WHAT GILEAD DID RIGHT AND WHY ITS SOFOSBUVIR (HEPATITIS C TREATMENT) PATENT WILL STAND

Hepatitis C (HVC) has been cured, and for the low, low price of $94,500 f you too can be cured of this disease.  HVC affects between 2.7 and 3.9 Million Americans and about 71 Million people worldwide with the opioid crisis driving the incidence of new cases higher every year, so news of a cure made many, many people happy.  The price tag for this cure is quite another thing.  Since the release of its wonder drug, Sovaldi, brand name sofosbuvir, and sofosbuvir containing cocktail, Harvoni, Gilead has been under constant fire for price gauging.  What’s more, the patent for sofosbuvir will remain in force until 2030, leading some commentators to believe that there is little hope that Gilead will lower the cost of either Solvaldi or Harvoni anytime soon, leaving millions of HVC suffers unable to afford treatment. 

We can argue about the pricing for Solvaldi and Harvoni another day.  Today’s post is about the sofosbuvir patent. U.S. Patent No. 7,964,580 (the ‘580 Patent), which covers sofosbuvir, was filed with claims directed to one compound, sofosbuvir itself, and compositions and methods related to this compound.  The choice to file a patent with extremely narrow claims is likely going to cause detractors, like the Initiative for Medicines, Access & Knowledge (I-MAK) who believe the ‘580 Patent is invalid, headaches.  This post explains why the choice to pursue narrow claims was the right choice. 

The ‘580 Patent was filed in March 21, 2008.  The application describes a genus of drugs for treating viral infections, particularly HVC.  The genus is encompassed by a class of compounds known as nucleotide analogues, which have been under development since the 70’s as a treatment for cancer and viral infections.  Nucleotide analogues look similar to the nucleotides that make up DNA.  Sofosbuvir, and other anti-viral nucleotide analogues, work by incorporating into the viral DNA strand, blocking DNA chain growth, and stopping viral replication.  The virus kills the cell (and itself) without sending new viral particles into the host until no viral particles remain in the host.  The HVC patient is cured.

In 2007, the earliest priority date for the subject matter of the ‘580 Patent, tens of thousands of patents and patent applications describing anti-viral nucleotide analogues had already been filed.  Here’s a look of the landscape in 2007.  The ‘580 Patent will fall within the circled area.   

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As you can see, there is a lot of prior art (dots) in this space overall.  For context, I included dots showing Pharmasset (the filer of the ‘580 Patent) prior art in yellow, competitor Idenix prior art in red, and Gilead prior art in blue.  Despite falling in a less well-developed valley, 133 patents and patent applications describing similar nucleotide analogues for treating HVC had already published in March, 2007, when the sofosbuvir patent was filed. 

Here is where Pharmassett made a very good choice.  Claim 1 of the ‘580 Patent as filed reads:

1.     (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fl- uoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid isopropyl ester or a stereoisomer thereof.

That is the IUPAC (International Union of Pure and Applied Chemistry) name for sofosbuvir or stereoisomers thereof.  Even though the specification of the ‘580 Patent describes genuses encompassing thousands of compounds, Pharmassett chose to pursue claims directed to 1 compound, their lead. 

The Pharmassett claims were allowed without a single rejection being issued, leading many patent lawyers to exclaim: “There’s no way this patent is valid!”  Most patents in the pharmaceutical space face years of prosecution, with the patent Examiner combining structural elements from compounds described in various references and arguing that the compounds are obvious.  Since this did not appear to occur for the ‘580 Patent, most commentators believe these claims can’t be valid, and in October 2017, I-MAK filed Inter Partes Review (IPR) petitions requesting that the U.S. Patent Office revoke the ‘580 Patent based on these very arguments.  Far from exploiting the patent system as I-MAK will have you believe, Pharmassett knew that they were entering a marketplace that was filled with prior art, and the likelihood of easily obtaining claims to even a modest genus of compounds was relatively low.  They made the strategic choice to pursue claims directed to one compound. 

The Examiner’s primary goal during is to find a single reference that describes any of the compounds encompassed by the genus of a claimed invention.  The reference doesn’t need to specifically describe the compound, but if they can combine variable elements of a genus described in reference and arrive at the compound, the claims are not novel.  Typically, the claims of the application are modified to exclude the hypothetical compound identified by the Examiner overcoming the novelty rejection, but setting the Examiner up for a strong obviousness argument.  Inventors must then prove non-obviousness, typically by comparing the activity of the compounds in the reference verses the compounds of the claims. 

By pursuing claims that Pharmassett knew were novel, they circumvented amending the claims and cluttering the prosecution record with non-obviousness arguments and data that could be interpreted differently by different experts.  The believed that the Examiner wouldn’t find a novelty destroying (anticipating) reference.  He didn’t, and at this point, none of some 375 prior art references identified in various venues have been found to anticipate the claims of the ‘580 Patent.  Without an anticipating reference, the Examiner knew that any obviousness rejection would be relatively weak, and rather than prolong prosecution, he allowed the claims, issuing the ‘580 Patent without rejection.

I-MAK is relying on obviousness to invalidate the ‘580 Patent.  This is a problem.  Under U.S. Patent law, obviousness can be overcome using a variety of “rebuttal arguments,” which developed judicially over the years.  Rebuttal arguments include long-felt need, commercial success, failure of others, and evidence that the invention yields unexpectedly improved properties.  Sofosbuvir as claimed in the ‘580 Patent meets the evidentiary burden for proving each of these rebuttal arguments.  As such, it is unlikely that I-MAK will succeed in invalidating the ‘580 Patent using obviousness arguments.  I suspect the ‘580 Patent will stand.

The genius of Pharmassett’s strategy is that they pursued claims that they knew were novel and that covered their product.  They didn’t attempt to pursue broad compound claims or try to cover competitor compounds they knew were in the prior art.  The result is a patent covering 1 compound and pharmaceutical compositions and methods for using the compound that drives a $59.3 Billion per year industry and is effectively uninvalidateable.  They probably spent $15,000 filing and prosecuting the patent, and obtained an invaluable patent.  I’d call that a win.  The take home message: Broad claims do not always equate to high value patents.