Today's call didn't cover any new ground, and was noteworthy, in my view, only for the fact that the attorney (Silbersher) offered up, when prodded, some rough odds on Amarin's success. If I were to find any fault in Silbersher's analysis, it would simply be in its lack of complete awareness of the trial record, which I appreciate was probably too much to expect. I do think that several posters here, myself included, are substantially more well versed on the details of the trial.
Setting aside any handicapping of the trial outcome, I'll just focus here on the two issues Silbersher spent most of his time on today.
INDUCEMENT
As I've stated previously, I think it is highly unlikely that Amarin will not prevail on the inducement issue. Judge Du knowingly tipped her hand on the inducement issue in her summary judgement decision. In that decision, she stated that she found Amarin's chronic condition argument persuasive. In my view, there was nothing that transpired during the trial that undermined Amarin's chronic condition argument in any meaningful way, with testimony from both Amarin's and defendants' experts (in part) bolstering that argument. Throughout the trial, and in their post-trial briefs, defendants tried to make the case that many physicians will not necessarily use the drug, as labeled, for chronic treatment. But that simply avoids the fact that inducement to infringe occurs when ANY physician is led by the label to use the medication for chronic treatment. It would be very, very difficult for Judge Du to convincingly construct a "no infringement" decision that finds that physicians who are well acquainted with severe hypertriglyceridemia as an often chronic condition would NEVER be led to prescribe this medication for 12 weeks or more based on the entirety of the label.
OBVIOUSNESS
In today's call, Silbersher focused primarily on the Mori prior art when discussing the obviousness issue. In my view, Silbersher failed to fully grasp the effectiveness of Amarin's dismissal of Mori as a basis for proving obviousness. Mori was a 59-person study that compared the effect of 4 grams per day of EPA to the effect of 4 grams per day of DHA on subjects with median triglyceride levels of 166 mg/dL and 199 mg/dL, respectively. Mori was a study that in no way studied the effects of EPA and DHA on subjects with triglyceride levels anywhere near 500 mg/dL. That's very significant, for, as stated by Dr. Toth, "We've already established that patients with very high triglycerides have a very different LDL response." Additionally, defendants' expert, Dr. Heineke, on cross-examination, acknowledged that a POSA would have understood patients with hypertriglyceridemia to be "entirely different" from patients with mixed dyslipidemia.
The generics argue that because EPA raised LDL levels less than DHA, a POSA would have found it obvious to eliminate EPA from any EPA/DHA therapy in order to more effectively treat severe hypertriglyceridemia without raising LDL levels. Amarin correctly argued a POSA would not have found this obvious for the following reasons:
- both EPA and DHA raised LDL levels in the study, with HDL raising LDL levels by 8%, and EPA raising LDL levels 3.5%
- the lower LDL raise in the EPA group can likely be attributed to the difference in baseline triglyceride levels between the two groups (DHA median level being 11% lower than EPA group triglyceride levels)
- the study included NO subjects with triglyceride levels over 500 mg/dL
- Severely hypertriglyceridemic patients (>500 mg/dL) had been shown to respond dramatically differently to triglyceride lowering therapies versus a <500 mg/dL population
Furthermore, Mori, rather than teaching that EPA offered any advantages over DHA, in fact taught that EPA was, by multiple measures, INFERIOR to DHA with respect to beneficial effects on subjects. Those measures include:
- inferior triglyceride lowering effects
- inferior ability to raise HDL
- inferior ability to increase LDL particle size
- inferior ability to not raise fasting glucose
For all of the above reasons, a POSA would clearly have not found it obvious to eliminate DHA from an EPA/DHA therapy in order to more effectively treat severe hypertriglyceridemia.
Note that the burden of proof for non-obviousness is on the generics, and that burden is a daunting one. They must prove that the USPTO clearly erred in issuing the Vascepa patents. To the extent they're relying on Mori to make that case, they fall far short of providing "clear and convincing" evidence that the examiner failed to grasp ways in which Mori demonstrated that Amarin's claims are obvious.
Today's call did not in any way change my view of the likely outcome of the trial. For more detail, see my previous post on the subject below, as it remains relevant.
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1) INDUCEMENT
The inducement issue hinges on intent. That is, can it be proven that the generics intend to induce prescribers to infringe. The legal standard for intent that applies in this case relates specifically to whether or not the label, considered in its entirety, so much as recommends or suggests that the product be used in a way that infringes on the claims in question. In my view, Amarin's argument on this issue is rock solid. At the core of their argument is the fact that Clinical Studies section of the label effectively instructs (or at a minimum, recommends or suggests) that patients take the drug for at least 12 weeks, and also instructs the doctor with respect to how administration of the drug will affect triglycerides, LDL levels, and ApoB reduction. This role of the Clinical Studies section in guiding how a medication is prescribed is supported by well-established case law (e.g. Sanofi), and real world practice as explained by expert testimony. The defendants' reliance on Grunenthal, Horizon, etc, is irrelevant, as all of those cases included carve-outs where the generics went to demonstrable lengths to avoid infringement, and they did not "encourage treatment of the specific condition that was the subject of the claimed methods", as is the case here.
The question of "substantial non-infringing use" is also irrelevant, as it simply does not apply to a case of induced infringement. Substantial non-infringing uses would only apply in a case of contributory infringement. For induced infringement to be proved, Amarin must only demonstrate that, by following the label in general, and the Clinical Studies section in particular, some doctors will prescribe the drug to some patients for more than 12 weeks, thereby infringing on Amarin's patents. They obviously will.
2) NON-OBVIOUSNESS
While there seems to be a lot going on around the non-obviousness issue, in my view it really comes down to just a couple of key issues. (And keep in mind that the bar for overturning the USPTO decision on Amarin's claims is very high. There must be clear and convincing evidence that the USPTO erred in approving the claims. In my view, the defendants don't come close to clearing that bar.)
The two key issues:
- Does the absence of severe hypertriglyceridemia patients or related findings from prior art render Amarin's claims non-obvious?
Amarin takes the correct position that the severe hypertriglyceridemia population is a distinctly different population from the sub-500 mg/dL population. The same triglyceride therapy will affect the two populations in very different ways. Amarin argues that any prior art that isn't in any way powered to identify how a given therapy works for this specific population (>500 mg/dL) teaches nothing about the efficacy of that therapy for this population. None of the prior art cited by the generics met this criteria, as they were all focused on populations <500 mg/dL. The generics work hard to persuade that one could conclude that the effects on the <500 mg/dL population can be obviously extrapolated to the >500 mg/dL population, but that's wrong on its face, and it's very effectively countered by Amarin. The statistically possible presence of 1 or 2 >500 mg/dL patients in Jelis or other prior art does little to change the argument, as none of their results were individually tracked or recorded, and therefore teach nothing about the effect of the therapy on that distinctly different population.
On the related issue of whether the prior art makes it obvious (i.e. provides a reasonable expectation of success") to a POSA that EPA will have a different effect on LDL levels than other triglyceride lowering therapies (i.e. niacin, fibrates, omega-3 fatty acids), the generics again try to make their case based on much of the same prior art, with the same result. A POSA looking at the prior art at the time would have had no reason to believe that purified EPA, administered to a population of severely hypertriglyceridemic patients, would do anything different from other triglyceride lowering therapies (i.e. raise LDL levels).
- Are the objective indicia supporting non-obviousness persuasive?
The objective indicia supporting non-obviousness are significant, as they were cited by the USPTO examiner as an important factor in the eventual approval of the Amarin claims in question. That, in itself, provides a difficult barrier for defendants to overcome here, and they don't do it. Using objective indicia such as long-felt need, unexpected results, widespread skepticism, widespread praise, and commercial success, Amarin makes an overwhelming case for the non-obviousness of the claims.
There are assorted other issues in the briefs related to non-obviousness, such as internal Amarin communications; REDUCE-IT nexus; late introduction of statin argument by defendants. However, while I think Amarin has the stronger position on most if not all of these issues, I think the key issues I've cited above are what will be the basis for the non-obviousness decision in Amarin's favor.
