us to. 0V
`Trials
`571-272-7822
`
`Paper 15
`. Entered: March 1, 2016
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`LUPIN LTD. and LUPIN PHARMACEUTICALS INC,
`
`Petitioner,
`
`V.
`
`POZEN INC.,
`Patent Owner.
`
`Case IPR2015-01775
`
`Patent 8,865,190 B2
`
`Before TONI R. SCHEINER, LORA M. GREEN, and
`JACQUELINE WRIGHT BONILLA, Administrative Patent Judges.
`
`BONILLA, Administrative Patent Judge.
`
`DECISION
`
`Institution of Inter Partes Review
`
`37 C.F.R. § 42.108
`
`

`

`IPR2015-01775
`
`Patent 8,865,190 B2
`
`I. INTRODUCTION
`
`Lupin Ltd. and Lupin Pharmaceuticals, Inc. (“Petitioner”) filed a
`
`Corrected Petition (Paper 4, “Pet.”) requesting an inter partes review of
`
`claims 1-8 of US. Patent No. 8,865,190 B2 (Ex. 1001, “the ’190 patent”).
`
`Pozen Inc. (“Patent Owner”) filed a Preliminary Response. Paper 14
`
`(“Prelim Resp”). Under 35 U.S.C. § 314, we may not institute an inter
`
`partes review “unless .
`
`.
`
`. there is a reasonable likelihood that the petitioner
`
`would prevail with respect to at least 1 of the claims challenged in the
`
`petition.”
`Upon consideration of information presented in the Petition and the
`
`Preliminary Response, we determine that Petitioner has established a
`
`reasonable likelihood that it would prevail in showing the unpatentability of
`
`challenged claims 1, 2, and 4—8, but not claim 3, of the ’ 190 patent. We
`
`institute inter partes review of claims 1, 2, and 4—8 of the ’ 190 patent.
`
`A.
`
`‘ Related Proceedings
`
`The parties identify a number ofjudicial matters involving the ’ 190
`
`patent (e.g., Horizon Pharma, Inc. v. Actavis Labs. FL, Inc., 3:15—cv-O3322
`
`(D.N.J.)), as well as a number ofjudicial and administrative matters
`
`involving patents related to the ’ 190 patent or directed to similar subject
`
`matter (e.g., AstraZeneca AB v. Dr. Reddy ’s Labs. Inc., 3:11-cv-02317
`
`(D.N.J.); Dr. Reddy’s Labs, Inc. v. Pozen Inc., Case IPR2015-00802
`
`(PTAB); Coalition for Aflordable Drugs VII LLC v. Pozen Inc., IPR2015-
`
`01241 (PTAB); Coalition for Aflordable Drugs VII LLC v. Pozen Inc.,
`
`

`

`IPR2015-01775
`
`Patent 8,865,190 B2
`
`Coalition for Aflordable Drugs VII LLC v. Pozen Ina, IPR2015-01344
`
`(PTAB); IPR2015-01680 (PTAB); Coalition for Aflordable Drugs VII LLC
`
`v. Pozen Ina, IPR2015-01718 (PTAB)). Pet. 3—4; Paper 8, 8—9. Petitioner
`
`also filed two other Petitions for inter partes review involving patents
`
`related to the ’ 190 patent in Case Nos. IPR2015-01773 and IPR2015-01774.
`
`Paper 8, 9.
`
`B.
`
`Asserted Grounds of Unpatentabilz'ty
`
`Petitioner asserts the challenged claims are unpatentable on the
`
`following grounds. Pet. 4—5, 11—60.
`
`Reference(s)
`The ’255 publication‘
`
`_.
`
`. m Claims Challenged
`§ 102(b)
`
`
`
`
`
`The ’556 patent2 and Chandramouli3
`
`1—8
`
`
`
`
`
`I
`
`1 US. Patent App. Pub. No. US 2003/0069255, published Apr. 10, 2003,
`filed by Plachetka (“the ’255 publication”) (Ex. 1006).
`
`2 US. Patent NO. 6,544,556, issued Apr. 8, 2003, to Chen et al. (“the ’556
`patent”) (Ex. 1007)
`
`3 Chandramouli et al., Prevention and management ofNSAID-Induced
`Gastropathy, J. PHARM. PAIN AND SYMPTOM CONTROL, 8(4):27—40 (2000)
`(“Chandramouli”) (Ex. 1009).
`
`4 US. Patent NO. 5,698,225, issued Dec. 16, 1997, to Gimet et al. (“the ’225
`patent”) (Ex. 1013).
`
`

`

`IPR2015-01775
`
`Patent 8,865,190 B2
`
`Reference(s)
`The ’118 patent,5 the ’225 patent,
`and the ’192 patent6
`
`m Claims Challenged
`§ 103(a)
`1—8
`
`
`
`
`The ’225 patent, Chandramouli and
`‘ WO ’1857
`
`§ 103(a)
`
`1—8
`
`
`
`
`Petitioner supports its challenges in the Petition with the Declaration of
`
`Umesh V. Banakar, Ph.D. (Ex. 1002).
`
`C.
`
`The ’190 Patent (Ex. 1001)
`
`The ’ 190 patent discloses pharmaceutical compositions “that provide
`
`for the coordinated release of an acid inhibitor and a non-steroidal anti—
`
`inflammatory drug (NSAID)” (Ex. 1001, 1:25—28), such that there is “a
`
`reduced likelihood of causing unwanted side effects, especially
`
`gastrointestinal side effects, when administered as a treatment for pain” (id.
`
`at 1:28—31).
`
`Specifically, the ’ 190 patent discloses “a pharmaceutical composition
`
`in unit dosage form .
`
`.
`
`. contain[ing] an acid inhibitor present in an amount
`
`effective to raise the gastric pH of a patient to at least 3.5” (id. at 3:31—37),
`
`5 U.S. Patent No. 5,204,118, issued Apr. 20, 1993, to Goldman et al. (“the
`’1 18 patent”) (EX. 1014).
`
`6 US. Patent No. 5,877,192, issued Mar. 2, 1999, to Lindberg et al. (“the
`’ 192 patent”) (Ex. 1008).
`7 PCT Int’l Patent Appl. WO 00/26185, published May 11, 2000, by Phillips
`(“WO’185”)(EX. 1015).
`
`

`

`IPR2015—01775
`
`Patent 8,865,190 B2
`
`and an NSAID “in an amount effective to reduce or eliminate pain or
`
`inflammation” (id. at 4:3—5). “The term ‘unit dosage form’ .
`
`.
`
`. refers to a
`
`single entity for drug administration. For example, a single tablet or capsule
`
`combining both an acid inhibitor and an NSAID would be a unit dosage
`
`form.” Id. at 4:46—49.
`
`A unit dosage form of the present invention preferably provides
`for coordinated drug release in a way that elevates gastric pH and
`reduces
`the deleterious
`effects of
`the NSAID on the
`
`gastroduodenal mucosa, i.e., the acid inhibitor is released first
`and the release of NSAID is delayed until after the pH in the GI
`tract has risen.
`
`In a preferred embodiment, the unit dosage form is a multilayer
`tablet, having an outer layer comprising the acid inhibitor and an
`inner core which comprises the NSAID.
`In the most preferred
`form, coordinated delivery is accomplished by having the inner
`core surrounded by a polymeric barrier coating that does not
`dissolve unless the surrounding medium is at a pH of at least 3.5,
`preferably at least 4 and more preferably, at least 5.
`
`Id. at 4:49—63.
`
`“The term ‘acid inhibitor’ refers to agents that inhibit gastric acid
`
`secretion and increase gastric pH.” Id. at 3:38—40. According to the ’ 190
`
`patent, preferred acid inhibiters are Hz-blockers, such as famotidine (id. at
`
`3:40—47), but “[o]ther preferred agents that may be effectively used as acid
`
`inhibitors are the proton pump inhibitors such as .
`
`.
`
`. esomeprazole,” for
`
`example, in a typical amount of 5—100 mg (id. at 3:48—51, 8:17—18).
`
`The ’ 190 patent also discloses that the NSAID may be a number of
`
`different options, such as aspirin, acetaminophen, etc., where the “most
`
`5
`
`

`

`IPR2015-01775
`
`Patent 8,865,190 B2
`
`preferred NSAID is naproxen in an amount of between 50 mg and 1500 mg,
`
`and more preferably, in an amount of between 200 mg and 600 mg.” Id. at
`
`4:5—18.
`
`D.
`
`Illustrative Claims
`
`Petitioner challenges claims 1—8 of the ’190 patent. Claim 1, the only
`
`independent claim, reproduced below, is illustrative.
`
`1. A process for preparing a pharmaceutical composition in
`unit dosage form comprising therapeutically effective amounts
`of esomeprazole and naproxen, said process comprising the
`steps of:
`
`a) providing a first layer comprising said naproxen; and
`
`b) applying a second layer to said first layer, wherein said
`second layer comprises said esomeprazole; wherein said unit
`dosage form provides for release of said esomeprazole such
`that upon introduction of said unit dosage form into a
`medium, at least a portion of said esomeprazole is released
`regardless of the pH of the medium and release of at least a
`portion of said naproxen is inhibited unless the pH of said
`medium is 3.5 or higher.
`‘
`
`Ex. 1001, 21:24-2216. In relation to the layer comprising naproxen,
`
`dependent claim 3 further requires that the “first layer comprises a coating
`
`that inhibits its release from said unit dosage form unless said dosage form is
`
`in a medium with a pH of 3.5 or higher.” Id. at 22:11—14. Dependent
`
`claims 4—6 require an “enteric film coa ” that surrounds, in some capacity,
`
`the layer comprising naproxen. Id. at 22:15—23.
`
`

`

`IPR2015-01775
`
`Patent 8,865,190 B2
`
`A.
`
`Claim Construction
`
`-
`
`II. ANALYSIS
`
`In an inter partes review, claim terms in an unexpired patent are
`
`interpreted according to their broadest reasonable construction in light of the
`
`specification of the patent in which they appear. 37 CPR. § 42.100(b); In
`
`re Cuozzo Speed Techs, LLC, 793 F.3d 1268, 1275—79 (Fed. Cir. 2015);
`
`cert. granted sub nom., Cuozzo Speed Techs., LLC v. Lee, No. 15-446, 2016
`
`WL 205946 (US. Jan. 15, 2016). Under that standard, claim terms are given
`
`their ordinary and customary meaning, as would be understood by one of
`
`ordinary skill in the art in the context of the entire disclosure. In re
`
`Translogz'c Tech, Inc, 504 F.3d 1249, 1257 (Fed. Cir. 2007).
`
`We determine that the only claim term requiring interpretation for
`
`purposes of this Decision is “inhibit.” The challenged claims recite the
`
`terms “inhibited” or “inhibits” in relation to the release of naproxen from a
`
`unit dosage form when introduced into a medium with a pH of 3.5 or higher.
`
`Petitioner asserts that the broadest reasonable interpretation of the term
`
`“inhibits” is “‘slows down,’ which allows for immediate release of some
`
`naproxen.” Pet. 11. Patent Owner contends that the ordinary meaning of
`
`“inhibits” refers to “prevents, hinders, or restrains” release of the NSAID.
`
`Prelim. Resp. 6—8 (citing Ex. 2014, Ex. 2015).
`
`The specification of the ’ 190 patent does not define expressly the term
`
`“inhibit.” Considering the ordinary and customary meaning of the term in
`
`View of the specification and the claims themselves, however, we construe
`
`

`

`IPR2015-01775
`
`Patent 8,865,190 B2
`
`“inhibit” to mean prevent (stop), hinder, or restrain, as Patent Owner
`
`proposes. Id. (citing Ex. 2014, Ex. 2015).
`
`For example, claim 1 of the ’ 190 patent recites “release ofat least a
`
`portion” of naproxen “is inhibited unless the pH of said medium is 3.5 or
`
`higher” (emphasis added). Dependent claim 3 recites a “coating that inhibits
`
`its release” from the unit dosage form “unless said dosage form is in a
`
`medium with a pH of 3.5 or higher” (emphasis added). Thus, “inhibit”
`
`refers to preventing, hindering, or restraining the release of naproxen
`
`“unless” the dosage form is exposed to a pH of 3.5 or higher. The use of
`
`“unless” in claim 1 and 3 and “at least a portion” in claim 1 indicates that the
`terms “inhibited” and “inhibits” in the claims do not encompass a “slowing
`
`down” of a release when the pH is below 3.5 (which would make “at least a
`
`portion” superfluous in claim 1), but rather refers to no release of “at least a
`
`portion” (claim 1) or all (claim 3) of the drug “unless” the dosage form is in
`
`a medium with a pH of 3.5 or higher.
`
`B.
`
`Asserted Anticipation by the ’255 publication
`
`As noted by both parties, the ’ 190 patent is a fifih generation
`
`descendent of an application (the ’216 application) that published as the ’255
`
`publication (Ex. 1006), and the ’ 190 patent claims priority to the ’216
`
`application and its parent provisional application. Pet. 9—10; Prelim. Resp.
`
`9—10; Ex. 1001, 1:7—21. Nonetheless, Petitioner asserts that the ’255
`’ publication is prior art to the ’190 patent under 35 U.S.C. § 102(b). Pet. 9—
`
`11.
`
`

`

`IPR2015-01775
`
`Patent 8,865,190 B2
`
`In this regard, Petitioner first notes that the ’255 publication published
`
`more than one year before the filing of its child continuation—in-part
`
`application (the ’320 application) in the chain. Id. at 9. Petitioner then
`
`contends that the ’216 application and its parent provisional (“the pre-2003
`
`applications”) do not provide written description support of the claims of the
`
`’ 190 patent, which creates a “priority break.” Id. at 9—10. Petitioner
`
`supports this contention with its arguments that the claims of the ’ 190 patent
`
`are broad enough to encompasses compositions “wherein some, or even
`
`most, of the naproxen is released before the medium is raised to 3.5 or
`
`higher.” Id. at 10—1 1. According to Petitioner, the “broadest reasonable
`
`construction of ‘inhibits’ in the context of the ’190 patent is ‘slows down,’
`
`which allows for immediate release of some naproxen,” and the “’255
`
`publication does not teach this immediate release.” Id. at 11. Rather,
`
`according to Petitioner, the pre-2003 applications only support compositions
`
`where “the NSAID is not released until the pH has been raised to 3.5 or
`
`higher.” Id. at 10.
`
`To put it another way, Petitioner essentially argues that the pre-2003 .
`
`applications provide written description support of only a species (release of
`
`all naproxen only when pH is 3.5 or higher) of a broader genus recited in
`
`claim 1 in the ’ 190 patent (encompassing release of at least some NSAID
`
`when pH is below 3.5 and when pH is 3.5 or higher), but not written
`
`description support of that genus. Id. at 10—1 1. Moreover, Petitioner
`
`suggests that because a species anticipates a genus, the species disclosed in
`
`

`

`IPR2015-01775
`
`Patent 8,865,190 B2
`
`the ’255 publication anticipates the genus recited in the challenged claims in
`
`the ’190 patent. Id. at 11—14.
`
`Patent Owner responds that the specifications of the ’255 publication
`
`(i.e., the ’216 application) and the ’ 190 patent “are extremely similar,”
`
`referring us to an exhibit that provides a “redline” comparison between the
`
`texts of the two documents. Prelim. Resp. 10—11 (citing Ex. 2016). Patent
`
`Owner also points us to certain paragraphs in the ’255 publication, stating
`
`that disclosures “in the ’216 application demonstrate its broad applicability
`
`to any type of pH sensitive coatings.” Prelim. Resp. 12—13 (citing Ex. 1008
`
`W 4, 8, 44). Patent Owner further argues that “depending on the amount of
`
`drug released, one of skill in, the art would recognize that delayed-release
`
`enteric coatings have differing levels of permeability that prevent, hinder,
`
`and/or restrain (i.e., inhibit) the release of the drug at low pH.” Id. at 14.
`
`Patent Owner points to paragraph 44 in the ’216 application as expressly
`
`disclosing “how to control these dissolution characteristics of a pH—sensitive
`
`coating.” Id. Patent Owner additionally contends that “[s]atisfying the
`
`written description requirement does not require express examples
`
`‘explicitly covering the full scope of the claim language.’” Id. at 15 (citing
`
`LizardTech, Inc. v. Earth Res. Mapping, Inc, 424 F.3d 1336, 1345 (Fed. Cir.
`
`2005)).
`
`In an inter partes review, the burden is on the petitioner to show a
`
`reasonable likelihood that it would prevail on a ground of unpatentability.
`
`35 U.S.C. § 314(a). With respect to entitlement to any earlier effective filing
`
`10
`
`

`

`IPR2015-01775
`
`Patent 8,865,190 B2
`
`date, however, a patent owner is not presumed to be entitled to the earlier
`
`filing dates of ancestral applications that do not share the same disclosure,
`
`such as in a continuation-in-part situation. Focal Therapeutics, Inc. v.
`
`SenoRx, Inc., Case IPR2014-00116, slip op. at 9 (Paper 8) (PTAB Apr. 22,
`
`2014); see also PowerOasis, Inc. v. T-Mobile USA, Inc, 522 F.3d 1299,
`
`1305—06 (Fed. Cir. 2008) (stating that once a defendant establishes that a
`
`reference is § 102(b) prior art, burden is on patent owner to come forward
`
`with evidence proving priority to an earlier filing date). Nonetheless, a
`
`petitioner first must raise the issue by identifying, specifically, the features,
`
`claims, and ancestral applications allegedly lacking written description
`
`support for the claims based on the identified features. Focal Therapeutics,
`
`Case [PR2014-00116, slip op. at 10 (Paper 8). Then, the patent owner must
`
`make a sufficient showing of entitlement to earlier filing date(s), in a manner
`
`that is commensurate in scope with the specific points and contentions raised
`
`by the petitioner. Id.
`
`We are persuaded that Patent Owner provides a sufficient showing of
`
`entitlement to the filing date of the ’216 application (the ’255 publication) in
`
`a manner that is commensurate in scope with the specific points and
`
`contentions raised by Petitioner. Although we recognize that the ’255
`
`publication (and similarly the ’ 190 patent specification itself) does not use
`
`the exact words “at least a portion” in relation to a release of naproxen, the
`
`’255 publication “does not have to describe exactly the subject matter
`
`claimed.” Vas—Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563 (Fed. Cir.
`
`11
`
`

`

`IPR2015—01775
`
`Patent 8,865,190 B2
`
`1991) (citing In re Gosteli, 872 F.2d 1008, 1012 (Fed. Cir. 1989). Rather,
`
`the description must “‘reasonably convey[] to the artisan that the inventor
`
`had possession at that time of the later claimed subject matter.”’ Id. at 1563
`
`(quoting Ralston Purina Co. v. Far—Mar—Co, Inc., 772 F.2d 1570, 1575
`
`(Fed. Cir. 1985)). Thus, we consider whether the ’255 publication as a
`
`whole conveys to one of ordinary skill in the art, either explicitly or
`
`inherently, that the inventors of the ’ 190 patent invented the subject matter
`
`claimed in the challenged claims. Reiflin v. Microsoft, 214 F.3d 1342, 1346
`
`(Fed. Cir. 2000) (citing Vas—Cath, 935 F.2d at 1563).
`
`As an initial matter, we note that Petitioner’s arguments regarding the
`effective filing date of the ’ 190 patent logically apply to certain challenged
`
`claims, but not dependent 3, in View of our claim construction of “inhibit.”
`
`Pet. 9—1 1. Claim 1 of the ’ 190 patent recites that the “release ofat least a
`portion ofsaid naproxen is inhibited unless the pH of said medium is 3.5 or
`
`higher” (emphasis added), which Petitioner suggests encompasses the
`
`release of at least some naproxen when the pH is below 3.5. Pet. 9
`
`(asserting that the challenged claims “allow for release of some amount of
`
`naproxen immediately at any pH”). Dependent claim 3 recites, however, “a
`
`coating that inhibits [naproxen] release from [the dosage form] unless said
`
`dosage form is in a medium with a pH of 3.5 or higher,” without reciting “at
`
`least a portion.” As discussed above, the term “inhibit” in the claims means
`
`to prevent (stop), hinder, or restrain. Petitioner does not explain adequately
`
`how claim 3 encompasses the release of at least some naproxen when the pH
`
`12
`
`

`

`IPR2015-01775
`
`Patent 8,865,190 B2
`
`is below 3.5 when those claims require inhibiting the release of naproxen
`
`(and not a portion of naproxen) at that lower pH. Pet. 9—1 1.
`
`In addition, as part of Petitioner’s argument, when stating that “[i]n
`
`each description of the invention of the ’255 publication, the NSAID is
`
`released only after stomach pH is raised above at least 3.5,” Petitioner
`
`contends that paragraphs 3, 5, and 20 in the ‘255 publication describe “[a]ll
`
`of the dosage forms” as pertaining to “sequential release of acid inhibitor
`
`followed by analgesic,” or “criticize[] prior art formulations that allow for
`
`the immediate release of NSAIDs.” Pet. 10 (citing Ex. 1006 llll 3, 5, 20).
`
`Those paragraphs are present in both the ‘25 5 publication and the ‘ 190
`
`patent. Ex. 2016, 2—3, 20. We do not (agree that those paragraphs indicate
`
`that the ’216 application (or the ’ 190 patent specification) merely describes
`
`formulations that only provide release of naproxen when the pH is 3.5 or
`
`higher.
`
`Patent Owner points us to paragraph 44 in the ’255 publication (the
`
`’216 application), for example. Prelim. Resp. 12—14 (citing Ex. 1006 11 44;
`Ex. 1001, 8:40—53). Paragraph 44 states that “[e]nteric coating layer(s) may
`
`be applied onto the core or onto the barrier layer of the core using standard
`coating techniques,” and that the “pH at which the enteric coat will dissolve
`
`can be controlled” and “dissolution characteristics of the polymer film can
`
`-be altered” by using different components in the enteric coating. Ex. 1006
`
`11 44. That description alone reasonably conveys that the inventors had
`
`possession of relevant formulations having different types of enteric
`
`13
`
`

`

`IPR2015—01775
`
`Patent 8,865,190 B2
`
`coatings, including those providing different dissolution profiles. We further
`
`see that paragraph 10 in the ’255 publication describes a release of NSAID
`
`that “minimizes the adverse effects of the NSAH) on the gastroduodenal
`
`mucosa.” Ex. 1006 11 10 (emphasis added). In addition, paragraph 82 in
`Example 7 refers to a coordinated delivery dosage that provides “the delayed
`
`release” of naproxen (emphasis added). Id. at fl 82. Considering such
`
`descriptions, we are persuaded that the inventors possessed a relevant
`
`composition where a portion (e.g., a small portion) of NSAID was released
`
`when the pH of the medium was below 3.5, even if most or nearly all of the
`
`drug was not released until the pH was 3.5 or higher.
`
`Additionally, not every species in a genus need be described in order
`
`for the genus to meet the written description requirement. Regents of U.
`
`California v. EliLilly & Ca, 119 F.3d 1559, 1568 (Fed. Cir. 1997) (citing
`
`Utter v. Hiraga, 845 F.2d 993, 998—99 (Fed. Cir. 1988)). In this case, the
`
`genus at issue has two easily identified species, i.e., inhibiting the release of
`
`all or a portion of a drug unless a pH is reached, in contrast to a complex
`
`chemical genus, for example, encompassing a large number of possible
`
`species. Id. ; see also Hynix Semiconductor Inc. v. Rambus Inc, 645 F.3d
`
`1336, 1352 (Fed. Cir. 2011) (stating that whether disclosure of a species
`
`supports a genus “depends upon the state of the art and the nature and
`
`breadth of the genus,” finding sufficient support where the genus consisted
`
`of only two species). We are persuaded that the ’255 publication as a whole
`
`conveys to one of ordinary skill in the art that the inventors of the ’ 190
`
`14
`
`

`

`IPR2015—01775
`
`Patent 8,865,190 B2
`
`patent invented the subject matter claimed in the challenged claims, i.e., a
`
`composition where release of all or at least a portion of naproxen is inhibited
`
`unless the pH is 3.5 or higher.
`
`In View of the information before us, Patent Owner establishes
`
`sufficiently that the challenged claims of the ’ 190 patent properly claim
`
`priority to the ’216 application. Thus, the ’255 publication is not prior art to
`
`the challenged claims under 35 U.S.C. § 102. Consequently, we are not
`
`persuaded that Petitioner has established a reasonable likelihood of
`
`prevailing in its challenge to claims 1—8 on the basis that the ’255
`
`publication anticipates those claim under 35 U.S.C. § 102(b).
`
`C.
`
`Asserted Obviousness over the ’55 6 patent alone, or in view of
`Chandramouli or the ’225 patent
`
`Petitioner asserts that claims 1—8 of the ’190 patent would have been
`
`obvious over the ’5 56 patent alone, or in View of Chandramouli or the ’225
`
`patent. Pet. 15—32.
`
`1. The ’556 patent (Ex. 1007)
`
`The ’556 patent discloses dosage forms, such as oral tablets,
`
`comprising a non—steroidal antiinflammatory drug (“NSAID”) and a proton
`
`pump inhibit (“PPI”). Ex. 1007, 128—13; 4:30—33. The ’556 patent lists a
`
`number of “well known examples of NSAIDs,” including naproxen. Id. at
`
`5258—625. It states that “NSAIDs have been widely used in arthritis therapy
`
`for several years,” and incorporates by reference a list of patents that
`
`“describe various NSAIDs suitable for use in the invention described herein,
`
`and processes for their manufacture.” Id. at 6:6—3 1.
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`IPR2015-01775
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`Patent 8,865,190 B2
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`The ’556 patent also discloses that PPIs “typically include
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`benzimidazole compounds,” and incorporates by reference a list of patents
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`disclosing “benzimidazole compounds suitable for use in the invention.” Id.
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`at 6:32—50. The ’556 patent states that in “certain preferred embodiments,
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`the proton pump inhibitor is omeprazole, either in racernic mixture or only
`the (-)enantiomer of omeprazole (i.e. esomeprazole), as set forth in US. Pat.
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`No. 5,877,192, hereby incorporated by reference.” Id. at 6:50—58 (citing the
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`’192 patent, Ex. 1008).
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`The ’556 patent teaches that “[a]s is well known in the art, proton
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`pump inhibitors are susceptible to degradation and/or transformation in
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`acidic and neutral media,” and that the half-life of “omeprazole in water
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`solutions at pH-values less than three is shorter than ten minutes.” Id. at
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`829—17. Thus, according to the ’556 patent, “it is preferable that in an oral
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`solid dosage form they be protected from contact with the acidic gastric
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`juice and the active substance must be transferred in intact form to that part
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`of the gastrointestinal tract where pH is near neutral and where rapid
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`absorption of the medication can occur.” Id. at 8:18—29.
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`Along these lines, the ’556 patent discloses embodiments where “the
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`tablet contains the NSAID within a sustained release matrix and the proton
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`pump inhibitor coated into the tablet in an enteric coated layer.” Id. at 12:4—
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`7. It discloses embodiments where “coatings are provided to permit either
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`pH—dependent or pH-independent release, e.g., when exposed to
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`gastrointestinal fluid.” Id. at 12:17—19. The ’556 patent further states that
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`IPR2015—01775
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`Patent 8,865,190 B2
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`“[a] pH—dependent coating serves to release the proton pump inhibitor in
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`desired areas of the gastro-intestinal (GI) tract, e.g., the small intestine, such
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`that an absorption profile is provided which is capable of providing at least
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`about twelve hour and preferably up to twenty—four hour relief to a patient.”
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`Id. at'12: 19—24. It states it is “preferable to formulate compositions which
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`release a portion of the dose, preferably the NSAID, in one desired area of
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`the GI tract, e.g., the stomach, and release the remainder of the dose,
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`preferably the proton pump inhibitor, in another area of the GI tract, e.g., the
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`small intestine.” Id. at 12:27—32.
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`2.
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`Analysis ofAsserted Obviousness over the ’55 6 patent
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`Petitioner asserts that the ’556 patent alone renders claims 1—8 of the
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`’ 190 patent obvious. Pet. 15—22, 24—32. In relation to the drug release
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`limitations of claims 1 and 3, Petitioner points us to column 12 in the ’556
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`patent as teaching “a combination tablet that releases the NSAID and PPI at
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`different times using pH—dependent and pH-independent coatings,” and the
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`“use of these coatings to ‘release a portion of the dose [.
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`. .] in one desired
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`area of the GI tract, e.g., the stomach, and release the remainder of the dose
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`[. . .] in another area of the GI tract, e.g., the small intestine.”’ Pet. 16, 18,
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`26—27 (citing Ex. 1007, 12:17—18, 27—40).
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`.
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`Although Petitioner acknowledges that “the ’556 patent discloses a
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`preferred formulation that would release the NSAID in the stomach and
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`omeprazole in the small intestine,” essentially the opposite of what is recited
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`in the challenged claims, Petitioner asserts that the ’556 patent “is not
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`Patent 8,865,190 B2
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`limited to such formulations.” Id. at 17. Citing Dr. Banakar’s Declaration in
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`support, Petitioner contends that a person of ordinary skill in the art
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`(“POSA”) “would have understood that PPIs are preferably released in the
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`gastrointestinal tract prior to reaching the small intestine” becauSe PPIs act
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`“by inhibiting H2 receptors on the surface of parietal cells,” which “are
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`primarily concentrated in the duodenum, the portion of the GI tract directly
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`following the stomach.” Id. at 17 (citing Ex. 1002 W 35, 49). Petitioner
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`also argues that it was known that NSAIDs “caused significant topical injury
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`to the GI tract when exposed to acidic environments,” and the risk of this
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`injury “is reduced if the NSAID is released in a more neutral environment,
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`such as the small intestine,” and a POSA would have “been motivated to
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`release the NSAID later in the GI tract.” Id. at 17—1 8 (citing 1002 W 32, 35,
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`49, 55).
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`In the specific portions of the reference cited by Petitioner, the ’556
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`patent teaches an “NSAID within a sustained release matrix and the proton
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`pump inhibitor coated into the tablet in an enteric coated layer,” where the
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`“pH-dependent coating serves to release the proton pump inhibitor in desired
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`areas of the gastro-intestinal (GI) tract, e.g., the small intestine” (where the
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`pH is higher than 3.5), and that it is “preferable” to release the NSAID in the
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`stomach (i.e., at a pH at 3.5 or lower). Id. at 16; EX. 1007, 12:4—7, 27—32;
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`Prelim. Resp. 19—21. Thus, Petitioner does not rely on teachings in the ’556
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`patent itself as disclosing or suggesting the particular release profiles of
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`esomeprazole (PPI) and naproxen (NSAID) based on pH as recited in
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`IPR2015-Ol775
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`Patent 8,865,190 B2
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`challenged claim 1.8 Instead, the Petition cites to Dr. Banakar’s testimony in
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`support of its contention that an ordinary artisan would have done the
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`opposite of what the ’556 patent itself teaches and suggets.
`Dr. Banakar’s testimony cites other references (not cited in the
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`Petition) in support of the contention that it was known PPIs act on parietal
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`cells in the GI tract. Ex. 1002 W 32, 35, 48, 49. Dr. Banakar thereafter
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`summarily concludes that a “POSA would have understood that
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`esomeprazole should be released early in the GI tract to reduce the acidity
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`8 In its analysis and claim chart pertaining to claim 1 and its “release”
`limitation, Petitioner quotes the ’556 patent in a manner that fails to include
`relevant portions of the cited passage. Pet. 16, 26—27 (citing Ex. 1007,
`12:33—40). The passage at column 12, lines 33—40, actually states:
`“Formulations according to the invention that utilize pH—dependent coatings
`to obtain formulations may also impart a repeat-action effect whereby
`unprotected drug, preferably the NSAID, is coated over the enteric coat
`and is released in the stomach, while the remainder, preferably
`containing the proton pump inhibitor, being protected by the enteric
`coating, is released further down the gastrointestinal tract.” Ex. 1007,
`12:33—40 (emphasis added, including to indicate portions omitted in
`Petition’s claim chart). Elsewhere in columns 8 and 12 of the ’556 patent,
`the ’556 patent repeatedly refers to using a pH dependent coating (e.g.,
`enteric coating) to facilitate release of PPI in the small intestines, while not
`coating NSAID so that it is released the stomach. Id. at 12:4—40, see also id.
`at 8: 17—40 (disclosing protecting PPIs so they are released “where the pH is
`near neutral”). Petitioner has not pointed adequately to where the ’556
`patent discloses or suggests doing the reverse, e.g., enterically coating
`NSAID so that it is released further down the GI tract (where the pH is
`higher), and releasing “unprotected” PPI at any pH, such as in the stomach
`(where the pH is 3.5 or lower).
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`IPR2015-01775
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`Patent 8,865,190 B2
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`(inhibit proton pumps) while naproxen may be released simultaneously, or
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`preferably later than the release of esomeprazole, in order to reduce the risk
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`of NSAID-associated gastroduodenal injury,” without citing additional
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`information in support. Id. at {[1] 35, 32, 48, 55.
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`Such conclusory statements by Petitioner and its declarant do not
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`explain sufficiently, nor provide adequate support as to, why an ordinary
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`artisan would have prepared the composition of claim 1 (requiring release of
`at least some esomeprazole regardless of the pH, e.g., in the stomach, not
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`just the small intestine), or done the opposite of what the ’556 patent taught
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`to address the issue of PPI stability at lower pHs. Ex. 1007, 8:17—40, 12:4—
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`40. Petitioner’s conclusory assertions that the subject matter of claim 1
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`would have been “obvious to try” are likewise inadequate to address these
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`points. Pet. 18.
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`Regarding a reasonable expectation of success, Petitioner also argues,
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`essentially,,that the ’556 patent fails to teach away from the challenged
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`claims. Pet. 18—22 (stating, for example, that the ’556 patent “does not
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`suggest formulas with non-enteric coated PPIs would result in no
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`bioavailability of the PPI,” id. at 18—19). A lack of teaching away regarding
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`the bioavailability of non-enteric coated esomeprazole in the ’556 patent, by
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`itself, does not indicate a reasonable expectation of success in making the
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`compositions recited in the challenged claims.
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`IPR2015-01775
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`Petitioner also relies on the Pilbrant reference (Ex. 1010)9 to support
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`the argument that “it would have been obvious to a POSA that a viable,
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`therapeutically effective formulation could be developed using non-enteric
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`coated esomeprazole.” Id. at 19—22. Petitioner refers to a decision by the
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`Federal Circuit, alleging that the court previously “acknowledged that
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`Pilbrant teaches non-enteric solid dosage forms of PPIs as a ‘viable
`7))
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`alternative to enteric coating.
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`Ex. 21-22 (citing Santarus, Inc. v. Par
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`Pharm, 694 F.3d 1344, 1355—56 (Fed. Cir. 2012)).
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`Consistent with the ’556 patent, Pilbrant teaches that “[o]meprazole
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`degrades very rapidly in water solutions at low pH-values.” Ex. 1010, 113.
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`In this context, Pilbrant describes the use of an “enteric—coated dosage form,
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`which releases omeprazole for absorption in the small intestine,” while
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`stating that a conventional oral dosage “was ruled out” because “more than
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`half of the omeprazole in a rapidly dissolving dosage form degrades in the
`stomach.” Id. at 114. In addition, Pilbrant states that a “rapidly dissolving
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`suspen