When true innovation is disclosed in the pages of a patent application, the innovator is rightfully granted a patent to secure what is presumably some inventive leap forward. While that may often be the case with first-generation pharmaceutical patents, follow-on patents covering blockbuster drugs more-often exhibit substantially less genius.
As a first example, consider the Humira patents. Humira was first approved by the FDA in 2002, and the first Humira patent expired in 2016.
AbbVie’s patent thicket for Humira (generally, adalimumab) includes several patents for which petitions to the PTAB were filed. These include U.S. Patent No. 8,889,135 (“the ‘135 patent”), one of a family that issued from applications that issued late in Humira’s lifecycle, shortly before the original patent expired. The alleged innovation disclosed and claimed in the ‘135 patent essentially reduces to this: Treat arthritis by arm-injecting (“subcutaneously”) with twice as much Humira (40mg instead of 20mg), at half the frequency (every 13-14 days—i.e., two weeks—instead of weekly).
Had a claimed “invention” of that magnitude been applied-for in the software arts, there is little doubt the patent examiners handling such an application would have rejected the claims out of hand.
AbbVie managed to convince the drug-patent examiner, however, that at the time of the alleged invention (around 2000), one of ordinary skill in the art would have considered it unreasonable to expect the newly-claimed dosing regimen would work, without clinical proof supplied by AbbVie. This was even though the prior art knew that a twice-as-long, half-as-often dosing regimen worked just-fine when administered by intravenous (IV) means; that a 20mg dose per week subcutaneously worked nearly as effectively as 40mg per week; and that the half-life for Humira is nearly two-weeks long (between 11.6 and 13.7 days), meaning that half of a 40mg dose still is circulating in a patient’s bloodstream for a time-range that overlaps the claimed time range.
Is it really impossible for one of skill in the art to reasonably predict that a subcutaneous injection wouldn’t work similarly to an intravenously-administered injection, and where 20mg of a 40mg dose remains after nearly two weeks?
The problem here seems to be that the patent examiners who work in the pharmaceutical arts (or at least some of them) apply much-closer to an FDA standard when assessing obviousness. The FDA might want clinical trials to make sure treatments are as effective subcutaneously as they are intravenously, but the Patent Office is supposed to apply a different standard. The Patent Office is supposed to be concerned with the advancement of innovation. The FDA is concerned with safety.
Ever since the Supreme Court decided KSR v. Teleflex, it has been appropriate to reject a patent claim because it was obvious to try. If twice the dose intravenously, half as often works, why wouldn’t the highly-educated person of skill in the art – who would hold an M.D. or Ph.D. level education with years of experience – not be tempted to try the same thing subcutaneously? And if they do try it and the results are as expected that should mean, under KSR, that the claimed invention is obvious. Somehow in the pharmaceutical arts KSR does not get applied that way.
With its issued claims drawn to a presumed-inventive, shot-in-the-arm treatment for arthritis, the ‘135 patent thus was armed to block biosimilar competition for years.
For all those who want to argue how expensive it can be when clinical trials fail – that may be true with truly-new compounds that revolutionize treatment of a disease. It is, however, not true when it comes to making exponentially smaller leaps of ingenuity in moving from one dosing regimen to another. In that scenario, there is essentially no downside-risk to the drug company in conducting clinical trials for a new dosing regimen or formulation for an existing drug, just the potential upside of convincing the PTO to issue a term extension for drug-market exclusivity, for no good reason.
Fortunately, in May and July 2017, three different panels of the Patent Trial and Appeal Board (PTAB) (with five different Administrative Patent Judges between them), saw through this charade. Armed with the benefit of evidence from experts on both sides of the issue through trial, they agreed with the petitioners that the prior art already knew how to correlate IV dosing regimens to the more convenient arm-shot method, routinely; that a 20 mg dose per week was “nearly equally efficacious when given weekly via arm-injection (subcutaneously); and that the half-life for Humira is between 11.6 and 13.7 days; or at least that it would have been on any skilled doctor’s very-short list of obvious things to try a double-dose, half-as-often regimen, with a reasonable expectation that it would succeed at treating arthritis. The patent was held to be invalid as obvious over the prior art.
The ‘135 patent does not appear to represent the kind of “innovation” or “invention” we should incentivize with a multi-billion-dollar annual bounty for the patentee, paid from the pockets of patients. And while it may be tempting to believe there is no real harm because insurance companies pay the bills, the undeniable truth is that one of the primary drivers for out-of-control medical insurance costs in America is the astronomical cost of drugs. So in the end, patients either pay themselves directly or indirectly through rising insurance premiums.
In the next installment, I will discuss another AbbVie blockbuster drug, which has been the subject of antitrust enforcement grounded in the exploitation of a major loophole in the drug-patent system arising from the listing of a drug patent in the so-called “Orange Book.”