Amarin Corp Plc (AMRN)

[HinduKush]

Apparently when it comes to objective indicia of obviousness favoring Amarin, Judge Du could be most perceptive and finickity regarding differences in population characteristics...pity she couldn't also apply this to her understanding of >500mg/dl and < 500 mg/dl populations in TG lowering...might have prevented her thinking Mori was some sort of Rosetta stone to unraveling EPA effects for year 2000 POSAs

REDUCE-IT
Plaintiffs point to the results of the REDUCE-IT study as objective evidence of
nonobviousness. (ECF No. 379 at 35-37.) The REDUCE-IT study was “a multicenter,
randomized, double-blind, placebo-controlled trial involving patients with established
cardiovascular disease or with diabetes and other risk factors, who had been receiving
statin therapy and who had a fasting baseline triglyceride level of 135 to 499” mg/dl and a
fasting baseline LDL-C level of 41 to 100 mg/dl. (Ex. 1641 at 1 (the “Bhatt Article”).)
Each subject in REDUCE-IT had a fasting baseline triglyceride level of 135 to 499
mg/dl. (Id. at 2.) “[B]ecause of the intraindividual variability of triglyceride levels, the initial
protocol allowed for a 10% lower triglyceride level from the target lower limit, which
permitted patients to be enrolled if they had a triglyceride level of at least 135 mg per
deciliter.” (Id.) In May 2013, the first protocol amendment “changed the lower limit of the
acceptable triglyceride level from 150 mg per deciliter to 200 mg per deciliter, with no
allowance for variability.” (Id.)
Nevertheless, there was a substantial fraction of patients in the REDUCE-IT Study
with median triglyceride values <150 mg/dL during the study, given that the inclusion
criteria for triglycerides was limited to the screening exam for entry into the study and
because triglyceride levels can vary over a wide range. More specifically, about 10% of
subjects had triglyceride levels below 150 mg/dl, about 30% had triglyceride levels
between 150 and 200 mg/dl, and the remaining subjects had triglyceride levels about 200
mg/dl. (Id. at 4, Table 1.)
While a small subset of patients had triglyceride levels that rose above 500mg/dl at
some point in time during the REDUCE-IT study due to intraindividual variability,
“REDUCE-IT focused on patients with triglycerides below 500.” (ECF No. 371 at 1894:12-
14.) Again, “eligible patients . . . had to have a fasting triglyceride level of 150 to 499
milligrams per deciliter. This is less than 500 milligrams per deciliter.” (ECF No. 367 at
818:18-21.) Thus, REDUCE-IT was not “designed to evaluate patients [with] triglycerides
above 500” and did not include any patients with a baseline triglyceride level of 500 mg/dl
or above. (Id. at 819:14-16.) Dr. Budoff agreed that “REDUCE-IT focused on a different
patient population than the patient population” for Defendants’ labels. (ECF No. 366 at
530:16-19.) In fact, the MARINE study and REDUCE-IT study, and thus the related
indications, involved “completely different patient populations.” (Id. at 589:21-1.)