IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Applicant:
`Appl. No.:
`Filed:
`Title:
`Art Unit:
`Examiner:
`Docket No.:
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`Manku et al.
`13/614,111
`September 13, 2012
`Stable Pharmaceutical Compositions and Methods of Using Same
`1629
`Sasan
`3717958-00248
`
`Mail Stop Amendment
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
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`SUPPLEMENTAL RESPONSE TO NON-FINAL OFFICE ACTION DATED
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`NOVEMBER 8, 2012
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`Amendments to the Claims begin on page 2.
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`Remarks/Arguments begin on page 4.
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`A Conclusion is provided on page 6.
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`Hikma Pharmaceuticals
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`IPR2022-00215
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`Ex. 1031, p. 1 of 6
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`

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`AMENDMENTS TO THE CLAIMS
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`This listing of claims will replace all prior versions, and listings, of claims in the
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`application.
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`1 - 30 (Cancelled)
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`31.
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`(Currently Amended) A method of treating mixed dyslipidemia in a subject on statin
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`therapy-aoo comprising, administering to the subject an effective amount of 2500 mg to
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`5000 mg of ethyl eicosapentaenoate daily, wherein upon 12 weeks of said administration
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`the subject exhibits a reduction in for a period effective to reduce triglycerides of at least
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`15% and a reduction in [[and]] LDL-C of at least 5% compared to placebo control-HJ:---the
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`subject.
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`32.
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`(Currently Amended) The method of claim 31 comprising, administering to the subject
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`an effective amount of ethyl eicosapentaenoate daily to reduce wherein upon 12 weeks of
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`said administration the subject exhibits a reduction in fasting triglycerides [[by]] of at
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`least [[ 10%]] 20% compared to placebo control in the subject.
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`33.
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`34.
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`(Cancelled).
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`(Currently Amended) The method of claim 31 comprising, administering to the subject
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`an effective amount of ethyl eicosapentaenoate daily to reduce wherein upon 12 weeks of
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`said administration the subject exhibits a reduction in fasting apolipoprotein B compared
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`to placebo control in the subject.
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`35.
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`(Currently Amended) The method of claim 31 comprising, administering to the subject
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`an effective amount of ethyl eicosapentaenoate daily to reduce wherein upon 12 weeks of
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`said administration the subject exhibits a reduction in fasting VLDL-C compared to
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`placebo control in the subject.
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`36.
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`(Currently Amended) The method of claim 31 comprising, administering to the subject
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`an effective amount of ethyl eicosapentaenoate daily to reduce wherein upon 12 weeks of
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`said administration the subject exhibits a reduction in fasting VLDL-C [[by]] of at least
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`10% compared to placebo control in the subject..
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`2
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`Hikma Pharmaceuticals
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`IPR2022-00215
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`Ex. 1031, p. 2 of 6
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`37.
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`(Currently amended) The method of claim 36 where the effective amount of ethyl
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`eicosapentaenoate is administered to the subject in compositions capsules each
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`comprising about 900 mg to about 1 g of ethyl eicosapentaenoate.
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`38.
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`(Currently Amended) The method of claim [[37]] 36 where the effective amount of ethyl
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`eicosapentaenoate is administered to the subject in compositions capsules each
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`comprising about 1 g of ethyl eicosapentaenoate.
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`3
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`Hikma Pharmaceuticals
`
`IPR2022-00215
`
`Ex. 1031, p. 3 of 6
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`REMARKS/ARGUMENTS
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`Claims 31, 32 and 34 - 38 are amended. Claim 33 is cancelled. No new matter is added.
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`Support for amended claim 31 can be found in the specification as filed at least at
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`paragraphs 0018, 0109, 0112 and 0138.
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`With respect to the range of 2500 mg to 5000 mg, Applicants respectfully direct the
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`Examiner's attention to In re Wertheim, 541 F.2d 257 (CCPA 1976) which states:
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`In the context of this invention, in light of the description of the invention as
`employing solids contents within the range of 25-60% along with specific
`embodiments of 36% and 50%, we are of the opinion that, as a factual matter,
`persons skilled in the art would consider processes employing a 35-60% solids
`content range to be part of appellants' invention ...
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`Applicants' specification discloses, inter alia, a daily dose of ethyl-EPA of 50 mg to
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`about 5000 mg per day as well as a specific amount of2500 mg per day at least at paragraph
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`[0020]. In view of Wertheim, wherein disclosure of a range of25-60% and a specific value of
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`36% properly supported a claim to the range of 35-60%, the presently claimed range of 2500 mg
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`to 5000 mg is also properly supported by disclosure of a range of 50 mg - 5000 mg and
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`disclosure of a specific embodiment of 2500 mg per day as discussed in paragraph [0018].
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`Support for amended claim 32 can be found in the specification as filed at least at
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`paragraphs O 107 and O 109.
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`Support for amended claim 34 can be found in the specification as filed at least at
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`paragraphs 0107 and 0113.
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`Support for amended claims 35 and 36 can be found in the specification as filed at least at
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`paragraphs 0107 and 0114.
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`Support for amended claims 37 and 38 can be found in the specification as filed at least at
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`paragraphs 0028 and 0018.
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`Attached herewith is a copy of Ballantyne et al., American Journal of Cardiology Volume
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`110, Issue 7, Pages 984-992, October 1, 2012 ("Ballantyne") setting forth details and results of
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`the ANCHOR trial. ANCHOR was a multicenter, placebo-controlled, randomized, double(cid:173)
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`blind, 12-week clinical trial evaluating the efficacy and safety of Vascepa® (also referred to as
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`AMRlOl and icosapent ethyl) in patients at high risk for coronary heart disease (CHD). These
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`4
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`Hikma Pharmaceuticals
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`IPR2022-00215
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`Ex. 1031, p. 4 of 6
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`I
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`patients had residual high triglyceride (TG) levels in the range of 200 mg/dl to 499 mg/dl despite
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`being on stable statin therapy for control oflow density lipoprotein cholesterol (LDL-C in the
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`range of 40-100 mg/dL ). Patients in the ANCHOR study are said to have mixed dyslipidemia
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`( as presently claimed), where the primary goal is to control LDL-C. As set forth in Ballantyne,
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`in the Anchor study 4 g per day ofVascepa® unexpectedly reduced LDL-C compared to placebo
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`control. By contrast with mixed dyslipidemic subjects in ANCHOR, subjects with triglyceride
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`levels ~ 500 mg/dL are characterized as having "very high triglycerides." For these patients the
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`primary treatment goal is to lower the elevated triglyceride levels in order to prevent pancreatitis.
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`Applicants respectfully note that it is settled law that unexpected results, no matter when
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`generated ( even after a patent issues), can be relied on to support patentability of a claimed
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`invention. In Knoll Pharmaceutical Company, Inc. et al., v. Teva Pharmaceuticals USA, Inc.,
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`367 F.3d 1381 (Fed. Cir. 2004), the Federal Circuit held that it was error for the district court to
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`refuse to consider unexpected results evidence because "the unexpected benefits or results were
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`discovered after the '252 patent had been issued." The Federal Circuit stated that" [t]here is no
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`requirement that an inventions's properties and advantages were fully known before the patent
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`application was filed, or that the patent application contains all of the work done in studying the
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`invention, in order for that work to be introduce into evidence in response to litigation attack." Id
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`at 1385. See also Genetics Institute, LLC, v. Novartis Vaccines and Diagnostics, Inc. No. 2010-
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`1264 (Fed. Cir. 2011) ("evidence of unexpected results may be used to rebut a case of prima
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`facie obviousness even if that evidence was obtained after the patent's filing or issue date.").
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`5
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`Hikma Pharmaceuticals
`
`IPR2022-00215
`
`Ex. 1031, p. 5 of 6
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`CONCLUSION
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`The application is believed to be in condition for allowance. Early and favorable
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`consideration is respectfully requested. The Commissioner is hereby authorized to charge
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`deposit account 02-1818 for any fees which are due and owing.
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`Respectfully s11bmitted,
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`
`BY - - - - - - - - ,
`David B. Fotimier
`Reg. No. 51,696
`Customer No. 24573
`
`Dated: January 11, 2013
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`Attachments
`
`Ballantyne et al., American Journal of Cardiology Volume 110, Issue 7, Pages 984-992, October
`1,2012
`
`6
`
`Hikma Pharmaceuticals
`
`IPR2022-00215
`
`Ex. 1031, p. 6 of 6
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`