The University of Rochester announced today that it has been awarded a pioneering patent for the use of the entire class of drugs known as cox-2 inhibitors, the popular new medications that have been heralded as "super aspirin" for their remarkable ability to ease pain and inflammation without causing side effects such as stomach pain, bleeding, or ulcers. Many experts believe that the drugs will replace aspirin and ibuprofen in the next century.
The class of drugs, which includes the blockbuster arthritis medication Celebrex, have become top-sellers since they were introduced last year. Doctors prescribed Celebrex to 6.4 million patients in 1999, pushing its first-year sales to $1.5 billion. Last year Celebrex eclipsed the anti-impotence medication Viagra as the fastest-selling new drug in history.
The patent awarded yesterday entitles the University of Rochester to royalties on the sale of all cox-2 inhibitors. Shortly after the patent was awarded, attorneys representing the University of Rochester filed an infringement suit in federal court against Searle and Pfizer, the pharmaceutical companies which jointly market Celebrex.
"We've filed a lawsuit against Searle and Pfizer to ensure that our legal rights are preserved, though we intend to begin discussions with both companies in an effort to negotiate licensing agreements," said Terrance O'Grady, an attorney for the University.
Over the 17-year life of the patent, royalty payments could yield the University royalties in the billions of dollars, making it the most lucrative pharmaceutical patent in history.
The new class of drugs was developed after researchers at the University of Rochester discovered the gene in humans that is responsible for producing an enzyme called cox-2 and revealed the enzyme's role in causing inflammation within individual cells. The discovery, made more than a decade ago, set in motion a worldwide race among pharmaceutical companies to identify drugs that would inhibit the action of the enzyme and, in turn, reduce inflammation and pain.
The University of Rochester research team was led by Donald Young, M.D., a physician and biochemist who for more than three decades has studied the mechanisms by which steroids reduce inflammation and produce other effects in cells.
"This patent recognizes the contributions of Dr. Young, an outstanding scientist who has devoted his career to understanding a problem that afflicts tens of millions of people," said Jay H. Stein, M.D., senior vice president for Health Affairs at the University of Rochester and chief executive officer of the University of Rochester Medical Center.
Young began his scientific career in the 1960s, studying the ways that steroids control the production of protein molecules inside cells. The work led him to question the role of a then-unknown protein that was produced in cells that were becoming cancerous. The protein appeared to be related to an enzyme then known as cyclooxygenase, or cox, made in every cell in the body and whose activity could be blocked by aspirin and other nonsteriodal anti-inflammatory drugs.
Young and two other researchers in his lab, Kerry O'Banion and Virginia Winn, studied the newly discovered protein and identified the gene that produces it. They found that, unlike cox, the production of the new protein could be virtually shut down by administering an anti-inflammatory steroid. This finding led Young to conclude that aspirin and other NSAIDs were effective at controlling inflammation because they were acting on the new protein - which was later named cox-2 - and that the unwanted side effects of gastro-intestinal irritation and bleeding were caused by the NSAIDs' effects on the original cox enzyme, which would later come to be known as cox-1.
Further study of the cox-1 enzyme revealed that its role is not related to inflammation. Rather, it is believed to have many roles - among them, to turn off the secretion of gastric acid in the stomach. Aspirin and other NSAIDs, while effectively blocking cox-2 also block cox-1, resulting in excessive production of stomach acid as well as ulceration and gastrointestinal bleeding. These and other side effects of aspirin and other NSAIDs caused 76,000 people to be hospitalized in 1998 and resulted in 16,500 deaths.
Young and his colleagues at the University of Rochester were the first to demonstrate that production of the cox-2 enzyme is triggered by two kinds of molecular messengers called inflammatory cytokines and growth factors. The team also genetically-engineered two types of cells - one that produces cox-2 but not cox-1, and vice-versa - to enable researchers to identify drugs that inhibit the production of cox-2 without inhibiting the production of cox-1. Several pharmaceutical companies used Young's cells, or similar methods, to develop cox-2 inhibitors.
In addition to the remarkable ability of cox-2 inhibitors to control pain and inflammation, research suggests that the drugs can also prove useful in preventing cancer and Alzheimer's disease. Young's work in 1990 established a link between cox-2 and cancer, an avenue that his lab and now hundreds of others are actively pursuing. Several studies by researchers across the country have demonstrated that the use of cox-2 inhibitors is able to reduce the incidence of colon cancer - and deaths from the disease - by nearly half. Other studies have suggested that the use of cox-2 inhibitors can also be effective in reducing the incidence of Alzheimer's disease by more than 60 percent.