‘Appl. No. 12/702,889 REJECTIONS UNDER 35 U: § 103(a) Claims 1-9, 12-13, 16-18, 20 ~ 21, 23 and 25 - 28 stand rejected under 35 U.S.C. § 103(a) as obvious over Katayama, and claims 14-15 and 22 stand rejected under 35 U.S.C. § 103(a) as obvious over Katayama in view of Saito. As a preliminary matter, Applicant notes that claims 5, 8, 14, 15, 17, 20, 2land 25 — 27 are cancelled hereby without prejudice and as such the instant rejections are moot with respect to those claims. Applicant reserves the right to prosecute one or more of those claims or any subject matter disclosed in the application in this application or in one or more continuing applications. Consistent with this right, Applicant has done so: Applicant brings to the Examiner’s attention the following recently filed unpublished prioritized ‘examination (track 1) applications claiming priority to U.S. 12/702,889 and directed to 2 g and 4 g per day administration as well as other aspects of the present invention: 13/284,409, 13/282,145, 13/349,150, 13/349,153 and 13/349,157. ‘The pending claims under consideration after amendment herein therefore include claims 1-4,6~7,9, 12-13, 16, 18, 22-24 and 28 ~36. Applicant respectfully traverses the outstanding rejections with respect to these clams for the reasons already of record as well as the reasons set forth below. In response to the Office Action dated August 18, 2010, Applicant presented evidence of unexpected results and satisfaction of a long felt, unmet medical need. The Office Action dated November 4, 2011 concluded that: (1) the evidence of unexpected results submitted by Applicant ‘was not sufficient to overcome the obviousness rejection because Epadel given to subjects with less than 00 mg/dl of triglycerides is allegedly more indicative of how ethyl-EPA (“E-EPA”) will affect LDL-C in individuals with triglycerides above 500 mg/dl than Lov: a given to subjects in the claimed triglyceride range of $00 mg/dl to 2000 mg/dl; and (2) the evidence of satisfaction of unmet medical needs were not considered sufficient to overcome the asserted prima facie case. Applicant respectfully submits that with respect to claims directed to 4 g E-EPA per day administration (as all claims now are) no prima facie case of obviousness has been established Furthermore, Applicant submits that its additional arguments and evidence with respect to ‘unexpected results flowing from 4 g E-EPA per day claims were not accorded the appropriate weight. Applicant also respectfully submits that the alleged prima facie case as set forth in the -10-Appl. No. 12/702,889 prior Office Action is based on several fundamental factual/technical errors. Lastly, Applicant submits that the USPTO impermissibly has not considered Applicant's evidence and arguments relating to satisfaction of a long-felt, unmet need and did not weigh the alleged prima facie case against the totality of Applicant’s evidence. These issues are discussed in tum below. I. No prima facie Case of Obviousness To establish a prima facie case of obviousness under 35 U.S.C. § 103, the Office must articulate a reason or rationale that would have prompted a person of ordinary skill in the relevant field to combine the elements in the way the claimed new invention does. See, ¢.g., KSR Int'l Co. v. Teleflex Inc., 127 8. Ct. 1727, 1741-1742 (2007). One rationale commonly employed by the PTO (as in this case) is that an applicant is combining prior art elements according to known methods to yield predictable results. MPEP 2143A. To reject a claim on this rationale, the Office must resolve the Graham factual inquiries, and then articulate the following: (1) a finding that the prior art included each element claimed, although not necessarily in a single prior art reference, with the only difference between the claimed invention and the prior art being the lack of actual combination of the elements in a single prior art reference; (2) a finding that one of ordinary skill in the art could have combined the elements as claimed by known methods, and that in combination, each element merely performs the same function as it does separately; (3) a finding that one of ordinary skill in the art would have recognized that the results of the combination were predictable; and (4) whatever additional findings based on the Graham factual inquiries may be necessary, in view of the facts of the case under consideration, to explain a conclusion of obviousness. If any of these findings cannot be made, this rationale cannot be used to support a conclusion that the claim would have been obvious to one of ordinary skill in the art. Id. As is discussed in detail below, in view of the claim amendments proposed herein, Applicant respectfully submits that findings under at least prongs (1) and (3) have not been made. A. Differences Between Prior Art and Claims 1, The Cited References Do Not Describe a Reduction in Apolipoprotein B Compared to Control aieAppl No. 12/702,889 Claim 1 as amended (and claims 2-4, 6-7, 9, 12, 13, 16, 18, 22-24 and 28-31 and 33 - 36 by dependency on claim 1) now specify that “upon administering the composition to the subject daily for a period of 12 weeks the subject exhibits a greater than 25% reduction in fasting triglycerides and greater than 5% reduction in apolipoprotein B compared to a second subject having a baseline triglyceride level of $00 mg/dl to about 2000 mg/dl who has not received the pharmaceutical composition.” New claim 32 also specifies a reduction in median apoB level of at least 5%. The claimed reduction in apoB is unexpected in view of the prior art of record as set forth in Table A on page 15 below. Further, as is discussed immediately below, Katayama discloses the treatment of a different patient population with different amounts of a different composition than now claimed Different Composition The pending claims require a composition comprising “at least about 96%, by weight ethyl eicosapentacnoate.” Applicant respectfully submits that with respect to the pending claims as proposed to be amended herein, Katayama does not describe a composition comprising at least about 96%, by weight, ethyl eicosapentaenoate, As such, Applicant submits that the first prong of the prima facie case has not been satisfied. In particular, as explained in the response to Office Action dated June 20, 2011 Katayama discloses a different composition from that specified in the present claims. Katayama enrolled subjects between 1995 and 1998. The literature makes clear that “Epadel”, during that time frame and beyond, did not contain “>98% E-EPA” as alleged by the PTO in the Office Action at page 4. For example, a paper by Nishikawa et al., attached herewith, discloses that Epadel was actually a 91% E-EPA preparation with an undisclosed balance of fatty acids as of 1997 (see page 430, 1" column), Moreover, a paper by Nasa, et al, attached herewith, discloses Epadel as being 89.2% as of 1998 (see page138, 2d column). Furthermore, a paper by Ando, et al,, attached herewith, discloses Epadel as being 91% ethyl-EPA as of 1999 (see at p. 2178, Ist column), [As such, the evidence of record makes clear that Katayama does not disclose the same composition specified by the present claims. This evidence stands unrebutted by any evidence put forth by the USPTO.