Biotech General Discussion

In an unusual development related to the Vascepa ANDA litigation, the lead investigator of the Reduce-It trial and two colleagues published an article online attacking the district court judge's ruling especially with respect to the Mori reference (Curfman et al., "Federal Judge Invalidates Icosapent Ethyl Patents –But Based on a Common Statistical Mistake" (2020)) (Electronic copy available at: https://ssrn.com/abstract=3618671)). Does this change Amarin's chance of winning the appeal? We do NOT think so.

It is noteworthy that we still believe that Amarin has a 25-40% chance of winning on appeal. Furthermore, there is at least one key factor in the litigation that will play out in this appeal that could affect Amarin's chances significantly. We will discuss this factor, and any other significant developments in future posts as the appeal unfolds. We continue to maintain our investment in Amarin in our tracking fund and in my personal account, with the same number of shares as before the district court ruling.

Why do we believe this recent Curfman et al. publication will have no impact on the outcome of the Vascepa ANDA appeal?

1. The specific detailed analysis of the Curfman et al. publication cannot be brought into the appellate procedure by Amarin. They needed to present this analysis in the district court phase of the litigation.

2. Even if the analysis in Curfman et al. was made of record in the appeal, in our view, it wouldn't affect the appellate court's obviousness ruling. Patent law regarding obviousness, as recognized by the District Court judge, does not require a guarantee of success, just a reasonable expectation (Pfizer, Inc. v. Apotex, Inc., 480 F.3d (Fed. Cir. 2007) at 1364). The district court judge in the Amarin litigation recognized that Mori's disclosure did not guarantee success, but concluded it was enough for a skilled artisan to have a reasonable expectation of success: "But even if Mori and other studies on patients with lower TGs did not provide “conclusive proof” of EPA’s effects, they were enough to form “a reasonable expectation of success.” citing Hoffmann-La Roche, 748 F.3d at 1331.

3. The district court's factual finding that Mori found that DHA and not EPA significantly increased LDL-C levels appears consistent with the conclusions in the Mori paper.

4. On the other hand, it is possible that the Fed Circuit could overturn the District Court's obviousness ruling in holding that its finding regarding Mori were clearly erroneous. However, that seems unlikely, especially with respect to the conclusion of differential effects of DHA vs. EPA on LDL-C levels.

5. We don't feel that an amicus brief citing the statistical analysis of Curfman et al. will be filed, or even if it was, would effect the appellate court's ruling regarding obviousness in this case.

If you are interested in the detailed considerations supporting our conclusions above, read on.

1. The specific detailed analysis of the Curfman et al. publication cannot be brought into the appellate procedure by Amarin. They needed to present this analysis in the district court phase of the litigation. Amarin could have presented this analysis during the district court litigation proceedings and it likely was aware of it, but chose not to. It cannot now get this analysis into the litigation through a "back door" because its consultant and supported researcher, Dr. Bhatt (See e.g., Curfman et al. 2020; and https://www.acc.org/membership/person?id=c968f275-bde8-45b6-b7db-00d6e6c909cf) publishes an article that performs a statistical analysis to challenge the district court judge's reliance on the Mori prior art reference. This would create an unfair situation to the generic defendants who have not had an opportunity to depose/examine any expert or these authors about the analysis in Curman et al., and did not have an opportunity to present an expert themselves, to rebut the article's analysis and conclusions. It appears to us, likely too late in this litigation for Amarin to present the analysis in Curfman et al. in the appeal at this point.

2. Even if the analysis in Curfman et al. was made of record in the appeal, in our view, it wouldn't affect the appellate court's obviousness ruling. Patent law regarding obviousness, as recognized by the District Court judge, does not require a guarantee of success, just a reasonable expectation (Pfizer, Inc. v. Apotex, Inc., 480 F.3d (Fed. Cir. 2007) at 1364). The district court judge in the Amarin litigation recognized that Mori's disclosure did not guarantee success, but concluded it was enough for a skilled artisan to have a reasonable expectation of success: "But even if Mori and other studies on patients with lower TGs did not provide “conclusive proof” of EPA’s effects, they were enough to form “a reasonable expectation of success.” citing Hoffmann-La Roche, 748 F.3d at 1331.

3. The district court's factual conclusion regarding Mori appears consistent with the conclusions in the Mori paper: "Mori also reports that “[s]erum LDL cholesterol increased significantly with DHA (by 8%; P = 0.019), but not with EPA (by 3.5%; NS),” (Ex. 1538 at 3), “strongly suggesting that these two Omega-3 fatty acids could have distinct effects on LDL cholesterol levels” (ECF No. 367 at 740:1-17) (emphasis added). Possibly the judge went too far in asserting the following: "Mori concludes that “EPA and DHA had differential effects on lipids.” (Ex. 1538 at 1; see also ECF No. 371 at 1827:8-19.) Therefore, “a skilled artisan would understand from Mori that DHA and EPA work differently.” (ECF No. 371 at 1829:6-8.)" However, it seems that this could be a skilled artisan's reasonable conclusion based on Mori's conclusion that DHA but not EPA significantly increased LDL-C. And it seems that the Federal Circuit will be hard-pressed to find clear error in this conclusion. In fact, that could be one reason that Amarin did not focus on this issue in its opening appeal brief. Furthermore, at least two other prior art references, Hayashi (1995) and Kurabayashi (2000) were cited by the district court for the factual finding that a skilled artisan would have understood that DHA but not EPA causes an increase in LDL-C (See pgs. 27-29, 34, and 58 of the DCt opinion).

4. On the other hand, it is possible that the Fed Circuit could overturn the District Court's obviousness ruling, or possibly remand to the District Court for further obviousness analysis, in holding that its finding regarding Mori were clearly erroneous. However, that seems unlikely, especially with respect to the conclusion of differential effects of DHA vs. EPA on LDL-C levels. If the Federal Circuit rules that the district court's factual findings on Mori are clearly erroneous, it will likely be based on the patient population analyzed in Mori et al., as focused on by Amarin in the opening appellate brief. But the clearly erroneous standard presents a high bar: "A finding is “clearly erroneous” when, although there is evidence to support it, the entire record leaves the reviewing court with a definite and firm conviction that a mistake was made. The reviewing court cannot reverse the trial judge’s account of the evidence if it is plausible in light of the entire record, even if the reviewing court is convinced that it would have weighed the evidence differently." (Litigating for Appeal-Practical Tips for Patent Trial Counsel; 2014; IP Litigator (citations omitted); Available at https://www.finnegan.com/en/insights/articles/litigating-for-appeal-practical-tips-for-patent-trial-counsel.html) The District Court judge relied on Mori for providing a reasonable expectation of success that unlike DHA, EPA would not cause an increase in LDL-C, as recited in the asserted claims. There is some discussion of Mori et al. and the issue of DHA vs. EPA and effects on LDL-C by Amarin in some of its district court briefs and its opening Appellate Brief (See pg. 15 "While, at Defendants’ urging, the district court seized on the LDL-C difference between DHA and EPA in Mori in assessing obviousness, Mori itself found it unremarkable. In fact, Mori comments about the rise in LDL-C observed in both groups and hypothesizes that it results, in part, from the same mechanism described in the literature discussed above—an increased conversion of VLDL to LDL: … .") Thus, the Federal Circuit could hone in on this issue and rule the district court judge's ruling regarding Mori's teachings was clearly erroneous. However, as discussed herein, the district court judge's analysis does not seem to rely on a statistical difference between DHA and EPA, which is the subject of the Curfman et al. 2000 paper. Rather, the district court judge appears to base her conclusion of reasonable expectation of success on the accurate finding the Mori indicated that DHA but not EPA significantly increased LDL-Cs. The fact that Amarin did not focus on this issue in its opening Appellate brief, but rather focused on Mori's patient population vs. the patient population in the recited claims, is telling regarding the argument against the judge's findings and Mori that Amarin feels are strongest. Indeed, Amarin tried to attack Mori's LDL-C findings in the district court, by relying on Von Schacky (2006), but that failed and was not reiterated by Amarin in its opening appellate brief.

5. It is possible that some organization, such as the American Medical Association* would try to submit an Amicus brief concluding that the trial court's factual findings regarding Mori were clearly erroneous based on the statistical analysis of Curfman et al. However, the Federal Circuit has to grant a party permission to file the Amicus brief. And in our experience factual error is not a typical, maybe not an appropriate basis for an Amicus brief. (See for example, "How to Be a Good Friend: Amicus Brief FAQs," by Lawrence S. Ebner (In-House Defense Quarterly; Summer 2013; Available here). Furthermore, it might be too late for the court to permit a party to admit an amicus brief in Amarin's favor since the defendant's brief is due within 1 week. Even if such an amicus brief was filed, for the reasons of 1-4 above, we don't think it will influence the court's decision in this appeal.

In summary, for the reasons provided above, we find it unlikely that the analysis of Curfman et al. will come into the Amarin ANDA litigation appeal, and even if it did, unlikely that it would impact the Federal Circuit's decision regarding obviousness of the Amarin patents in view of Mori and the other cited prior art. Having said this, as we indicated in our introductory paragraph we still believe that Amarin has a 25%-40% chance of winning on this appeal. We continue to maintain our investment in Amarin in our tracking fund and in my personal account, with the same number of shares as before the district court ruling.

Manny Vacchiano, JD, PhD

Registered patent attorney

Michael Mand, PhD (registered patent agent and law student) assisted me with research for this article

*The corresponding author of the Curfman et al. article that is the focus of this article is apparently employed by the Journal of the American Medical Association (https://ssrn.com/abstract=3618671).

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*Emanuel "Manny" Vacchiano, J.D., PhD., is a licensed U.S. patent attorney.

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