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`Paper 8
`Filed: October 7, 2022
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`__________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________________
`
`
`MYLAN PHARMACEUTICALS INC.,
`
`Petitioner,
`
`v.
`
`BAUSCH HEALTH IRELAND LIMITED,
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`Patent Owner.
`
`__________________
`
`Case IPR2022-01104
`U.S. Patent No. 9,919,024
`__________________
`
`PATENT OWNER’S PRELIMINARY RESPONSE
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`
`

`

`Case IPR2022-01104
`Patent No. 9,919,024
`
`I.
`II.
`
`TABLE OF CONTENTS
`INTRODUCTION ........................................................................................... 1
`BACKGROUND ............................................................................................. 4
`Claims of the ’024 Patent ...................................................................... 4
`Grounds 1-4 of the Petition ................................................................... 6
`Summary of the Asserted References ................................................... 7
`Shailubhai (EX1005) .................................................................. 8
`Camilleri (EX1031)..................................................................... 8
`Remington (EX1006) .................................................................. 9
` Mihranyan (EX1007) .................................................................. 9
`Currie (EX1032) ....................................................................... 10
`2009 Abstract (EX1009) ........................................................... 10
`Doelker (EX1010) ..................................................................... 11
`Prosecution History ............................................................................. 12
`Prosecution History of the ’097 Patent ..................................... 12
`Prosecution History of the ’321 Patent ..................................... 16
` Mylan’s Statements Regarding Prosecution History ................ 17
` Mylan’s Mischaracterization of Comiskey Declarations .................... 18
`III. The Board Should Deny Institution Under 35 U.S.C. § 325(d) .................... 23
`Legal Framework ................................................................................ 23
`The Petition Relies on the Same or Substantially the Same Art
`or Arguments Overcome During Prosecution ..................................... 25
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`b.
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`Case IPR2022-01104
`Patent No. 9,919,024
`Ground 1 – Shailubhai (EX1005), Camilleri (EX1031),
`Remington (EX1006), and Mihranyan (EX1007) .................... 25
`a.
`Shailubhai ’683 (EX2001) contains substantially
`the same disclosure as Shailubhai (EX1005),
`which the Applicants overcame during prosecution ...... 26
`Camilleri (EX1031) contains substantially the
`same disclosure as Business Wire News (EX2014),
`which the Applicants overcame during prosecution ...... 28
`The Examiner considered Remington (EX1006)
`during prosecution .......................................................... 30
`The Applicants overcame Mihranyan (EX1007)
`during prosecution .......................................................... 31
`Ground 3 – 2009 Abstract (EX1009) and Doelker
`(EX1010) ................................................................................... 33
`a.
`The Shailubhai Poster contains substantially the
`same disclosure as the 2009 Abstract (EX1009),
`which the Applicants overcame during prosecution ...... 33
`Doelker (EX1010) contains substantially the same
`disclosure as Mihranyan (EX1007) and Currie
`(WO 2005/016244), both of which the Applicants
`overcame during prosecution .......................................... 36
` Mylan Has Not Demonstrated That the Office Erred in a
`Manner Material to the Patentability of Challenged Claims .............. 38
`IV. The Petition Should Be Denied Because Mylan Has Failed to
`Establish a Reasonable Likelihood that Any Challenged Claim Is
`Unpatentable .................................................................................................. 40
`Person of Ordinary Skill in the Art (“POSA”) .................................... 41
`Formulating Peptides Was (and Remains) Complicated and
`Unpredictable ...................................................................................... 44
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`c.
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`d.
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`b.
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`ii
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`b.
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`Case IPR2022-01104
`Patent No. 9,919,024
`Ground 1: The Challenged Claims Would Not Have Been
`Obvious over Shailubhai, Camilleri, Remington, and
`Mihranyan ........................................................................................... 47
` Mylan Fails to Identify a Lead or Reference Composition
`from Shailubhai (EX1005) ........................................................ 47
` Mylan’s Alleged Motivation to Combine the References
`Is Based on Hindsight ............................................................... 52
` Mylan Fails to Establish a Reasonable Expectation of
`Success ...................................................................................... 55
`a.
`Shailubhai does not disclose an oral dosage
`formulation of plecanatide having a “purity of no
`less than 91% after storage for at least three
`months” ........................................................................... 55
`Camilleri does not establish a reasonable
`expectation of success of treating or alleviating
`symptoms associated with chronic constipation or
`IBS .................................................................................. 58
`c. Mylan’s recourse to “routine methods” cannot
`support its obviousness arguments ................................. 61
` Ground 3: The Challenged Claims Would Not Have Been
`Obvious over the 2009 Abstract in view of Doelker .......................... 62
` Mylan Fails to Identify a Lead or Reference Composition
`from the 2009 Abstract ............................................................. 63
` Mylan’s Alleged Motivation to Combine the References
`Is Based on Hindsight ............................................................... 64
` Mylan Fails to Establish a Reasonable Expectation of
`Success ...................................................................................... 66
`a.
`The 2009 Abstract does not disclose an oral dosage
`formulation of plecanatide having a “purity of no
`less than 91% after storage for at least three
`months” ........................................................................... 67
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`Case IPR2022-01104
`Patent No. 9,919,024
`b. Mylan has not established a reasonable expectation
`of success based on the 2009 Abstract ........................... 67
`c. Mylan’s recourse to “routine methods” cannot
`support its obviousness arguments ................................. 68
`Grounds 2 and 4: Dependent Claims Would Not Have Been
`Obvious................................................................................................ 69
`Conclusion ..................................................................................................... 70
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`V.
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`iv
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`
`TABLE OF AUTHORITIES
`
`Case IPR2022-01104
`Patent No. 9,919,024
`
` Page(s)
`
`Cases
`Advanced Bionics, LLC v. MED-EL Elektromedizinische Geräte
`GmbH,
`IPR2019-01469, Paper No. 6 (P.T.A.B. Feb. 13, 2020) ......................... 24, 30, 38
`Becton, Dickinson & Co. v. B. Braun Melsungen AG,
`IPR2017-01586, Paper No. 8 (P.T.A.B. Dec. 15, 2017) .............................passim
`Best Med. Int’l, Inc. v. Elekta Inc.,
`46 F.4th 1346 (Fed. Cir. 2022) ........................................................................... 43
`Biocon Pharma Ltd. v. Novartis Pharms. Corp.,
`IPR2020-01263, Paper No. 12 (P.T.A.B. Feb. 16, 2021) ................................... 30
`Boragen, Inc. v. Syngenta Participations AG,
`IPR2020-00124, Paper 18 (PTAB Aug. 10, 2020) ............................................. 39
`Edge Endo, LLC v. Michael Scianamblo,
`IPR2018-01321, Paper 15 (PTAB Jan. 14, 2019) .............................................. 40
`Eli Lilly & Co. v. Teva Pharms. Int’l GmbH,
`8 F.4th 1331 (Fed. Cir. 2021) ....................................................................... 31, 59
`Insite Vision Inc. v. Sandoz, Inc.,
`783 F.3d 853 (Fed. Cir. 2015) ...................................................................... 55, 67
`Jansen v. Rexall Sundown, Inc.,
`342 F.3d 1329 (Fed. Cir. 2003) .......................................................................... 58
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ...................................................................................... 55, 66
`Kyocera Senco Indus. Tools Inc. v. ITC,
`22 F.4th 1369 (Fed. Cir. 2022) ..................................................................... 43, 44
`Novartis Pharm. Corp. v. Watson Labs., Inc.,
`611 F. App’x 988 (Fed. Cir. 2015) ............................................................... 53, 66
`
`v
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`Case IPR2022-01104
`Patent No. 9,919,024
`
`In re Omeprazole Patent Litig.,
`536 F.3d 1361 (Fed. Cir. 2008) .................................................................... 48, 63
`Ortho-McNeil Pharm. v. Mylan Lab'ys, Inc.,
`520 F.3d 1358 (Fed. Cir. 2008) .......................................................................... 57
`Oxford Nanopore Techs. Ltd. v. Univ. of Wash.,
`IPR2014-00512, Paper 12 (P.T.A.B. Sept. 15, 2014)................................... 48, 63
`Procter & Gamble Co. v. Teva Pharm. USA, Inc.,
`566 F.3d 989 (Fed. Cir. 2009) ................................................................ 57, 61, 68
`Regeneron Pharms., Inc. v. Kymab Ltd.,
`IPR2019-01579, Paper 9 (PTAB Mar. 20, 2020) ............................................... 40
`Sanofi Mature IP v. Mylan Labs. Ltd.,
`757 F. App’x 988 (Fed. Cir. 2019) ..................................................................... 59
`Unigene Labs., Inc. v. Apotex, Inc.,
`655 F.3d 1352 (Fed. Cir. 2011) .............................................................. 47, 48, 63
`Statutes
`35 U.S.C. § 102 ........................................................................................................ 13
`35 U.S.C. § 103 ............................................................................................ 13, 14, 16
`35 U.S.C. § 311 .......................................................................................................... 2
`35 U.S.C. § 314 ........................................................................................................ 40
`35 U.S.C. § 325 .................................................................................................passim
`
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`Case IPR2022-01104
`Patent No. 9,919,024
`Patent Owner Bausch Health Ireland Limited (“Bausch” or “Patent Owner”)
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`submits this Preliminary Response to the Petition for Inter Partes Review of U.S.
`
`Patent No. 9,919,024 (“the ’024 patent”) filed by Mylan Pharmaceuticals Inc.
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`(“Mylan” or “Petitioner”).
`
`I.
`
`INTRODUCTION
`Mylan challenges claims 1-16 of the ’024 patent, directed to methods for
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`treating or alleviating symptoms associated with chronic constipation or irritable
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`bowel syndrome (“IBS”) by administering oral dosage formulations consisting of a
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`sequence-defined peptide (hereinafter “plecanatide”), an inert low moisture carrier,
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`and a lubricant, wherein the plecanatide has a chromatographic purity of no less than
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`91% after storage for at least three months. Mylan’s Petition asserts that these claims
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`would have been obvious over Shailubhai in view of Camilleri, Remington and
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`Mihranyan (Ground 1) or over the 2009 Abstract in view of Doelker (Ground 3),
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`adding Currie to each combination for certain dependent claims (Grounds 2 and 4,
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`respectively). The Board should reject Mylan’s arguments and deny institution for
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`at least two independent reasons.
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`First, the ’024 patent is a continuation of U.S. Patent Nos. 9,616,097 (“the
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`’097 patent”) and 9,610,321 (“the ’321 patent”), and Mylan’s asserted references
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`and obviousness arguments are substantially the same as those considered by the
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`Office and overcome during prosecution of the ’097 and ’321 patents, recycling
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`1
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`Case IPR2022-01104
`Patent No. 9,919,024
`verbatim arguments made by the Examiner in rejecting the claims as anticipated or
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`obvious. To avoid discretionary denial, Mylan engages in unprofessional rhetoric
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`and personal attacks, repeatedly and wrongly alleging that “Bausch loaded the dice”
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`and “misled” and “misdirected” the Examiner with “false impressions” and “bad
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`science” by submitting the Comiskey declarations, which compared differences in
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`impurity levels between formulations containing a regular-grade carrier (Avicel 102)
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`and formulations containing a low-moisture carrier (Avicel PH 112). Pet., 2-3, 62-
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`63, 65. Mylan effectively takes issue with the fact that the initial impurity levels of
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`the formulations varied. But contrary to Mylan’s allegations, the unexpected results
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`are reflected in the differences in impurity levels between the formulations initially
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`and throughout the duration of the test. Thus, the reduction in total impurities
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`initially (39%) is itself evidence of the unexpected superior stability of the claimed
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`formulations as set forth in the Comiskey Declarations. Stripped to its essence,
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`Mylan’s Petition amounts to an allegation of fraud, which is neither meritorious nor
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`a proper ground for an IPR petition. 35 U.S.C. § 311. The Board should therefore
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`exercise discretion under 35 U.S.C. § 325(d) and deny institution.
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`Second, Mylan’s obviousness arguments are fundamentally flawed and
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`thoroughly tainted by hindsight. Mylan begins by incorrectly characterizing its
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`primary references. Shailubhai (EX1005) is a patent directed to the active
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`pharmaceutical ingredient plecanatide itself, and Mylan has failed to identify any
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`2
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`Case IPR2022-01104
`Patent No. 9,919,024
`particular formulation in Shailubhai that might constitute a “lead” formulation.
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`What Mylan calls “good reason” to make “simple direct-compression plecanatide
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`tablets” is based on Mylan’s improper general reliance on potential dosage forms.
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`Similarly, Mylan has failed to establish that the 2009 Abstract (EX1009), a one
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`paragraph disclosure of a phase I clinical study administering an “oral, ascending
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`dose (0.1 mg to 48.6 mg),” discloses any “lead” formulation. Despite Mylan’s
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`repeated arguments that “tablets [were] a simple, conventional, and popular oral
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`dosage form providing many benefits,” the formulation used in the clinical study
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`described in the 2009 Abstract was a solution.
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`Mylan attempts to compensate for these deficiencies in its Petition by picking
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`and choosing isolated disclosures from multiple references, using the challenged
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`claims as a roadmap through the prior art. As but one example, Mylan asserts that a
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`person of ordinary skill in the art (“POSA”) would have had “good reason” to use a
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`low moisture carrier because, according to Mylan, peptides generally are moisture
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`sensitive. Pet., 17, 46. Yet Mylan’s Petition is completely devoid of any teaching
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`or suggestion that plecanatide is moisture sensitive, and the reference Mylan cites
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`for its argument that peptides are moisture sensitive in fact recognizes that the effects
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`of moisture are not “widely reported or understood” and describes instances in which
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`peptides are less stable at lower moisture contents. EX1016, 492-94.
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`3
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`Case IPR2022-01104
`Patent No. 9,919,024
`Mylan fails to establish that a POSA would have selected these isolated
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`disclosures, much less had a reasonable expectation of successfully combining the
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`specific two types of inactive ingredients—an inert low moisture carrier and a
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`lubricant—as claimed in the ’024 patent. Mylan does not, and cannot, overcome the
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`well-known unpredictability and difficulties associated with preparing stable peptide
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`formulations that existed at the time of invention. The large number of potential
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`problems with formulating peptides, and even larger number of potential avenues to
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`address them, further diminished any reasonable expectation of successfully
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`achieving the claimed oral dosage formulation having an inert low moisture carrier
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`and a lubricant.
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`For each of these reasons, and as detailed below, denial of institution is
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`warranted.
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`II. BACKGROUND
`The ’024 patent covers Trulance® (3 mg tablets), a prescription medicine used
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`in adults to treat irritable bowel syndrome with constipation (IBS-C) and chronic
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`idiopathic constipation (CIC). The active pharmaceutical ingredient (“API”) in
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`Trulance® is plecanatide, a 16-amino acid peptide.
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` Claims of the ’024 Patent
`The claims of the ’024 patent are directed to methods for treating or alleviating
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`symptoms associated with chronic constipation or IBS by orally administering
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`4
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`Case IPR2022-01104
`Patent No. 9,919,024
`compositions of plecanatide. The ’024 patent has two independent claims (claims 1
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`and 3) and fourteen dependent claims (claims 2 and 4-16). The independent claims
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`recite:
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`Claim 1 recites:
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`1. A method for treating chronic constipation in a human subject
`comprising orally administering to said human subject a
`composition consisting of SEQ ID NO:1 wherein the peptide is
`a [4,12; 7,15] bicycle, an inert low moisture carrier, and a
`lubricant, and wherein the peptide has a chromatographic purity
`of no less than 91% after storage for at least three months.
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`Claim 3 recites:
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`3. A method of treating or alleviating a symptom associated with
`chronic idiopathic constipation or irritable bowel syndrome in a
`human subject comprising orally administering to said human
`subject a composition consisting of SEQ ID NO:1 wherein the
`peptide is a [4,12; 7,15] bicycle, an inert low moisture carrier,
`and a lubricant, and wherein the peptide has a chromatographic
`purity of no less than 91% after storage for at least three months.
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`5
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`

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`Case IPR2022-01104
`Patent No. 9,919,024
`EX1001, claims 1 and 3. Mylan concedes, as it must, that the peptide recited in
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`claims 1 and 3 of the ’024 patent is plecanatide. Pet., 1.
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`Claims 2 and 4-16 recite various additional elements. Claim 2 recites that
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`“the constipation is associated with irritable bowel syndrome or chronic idiopathic
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`constipation,” and claim 4 recites that “the symptom is constipation or abdominal
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`pain.” Claims 5 and 8 recite that the methods of claims 1 and 3 further comprise
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`“administering to said patient an effective dose of an inhibitor of cGMP-dependent
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`phosphodiesterase either concurrently or sequentially with said guanylate cyclase
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`receptor agonist.” Claims 6 and 9 recite that the “inhibitor of cGMP-dependent
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`phosphodiesterase is selected from the group consisting of sulindac sulfone,
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`zaprinast, and motapizone.” Claims 7 and 10 recite that the methods of claims 1 and
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`3 further comprise “administering to said patient an effective dose of a laxative.”
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`Claims 11 and 14 recite that “the inert low moisture carrier is microcrystalline
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`cellulose,” claims 12 and 15 recite that “the lubricant is magnesium stearate,” and
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`claims 13 and 16 recite that “the inert low moisture carrier is microcrystalline
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`cellulose and the lubricant is magnesium stearate.”
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` Grounds 1-4 of the Petition
`Mylan proposes four grounds of unpatentability, asserting that claims 1-16
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`would have been obvious over various combinations of references. With respect to
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`claims 1 and 3—the independent claims of the ’024 patent—the Petition proposes
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`6
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`Case IPR2022-01104
`Patent No. 9,919,024
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`only two grounds of unpatentability (Grounds | and 3), asserting in Ground 1
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`obviousness over Shailubhai in view of Camilleri, Remington and Mihranyan, and
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`in Ground 3 obviousnessover the 2009 Abstract in view of Doelker. Grounds 2 and
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`4 challenge certain claims that depend from claim | or claim 3. Grounds 2 and 4 do
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`not raise any additional arguments regarding the alleged obviousnessof claims | or
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`3; rather, they address only the additional elements that the dependentclaimsrecite.
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`Shailubhai, Camilleri, Remington, Mihranyan, and
`Currie (EX 1032)
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`1-4, 11-16 2009 Abstract (EX1009) and Doelker (EX1010)
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` 5-10
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`1-6, 8-9, and
`11-16
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`Shailubhai (EX1005), Camilleri (EX1031),
`Remington (EX1006) and Mihranyan (EX1007)
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`Obvious from the Combined Teachings of
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`2009 Abstract, Doelker and Currie
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`Pet., 6-7. Becausethe Petition fails to establish that claims 1 and 3 would have been
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`obvious for the reasons discussed below,the Petition necessarily fails to establish
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`that dependentclaims 2 and 4-16 are obvious.
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`C.
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`Summary of the Asserted References
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`Mylan relies on a combination of four references (Shailubhai, Camilleri,
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`Remington, and Mihranyan) in Ground | andtwo references (2009 Abstract and
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`Doelker) in Ground 3. In Grounds 2 and 4, Mylan additionally relies on Currie.
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`

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`Case IPR2022-01104
`Patent No. 9,919,024
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`Shailubhai (EX1005)
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`Shailubhai, which is Patent Owner’s patent, describes the novel peptide
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`plecanatide, which is the API in Trulance®. While Shailubhai generally states that
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`plecanatide can be “in a pharmaceutical composition in unit dose form” (EX1005,
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`3:32-36), Shailubhai does not disclose any specific formulation of plecanatide.
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`Rather, Shailubhai merely list various possible dosage forms, including “solutions,
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`powders, suspensions, emulsions, tablets, capsules, transdermal patches, [or]
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`ointments.” EX1005, 13:24-30. Moreover, Shailubhai does not teach that
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`plecanatide is moisture sensitive. EX1005.
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`Camilleri (EX1031)
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`Camilleri is a review article, titled “Challenges to the Therapeutic Pipeline for
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`Irritable Bowel Syndrome: End Points and Regulatory Hurdles.” Table 1 of
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`Camilleri lists “[s]everal of the drugs in development that are in ongoing or planned
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`clinical trials for IBS.” Guanilib (plecanatide) is indicated as in a phase I clinical
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`trial.
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`8
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`Case IPR2022-01104
`Patent No. 9,919,024
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`
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`EX1031, Table 1. Camilleri contains no other disclosure related to plecanatide.
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`Remington (EX1006)
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`Remington is a pharmaceutical sciences reference that discloses generalized
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`information regarding pharmaceutical formulations. Remington does not disclose
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`plecanatide, let alone formulations of plecanatide. Indeed, the information that
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`Mylan cites from Remington is not directed to any specified protein; it is merely
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`generalized information.
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` Mihranyan (EX1007)
`Mihranyan is an article titled “Moisture sorption by cellulose powders of
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`varying crystallinity.” Mihranyan is not directed to any specified protein; instead, it
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`discloses generalized
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`information
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`regarding pharmaceutical
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`formulations.
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`9
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`Patent No. 9,919,024
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`Mihranyan does not disclose plecanatide, let alone formulations of plecanatide.
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`While Mihranyanstates that “|f]or moisture sensitive drugs, low moisture grades of
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`MCCare available”(id., 433), Mylan has notestablishedthatat the time of invention
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`plecanatide was knownto be moisture sensitive. Additionally, Mihranyan cautions
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`that “the structure of cellulose should be thoroughly considered when manufacturing
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`low moisture grades of MCC.” EX1007, 441.
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`5.
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`Currie (EX1032)
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`Currie is a U.S. patent publication that discloses linaclotide,
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`the active
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`ingredient of Linzess®. Currie doesnot disclose plecanatide, let alone formulations
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`of plecanatide.
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`6.
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`2009 Abstract (EX1009)
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`Authored by an inventor of the ’024 patent, Shailubhai’s 2009 Abstract
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`(EX1009) is a one-paragraph disclosure of a phaseI clinicaltrial, which used a liquid
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`solution of plecanatide as the test product.
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`Infra § IV-E.1-2 (citing EX2012, 42;
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`EX2013, 5). The only ingredients in the liquid solution were po
`Po EX1009, A-641. That the test product usedin the clinical
`trial was in the form ofa liquid solutiona
`po demonstrates the impermissible hindsight in Mylan’sassertions that
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`“direct-compression tablet|s]” were “one simple, conventional, solid oral-dosage
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`form.” Pet., 1.
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`10
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`Case IPR2022-01104
`Patent No. 9,919,024
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`Doelker (EX1010)
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`Doelker compares performance of the six Avicel PH grades. Doelker
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`illustrates “the main properties” of the listed five Avicel PH grades “evaluated
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`relative[] to the standard Avicel PH-101 product.” EX1010, 658-59. Doelker does
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`not teach that Avicel PH112 (a low moisture grade) has any superior properties
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`compared to other grades.
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`
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`EX1010, 659. Doelker does not disclose plecanatide, let alone formulations of
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`plecanatide. Notably, the sample tablets disclosed in Doelker (EX1010) do not
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`include any APIs. Id., 652-56. Instead, they include only inactive ingredients. Id.
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`11
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`Case IPR2022-01104
`Patent No. 9,919,024
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`D.
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`‘Prosecution History
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`1.
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`Prosecution History of the ’097 Patent
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`Mylan admits that the prosecution history of the ’097 patent is applicable to
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`the patentability analysis of the 024 patent. Pet., 9 (“During the ’097 patent’s
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`examination Bausch alleged an unexpected discovery .. . .). Indeed, Mylan largely
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`discusses the prosecution history of the ’097 patent instead of the 024 patent in the
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`“Prosecution History”section of the Petition. Pet., 9-10.
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`The application that ultimately issued as the ’097 patent underwent extensive
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`and thorough examination. The Examiner allowed the application only after four
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`rounds of substantive office actions and responses involving novelty and/or
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`obviousness issues. This highly substantive examination—from thefirst non-final
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`office action to allowance—took more than twoandhalf years. The office actions
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`and responses involving novelty and/or obviousnessissuesare listed in the following
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`table:
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`Brief Description of the Event During Prosecution of the ’097 Patent
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`12
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`Case IPR2022-01104
`Patent No. 9,919,024
`
`Non-Final Office
`Action Dated
`August 19, 2014
`
`Response Dated
`February 19, 2015
`
`Final Office Action
`Date May 20, 2015
`
`Response Dated
`November 20, 2015
`
`Rejections under 35 U.S.C. § 102(b) over WO 02/078683
`(Shailubhai ’683) (EX2001)1
`Rejections under 35 U.S.C. § 103 over:
`(1) Shailubhai ’683 in view of WO2010/027404
`(Fretzen); and
`(2) Shailubhai ’683 and Fretzen further in view of
`US2009/0253634 (Currie).
`
`• Amendments and Arguments/Remarks were filed with
`First Declaration of Stephen Comiskey including
`stability data.
`• Pending claim was amended to recite, “the
`formulation comprises an inert low moisture carrier.”
`Rejections under 35 U.S.C. § 103 over Shailubhai ’683,
`Currie, and Mihranyan (EX1007) in view of Avicel PH
`product instruction (FMC 2005).
`
`• Amendments and Arguments/Remarks were filed.
`• Applicant provided arguments that the pending claims
`would have been non-obvious over Shailubhai ’683,
`Currie, Mihranyan in view of Avicel PH product
`instruction (FMC 2005).
`
`
`1 Shailubhai ’683 (EX2001) is in the same family as Shailubhai (EX1005).
`
`Shailubhai ’683 and Shailubhai have substantially the same specification, except a
`
`few minor differences such as a reference list. Cf. EX2001 with EX1005.
`
`13
`
`

`

`Case IPR2022-01104
`Patent No. 9,919,024
`
`Non-Final Office
`Action Dated
`January 4, 2016
`Response Dated
`July 5, 2016
`
`Interview of
`September 14, 2016
`Supplemental
`Response Dated
`September 14, 2016
`
`Final Office Action
`Dated October 5,
`2016
`
`Response Dated
`January 5, 2017
`
`Interview of
`February 24, 2017
`
`Rejections under 35 U.S.C. § 103 over Shailubhai ’683,
`Mihranyan in view of US 2010/0048489 (Fretzen).
`
`• Amendments and Arguments/Remarks were filed.
`• Pending claim was amended to recite, “An oral dosage
`formulation comprising consisting of at least one
`Guanylate Cyclase C (GCC) agonist peptide, an inert
`low moisture carrier, and a lubricant.”
`
`• The Examiner discussed claim amendments with
`Applicant.
`
`• Amendments and Arguments/Remarks were filed.
`• Claims were re-arranged and amended to recite “per
`unit dose of 3.0 mg or 6.0 mg of a peptide.”
`Rejections under 35 U.S.C. § 103 over Currie
`(WO2005/016244), FMC 2005, Fretzen, and in view of
`Shailubhai et al (Digestive Disease Week, San Diego,
`2008) (Shailubhai Poster).
`
`• Amendments and Arguments/Remarks were filed with
`Second Declaration of Stephen Comiskey.
`• The Declaration effectively includes the same stability
`data that were filed on February 19, 2015.
`• Pending independent claim was not amended.
`• The Examiner discussed with Applicant regarding
`claim amendments.
`
`14
`
`

`

`Case IPR2022-01104
`Patent No. 9,919,024
`
`Notice of Allowance
`Dated February 24,
`2017
`
`As shown in the table above, making four substantive novelty and obvious
`
`• The Examiner provided detailed reasons of allowance
`but did not mention the Comiskey Declarations and/or
`unexpected results as a reason for her allowance.
`
`rejections, the Examiner generally cited a reference disclosing plecanatide as a
`
`primary reference, and combined it with references disclosing generalized
`
`information regarding pharmaceutical formulations, not specific to any active
`
`ingredient, as secondary references.2 To overcome the rejections, the Applicants
`
`argued that cited combinations of references would not have provided any
`
`reasonable expectation of success and also amended the claims. The Examiner
`
`eventually allowed the application, providing more than a page of her reasons for
`
`allowance for the ’097 patent. The reasons for allowance of the ’097 patent state
`
`that “to differentiate this instant invention from the prior art teachings,” the
`
`Applicants amended the claims “to be consisting of 3 mg or 6 mg of [plecanatide],
`
`an inert low moisture carrier, and a lubricant having a chromatographic purity of no
`
`less than 91% after storage for at least three months.” EX1022, 5104. The Examiner
`
`stated that “therefore, this instant invention is allowable.” Id.
`
`
`2 While this is also what Mylan argued in this Petition, the Examiner made
`
`more robust arguments during prosecution, citing more detailed publications.
`
`15
`
`

`

`Case IPR2022-01104
`Patent No. 9,919,024
`
`2.
`
`Prosecution History of the ’321 Patent
`
`The ’024 patent is a continuation of the °321 patent. Its prosecution history is
`
`also applicable to the patentability analysis of the ’024 patent for the same reasons
`
`that the °097 patent’s prosecution history is applicable. See supra § II.D.1. The
`
`Examiner issued several substantive office actions and responses involving
`
`obviousness issues during prosecution of the ’321 patent, which are listed in the
`
`followingtable:
`
`Events
`
`Non-Final Office
`
`Action Dated
`
`January 29, 2016
`
`Response Dated
`
`April 29, 2016
`
`During Prosecution of the ’321 Patent
`
`Brief Description of the Event
`
`Rejections under 35 U.S.C. § 103 over Shailubhai (WO
`
`08/151257) in view of Business Wire News (EX2014)
`
`e Amendments and Arguments/Remarks werefiled with
`
`Declaration of KunwarShailubhai regarding unit dose.
`
`e Pending claim was amendedto recite, “human
`
`subject” instead of “patent”
`
`Final Office Action|Rejections under 35 U.S.C. § 103 over Shailubhai, (WO
`
`Date June 3, 2016=|08/151257) in view of the Shailubhai Poster (EX2003).
`
`
`
`unit dose of 3 mg or 6 mg of[plecanatide], an inert
`
`Response Dated
`
`September 6, 2016
`
`e Amendments and Arguments/Remarks were filed with
`
`Declaration ofStephen Comiskey.
`
`e Pending claim was amendedto recite “consisting of a
`
`16
`
`

`

`Case IPR2022-01104
`Patent No. 9,919,024
`low moisture carrier, and a lubricant, and wherein the
`peptide has a chromatographic purity of no less than
`91 % after storage for at least three months”
`The amendments are not entered. The Examiner indicated
`that if the amendments are entered, the same rejection has
`been applied to the co-pending application 13/421,769
`that issued as the ’097 patent.
`
`Advisory Action
`Dated September
`29, 2016
`
`Response Dated
`December 5, 2016
`
`• Amendments and Arguments/Remarks were filed.
`• The above amendments were filed again.
`• The Examiner provided detailed reasons of allowance
`but did not mention the Comiskey Declarations and/or
`unexpected results as a reason for her allowance.
`
`Notice of Allowance
`Dated February 10,
`2017
`
`The Examiner allowed the claims of the ’321 patent after three rounds of
`
`substantive office actions and responses involving obviousness issues. The reasons
`
`for allowance of the ’321 patent state “the amended claims are allowable” because
`
`the cited prior art does not teach or suggest certain elements of the claims. EX1021,
`
`0726-27.
`
` Mylan’s Statements Regarding Prosecution History
`Mylan provides a one-paragraph summary of the prosecution history, mainly
`
`of the ’097 patent, focusing o