I’m glad that the New York Times is digging into this story, the dispute between Moderna and the NIH, which has been boiling away in the background for a long time now. The question of inventorship on a pharma patent can get messy, and when you add in the overlap between publicly funded research and industrial for-profit research, things get even more tangled. Now throw in the life-saving vaccine that emerged from somewhere in this tangle, and stand back.
What’s not in dispute is that Moderna and the NIH have collaborated on mRNA vaccine work, and specifically on coronavirus mRNA vaccine work. Moderna of course has filed a patent application for the current vaccine, which includes no NIH scientists, but those NIH scientists themselves have filed relevant patent applications of their own (see the note at the end of this manuscript) and these do not seem to include anyone from Moderna. For better or worse, what I am not going to do here is bring up all the applications and compare their claims in detail, because (for one thing) I am not actually a patent attorney, so my opinions are of limited usefulness in this matter, and for another, that’s several days’ work and anyone who can do a thorough job on it should be paid for their efforts!
But let’s keep in mind the basic patent facts. The current patent system in the US bases priority on first-to-file, not first-to-invent. The latter was the case until 2013, and led to all the stories you hear about where people have to pull their lab notebooks out in court and prove the dates on which they had their inspirations. That’s all gone now, though, because it’s down to a much easier and much less arguable point: the date the patent office stamped on your application. The arguments, then, are what exactly each party claimed, and whether the earliest claims are valid on the face of them to start with, and if so, whether the later patents’ claims overlap them. You need novelty and utility for a patent, and if anyone doesn’t agree that mRNA vaccines for the coronavirus have passed the utility test then I can do without hearing from them. So, novelty. At that point you’re talking prior art – was your invention described somewhere else before your filing? There are all sorts of considerations about the timing of such disclosures relative to the patent filing, and what actually counts as a disclosure. Another factor is obviousness – even if your claims are distinguishable from the prior art, they can be rejected if “one skilled in the art” would have found them obvious from having read the previous work. So even though we’ve gotten rid of the fights about who had the actual inspiration first, we still very much have the fights about what was known, whether people could have or should have known it, and whether your own idea is actually new in light of all that.
And although it’s not as common a battleground, there’s also inventorship. This is largely a complication of US patent law; most other countries don’t get quite as convoluted as we do on this issue. The law is that every inventor needs to be on the patent, and that everyone on the patent must be an inventor. You can actually invalidate a patent on these issues – it’s not easy, but it’s possible. So what’s an inventor? The short answer is, someone who was in on the conception of the invention. If person A had the idea and asked person B to go try it out, and person B therefore became the first person to ever make the invention work with their own hands, person B is not an inventor. . .unless they had their own ideas along the way that were crucial to getting things to work, in which case maybe now they’re both inventors. But if you just carried out the work without adding such ideas, you’re not on the patent (or at least you shouldn’t be!) These concepts are generally explained to everyone who’s doing industrial research as they start their work, but they often have to be explained again. And as you can imagine, disputes can arise about who had the brainstorm and what the most important parts of it were.
Now you can see where the Moderna-NIH dispute is going to play out, and perhaps you can also see how difficult it might be to resolve. For example, the two parties worked on mRNA vaccines for the MERS virus, and apparently gave a good deal of thought to general strategies against coronaviruses in general. Which of those insights was crucial for the current vaccine? Did knowledge of the earlier SARS and MERS work make any of the later work obvious to one skilled in the art? As the world knows, the mRNA vaccines in general are directed towards the Spike protein: is that idea the crucial inventive step, and is sequencing the particular Spike for a given coronavirus of this type and directing an mRNA sequence to it merely an obvious step? Probably not, because as we know, if you just go with the native mRNA sequence it doesn’t work very well. There are plenty of inventive steps to get to a working vaccine. You have to add things at the start and end of the RNA sequence, you have to change some of the uridine residues to things like pseudouridine (which ones? how many?), you have to decide if you’re leaving in the furin cleavage site or not, you will want to “codon-optimize” the sequence, since there are often several ways to code in the RNA for a particular amino acid and some of those work better than others, and it turns out that you will also probably want to throw in the sequence for a couple of rigidifying prolines to keep the resulting protein in the “prefusion” conformation.
And that’s just at the RNA sequence step! But that (by all indications) is going to be one of the main points in this inventorship fight. To zero in on one example, that crucial prefusion stabilization trick was in fact patented by the NIH (and by some of the very same researchers involved in this broader dispute!) BioNTech and others have paid to license that patent. But Moderna has not. We’re going to see arguments about that, about who sequenced the virus and made that sequence available to whom, and about all the modifications that were made to it to turn it into a working vaccine. It’s going to be detailed, complicated, and ugly, and a great many legal hours are going to be billed along the way.
But as the Times article notes, it’s not just about bragging rights. Moderna has already stated that they are not going to enforce their patents during the pandemic, and as far as I can see, they have not been. Manufacturing of the mRNA vaccines, as I’ve said several times, has technical issues beyond what’s in the patent filings and technology transfer is not easy. But if the NIH really is a co-inventor, then they have a say in how the patent does eventually get licensed and in the profits to be made from the invention. I’m well aware that I have written many a blog post against the idea that all drugs are discovered by academia (NIH and NIH funding) and that pharma just swoops down and skims off the good stuff. And I stand by all that, because for the most part those folks are confusing basic research with what it takes to actually develop a drug. But when the NIH is collaborating directly with a pharma company on a particular type of vaccine, that’s another case entirely. That doesn’t happen often; this isn’t the rule at all in drug research. But we need to straighten this one out.
