The Atlantic is out with a list of “Brave Thinkers”, and one of them is Jay Bradner at Harvard Medical School. He’s on there for JQ1, a small-molecule bromodomain ligand that was reported in 2010. (I note, in passing, that once again nomenclature has come to the opposite of our rescue, since bromodomains have absolutely nothing to do with bromine, in contrast to 98% of all the other words that begin with “bromo-“)
These sorts of compounds have been very much in the news recently, as part of the whole multiyear surge in epigenetic research. Drug companies, naturally, are looking to the epigenetic targets that might be amenable to small-molecule intervention, and bromodomains seem to qualify (well, some of them do, anyway).
At any rate, JQ1 is a perfectly reasonable probe compound for bromodomain studies, but it got a lot of press a couple of months ago as a potential male contraceptive. I found all that wildly premature – a compound like this one surely sets off all kinds of effects in vivo, and disruption of spermatogenesis is only one of them. Note (PDF) that it hits a variety of bromodomain subtypes, and we only have the foggiest notion of what most of these are doing in real living systems.
The Atlantic, for its part, makes much of Bradner’s publishing JQ1 instead of patenting it:
The monopoly on developing the molecule that Bradner walked away from would likely have been worth a fortune (last year, the median value for U.S.-based biotech companies was $370 million). Now four companies are building on his discovery—which delights Bradner, who this year released four new molecules. “For years, drug discovery has been a dark art performed behind closed doors with the shades pulled,” he says. “I would be greatly satisfied if the example of this research contributed to a change in the culture of drug discovery.”
But as Chemjobber rightly says, the idea that Bradner walked away from a fortune is ridiculous. JQ1 is not a drug, nor is it ever likely to become a drug. It has inspired research programs to find drugs, but they likely won’t look much (or anything) like JQ1, and they’ll do different things (for one, they’ll almost surely be more selective). In fact, chasing after that sort of selectivity is one of the things that Bradner’s own research group appears to be doing – and quite rightly – while his employer (Dana-Farber) is filing patent applications on JQ1 derivatives. Quite rightly.
Patents work differently in small-molecule drug research than most people seem to think. (You can argue, in fact, that it’s one of the areas where the system works most like it was designed to, as opposed to often-abominable patent efforts in software, interface design, business methods, and the like). People who’ve never had to work with them have ideas about patents being dark, hidden boxes of secrets, but one of the key things about a patent is disclosure. You have to tell people what your invention is, what it’s good for, and how to replicate it, or you don’t have a valid patent.
Admittedly, there are patent applications that do not make all of these steps easy – a case in point would be the ones from Exelixis – I wrote here about my onetime attempts to figure out the structures of some of their lead compounds from their patent filings. Not long ago I had a chance to speak with someone who was there at the time, and he was happy to hear that I’d come up short, saying that this had been exactly the plan). But at the same time, all their molecules were in there, along with all the details of how to make them. And the claims of the patents detailed exactly why they were interested in such compounds, and what they planned to do with them as drugs. You could learn a lot about what Exelixis was up to; it was just that finding out the exact structure of the clinical candidate that was tricky. A patent application on JQ1 would have actually ended up disclosing most (or all) of what the publication did.
I’m not criticizing Prof. Bradner and his research group here. He’s been doing excellent work in this area, and his papers are a pleasure to read. But the idea that Harvard Medical School and Dana-Farber would walk away from a pharma fortune is laughable.