Replies to post #278315 on Amarin Corp Plc (AMRN)

[Bouf]

Inconceivable AMRN would not point this out at trial.

[HinduKush]

Mori in 2000


Woodman and Mori 2002

"Many of Plaintiffs’ arguments depend on the premise that a POSA as of March 2008 would not have expected that using a composition of purified EPA would not increase LCL-C levels. But this premise is not supported by the evidence. To explain, Plaintiffs primarily point to testimony from Dr. Toth to support this premise. …. But there are at least three issues with Dr. Toth’s testimony. First, he agreed under questioning that, as of “March 2008 the prior art reflect[ed] that all these treatments increased LDL-C in patients with very high triglycerides.” But that cannot be correct, because Mori taught that EPA did not increase LDL-C levels like DHA did." p. 59 Judge Du verdict

Let us look at two Mori papers with entirely differing findings from the same period and ascertain the wisdom taught: What emerges is that they taught in MILDLY hypertriglyceridemic subjects, COMPLETELY DIFFERENT outcomes can occur. In his 2000 paper Mori shows NO change in LDL for EPA and significant elevation in LDL for DHA, yet in another paper that followed in 2002 he shows NO change in LDL for either EPA or DHA, though both papers showed 15-20% reductions in Triglycerides (TG). Both populations are biased in sample towards middle aged men (with a smattering of menopausal women in the 2002 paper and very small sample sizes). What then did this definitively teach a POSA in 2000-2002?
(1) Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension; Mori et al. Am J Clin Nutr 2000; 71:1085-1094 (cited by Du)
Versus
(2) Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension Woodman, Mori, et al Am J Clin Nutr 2002; 76:1007-1015 (may have been cited by Covington)
The Woodman/Mori paper is key because it shows that conflicting EPA vs. DHA results on LDL were obtained during TG lowering by the SAME author…not exactly resounding evidence of obviousness.
In fact, far from thinking EPA was the holy grail, MORI favored DHA as an enticing clinical therapeutic approach. Indeed in 2000 using the same subjects he used in the Am J clin Nutr 2000 paper Mori published a mechanistic forearm blood flow analysis in Circulation 2000;102:1264-1269 in which he concluded : “Relative to placebo, DHA, but not EPA, enhances vasodilator mechanisms and attenuates constrictor responses in the forearm microcirculation. Improvements in endothelium-independent mechanisms appear to be predominant and may contribute to the selective blood pressure–lowering effect observed with DHA compared with EPA in humans.” Then again in 2003, again Mori et al are enamored of DHA (not EPA): “Woodman RJ, Mori TA, Burke V, et al. Effects of purified eicosapentaenoic acid and docosahexaenoic acid on platelet, fibrinolytic and vascular function in hypertensive type 2 diabetic patients. Atherosclerosis 2003; 166:85–93: “Highly purified DHA may be a more effective anti-thrombotic agent than EPA. However, longer-term studies assessing morbidity and mortality are needed in order to establish if DHA contributes to reducing CHD amongst Type 2 diabetic patients with treated hypertension.” Sound like anyone feels EPA effects are obvious or certain?

[ggwpq]

TTE, poster rmitra (Math professor?) pointed it out on 4/2/2020:

https://investorshub.advfn.com/boards/read_msg.aspx?message_id=154745267

I believe at least five different IHUB posters including me had emailed Elisabeth or Covington about this particular "Du" error as soon as rmitra mentioned it.