UNITED STATES PATENT AND TRADEMARK OFFICE
`__________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________________
`
`AYLA PHARMA LLC,
`Petitioner,
`
`v.
`
`NOVARTIS AG,
`Patent Owner.
`__________________
`
`Case No. IPR2020-00295
`Patent 9,533,053
`__________________
`
`PATENT OWNER’S PRELIMINARY RESPONSE
`
`
`
`
`
`
`
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`

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`
`
`TABLE OF CONTENTS
`
`Case No. IPR2020-00295
`Patent 9,533,053
`
`INTRODUCTION ..................................................................................................... 1 
`
`BACKGROUND ....................................................................................................... 3 
`
`  Olopatadine, Patanol®, and Pataday® .................................................. 3 
`
` 
`
` 
`
` 
`
`The ’154 and ’053 Patents ..................................................................... 4 
`
`1. 
`
`2. 
`
`3. 
`
`The Specification of the ’154 and ’053 Patents .......................... 4 
`
`The File Histories of the ’154 and ’053 Patents ......................... 6 
`
`The Claims of the ’154 and ’053 Patents .................................... 9 
`
`Patent Owner’s Pazeo® Product ......................................................... 13 
`
`Prior Proceedings Involving the ’154 and ’053 Patents ...................... 14 
`
`1. 
`
`2. 
`
`3. 
`
`Argentum’s 2016 IPR Petition .................................................. 14 
`
`The District Court Trial and Final Decision ............................. 15 
`
`Cipla’s 2018 IPR Petition ......................................................... 22 
`
` 
`
`Ayla’s IPR Petition .............................................................................. 23 
`
`1. 
`
`2. 
`
`3. 
`
`4. 
`
`Ayla Pharma LLC ..................................................................... 23 
`
`Ayla’s Petition Is a Copy of Cipla’s 2018 Petition ................... 24 
`
`Ayla’s Arguments Ignore the District Court’s Contrary
`Factual Findings ........................................................................ 25 
`
`Ayla’s Petition Presents No New Claim Construction
`Issues ......................................................................................... 27 
`
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`i
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`ARGUMENT ........................................................................................................... 28 
`
`Case No. IPR2020-00295
`Patent 9,533,053
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`The Board Should Exercise Its Discretion under §ֻ§ 325(d) and 314(a) to
`Deny Institution. ............................................................................................ 28 
`
` 
`
` 
`
`The Board Should Deny Institution of Ayla’s Petition under
`§ 325(d) as a Rehash of the Same Art and Arguments
`Previously Presented to the Office ...................................................... 29 
`
`1. 
`
`2. 
`
`The Same Art and Substantially the Same Arguments
`Previously Were Presented to the Office .................................. 30 
`
`Ayla’s Petition Does Not Demonstrate that the Office
`Erred .......................................................................................... 38 
`
`The Board Should Exercise Its Discretion under § 314(a) and
`Decline to Institute Trial ..................................................................... 42 
`
`1. 
`
`2. 
`
`3. 
`
`4. 
`
`5. 
`
`Apple Factors (1), (2), and (3)—Involving the Existence
`of a Stay, the Timing of the Trial, and the Expenditure of
`Resources—Weigh in Favor of Denying Institution ................ 43 
`
`Apple Factor (4), Involving the Overlap between Issues
`in the Petition and the Litigation, Weighs in Favor of
`Denying Institution ................................................................... 45 
`
`Apple Factor (5), Involving the Identities of the Parties
`and the Duplication of the Proceedings, Weighs in Favor
`of Denying Institution ............................................................... 53 
`
`Under Apple Factor (6), Ayla’s Disregard of the District
`Court’s Findings of Secondary Considerations Favors
`Denying Institution ................................................................... 56 
`
`Ayla’s Generalized Arguments Regarding the District
`Court Decision Do Not Justify Institution ................................ 60 
`
`CONCLUSION ........................................................................................................ 62 
`
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`ii
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`Case No. IPR2020-00295
`Patent 9,533,053
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`TABLE OF AUTHORITIES
`
`
`Alcon Research, Ltd. v. Watson Labs., Inc.,
`1:15-cv-01159 (D. Del.) (EX1030) .............................................................passim
`
`Harmonic Inc. v. Avid Tech, Inc.,
`815 F.3d 1356 (Fed. Cir. 2016) .......................................................................... 28
`
`Oil States Energy Servs., LLC v. Greene’s Energy Grp., LLC,
`138 S. Ct. 1365 (2018) ........................................................................................ 28
`
`St. Regis Mohawk Tribe v. Mylan Pharm. Inc.,
`896 F.3d 1322 (Fed. Cir. 2018) .......................................................................... 28
`
`WBIP, LLC v. Kohler Co.,
`829 F.3d 1317 (Fed. Cir. 2016) .......................................................................... 58
`
`Advanced Bionics, LLC v. MED-EL Elektromedizinische Geräte GmbH,
`IPR2019-01469, Paper 6 (PTAB Feb. 13, 2020) .........................................passim
`
`Alarm.com Inc. v. Vivint, Inc.,
`IPR2015-01967, Paper 12 (PTAB Mar. 30, 2016) ............................................. 40
`
`Apple Inc. v. Fintiv, Inc.,
`IPR2020-00019, Paper 11 (PTAB Mar. 20, 2020) ......................................passim
`
`Becton, Dickinson & Co. v. B. Braun Melsungen AG,
`IPR2017-01586, Paper 8 (Dec. 15, 2017)............................................... 30, 39, 41
`
`Clim-A-Tech Ind., Inc. v. William A. Ebert,
`IPR2017-01863, Paper 13 (PTAB Feb. 12, 2018) .............................................. 40
`
`E-One, Inc. v. Oshkosh Corp.,
`IPR2019-00161, Paper 16 (PTAB May 15, 2019) ....................................... 54, 55
`
`E-One, Inc. v. Oshkosh Corp.,
`IPR2019-00162, Paper 16 (PTAB June 5, 2019) ............................................... 55
`
`NHK Spring Co., Ltd. v. Intri-Plex Techs. Inc.,
`IPR2018-00752, Paper 8 (PTAB Sept. 12, 2018) ........................................passim
`
`iii
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`

`
`Robert Bosch Tool Corp. v. SD3, LLC,
`IPR2016-01751, Paper 15 (PTAB Mar. 22, 2007) ............................................. 59
`
`Case No. IPR2020-00295
`Patent 9,533,053
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`Stryker Corp. v. KFx Med., LLC,
`IPR2019-00817, Paper 10 (PTAB Sept. 16, 2019) ....................................... 59, 60
`
`ZTE (USA) Inc. v. Fractus, S.A.,
`IPR2018-01457, Paper 20 (PTAB Oct. 4, 2019) .......................................... 38, 41
`
`35 U.S.C. § 314(a) ............................................................................................passim
`
`35 U.S.C. § 325(d) ............................................................................................passim
`
`
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`Case No. IPR2020-00295
`Patent 9,533,053
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`EXHIBIT LIST
`
`Description
`Exhibit
`EX2001 File History of U.S. Patent 9,533,053
`EX2002 Pazeo® Prescribing Information (April 2016)
`EX2003 Declaration of Erning Xia, Argentum Pharm. v. Alcon Research,
`IPR2016-00544 (PTAB Jan. 31, 2016)
`EX2004 Declaration of Leonard Bielory, Argentum Pharm. v. Alcon
`Research, IPR2016-00544 (PTAB Feb. 2, 2016)
`EX2005 Day 1 Trial Transcript, Oct. 2, 2017, Alcon v. Watson, No. 15-cv-
`1159 (D. Del.)
`EX2006 Day 2 Trial Transcript, Oct. 3, 2017, Alcon v. Watson, No. 15-cv-
`1159 (D. Del.)
`EX2007 Day 3 Trial Transcript, Oct. 4, 2017, Alcon v. Watson, No. 15-cv-
`1159 (D. Del.)
`EX2008 Day 4 Trial Transcript, Oct. 5, 2017, Alcon v. Watson, No. 15-cv-
`1159 (D. Del.)
`EX2009 Petition, Cipla Ltd. v. Alcon Research, IPR2018-01021 (PTAB June
`5, 2018)
`EX2010 Order, Termination of the Proceedings, Cipla Ltd. v. Alcon Research,
`IPR2018-01020, IPR2018-01021 (PTAB Sept. 17, 2018)
`EX2011 Ayla Pharma LLC Articles of Organization (Nov. 26, 2019)
`EX2012 Ayla Pharma LLC Statement of Information (Dec. 18, 2019)
`EX2013 Dubai Angel Ventures LLC Articles of Organization (Dec. 3, 2019)
`EX2014 Dubai Angel Ventures LLC Statement of Information (Dec. 30,
`2019)
`EX2015 Thompson Capital Holdings LLC Articles of Organization (Nov. 26,
`2019)
`EX2016 Thompson Capital Holdings LLC Statement of Information (Jan. 16,
`2020)
`
`
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`
`v
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`
`
`INTRODUCTION
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`Case No. IPR2020-00295
`Patent 9,533,053
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`Ayla begins its petition with reference to “[t]he patent family to which the
`
`’053 patent belongs,” arguing that institution is warranted because “the claims of
`
`the ’053 patent are similar to the claims of the ’154 (parent) patent.” Pet. 1-2.
`
`Given Ayla’s admission of the relevance of the parent ’154 patent, the most
`
`noteworthy thing about its petition is what it omits.
`
`Not once does Ayla acknowledge in its petition that the examiner, during
`
`prosecution of the ’053 patent, considered not just the same references relied upon
`
`by Ayla but also virtually the same arguments—via the disclosure to the examiner
`
`of Argentum’s prior IPR petition targeting the ’154 patent based on the same
`
`references and largely the same arguments as in Ayla’s petition. Nor does Ayla
`
`suggest that the examiner, in considering those references and arguments, erred in
`
`any respect by allowing the ’053 patent.
`
`Ayla also ignores that the District Court, in a lengthy post-trial decision
`
`upholding the validity of the ’154 patent, made numerous factual findings
`
`concerning all but one of the references making up Ayla’s grounds. And, with
`
`only a single exception, Ayla fails to acknowledge that many of those findings run
`
`directly counter to Ayla’s arguments. In order to institute, therefore, the Board
`
`would have to credit arguments expressly rejected by the District Court—and yet
`
`Ayla offers no justification whatsoever for doing so.
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`1
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`

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`To top it off, Ayla wholly disregards extensive findings by the District Court
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`Case No. IPR2020-00295
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`regarding objective evidence of nonobviousness relating to Patent Owner’s
`
`commercial product covered by both the ’053 and ’154 patents. Inexplicably, Ayla
`
`ignores that evidence despite the Board’s repeated warnings to petitioners that
`
`failure to address known objective evidence weighs in favor of denying institution.
`
`Ayla’s decision to omit each of those points would be understandable if
`
`Argentum’s prior IPR petition and the District Court’s final decision had involved
`
`an unrelated patent with claims directed to dissimilar subject matter. But that is
`
`not the case. Ayla itself repeatedly trumpets the high degree of similarity between
`
`the claims of the related ’053 and ’154 patents. The patent examiner recognized
`
`this overlap as well, allowing the ’053 patent only after Patent Owner terminally
`
`disclaimed it against the ’154 patent. In light of the undisputed similarity between
`
`the claims of the ’053 and ’154 patents, Ayla’s decision to ignore all of this
`
`evidence constitutes a glaring deficiency in its petition.
`
`Denial of institution is warranted. Under § 325(d), not only did the
`
`examiner, in allowing the ’053 patent over Argentum’s prior IPR petition, consider
`
`the same art and virtually the same arguments as in Ayla’s petition, but Ayla offers
`
`no suggestion that the Office erred in considering those materials. And under
`
`§ 314(a), it would be highly inefficient for the Board to revisit the District Court’s
`
`specific factual findings—particularly in the absence of any justification from Ayla
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`2
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`

`

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`for doing so. Taken together, the Board should exercise its discretion and deny
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`Case No. IPR2020-00295
`Patent 9,533,053
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`institution of Ayla’s petition.
`
`BACKGROUND
` Olopatadine, Patanol®, and Pataday®
`Olopatadine is an antihistamine and mast-cell stabilizer used for treating the
`
`signs and symptoms of ocular allergic conjunctivitis. As of 2011, two aqueous
`
`solutions of olopatadine were approved for use. EX1002 (’053 Patent) at 1:28-35;
`
`EX1030 (District Court Op.) at 015-016. Patanol® contains 0.1 w/v % olopatadine
`
`in solution and is dosed twice daily.1 EX1030 at 015. Pataday®, containing 0.2
`
`w/v % olopatadine in solution, is dosed once per day. Id. Whereas twice-daily
`
`Patanol® treated both the redness and itching associated with allergic
`
`conjunctivitis, once-daily Pataday® was approved for treatment of only the
`
`itching—not the redness. Id. at 015-016, 047. Both products were developed by
`
`Patent Owner.2 EX1002 at 1:28-35. As of 2011, the 0.2 w/v % concentration in
`
`
`1 The olopatadine concentrations recited in this brief exclude the weight of the
`
`chloride counterion.
`
`2 The original developer, Alcon Laboratories, later became a subsidiary of
`
`Novartis. For simplicity, this brief uses “Patent Owner” to refer to Alcon and/or
`
`Novartis.
`
`3
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`

`

`
`Pataday® was the most concentrated olopatadine solution approved for ophthalmic
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`Case No. IPR2020-00295
`Patent 9,533,053
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`use. EX1030 at 015-016. Furthermore, the solubility limit of olopatadine in water
`
`was known to be about 0.18 w/v % at neutral pH. EX1002 at 2:4-6.
`
`
`The ’154 and ’053 Patents
`The ’053 patent challenged by Ayla is a continuation of the ’154 patent. See
`
`EX1001 (’154 Patent); EX1002 (’053 Patent). The two patents claim priority to
`
`the same provisional applications filed in 2011; they share an identical
`
`specification; and they claim similar subject matter, with many common claim
`
`limitations.
`
`1.
`
`The Specification of the ’154 and ’053 Patents
`
`The shared specification of the ’154 and ’053 patents explains the
`
`inventiveness of their claimed high-concentration olopatadine ophthalmic
`
`solutions.
`
`The specification explains that the two available ophthalmic olopatadine
`
`solutions, Patanol® and Pataday®, “were generally believed to be the most
`
`efficacious products known for addressing symptoms of allergic conjunctivitis.”
`
`EX1002 at 1:36-38. Although “relatively high concentration solutions of
`
`olopatadine” could potentially “relieve late phase ocular allergic conjunctivitis
`
`symptoms,” the problem of solubilizing high concentrations of olopatadine was
`
`“extremely difficult and complex.” Id. at 1:61 – 2:2. This was due in part to
`
`4
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`

`

`
`olopatadine’s low solubility at near-neutral pH—i.e., the pH most suitable for
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`administration to the eye. Id. at 2:5-6.
`
`As the specification explains, achieving a high-concentration olopatadine
`
`solution at near-neutral pH that is safe, stable, and efficacious for use in the eye
`
`posed significant challenges. For example, “excipients such as polyethylene glycol
`
`(PEG) 400 and polyvinylpyrrolidone (PVP), when used at reasonably desirable
`
`concentrations, have proven incapable, alone or in combination, of solubilizing
`
`sufficient concentrations of olopatadine in compositions having approximately
`
`neutral pH.” Id. at 2:11-16. Moreover, high-concentration olopatadine
`
`compositions containing “a combination of solubilizing agents” such as PEG and
`
`PVP “typically lack long term stability or shelf life.” Id. at 5:60-65.
`
`Alternate approaches presented further difficulties. Although “higher
`
`molecular weight PEGs such as PEG 6000 can significantly enhance solubility of
`
`olopatadine, … such PEGs cause risk of discomfort when administered to
`
`humans.” Id. at 2:20:23. Cyclodextrins, a class of compounds with “the ability to
`
`solubilize significantly higher concentrations of olopatadine,” also had significant
`
`drawbacks, notably that the “use of undesirably high concentrations of
`
`cyclodextrins” would “reduce olopatadine efficacy and/or preservation efficacy of
`
`solutions.” Id. at 2:23-29. Indeed, cyclodextrins “can significantly interfere with
`
`preservation efficacy” of olopatadine. Id. at 5:41-48; see also id. at 15:32-34.
`
`5
`
`

`

`The inventors nonetheless discovered that a desirable set of properties could
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`Case No. IPR2020-00295
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`be obtained by using “two or more solubilizing agents, in addition to
`
`cyclodextrin.” Id. at 6:6-7. The specification thus discloses multi-component
`
`formulations containing PVP “to aid in the solubilization of the olopatadine,” PEG
`
`“for enhancing solubility,” and a cyclodextrin. Id. at 2:46-62. Moreover,
`
`notwithstanding the propensity of “cyclodextrin derivatives [to] significantly
`
`inhibit the ability of a preservative to provide desired preservation to an aqueous
`
`formulation,” id. 15:32-34, the inventors managed to “achiev[e] desired
`
`preservation” profiles by including benzalkonium chloride, borate, and a polyol in
`
`certain multi-component olopatadine formulations, id. at 2:67 – 3:6. The
`
`specification contains examples and extensive data demonstrating the beneficial
`
`properties of the disclosed formulations, including high olopatadine solubilization
`
`and desirable preservation profiles. See, e.g., id. at 13:64 – 21:42.
`
`2.
`
`The File Histories of the ’154 and ’053 Patents
`
`During examination of the application leading to the parent ’154 patent, the
`
`examiner considered the patentability of claims reciting ophthalmic compositions
`
`for the treatment of ocular allergic conjunctivitis, comprising “at least 0.67 w/v %
`
`olopatadine,” “a γ-cyclodextrin derivative, a β-cyclodextrin derivative or both,”
`
`“polyvinylpyrrolidone,” “polyethylene glycol,” and “water.” See EX1008 at 726-
`
`729.
`
`6
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`

`

`The examiner lodged an anticipation rejection, asserting that Schneider
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`(EX1006) disclosed an “aqueous, sterile ophthalmic solution, suspension, or
`
`emulsion” wherein olopatadine’s “concentration lower limit is 0.05 % w/v without
`
`any upper limit.” EX1008 at 739. The examiner further asserted that Schneider’s
`
`formulations contained “water,” “polyethylene glycols (PEGs),” and
`
`“polyvinylpyrrolidones (PVPs),” among other excipients. Id. The examiner also
`
`asserted obviousness over Schneider in combination with Abelson (EX1039).
`
`EX1008 at 739-745. The examiner alleged that Abelson discloses pharmaceutical
`
`compositions comprising agents including olopatadine, as well as “solubilizers
`
`includ[ing] a cyclodextrin such as alpha-, beta-, or gamma-cyclodextrin.” Id. at
`
`741. According to the examiner, it would have been obvious to make the
`
`compositions of Schneider using a cyclodextrin as disclosed in Abelson. E.g., id.
`
`at 741, 744.
`
`Patent Owner, in response, amended the claims to replace “ophthalmic
`
`composition” with “ophthalmic solution” and to add certain other limitations. Id.
`
`at 779-788. The examiner allowed the claims, and the ’154 patent issued in 2014.
`
`Id. at 803; EX1001.
`
`Patent Owner also filed a continuation application, which was assigned to
`
`the same examiner and which ultimately issued as the ’053 patent. In the first
`
`substantive office action, the examiner rejected the pending claims for
`
`7
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`

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`obviousness-type double patenting (OTDP) over the claims of the ’154 patent. See
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`EX2001, at 119-120 (pending claims), 157-169 (office action). The basis of the
`
`rejection, the examiner explained, was that the pending claims had “similar
`
`structural features” as those of the ’154 patent, and certain pending claims were
`
`“generic to” and “anticipated by” the claims of the ’154 patent. See id. at 164-168.
`
`Patent Owner did not dispute the similarity of the claims, and instead filed a
`
`terminal disclaimer over the ’154 patent. Id. at 213, 574. In response, the
`
`examiner allowed the claims. Id. at 575-577, 611-614, 628-635.
`
`Patent Owner also filed several information disclosure statements during
`
`prosecution of the application leading to the ’053 patent. As relevant here, the
`
`examiner considered the Bhowmick, Castillo, Hayakawa, Schneider, and Yanni
`
`references—i.e., every reference constituting every ground in Ayla’s present IPR
`
`petition. EX1002 at 001-003 (each reference listed among the ’053 patent’s
`
`“References Cited”); see also EX2001 at 182, 184, 193 (each reference considered
`
`by the examiner). Patent Owner also disclosed to the examiner a petition, two
`
`declarations, and numerous exhibits from a 2016 IPR filing by Argentum
`
`Pharmaceuticals targeting the ’154 patent. EX2001 at 653. The examiner
`
`explained that the “cited prior art[]” references in these IPR filings “do not teach or
`
`suggest the claimed composition.” Id. at 633-634; see also EX1002 at 003
`
`(Argentum’s IPR filings listed among the ’053 patent’s “References Cited”).
`
`8
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`

`

`The examiner allowed the claims over each of these references, and the ’053
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`patent issued in 2017. EX1002.
`
`3.
`
`The Claims of the ’154 and ’053 Patents
`
`As shown below, the claim limitations of the ’053 and ’154 patents overlap
`
`significantly. And although the two sets of claims are not identical, Ayla not once
`
`contends that any difference between them is material for purposes of considering
`
`whether the Board should institute its petition.
`
`Claims 1 and 8 of the ’053 patent. Claim 1 is the first of two independent
`
`claims of the ’053 patent, and its overlap with the claims of the ’154 patent is
`
`striking.
`
`As shown in the following table, for example, claim 1 of the ’053 patent and
`
`claim 8 of the ’154 patent both recite “[a]n aqueous ophthalmic solution for
`
`treatment of ocular allergic conjunctivitis” containing “at least 0.67% w/v %” of
`
`“olopatadine dissolved in the solution,” along with “PEG,” “polyvinyl-
`
`pyrrolidone,” a “cyclodextrin,” and “water”:
`
`’053 patent (EX1002), claim 1
`1. An aqueous ophthalmic solution
`for treatment of ocular allergic
`conjunctivitis, the solution
`comprising:
`
`at least 0.67 w/v % olopatadine
`dissolved in the solution;
`
`
`
`’154 patent (EX1001), claim 8
`8. An aqueous ophthalmic solution
`for treatment of ocular allergic
`conjunctivitis, the solution
`comprising:
`
`at least 0.67 w/v % but no greater
`than 1.0 w/v % olopatadine
`dissolved in the solution;
`
`9
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`Case No. IPR2020-00295
`Patent 9,533,053
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`2.0 w/v % to 6.0 w/v % PEG having
`a molecular weight of 300 to 500;
`
`2.0 w/v % to 6.0 w/v %
`polyvinylpyrrolidone;
`
`at least 0.5 w/v % but no greater than
`2.0 w/v % hydroxypropyl-γ-
`cyclodextrin; and
`
`water.
`
`
`
`
`
`
`
`PEG having a molecular weight of
`200 to 800;
`
`polyvinylpyrrolidone;
`
` a
`
` cyclodextrin selected from the
`group consisting of SAE-β-
`cyclodextrin, hydroxypropyl-β-
`cyclodextrin and hydroxypropyl-γ-
`cyclodextrin; and
`
`water.
`
`The other independent claim of the ’053 patent is claim 8. It recites the
`
`
`
`
`
`
`
`
`
`identical limitations as claim 1 and further recites “benzalkonium chloride” and
`
`“hydroxypropylmethyl cellulose.” Those limitations similarly are found in the
`
`claims of the ’154 patent, including claim 21 (“benzalkonium chloride”) and claim
`
`22 (“hydroxypropylmethyl cellulose”).
`
`Claim 2 of the ’053 patent. Claim 2 depends from claim 1 and recites
`
`“further comprising benzalkonium chloride.” As just noted, benzalkonium
`
`chloride is a limitation of the ’154 patent, including in claim 21.
`
`Claims 3 and 9 of the ’053 patent. Claim 3 depends from claim 2, and claim
`
`9 depends from claim 8. Both claims 3 and 9 recite a solution “further comprising
`
`borate.” Borate also is a limitation of the ’154 patent, including in claim 9
`
`(“further comprising borate”).
`
`10
`
`

`

`Claims 4 and 10 of the ’053 patent. Claim 4 depends from claim 3, and
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`Case No. IPR2020-00295
`Patent 9,533,053
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`claim 10 depends from claim 9. Both claims 4 and 10 recite a solution “further
`
`comprising a polyol.” The claims of the ’154 patent also recite a polyol, including
`
`in claim 10 (“further comprising a polyol”). Moreover, mannitol is a polyol (see,
`
`e.g., ’154 patent, claim 18), and claim 24 of the ’154 patent recites a solution
`
`“further comprising … mannitol.”
`
`Claims 5 and 6 of the ’053 patent. Claims 5 depends from claim 1 and
`
`recites an olopatadine concentration “no greater than 1.0 w/v %.” Claim 6 depends
`
`from claim 1 and recites concentration ranges for PEG, PVP, and cyclodextrin. As
`
`shown in the following table, claim 8 of the ’154 patent also recites an olopatadine
`
`concentration “no greater than 1.0 w/v %” and the same concentration ranges for
`
`PEG, PVP, and cyclodextrin:
`
`’053 patent (EX1002), claims 5
`and 6
`5. A solution as in claim 1
`wherein the concentration of
`olopatadine is no greater than
`1.0 w/v %.
`
`6. A solution as in claim 1
`wherein
`
`the concentration of PEG is 2.0
`w/v % to 6.0 w/v %,
`
`
`’154 patent (EX1001), claim 8
`
`8. An aqueous ophthalmic solution for
`treatment of ocular allergic
`conjunctivitis, the solution comprising:
`
`at least 0.67 w/v % but no greater than
`1.0 w/v % olopatadine dissolved in the
`solution;
`
`2.0 w/v % to 6.0 w/v % PEG having a
`molecular weight of 300 to 500;
`
`
`
`
`11
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`

`

`
`
`the concentration of
`polyvinylpyrrolidone is 2.0 w/v
`% to 6.0 w/v % and
`
`the concentration of cyclodextrin
`is at least 0.5 w/v % but no
`greater than 2.0 w/v %.
`
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`Case No. IPR2020-00295
`Patent 9,533,053
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`2.0 w/v % to 6.0 w/v %
`polyvinylpyrrolidone;
`
`
`at least 0.5 w/v % but no greater than
`2.0 w/v % hydroxypropyl-γ-
`cyclodextrin; and
`
`
`Claims 11 and 12 of the ’053 patent. These claims, both of which depend
`
`water.
`
`from claim 8, mirror dependent claims 5 and 6. Like claim 5, claim 11 recites an
`
`olopatadine concentration “no greater than 1.0 w/v %.” Like claim 6, claim 12
`
`recites concentration ranges for PEG, polyvinylpyrrolidone, and cyclodextrin.
`
`Claim 8 of the ’154 patent recites these same limitations.
`
`Claims 7 and 13 of the ’053 patent. These claims, which depend from
`
`claims 1 and 8, respectively, both recite “wherein the solution provides more than a
`
`1.0 unit difference relative to vehicle in relief of redness at onset of action
`
`according to FDA accepted CAC model.” The claims of the ’154 patent recite
`
`treating an “ocular allergy symptom” (see claims 12 and 25) which includes
`
`“redness.” E.g., EX1001 at 1:25-26 (referring to “allergic conjunctivitis …
`
`symptoms” including “ocular … redness”).
`
`*
`
`*
`
`*
`
`Accordingly, each claim of the ’053 patent recites subject matter that is also
`
`recited either identically or similarly in the claims of the ’154 patent—including
`
`12
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`

`
`claims 8, 9, and 21-24 of the ’154 patent, which as discussed below were the
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`Patent 9,533,053
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`subject of the related District Court decision.
`
`
`Patent Owner’s Pazeo® Product
`The ’154 and ’053 patents cover the same commercial product: Pazeo®, a
`
`high-concentration olopatadine ophthalmic solution for treating symptoms of
`
`ocular allergic conjunctivitis. EX2002 at 1; EX1032 at 003. Approved by the
`
`FDA in 2015, Pazeo® contains a 0.7 w/v % olopatadine solution—and thus is
`
`several times more concentrated than both Patanol® and Pataday®. The Pazeo®
`
`ophthalmic solution contains excipients including PEG, PVP, hydroxylpropyl-γ-
`
`cyclodextrin, and water. EX2002 at 4. Pazeo® is used by instilling a single drop
`
`in each affected eye once per day. Id. at 2; EX1031.
`
`The ’154 and ’053 patents explain that a high-concentration 0.7 w/v %
`
`olopatadine solution (i.e., the concentration in Pazeo®) provides surprising
`
`benefits in efficacy. For example, although the relevant IC50 and Ki values
`
`suggested that “a 0.1% or 0.2% solution of olopatadine should provide full
`
`inhibition of redness at onset of action since both of these solutions provide excess
`
`olopatadine for inhibiting mast cell degranulation,” the inventors unexpectedly
`
`found that a 0.7% solution of olopatadine provided “a statistically significant
`
`difference in redness inhibition relative to the 0.2% solution at onset of action.”
`
`13
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`

`

`
`EX1002 at 23:33-44, 24:31-40, Table K, Fig. 1. This discovery, the patents
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`Case No. IPR2020-00295
`Patent 9,533,053
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`explain, was both “surprising” and “quite unique.” Id. at 24:38, 26:2.
`
`
`Prior Proceedings Involving the ’154 and ’053 Patents
`Several prior proceedings involving the ’154 and ’053 patents provide
`
`important context for Ayla’s IPR petition: (1) Argentum’s IPR petition filed in
`
`February 2016 involving the ’154 patent; (2) the District Court trial involving the
`
`’154 patent and the Court’s subsequent final decision in March 2018; and (3) an
`
`IPR petition filed by Cipla Ltd. in May 2018 involving the ’053 patent.
`
`1.
`
`Argentum’s 2016 IPR Petition
`
`Argentum filed an IPR petition in early 2016 challenging the ’154 patent.
`
`EX1021. The petition was accompanied by two declarations. EX2003; EX2004.
`
`As noted above, Argentum’s IPR petition, its two declarations, and other related
`
`materials were disclosed to and considered by the examiner prior to issuance of the
`
`’053 patent. See supra at 8.
`
`Argentum’s petition presented two grounds: the first alleging obviousness
`
`over Bhowmick, Yanni, and Castillo; the second alleging obviousness over
`
`Schneider, Hayakawa, Bhowmick, and Castillo. EX1021 at 024, 049. As
`
`explained below, those are the identical groups of references making up Ayla’s
`
`first two grounds, and Argentum’s arguments are also either identical or highly
`
`similar to Ayla’s. See infra at 31-35.
`
`14
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`

`Argentum’s IPR petition noted that the ’154 patent was the subject of a
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`
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`lawsuit in the U.S. District Court for the District of Delaware. Id. at EX1021 at
`
`008 (citing Alcon Research, Ltd. v. Watson Labs., Inc., 1:15-cv-01159 (D. Del.)
`
`(EX1030)). At that point in time, however, the litigation had only recently been
`
`filed and a final decision was years away. See EX1030.
`
`After no preliminary patent owner response was filed, the Board instituted
`
`Argentum’s petition and soon thereafter the parties resolved the dispute. See
`
`EX1024.
`
`2.
`
`The District Court Trial and Final Decision
`
`As noted, in December of 2015, Alcon filed a Hatch-Waxman lawsuit in the
`
`District of Delaware against Watson Laboratories for infringement of the ’154
`
`patent. EX1030 at 010. That action was consolidated with a subsequent action
`
`against Lupin. Id. at 011.
`
`In October of 2017 the Court held a four-day bench trial, receiving
`
`testimony from numerous individuals including two inventors and six expert
`
`witnesses. Id.; see generally EX2005 (Trial Day 1), EX2006 (Trial Day 2),
`
`EX2007 (Trial Day 3), EX2008 (Trial Day 4). Alcon’s witnesses included Orest
`
`Olejnik, Ph.D., who has more than 35 years of experience formulating ophthalmic
`
`compositions and formerly served as the senior vice president of global
`
`pharmaceutical sciences at Allergan. EX1030 at 039. The Court accepted Dr.
`
`15
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`

`
`Olejnik as an expert in the field of ophthalmic formulation. EX2006 (Trial Day 2)
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`at 401:12-17. Alcon also offered testimony from Gail Torkildsen, M.D., an
`
`ophthalmologist who has performed more than a hundred clinical research studies
`
`and has treated thousands of patients for eye allergies. EX1030 at 025; EX2007
`
`(Trial Day 3) at 645:21-649:21. The Court accepted Dr. Torkildsen as an expert in
`
`the field of ophthalmology and the development of ophthalmic products, including
`
`eye allergy products. EX2007 at 649:15-21.
`
`The ’154 patent claims asserted at trial were claims 8, 9, and 21-24.
`
`EX1030 at 4. Because the defendants had stipulated to infringement, the entire
`
`trial focused solely on the issue of validity. The defendants argued at trial that the
`
`asserted claims would have been obvious over several prior-art references,
`
`including Bhowmick, Castillo, Hayakawa, Schneider, and Yanni. Experts from
`
`both sides provided testimony concerning the teachings of the asserted references
`
`as well each of the other Graham factors.
`
`Following trial, in March of 2018, the District Court issued its final
`
`judgment upholding the validity of the ’154 patent, along with a 47-page opinion
`
`setting forth the Court’s findings of fact concerning the asserted references and the
`
`objective evidence of nonobviousness. EX1030.
`
`16
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`Case No. IPR2020-00295
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`a.
`
`The District Court’s Factual Findings Regarding
`Ayla’s Relied-Upon References
`
`The District Court’s opinion addressed each of Bhowmick, Castillo,
`
`Hayakawa, Schneider, and Yanni—i.e., all five references making up all three
`
`grounds in Ayla’s IPR petition—and the Court made detailed factual findings with
`
`respect to four