`
`
`Trials@uspto.gov
`571.272.7822
` Entered: August 13, 2018
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`CATALENT PHARMA SOLUTIONS, INC.
`Petitioner,
`
`v.
`
`PATHEON SOFTGELS INC.,
`Patent Owner.
`____________
`
`Case No. IPR2018-00421
`Patent 9,693,978 B2
`____________
`
`
`
`Before ERICA A. FRANKLIN, 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)
`
`
`
`
`
`
`
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`IPR2018-00421
`Patent 9,693,978 B2
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`INTRODUCTION
`
`I.
`
`A. Background
`Catalent Pharma Solutions, Inc. (“Petitioner”) filed a Petition
`requesting inter partes review of claims 1–38 of U.S. Patent No. 9,693,978
`B2 (Ex. 1003, “the ’978 patent”). Paper 2 (“Pet.”). Patheon 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
`1–38 challenged by the Petition. Accordingly, we decline to institute an
`inter partes review of claims 1–38 of the ’978 patent.
`
`B. Additional Proceedings
`Petitioner represents that the ’978 patent is at issue in Patheon
`Softgels Inc. v. Apotex Inc. et al., No 3:17-cv-13819 (D.N.J.) and Patheon
`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. 9,693,979 B2, which is now
`IPR2018-00422.
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`IPR2018-00421
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`C. The ’978 Patent (Ex. 1003)
`The ’978 patent, titled “SOLVENT SYSTEM FOR ENHANCING
`THE SOLUBILITY OF PHARMACEUTICAL AGENTS,” purports to
`disclose oral pharmaceutical compositions comprising liquid dosage forms
`of sodium naproxen in soft gel capsules. Ex. 1003, (54), Abstract.
`Softgel capsules using concentrated solutions are known in the art and
`often use polyethylene glycol as part of the solvent system. Id. at col. 1, ll.
`58–65. 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. Id. at col. 2, ll.
`25–30.
`The specification of the ’978 patent describes pharmaceutical
`compositions comprising the salt of one or more active agents such as
`naproxen and a de-ionizing agent. Id. at 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. Id. at col. 2, ll. 45–49.
`
`D. Illustrative Claim
`Of the challenged claims, claims 1, 10, 18, 20, and 21 are
`independent. Claims 2–9 and 22–25 depend from claim 1; claims 11–17, 26,
`and 27 depend from claim 10; claims 19 and 28–30 depend from claim 18;
`claims 31–34 depend from claim 20; and claims 35–38 depend from claim
`21. Claim 1 below is illustrative of the claimed subject matter and reads as
`follows:
`A pharmaceutical composition comprising soft gelatin
`1.
`capsule comprising a fill material comprising:
` (a) a naproxen salt;
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` (b) about 5% lactic acid by weight of the fill material; and
` (c) polyethylene glycol.
`
`Ex. 1003, col. 9, ll. 63–67. The other independent clams, claims 10, 18, 20,
`and 21, are similar to claim 1 and include limitations regarding the amount
`of naproxen salt and polyethylene glycol that should be present and
`limitations calling for the presence of additional solubilizers. Ex. 1003, col.
`10, ll. 30–32, 57–64, col. 11, ll. 1–17.
`
`E. The Alleged Grounds of Unpatentability
`Petitioner contends that the challenged claims of the ’978 patent are
`unpatentable on the following grounds.1
`References
`Basis
`Chen2
`§ 102; § 103(a)
`Kim3
`§ 103(a)
`Kim and Chen
`§ 103(a)
`Schoenhard4
`§ 102; § 103(a)
`
`
`Claims Challenged
`1–38
`1–38
`1–38
`1–38
`
`
`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).
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`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 specification 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 fill material.” See, e.g.,
`Ex. 1003, col. 9, l. 66.
`Petitioner contends that the term “about 5% . . . by weight” should be
`interpreted as embracing the range of from 2 to 8%. Pet. 12–13. Petitioner
`argues that this range is supported by Examples 8–12 in the specification,
`which specify 0.24 to 0.35 mole equivalents of 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 fill
`material. Id.
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`Patent Owner contends that the term about 5% should be given its
`plain and ordinary meaning of approximately 5%. Prelim. Resp. 8–9 (citing
`Merck & Co. v. Teva Pharms. 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. Id.
`at 10–11.
`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 the claims that recited the limitation
`calling for “about 0.2 to about 1.0 mole equivalents of lactic acid per mole
`of naproxen sodium.” Ex. 1006, 173–79. As Patent Owner points out, this
`is nearly the same amount of lactic acid as the range proposed by Petitioner
`in its proposed construction. Prelim. Resp. 11. In response to a rejection
`over the art, Patent Owner amended all the independent claims to recite the
`narrower limitation calling for 5% lactic acid by weight of the matrix. Ex.
`1006, 207–16. 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 range of lactic acid given up
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`during prosecution. Prelim. Resp. 10–11. “[T]he 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
`specification and the record evidence.” In re NTP, Inc., 654 F.3d 1279,
`1288 (Fed. Cir. 2011).
`
`2. Fill Material
`The term “fill material” appears in each of the challenged claims.
`Petitioner contends that the term “fill material” should be construed as “‘the
`material for filling the soft gelatin capsule prepared by mixing the claimed
`ingredients in the claimed amounts prior to encapsulation.” Pet. 13 (quoting
`Ex. 1001 ¶ 80). 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. 5, ll.
`51–55.
`Patent Owner does not agree with Petitioner’s proposed construction.
`Prelim. Resp. 12. Patent Owner contends that construction of the term “fill
`material” 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 “fill material.”
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`III. ANALYSIS
`
`Petitioner contends that claims 1–38 are: (1) anticipated by Chen; (2)
`obvious over Chen; (3) obvious over Kim; (4) obvious over Kim in view of
`Chen; (5) anticipated by Schoenhard; or (6) obvious over Schoenhard. 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 1–38.
`
`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. Id. at 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. Id. at 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.
`Id. at 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:
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`(a) sodium naproxen salt; (b) about 5% lactic acid by weight of the matrix;
`and (c) polyethylene glycol.
`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
`fill material. Id. at 15–16. Patent Owner contends that Chen does not
`disclose the specific amounts of naproxen salt as required by claim 18. Id. at
`21. Patent Owner also contends that even if all the elements of the claims
`were present in Chen, they are not arranged in the same manner as in claim
`1. Id. at 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. Id. at 26–28.
`The issue of whether Chen discloses the presence of lactic acid in an
`amount equal to 5% by weight of the fill material 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. Id. at 19.
`Petitioner’s expert, Mr. Draper, opines that one skilled in the art after
`reading Chen would use an “880 ml” capsule5 to encapsulate 220 mg of
`
`
`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
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`naproxen sodium. Ex. 1001 ¶ 89; Pet. 19–20. Petitioner also contends that
`Chen “inherently teaches combining 250 mg [of] naproxen sodium and 60
`mg [of] sodium lactate . . . . [which] equates to 48 grams of lactic acid.” Pet.
`25. 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 ¶ 89. 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. 25.
`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. at 16–17.
`Patent Owner also argues that Chen is silent as to the size of the capsule to
`be used. Id. at 17–18. Finally, Patent Owner contends that nothing in Chen
`teaches that the remainder of the matrix ingredients would have a density of
`1 g/ml. Id. at 19.
`
`
`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 Exhibit 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, Exhibit 1010 reports the
`use of an 800 mg capsule not an 800 ml capsule. Ex. 1010 ¶ 36.
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`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 fill
`material. 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
`fill material. Pet. 19–20. Instead Petitioner relies on the teachings of
`additional references and assumptions based outside the teachings of Chen.
`See, e.g., Pet. 19 (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. 25), 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 10, 18, 20, and 21 also include the limitation
`calling for 5% lactic acid by weight of the fill material. Ex. 1003, col. 10, ll.
`33, 64, col. 11, ll. 5, 12. Since, as discussed above, Chen does not teach this
`element, Chen does not anticipate these claims.
`The remaining claims depend from claims 1, 10, 18, 20, or 21. Id. at
`col. 10, l. 1–col. 12, l. 25. The dependent claims also include the limitation
`calling for 5% lactic acid by weight of the fill material. Since Chen does not
`disclose this limitation, Chen does not anticipate the dependent claims.
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`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. Id. at 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. Id. at 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. Id. at 35–36.
`Patent Owner also argues that there is evidence of unexpected results, which
`supports a conclusion of non-obviousness. Id. at 36–41.
`A proper section 103 analysis requires “a searching comparison of the
`claimed invention—including all its limitations—with the teachings of the
`prior art.” In re Ochiai, 71 F.3d 1565, 1572 (Fed. Cir. 1995).
`“[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).
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`“[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 fill material
`would have been a routine choice by one skilled in the art. Pet. 23–24. 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 fill
`material would naturally flow from the teachings of Chen and other
`references. Id. at 24–25.
`Petitioner’s contentions with respect to the amount of lactic acid being
`a matter of routine choice are based on an 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 220 mg and 250 mg. Pet. 19, 23–25.
`Petitioner, however, does not sufficiently explain why one skilled in the art
`would use 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 oval capsule for
`his calculations other than to suggest that it is a capsule size that one skilled
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`in the art would use following the teachings of Chen. Ex. 1001 ¶ 89.
`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.
`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. 25.
`Petitioner and Mr. Draper also fail to explain why Mr. Draper chose to
`use an oblong capsule for his calculations. Ex. 1001 ¶ 89. 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.
`19. 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; Ex. 2021, 611 (Fig.
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`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 Roche’s FDA filing to show that naproxen sodium is
`typically used in dosages of 220 mg and 250 mg. Pet. 24–25; Ex. 1010 ¶¶
`84–85, Tables 4a, 4b; Ex. 1025, 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” activity 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
`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
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`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 fill material. 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. 35. Petitioner contends that Kim teaches solubilizing naproxen
`in a pharmaceutical composition by neutralizing a portion of the naproxen
`using sodium citrate. Id. at 35–36. Petitioner contends that Kim also
`teaches the use of polyethylene glycol and other solubilizers. Id. at 38.
`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 of the acid salts to neutralize naproxen would have been
`the same as using the respective acids to neutralize naproxen sodium. Id.
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`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. 37.
`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. Id. at 39 (“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. Id.
`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. Id. at 45. Patent Owner argues that the evidence
`of equivalence cited by Petitioner in fact demonstrates that the two acids are
`not equivalent. Id. at 46–47. Patent Owner also notes that Kim teaches that
`dexibuprofen and naproxen have very different solubilities depending on the
`solvent used. Id. at 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 modifying the compositions
`of Kim nor has Petitioner established that the amounts of naproxen used by
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`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 fill material 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. 37;
`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. 36; Ex. 1001 ¶
`98. Mr. Draper assumes that one skilled in the art would use the same
`amount of lactic acid as citric acid in making his calculation of the
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`percentage of lactic acid that would be used in a naproxen sodium
`containing composition. See Ex. 1001, ¶¶ 62–63.
`As Patent Owner points out, Petitioner has not demonstrated
`sufficiently that citric acid and lactic acid are functional equivalents. Prelim.
`Resp. 44–47. 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; Ex. 2022, 189–190. 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, 414–21. 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. Id. at 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.
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`Kim also does not teach a co