Paper No. 6
`Filed: October 12, 2021
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`———————————
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`———————————
`
`APOTEX INC.,
`Petitioner
`
`v.
`
`PFIZER INC.,
`Patent Owner.
`
`———————————
`
`IPR2021-01132
`Patent 6,890,927
`
`TARTRATE SALTS OF 5,8, 14-TRIAZATERACYCLO[10.3.1.02,11 04.9]-
`HEXADECA-2(11),3,5,7,9-PENTAENE AND PHARMACEUTICAL
`COMPOSITIONS THEREOF
`
`———————————
`
`
`PATENT OWNER PFIZER INC.’S
`PRELIMINARY RESPONSE
`
`
`
`
`
`
`
`
`
`
`

`

`
`
`Paper No. 6
`Filed: October 12, 2021
`
`I.
`II.
`
`TABLE OF CONTENTS
`Introduction ...................................................................................................... 1
`Background ...................................................................................................... 4
`A.
`The ’927 Patent ..................................................................................... 4
`B.
`References Cited in Petition .................................................................. 5
`1.
`PCT Publication No. WO 99/35131 (“Coe”) ............................. 5
`2.
`U.S. Patent No. 6,14,550 (“US ’550”) ........................................ 6
`3.
`Berge ........................................................................................... 7
`4.
`Gould ........................................................................................... 7
`5.
`Nyqvist ........................................................................................ 8
`Prosecution History of the ’927 Patent ................................................. 8
`C.
`III. The Board Should Deny Institution Under § 325(d) ..................................... 10
`The Office has Substantively Considered the Same Prior Art
`A.
`and Arguments (Advanced Bionics Factor 1; Becton Dickinson
`Factors (a), (b), and (d)) ...................................................................... 11
`Becton, Dickson Factor (a): “whether the same or
`1.
`substantially the same art previously was presented to the
`Office or whether the same or substantially the same
`arguments previously were presented to the Office” ................ 12
`Becton, Dickson Factor (b): “the cumulative nature of the
`asserted art and the prior art evaluated during
`examination” ............................................................................. 14
`Becton, Dickson Factor (d): “the extent of the overlap
`between the arguments made during examination and the
`manner in which petitioner relies on the prior art” ................... 22
`The Petitioner Cannot Demonstrate that the Office Erred in a
`Manner Material to the Patentability of the Challenged Claims
`(Advanced Bionics Factor 2; Becton Dickinson Factors (c), (e),
`and (f)) ................................................................................................. 26
`Becton, Dickson Factor (c): “the extent to which the
`1.
`asserted art was evaluated during examination, including
`whether the prior art was the basis for rejection” ..................... 26
`
`2.
`
`3.
`
`B.
`
`ii
`
`
`

`

`
`
`2.
`
`Becton, Dickson Factors (e) and (f): “whether petitioner
`has pointed out sufficiently how the examiner erred in its
`evaluation of the asserted prior art” and “the extent to
`which additional evidence and facts presented in the
`petition warrant reconsideration of the prior art or
`arguments.” ............................................................................... 27
`IV. Conclusion ..................................................................................................... 32
`
`
`
`Paper No. 6
`Filed: October 12, 2021
`
`iii
`
`
`

`

`
`
`TABLE OF AUTHORITIES
`
`Paper No. 6
`Filed: October 12, 2021
`
`CASES
`Advanced Bionics, LLC v. Med-El Elektromedizinische Gerate GmbH
`IPR2019-01469, Paper 6 (Feb. 13, 2020) ......................................... 11, 13, 26, 27
`Argentum Pharmaceuticals LLC v. Merck Patentgesellschaft
`IPR2018-00423, Paper 7 (July 23, 2018) ........................................................... 18
`Becton, Dickinson & Co. v. B. Braun Melsungen AG
`IPR2017-01586, Paper 8 (Dec. 15, 2017) ...................................................passim
`Canon Inc. v. Papst Licensing GMBH & Co. KG
`IPR2016-01202, Paper 15 (Dec. 15, 2016) .................................................. 18, 27
`CSL Behring GMBH v. Shire Viropharma Inc.
`IPR2019-00459, Paper 8 (July 2, 2019) ............................................................ 29
`Microsoft Corp. v. Koninklijke Philips N.V.
`IPR2018-00277, Paper 11 (June 8, 2018) ........................................................... 18
`NHK Spring Co., Ltd. v. Intri-Plex Techs., Inc.
`IPR2018-00752, Paper 8 (Sept. 12, 2018) .......................................................... 14
`Pfizer, Inc. v. Apotex, Inc.
`480 F.3d 1348 (Fed. Cir. 2007) .................................................................... 30, 31
`Puma N.A., Inc. v. Nike Inc.
`IPR2019-01042, Paper 10 (Oct. 31, 2019) .................................................. 12, 26
`R.J. Reynolds Vapor Co. v. Fontem Holdings 1 B.V.
`IPR2017-01642, Paper 10 (Jan. 16, 2018) .......................................................... 16
`Regeneron Pharm., Inc. v. Merus N.V.
`864 F.3d 1343 (Fed. Cir. 2017) .......................................................................... 14
`Roku Inc. v. Universal Elecs., Inc.
`IPR2019-01619, Paper 11 (Apr. 2, 2020) ........................................................... 14
`Sanofi-Synthelabo v. Apotex, Inc.
`550 F.3d 1075 (Fed. Cir. 2008) .......................................................................... 31
`
`iv
`
`
`

`

`Paper No. 6
`Filed: October 12, 2021
`
`
`Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd.
`492 F.3d 1350 (Fed. Cir. 2007) .......................................................................... 31
`Unified Patents Inc. v. Berman
`IPR2016-01571, Paper 10 (Dec. 14, 2016) ........................................................ 22
`Valeant Int'l (Barbados) SRL v. Watson Pharms., Inc.
`No. 10-20526-CIV, 2011 WL 6792653 (S.D. Fla. Nov. 8, 2011), aff'd sub
`nom. Valeant Int'l Bermuda v. Actavis, Inc., 534 F. App'x 999 (Fed. Cir.
`2013) ................................................................................................................... 31
`STATUTES
`35 U.S.C. § 325(d) ............................................................................................passim
`
`
`
`v
`
`
`

`

`
`I.
`
`Paper No. 6
`Filed: October 12, 2021
`
`Introduction
`The Board should deny institution under 35 U.S.C. § 325(d) because the
`
`Petition recycles the same prior art and arguments considered by the Examiner
`
`during prosecution of the ’927 patent. Although Petitioner raises five separate
`
`grounds for invalidity, each ground hinges on Coe or an identical disclosure in
`
`US ’550. During prosecution, the Examiner rejected the challenged claims as
`
`obvious over Coe in two separate office actions, and the applicant overcame these
`
`rejections by demonstrating that Coe does not disclose or render obvious the claimed
`
`tartrate salt of varenicline. While Petitioner might disagree with the Examiner’s
`
`decision to allow the challenged claims over Coe, Petitioner cannot demonstrate the
`
`Examiner overlooked any relevant disclosures or otherwise erred in his evaluation
`
`of the prior art. As such, Petitioner’s anticipation arguments based on Coe fall
`
`squarely within the type of invalidity challenge that should be denied under § 325(d).
`
`Petitioner’s anticipation argument based on US ’550 fares no better. US ’550
`
`issued from the application published as Coe, and even Petitioner admits the
`
`specification of both references are “identical in all relevant material respects.”
`
`Paper 1 at 9. Thus, US ’550 is entirely cumulative of Coe and warrants no separate
`
`consideration by the Board.
`
`Petitioner’s obviousness grounds—all based on Coe in combination with
`
`Berge, Gould, and/or Nyqvist—similarly fall short. Berge and Gould mention
`
`1
`
`
`

`

`
`tartrate salts only in the context of a general discussion of salt selection, whereas
`
`Paper No. 6
`Filed: October 12, 2021
`
`Nyqvist discloses the tartrate salt for an altogether different drug. These secondary
`
`references simply identify tartrate salt as one of many potential counter-ions for
`
`pharmaceutical salts in general, and would not have directed the POSA to the tartrate
`
`salt of varenicline. As such, the secondary references do not cure the deficiencies in
`
`Coe, and are cumulative of multiple references in the file history that also list known
`
`pharmaceutical salts (including tartrate) and their methods of preparation.
`
`Unable to identify any references that differ materially from the prior art
`
`considered by the Examiner, Petitioner relies on misdirection instead. Petitioner
`
`asserts the Examiner allowed the claims because “Pfizer argued that Coe’s genus did
`
`not render obvious the alleged varenicline ‘species.’” Paper 1 at 69–70. This is an
`
`illogical reading of the file history and a mischaracterization of the applicant’s
`
`arguments during prosecution. The applicant explained during prosecution that Coe
`
`only discloses tartrate salts (along with a list of other pharmaceutically acceptable
`
`acid addition salts) in connection with Formula I, a generic formula that includes a
`
`myriad of other compounds. The applicant never suggested that Coe does not
`
`disclose varenicline at all. To the contrary, the applicant submitted an inventor
`
`declaration that specifically calls out Coe’s disclosure of varenicline hydrochloride,
`
`and compares the properties of the prior art hydrochloride salt with the claimed
`
`tartrate salt. EX1004 at 297. Moreover, the ’927 specification itself acknowledges
`
`2
`
`
`

`

`
`that Coe discloses the hydrochloride salt of varenicline. EX1001, 2:13–28.
`
`Paper No. 6
`Filed: October 12, 2021
`
`(“Compounds that bind to neuronal nicotinic receptor sites, including [varenicline],
`
`and its hydrochloride salt, are referred to in WO 99/35131 [i.e., Coe], published Jul.
`
`15, 1999.”). The notion that the Examiner only allowed the claims because he
`
`somehow overlooked Coe’s disclosure of varenicline as a “species” is flatly
`
`inconsistent with the file history.
`
`Petitioner also contends that “Pfizer has represented to two patent offices that
`
`one may use the methods of US ’550 and Coe (i.e., Example 26) to prepare the
`
`tartrate salt of varenicline.” Paper 1 at 23. This is another mischaracterization of
`
`the record. Pfizer represented to the U.S. and Canadian patent offices that Coe and
`
`US ’550 disclose varenicline as a drug substance, not the specific tartrate salt.
`
`Regardless, the premise of Petitioner’s argument—that Coe’s Example 26 somehow
`
`discloses a method of producing the tartrate salt of varenicline—is plainly untenable;
`
`Example 26 is entitled “[varenicline] hydrochloride” and never once mentions the
`
`tartrate salt.
`
`Because the Examiner already considered the prior art references and
`
`arguments cited in the Petition, and Petitioner cannot demonstrate the Examiner
`
`erred in any material respect, the Board should deny institution under § 325(d).
`
`3
`
`
`

`

`Paper No. 6
`Filed: October 12, 2021
`
`
`II. Background
`A. The ’927 Patent
`The ’927 patent is directed to the tartrate salt of varenicline, the active
`
`pharmaceutical ingredient in Pfizer’s smoking cessation drug Chantix®. EX2001
`
`at 5. Varenicline binds to α4β2 neuronal nicotinic acetylcholine receptors, where it
`
`acts as an agonist and prevents nicotine binding. Id. Clinically, varenicline can help
`
`reduce nicotine cravings and withdraw symptoms in individuals who quit smoking.
`
`Id. at 1.
`
`The specification acknowledges that varenicline itself is known in the prior
`
`art and disclosed in Coe. EX1001, 2:13–18 (“Compounds that bind to neuronal
`
`nicotinic receptor sites, including [varenicline], and its hydrochloride salt, are
`
`referred to in [Coe].”). However, the specification explains the majority of known
`
`varenicline salts “are so significantly hygroscopic as to render them poor candidates
`
`for pharmaceutical formulation use.” Id. 9:20–23. By contrast, “[t]he L-tartrate salt
`
`of [varenicline] is very slightly hygroscopic, has high aqueous solubility and is high
`
`melting. These characteristics, combined with its relative inertness towards common
`
`excipients, make it highly suitable for pharmaceutical formulation use.” Id. 9:23–
`
`27. The claims are thus limited to tartrate salts of varenicline.
`
`Petitioner challenges claims 1 and 2 of the ’927 patent:
`
`4
`
`
`

`

`
`
`Paper No. 6
`Filed: October 12, 2021
`
`1. The tartrate salt of 5,8,14-triazatetracyclo[10.
`3.1.02,11.04,9]-hexadeca-2(11),3,5,7,9-pentaene.
`
`2. A compound according to claim 1 which is the L-
`tartrate salt.
`
`EX1001, claims 1–2.
`
`B. References Cited in Petition
`Petitioner contends that claims 1–2 of the ’927 patent are anticipated by Coe
`
`and/or US ’550. In addition, Petitioner also asserts the challenged claims are
`
`obvious over Coe in combination with Berge, Gould, and/or Nyqvist. As explained
`
`below, the Examiner considered the relevant disclosures in Coe and US ’550 during
`
`prosecution, and the secondary references are cumulative of the references cited in
`
`the file history.
`
`PCT Publication No. WO 99/35131 (“Coe”)
`1.
`Coe discloses aryl fused azapolycyclic compounds that share a common core
`
`structure identified as Formula I:
`
`
`
`5
`
`
`

`

`
`EX1005 at 3–4. Coe explains the disclosed compounds can be used to treat a variety
`
`Paper No. 6
`Filed: October 12, 2021
`
`of conditions, including “chemical dependencies and addictions (e.g., dependencies
`
`on, or addictions to nicotine (and/or tobacco products) [among other products]).” Id.
`
`at 3. In addition, Coe notes “[t]he invention also relates to the pharmaceutically
`
`acceptable acid addition salts of the compounds of formula I,” and states
`
`“[e]xamples of pharmaceutically acceptable acid addition salts of the compounds of
`
`formula I are the salts of hydrochloric acid, p-toluenesulfonic acid, fumaric acid,
`
`citric acid, succinic acid, salicylic acid, oxalic acid, hydrobromic acid, phosphoric
`
`acid, methanesulfonic acid, tartaric acid, malate, di-p-toluoyl tartaric acid, and
`
`mandelic acid.” Id. at 12.
`
`
`
`Coe also provides at least 49 examples of how to synthesize specific aryl fused
`
`azapolycyclic compounds. Id. at 39–75. Example 26, in particular, discloses a
`
`process for making the hydrochloride salt of varenicline, which is the only salt form
`
`of varenicline described in Coe. Id. 57–58.
`
`U.S. Patent No. 6,14,550 (“US ’550”)
`2.
`US ’550 is the U.S. Patent that stems from the application published as Coe.
`
`EX1006 at 1. The specification of US ’550 and Coe are identical. Claim 1 of
`
`US ’550 is directed to a compound of formula I, whereas claim 8 specifically recites
`
`“[a] compound according to claim 1 which is [varenicline] or a pharmaceutically
`
`acceptable salt thereof.” Id. at 27–28. As in Coe, the only pharmaceutical salt of
`
`6
`
`
`

`

`
`varenicline disclosed in US ’550 is the hydrochloride salt, disclosed in Example 26
`
`Paper No. 6
`Filed: October 12, 2021
`
`of the specification. Id. at 20–21.
`
`Berge
`3.
`Berge is a 1977 review article titled “Pharmaceutical Salts.” EX1009 at 2.
`
`Berge provides a summary of different salt forms, and states that “the salt form is
`
`known to influence a number of physiochemical properties of the parent compound
`
`including dissolution rate, solubility, stability and hygroscopicity.” Id. at 7. Table
`
`1 of Berge lists every FDA approved commercially marketed salt at the time, and it
`
`identifies tartrate among 53 anions and 14 cations that have appeared in FDA
`
`approved commercially marketed salt forms. EX1009 at 4. Berge explains “there
`
`is no reliable way of predicting the influence of a particular salt species on the
`
`behavior of the parent compound.” EX1009 at 3. Thus, “even after many salts of
`
`the same basic agent have been prepared, no efficient screening techniques exist to
`
`facilitate selection of the salt most likely to exhibit the desired pharmacokinetic,
`
`solubility, and formulation profiles.” EX1009 at 3.
`
`4. Gould
`Gould is a 1986 review article titled “Salt Selection for Basic Drugs.”
`
`EX1010 at 3. Gould states that “[s]alt formation provides a means of altering the
`
`physiochemical and resultant biological characteristics of a drug.” Id. Gould notes
`
`that “although salt form can have a dramatic influence on the overall properties of a
`
`7
`
`
`

`

`
`drug, the selection of the salt form that exhibits the desired combination of properties
`
`Paper No. 6
`Filed: October 12, 2021
`
`remains a difficult semi-empirical choice.” Id. Gould also reproduces Table 1 from
`
`Berge, and thus identifies tartrate within the same lengthy list of all FDA approved
`
`commercially marketed salt forms at the time Berge was published. Id. at 4 (noting
`
`that Table 1 was reproduced from Berge).
`
`Nyqvist
`5.
`Nyqvist is a PCT Application titled “A New Salt,” and is directed to (R)-3-
`
`N,N-dicyclobutylamino-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxamide
`
`hydrogen tartrate. EX1016 at 3. This is an entirely different drug than varenicline.
`
`Further, Nyqvist notes how discovering that a tartrate salt is physically more stable
`
`than the corresponding hydrochloride salt was “surprising[].” Id.
`
`Prosecution History of the ’927 Patent
`C.
`The ’927 patent issued from the U.S. Patent Application No. 10/139,730,
`
`which was filed on May 6, 2002 and claims priority to a provisional patent
`
`application filed on May 14, 2001. EX1001. Original claims 1–2 of the ’730
`
`application are directed to the tartrate salt of varenicline and the L-tartrate salt,
`
`respectively, and are identical to claims 1–2 of the issued ’927 patent. EX1004 at
`
`134.
`
`Early in prosecution, the Examiner rejected all claims as obvious over Coe.
`
`In particular, the Examiner stated:
`
`8
`
`
`

`

`
`
`Paper No. 6
`Filed: October 12, 2021
`
`Claims 1–66 are rejected under 35 U.S.C. 103(a) as being
`unpatentable over Coe et al. (WO 99/35131). The
`reference teaches a generic group of salts of the instant
`compound including the tartaric acid salt (See page 10,
`lines 12-16). The claims differ from the reference by
`reciting a specific salt of the reference. However, it would
`have been obvious to one having ordinary skill in the art
`at the time of the invention to select any of the salts from
`the genus taught by the reference, including the tartrate
`salt instantly claimed, because the skilled chemist would
`have the reasonable expectation that any of the salts of the
`genus would have similar properties and, thus, the same
`use as taught for the genus as a whole.
`
`EX1004 at 199–200. After the applicant cancelled claims 1–2 and reinstated them
`
`as claims 67–68, EX1004 at 270, the Examiner again rejected the claims as obvious
`
`over Coe in a subsequent office action, EX1004 at 285. In doing so, the Examiner
`
`explained:
`
`Id.
`
`Claims 67–70 and 38 are rejected under 35 U.S.C. 103(a)
`as being unpatentable over Coe et al. (WO 99/35131). The
`reference teaches a list of salts of the instant compound
`including the tartaric acid salt (See page 10, lines 12-16).
`The claims differ from the reference by reciting a specific
`salt of the reference.
`
`9
`
`
`

`

`In response to the examiner’s rejection, the applicant explained that Coe only
`
`Paper No. 6
`Filed: October 12, 2021
`
`
`
`“teaches a generic list of salts, including the tartaric acid salt among many others of
`
`a compound of [formula I] as well as numerous related structures.” EX1004 at 294.
`
`The applicant also argued the claimed invention was limited to “tartrate salts and
`
`polymorphs of [varenicline]” only. Id. Thus, “Coe et al. does not suggest or disclose
`
`specific tartrate salts and polymorphs of [varenicline].” Id. Although Coe provides
`
`a generic list of salts, that list applies only to formula I, and “Coe et al does not
`
`motivate one skilled in the art to pick and choose from the myriad of possible
`
`substituents disclosed in the generic structures in Coe et al. necessary to arrive at the
`
`specific tartrate salt of [varenicline].” Id. at 295 (emphasis added.)
`
`Along with its response, the applicant also submitted a declaration from Peter
`
`Rose, an inventor on the ’927 patent. Id. at 925, 927. In his declaration, Mr. Rose
`
`“compared the tartrate salt claimed in this application with the hydrochloride salt of
`
`the prior art.” EX1004 at 297. This comparison demonstrates the “tartrate salt
`
`produces superior and unexpected results when compared with the hydrochloride
`
`salt of [varenicline].” Id. at 297–98. Immediately after the applicant submitted this
`
`declaration, the Examiner issued a notice of allowance. EX1004 at 301–02.
`
`III. The Board Should Deny Institution Under § 325(d)
`The Board should deny institution under § 325(d) because the Examiner
`
`considered the relevant disclosure in Coe, and Petitioner’s other references are either
`
`10
`
`
`

`

`
`cumulative of Coe or, in the case of US ’550, entirely identical. The Board applies
`
`Paper No. 6
`Filed: October 12, 2021
`
`a two-part framework for evaluating whether to institute under § 325(d): “(1)
`
`whether the same or substantially the same art previously was presented to the Office
`
`or whether the same or substantially the same arguments previously were presented
`
`to the Office; and (2) if either condition of first part of the framework is satisfied,
`
`whether the petitioner has demonstrated that the Office erred in a manner material
`
`to the patentability of challenged claims.” Advanced Bionics, LLC v. Med-El
`
`Elektromedizinische Gerate GmbH, IPR2019-01469, Paper 6 at 8 (Feb. 13, 2020)
`
`(precedential). “This framework reflects a commitment to defer to previous Office
`
`evaluations of the evidence of record unless material error is shown.” Id. at 9. Both
`
`factors weigh strongly against institution.
`
`A. The Office has Substantively Considered the Same Prior Art and
`Arguments (Advanced Bionics Factor 1; Becton Dickinson Factors
`(a), (b), and (d))
`The first part of the Advanced Bionics framework looks at whether the same
`
`prior art or arguments were previously presented to the Office. To do so, the Board
`
`considers Becton, Dickson factors (a), (b) and (d), which are “(a) the similarities and
`
`material differences between the asserted art and the prior art involved during
`
`examination; (b) the cumulative nature of the asserted art and the prior art evaluated
`
`during examination;” and “(d) the extent of the overlap between the arguments made
`
`during examination and the manner in which petitioner relies on the prior art.”
`
`11
`
`
`

`

`
`Becton, Dickinson & Co. v. B. Braun Melsungen AG, IPR2017-01586, Paper 8 at
`
`Paper No. 6
`Filed: October 12, 2021
`
`17–18 (Dec. 15, 2017) (precedential as to § III.C.5, first paragraph).
`
`All three factors support denying institution under § 325(d). In particular,
`
`(1) the examiner issued rejections over Coe in two separate office actions during
`
`prosecution, and US ’550 is identical in all material respects to Coe, (2) the
`
`secondary references in the Petition’s obviousness grounds are cumulative of Coe
`
`(3) the Examiner considered, and ultimately rejected, the same arguments that
`
`Petitioner raises in its grounds of invalidity.
`
`1.
`
`Becton, Dickson Factor (a): “whether the same or
`substantially the same art previously was presented to the
`Office or whether the same or substantially the same
`arguments previously were presented to the Office”
`It is undisputed that Coe was considered by the Examiner during prosecution,
`
`and thus Becton, Dickson factor (a) weighs against institution with respect to Coe.
`
`See Puma N.A., Inc. v. Nike Inc., IPR2019-01042, Paper 10 at 10 (Oct. 31, 2019)
`
`(informative) (factor (a) “weighs in favor of exercising discretion to deny
`
`institution” where the “prior art asserted in the Petition is identical to that involved
`
`during examination”).
`
`Petitioner’s second ground of anticipation relies on US ’550. Although the
`
`Examiner did not expressly consider US ’550, this reference is “identical in all
`
`relevant material respects to Coe,” Paper 1 at 9. Thus, Becton, Dickson factor (a)
`
`12
`
`
`

`

`
`also weighs in favor of denying institution with respect to US ’550. See Advanced
`
`Paper No. 6
`Filed: October 12, 2021
`
`Bionics, IPR2019-01469, Paper 6 at 16 (finding that factor (a) weighed against
`
`institution where the Petitioner cited references that were not before the examiner,
`
`but were “substantially the same” as the prior art considered during examination).
`
`In attempting to differentiate US ’550 from Coe, Petitioner leans on claim 8
`
`of US ’550, which recites “a compound according to claim 1 which is [varenicline]
`
`or a pharmaceutically acceptable salt thereof.” EX1006 at 28. Petitioner contends
`
`that “US ’550 pointed a POSA directly to varenicline via claim 8” and thus US ’550
`
`is “materially different than . . . the genus disclosure in the examiner’s primary
`
`reference Coe.” Paper 1 at 70. This distinction makes no sense—Coe and US ’550
`
`both specifically disclose varenicline as a “species,” and neither reference discloses
`
`the tartrate salt form of varenicline. See EX1005 at 57–58; EX1006 at 20–21. Like
`
`Coe, US ’550 only discloses varenicline hydrochloride. Id. Stated otherwise, claim
`
`8 of US ’550 is directed to an embodiment taught by both US ’550 and Coe, and
`
`addressed by the Examiner during prosecution. Contrary to Petitioner’s assertion,
`
`claim 8 does not materially distinguish US ’550 from Coe, but rather “disclos[es]
`
`substantially the same information already considered by the Office.” Advanced
`
`Bionics, IPR2019-01469, Paper 6 at 18.
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`Paper No. 6
`Filed: October 12, 2021
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`2.
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`Becton, Dickson Factor (b): “the cumulative nature of the
`asserted art and the prior art evaluated during
`examination”
`Because the disclosure in Coe and US ’550 (which are materially identical)
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`was considered during prosecution, the Board does not need to consider Becton,
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`Dickson factor (b) with respect to either reference. NHK Spring Co., Ltd. v. Intri-
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`Plex Techs., Inc., IPR2018-00752, Paper 8 at 13 (Sept. 12, 2018) (precedential) (no
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`need to address factor (b) where “Petitioner relies on the same prior art that the
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`Examiner considered during prosecution”).
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`In addition to its anticipation grounds, Petitioner also raises three obviousness
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`grounds, each of which relies on Coe as its primary reference in addition to Berge,
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`Gould, and/or Nyqvist. Paper 1 at 7. Although the Examiner did not cite these
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`secondary references, the relevant disclosure in each is cumulative of the references
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`considered during prosecution, including Coe, and do not warrant separate
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`consideration. “A reference is cumulative when it teaches no more than what a
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`reasonable examiner would consider to be taught by the prior art already before the
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`PTO.” Roku Inc. v. Universal Elecs., Inc. IPR2019-01619, Paper 11 at 16 (Apr. 2,
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`2020) (quoting Regeneron Pharm., Inc. v. Merus N.V., 864 F.3d 1343, 1350 (Fed.
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`Cir. 2017)). As described above, Berge and Gould are review articles that discuss
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`salt selection generally, whereas Nyqvist is directed to a tartrate salt of an entirely
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`different drug compound. See supra pp. 7–8. A reasonable examiner would not
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`have considered the secondary references to have taught any information material to
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`Paper No. 6
`Filed: October 12, 2021
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`patentability that is not already contained in the references cited during prosecution.
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`a.
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`Berge and Gould are cumulative of references
`considered by the Examiner
`Berge and Gould both provide high-level overviews of salt selection, but do
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`not mention varenicline or its salt forms. EX1005; EX1006. In its obviousness
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`grounds III and IV, Petitioner contends that Berge and Gould “show[] tartrate salts
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`(including stereoisomers) were known, and taught the routine salt-selection
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`rationales.” Paper 1 at 3; id. at 46 (“Berge confirms the tartrate salt’s common use
`
`in FDA-approved dosage forms.”); id. at 54 (“Gould confirms the tartrate salt’s
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`common use in FDA-approved dosage forms.”). This general disclosure of salt-
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`selection rationales, however, is cumulative of the teachings in the references
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`considered by the Examiner.
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`The prosecution history makes clear the Examiner was aware of general
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`principles of salt selection and formation, and indeed considered references that
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`disclose various pharmaceutical salts, including tartrates. EX1004 at 230 (IDS citing
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`references that discuss pharmaceutical salts). As explained above, Coe itself refers
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`to salt selection and pharmaceutical salts, including tartrate salts. EX1005 at 5
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`(disclosing pharmaceutically acceptable salts of aryl fused aryl fused azapolycyclic
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`compounds of formula I); id. at 10 (disclosing the administration of a
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`pharmaceutically acceptable salt of a compound of formula I); id. at 12 (identifying
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`Paper No. 6
`Filed: October 12, 2021
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`examples of pharmaceutically acceptable salts). Other references cited in the file
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`history also teach pharmaceutical salt selection. For example, U.S. Patent 3,471,503
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`(EX2002) was cited in an IDS and initialed by the Examiner as considered during
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`prosecution. EX1004 at 230. See R.J. Reynolds Vapor Co. v. Fontem Holdings 1
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`B.V., IPR2017-01642, Paper 10 at 6, 12 (Jan. 16, 2018) (prior art cited in IDS was
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`considered by examiner). The ’503 patent discloses compounds and their salt forms,
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`and explains that
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`The therapeutically active non-toxic acid addition salts of
`the basic nitrogen containing compounds are prepared by
`treatment with an appropriate acid such as an inorganic
`acid, e.g., hydrochloric, hydrobromic, hydriodic, sulfuric,
`nitric or phosphoric; an organic acid such as acetic,
`propionic, glycolic, lactic, pyruvic, malonic, succinic,
`maleic, malic, fumaric, tartaric, citric, benzoic, mandelic,
`cinnamic, methane sulfonic, benzene sulfonic, salicylic, 2-
`phenoxybenzoic. Conversely, the salt form may be
`converted in the usual manner into the free base.
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`EX2002, 1:60–70 (emphasis added). Similarly, European Patent 1078637, EX2003,
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`(“EP ’637”) which was also cited in an IDS and initialed by the Examiner, EX1004
`
`at 230, discloses pharmaceutical salts in the context of a pharmaceutical composition
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`to treat nicotine dependency. EX2003 at 2. EP ’637 explains:
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`Paper No. 6
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`Thus, for example some of the compounds of this
`invention are acidic and they form a salt with a
`pharmaceutically acceptable cation. All such salts are
`within the scope of this invention and they can be prepared
`by conventional methods. For example, they can be
`prepared simply by contacting the acidic and basic entities,
`usually in a stoichiometric ratio, in either an aqueous,
`nonaqueous or partially aqueous medium, as appropriate.
`The salts are recovered either by filtration, by precipitation
`with a non-solvent followed by filtration, by evaporation
`of the solvent, or, in the case of aqueous solutions, by
`lyophilization, as appropriate.
`
`EX2003 at 10.
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`Even though the file history contains several references that discuss
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`pharmaceutical salts, Petitioner nevertheless relies on Berge and Gould for the
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`notion that a POSA would have selected the tartrate salt of varenicline based on
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`routine salt selection and screening. Paper 1 at 44, 52 (“[S]alt-screens are routinely
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`conducted by a POSA.”); id. at 46 (“Berge confirms the tartrate salt’s common use
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`in FDA-approved dosage forms”); id. at 53 (“Gould guides a POSA on how to
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`optimize salt selection.”). The Board, however, has routinely denied to institute
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`petitions where the only cited references not considered during examination are
`
`directed to general principles or routine techniques that would have been known to
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`a person of ordinary skill in the art. See, e.g., Argentum Pharmaceuticals LLC v.
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`Paper No. 6
`Filed: October 12, 2021
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`Merck Patentgesellschaft, IPR2018-00423, Paper 7 at 23–24, (July 23, 2018)
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`(declining to institute review where the secondary references “appear to be
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`introductory textbooks” that describe “routine techniques,” and the Petitioner could
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`not “sufficiently show that the Examiner would not have been aware of such
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`[routine] techniques”); Canon Inc. v. Papst Licensing GMBH & Co. KG, IPR2016-
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`01202, Paper 15 at