce Downey, CEO of Barr Laboratories in Pomona, N.Y.

The product could hit the market in late 2002. The new pill isn't expected to displace existing oral contraceptives, but it could win a significant portion of the $1.6 billion market. Eastern Virginia Medical School, meanwhile, will head up the clinical trials and collect data needed to put the new product before the FDA.

It's been two years since researchers from Eastern Virginia Medical School's Diabetes Research Institute and McGill University in Montreal first discovered a gene that regenerates insulin-producing cells. The Ingap gene, which stands for islet neogenesis associated protein, could help identify patients who are predisposed to diabetes and potentially rewire their genes to properly generate insulin. The hope is that Ingap will cure diabetes altogether someday.

In June, researchers will present their latest findings to the National Diabetes Institute: Healthy animals given a synthetic form of Ingap produce double the number of islets, the cells that make insulin.

There are two types of diabetes. Type I is where the body kills off islet cells so insulin can't be produced. In Type II the pancreas makes insulin, but the body can't use it. "What we have shown ... is that we can increase the capacity to make insulin" in either case, says Dr. Aaron Vinik, director of the Diabetes Research Institute. "The next step is finding the right dose and administration."

Insulin is also the key to research conducted by Charlottesville-based Insmed Pharmaceuticals. The company's INS-1 compound can treat both Type II diabetes and polycystic ovary syndrome.

Though quite different, the two diseases have one thing in common: They make the body resistant to insulin. In Type II diabetes, insulin resistance wreaks havoc on glucose levels, which then can destroy body tissue. In polycystic ovary syndrome, the ovaries overproduce testosterone and become infertile. INS-1's job is to reverse insulin resistance.

"In clinical studies, the drug has shown great promise," says Insmed President Geoff Allan. "It can resume ovulation in a female."

There is no treatment available for polycystic ovary syndrome today, so Insmed is breaking new ground. The company already has conducted several clinical trials, and could have a drug available by the end of 2001. Allan estimates that the drug could generate $500 million a year in sales.

The diabetes version of the INS-1 drug, meanwhile, would join the $1.5 billion market for insulin sensitizers. The two big products today are Bristol-Meyers Squibb's Glucophage and Warner-Lambert's Rezulin, which can cause serious side effects. It is unlikely that INS-1 could be toxic, Allan says, since it "is found naturally in a number of fruits and vegetables we eat every day."

Someday, when you go get your flu shot, you may get a cancer shot, too. A Charlottesville company is working on a vaccine that directs "killer" T cells to attack invading cancer cells.

The idea is to kill cancer cells with proteins from those cells, much like allergists have done for years with allergy shots. "We are trying to develop a vaccine that bolsters the patient's immune system to fight cancer," says Aris Persidis, vice president of business development for Argonex, which has licensed the technology from U.Va.

Argonex extracts from cancer cells small bits of protein that sit on the surface of cells and label them as diseased. The sequence of these peptides differs for each type of cancer. Argonex has identified sequences for melanoma and is working on breast, colorectal, prostate, ovarian, lung, and head and neck cancer.

Early clinical trials are under way with melanoma patients at U.Va. and Duke University, mostly for identifying any problems or side effects. An actual cancer vaccine won't become available for at least five years, and the initial vaccine will be a companion treatment for chemotherapy to prevent recurrences.

Think of it as hormone replacement therapy for Parkinson's Disease: The lack of dopamine makes people with Parkinson's suffer from uncontrolled tremors and muscle rigidity. Discovery Therapeutics Inc. of Richmond produces a drug that mimics dopamine, the neurotransmitter that controls muscle movement.

Discovery, along with Schwarz Pharma Inc. in Mequon, Wis., is packaging the drug in a patch, which a patient would affix to his abdomen. The drug is scheduled to be released in two to three years, when the clinical trials are complete. This isn't the first patch-based drug for Parkinson's Disease, but it is unique. "It's specific in that it mimics only dopamine, nothing else," says Don McAfee, president of Discovery Therapeutics. "This reduces side effects."

The advantage of a patch over an oral Parkinson's medication is that it provides a continuous, steady dose. "You don't get the peaks and valleys of taking four or five oral doses a day," McAfee says. Discovery has licensed the patch drug to a Japanese pharmaceutical firm, Yoshitomi Phar-maceutical Industries Ltd., which will market the product in Japan. The worldwide market for Parkinson's therapy is $1.3 billion.

Discovery also is preparing to offer a diagnostic product using its hormone technology. The company has licensed what it calls "treadmill in a bottle" to Medco Research Inc. of North Carolina. The diagnostic test can be used in place of a treadmill stress test.

It's a geneticist's worst nightmare: Once you take DNA apart and sequence it, the "lanes" where genetic patterns are shown can get mixed up and compromise the data. "It's difficult to keep track of what sequence belongs on what DNA," says Richard Freer, chairman of Richmond-based Commonwealth Bio-technologies Inc. "Mistakes can be made."

Commonwealth's own researchers experienced the same headaches in their DNA sequencing. So the company came up with a solution it calls AccuTrac, which it now sells to other biotech firms. AccuTrac is a dye that keeps the DNA lane assignments in order. This is the first tool of its kind, and Commonwealth estimates that there is a $5 million to $7 million market for it. The Institute for Genomic Research in Washington, D.C., is test-driving AccuTrac for its work on the Human Genome Project.

Commonwealth also is about a year away from filing for FDA approval for HepArrest, a drug that restores blood clotting after cardiovascular surgery. Patients typically are given the drug Heparin to prevent blood clots during surgery, then Protamine to neutralize Heparin and resume clotting. HepArrest would be an alternative to Protamine. "Protamine has a lot of side effects, and physicians only use it when absolutely necessary," Freer says. It can cause blood pressure to drop as well as complications with blood platelets, which control the blood-clotting process, he says.

With research from Virginia Tech, CropTech rocked the pharmaceutical world in the mid-1990s by genetically engineering tobacco plants to make medicinal proteins.

So far, Blacksburg-based CropTech has grown plants that produce human hormones for cancer therapy and blood proteins for cardiovascular therapy, among other things. "All we are doing is proposing a new way of manufacturing them at a cheaper price," explains CropTech President David Radin.

CropTech takes a human protein, such as a cancer protein, and soaks hole-punched discs from young tobacco leaves in the solution. The protein "gets transmitted into the chromosomes of the plants," says Radin. Then these genetically engineered plants with the foreign genes reproduce and propagate the proteins.

Once CropTech perfects the process, it plans to get local tobacco farmers to grow the genetically engineered plants in full-scale production.

CropTech also is competing head-on with Genzyme, a large pharmaceutical company that manufactures an enzyme-replacement drug for a rare genetic disorder called Gaucher's Disease. And the company is working on a blood-clot "buster" protein for anticoagulants, which soon could be in full production.

Don't tell Genie the pig that her biggest rival is a tobacco plant. Researchers at Virginia Tech's Pharmaceutical Engineering Institute have genetically engineered about 100 pigs to produce the human protein C. The protein, which is produced in the sow's milk, will be used for a special fibrin glue that can stop bleeding in seconds. It also could reconstruct damaged tissue and deliver cancer treatments directly to tumors.

"When a tumor is removed, there are always residual cells at the wound. You could treat the wound and continue to deliver therapy there locally where cancer cells can regenerate," says William Velander, director of the institute. His organization has been working on the proteins for 12 years with the help of the American Red Cross.

Genie and friends were engineered with the protein when they were just embryos. "The gene gets naturally incorporated into the embryo's chromosome, then the surrogate mom gets pregnant and delivers piglets four months later," says Velander. "Thirty percent of them will have the gene, which turns on only in the mammary gland during lactation." Researchers then harvest the protein from the sow's milk. "We harvest one to three liters and leave the rest for the piglets," says Velander. Virginia Tech plans to begin FDA trials in the next three years.

Pharming Healthcare Inc., a Dutch biotech company, plans to manufacture the fibrin glue and another protein through a Virginia subsidiary. Velander says the market for fibrin glue could be as big as $500 million to $1 billion.

The idea for Fuisz Technologies hit Richard Fuisz when his daughter bought some cotton candy at a carnival.

Fuisz was fascinated by how cotton candy was mechanically -- rather than chemically -- transformed from crystalline sugar to fibrous sugar. He started fiddling with cotton candy machines in his garage, experimenting with different ways to cook up pills and tablets. He eventually developed a new way to formulate them using a spinning centrifuge and a flash of heat that forms a "bead" of medicine out of tiny microspheres.

The process is dry, meaning it doesn't use solvents like standard manufacturing methods. "If you don't get all of the solvent out of the packaging, it can eat away or destroy the characteristics of the drug," says John Redd, director of investor relations for Fuisz Technologies Ltd. of Chantilly. The new technology also lets pharmaceutical companies combine drugs into one pill by spinning them into the bead.

Big-name drug companies are taking notice. Fuisz is doing some development work for American Home Products, Bayer AG, Merck & Co. and Pfizer. Redd won't give exact details, but the work includes tablets that quickly dissolve in your mouth and other types of combination-drug formats for cardiovascular, anti-inflammatory and central nervous system drugs. Rapid-dissolve pills, which are made for patients who have difficulty swallowing, aren't unique. But Fuisz's technique for coating the pills -- so that they taste good -- is. "A perfect sphere is the dream in all drug formulation -- it's easier to coat," Fuisz says.

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Time will tell which of these breakthroughs will succeed in the commercial world. And in many cases, it will take a lot of time.

Development of a pharmaceutical product, for example, takes several years, and FDA approval for the new drug may take another six to 18 months. "Folks working on human injectable products or traditional vaccines are looking at anywhere from three to seven years to get their first product on the market," says BioEnhance's Carson.

Ron Gunn, Insmed's vice president for business development, concurs. "It takes a long time to get a product to market, so you have to fund it for a long period of time. And time is money."

© April 1999, Media General Business Publications Inc.,
publisher of Virginia Business Magazine