Replies to post #263904 on Amarin Corp Plc (AMRN)

[anfla]

What do you mean is the stat sig difference from baseline in the Apo B arm close enough?

That arm alone tells us nothing about EPA treatment effect at all. Not a little, not a small amount. It tells you zero.

For example -
What if you asked 30 overweight individuals to fast and half were randomized to EPA and half were control. And both lost weight. Can you use the weight loss in the epa group to assess weight loss from epa? No.

[stockmantoday]

The funny thing is that MARINE proved, in some sense, the ambiguity that exists in the Kurabayashi study.

Remember, Kurabayashi was 1.8 g / day. MARINE dosed two treatment groups: a 2 g and 4 g / day group.

There was no statistically significant reduction in ApoB in the 2g / day group in MARINE. In fact, the 2 g / day group saw an INCREASE in ApoB from baseline and a statistically insignificant decline relative to placebo. ANCHOR saw reductions that were marginally significant. If anything, the combination of MARINE/ANCHOR/Kurabayashi lead one to conclude, today, that 2 g / day of EPA has no impact on ApoB. It's the 4 g dosing that makes the big difference.

None of this is legally relevant, but it just points out that if Table 3 in Kurabayashi is enough to make the clear, statistically significant reduction in ApoB seen with 4g/day of EPA a "not unexpected success," we probably have too high a standard for patentability.

[amarininvestor]

Here is what the judge says

Kurabayashi further reports a statistically significant reduction in Apo B levels in the EPA group of 6.9%. (Id. at 4-5.) With a p-value of < .001, EPA’s effects on Apo B were highly significant. (Id.; see also ECF No. 367 at 737:1-23.) In contrast, Kurabayashi reports a non-statistically significant 1.5% reduction in Apo B levels in the control group. The results reported in Kurabayashi do not suggest any interaction or synergy between EPA and estriol. (ECF No. 367 at 735:21-736:9.) Instead, synergy is usually only seen between drugs that have similar effects, such as two drugs that reduce blood pressure. (Id.) In light of the statistically-significant differential effects reported between the EPA and control groups, a POSA would have attributed the reduction in Apo B to EPA

Now see the below from Kurabayashi’s conclusions (which is supported by the analysis of table-3). Let’s remember that the below is not an opinion, it is a basic conclusion of that paper (a fact), therefore a POSA would not be expected to read the paper and its conclusion in a different way. In my opinion what the judge says: “In light of the statistically-significant differential effects reported between the EPA and control groups” is just an incorrect interpretation of the facts.

"The apolipoprotein B level in the eicosapentaenoic acid group was significantly lower at week 48 compared with the baseline level, but there was no significant difference between the groups".

[rafunrafun]

From the same document:

REBUTTAL OF PRIMA FACIE CASE OF OBVIOUSNESS
Applicants can rebut a prima facie case of obviousness based on overlapping ranges by showing the criticality of the claimed range. "The law is replete with cases in which the difference between the claimed invention and the prior art is some range or other variable within the claims. . . . In such a situation, the applicant must show that the particular range is critical, generally by showing that the claimed range achieves unexpected results relative to the prior art range." In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See MPEP § 716.02 - § 716.02(g) for a discussion of criticality and unexpected results.
A prima facie case of obviousness may also be rebutted by showing that the art, in any material respect, teaches away from the claimed invention. In re Geisler, 116 F.3d 1465, 1471, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997) (Applicant argued that the prior art taught away from use of a protective layer for a reflective article having a thickness within the claimed range of "50 to 100 Angstroms." Specifically, a patent to Zehender, which was relied upon to reject applicant’s claim, included a statement that the thickness of the protective layer "should be not less than about [100 Angstroms]." The court held that the patent did not teach away from the claimed invention. "Zehender suggests that there are benefits to be derived from keeping the protective layer as thin as possible, consistent with achieving adequate protection. A thinner coating reduces light absorption and minimizes manufacturing time and expense. Thus, while Zehender expresses a preference for a thicker protective layer of 200-300 Angstroms, at the same time it provides the motivation for one of ordinary skill in the art to focus on thickness levels at the bottom of Zehender’s ‘suitable’ range- about 100 Angstroms- and to explore thickness levels below that range. The statement in Zehender that ‘n general, the thickness of the protective layer should be not less than about [100 Angstroms]’ falls far short of the kind of teaching that would discourage one of skill in the art from fabricating a protective layer of 100 Angstroms or less. [W]e are therefore ‘not convinced that there was a sufficient teaching away in the art to overcome [the] strong case of obviousness’ made out by Zehender."). See MPEP § 2145, paragraph X.D., for a discussion of "teaching away" references.
Applicant can rebut a presumption of obviousness based on a claimed invention that falls within a prior art range by showing "(1) [t]hat the prior art taught away from the claimed invention...or (2) that there are new and unexpected results relative to the prior art." Iron Grip Barbell Co., Inc. v. USA Sports, Inc., 392 F.3d 1317, 1322, 73 USPQ2d 1225, 1228 (Fed. Cir. 2004). The court found that patentee offered neither evidence of teaching away of the prior art nor new and unexpected results of the claimed invention drawn to a weight plate having 3 elongated handle openings. 392 F.3d at 1323, 73 USPQ2d at 1229. The court then turned to considering substantial evidence of pertinent secondary factors such as commercial success, satisfaction of a long-felt need, and copying by others may also support patentability. Id. Nevertheless, the court found that Iron Grip failed to show evidence of commercial success, copying by others, or satisfaction of a long felt need for the following reasons: (A) Iron Grip’s licensing of its patent to three competitors was insufficient to show nexus between the "merits of the invention and the licenses," and thus did not establish secondary consideration of commercial success; (B) in response to Iron Grip’s argument that the competitor’s production of a three-hole plate is evidence of copying, the court stated that "[n]ot every competing product that falls within the scope of a patent is evidence of copying" since "[o]therwise every infringement suit would automatically confirm the nonobviousness of the patent;" and (C) although Iron Grip offered as evidence that the absence of the three-grip plate on the market prior to its patent showed that the invention was nonobviousness, the court stated that "[a]bsent a showing of a long-felt need or the failure of others, the mere passage of time without the claimed invention is not evidence of nonobviousness." 392 F.3d at 1324-25, 73 USPQ2d at 1229-30.

https://mpep.uspto.gov/RDMS/MPEP/print?version=E8r8&href=d0e211255.html

[larry8]

Agree not simple but DU thinks she is qualified to give a complex decision when she clearly is not. She is an amateur in the field at best. Far to complex for a first time pharma patent case.