Amarin: What does Amarin’s opening appellate brief say?
Zachary Silbersher
On May 12, 2020, Amarin ($AMRN) filed its opening appeal brief in its appeal of the decision by the District of Nevada wherein the Honorable Miranda M. Du invalidated six patents that were asserted against prospective generics, Hikma and Dr. Reddy’s. What does the brief say?
Amarin’s brief embraces a clear theme: hindsight. Amarin starts with the premise that hindsight infected nearly all aspects of the lower court’s analysis. It makes three principle arguments in favor of reversal, and it threads the idea of hindsight through each of them. The first two arguments both relate to the lower court’s assessment of the objective indicia of non-obviousness, otherwise known as secondary considerations. The third argument relates to a factual finding, namely, whether it was truly unexpected that pure EPA would not increase bad cholesterol in patients with TG levels above 500 mg/dL.
The Cyclobenzaprine Argument.
First, Amarin argues that the lower court improperly considered the secondary considerations by shifting the burden to Amarin to prove they should overcome the prima facie case of obviousness. This is the Cyclobenzaprine argument that we previously discussed at length in an earlier post. In that post, we remarked that making this argument may be challenging because the face of the lower court’s Bench Order does not necessarily smack of this error.
Likewise, Amarin’s brief acknowledges that this argument is not so simple as pointing out that the lower court first made a prima facie determination of obviousness before moving onto secondary considerations. Indeed, Amarin acknowledges that employing the phrase “prima facie case,” by itself, does not render an obviousness decision reversible. Amarin contemplates further retorts to this argument, such as acknowledging the lower court paid lip service to the law on secondary considerations and that its argument is not merely one of semantics.
These slightly defensive tactics speak to the challenges of this argument. As we discussed in our earlier post, there does not appear to be a consensus among the Judges at the Federal Circuit that the holding in Cyclobenzaprine addressed a problem that needs fixing. Put another way, how do you actually show that a lower court improperly relegated the secondary considerations to secondary status?
The generics will likely argue that Judge Du’s analysis was proper. The lower court’s Bench Order took each secondary consideration in turn and assessed whether it weighed in favor of obviousness or patentability. The court then concluded by stating that, “in view of all four Graham factors (including alleged secondary considerations), the patents are deemed obviousness.” (Bench Order at 69). The court then cited to Zup, which held that it was not improper to assess secondary considerations separate from the prima facie case. Nor is there any dispute—and Amarin is not arguing—that simply because one or two secondary considerations weigh against invalidating a patent necessarily means that the clear-and-convincing-evidence burden has not been met. So, given all that, the generics will likely argue Amarin’s first argument cannot stick.
Anticipating these arguments, Amarin takes care to explain that the way that Judge Du assessed the evidence dictated the incorrect outcome. This is one of the more powerful sections of the brief. For instance, Amarin points out that, if Mori clearly taught that pure EPA would not increase LDL-C in patients with severe hypertriglyceridemia, then why did no one else develop or even study that formulation before Amarin? (Amarin, interestingly, emphasizes that Mori actually preceded Lovaza®. (Br. at 36.)) If Mori’s conclusions about pure EPA’s effect on bad cholesterol in patients with TG levels exceeding 500 mg/dL were so obvious, then why did the inventor of Amarin’s patents face so much skepticism? If a drug that could lower TG levels in severe hypertriglyceridemic patients was so obvious, then why was Vascepa® met with noteworthy praise and significant commercial success?
Stripped of all the legal mumbo-jumbo, Amarin is essentially arguing that Judge Du weighed the evidence incorrectly. By making the prima facie case of obviousness based upon Mori, that prejudiced the lower court from recognizing the true weight of the secondary considerations. For instance, although the lower court found evidence of long-felt need, it failed to appreciate why that long-felt need persisted for so long. The reason, according to Amarin, as argued extensively at trial, is that persons of skill did not view Mori in the manner that Judge Du did. Rather, in Amarin’s view, they believed that all TG-lowering drugs would lead to a surge in LDL-C in patients with severe hypertriglyceridemia.
There are some risks to this argument. For one thing, as previously discussed, not all Judges on the Federal Circuit appear to agree that the holding of Cyclobenzaprine is necessarily correct. Accordingly, the composition of the panel may be determinative of Amarin’s chance of success. Some judges may be hesitant to announce a sweeping change to the law on obviousness, undoubtedly one of the most important aspects of patent law, without the winds of change demanding it. This probably explains why although Amarin leads with the Cyclobenzaprine argument, it nonetheless holds back from trying to start a revolution. In other words, it is not clamoring on about a rot in the law of obviousness, and unless the Court adopts the rationale of Cyclobenzaprine, scores of otherwise meritorious patents will be invalidated.
That said, the arguments that you lead with do matter. Despite the foregoing risks, leading with the Cyclobenzaprine argument nevertheless has the advantage that it is assessed against the de novo standard. It is therefore possible that the panel of Judges do not necessarily agree new precedent must be set on the method of assessing secondary considerations, but they might nonetheless buy into what is at issue in this particular case—namely, that the lower court gave too little weight to the evidence of long-felt need or commercial success. And that alone might be enough to move the needle.
The Weighing of the Secondary Considerations Argument.
Amarin next argues that the lower court improperly “weighed” the secondary considerations against each other. We anticipated this argument in our earlier post. This is a strong legal argument because there does not appear to be any caselaw for weighing secondary considerations against each other in the manner performed by the lower court. As Amarin argues in its brief, “[f]ollowing the district court’s logic, Amarin would have been better off had it simply brought less evidence, because then there would have been fewer categories of objective indicia to count against those that the district court found. This cannot be the law.” (Br. at 45).
This is powerful stuff. If you are arguing for reversal on appeal, you typically yearn for the opportunity to point out that the actual law applied by the district court does not, in fact, have any basis in the caselaw.
Moreover, this argument is essentially a backstop to Amarin’s procedural argument. As discussed above, the Cyclobenzaprine argument suffers from the fact that it potentially lacks consensus at the Federal Circuit. By contrast, this “weighing the secondary considerations” argument appears, at least as of now, to be a relatively clear error of law on which there is not tremendous disagreement. (If there is, in fact, support in the law for weighing secondary considerations against each other, the generics are sure to cite to it in their response brief.)
Yet, both Amarin’s first and second arguments essentially plead the same grievance—namely, the lower court took the evidence and weighed it incorrectly. It gave too much weight to secondary considerations that did not weigh in favor of nonobviousness (such as skepticism, praise, unexpected benefits), and not enough weight to those that did (commercial success, long-felt need.) By discounting the weight of long-felt need and commercial success based upon the evidence of skepticism, praise and unexpected benefits, the lower court essentially added another stone to the scales in favor of the generics. That made it easier for the generics to reach their clear-and-convincing evidence standard. Removing those stones should recalibrate the balance, and, as Amarin argues, reveal the generics to be shy of satisfying their burden.
The Two Patient Populations Argument.
Amarin’s final argument relates to the factual question that was the centerpiece of the entire case: At the time the patents were filed, was it surprising to persons of skill that administering pure EPA to patients with severe hypertriglyceridemia would not increase bad cholesterol (LDL-C)? Judge Du found it was not surprising. Amarin contends that was clearly erroneous. This is the meat of what this case is all about.
What is, in fact, not surprising is that Amarin has returned to this argument on appeal. It devoted considerable time at trial to create a record to support it. It cites extensively to that record in its brief. It hammers the theme that there are essentially two patient populations—those with TG levels above 500 mg/dL and those below, and the evidence showed they responded differently TG-lowering drugs. It recounts the evidence solicited at trial that all existing drugs for lowering TG levels (niacins, fibrates and Lovasa®) also increased LDL-C in patients with severe hypertriglyceridemia.
That said, there remain essentially two sides of this argument. The generics argued that Mori showed that DHA, rather than EPA, was responsible for increases in LDL-C in patients with high TG levels. In their view, that made it obvious that the same would be true for patients with severely high TG levels. On its face, that is not a terrible argument. For a benefit to be “unexpected” does not require that it was absolutely proven within the prior art. Oftentimes a guidepost or suggestion in the prior art is enough. (To be anticipatory, prior art also does not need to teach with the same rigor required by peer-reviewed journals or FDA approval.)
Yet, Amarin added another layer to this narrative during the trial, and now again on appeal. It argues that the general understanding in 2008 was that it was not the drug, but the condition, that mattered. The evidence at trial showed that persons of skill as of 2008 doubted that any drug could lower TG levels in patients with severe hypertriglyceridemia without simultaneously increasing LDL-C. Rather, they believed that, for patients with TG levels above 500 mg/dL, activating the enzyme that would break the TG logjam would necessarily lead to a clearance from VLDL to IDL and to an eventual spike in LDL.
All of this, Amarin argues, was overlooked by Judge Du. Had it been considered, the lower court would not have found Mori’s findings to read through from patients below 500 mg/dL to patients above that threshold. Rather, the court would have appreciated the difference between the two patient populations. And that would have meant that Mori taught nothing about what the patents require.
There is weight to this argument, and unlike the first two “procedural” legal arguments, this “two patient populations” argument really speaks to what this case, and these patents, are all about. Judges often prefer to limit their holdings to the facts of a specific case so as to avoid a venture into unnecessary pronouncements on the law. This factual argument gives the Court the chance to do just that.
On the other hand, the generics are likely to emphasize in response that Amarin’s “two patient populations” narrative is a ruse. The patents do not claim their invention this way, but rather encompass an arbitrary patient cutoff at 500 mg/dL. Because there is no evidence to support a meaningful difference between a patient at 499 and another patient at 501, Amarin is rumbling on and on about a distinction between patient populations that irrelevant to the patent claims.
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On balance, even if appeals are difficult to win, for the reasons discussed above, this appeal has traction. That said, this appeal suffers from certain obstacles that no one can do anything about. This case does not touch upon any major hot-button policy considerations in the fields of patent law or pharmaceuticals. Nor does Amarin marshal any, apart from possibly the Cyclobenzaprine issue. The Federal Circuit has affirmed the invalidity of scores of branded pharmaceutical patents in the past, and it will most likely continue to do so without concern that it will diminish investment in pharmaceutical R&D. Moreover, while Amarin does a very diligent job of detailing an inventor story, the patents do not really jump out as groundbreaking stuff. For all the talk about how surprising it was that pure EPA would not increase LDL-C in certain patients, that data is not in the patents themselves. While none of this stuff is necessarily case-dispositive, the Federal Circuit—a court that hears more patent cases than any court in the country—approaches its cases with many of these background considerations in mind.
Nevertheless, handicapping Amarin’s appeal cannot be adequately done without reviewing the generic’s response brief. They will develop their own themes and their own narratives for why, even if marginal errors of law or fact occurred in the Bench Order, they remain harmless, and the patents should remain invalidated. For that, we wait another month.