Trials@uspto.gov
`571.272.7822
`
`
`Paper No. 9
`
` Entered: August 13, 2018
`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`____________
`
`CATALENT PHARMA SOLUTIONS, INC.
`Petitioner,
`
`v.
`
`PANTHEON SOFTGELS INC.,
`Patent Owner.
`____________
`
`Case No. IPR2018-00422
`Patent 9,693,979 B2
`____________
`
`
`
`Before ERICA A. FRANKILN, TINA E. HULSE, and
`JOHN E. SCHNEIDER, Administrative Patent Judges.
`
`SCHNEIDER, Administrative Patent Judge.
`
`
`
`
`
`
`
`DECISION
`Denying Institution of Inter Partes Review
`35 U.S.C. § 314(a)
`
`
`
`
`
`

`

`IPR2018-00422
`Patent 9,693,979 B2
`
`
`I.
`
`INTRODUCTION
`
`A. Background
`Catalent Pharma Solutions, Inc. (“Petitioner”) filed a Petition
`requesting inter partes review of claims 1–19 of U.S. Patent No. 9,693,979
`B2 (Ex. 1003, “the ’979 patent”). Paper 1 (“Pet.”). Pantheon Softgels Inc.
`(“Patent Owner”) filed a Preliminary Response contending that the Petition
`should be denied as to all the challenged claims. Paper 8 (“Prelim. Resp.”).
`We have authority under 37 C.F.R. § 42.4(a) and 35 U.S.C. § 314(a)
`to institute an inter partes review, which provides that an inter partes review
`may not be instituted unless the information presented in the Petition “shows
`that there is a reasonable likelihood that the petitioner would prevail with
`respect to at least 1 of the claims challenged in the petition.” Having
`considered the arguments and the evidence presented, for the reasons
`described below, we determine that Petitioner has failed to demonstrate that
`there is a reasonable likelihood that it would prevail with respect to claims
`1–19 challenged by the Petition. Accordingly, we decline to institute an
`inter partes review of claims 1–19 of the ’979 patent.
`
`B. Additional Proceedings
`Petitioner represents that the ’979 patent is at issue in Pantheon
`Softgels Inc. v. Apotex Inc. et al., No 3:17-cv-13819 (D.N.J.) and Pantheon
`Softgels Inc. v. Apotex Inc. et al., No. 1:18-cv-00003 (D. Del.). Petitioner
`also represents that a petition for inter partes review has been filed
`challenging related patent U.S. Patent No. 9,693,978 B2, which is now
`IPR2018-00421.
`
`2
`
`

`

`IPR2018-00422
`Patent 9,693,979 B2
`
`
`C. The ’979 Patent (Ex. 1003)
`The ’979 patent, titled “Liquid Dosage Forms of Sodium Naproxen,”
`purports to disclose oral pharmaceutical compositions comprising liquid
`dosage forms of sodium naproxen in soft gel capsules. Ex. 1003, Abstract.
`Softgel capsules using concentrated solutions are known in the art and
`often use polyethylene glycol as part of the solvent system. Ex. 1003, col. 1,
`ll. 56–63. Use of polyethylene glycol with certain pharmaceutical agents
`such as naproxen sodium, can lead to the formation of polyethylene glycol
`esters, which reduce the availability of the pharmaceutical agent. Ex. 1003,
`col. 2, ll. 23–28.
`The Specification of the ’979 patent describes pharmaceutical
`compositions comprising the salt of one or more active agents such as
`naproxen and a de-ionizing agent. Ex. 1003, col. 2, ll. 41–44. The de-
`ionizing agent causes partial de-ionization of the salt of the active ingredient,
`which enhances bioavailability of the active agent and reduces the formation
`of polyethylene glycol esters. Ex. 1003, col. 2, ll. 45–49.
`
`D. Illustrative Claim
`Of the challenged claims, claims 1, 8, and 17 are independent. Claims
`2–7 depend from claim 1, claims 9–16 depend from claim 8, and claims 18
`and 19 depend from claim 17. Claim 1 below is illustrative of the claimed
`subject matter and reads as follows:
`1. A pharmaceutical composition comprising a soft gelatin
`capsule encapsulating a liquid matrix comprising:
` (a) naproxen sodium;
` (b) about 5% lactic acid by weight of the matrix;
` (c) one or more polyethylene glycols; and
`
`3
`
`

`

`IPR2018-00422
`Patent 9,693,979 B2
`
`
` (d) one or more solubilizers comprising
`polyvinylpyrrolidone, propylene glycol, or a combination
`thereof.
`
`Ex. 1003, col. 10, ll. 54–61. The other independent clams, claims 8 and 17,
`are similar to claim 1 and include limitation that the sodium naproxen
`comprises about 25% by weight of the liquid matrix as well as limitations
`relating to the amounts of polyethylene glycol and solubilizes. Ex. 1003,
`col. 11, ll. 13–22, col. 12, ll. 18–25.
`
`E. The Alleged Grounds of Unpatentability
`Petitioner contends that the challenged claims of the ’979 patent are
`unpatentable on the following grounds.1
`References
`Basis
`Chen2
`§ 102 §
`103(a)
`§ 103(a)
`§ 103(a)
`§ 103(a)
`§ 103(a)
`
`
`Kim3
`Kim and Chen
`Schoenhard4
`Schoenhard and Chen
`
`Claims Challenged
`1–19
`
`1–19
`1–19
`1–19
`1–19
`
`
`1 Petitioner supports its challenge with the Declaration of Peter Draper. Ex.
`1001.
`2 Chen et al., US 6,383,471 B1; issued May 7, 2002 (“Chen”) (“Ex. 1009”).
`3 Kim et al., US 2004/0157928 A1; published Aug. 12, 2004 (“Kim”) (“Ex.
`1010”).
`4 Schoenhard, US 2004/0224020 A1; published Nov. 11, 2004
`(“Schoenhard”) (“Ex. 1011”).
`
`4
`
`

`

`IPR2018-00422
`Patent 9,693,979 B2
`
`
`CLAIM CONSTRUCTION
`
`II.
`A. Legal Standard
`“A claim in an unexpired patent that will not expire before a final
`written decision is issued shall be given its broadest reasonable construction
`in light of the [S]pecification of the patent in which it appears.” 37 C.F.R.
`§ 42.100(b). Under that standard, the claim terms are generally given their
`ordinary and customary meaning as would be understood by one of ordinary
`skill in the art in the context of the entire disclosure. See In re Translogic
`Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007) (“The ordinary and
`customary meaning ‘is the meaning that the term would have to a person of
`ordinary skill in the art in question.’” (quoting Phillips v. AWH Corp.,
`415 F.3d 1303, 1313 (Fed. Cir. 2005))). Only terms that are in controversy
`need to be construed and only then to the extent necessary to resolve the
`controversy. Vivid Techs., Inc. v. Am. Science & Eng’g, Inc., 200 F.3d 795,
`803 (Fed. Cir. 1999).
`
`1. About 5%
`Each of the claims includes the limitation that the composition
`comprise “about 5% lactic acid by weight of the liquid matrix.” See, e.g.,
`Ex. 1003, col. 10, l. 57.
`Petitioner contends that the term “about 5% . . . by weight” should be
`interpreted as embracing the range of from 2 to 8%. Pet. 13. Petitioner
`argues that this range is supported by examples 8–12 in the Specification,
`which0.24 to 0.35 moles equivalents of lactic acid lactic acid per mole
`equivalent of sodium naproxen. Pet. 12–13. Petitioner contends that this
`mole equivalent range equals a range of from 2 to 8% by weight of the liquid
`matrix. Id.
`
`5
`
`

`

`IPR2018-00422
`Patent 9,693,979 B2
`
`
`Patent Owner contends that the term about 5% should be given its
`plain and ordinary meaning of approximately 5%. Prelim. Resp. 8 (citing
`Merck & Co. v. Teva Pharm. USA, 395 F.3d 1364, 1372 (Fed. Cir. 2005)
`(“the term ‘about’ should be given its ordinary and accepted meaning of
`‘approximately’”). Patent Owner argues that Petitioner’s proposed
`construction is improper in that it embraces the original scope of the claims,
`which was given up when the claims were amended to recite 5% by weight.
`Prelim. Resp. 10. Patent Owner also contends that only claim 8 embraces
`the range recited by Petitioner and that one skilled in the art would interpret
`Examples 7 and 9–12 as teaching from 5 to 5.27% by weight lactic acid.
`Prelim. Resp. 9–10.
`We have considered the parties’ arguments and conclude that, for
`purposes of this decision, the term “about 5% . . . by weight” should be
`given its ordinary meaning — approximately 5% by weight. During
`prosecution, Patent Owner pursued then claim 10 that recited the limitation
`calling for “about 0.2 to about 1.0 mole equivalents of lactic acid per mole
`of naproxen sodium.” Ex. 1008, 121. As Patent Owner points out, this is
`nearly the same amount of lactic acid as the range included in Petitioner’s
`proposed construction. Prelim. Resp. 11. In response to a rejection over the
`art, Patent Owner amended the independent claims, including then claim 10,
`to recite the narrower limitation calling for 5% lactic acid by weight of the
`matrix. Ex. 1008, 193–200. Given that Patent Owner intentionally
`narrowed the scope of the claims to exclude a broader amount of lactic acid,
`we decline to adopt a construction that would enlarge the scope of the
`claims. We agree with Patent Owner that Petitioner’s proposed
`construction would improperly broaden the scope of the claims to embrace a
`
`6
`
`

`

`IPR2018-00422
`Patent 9,693,979 B2
`
`range of lactic acid given up during prosecution. Prelim. Resp. 10. “The
`Prosecution history, while not literally within the patent document, serves as
`intrinsic evidence for purposes of claim construction. This remains true in
`construing patent claims before the PTO.” Tempo Lighting Inc. v. Tivoli,
`LLC, 742 F.3d 973, 977 (Fed. Cir. 2014). While we “must give the terms
`their broadest reasonable construction, the construction cannot be divorced
`from the [S]pecification and the record evidence.” In re NTP, Inc., 654 F.3d
`1279, 1288 (Fed. Cir. 2011).
`
`2. Liquid matrix
`The term “liquid matrix” appears in each of the challenged claims.
`Petitioner contends that the term “liquid matrix” should be construed as “the
`material for filling the soft gelatin capsule prepared by mixing the claimed
`amounts prior to encapsulation.” Pet. 13 (quoting Ex. 1001 ¶ 85). Petitioner
`contends that this is consistent with the instant Specification, which teaches
`that “[t]he fill material is prepared by mixing the agent (such as a salt of the
`drug), the deionizing agent, water and polyethylene glycol at a temperature
`of 50°C to 70°C. The resulting solution is encapsulated using the
`appropriate gel mass.” Ex. 1003, col. 6, ll. 59–63.
`Patent Owner does not agree with Petitioner’s proposed construction.
`Prelim. Resp. 12. Patent Owner contends that construction of the term
`“liquid matrix” is not necessary to resolve the issues in the present
`proceeding. Id.
`We have considered the parties’ arguments. We agree with Patent
`Owner that the term need not be construed to resolve the issues presented in
`the Petition. Therefore, for purposes of this decision, we decline to
`expressly construe the term “liquid matrix.”
`
`7
`
`

`

`IPR2018-00422
`Patent 9,693,979 B2
`
`
`III. ANALYSIS
`
`Petitioner contends that claims 1–19 are: (1) anticipated by Chen; (2)
`obvious over Chen; (3) obvious over Kim; (4) obvious over Kim in view of
`Chen; (5) obvious over Schoenhard; or (6) obvious over Schoenhard in view
`of Chen. As discussed more fully below, we conclude that, on the record
`before us, Petitioner has not demonstrated that there is a reasonable
`likelihood that it will prevail on any of the listed grounds with respect to
`claims 1–19.
`
`A. Anticipation by Chen
`Chen discloses methods and compositions for improving the delivery
`of a hydrophobic therapeutic agent having at least one ionizable functional
`group by combining the therapeutic agent with an ionizing agent, a
`surfactant and one or more solubilizers. Ex. 1009, Abstract. The therapeutic
`agents useful in the compositions of Chen include naproxen and salts of
`naproxen. Ex. 1009, col. 7, ll. 40–46, col. 10, ll. 36–41. Ionizing agents
`used in Chen include citric and lactic acids that can be present in amounts
`ranging from 0.1 to 0.5 mole equivalents per mole equivalent of therapeutic
`agent with 0.5 mole equivalents preferred. Ex. 1008, col. 11, ll. 9–25, col.
`12, ll. 30–35. Chen also discloses the addition of solubilizers including
`polyethylene glycol, polypropylene glycol, polyvinylpyrrolidone, and
`mixtures thereof. Ex. 1009, col. 31, l. 40–col. 32, l. 26.
`“Under 35 U.S.C. § 102, every limitation of a claim must identically
`appear in a single prior art reference for it to anticipate the claim.” Gechter
`v. Davidson, 116 F.3d 1454, 1457 (Fed. Cir. 1997).
`Claim 1 is representative of the challenged claims and is directed to a
`pharmaceutical composition comprising a soft gelatin capsule containing:
`
`8
`
`

`

`IPR2018-00422
`Patent 9,693,979 B2
`
`(a) naproxen sodium; (b) about 5% lactic acid by weight of the matrix; (c)
`one or more polyethylene glycols; and (d) polyvinylpyrrolidone,
`polypropylene glycol or mixtures thereof.
`Petitioner contends that “Chen discloses the same active agent,
`neutralized with the same acid, dissolved in the same solvent system, and
`encapsulated in the same soft gelatin capsules.” Pet. 21.
`Patent Owner contends that Chen does not teach all of the elements of
`claim 1. Prelim. Resp. 14. Specifically Patent Owner argues that Chen does
`not disclose a composition comprising about 5% lactic acid by weight of the
`matrix. Prelim. Resp. 15–16. Patent Owner contends that Chen does not
`disclose 25% naproxen nor does Chen disclose about 1 to about 10%
`solubilizers as required by claims 8 and 17. Prelim. Resp. 20–21. Patent
`Owner also contends that even if all the elements of the claims werepresent
`in Chen, they are not arranged in the same manner as in claim 1. Prelim.
`Resp. 21–26. Patent Owner contends that Petitioner has not established
`anticipation by Chen in that Petitioner’s analysis relies on a reference in
`addition to Chen. Prelim. Resp. 26–28.
`The issue of whether Chen discloses the presence of lactic acid in an
`amount equal to 5% by weight of the matrix is dispositive.
`Petitioner contends that Chen discloses a composition containing
`about 5% lactic acid based on the weight of the combined ingredients. Pet.
`19–20. Petitioner bases this conclusion on the teaching in Chen that the
`ionizing agent should be preferably present in the composition in an amount
`equal to 0.5 mole equivalents per mole of therapeutic agent. Pet. 19.
`Petitioner’s expert, Mr. Draper, opines that one skilled in the art after
`
`9
`
`

`

`IPR2018-00422
`Patent 9,693,979 B2
`
`reading Chen would use an “880 ml” capsule5 to encapsulate 220 mg of
`naproxen sodium. Ex. 1001 ¶ 93; Pet. 19–20. Petitioner also contends that
`Chen “inherently teaches combining 250 mg of naproxen sodium with 60
`mg of sodium lactate . . . . which equates to 48 mg of lactic acid.” Pet. 26.
`Using these values, Mr. Draper calculates that lactic acid would be present
`in a composition containing 220 mg sodium naproxen in an amount of 4.4%,
`which the expert opines is about 5%. Ex. 1001 ¶ 93. Mr. Draper also opines
`that if an 800 ml capsule is used with a dosage of 250 mg of sodium
`naproxen as taught by Kim, then the amount of lactic acid would be about
`5.5%. Id. Petitioner also contends that the examples of Chen supports the
`conclusion that 48 grams of lactic acid in one gram of filler material equates
`to about 5%. Pet. 26.
`Patent Owner contends that while Chen discloses using lactic acid in a
`mole ratio of 0.5 moles of lactic acid per mole of active ingredient, there is
`nothing in Chen that discloses a specific amount of naproxen sodium to be
`included in the composition. Prelim. Resp. 16. Patent Owner contends that
`without knowing how much sodium naproxen is present, one skilled in the
`art cannot calculate how much lactic acid should be used. Id. Patent Owner
`also argues that Chen is silent as to the size of the capsule to be used.
`Prelim. Resp. 17–18. Finally, Patent Owner contends that nothing in Chen
`
`
`5 Patent Owner points out that Petitioner’s and Mr. Draper’s reference to an
`“880 ml capsule” appears to be an error in that such a capsule would be
`extremely large and impractical for human consumption. Prelim. Resp. 18,
`n 2. We agree with Patent Owner. According to the chart attached as
`exhibit A to Ex. 1001, a size 14 oblong gel cap would have a maximum
`volume of 1.06 ml, not 880 ml. Ex. 1001 A-1. None of the gel caps listed in
`exhibit A show a volume of 880 ml. Similarly, Ex. 1010 reports the use of
`an 800 mg capsule not an 800 ml capsule. Ex. 1010 ¶ 36.
`
`10
`
`

`

`IPR2018-00422
`Patent 9,693,979 B2
`
`teaches that the remainder of the matrix ingredients would have a density of
`1g/ml.
`We have considered the parties’ arguments and the teachings of Chen
`and conclude that Petitioner has not adequately demonstrated that Chen
`discloses a composition comprising about 5% lactic acid by weight of the
`matrix. Petitioner has pointed to nothing in Chen that discloses the amount
`of naproxen to be used or the total amount of ingredients that comprise the
`matrix. Pet. 19–20. Instead Petitioner relies on the teachings of additional
`references and assumptions based outside the teachings of Chen. See, e.g.,
`Pet. 20 (relying on teachings of Kim for 250 mg dose of naproxen). Since
`Petitioner has not shown that Chen, by itself, discloses a composition
`comprising 5% lactic acid by weight of the matrix, Chen does not anticipate
`claim 1. “Anticipation requires that all of the claim elements and their
`limitations are shown in a single prior art reference.” In re Skvorecz, 580
`F.3d 1262, 1266 (Fed. Cir. 2009).
`With respect to Petitioner’s argument that Chen inherently teaches
`250 mg of naproxen sodium with 48 mg of lactic acid, Pet. 26, we agree
`with Patent Owner that Petitioner has not pointed to any teaching in Chen
`that indicates that these amounts are necessarily present in the compositions
`of Chen. In re Robertson, 169 F.3d 743, 745 (Fed. Cir. 1999).
`Independent claims 8 and 17 also include the limitation calling for 5%
`lactic acid by weight of the matrix. Ex. 1003, col. 11, l. 16, col. 12, l. 21.
`Since, as discussed above, Chen does not teach this element, Chen does not
`anticipate these claims.
`The remaining claims depend from claim 1, 8 or 17. Ex. 1003, col.
`10, l. 62–col. 12, l. 31. The dependent claims also include the limitation
`
`11
`
`

`

`IPR2018-00422
`Patent 9,693,979 B2
`
`calling for 5% lactic acid by weight of the matrix. Since Chen does not
`disclose this limitation, Chen does not anticipate the dependent claims.
`
`B. Obviousness over Chen
`The teachings of Chen are discussed above. Petitioner contends that if
`Chen does not anticipate the challenged claims, it renders the subject matter
`of the claims obvious. Pet. 21. Petitioner does not present an analysis
`showing obviousness based on Chen separate from its showing of
`anticipation by Chen. Id.
`Patent Owner contends that Petitioner has failed to meet its burden of
`properly articulating the reasons behind its different grounds in the Petition.
`Prelim. Resp. 13. Patent Owner contends that Petitioner has failed to
`articulate why one skilled in the art would modify the teachings of Chen to
`produce the claimed invention. Prelim. Resp. 31–33. Patent Owner also
`contends that Petitioner has failed to make a showing that one skilled in the
`art would have had a reasonable expectation of success in modifying Chen
`to achieve the claimed composition. Prelim. Resp. 33–35. Patent Owner
`argues that Petitioner has not shown that the claimed amounts of lactic acid
`and naproxen sodium would have been generated through routine
`optimization. Prelim. Resp. 35–36. Patent Owner also argues that there is
`evidence of unexpected results which supports a conclusion of non-
`obviousness. Prelim. Resp. 36–42.
`A proper section 103 analysis requires “a searching comparison of the
`claimed invention—including all its limitations—with the teaching of the
`prior art.” In re Ochiai, 71 F.3d 1565, 1572 (Fed. Cir. 1995).
`
`
`12
`
`

`

`IPR2018-00422
`Patent 9,693,979 B2
`
`
`“[A] patent composed of several elements is not proved obvious
`merely by demonstrating that each of its elements was, independently,
`known in the prior art.” KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 398, 418
`(2007).
`
`“[I]t can be important to identify a reason that would have prompted a
`person of ordinary skill in the relevant field to combine elements in the way
`the claimed new invention does.
`
`We have considered the parties’ arguments and conclude that, on the
`present record, Petitioner has not established a reasonable likelihood that it
`would prevail in showing that the subject matter of the challenged claims
`would have been obvious over Chen. Petitioner has not shown why one
`skilled in the art, based on the teachings of Chen, either alone or in
`combination with other references, would have used 5% lactic acid in
`combination with naproxen sodium as required by the claims.
`Petitioner contends that 5% lactic acid by weight of the matrix would
`have been a routine choice by one skilled in the art. Pet. 24–25. In support
`of this contention Petitioner relies on various calculations by Mr. Draper
`purporting to show that use of 5% lactic acid by weight of the matrix would
`naturally flow from the teachings of Chen and other references. Pet. 25–26.
`Petitioner’s contentions with respect to the amount of lactic acid being
`a matter of routine choice are based on the assumption that one skilled in the
`art would use either an 800 mg capsule or an 880 ml capsule and would use
`dosages of naproxen sodium of 220mg and 250mg. Pet. 26–27. Petitioner,
`however, does not sufficiently explain why one skilled in the art would use
`
`13
`
`

`

`IPR2018-00422
`Patent 9,693,979 B2
`
`the specific capsules and amounts of naproxen sodium used by its expert.
`See, Id.
`Mr. Draper does not explain why he chose the 880 ml oblong capsule
`for his calculations other than to suggest that it is a capsule size that one
`skilled in the art would use following the teachings of Chen. Ex. 1001 ¶ 93.
`Petitioner and Mr. Draper point to nothing in Chen to support this
`conclusion. See, id. A review of the evidence in this proceeding shows no
`teaching of an 880 ml capsule. Petitioner refers to a size 14 oblong capsule
`as having such a volume, however, Exhibit A to Petitioner’s expert’s
`declaration shows that a number 14 oblong capsule has a volume of from .75
`to 1.06 ml, not 880 ml as stated by Petitioner and its expert Mr. Draper. Pet.
`19–20; Ex. 1001, A–1.
`Even if there were evidence of an 880 ml oval capsule, neither
`Petitioner nor Mr. Draper, have explained why one skilled in the art would
`have chosen such a capsule to encapsulate 220 mg of naproxen sodium.
`Selection of a different volume would result in a different weight percent of
`lactic acid since it is based on the total weight of all the ingredients included
`in the capsule. See Pet. 26.
`Petitioner and Mr. Draper also fail to explain why Mr. Draper chose to
`use an oval capsule for his calculations. Ex. 1001 ¶ 93. As Patent Owner’s
`expert, Dr. Kahn explains, the art teaches that softgels are made in a variety
`of shapes including round, oval and oblong, which can accommodate a
`variety of different fill volumes. Ex. 2001 ¶ 38; Ex. 2023, 400.
`With respect to an 800 mg capsule, while Kim teaches the use of an
`800 mg capsule, Petitioner does not explain why one would use that size
`capsule other than to say that it would be a conventional capsule size. Pet.
`
`14
`
`

`

`IPR2018-00422
`Patent 9,693,979 B2
`
`27. Referring again to the table attached to Mr. Draper’s declaration, there
`are numerous conventional capsule sizes and shapes, each having different
`volume ranges. Ex. 1001 A-1, see also, Ex. 2001 ¶ 38; and Ex. 2021, 611
`Fig. 17.1. Mr. Draper does not explain why one skilled in the art would use
`an 800 mg capsule over the other capsule sizes. As noted above, the volume
`of the capsule affects the calculation of the weight percent of lactic acid in
`the composition.
`With respect to the amounts of naproxen sodium used by Mr. Draper
`in his calculations, as noted above, Chen is silent as to the amount of active
`agent to be used in his formulations. To remedy this deficiency, Petitioner
`turns to Kim and Banner’s FDA filing to show that naproxen sodium is
`typically used in dosages of 220 mg and 250 mg. Pet. 26–27; Ex. 1010 ¶ 36;
`Ex. 1021, 1. However, as Patent Owner points out, the art teaches that
`dosages for naproxen sodium range from as low as 50 mg to as high as
`1.65 g. Prelim. Resp. 16–17. The evidence advanced by Petitioner discloses
`typical dosages of naproxen sodium of 275 mg and 500 mg. Ex. 1025.
`Neither Petitioner nor Mr. Draper explains why one skilled in the art would
`have chosen the specific amounts used by Mr. Draper to arrive at 5% lactic
`acid.
`Given the unexplained “picking-and-choosing” in Petitioner’s
`analysis, we are persuaded that Petitioner and its expert have impermissibly
`relied on hindsight in reaching their conclusion that the subject matter of the
`claims would have been obvious. It appears that Mr. Draper, with the
`limitation of 5% lactic acid in mind, selected the capsule sizes and naproxen
`sodium amounts that would lead to that specific weight percent of lactic
`acid. If different capsule sizes or different amounts of naproxen sodium
`
`15
`
`

`

`IPR2018-00422
`Patent 9,693,979 B2
`
`were used, the calculated amount of lactic acid would be different. “We
`must still be careful not to allow hindsight reconstruction of references to
`reach the claimed invention without any explanation as to how or why the
`references would be combined to produce the claimed invention.”
`Innogenetics, N.V. v. Abbott Labs., 512 F.3d 1363, 1374 n.3 (Fed. Cir.
`2008).
`As noted above, all of the claims challenged by Petitioner include the
`limitation calling for 5% lactic acid by weight of the matrix. Therefore, the
`subject matter of the challenged claims would not have been obvious over
`Chen.
`For the reasons given above, we conclude that Petitioner has not
`established a reasonable likelihood that it would prevail in establishing that
`at least one of the challenged claims would have been unpatentable over
`Chen.
`C. Obviousness over Kim, Either Alone or in Combination with Chen
`Petitioner contends that the subject matter of the challenged claims
`would have been obvious over either Kim alone or in combination with
`Chen. Pet. 36. Petitioner contends that Kim teaches solubilizing naproxen
`in a pharmaceutical composition by neutralizing a portion of the naproxen
`using sodium citrate. Id. Petitioner contends that Kim also teaches the use
`of polyethylene glycol and other solubilizers. Id at 36–37. Petitioner
`contends that one skilled in the art would have substituted sodium or
`potassium lactate for sodium citrate as they are pharmaceutically acceptable
`salts of lactic acid and citric acid. Pet. 36. Petitioner further contends that
`one skilled in the art would have seen the two acids as equivalent with
`respect to neutralizing sodium naproxen. Id. Petitioner argues that the use
`
`16
`
`

`

`IPR2018-00422
`Patent 9,693,979 B2
`
`of the acid salts to neutralize naproxen would have been the same as using
`the respective acids to neutralize naproxen sodium. Id. Petitioner contends
`that it would have been obvious to one skilled in the art to use lactic acid to
`neutralize naproxen sodium. Id.
`With respect to Chen, Petitioner contends that Chen teaches that lactic
`acid and citric acid can both be used to partially neutralize naproxen sodium.
`Pet. 38.
`Using the examples of Kim as a guide, Petitioner contends that one
`skilled in the art would use the same moles of lactic acid as the moles of
`sodium citrate present in the examples of Kim. Pet. 41. (“One can thus
`arrive at ‘about 5% lactic acid’ by showing that an equivalent amount of
`citric acid would be present . . . .”). Petitioner contends that based on the
`amount of naproxen present in the examples and the total amount of
`ingredients in the examples, lactic acid would be present in an amount of 5%
`by weight of the matrix. Pet. 41.
`Patent Owner contends that neither Kim nor Chen shows that lactic
`acid and citric acid are functional equivalents. Prelim. Resp. 44. Patent
`Owner contends that Petitioner has not identified any reason why one skilled
`in the art would have substituted lactic acid for citric acid and expected to
`achieve the same results. Prelim. Resp. 45. Patent Owner argues that the
`evidence of equivalence cited by Petitioner in fact demonstrates that the two
`acids are not equivalent. Prelim. Rep. 46–47. Patent Owner also notes that
`Kim teaches that dexibuprofen and naproxen have very different solubilities
`depending on the solvent used. Prelim. Resp. 48–49 (citing Ex. 1010 ¶ 80,
`Table 2). Patent Owner also contends that Petitioner has not shown that one
`skilled in the art would have had a reasonable expectation of success in
`
`17
`
`

`

`IPR2018-00422
`Patent 9,693,979 B2
`
`modifying the compositions of Kim nor has Petitioner established that the
`amounts of naproxen used by its expert are ones that are routinely used by
`those in the art. Prelim. Resp. 50–51.
`Having considered the parties’ arguments and evidence, we conclude
`that on this record and for purposes of this decision, Petitioner has not
`established a reasonable likelihood that it would prevail in showing that any
`of the challenged claims would have been unpatentable over Kim alone or
`Kim in combination with Chen.
`Once again, the issue of whether the references teach or suggest the
`use of 5% lactic acid by weight of the matrix is dispositive of the issue of
`whether Petitioner has shown that the subject matter of the challenged
`claims would have been obvious over Kim alone or combined with Chen.
`Since we find that the combination of references do not teach or suggest this
`limitation, we need not address the remainder of Patent Owner’s arguments.
`As Patent Owner points out, Kim does not disclose the use of lactic
`acid but teaches the use of potassium and sodium citrate as de-ionizing agent
`for naproxen. Prelim. Resp. 43; Ex. 1010 ¶ 41. Petitioner points to nothing
`in Kim that teaches the interchangeability of sodium citrate or potassium
`citrate with lactic acid. To address this deficiency in Kim, Petitioner points
`to Chen, which teaches that lactic acid and citric acid can both be used as
`ionizing agents to deprotonate active ingredients such as naproxen. Pet. 38;
`Ex.1009, col. 11, ll. 10–25. Petitioner also relies on the declaration of Mr.
`Draper to show that one skilled in the art would understand that when using
`naproxen sodium versus naproxen one would use an organic acid instead of
`the salt and that one could use lactic acid for citric acid. Pet. 37; Ex. 1001 ¶
`103. Mr. Draper assumes that one skilled in the art would use the same
`
`18
`
`

`

`IPR2018-00422
`Patent 9,693,979 B2
`
`amount of lactic acid as citric acid in making his calculation of the
`percentage of lactic acid that would be used in a naproxen sodium
`containing composition. See, Ex. 1001 ¶¶ 66–67.
`As Patent Owner points out, citric acid and lactic acid are not
`functional equivalents. Prelim. Resp. 46–47. Citric acid and lactic acid are
`structurally different, with citric acid having three carboxyl groups and is
`capable of donating three protons, whereas lactic acid has only one carboxyl
`group and can only donate one proton. Ex. 1023; Ex. 2001 ¶ 45; and Ex.
`2022, 189–90. Moreover, while Chen may teach that lactic acid and citric
`acid can both be used as ionizing agents, Chen does not teach that they can
`be used in equal amounts. Prelim. Resp. 48. In fact given the different
`number of protons that the acids can deliver, one skilled in the art would not
`expect to use them in the same amounts. See Ex. 2001 ¶¶ 45–46.
`The functional differences between lactic acid and citric acid is borne
`out by the data submitted by Patent Owner to the European Patent Office in
`connection with a related application. Ex. 1007, 414–421. The data
`demonstrates that when equal amounts of citric acid and lactic acid are used
`with equal amounts of naproxen sodium, different results are achieved. For
`example, compositions 8 and 11, which contain lactic acid, produced a
`“clear solution,” whereas compositions 13–15, comprising citric acid,
`produced precipitates or a white paste. Ex. 1007, 419–20 (Table 8). In
`addition, the lactic acid-containing compositions showed undetectable levels
`of PEG ester after stress at 60° C for 7 days whereas the citric acid
`compositions showed significant levels of PEG esters when subjected to the
`same stress. Id.
`
`19
`
`

`

`IPR2018-00422
`Patent 9,693,979 B2
`
`
`Kim also does not teach a composition containing both naproxen and
`sodium citrate.