Here’s an article on a company called Molecular Isotope Technologies, and their bid to “revolutionize the drug industry”. From the name, you might expect that this is another deuterium-for-proton idea, and you would say to yourself “But that’s already been done”. But read on.
The company is perhaps better known by the name of one of their divisions, Nature’s Fingerprint. Through the use of painstaking stable-isotope analysis, they’ve been able to assist in drug-counterfeiting and drug-authentication cases – a surprising amount of information about the starting materials and process chemistry involved in a given pharmaceutical can be learned this way. (Here’s a short paper they’ve published on the subject). But the idea they’re talking about here is a bit more aggressive:
Jasper, founder and chief executive of Niantic-based Nature’s Fingerprint, will publish a paper next month in the leading scientific journal Pharmaceutical Technology that opens the possibility of essentially re-patenting existing drugs and extending their lives for up to 20 years through a new process known as molecular isotopic engineering.
“Because MIE designed drug molecules are essentially new chemical entities, MIE has some potentially interesting intellectual property implications,” Jasper and colleagues Peter Farina, Ann Person, Peter S. Mezes and Anthony D. Sabatelli said in the journal article, which he released with approval early to The Day.
Jasper said that by using isotopic engineering, pharmaceutical companies may be able to tinker with existing formulations using his patented method to make subtle changes that could be considered by regulators as distinct chemical entities. The result could be companies being able to patent multiple versions of the drug, allowing pharmaceutical firms to essentially extend the lives of their brands — if, Jasper emphasized, U.S. and other regulators approve the new idea.
Hmm. The paper isn’t online yet, as far as I can see, but this certainly sounds like taking an existing drug, coming in with a new synthesis using stable isotopes (such as carbon-13) and calling the resulting compound a new molecular entity. And it’s one that should work exactly like the old one, because that sort of isotope change should have zero (or very close to zero) effect on metabolism, mode of action, or anything else. (That’s as opposed to the deuterated-drug idea, where you place the D atoms in just the spots where bonds are being made and broken, in order to have a real effect on metabolism and clearance).
So sure, you can make isotopically labeled versions of drugs. But I can see a number of problems with using this idea to “revolutionize the drug industry” (no doubt the paper will address these?) First off, will these compounds be patentable? There will be interesting questions of novelty and utility, and it seems to me as if the doctrine of equivalents would come into the picture (is a difference that makes no difference really a difference?) That’s one hurdle. Next is the fact that if you’re claiming that these compounds are different enough to have their own patent lifetimes and their own regulatory approvals, then they’re different enough to have their own clinical trials run on them. You will, of course, have the huge advantage of knowing that they’re going to work up front, but you won’t be able, I think, to waltz right to market without presenting the usual sort of package to the FDA.
But that takes us to the third problem, which is a big one: will the FDA accept such an application, and will they approve it? From a pure efficacy-and-safety viewpoint they might have little choice, but then again, the agency hasn’t been faced with the request to approve what is, safe for an almost meaningless distinction, the exact same drug as something that’s already available. The sort of people who get worked up over “me-too” drugs will absolutely blow a fuse about these, and for once, I might join them.
There’s an even bigger problem waiting after that one, and to me, it’s the one that sinks this whole idea: who will pay for these isotopic drugs even if they’re approved? If the idea is, as stated in that article from The Day, to extend the patented lifetime of a given drug, that means that the new fresh Isotopically Distinct! version is going to be competing with the generic form of its parent drug. And if sticking in some carbon-13s or what have you confers no benefit at all, what insurance company would possibly go for it? I just don’t see it happening.
Reading the article, it appears that one advantage that the isotopic-labeling method would offer is a way to make the compound so distinct (by mass spec) that it’s expensive to counterfeit. That’s not a negligible benefit, but (if I’m interpreting the press material from Nature’s Fingerprint correctly), existing isotope fingerprint methods already offer this sort of protection, albeit with more work on the analytical chemistry end of things. I’m just not sure that this is enough to drive this whole idea.
And to be honest, I hope it isn’t. This sort of evergreening will advance medical science not one tiny bit, and just the possibility of it being feasible (from a legal, regulatory, and financial standpoint) seems to me to be a moral hazard. We actually don’t need brand new rent-seeking methods and new opportunities to play games with patent lifetimes and product compositions. Discovering drugs is brutally hard work, and I can understand why people are looking for easy and lucrative ways to bypass the whole thing, but we’re better off when the industry has to make new discoveries in order to keep going. Short-circuiting this arrangement, by any means, seems like a really bad idea.