IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Applicant: Brian Ault, et al.
`
`Filed: September 3, 2009
`
`Application No: 12/553,107
`
`Examiner: Gina C. Yu Justice
`
`Attorney Docket No: POZN.PO026US
`
`Confirmation No. 5949
`
`Title: Method for Delivering a Pharmaceutical Composition to Patient
`
`in Need Thereof
`
`CERTIFICATE OF ELECTRONIC TRANSMISSION
`
`I hereby certify that this correspondence is being electronically filed with the
`United States Patent and Trademark Office via EFS-Web on the date below:
`
`September 25, 2015
`Date
`
`/Steven
`
`L. Highlander/
`
`Steven L. Highlander
`
`RESPONSE TO FINAL OFFICE ACTION MAILED MARCH 26,2015
`
`Commissioner for Patents
`PO Box 1450
`Alexandria, VA 22313-1450
`
`Commissioner:
`
`This is in response to the Office Action ("Action") mailed on March 26, 2015,
`
`to
`
`which a response is due on September 26, 2015, by virtue of the accompanying Petition for
`
`Extension of Time (3 months) and payment of
`
`fees.
`
`No other
`
`fees are believed due in
`
`connection with this response; however,
`
`should applicants payment be missing, or any other
`
`fees due,
`
`the Commissioner is authorized to debit Parker Highlander PLLC Deposit Acct. No.
`
`50-5902/POZN.PO026US/SLH.
`
`A Listing of Claims begins on page 2 of this response; Remarks begin on page 5.
`
`(002741861
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`

`LISTING OF CLAIMS
`
`The following listing of claims replaces all previous listings or versions thereof:
`
`1-18.
`
`(Canceled)
`
`19.
`
`(Previously presented) A method for treating osteoarthritis, rheumatoid
`
`in need thereof
`arthritis, or ankylosing spondylitis comprising orally administering to a patient
`an AM unit dose form and, 10 hours (±20%) later, a PM unit dose form, wherein:
`the AM and PM unit dose forms each comprises:
`
`naproxen, or a pharmaceutically acceptable salt thereof,
`
`in an
`
`amount
`
`to provide 500 mg of naproxen, and
`
`esomeprazole, or a pharmaceutically acceptable salt thereof,
`
`in an
`
`amount
`
`to provide 20 mg of esomeprazole;
`
`said esomeprazole, or pharmaceutically acceptable salt thereof,
`AM and PM unit dose forms at a pH of 0 or greater,
`the AM and PM unit dose forms target:
`
`is released from said
`
`i)
`
`ii)
`
`a pharmacokinetic
`
`(pk) profile for naproxen where:
`for the AM dose of naproxen,
`
`the mean Cmax is 86.2 Vg/mL (±20%)
`
`a)
`
`b)
`
`and the median Tmax is 3.0 hours (±20%); and
`for the PM dose of naproxen,
`
`the mean C.x is 76.8 Vg/mL (±20%)
`
`and the median Tmax is 10 hours (±20%); and
`
`a)
`
`(pk) profile for esomeprazole where:
`a pharmacokinetic
`for the AM dose of esomeprazole,
`the mean area under the plasma
`concentration-time curve from when the AM dose is administered
`to 10 hours (±20%) after the AM dose is administered (AUCO-10,.)
`
`is 1216 hr* Vg/mL (±20%),
`
`b)
`
`for the PM dose of esomeprazole,
`
`the mean area under the plasma
`
`concentration-time curve from when the PM dose is administered
`
`to 14 hours (±20%) after the PM dose is administered (AUCO-14,pm)
`
`is 919 hr*pg/mL (±20%), and
`
`C)
`
`the total mean area under the plasma concentration-time curve for
`esomeprazole from when the AM dose is administered to 24 hours
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`

`(±20%) after the AM dose is administered (AUCO-24)
`
`is 2000
`
`hr*pg/mL (±20%); and
`the AM and PM unit dose forms further target a mean % time at which intragastric
`
`pH remains at about 4.0 or greater for about a 24 hour period after reaching steady state
`
`that is at least about 60%.
`
`20-28.
`
`(Canceled)
`
`29.
`
`(Previously presented) The method according to claim 19, wherein the mean %
`
`time at which intragastric pH remains at about 4.0 or greater for about a 24 hour period after
`
`reaching steady state is at least about 7 1 %.
`
`30-32.
`
`(Canceled).
`
`33.
`
`(Previously presented) The method according to claim 19, wherein said AM
`and PM unit dose forms are administered for a period of at least about 6 days.
`
`34.
`
`(Previously presented) The method according to claim 19, wherein said AM
`and PM unit dose forms are administered for a period of at least about 9 days.
`
`35-39.
`
`(Canceled)
`
`40.
`
`(Previously presented) The method according to claim 19, wherein said AM
`and PM unit dose forms are each a multilayer tablet comprising at least one core and at least a
`
`first
`
`layer and a second layer, wherein:
`
`i)
`
`ii)
`
`said core comprises naproxen, or pharmaceutically acceptable salt thereof;
`
`said first
`
`layer is a coating that at least begins to release the naproxen, or
`
`pharmaceutically acceptable salt thereof, when the pH of the surrounding
`
`medium is about 3.5 or greater; and
`
`iii)
`
`said second layer comprises esomeprazole or a pharmaceutically acceptable
`
`salt thereof, wherein said esomeprazole or pharmaceutically acceptable salt
`
`thereof is released at a pH of from 0 or greater.
`
`41.
`
`(Canceled)
`
`(002741861
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`42.
`
`(Previously presented) The method according to claim 40, wherein said
`
`esomeprazole or pharmaceutically acceptable salt thereof is released at a pH of from 0 to
`
`about 2.
`
`43-44.
`
`(Canceled)
`
`45.
`
`(Previously presented) The method according to claim 40, wherein said multi-
`
`layer tablet
`
`is substantially free of sodium bicarbonate.
`
`46-47.
`
`(Canceled)
`
`(002741861
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`1.
`
`Status of the claims
`
`REMARKS
`
`Claims 19, 29, 33, 34, 40, 42 and 45 are pending in the application and stand rejected
`
`under 35 U.S.C. §103 and for obviousness-type
`
`double-patenting.
`
`The specific grounds for
`
`rejection, and applicants'
`
`response thereto, are set out in detail below.
`
`11.
`
`Reiection under 35 U.S.C. §103
`
`Claims 19, 29, 33, 34, 40, 42, and 45 are rejected over Hassan-Alin et al.
`
`in view of
`
`Plachetka (U.S. Patent 6,926,907). Applicants traverse.
`
`Hassan-Alin is cited as
`
`teaching that
`
`there are no drug-drug interactions
`
`between
`
`esomeprazole and naproxen,
`
`as demonstrated by a study in human subjects.
`
`In addition,
`
`the
`
`reference indicates that esomeprazole is expected to be more effective than other PPI's against
`
`NSAID- associated ulcers and to provide GI protection.
`
`Plachetka is cited as
`
`teaching a
`
`coordinated delivery of NSAIDS,
`
`including naproxen, with an acid inhibitor. From this,
`
`the
`
`examiner argues that use of esomeprazole in combination with naproxen, using an AM-PM
`
`dosing regimen, would be obvious.
`
`To establish prima facie obviousness of a claimed invention,
`
`all
`
`the claim features
`
`must be taught or suggested by the prior art.
`
`In re Royka, 490 F.2d 981, 180 USPQ 580
`
`(CCPA 1974).
`
`Indeed, all words in a claim must be considered in judging the patentability of
`
`that claim against
`
`the prior art.
`
`In re Wilson, 424 F.2d 1382,
`
`1385,
`
`165 USPQ 494, 496
`
`(CCPA 1970). Once again,
`
`the examiner has not addressed at least the following highlighted
`
`claim features:
`
`A method
`
`for treating
`
`osteoarthritis,
`
`rheumatoid arthritis,
`or ankylosing
`in need thereof an AM unit
`spondylitis comprising orally administering to a patient
`dose form and, 10 hours (±20%) later, a PM unit dose form, wherein:
`the AM and PM unit dose forms each comprises:
`naproxen, or a pharmaceutically acceptable salt
`an amount
`to provide 500 mg of naproxen, and
`
`[002741861
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`Page 5
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`thereof,
`
`in
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`

`thereof,
`
`is released
`
`is 86.2
`
`is 3.0 hours (±20%);
`
`esomeprazole, or a pharmaceutically acceptable salt thereof,
`in an amount
`to provide 20 mg of esomeprazole;
`said esomeprazole, or pharmaceutically acceptable salt
`from said AM and PM unit dose forms at a pH of 0 or greater,
`the AM and PM unit dose forms target:
`(pk) profile for naproxen where:
`i) a pharmacokinetic
`for the AM dose of naproxen,
`the mean C.a,,
`,ug1mL (±20%) and the median T.a.,
`and
`for the PM dose of naproxen, the mean C.a., is 76.8,ugImL
`(±20%) and the median T.a,, is 10 hours (±20%); and
`(pk) profile for esomeprazole where:
`ii) a pharmacokinetic
`for the AM dose of esomeprazole,
`the mean area under the
`plasma concentration-time curve from when the AM dose
`is administered to 10 hours (±20c1c) after the AM dose is
`is 1216 hr*,ugJmL (±20%),
`administered (A UCO-10'a.)
`for the PM dose of esomeprazole,
`the mean area under the
`plasma concentration-time curve from when the PM dose
`is administered to 14 hours (±20%) after the PM dose is
`is 919 hr*,ugJmL (±20c1c), and
`administered (A UCO-14,p.)
`the total mean area under the plasma concentration-time
`the AM dose is
`from when
`curve for esomeprazole
`the AM dose is
`administered to 24 hours (±20%) after
`administered (A UCO-24) is 2000 hr*,ugJmL (±20%); and
`the AM and PM unit dose forms further target a mean % time at which
`intragastric pH remains at about 4. 0 or greater for about a 24 hour period after
`reaching steady state that is at least about 60%.
`
`a)
`
`b)
`
`a)
`
`b)
`
`c)
`
`There simply is no question, on the record,
`
`that the cited art lacks any teaching or suggestion
`
`of these features.
`
`Applicants begin by directing the examiner to the decision in In re Cyclobenzaprine
`
`Hydrochloride Extended-Re lease Capsule Patent Litigation (Fed. Cir. 2012),
`
`the facts and
`
`holding of which are relevant
`
`to the instant application. There,
`
`the Federal Circuit concluded
`
`that
`
`the district court's determination of obviousness was in error because the district court
`
`failed to consider
`
`the lack of a known pharmacokinetic
`
`(pK)Ipharmacodynamics
`
`(pD)
`
`(002741861
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`

`relationship for the claimed drug formulation.'
`
`The same arguments apply to the instant
`
`application.
`
`In In re Cyclobenzaprine,
`
`the Federal Circuit criticized the district
`
`court
`
`in its
`
`improper assumption of bioequivalence
`
`between immediate release and extended release drug
`
`forms. Here,
`
`the examiner similarly argues expected equivalence between immediate release
`
`esomeprazole
`
`(present claims) and extended release esomeprazole
`
`(Hassan-Alin), which as
`
`shown in the present specification,
`
`is not supported by the data.
`
`2
`
`Key in this aspect of
`
`the
`
`Federal Circuit's holding was that cyclobenzaprine
`
`"lacked a known pK/pD relationship at
`
`the time of invention," which the Federal Circuit believed was critically important because
`
`"[w]ithout
`
`such a known
`
`relationship [],
`
`skilled artisans could not predict whether any
`
`particular pK profile,
`
`including a bioequivalent one, would produce a therapeutically effective
`
`formulation"
`
`(emphasis added).
`
`Likewise,
`
`in the instant application,
`
`claim 19 focuses on esomeprazole and naproxen
`
`pharmacokinetic
`
`("pK")
`
`profiles
`
`(see Applicants'
`
`specification,
`
`pp.
`
`43-53),
`
`and
`
`the
`
`pharmacodynamic ("pl)") endpoint wherein the mean % of
`
`time for which the patient's
`
`intragastric pH remains at about 4.0 or greater for about 24 hours after reaching steady state is
`
`at
`
`least about 60% (see Applicant's specification, Table 4, p. 41 (mean % time of pH 4.0 =
`
`71.35
`
`(SD = 13.01))),
`
`for PN400/E20
`
`(having
`
`immediate release
`
`esomeprazole)
`
`in
`
`Example 1. These profiles and endpoint were not a "known pK/pD relationship at the time of
`
`invention," and in fact were unexpected
`
`and surprising in light of
`
`the data also found in
`
`Applicants'
`
`specification showing
`
`significantly
`
`different
`
`results
`
`for EC E20+naproxen
`
`(having extended release esomeprazole), as shown at least by the following results:
`
`focused on the pharmacokinetic
`In particular, the court
`See discussion of Hassan-Alin et al., 2005 in Section II(A), below,
`Page 7
`
`[002741861
`
`values in claim 3.
`
`regarding this point.
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`•
`
`9,
`
`... PN400/E20
`
`"On Day
`intragastric 4.0 than
`
`treatments
`
`resulted
`
`in a greater percent
`
`time with
`
`treatment with EC E20
`
`+
`
`naproxen"
`
`(Applicants'
`
`specification,
`
`p. 41 and see Table 4);
`
`•
`
`"By Day 9, however,
`
`the esomeprazole AUCO-10 for the PN400/E20
`
`treatment group
`
`was greater
`
`than the EC E20 + naproxen treatment group (1216 vs 1046 hr-ng/mL,
`
`respectively) and Cmax,am from the PN400/E20 treatment group was almost double that
`
`of
`
`the EC E20+naproxen
`
`treatment group
`
`(715 vs 435 ng/mL,
`
`respectively)."
`
`(Applicants specification,
`
`p. 47);
`
`•
`
`"Repeat doses of PN 400/E30 and PN 400/E20 resulted in faster onset of increased
`
`intragastric pH (at about
`
`I hour post dose)
`
`than EC E20 + naproxen, which was at
`
`about 1.5 hours post-dose (Figure 1). As shown in the Figure 8A,
`
`the release of
`
`naproxen from PN 400 occurred 1.5 to 2 hours post AM dose. Before naproxen was
`
`absorbed to peak concentrations
`
`following PN 400 treatment,
`
`intragastric pH had
`
`already achieved high levels, well above pH 4.0 (Figure 8A).
`
`In fact, with the BID
`
`regimen of PN 400/E20,
`
`given
`
`I hour before
`
`a meal,
`
`the intragastric pH was
`
`maintained at above 4.0 for greater
`
`than 70% of time over a 24-hour period, which
`
`would encompass any rise in plasma naproxen concentrations
`
`throughout
`
`the day.
`
`In
`
`contrast, EC E20 + naproxen produced peak naproxen concentrations
`
`that preceded
`
`the increase in intragastric pH (Figure 8B).
`
`In fact, peak naproxen
`
`concentrations
`
`occurred
`
`I
`
`to 2 hours post
`
`dose, which coincided with the
`
`time period when
`
`intragastric pH was lowest."
`
`(Applicants' specification,
`
`p. 54).
`
`This extended period of pH at 4.0 or greater provided by PN400/E20
`
`(having
`
`immediate
`
`release esomeprazole)
`
`over EC E20+naproxen
`
`(having extended release esomeprazole)
`
`is
`
`believed to be advantageous toward protecting patients from adverse effects of naproxen, and
`
`is a surprising and unexpected result given that this difference is maintained over an extended
`
`(002741861
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`

`period of time even though both formulations include esomeprazole, which as the examiner
`
`asserts, was known to provide "more time with intragastric 4 than other proton pump
`
`inhibitors." See Action at page 3. Therefore,
`
`as shown above,
`
`it
`
`is improper for the examiner
`
`to assume bioequivalence
`
`between immediate release and extended release esomeprazole drug
`
`forms Oust as the district court did in In re Cyclobenzaprine,
`
`before being reversed by the
`
`Federal Circuit).
`
`In In re Cyclobenzaprine,,
`
`the Federal Circuit also distinguished its findings over KSR
`
`Int'l Co.
`
`v. Teleflex Inc., quoting that opinion for the proposition that an invention is obvious
`
`when the skilled worker pursues "known
`
`options"
`
`from "a finite number of identified,
`
`predictable solutions" (emphasis added) The Federal Circuit went on to analogize the district
`
`court's opinion with the Federal Circuit's language in In re Kubin, 561 EM 1351, 1359 (Fed.
`
`Cir. 2009) as an improper obviousness analysis that
`
`is really hindsight reconstruction: when a
`
`defendant
`
`is "'merely throw[ing] metaphorical darts at a board'
`
`in hopes of arriving at a
`
`successful
`
`result," and "the prior art gave either no indication of which parameters were
`
`critical or no direction as to which of many possible choices is likely to be successful,"
`
`this is
`
`not obviousness but hindsight reconstruction.
`
`In summary, on facts very similar to those presented here,
`
`the USPTO's reviewing
`
`court struck down a comparable finding of unpatentability on the grounds that
`
`the prior art's
`
`general guidance was insufficient
`
`to render a claim obvious where that claim recited specific
`
`pK/pD parameters that were nowhere present
`
`in the art, nor could they be selected from a
`
`"finite" number of options readily apparent
`
`to those of skill
`
`in the art.
`
`As such,
`
`there is no
`
`justification for holding that the presently claimed subject matter was reasonable suggested by
`
`Hassan-Alin, even when taken in view of Plachetka.
`
`(002741861
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`A.
`
`Enteric Coating
`
`Applicants previously asserted that
`
`it was almost certain that
`
`the esomeprazole used
`
`by Hassan-Alin was enterically-coated.
`
`Thus, any attempted extrapolation from this material
`
`to the pharmacokinetic
`
`profile of esomeprazole
`
`of
`
`the present
`
`claims is completely
`
`inappropriate due to the fact
`
`that the esomeprazole used to generate the data that is embodied
`
`in the present claims was not enterically-coated.
`
`This provides yet another
`
`reason that
`
`the
`
`skilled artisan could not have envisioned, nor expected to succeed with, the presently claimed
`
`subject matter.
`
`The examiner argues that Applicants have presented no evidence that
`
`the form of
`
`esomeprazole in Hassan-Alin is enterically-coated.
`
`As a preliminary matter,
`
`it should be noted
`
`that
`
`it
`
`is the examiner's burden, not Applicants',
`
`to establish that
`
`the cited art
`
`is in fact
`
`relevant
`
`to the claimed subject matter, as well as how. Here all Applicants need to do is point
`
`out
`
`there is no evidence of record that Hassan-Alin's esomeprazole was not enteric coated
`
`(which was the state of the art at
`
`the time of publication), and the rejection is rebutted.
`
`Simply put, Applicants need not disprove that which has not been proven.
`
`Nevertheless,
`
`in the
`
`interest of advancing
`
`prosecution,
`
`Applicants provide the
`
`following additional
`
`information.
`
`In 2005,
`
`in what was undoubtedly the follow up publication
`
`to the presently cited reference, Hassan-Alin et al.
`
`stated in "Lack of Pharmacokinetic
`
`Interaction between Esomeprazole
`
`and the Nonsteroidal Anti-Inflammatory Drugs Naproxen
`
`and Rofecoxib in Healthy Subjects," Clin. Drug.
`
`Invest. 25(11):731-740,
`
`that
`
`their patients
`
`took Nexiumo, AstraZeneca
`
`Tablet Production,
`
`Sweden, which is well
`
`known
`
`to be
`
`enterically-coated. Notably, that paper further provides a very different pK/pD profile than the
`
`pending claims,
`
`thereby completely undercutting
`
`the examiner's argument
`
`that one could
`
`necessarily achieve the same result if following Hassin-Alin's 2003 teachings.
`
`(002741861
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`

`B.
`
`Inherency
`
`Without explicitly invoking the doctrine,
`
`the examiner attempts to sweep away the fact
`
`that
`
`the cited references provide none of
`
`the preceding claim recitations by resorting to an
`
`inherency theory, noting that "the resulting pharmacokinetics
`
`necessarily flow from such [an]
`
`obvious administration method."
`
`As will be explained below,
`
`the examiner
`
`is applying
`
`inherency in a way that cannot be supported by the relevant
`
`legal precedent.
`
`Even assuming the examiner's characterization
`
`of
`
`the art
`
`to be correct - something
`
`that is conceded only for the purpose of the following argument - the claims are nonetheless
`
`patentable.
`
`The critical mistake arises in the examiner's implicit assertion that inherency can
`
`address the limitations of applicants'
`
`claims that are missing from the art.
`
`The topic of
`
`inherency,
`
`in the context of obviousness,
`
`is discussed in MPEP § 2141,
`
`the relevant portion of
`
`which is reproduced below:
`
`recited
`
`the invention as a whole would have been obvious under 35
`In determining whether
`103, we must
`first delineate the invention as a whole.
`U.S.C.
`In delineating the
`invention as a whole, we look not only to the subject matter which is literally
`in the claim in question... but also to those properties of the subject matter which are
`Just as we look
`inherent in the subject matter and are disclosed in the specification...
`to a chemical and its properties when we examine the obviousness of a composition of
`is this invention as a whole, and not some part of it, which must be
`matter claim, it
`In re Antonie, 559 F.2d 618, 620, 195 USPQ 6,8
`35 U.S.C. 103."
`obvious under
`(CCPA 1977)
`(The claimed wastewater
`(citations omitted)
`in original)
`(emphasis
`treatment device had a tank volume to contractor area of 0.12 gal./sq.
`ft. The court
`found the invention as a whole was the ratio of 0. 12 and its inherent property that
`claimed devices maximized treatment
`capacity regardless of other variables
`in the
`devices. The prior art did not recognize that
`treatment capacity was a function of the
`tank volume to contractor
`the parameter optimized was not
`and therefore
`ratio,
`to be a result-effective variable.). See also In re Papesch, 315
`recognized in the art
`F.2d 381, 391, 137 USPQ 43, 51 (CCPA 1963) ("From the standpoint of patent
`law, a
`compound and all
`its properties are inseparable.").
`
`the
`
`Obviousness cannot be predicated on what
`is not known at the time an invention is
`made, even if the inherency of a certain feature is later established.
`In re Rijckaert, 9
`F.2d 1531, 28 USPQ2d 1955 (Fed. Cir. 1993). See MPEP § 2112 for the requirements
`of rejections based on inherency.
`
`Emphasis
`
`added.
`
`Thus,
`
`it
`
`is quite clear
`
`that,
`
`in the context of obviousness,
`
`inherency
`
`is a
`
`very, very limited doctrine.
`
`The examiner also makes reference to MPEP § 2112 (mentioned
`
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`

`in the passage
`
`above), which must be examined to better understand the limited use of
`
`inherency in obviousness:
`
`There is no requirement
`
`a person of ordinary skill
`the time of invention,
`recognized the inherent disclosure at
`
`that
`
`matter is in fact
`
`inherent
`
`in the art would have
`
`but only that
`the subject
`v. Geneva Pharm.
`
`in the prior art reference. Schering Corp.
`Inc., 339 EM 1373,
`67 USPQ2d 1664, 1668
`1377,
`(Fed. Cir. 2003)
`(rejecting the
`contention that inherent anticipation requires recognition by a person of ordinary skill
`testimony with respect
`in the art before the critical date and allowing expert
`to post-
`trials to show inherency); see also Toro Co. v. Deere
`Co., 355
`critical date clinical
`69 USPQ2d
`1320,
`1584,
`1590 (Fed. Cir. 2004)("[T]he
`fact
`is a necessary feature or result of a prior-art embodiment (that
`is enough for inherent anticipation,
`even if
`sufficiently described and enabled)
`that fact
`was unknown
`the prior invention."); Abbott Labs v. Geneva Pharms.,
`the time of
`Inc., 182 EM 1315,
`1319, 51 USPQ2d 1307, 1310 (Fed.Cir.1999) ("If a product
`that
`is offered for sale inherently possesses each of the limitations of the claims, then the
`invention is on sale, whether or not
`the parties to the transaction recognize that
`the
`product possesses the claimed characteristics."); Atlas Powder Co. v.
`Inc., 190
`Ireco,
`EM 1342, 1348-49 (Fed. Cir. 1999)
`("Because 'sufficient aeration' was inherent
`that the prior art did not recognize the key aspect of
`is irrelevant
`the prior art,
`An inherent structure,
`function is
`not necessarily
`invention....
`v. Apotex Corp., 403 EM 1331, 1343-44, 74
`known."); SmithKline Beecham Corp.
`USPQ2d
`1406-07 (Fed. Cir. 2005)
`to an
`(holding that
`a prior art patent
`1398,
`anhydrous form of a compound "inherently" anticipated the claimed hemihydrate form
`to manufacture
`of the compound because practicing the process in the prior art
`the
`trace amounts of'
`compound
`least
`"inherently results in at
`anhydrous
`hemihydrate even if
`the prior art did not discuss or recognize the hemihydrate) ....
`
`that
`
`a
`
`is itself
`
`&
`
`in
`
`[the]
`
`the claimed
`
`EM 1313,
`
`characteristic
`
`at
`
`it
`
`composition, or
`
`inconsistent
`
`Where applicant claims a composition in terms of a function, property or characteristic
`and the composition of the prior art is the same as that of the claim but
`the function is
`the examiner may make a rejection under
`not explicitly disclosed by the reference,
`both 35 U.S.C.
`102 and 103, expressed as a 102/103
`"There is nothing
`rejection.
`in concurrent
`for obviousness under
`35 U.S.C.
`103 and for
`rejections
`1255 n.4, 195 USPQ
`In re Best, 562 F.2d 1252,
`anticipation under 35 U.S.C. 102."
`430, 433 n.4 (CCPA 1977).
`same rationale should also apply to product,
`apparatus, and process claims claimed in terms of function, property or characteristic.
`a 35 U.S.C.
`102/103
`rejection is appropriate for these types of claims as
`Therefore,
`well as for composition claims ....
`
`'Ibis
`
`Products
`of
`chemical
`not
`exclusive
`have mutually
`composition can
`identical
`properties." A chemical composition and its properties are inseparable. Therefore,
`the prior art teaches the identical chemical structure,
`the properties applicant discloses
`In re Spada, 911 F.2d 705, 709, 15 USPQ2d
`and/or claims are necessarily present.
`the claimed composition was a
`1658 (Fed. Cir. 1990)
`1655,
`(Applicant argued that
`a tacky polymer while the product of
`pressure sensitive adhesive containing
`the
`"The Board correctly found that
`reference was hard and abrasion resistant.
`the virtual
`identity of monomers and procedures
`a prima facie case of
`sufficed to support
`unpatentability of Spada's polymer latexes for lack of novelty.")
`
`....
`
`if
`
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`

`

`From all of the foregoing, it
`
`is evident
`
`that
`
`inherency is a doctrine that primarily focuses on
`
`anticipation, usually where a composition in the prior art appears to be the same as that being
`
`claimed,
`
`and must therefore exhibit
`
`the same properties or activities as the prior art, even
`
`though that property or activity was unrecognized.
`
`However,
`
`as stated in In re Rijckaert, it
`
`is
`
`quite illogical
`
`to rely on inherency in the context of obviousness, which requires an analysis
`
`of what
`
`those of ordinary skill
`
`in the art would have known at the time the invention was
`
`made. Where the reference is silent on a feature, how could the skilled artisan be presumed to
`
`be imbued with such knowledge?
`
`In stark contrast
`
`to the focus on anticipation and compositions of matter,
`
`there is only
`
`a passing mention of obviousness and methods in these sections of the MPEP. Yet the issue
`
`presented here is precisely that - the obviousness of a method.
`
`If
`
`this rejection is to be
`
`sustained, applicants submit that some case law citation is required supporting a rejection that
`
`on inherent obviousness of a method, based on the combination of two references, when it
`
`is
`
`admitted by all parties that no one has ever practiced that method in the past. Without such a
`
`citation,
`
`there simply can be no reason to sustain this rejection.
`
`Significantly,
`
`the Federal Circuit has just issued further guidance on the notion of
`
`applying inherency
`
`in the context of obviousness in Par Pharm.
`
`Inc.
`
`v. Alkermes Pharma
`
`Ireland Ltd., Case No. 2014-1391 (Fed. Cir. 2014). Not surprisingly,
`
`the court cited In re
`
`Rijckaert, discussed above,
`
`in arriving at
`
`the conclusion
`
`that an "inherent
`
`obviousness"
`
`rejection, while possibly proper,
`
`is highly constrained and "must be carefully circumscribed in
`
`the context of obviousness."
`
`Indeed,
`
`this is not the sort of case where the "[m]ere recitation of
`
`a newly discovered function or property, inherently possessed by things in the prior art, does
`
`not distinguish a claim drawn to those things from the prior art," citing In re Oelrich, 666.
`
`F.2d 578, 581 (CCPA 1981) (emphasis added). Clearly the claimed methods do not constitute
`
`part of the prior art, or the rejection would be under §102 and not §103. As such,
`
`the
`
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`

`

`fundamental principle that "obviousness
`
`cannot be predicated on what
`
`is unknown"
`
`controls
`
`here.
`
`C.
`
`Conclusion
`
`To conclude,
`
`the examiner has failed to establish that the general
`
`teachings of the cited
`
`art would lead the skilled artisan to the pending
`
`claims, and
`
`do so with a reasonable
`
`expectation
`
`of
`
`success. Applicants
`
`therefore
`
`respectfully
`
`request
`
`reconsideration
`
`and
`
`withdrawal of this rejection.
`
`111.
`
`Reeections for Obviousness-Type Double-Patentim
`
`A.
`
`Plachetka and Hassan-Alin
`
`Claims 19, 29, 33, 34, 30, 42, and 45 have been rejected as being obvious over claims
`
`1-55 of Plachetka in view of Hassan-Alin, both cited above. Applicants traverse.
`
`In essence,
`
`this rejection is the same as
`
`the one immediately above, except
`
`that
`
`Platchetka
`
`is used here as
`
`the primary reference,
`
`and only the claims of Plachetka
`
`are
`
`available for citation against
`
`the present claims. Therefore,
`
`the arguments advanced above
`
`apply to Platchetka in view of Hassan-Alin with equal, and perhaps greater
`
`force, given the
`
`limited scope of citable disclosure from Plachetka. Applicants therefore respectfully request
`
`reconsideration
`
`and withdrawal of this rejection.
`
`B.
`
`U.S. Serial No. 14/045,156
`
`Claims 19, 29, 33, 34, 30, 42, and 45 have been provisionally rejected as being
`
`obvious over claims 57-75 of U.S. Serial no. 14/045,156. Applicants traverse.
`
`Once again,
`
`this rejection is effectively based on the same logic as above, except
`
`that
`
`here, there is no secondary reference to rely upon, and only the claims of the '156 application
`
`are available for citation against
`
`the present claims. Therefore,
`
`the arguments advanced above
`
`apply here with equal, and perhaps greater
`
`force, given the limited scope of citable material
`
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`

`from the '156 application.
`
`Applicants therefore respectfully request
`
`reconsideration
`
`and
`
`withdrawal of this rejection as well. Applicants therefore respectfully request reconsideration
`
`and withdrawal of this rejection.
`
`C.
`
`U.S. Serial No. 12/822,612
`
`Claims 19, 29, 33, 34, 30, 42, and 45 have been provisionally rejected as being
`
`obvious
`
`over claims 1-4, 18-20, 25,
`
`26,
`
`31, 38, 46-48,
`
`64 and
`
`65 of U.S. Serial no.
`
`12/822,612.
`
`Applicants traverse, but given that
`
`the rejection is provisional
`
`in nature,
`
`request
`
`that
`
`the rejection be held in abeyance until one of the applications
`
`at
`
`issue has matured into an
`
`issued patent.
`
`IV.
`
`Conclusion
`
`In light of the foregoing, applicants respectfully submit that all claims are in condition
`
`for allowance, and an early notification to that effect
`
`is earnestly solicited.
`
`The examiner is
`
`invited to contact
`
`the undersigned with any questions or comments regarding this response.
`
`Respectfully submitted,
`
`/Steven L. Highlander/
`
`Steven L. Highlander
`Reg. No. 37,642
`Attorney for Applicants
`
`Parker Highlander PLLC
`1120 S. Capital of Texas Highway
`Building One, Suite 200
`Austin, Texas 78746
`512-334-2900
`
`(Telephone)
`
`512-334-2999
`
`(Fax)
`
`Date: September 25, 2015
`
`(002741861
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`

`

`APPENDIX
`APPENDIX
`
`Page 16 of 26
`
`HZ213868
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`Patent OwnerEx. 2004
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`IPR2018-01341
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`Patent Owner Ex. 2004
`DRL v. Horizon
`IPR2018-01341
`
`Page 16 of 26
`
`

`

`ORIGINAL RESEARCH ARTICLE
`
`2W-5 Ad~ Dc~o
`
`DV. A;1 F:gh~s
`
`rcll~, eU
`
`Lack of Pharmacokinetic Interaction
`between Esomeprazole and the
`Nonsteroidal Anti-Inflammatory
`Drugs Naproxen and Rofecoxib in
`Healthy Subjects
`
`M. Hassani-Aliri,' J. NTaeMal,' C. Nilsson-Piescffl,' G. TAngstro"in"
`
`and T'. Anderssoal
`
`I
`
`AstraZeneca R&D M61ndal, 1%461ndal, Sweden
`LP, WifraMgtor,, Delawarc., USA
`
`2 Astrii:/eneca
`
`Abstract
`
`BacAgrourid: W(~ investigated tho poieniial
`
`j.weuactions
`
`between esonieprazolo
`
`and a non-selective rionsteroidal anfi-inflarornatory
`cyclo-oxygenase (COX)-2-selective NSAID (rofecosib)
`Method,%-. Two studies of identical
`
`(11"Lig
`
`(NSAID-1 n',ipr0Xt!13) Or a
`
`in lwalthy subjects.
`
`three-way crossover design
`randornisod, open,
`I weeWs
`(n = 32 for both studies) were to receive
`were conducted.
`Subjects
`treatruCTIt with esomeprazole 40nig once daily (studies, Aand B), naproxon 250ing
`twice daily (StWiv A), rofecoxib 17.5rnk)
`ortct~ diffly (,,wdy B)2 and esomoprazole
`
`in combination with naproxert (study A) or rofecoxib (study B). Study periods
`
`were separated
`
`by it
`
`'-)-week washutti period.
`
`Results:
`
`011 day 7 of dosing,
`
`Ific
`
`ratio,;
`
`(atid 9-51;,,',. 0s) for the area under
`
`the
`
`(AUCT.) and observed
`Plasma conecruration-thric cLirve during the (losing interval
`of esornoprazole and NSAID cornbina-
`maximum plasma concontration
`fion/iNSAID alone were 0,98 (0.94,
`1,01) and 1.00 (0,971 1.0-4).
`
`respectively,
`
`for
`
`for study B. The
`study Aj and 1, 15 (1.06, 1.241) and 1. 14 (1-02, 128),
`rc~,pectively,
`ralios (and 95'~(- Cls) for MiC, ai)d
`of esomeprazole andNSAID co-mbina-
`
`tion/esomeprazoie alone were 0.96 (0M. 1.03) and 0.92 (0.85~ 1.00). respective-
`
`ly,
`
`for study A., and 1.05 (0,96, 1,15) and 1,05 (0.94,
`
`1, 18)~ respectively,
`
`for study
`
`B.All treatments were well
`
`tolerated (luring the study period,
`
`Conclusion: Naproxen and rofecoxib do not
`
`interact with esomeprazole, aiid
`
`eson-teprazole
`
`does not. affect
`
`the pharmacokinelics of naproxen or rofe;coxib.
`
`These findings
`NSAID~ without
`
`indicate tha~ esomeprazole can be used in cornbinafion with
`
`the risk of a pharmacoki ne tic interaction,
`
`Patent Owner Ex. 2004
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`IPR2018-01341
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`
`

`

`732
`
`Ha~~ari-Ahn
`
`e., al.
`
`'Nonsteroidal anti-inflammal.ory druos (NSAIDs)
`0
`
`are widely [Bed
`(RA). osicoartbritis (OA) anda wide va