November 14, 2021 § Leave a comment

The family in the title is, of course, the scientific community.  As reported in many places, including the New York Times, Moderna and the National Institutes of Health (NIH) are feuding regarding patent rights and inventorship of the key patent applications covering the Moderna version of the mRNA vaccine for Covid 19.

Lightly discussed in the press, but mentioned as a further point of contention, is that the NIH has a seminal patent for enabling the action of mRNA based vaccines.  The Covid 19 virus (SARS-CoV-2) has a structure resembling a crown, hence the name corona virus (see figure).  Note the spikes jutting out beyond the main body. This is composed of the spike protein. When the mRNA is introduced into the body it produces the spike protein, mostly in the liver.  However, merely being produced is not enough, because what matters to the immune system is not just the sequence of the protein, but the shape. Left to their own devices the produced proteins wouldn’t fold into the signature spike shape, so tricks are needed to nudge them in the right direction.

SARS-CoV-2 transmission electron microscopy image, courtesy NIAID-RML

To achieve this, NIH and university collaborators arrived at a method of covalently stabilizing the produced protein using a divalent sulfide bond.  The resulting “closed structure” is sufficiently like the SARS-CoV-2 spike protein as to stimulate the production of antibodies providing immunity from the disease.   A more scientific discourse on what was done is in a recent Nature paper.

The technique described above applies to all corona viruses.  The patent US 10,960,070, which issued just in March this year, covers all viruses with spike proteins.  The importance of this is twofold.  Firstly, any variant of the mRNA approach for addressing Covid 19 appears to need this technology to be effective.  More on that later.  Secondly, one concern continues to be that more corona virus mediated diseases are likely, particularly if the animal to human transmission with SARS originally from civets in 2002, MERS reportedly from camels in 2012, and now Covid 19, likely from bats, broadens to other species.  Were this to happen, it appears we have the technology to quickly produce mRNA vaccines to combat them.  Even this time around, the time scale of vaccine production was unprecedentedly short.

Now, back to the main dispute between Moderna and the NIH.  Facts not in dispute are that the NIH funded Moderna to the tune of USD 1.4 billion (yes with a b) to develop the vaccine.  This was a company that had never commercialized any product previously. NIH also provided experienced collaborators.  Three of them, Drs. Graham, McLellan, and Corbett, were inventors on the technique described above, and Graham was the lead inventor (in the eyes of the law all inventors are equal, but it is customary to have the largest contributor be named first; accordingly, the patent is referred to as the Graham patent).  Also, seemingly not in dispute is that US 10,960,070 is vital to the efficacy of any mRNA-based coronavirus vaccine.  Certainly, the creators of the other mRNA vaccine, Pfizer-BioNTech, licensed the patent.  Curiously, Moderna did not, and yet nobody is arguing that they are not using the technology in their vaccine technology.  My not very expert read of the claims in the patent is that the claims are strong and hard to work around.

If Moderna is using US 10,960,070 and not licensing it, why has the NIH not taken infringement action?  One explanation could be that the four-year collaboration certainly commenced prior to the March 2021 issuance of the patent, and until early this year, there was no certainty of issuance.  But it did issue.  Ordinarily, that would lead to some legal resolution.  Muddying matters is that NIH scientists collaborated and quite possibly the “background” technology, comprising the technique underlying the NIH patent was offered for non-exclusive use. This is normal in collaboration, but often includes “normal and customary” royalties in the event of commercialization. Perhaps it did not in this case. 

Now to the essence of the dispute.  NIH claims that the three scientists mentioned above ought to be named inventors.  The Moderna spokesperson says, “the company was legally bound to exclude the agency from the core application, because “only Moderna’s scientists designed” the vaccine”.  On the face of it the legal aspect is correct.  Being a collaborator is not sufficient.  Inventorship has the higher bar of direct contribution to at least one of the claims in the patent. This is a fact issue.

In context, the Times story states that the patent office “role is simply to determine whether a patent is warranted”.  While that is the case at this stage, if the validity of the patent is placed in dispute, inventorship is something that plays an important role.  Leaving out (provably) legitimate inventors can render the patent unenforceable, although the bar for proof is high. These days, the lowest cost means to challenge a patent is to appeal to a federal body through the Inter Parte Review (IPR) process.  Aside from being cheaper than conventional litigation, to date the IPR process has been substantially more challenge friendly than the courts.

Inventorship does not automatically grant ownership rights to the employers of the named inventors.  But it is usual for the patent to be co-owned in these cases, especially when both entities have invested in the discovery.  US 10,960,070, for example is assigned to NIH, Scripps, and Dartmouth.  Yet, the reporting has it owned by the NIH.  As is usual in these situations, there must be a side agreement on respective rights.  Absent that, each co-owner has the legal right to do what they want to with the property, which gets to be a mess. 

There is a hint in the reporting that part of the impetus for the NIH asserting co-ownership in the recent Moderna patent application is the desire to make it available to poorer countries.  If it did so by licensing, there is the risk of the licensee improperly executing, thus bringing disrepute to Moderna’s offering.  I have faced this in my career and always required safeguards, which would not be possible if Moderna was not directly involved in the licensing. The better resolution to this dispute is a royalty share rather than rights to license by the NIH, and an agreement for Moderna to make the vaccine available at lower cost to those poorer countries.  AstraZeneca is reputed to have done that.  When the Gates Foundation invested in CureVac (Germany) they made such a provision a condition.  The NIH ought to have done so at the outset.  In all fairness, the civilian bosses at the time may not have felt that way.  Now that horse has all but bolted*.

A feel-good story has turned into a horror show.  The poster child for public-private partnerships has become Exhibit 1 in the short course on how not to conduct collaborative innovation.

Vikram Rao

November 14, 2021

*”I drove my Chevy to the levee, and the levee was dry” from American Pie written and performed by Don McLean (1971)

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