The Johns Hopkins Gazette: August 16, 1999
August 16, 1999
VOL. 28, NO. 42


Invention Brings New Recognition

By Greg Rienzi
The Gazette
Johns Hopkins Gazette Online Edition

Curt Civin, King Fahd Professor of Oncology and Pediatrics, has learned that patience, pardon the cliché, is indeed a necessary virtue for any scientist. Countless lab hours and years of research might ultimately lead to a breakthrough discovery, but sometimes that is only the beginning. How about waiting an additional 15 years before your discovery can be mass marketed?

Civin knows that feeling. And now he knows one more cliche: Good things do, in fact, come to those who wait.

Civin was recently named the 1999 Inventor of the Year in recognition of a discovery he made in 1984--a stem-cell selection process that has paved the way for more effective and less toxic cancer therapies.

Curt Civin explaining his stem-cell selection process at the recent 1999 Inventor of the Year Award ceremony in Washington.

The honor is given annually by the Intellectual Property Owners Association, a nonprofit organization that serves inventors and companies that own patented inventions. The Inventor of the Year Award is open to innovations of all types, whether it be a pharmaceutical drug, an electronic gadget or a new type of plastic.

The guidelines state that eligible inventions are those patented or FDA approved within the preceding four years. Biological patents to a drug typically take from 12 to 15 years to be granted, and Civin's 1984 discovery was patented and received Food and Drug Administration approval in 1996.

Civin's breakthrough came when he developed the CD34 monoclonal antibody, which made it possible for the first time to identify, isolate and collect hematopoietic stem cells, the immature cells in our bodies that give rise to mature blood, marrow and immune cells. Civin's antibody in essence works as a highly specific "hook" that selectively captures the stem cells, which are usually located in bone marrow.

One major clinical application for Civin's discovery was speeding up recovery time for cancer patients following high-dosage chemotherapy. Prior to CD34, physicians would harvest the patient's bone marrow before chemotherapy and then return it to the body. However, the transplanted bone marrow could still contain cancerous cells, which could then spread to the rest of the body. The cancer therapies also damage and often destroy blood cells and the immune system, leaving patients vulnerable to infections and other life-threatening complications.

By using CD34, a patient's healthy stem cells can be harvested from the marrow and after chemotherapy returned to the body, where they migrate to the marrow and start producing new blood cells, renewing the body's blood and immune systems.

Civin also invented a process that could purify cells on a large scale, isolating the rarer, more formative stem cells while weeding out the more numerous, but less desirable, mature cells.

Clinical trials of the selection process began in 1990, and since that time, more than 10,000 patients have received transplants of stem cells purified using Civin's monoclonal antibodies.

Stem-cell selection also can greatly reduce graft vs. host disease that occurs when transplanted cells reject the body as foreign, rather than vice versa. For instance, foreign T-cells in transplanted bone marrow can lead to major complications, but by using CD34 physicians can purify the marrow by getting rid of the T-cells before it is transplanted. Civin's process also is useful in targeting stem cells for the purpose of gene therapy.

Martin Abeloff, professor and director of Oncology in the School of Medicine, says Civin's discovery has wide-reaching applications.

"Being able to identify adult blood stem cells opens up all sorts of opportunities for studying diseases of the blood. It's not just limited to oncology," Abeloff says. "It ends up being a pivotal discovery in that we can now learn more about the fundamental science that will enable curing therapies to be developed in the future."

Civin takes great pride in those patients currently receiving benefits from his stem cell treatments and is quite optimistic about the potential of his discovery leading to possible cures and further clinical improvements, such as treating sickle-cell anemia and autoimmune diseases.

He also is intrigued about how stem-cell selection has already become such an accepted medical practice.

"It is really interesting how it has become kind of like the wallpaper. Everybody knows about and uses it," Civin says.

He also acknowledges that potential royalties from his invention could be quite significant.

"The transplantation field is growing astronomically, and the gene field is, too," Civin says. "Its use is still growing. Hopefully, this process will become a vital part of both fields."

Civin has nine U.S. patents for biomedical inventions related to his stem cell research. Hopkins licensed his invention to Becton Dickinson Corp., which in turn has sublicensed it to several other companies, including Baxter Healthcare Corp. and Nexell Therapeutics Inc.

Both Hopkins and Civin will receive royalties from the sales of a device called the Isolex 300i Cell Selection System, a machine manufactured by Nexell that uses Civin's technology. The device is nearing FDA approval and should become commercially available in the United States this year.

Civin, who received his medical degree from Harvard Medical School in 1974, joined the Hopkins faculty in 1979. Since then he has been an active leader and innovator in childhood cancer patient care, laboratory research on blood and immune system development, clinical investigations in pediatric oncology and bone marrow transplantation. He is currently on the board of five medical journals and has published more than 135 articles in peer-reviewed journals.

Being named Inventor of the Year, Civin says, is "a very great honor." And the award, coupled with the pending commercial availability of his invention, has made 1999 a very good year for Civin and for Hopkins.

The Intellectual Property Owners Association award honors inventions that have a significant impact on the population. Past winners include Chrysler engineers Howard Benford, Gerald Holbrook and Maurice Leising, who developed the electronically controlled automatic transmission; Harold Aller and Adam Hsu for Confirm, an agricultural insecticide; and Jewell Osterholm of Thomas Jefferson University for his development of a stroke treatment system.

"It would be a great honor if this was just an award for medical discoveries, but the real neat thing about this is that it's an award for all inventions," Civin says, noting that there were "many worthy inventions" eligible this year, including an IBM microchip that is 500 times faster than its predecessors. "I take great pride in that."

Abeloff agrees that receiving an award that cuts across research fields is significant, and he says it reflects well on both Civin's work and Hopkins.

"Hopefully, this is a sign of more good things to come," Abeloff says.

Civin already sees good things to come.

He cites the new cancer building with an entire floor devoted to leukemia and stem cell research, and how the level of stem cell research has grown on a national level. And he says CD34 should help scientists find out even more about the once elusive stem cell.

"This research started as a Hopkins and a Baltimore thing," Civin says. "Now it's out there for everyone."