Scripps Chemistry Idea “Clicks” With Big Pharma, Seattle’s Integrated Diagnostics
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through phases of testing, Finn says.
“A lot of this is going on in Big Pharma. I know this for a fact. People in Big Pharma have incorporated this as part of their workflow,” Finn says. Materials science guys who work on things like adhesives, maybe because they don’t need to explain everything they do to the FDA, jumped on the click method as early adopters, Sharpless says.
The turning point for “click chemistry” came in 2001 when Sharpless and Fokin showed a reaction that combined azide with an alkyne that was catalyzed by copper. The functional groups themselves are stable, and don’t react with much, Finn says. When you’re ready, you put the chemicals together and they click into an irreversible bond. Basically, you can staple two things together. The paper has been cited more than 1,500 times, Finn says.
“It’s an awfully easy reaction to do and very stable. Manufacturing-wise, it’s incredibly important,” Finn says. The irreversible act of clicking separates winners from losers. If it clicks, you know there’s something special about the reaction.”
Once you have molecules that bind in this fashion, a lot of possibilities open up. You can have drug candidates that bind tightly, and irreversibly with a target, what’s known as a “high affinity,” property. Getting that high-affinity property in a drug early in the screening process can speed things up, and allow more time for checking out other properties to make sure the drug isn’t too toxic, or to see whether you can link it to some other molecule with desired characteristics, like a long-lasting polymer, or a potent toxin to kill tumors. In the long slog of drug development, when it often takes a decade or more of work, “if you can shave a couple years off a process, that’s worth something,” Finn says.
One hot application of the moment involves linking biologic molecules to toxins, through what is called “conjugation.” This is a notoriously tough problem that has eluded scientists for decades. It’s a quest to develop targeted antibody drugs, loaded with toxins, that would be like “magic bullets” or “smart bombs” for tumors. Creating stable linkages between drug and toxin has been a major challenge, but a couple of different cancer drug candidates—one from Roche and Waltham, MA-based ImmunoGen, and another from Seattle Genetics and Millennium: The Takeda Oncology Company—have shown a striking ability to shrink tumors this way. That has prompted renewed interest among other pharmaceutical companies to get into this “conjugation” game, and find other scientific techniques to help them catch up. That’s partly what has made the phone ring at Scripps, Finn says.
Scripps’ Forrest, the tech transfer officer, says he isn’t ready to name names or talk terms yet, but there are a number of partnerships in the works.
Not much of all this business activity seemed to interest Sharpless very much. His mind famously moves faster than his mouth, and he is known for stopping in the middle of a sentence and changing his train of thought. Listening to the digital recording of my 59-minute conversation with Sharpless made me smile and laugh yesterday. He truly comes across as a sincere-but-absent-minded professor. When I told him about how I write about innovative life sciences people and companies in San Diego, he launched into a friendly riff about how I must have to listen to a bunch of bunk.
Clearly, somebody else will do the negotiating for him.
“I’m sort of the old mad dog who doesn’t believe in a lot of stuff. I have a hard time with biotechnology and green chemistry. It’s hard for me,” Sharpless says. “The point of chemistry is in the middle where everything gets connected. Function is what matters. To me, it wouldn’t matter if you can make malignancies regress with three different types of inorganic salts as long as they weren’t toxic.”