claims for molecules in areas where they already had shut down their own projects, Boger ridiculed Searle’s Markush structure. Searle hadn’t made a sulfonamide and had no experimental data on whether it would work. Aldrich told them Vertex wanted to “work something out and get this important drug to patients.” The discussions dragged on for months afterward, until Glaxo Wellcome’s lawyers also took an unsuccessful stab at it.
In April Boger got a fax from Glaxo Wellcome. “I remember I was on vacation, golfing in Hilton Head, and Josh sent me an email saying we just took a torpedo below the waterline,” Aldrich recalls. “Josh is always very positive about things and always pooh-poohs anyone else’s science or any problem, but this was clearly a problem that shook him up. Searle was a problem for us and Glaxo.”
A delegation from Glaxo Wellcome arrived at Vertex to tell Boger and Aldrich that they were shutting down the VX-478 clinical trials because they couldn’t get the patent cleared. The timing—on the cusp of testing whether the drug worked—could scarcely be worse. “We’re a public company and HIV is our lead program, so we’re looking into thefreakin’ abyss,” Aldrich says. “I said, ‘Before we do this, there’s one thing we could try.’ ” Searle’s position made no sense: if Glaxo and Vertex shut down the program, Searle got nothing. Aldrich suggested sending a joint letter offering to pay $25 million and a 5 percent royalty in exchange for the exclusive license to all Searle’s patent applications in the area of HIV protease inhibition, and warning that if they didn’t hear back in a week they would go the New York Times with the story that they were shutting down the trial because of an IP dispute with Searle. “A Hail Mary pass,” Aldrich called the proposal. Searle took the deal.
“We would have been blown up. We were toast. We wouldn’t have been able to raise money. Our stock would have gone from fourteen dollars to two. It was very stressful. It was a very nervous place. People could just see that Josh and I were freaked out. That Friday after we got that yes, I had a few pops.”
The dispute was settled none too soon. Two weeks later, at the 1996 international AIDS conference in Vancouver, British Columbia, a cascade of encouraging reports showed that HIV could be suppressed indefinitely by a combination of antiviral drugs built around protease inhibitors. Three years after the despair in Berlin, combination therapy—drug cocktails—transformed AIDS from a death sentence to a manageable disease. The epidemic peaked in the United States with fifty thousand deaths in 1995. With the first of the drugs—Hoffman–La Roche’s Invirase, Abbott’s Norvir, and Merck’s Crixivan—reaching the market during the previous six months, people who had been planning to die sooner than later suddenly and unexpectedly could see futures for themselves. New York, San Francisco, and other urban centers started to fade as “cities of ghosts.” Other drugs—better absorbed, with fewer side effects—were still desperately needed.
Vertex, its near-death scare with Searle concluded, remained squarely in the race.
In the labs, the hepatitis C virus continued to pose extreme problems at every stage. A critical challenge in coaxing individual proteins, which are floppy and active, to rigidify and lock themselves into crystals is learning how to subdue them with the right mother liquor. Researchersanthropomorphize enzymes, describing them as “happy” or “perturbed.” Organic molecules prefer certain conditions to others—some dissolve better in water, others in fats. The goal is to induce a kind of nirvana: amniotic fluid laced with heroin. And yet the insertion of the synthetic peptide caused the team to have to grind hard for months, substituting endless experimental conditions, amid rumors that another company had solved the structure of the protease and was rushing it
In April Boger got a fax from Glaxo Wellcome. “I remember I was on vacation, golfing in Hilton Head, and Josh sent me an email saying we just took a torpedo below the waterline,” Aldrich recalls. “Josh is always very positive about things and always pooh-poohs anyone else’s science or any problem, but this was clearly a problem that shook him up. Searle was a problem for us and Glaxo.”
A delegation from Glaxo Wellcome arrived at Vertex to tell Boger and Aldrich that they were shutting down the VX-478 clinical trials because they couldn’t get the patent cleared. The timing—on the cusp of testing whether the drug worked—could scarcely be worse. “We’re a public company and HIV is our lead program, so we’re looking into thefreakin’ abyss,” Aldrich says. “I said, ‘Before we do this, there’s one thing we could try.’ ” Searle’s position made no sense: if Glaxo and Vertex shut down the program, Searle got nothing. Aldrich suggested sending a joint letter offering to pay $25 million and a 5 percent royalty in exchange for the exclusive license to all Searle’s patent applications in the area of HIV protease inhibition, and warning that if they didn’t hear back in a week they would go the New York Times with the story that they were shutting down the trial because of an IP dispute with Searle. “A Hail Mary pass,” Aldrich called the proposal. Searle took the deal.
“We would have been blown up. We were toast. We wouldn’t have been able to raise money. Our stock would have gone from fourteen dollars to two. It was very stressful. It was a very nervous place. People could just see that Josh and I were freaked out. That Friday after we got that yes, I had a few pops.”
The dispute was settled none too soon. Two weeks later, at the 1996 international AIDS conference in Vancouver, British Columbia, a cascade of encouraging reports showed that HIV could be suppressed indefinitely by a combination of antiviral drugs built around protease inhibitors. Three years after the despair in Berlin, combination therapy—drug cocktails—transformed AIDS from a death sentence to a manageable disease. The epidemic peaked in the United States with fifty thousand deaths in 1995. With the first of the drugs—Hoffman–La Roche’s Invirase, Abbott’s Norvir, and Merck’s Crixivan—reaching the market during the previous six months, people who had been planning to die sooner than later suddenly and unexpectedly could see futures for themselves. New York, San Francisco, and other urban centers started to fade as “cities of ghosts.” Other drugs—better absorbed, with fewer side effects—were still desperately needed.
Vertex, its near-death scare with Searle concluded, remained squarely in the race.
In the labs, the hepatitis C virus continued to pose extreme problems at every stage. A critical challenge in coaxing individual proteins, which are floppy and active, to rigidify and lock themselves into crystals is learning how to subdue them with the right mother liquor. Researchersanthropomorphize enzymes, describing them as “happy” or “perturbed.” Organic molecules prefer certain conditions to others—some dissolve better in water, others in fats. The goal is to induce a kind of nirvana: amniotic fluid laced with heroin. And yet the insertion of the synthetic peptide caused the team to have to grind hard for months, substituting endless experimental conditions, amid rumors that another company had solved the structure of the protease and was rushing it
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