Case 2:15-cv-03324-SRC-CLW Document 160 Filed 11/12/18 Page 1 of 22 PageID: 4140
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF NEW JERSEY
`
`HORIZON PHARMA, INC., HORI-
`ZON PHARMA USA, INC., and
`POZEN INC.,
`
`Plaintiffs,
`
`v.
`DR. REDDY’S LABORATORIES,
`INC. and DR. REDDY’S LABORA-
`TORIES,
`
`Defendants.
`HORIZON PHARMA, INC., HORI-
`ZON PHARMA USA, INC., and
`POZEN INC.,
`
`Plaintiffs,
`
`v.
`MYLAN PHARMACEUTICALS
`INC., MYLAN LABORATORIES
`LIMITED, and MYLAN, INC.,
`Defendants.
`HORIZON PHARMA, INC., HORI-
`ZON PHARMA USA, INC., and
`POZEN INC.,
`
`Plaintiffs,
`
`v.
`LUPIN LTD. and LUPIN PHARMA-
`CEUTICALS INC.,
`
`Defendants.
`
`Civil Action Nos. 15-cv-03324 (SRC) (CLW)
` 16-cv-04918 (SRC) (CLW)
` 16-cv-09035 (SRC) (CLW)
`
`
`
`
`Civil Action Nos. 15-cv-03327 (SRC) (CLW)
` 16-cv-04921 (SRC) (CLW)
`
`
`
`
`
`Civil Action Nos. 15-cv-03326 (SRC) (CLW)
` 16-cv-04920 (SRC) (CLW)
`
`
`
`
`
`
`
`(Return Date: September 4, 2018)
`
`Oral Argument is Requested
`
`
`
`MEMORANDUM OF MYLAN AND DRL IN SUPPORT OF
`THEIR MOTION FOR SUMMARY JUDGMENT OF INVALIDITY
`OF U.S. PATENT NOS. 9,220,698 AND 9,393,208
`
`
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`TABLE OF CONTENTS
`
`
`Page
`
`
`Introduction ................................................................................................... 1
`I.
`II. Background ................................................................................................... 3
`III. Legal Standards ............................................................................................ 6
`IV. The Aspirational “Target” PK/PD Limitations Render the Claims
`Invalid for Indefiniteness ............................................................................. 8
`A.
`The patents provide no boundaries regarding when a particular
`PK/PD value is “target[ed].” .............................................................. 10
`The patents fail to specify with reasonable certainty who
`“target[s]” the claimed PK and PD values. ........................................ 16
`V. Conclusion ................................................................................................... 18
`
`B.
`
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`TABLE OF AUTHORITIES
`
`
`
`CASES
`Anderson v. Liberty Lobby, Inc.,
`477 U.S. 242 (1986) .............................................................................................. 7
`
`Biosig Instruments, Inc. v. Nautilus, Inc.,
`783 F.3d 1374 (Fed. Cir. 2015) ............................................................................ 7
`
`Dow Chem. Co. v. Nova Chems. Corp.,
`803 F.3d 620 (Fed. Cir. 2015) ............................................................................ 17
`
`EKR Therapeutics, Inc. v. Sun Pharm. Indus., Ltd.,
`633 F. Supp. 2d 187 (D.N.J. 2009) ................................................................... 6, 7
`
`Halliburton Energy Servs., Inc. v. M-I LLC,
`514 F.3d 1244 (Fed. Cir. 2008) ...................................................................... 9, 17
`
`In re TR Labs Patent Litig.,
`No. 09-3883-PGS, 2014 WL 3500596 (D.N.J. July 14, 2014) ........................ 8, 9
`
`Interval Licensing LLC v. AOL, Inc.,
`766 F.3d 1364 (Fed. Cir. 2014) ...................................................................... 9, 10
`
`Media Rights Techs., Inc. v. Capital One Fin. Corp.,
`800 F.3d 1366 (Fed. Cir. 2015) .......................................................................... 17
`
`Nautilus, Inc. v. Biosig Instruments, Inc.,
`134 S. Ct. 2120 (2014) ................................................................................ 7, 8, 17
`
`Robert Bosch, LLC v. Snap-On Inc.,
`769 F.3d 1094 (Fed. Cir. 2014) .......................................................................... 18
`
`STATUTES AND RULES
`
`35 U.S.C. § 112(b) ..................................................................................................... 8
`
`35 U.S.C. § 112, ¶ 2 ..........................................................................................passim
`
`Fed. R. Civ. P. 56 ....................................................................................................... 2
`
`
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`-ii-
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`
`I.
`
`Introduction
`
`The patent statutes require that the specification of a patent must conclude
`
`with one or more claims “particularly pointing out and distinctly claiming” the in-
`
`vention. 35 U.S.C. § 112, ¶ 2. That requirement for clarity, or definiteness, in claim
`
`language ensures that the public receives fair notice regarding the extent of the pa-
`
`tentee’s exclusive rights and that the patent office and the courts receive a clear
`
`measure of the invention for evaluating patentability in light of the supporting dis-
`
`closure and the prior art. A claim that is indefinite—too unclear to fulfill those re-
`
`quirements—is invalid.
`
`Here, the asserted claims of the ʼ698 and ʼ208 patents recite dosage forms
`
`that “target” a set of pharmacokinetic (“PK”) and pharmacodynamic (“PD”) pa-
`
`rameters. Those claims are indefinite in scope, and therefore invalid, due to their
`
`“target” PK and PD terms. The Court has construed “target” to mean “set as a
`
`goal.” ECF No. 82 at 11.1 From that construction, it is clear that the “target” PK
`
`and PD parameters in the claims merely convey a set of goals that need not neces-
`
`sarily be achieved. There can be no genuine dispute that these aspirational “target”
`
`parameters render the claims invalid.
`
`The “targeted” PK and PD ranges are indefinite because they are presented
`
`as aspirational goals that need not be met in all instances, and the ʼ698 and ʼ208
`
`1 Unless otherwise noted, all ECF citations in this brief refer to the Court’s
`
`docket for Case No. 15-cv-03324.
`
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`patents provide no guidance regarding how often, if ever, the recited ranges must
`
`be met or how close one must come to those ranges to infringe the asserted claims.
`
`In fact, the patents’ shared specification demonstrates that administering the
`
`claimed drug formulations leads to wide variation between patients in the claimed
`
`properties, with outcomes that can and commonly do fall well outside of the
`
`claimed ranges. Nothing in the claims, the specification, or the prosecution history
`
`allows those skilled in the art to discern with any reasonable certainty where the
`
`boundaries of the asserted claims lie.
`
`The definiteness requirement of 35 U.S.C. § 112, ¶ 2, exists to protect the
`
`public from precisely this type of uncertainty. Enforcing definiteness standards en-
`
`sures that patent claims provide clear notice of the patentee’s rights and how far
`
`those rights extend as a condition for the exclusivity those claims confer upon their
`
`owner. The claims of the ʼ698 and ʼ208 patents lack reasonably clear boundaries
`
`and cast doubt and uncertainty over an indeterminate swath of commercial and
`
`clinical activities.
`
`There are no material facts in dispute. The asserted claims fall short of the
`
`definiteness required by § 112, ¶ 2, as a matter of law, and summary judgment of
`
`invalidity is appropriate. Fed. R. Civ. P. 56.
`
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`II. Background
`The asserted ʼ698 and ʼ208 patents claim methods of administering a drug
`
`formulation that combines naproxen, a non-steroidal anti-inflammatory drug
`
`(“NSAID”), and esomeprazole, a proton pump inhibitor (“PPI”) that reduces stom-
`
`ach acidity. Naproxen (e.g., Aleve®) has long been used for treating pain and in-
`
`flammation in chronic conditions such as arthritis. SUMF ¶ 6.2 It is also well
`
`known, however, that long-term naproxen administration can cause stomach inju-
`
`ry. SUMF ¶ 7. Esomeprazole (e.g., Nexium®) and other PPIs were used before the
`
`asserted patents’ priority date to mitigate gastric complications from long-term use
`
`of naproxen and other NSAIDs. SUMF ¶ 8.
`
`The ʼ698 and ʼ208 patents share a common specification—the ʼ208 patent
`
`was filed as a continuation of the ʼ698—and feature nearly identical claims. All
`
`claims of the ’698 and ’208 patents recite methods of administering a co-
`
`formulation of naproxen and esomeprazole. The recited formulation comprises 500
`
`mg of naproxen and 20 mg of esomeprazole, identified in the patents’ shared speci-
`
`fication as formulation “PN400/E20.” SUMF ¶ 9. Independent claim 1 of the ʼ698
`
`patent begins:
`
`1. A method for treating osteoarthritis, rheumatoid arthritis, or anky-
`losing spondylitis comprising orally administering to a patient in need
`
`2 Citations to “SUMF ¶ __” reference numbered paragraphs from the State-
`
`ment of Material Facts Not in Dispute submitted by Mylan and DRL and filed con-
`currently herewith.
`
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`thereof 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, is
`released from said AM and PM unit dose forms at a pH of 0 or
`greater, …
`SUMF ¶ 10; Ex. 1 at 52:25-38 (claim 1).3, 4
`
`
`
`In addition to the administration steps and formulation limitations recited
`
`above, Plaintiffs added certain intended pharmacokinetic (“PK”) and pharmacody-
`
`namic (“PD”) properties to the claims of the ʼ698 and ʼ208 patents. Upon adminis-
`
`tering a drug to a patient, various pharmacological effects can be observed in the
`
`body—for example, a drug may act quickly or slowly, it may reduce pain, or it
`
`may alter stomach pH. ECF No. 50-33 at ¶ 20; see also ECF No. 82 at 5. Scientists
`
`and clinicians measure such effects in terms of PK and PD values. SUMF ¶ 15. PK
`
`values measure the rate at which the body absorbs and processes the drug, and PD
`
`values measure the drug’s effect on the body. SUMF ¶ 16.
`
`The claims of the ’698 and ʼ208 patents recite certain PK and PD results in a
`
`patient who is administered the PN400/E20 formulation as recited in the claims.
`
`3 Claim 1 of the ʼ208 patent is nearly identical to claim 1 of the ʼ698 patent
`
`but is framed more broadly as a “method for delivering a pharmaceutical composi-
`tion to a patient in need thereof.” SUMF ¶ 14; See Ex. 2 at 46:33-34.
`4 Citations to “Ex. __” reference numbered exhibits attached to the Declara-
`
`tion of Bryan D. Beel, concurrently filed herewith.
`
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`SUMF ¶ 18. Specifically, the ’698 and ʼ208 patents describe PK parameters that
`
`include certain terms of art: “Cmax” “Tmax,” and “area under the curve” or “AUC.”
`
`To a skilled artisan, Cmax refers to the maximum concentration the drug achieves in
`
`the patient’s plasma. SUMF ¶ 19. Tmax identifies the time after administration at
`
`which the patient’s Cmax is achieved. SUMF ¶ 19. Finally, “area under the curve” or
`
`AUC measures the cumulative amount of a drug in the plasma over a certain peri-
`
`od after administration, for example after ten hours (AUC0-10) or after twenty-four
`
`hours (AUC0-24). SUMF ¶ 19. The asserted claims recite certain PK parameters for
`
`naproxen, certain PK parameters for esomeprazole, and a PD effect of administer-
`
`ing esomeprazole (i.e., raising the stomach pH), as exemplified by the PK/PD val-
`
`ues recited in claim 1 of the ʼ698 patent:
`
`… the AM and PM unit dose forms target:
`i) a pharmacokinetic (pk) profile for naproxen where:
`a) for the AM dose of naproxen, the mean Cmax is 86.2 μg/mL
`(±20%) and the median Tmax is 3.0 hours (±20%); and
`b) for the PM dose of naproxen, the mean Cmax is 76.8 μg/mL
`(±20%) and the median Tmax is 10 hours (±20%); and
`ii) a pharmacokinetic (pk) profile for esomeprazole where:
`a) 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 (AUC0-10,am) is 1216 hr*ng/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 (AUC0-14,pm) is 919 hr*ng/mL (±20%), and
`
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`c) the total mean area under the plasma concentration-time
`curve for esomeprazole from when the AM dose is admin-
`istered to 24 hours (±20%) after the AM dose is adminis-
`tered (AUC0-24) is 2000 hr*ng/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%.
`
`SUMF ¶ 10; Ex. 1 at 52:39-67 (claim 1) (emphases added).
`
`
`
`As emphasized above, the claims of the ʼ698 and ʼ208 patents specify that
`
`the recited naproxen-esomeprazole formulations merely “target” the stated PK and
`
`PD values, not that the administered doses achieve PK or PD results within the re-
`
`cited ranges. Because the Court has construed “target” to mean “set as a goal,” the
`
`PK and PD ranges set forth in the claims represent goals aspired to, but not neces-
`
`sarily met, for every patient. ECF No. 82 at 11. The Court “recognize[d] that this
`
`construction of ‘target’ could conceivably impact the validity of the claim,” id., but
`
`expressly deferred deciding whether the “targeted” PK and PD values render the
`
`claims indefinite, id. at 10 (“This Court considers indefiniteness arguments on
`
`summary judgment or at trial, and not at claim construction.”).
`
`III. Legal Standards
`“Summary judgment is appropriate where there is no genuine issue of mate-
`
`rial fact and the moving party is entitled to judgment as a matter of law.” EKR
`
`Therapeutics, Inc. v. Sun Pharm. Indus., Ltd., 633 F. Supp. 2d 187, 192 (D.N.J.
`
`2009) (citing Celotex Corp. v. Catrett, 477 U.S. 317, 322 (1986)). A dispute about
`
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`a material fact is genuine “if the evidence is such that a reasonable jury could re-
`
`turn a verdict for the nonmoving party.” Anderson v. Liberty Lobby, Inc., 477 U.S.
`
`242, 248 (1986). The court must view the facts and reasonable inferences drawn
`
`therefrom “in the light most favorable to the party opposing the motion.” EKR
`
`Therapeutics, 633 F. Supp. at 192 (quoting Matsushita Elec. Indus. Co. v. Zenith
`
`Radio Corp., 475 U.S. 574, 587 (1986)). But the non-moving party must “do more
`
`than simply show that there is some metaphysical doubt as to material facts” and
`
`must instead produce evidence upon which a reasonable fact finder could rely. Id.
`
`(quoting Matsushita, 475 U.S. at 586).
`
`A patent is invalid for indefiniteness “if its claims, read in light of the speci-
`
`fication delineating the patent, and the prosecution history, fail to inform, with rea-
`
`sonable certainty, those skilled in the art about the scope of the invention.” Nauti-
`
`lus, Inc. v. Biosig Instruments, Inc., 134 S. Ct. 2120, 2124 (2014). In particular, “a
`
`patent must be precise enough to afford clear notice of what is claimed, thereby
`
`apprising the public of what is still open to them.” Id. at 2129 (quotation & cita-
`
`tions omitted). Definiteness, like claim construction, is a question of law some-
`
`times involving subsidiary factual determinations. Biosig Instruments, Inc. v. Nau-
`
`tilus, Inc., 783 F.3d 1374, 1382 (Fed. Cir. 2015). In assessing definiteness, “claims
`
`are to be read in light of the patent’s specification and prosecution history,” and
`
`courts apply the “viewpoint of a person skilled in the art at the time the patent was
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`filed.” Nautilus, 134 S. Ct. at 2128 (alterations and citation omitted). Summary
`
`judgment of indefiniteness is appropriate when the language of a claim lacks the
`
`precision necessary to “appris[e] the public what is still open to them.” In re TR
`
`Labs Patent Litig., No. 09-3883-PGS, 2014 WL 3500596, at *4 (D.N.J. July 14,
`
`2014) (citations omitted).
`
`IV. The Aspirational “Target” PK/PD Limitations Render the Claims Inva-
`lid for Indefiniteness
`
`The asserted claims must be held invalid for indefiniteness under 35 U.S.C.
`
`§ 112, ¶ 2.5 The claims of the ʼ698 and ʼ208 patents recite dose forms that “tar-
`
`get”—but need not necessarily achieve—particular PK/PD properties, leaving
`
`those skilled in the art to guess at the boundaries and ultimate scope of the claims.6
`
`To meet the definiteness requirement, claims must “inform those skilled in
`
`the art about the scope of the invention with reasonable certainty.” Nautilus, 134 S.
`
`Ct. at 2129. Enforcing the definiteness standard serves the “public notice function
`
`of patent claims.” Halliburton Energy Servs., Inc. v. M-I LLC, 514 F.3d 1244, 1249
`
`
`5 Section 112, ¶ 2 was re-designated as § 112(b) when the AIA took effect
`
`on September 16, 2012. The ʼ698 and ʼ208 patents both claim priority from appli-
`cations filed before that date, so Defendants refer to the pre-AIA version of § 112
`for purposes of this motion.
`6 Defendants have asserted, and maintain, that the “target” PK/PD values
`
`recited in the claims are non-limiting, and the Court has yet to resolve that issue.
`ECF No. 82 at 11 n.3. In contrast, Plaintiffs contend that the “target” terms are lim-
`iting, substantive requirements of the asserted claims. ECF No. 49 at 20-22. De-
`fendants disagree with Plaintiffs’ view of the claims, but if that view is accepted,
`the asserted claims are invalid for indefiniteness as explained in this brief.
`
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`(Fed. Cir. 2008). Accordingly, the Federal Circuit has explained that § 112, ¶ 2,
`
`requires patent claims to “provide objective boundaries for those of skill in the
`
`art.” Interval Licensing LLC v. AOL, Inc., 766 F.3d 1364, 1371 (Fed. Cir. 2014);
`
`see also In re TR Labs, 2014 WL 3500596, at *4 (explaining that the definiteness
`
`standard “requires every ‘patent to be precise enough to afford clear notice of what
`
`is claimed’” (alterations omitted) (quoting Nautilus, 134 S. Ct. at 2129)).
`
`The independent claims of both patents recite methods for administering co-
`
`formulated naproxen and esomeprazole where the dose forms “target” specified
`
`PK values and “further target” a PD benchmark for intragastric pH levels. SUMF
`
`¶¶ 10, 12, 22; Ex. 1 at 52:39-67; Ex. 2 at 46:48–47:9. As used in the claims of the
`
`ʼ698 and ʼ208 patents, “target” means to “set as a goal.” ECF No. 82 at 11. The PK
`
`and PD profiles in the claims thus represent “statements of a goal aspired to, but
`
`not met, for every patient.” Id.
`
`So construed, the claims are indefinite. There can be no genuine dispute that
`
`the aspirational “target” elements prevent those skilled in the art from determining
`
`the metes and bounds of the claims with reasonable certainty. Plaintiffs acknowl-
`
`edged as much during the Markman hearing:
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`THE COURT: Okay. Look, the bottom line is this: If “target” is con-
`strued as being aspirational, is this claim viable anymore?
`
`[Plaintiffs’ Counsel]: No, it’s not. That’s their indefiniteness argu-
`ment.
`
`SUMF ¶ 23; Ex. 6 at 20:15-19 (emphasis added). The “target” PK and PD ele-
`
`ments in the claims have now been definitively construed as aspirational, and
`
`Plaintiffs correctly recognized the effects of that construction under § 112, ¶ 2.
`
`A. The patents provide no boundaries regarding when a particular
`PK/PD value is “target[ed]”
`
`
`
`The claims of the ʼ698 and ʼ208 patents recite ranges of PK/PD values, in-
`
`cluding numerous PK values encompassing “±20%” and a mean steady-state inter-
`
`val of elevated intragastric pH “for about a 24 hour period … that is at least about
`
`60%.” SUMF ¶¶ 10, 12. That the dose forms merely “target,” and need not
`
`achieve, those values opens the claims to additional breadth of indeterminate scope
`
`beyond the stated ranges.
`
`
`
`In other words, claims that target PK and PD values as a goal for the dosage
`
`forms lack the “objective boundaries” required under § 112, ¶ 2 because they pro-
`
`vide no discernable standard for how far a particular formulation administered to
`
`any given patient or group of patients can stray from the stated goals and still in-
`
`fringe the claims. See Interval Licensing, 766 F.3d at 1371. By analogy, “target-
`
`ing” a bullseye is not the same as hitting the bullseye. Indeed, one can hit a bull-
`
`seye without targeting it, and two shots targeted at the same bullseye with the same
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`arrow can have different results under different conditions. Whether at a target
`
`range or in the clinic, persons of ordinary skill can only wonder whether any par-
`
`ticular arrow or dose form “targets” a stated goal, regardless of their objective per-
`
`formance.
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`
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`The record provides no basis to identify, with reasonable certainty, how
`
`much a formulation that “targets” the stated PK and PD values can deviate from
`
`those goals. In short, it is not clear what must be done to infringe the asserted
`
`claims, and if the infringing acts involve particular PK and PD results, it is not
`
`clear what those results must be. Because the ʼ698 and ʼ208 patents provide no an-
`
`swer to those questions, the claims are indefinite.
`
`
`
`Nothing in the patents’ shared specification sheds any light on the objective
`
`scope of the claims—the term “target” appears only in passages that mirror the
`
`claim language itself, without further elaboration. SUMF ¶ 24. Similarly, the pros-
`
`ecution histories do not address what it means for a dose form to “target” a particu-
`
`lar PK or PD value. SUMF ¶ 25.
`
`
`
`Defendants’ expert Dr. Forrest explained that the examples disclosed in the
`
`ʼ698 and ʼ208 patents confirm that administering the disclosed dose forms resulted
`
`in varied PK values that often fell outside the ranges specified in the claims, SUMF
`
`¶ 26, but the patents provide no reasonably certain limits on the breadth of permis-
`
`sible variation. In Example 1 of the patents’ specification, the claimed PN400/E20
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`formulation was administered to a group of patients according to the claimed
`
`methods, and the resulting PK/PD data were measured. SUMF ¶ 27. The patents’
`
`specification reported various mean or median PK and PD values observed in the
`
`study participants, and several of those values were incorporated into the claims.
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`SUMF ¶ 28. As demonstrated by the specification, however, the claimed methods
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`often failed to achieve the aspirational PK and PD results specified in the claims.
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`On their face, the claims of the ʼ698 and ʼ208 patents recite methods for ad-
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`ministering the specified naproxen/esomeprazole dose forms to an individual pa-
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`tient. SUMF ¶ 29. The Court therefore concluded the PK and PD values in the
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`claims apply to a single patient, “not to results from multiple individuals.” ECF
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`No. 82 at 6-7. Yet the results reported in the patents’ specification show that many
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`individual patients exhibited PK values well outside the ranges specified in the
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`claims upon receiving the claimed dosing regimen. This is not an instance of a pa-
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`tentee merely pursuing claims narrower than the scope of the disclosure. Rather,
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`the disclosed experimental results show that the disclosed and claimed methods fall
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`short of achieving the “target” PK ranges recited in the claims in many individual
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`patients, but offer no standard for determining how close is close enough.
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`For example, the minimum AUC found for the AM esomeprazole dose in
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`the PN400/E20 study group was 188 hr*ng/mL and the maximum AUC observed
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`for the same dose was 2931 hr*ng/mL—both well outside the claimed range of
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`-12-
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`IPR2017-01995
`Page 15 of 22
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`1216 hr*ng/mL ±20% (i.e., 973–1459 hr*ng/mL). SUMF ¶ 30.
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`Moreover, the statistical data disclosed in the specification shows that the
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`claimed PK and PD properties varied widely among study participants. For exam-
`
`ple, the reported coefficient of variation7 for the patients’ observed AUC values for
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`the AM esomeprazole dose was ±69%, which means that only about 68% of the
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`patient data fell within a range of 377-2055 hr*ng/mL. SUMF ¶ 32. The discrepan-
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`cy between the AUC range for the AM esomeprazole dose recited in the claims
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`and the actual patient data reported in the specification is illustrated below:
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`7 Table 6 of the ʼ698 and ʼ208 patents’ specifications expresses variation in
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`terms of % CV, or coefficient of variation. SUMF ¶ 31. A coefficient of variation
`is defined as the standard of deviation of a sample, divided by the sample mean.
`SUMF ¶ 31. Large coefficients of variation reflect large interpatient variation.
`SUMF ¶ 31.
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`IPR2017-01995
`Page 16 of 22
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`SUMF ¶ 32; Ex. 4 at ¶ 52. Other PK values recited in the claims showed even
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`greater discrepancy from actual results during the disclosed study—for example,
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`the reported coefficient of variation for the esomeprazole PM dose was ±84%.
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`SUMF ¶ 33.
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`Thus, the PK values disclosed in the specification demonstrate that adminis-
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`tering the recited dose forms as claimed only sometimes achieved the targeted PK
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`values. As described in the ʼ698 and ʼ208 patents, administering the naproxen-
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`esomeprazole co-formulations as claimed can and does yield individual PK values
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`well outside the ±20% ranges recited in the claims, and the differences vary from
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`patient to patient. SUMF ¶ 34. The ʼ698 and ʼ208 patents, however, provide no
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`reasonably certain boundaries on the breadth of permissible variation under the
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`claims before one can conclude that the PK/PD results are not “targeted.”
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`The uncertainty of the scope of these claims is amplified when one considers
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`Plaintiffs’ infringement allegations in this action. Plaintiffs’ theories of infringe-
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`ment boil down to bioequivalence; Plaintiffs contend that Defendants infringe be-
`
`cause their proposed ANDA product is bioequivalent to Plaintiffs’ reference listed
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`drug (Vimovo®), SUMF ¶ 20, which has a formulation that matches the
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`PN400/E20 formulation in the ʼ698 and ʼ208 patents. Thus, according to Plaintiffs,
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`Defendants’ bioequivalent ANDA products would present the same PK and PD
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`profile as Plaintiffs’ formulations. But as discussed above, the PK characteristics of
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`that formulation vary so widely relative to the claims that the results of administer-
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`ing the PN400/E20 formulation frequently fall outside of the recited ranges. And
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`even if a skilled artisan could extrapolate PK and PD characteristics from the bioe-
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`quivalence of Defendants’ formulations, Plaintiffs have offered no evidence that
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`anyone has “target[ed]” the claimed PK and PD values. SUMF ¶ 21.
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`Thus, given the demonstrated gulf between real-world variation in PK values
`
`and the ranges in the claims, and the pervasive ambiguity about what and how
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`much beyond the stated ranges the term “target” will indulge, the patents afford no
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`reasonable certainty on where the ultimate boundaries of the claims lie and wheth-
`
`er the proposed ANDA products or any others would infringe the patents-in-suit.
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`B.
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`The patents fail to specify with reasonable certainty who “tar-
`get[s]” the claimed PK and PD values
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`
`
`The claims create further ambiguity because they fail to specify with reason-
`
`able certainty who or what must “target” the PK and PD values in the recited
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`methods. To continue the analogy to targeting an arrow: Is it the archer? The
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`fletcher? Or the arrow itself?
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`
`
`The literal claim language appears to specify that the dose form itself “tar-
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`gets” the various PK and PD properties. E.g., Ex. 1 at 52:39 (reciting that “the AM
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`and PM unit dose forms target” specified PK values). While confounding on its
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`face—it is difficult to understand how an inanimate drug composition could set
`
`any goal, whether PK/PD values or otherwise—that possibility reflects the actual
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`language chosen by the patentee. Alternatively, one could plausibly envision that
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`under the claimed methods, the prescribing physician must “target” the recited ef-
`
`fects through administering the specified regimen. But that is problematic given
`
`that the formulation and dosing regimen are fixed and the prescribing physician
`
`cannot affect the PK and PD values arising in an individual patient beyond choos-
`
`ing whether to administer the drug. Still another possibility might identify the rele-
`
`vant entity as the drug maker, preparing a dose form in hopes of targeting a partic-
`
`ular PK/PD profile. But, as in this case, a drug maker might develop an accused
`
`product without setting any of the recited PK/PD ranges as a goal, or without
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`knowledge of those ranges at all.
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`Those various alternative possibilities would require different acts from dif-
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`ferent actors under the claims, and nothing in the claims, the specification, or the
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`file history provides guidance as to which is correct. A claim is indefinite where, as
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`here, “its language might mean several different things and no informed and confi-
`
`dent choice is available among the contending definitions.” Media Rights Techs.,
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`Inc. v. Capital One Fin. Corp., 800 F.3d 1366, 1371 (Fed. Cir. 2015) (internal quo-
`
`tation marks omitted) (quoting Nautilus, 134 S. Ct. at 2130 n.8); see Dow Chem.
`
`Co. v. Nova Chems. Corp., 803 F.3d 620, 634-35 (Fed. Cir. 2015) (holding that the
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`existence of multiple approaches leading to different results with no intrinsic guid-
`
`ance as to which should be used rendered claims indefinite).
`
`
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`The record provides no basis to identify, with reasonable certainty, who or
`
`what “targets” the stated PK and PD values or how much the results of such target-
`
`ing can deviate from those goals and still fall under the claims. It is not sufficient
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`that the Court was able to construe “target” as used in the claims. The fact that a
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`court “can ascribe some meaning to a patent’s claims” does not satisfy § 112, ¶ 2.
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`Nautilus, 134 S. Ct. at 2130. “Even if a claim term’s definition can be reduced to
`
`words, the claim is still indefinite if a person of ordinary skill in the art cannot
`
`translate the defi