Amarin Corp Plc (AMRN)

[mc1988]

Applicant was able to overcome the above 103 obviousness rejection by showing: … The prior art is either silent or teaches that there is no statistically significant change in Apo-B levels when patients with TG levels less than 150 mg/dl or between 150-499 mg/dl are treated with either 96% pure ethyl-EPA or a mixture of ethyl-EPA and DHA

The bolded "prior art" above does not necessarily refer solely to Kurabayashi, but let's assume it does. I checked Kurabayashi (Kurabayashi, T., et al., "Eicosapentaenoic acid effect on hyperlipidemia in menopausal Japanese women." Obstet Gynecol 96:521-8 (2000).) Copy here https://sci-hub.tw/https://www.sciencedirect.com/science/article/pii/S0029784400009881

and in Table 3 of that paper (page 525), the difference is statistically NOT significant.

Notice that under Table 3 the legend distinguishes between:
- P of differences in changes over time, vs
- P of intergroup differences

You might have misinterpreted P of differences in changes over time in the EPA group being statistically significant as "Kurabayashi teaches differently: ss changes in Apo-B exist". What I'm reading from Table 3 of Kurabayashi is that there is NO statistically significant changes in Apo-B between the Control group and the EPA group.

As a confirmation of my point, page 523 of the Kurabayashi paper contains a description of the findings:

The changes in serum levels of apolipoproteins from baseline to week 48 are shown in Table 3. The apolipoprotein A-II level in the eicosapentaenoic acid group significantly decreased from baseline to week 48, and there were significant differences between the two groups at weeks 12 and 24. 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. The atherosclerotic index of the eicosapentaenoic acid group decreased significantly from baseline to week 48. In the eicosapentaenoic acid group, the level of lipopro- tein(a) significantly decreased from baseline to week 48. The difference in remnant lipoprotein cholesterol was not statistically significant.