Trials@uspto.gov
`571-272-7822
`
`
`
` Paper 45
`
`Entered: October 8, 2021
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`____________
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`LIQUIDIA TECHNOLOGIES, INC.,
`Petitioner,
`
`v.
`
`UNITED THERAPEUTICS CORPORATION,
`Patent Owner.
`____________
`IPR2020-00770
`Patent 9,604,901 B2
`____________
`
`
`Before ERICA A. FRANKLIN, ZHENYU YANG, and
`JOHN E. SCHNEIDER, Administrative Patent Judges.
`
`PER CURIAM
`
`
`JUDGMENT
`
`Final Written Decision
`Determining Some Challenged Claims Unpatentable
`35 U.S.C. § 318(a)
`
`Denying Petitioner’s Request to Strike
`37 C.F.R. § 42.5
`
`Denying Patent Owner’s Motion to Exclude
`37 C.F.R. § 42.64(c)
`
`Granting Petitioner’s Motion to Submit Supplemental Information
`37 C.F.R. § 42.123(b)
`
`
`
`
`571-272-7822
`
`
`
` Paper 45
`
`Entered: October 8, 2021
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`____________
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`LIQUIDIA TECHNOLOGIES, INC.,
`Petitioner,
`
`v.
`
`UNITED THERAPEUTICS CORPORATION,
`Patent Owner.
`____________
`IPR2020-00770
`Patent 9,604,901 B2
`____________
`
`
`Before ERICA A. FRANKLIN, ZHENYU YANG, and
`JOHN E. SCHNEIDER, Administrative Patent Judges.
`
`PER CURIAM
`
`
`JUDGMENT
`
`Final Written Decision
`Determining Some Challenged Claims Unpatentable
`35 U.S.C. § 318(a)
`
`Denying Petitioner’s Request to Strike
`37 C.F.R. § 42.5
`
`Denying Patent Owner’s Motion to Exclude
`37 C.F.R. § 42.64(c)
`
`Granting Petitioner’s Motion to Submit Supplemental Information
`37 C.F.R. § 42.123(b)
`
`
`
`
`
`IPR2020-00770
`Patent 9,604,901 B2
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`INTRODUCTION
`I.
`Liquidia Technologies, Inc. (“Petitioner”) filed a Petition (Paper 1
`(“Pet.”)), seeking an inter partes review of claims 1–9 of U.S. Patent
`No. 9,604,901 B2 (Ex. 1001, “the ’901 patent”). We instituted trial to review
`the challenged claims. Paper 7 (“Dec.” or “Decision to Institute”).
`Thereafter, United Therapeutics Corporation (“Patent Owner”) filed a
`Response to the Petition (Paper 12, “PO Resp.”), Petitioner filed a Reply
`(Paper 15), and Patent Owner filed a Sur-reply (Paper 25).
`The parties filed a Joint Paper Concerning Petitioner’s Request to
`Strike Portions of Patent Owner’s Paper Nos. 12 and 25 and Exhibits 2002
`and 2025. Paper 29. The parties also briefed the issues of (1) whether we
`should exclude Exhibits 1002 and 1012 (Papers 31, 32, 37), and (2) whether
`Petitioner may submit, as supplemental information, the transcript and order
`from the Markman hearing in a parallel district court case (Papers 38, 40).
`An oral hearing for this proceeding was held on June 23, 2021, and the
`transcript of that hearing is of record. See Paper 44 (“Tr.”).
`The Board has jurisdiction under 35 U.S.C. § 6 and issues this final
`written decision pursuant to 35 U.S.C. § 318(a) and 37 C.F.R. § 42.73. For
`the reasons provided below, we conclude Petitioner has established by a
`preponderance of the evidence that claims 1–5, 8, and 9 are unpatentable.
`Petitioner, however, has not established by a preponderance of the evidence
`that claims 6 and 7 are unpatentable.
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`A. The ’901 Patent
`The ’901 patent relates to “an improved process to convert benzindene
`triol to treprostinil via salts of treprostinil and to purify treprostinil.”
`Ex. 1001, Abstract.
`Prostacyclin derivatives are useful pharmaceutical compounds. Id.
`at 1:23–26. Treprostinil, a known prostacyclin derivative, is the active
`ingredient in Remodulin. Id. at 1:27–32. Before the ’901 patent, treprostinil
`had been prepared as described in Moriarty1 and other prior-art references.
`Id. According to the ’901 patent, because treprostinil is “of great importance
`from a medicinal point of view, a need exists for an efficient process to
`synthesize th[is] compound[] on a large scale suitable for commercial
`production.” Id. at 1:66–2:3.
`The ’901 patent discloses “a process for the preparation of a
`compound having formula IV, or a hydrate, solvate, or pharmaceutically
`acceptable salt thereof.” Id. at 8:44–46. Petitioner represents that Formula IV
`is treprostinil. Pet. 11; Ex. 1002 ¶ 30. Formula IV has the following
`structure:
`
`
`1 Moriarty et al., The Intramolecular Asymmetric Pauson-Khand Cyclization
`as a Novel and General Stereoselective Route to Benzindene Prostacyclins:
`Synthesis of UT-15 (Treprostinil), 69 J. ORG. CHEM. 1890–1902 (2004)
`(Ex. 1009). Moriarty is one of the prior-art references asserted in this
`proceeding.
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`The figure above shows the structure of Formula IV. Ex. 1001,
`8:48–63.
`The process of the ’901 patent comprises
`alkylating a compound of structure V with an alkylating
`(a)
`agent such as ClCH2CN to produce a compound of formula VI,
`hydrolyzing the product of step (a) with a base such as
`(b)
`KOH,
`contacting the product of step (b) with a base B such as
`(c)
`diethanolamine to for [sic] a salt of the following structure, and
`reacting the salt from step (b) with an acid such as HCl to
`(d)
`form the compound of formula IV.
`Id. at 8:65–9:48. Structure V, formula VI, and the salt formed in step (c)
`have the following structures:
`
`
`
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`The figures above show the structures of structure V, formula VI, and
`the salt formed in step (c). Id. at 9:1–28, 9:33–45. The ’901 patent states that
`“[i]n one embodiment, the purity of compound of formula IV is at least
`90.0%, 95.0%, 99.0%, 99.5%.” Id. at 9:49–50.
`According to the ’901 patent:
`The quality of treprostinil produced according to this invention
`is excellent. The purification of benzindene nitrile by column
`chromatography is eliminated. The impurities carried over from
`intermediate steps (i.e. alkylation of triol and hydrolysis of
`benzindene nitrile) are removed during the carbon treatment and
`the salt formation step. Additional advantages of this process are:
`(a) crude treprostinil salts can be stored as raw material at
`ambient temperature and can be converted to treprostinil by
`simple acidification with diluted hydrochloric acid, and (b) the
`treprostinil salts can be synthesized from the solution of
`treprostinil without isolation. This process provides better
`quality of final product as well as saves significant amount of
`solvents and manpower in purification of intermediates.
`Id. at 16:66–17:12, see also id. at 6:4–18 (the same).
`B. Illustrative Claim
`Claim 1 is the only independent claim. With the Certificate of
`Correction (Ex. 1006, 2) incorporated, it is reproduced below:
`A pharmaceutical batch consisting of treprostinil or a salt
`1.
`thereof and impurities resulting from (a) alkylating a benzindene
`triol, (b) hydrolyzing the product of step (a) to form a solution
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`comprising treprostinil, (c) contacting the solution comprising
`treprostinil from step (b) with a base to form a salt of treprostinil,
`(d) isolating the salt of treprostinil, and (e) optionally reacting
`the salt of treprostinil with an acid to form treprostinil, and
`wherein the pharmaceutical batch contains at least 2.9 g of
`treprostinil or its salt.
`C. Instituted Grounds of Unpatentability
`We instituted trial to determine whether the challenged claims are
`unpatentable based on the following grounds:
`References
`Claims Challenged 35 U.S.C. §2
`Phares3
`1–9
`103(a)
`Moriarty, Phares
`1–9
`103(a)
`To support their respective arguments, Petitioner relies on the
`Declaration of Jeffrey D. Winkler, Ph.D. (Exs. 1002, 1017) and Sylvia
`Hall-Ellis, Ph.D. (Exs. 1015, 1052); and Patent Owner relies on the
`Declarations of Rodolfo Pinal, Ph.D. (Exs. 2002, 2025).
`D. Related Matters
`Patent Owner asserted the ’901 patent against Petitioner in United
`Therapeutics Corporation v. Liquidia Technologies, Inc., No. 1:20-cv-00755
`(D. Del.) (“the district court case”). Paper 5, 1.
`Petitioner filed IPR2020-00769, challenging the claims of U.S. Patent
`No. 9,593,066 (“the ’066 patent”), a patent in the same family as
`
`
`2 The Leahy-Smith America Invents Act (“AIA”), Pub. L. No. 112-29,
`125 Stat. 284, 287–88 (2011), amended 35 U.S.C. §§ 102 and 103, effective
`March 16, 2013. Because the ’901 patent has an effective filing date prior to
`March 16, 2013, we apply the pre-AIA version of § 103.
`3 PCT Application No. WO 2005/007081 A9, published Jan. 27, 2005
`(Ex. 1008).
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`the ’901 patent. Id. We declined to institute trial in that case.
`IPR2020-00769, Paper 7.
`U.S. Patent No. 8,497,393 (Ex. 1004, “the ’393 patent”) is a parent of
`the ’901 patent. Ex. 1001, code (63). The ’393 patent is the subject of
`SteadyMed Ltd. v. United Therapeutics Corp., IPR2016-00006
`(“the ’393 IPR”). The petition for the ’393 IPR challenged claims 1–5, 7–9,
`11–14, and 16–20 of the ’393 patent as anticipated by Phares, and as obvious
`over Moriarty and Phares. IPR2016-00006, Paper 82 (PTAB March 31,
`2017) (“the ’393 Decision” or “the ’393 Dec.”), 7. It also challenged claims
`6, 10, 15, 21, and 22 as obvious over Moriarty, Phares, and additional prior
`art. Id.
`Claim 9 of the ’393 patent recites:
`9. A product comprising a compound of formula IV
`
`
`or a pharmaceutically acceptable salt thereof, wherein said
`product is prepared by a process comprising
`(a) alkylating a compound of structure V with an alkylating agent
`to produce a compound of formula VI,
`
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`(b) hydrolyzing the product of formula VI of step (a) with a base,
`(c) contacting the product of step [(b)] with a base B to form a
`salt of formula IVs, and
`
`
`(d) optionally reacting the salt formed in step (c) with an acid to
`form the compound of formula IV.
`Formula IV of the ’393 patent is the same as that of the ’901 patent,
`and shows the structure of treprostinil. See the ’393 Dec. 24 (“Claim 9 . . . is
`drawn to a product comprising the specific treprostinil compound.”).
`On March 31, 2017, the ’393 IPR panel held that the petitioner in the
`’393 IPR prevailed in all asserted grounds, and that claims 1–22 of
`the ’393 patent are unpatentable. Id. at 44, 67, 84, 90. Specifically, it
`determined that the petitioner there demonstrated the obviousness of claim 9
`over the combination of Moriarty and Phares. Id. at 44, 68.
`In reaching that conclusion, the ’393 IPR panel found that “an
`ordinarily skilled artisan at the time of invention of the ’393 patent would
`have had a doctorate in chemistry, pharmaceutics, pharmaceutical sciences,
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`medicine, or a related discipline, or a lesser degree in one of those fields,
`with correspondingly more experience.” Id. at 49. It also found that the
`relevant skilled artisan “would have had experience in synthesizing and
`analyzing complex organic compounds.” Id.
`Dr. Winkler, Petitioner’s expert in this proceeding, also provided
`testimony in the ’393 IPR. He testified that “an ordinarily skilled artisan
`would have sought to combine Moriarty and Phares in order to eliminate the
`intermediate purification step taught by Moriarty, thereby increasing
`synthetic efficiency and lowering production costs for treprostinil
`diethanolamine salt.” Id. at 46. The ’393 IPR panel credited this testimony,
`finding that Phares teaches “intermediate purification is unnecessary to the
`production of treprostinil diethanolamine salt by the disclosed process.” Id.
`at 47; see also id. at 50 (“[T]he proposed combination of Moriarty and
`Phares would eliminate the need for intermediate purification as required by
`Moriarty alone, and thereby confer efficiency and cost benefits.”). Thus, it
`determined that “an ordinarily skilled artisan would have sought to combine
`Moriarty and Phares in order to reap these efficiency and cost benefits.” Id.
`at 50.
`The ’393 IPR panel also found “an ordinarily skilled artisan would
`have sought to make the proposed combination for the independent reason
`that Phares is directed to improving treprostinil, and the Moriarty process . . .
`was a well-known way to make treprostinil.” Id. It further found “an
`ordinarily skilled artisan would have a reasonable expectation of success in
`combining Moriarty and Phares.” Id. at 52. The ’393 IPR panel analyzed the
`evidence of objective indicia, including long-felt but unmet need and
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`unexpected results, but found that the evidence did not show nonobvious. Id.
`at 57–67. Thus, it concluded that the combination of Moriarty and Phares
`renders claim 9 of the ’393 patent obvious. Id. at 68.
`The Federal Circuit affirmed that decision. United Therapeutics Corp.
`v. SteadyMed Ltd., 702 F. App’x. 990 (Fed. Cir. 2017).
`E. The Prosecution of the ’901 Patent
`During the prosecution of the ’901 patent, the applicant submitted the
`petition for the ’393 IPR in an IDS. Ex. 1006, 127. Thereafter, the examiner
`issued an office action, rejecting then pending claims 1–3, 6, 8, and 9 as
`anticipated by Moriarty. Id. at 118. The examiner found that those claims are
`product-by-process claims and stated
`[E]ven though product-by-process claims are limited by and
`defined by the process, determination of patentability is based on
`the product itself. The patentability of a product does not depend
`on its method of production. If the product in the product-by-
`process claim is the same or obvious from the product of the prior
`art, the claim is unpatentable even though the prior art product
`was made by a different process.
`Id. at 119 (quoting In re Thorpe, 777 F.2d 695, 698 (Fed. Cir. 1985)).
`The examiner found that
`Moriarty et al disclose[s] a method for preparing treprostinil.
`Said method comprises the steps of: (a) alkylation of benzindene
`triol and (b) hydrolysis of the product of step (a) . . . . 441 g of
`treprostinil (a therapeutically effective amount) was prepared at
`99.7% purity. Moriarty also discloses removing impurities via
`extraction and further purification via crystallization. Although
`the method of Moriarty and the steps recited in the instant claims
`are not identical, the product obtained is the same.
`Id. at 118–19.
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`The examiner also rejected then pending claims 10–12 as obvious
`over Moriarty and Phares. Id. at 120. The examiner acknowledged that
`Moriarty fails to teach the “preparation of a diethanolamine salt of
`treprostinil” and the “preparation of a pharmaceutical product comprising
`diethanolamine salt.” Id. The examiner, however, found “Phares et al
`teach[es] preparation of treprostinil diethanolamine by dissolving treprostinil
`acid and treating it with diethanolamine.” Id. at 121.
`According to the examiner,
`One skilled in the art practicing the invention of Phares would
`have found it obvious to prepare a diethanolamine salt of
`treprostinil prepared by the method of Moriarty. Moriarty
`discloses a method for preparing a treprostinil acid which is a
`needed starting material for the process of Phares. The resulting
`salt would meet the limitations directed to pharmaceutical
`product because treprostinil diethanolamine is the sole claimed
`component of the claimed pharmaceutical product.
`One skilled in the art would have found it obvious to prepare a
`pharmaceutical product from the treprostinil diethanolamine salt
`of Phares prepared from the treprostinil free acid that has been
`obtained by the process of Moriarty.
`
`Id.
`
`In response to the rejections, the applicant cancelled then pending
`claims 2 and 3, and amended other claims. Id. at 96–97. Most significantly,
`the applicant amended claim 1 as follows:
` (Currently Amended) A pharmaceutical batch comprising
`1.
`consisting of treprostinil or a salt thereof and impurities resulting
`from prepared by (a) alkylating a benzindene triol, (b)
`hydrolyzing the product of step (a) to form a solution comprising
`treprostinil, (c) contacting the solution comprising treprostinil
`from step (b) with a base to form a salt of treprostinil, (d)
`isolating the salt of treprostinil, and (e) optionally reacting the
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`salt of treprostinil with an acid to form treprostinil, and, wherein
`the pharmaceutical batch contains at least 2.9 g of treprostinil or
`its salt.
`Id. at 96.
`The applicant also submitted “Patent Owner’s Response and expert
`declarations from Dr. Williams and [Dr.] Ruffolo” from the ’393 IPR. Id.
`at 98. Relying on the expert declarations, the applicant argued that “a
`pharmaceutical batch produced according to steps (a)-(e) of claim l is
`different from the product produced by the process described in
`Moriarty 2004” because “the processes result in products having different
`impurity profiles, and in fact, the pharmaceutical batch of claim 1 has higher
`average purity.” Id. at 99. The applicant highlighted that
`As noted in the Patent Owner’s [’393] IPR Response, the
`differences between claim 1’s pharmaceutical batch and a
`product produced according to the process of Moriarty were
`significant enough to result in FDA’s acceptance of a new purity
`specification for the commercial product, thus proving that the
`products are not the same in the eyes of the FDA.
`Id. As a result, the applicant requested that the examiner withdraw the
`anticipation rejection. Id.
`Regarding the obviousness rejection, the applicant contended that “the
`differences in the resulting products, as explained above, would not have
`been expected based on the prior art.” Id. According to the applicant, “it
`would not have been obvious to use the salt formation step of Phares to
`decrease amounts of stereoisomer impurities of treprostinil” and an
`ordinarily skilled artisan “would have had no reasonable expectation of
`success in removing any undesired treprostinil stereoisomer impurities by
`salt formation and subsequent regeneration of the free acid.” Id. at 99–100.
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`The applicant again emphasized that “even small changes in impurity are
`important to FDA.” Id. at 100. Thus, according to the applicant, “FDA’s
`decision to adopt a new purity specification for the resulting product further
`establishes unobviousness of the presently claimed invention.” Id.
`Thereafter, the examiner withdrew the anticipation and obviousness
`rejections “in view of applicants’ arguments, amendments and the
`accompanying declarations.” Id. at 87. And, after the applicant filed a
`terminal disclaimer to overcome a double-patenting rejection (id. at 73–75),
`the examiner allowed claims 1, 6, and 8–14 (id. at 62), and they issued as the
`challenged claims 1–9. The ’901 patent issued on March 28, 2017, three
`days before the Board issued the ’393 Decision.
`II. ANALYSIS
`A. Principles of Law
`To prevail in this inter partes review, Petitioner “shall have the
`burden of proving a proposition of unpatentability by a preponderance of the
`evidence.” 35 U.S.C. § 316(e); 37 C.F.R. § 42.1(d) (2019).
`A patent claim is unpatentable under 35 U.S.C. § 103(a) if the
`differences between the claimed subject matter and the prior art are such that
`the subject matter, as a whole, would have been obvious at the time the
`invention was made to a person having ordinary skill in the art to which said
`subject matter pertains. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406
`(2007). The question of obviousness is resolved on the basis of underlying
`factual determinations, including (1) the scope and content of the prior art;
`(2) any differences between the claimed subject matter and the prior art;
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`(3) the level of skill in the art; and (4) objective evidence of nonobviousness.
`Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966); KSR, 550 U.S. at 406.
`We analyze the instituted grounds of unpatentability in accordance
`with these principles.
`
`B. Prior Art Disclosures
`1. Moriarty
`Moriarty describes synthesizing treprostinil “via the stereoselective
`intramolecular Pauson-Khand cyclization.” Ex. 1009, 1.4 Formula 7 of
`Moriarty is reproduced below:
`
`
`Id. at 3. Formula 7 of Moriarty depicts the chemical structure of treprostinil.
`Id.
`
`An excerpt of Scheme 4 of Moriarty is reproduced below:
`
`
`4 For Moriarty, the parties cite to the pagination added by Petitioner. For
`consistency, we do the same.
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`Id. at 6. The excerpted portion of Scheme 4 of Moriarty illustrates that
`“[t]riol 34 was alkylated at the phenolic hydroxyl group with use of
`chloroacetonitrile in refluxing acetone with potassium carbonate (34 → 35)
`and nitrile 35 was hydrolyzed with ethanolic potassium hydroxide to yield
`UT-15 (7),” treprostinil. Id. at 8.
`
`2. Phares
`Phares teaches compounds, including treprostinil and derivatives
`thereof, “and methods for inducing prostacyclin-like effects in a subject or
`patient.” Ex. 1008, 8.5 “Treprostinil is a chemically stable analog of
`prostacyclin, and as such is a potent vasodilator and inhibitor of platelet
`aggregation.” Id. Phares states that “[t]he compounds provided herein can be
`formulated into pharmaceutical formulations and medicaments that are
`useful in the methods of the invention.” Id.; see also id. at 48 (“provid[ing]
`for compositions which may be prepared by mixing one or more compounds
`of the instant invention, or pharmaceutically acceptable salts thereof, with
`pharmaceutically acceptable carriers, excipients, binders, diluents or the like,
`to treat or ameliorate a variety of disorders related vasoconstriction and/or
`platelet aggregation”).
`The chemical structure of treprostinil, as shown in Phares, is
`reproduced below:
`
`
`5 For Phares, the parties cite to the original page numbers of the exhibits, and
`not the pagination added by Petitioner. For consistency, we do the same.
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`The figure above shows the structure of treprostinil. Id. at 8.
`Phares teaches that “[a] preferred embodiment of the present
`invention is the diethanolamine salt of treprostinil.” Id. at 9. The structure of
`the diethanolamine salt of treprostinil, as shown in Phares, is reproduced
`below:
`
`
`The figure above shows the structure of treprostinil diethanolamine salt. Id.
`at 96 (claim 49).
`Phares teaches two crystalline forms of treprostinil diethanolamine
`salt, the metastable Form A and the thermodynamically more stable Form B.
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`Id. at 85. Phares states that “[a] particularly preferred embodiment of the
`present invention is form B of treprostinil diethanolamine.” Id. at 9.
`Phares teaches the synthesis of (-)-treprostinil, the enantiomer of
`(+)-treprostinil. Id. at 39–40. Specifically, Phares teaches the following
`reaction procedure:
`
`
`Id. at 40. The figure above shows the reaction procedure for the conversion
`of 11b to 2. Id. Phares describe it as: “(l) i. ClCH2CN, K2CO3. ii, KOH,
`CH3OH, reflux. 83% (2 steps).” Id.
`Phares further teaches that “the enantiomer of the commercial drug
`(+)-treprostinil was synthesized using the stereoselective intramolecular
`Pauson Khand reaction as a key step and Mitsunobu inversion of the side-
`chain hydroxyl group.” Id., see also id. at 39 (“Enantiomers of these
`compounds . . . can be synthesized using reagents and synthons of
`enantiomeric chirality of the above reagents.”).
`C. Claim Construction
`In an inter partes review, we construe a claim term “using the same
`claim construction standard that would be used to construe the claim in a
`civil action under 35 U.S.C. [§] 282(b).” 37 C.F.R. § 42.100(b). Under that
`standard, the words of a claim “are generally given their ordinary and
`customary meaning,” which is “the meaning that the term would have to a
`person of ordinary skill in the art in question at the time of the invention, i.e.,
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`as of the effective filing date of the patent application.” Phillips v. AWH
`Corp., 415 F.3d 1303, 1312–13 (Fed. Cir. 2005) (en banc).
`1. “Pharmaceutical Batch”
`In the Petition, Petitioner argues that no construction of claim terms is
`required and “[a]ll terms should be given their plain and ordinary meaning in
`the art” at the priority date of the ’901 patent. Pet. 18–19. In the Preliminary
`Response, Patent Owner emphasizes the difference between a “compound,”
`as recited in the claims of the ’393 patent, and a “pharmaceutical batch,” as
`recited in challenged claim 1. Paper 6 (“Prelim. Resp.”), 8. In proposing the
`construction for “pharmaceutical batch,” Patent Owner relies on the FDA
`definition of “batch.” Id. at 9.
`In our Decision to Institute, we generally agreed with Patent Owner’s
`proposed construction that
`The POSA viewing the ’901 patent claims in light of the ’901
`patent specification would have understood claim 1’s
`‘pharmaceutical batch’ to be a specific quantity of treprostinil (or
`its salt) that is intended to have uniform character and quality,
`within specified limits, and is produced according to a single
`manufacturing order during the same cycle of manufacture,
`wherein the uniform character and quality is such that it still
`contains impurities resulting from the method by which it is
`produced.
`Dec. 15–16 (quoting Prelim. Resp. 9). Later, in our Decision Denying Patent
`Owner’s Request on Rehearing of Decision on Institution, we clarified that
`“we did not construe the term ‘pharmaceutical batch’ in claim 1 to require
`storage stability.” Paper 14, 6 (citing Dec. 15–16).
`In its Reply, Petitioner argues that Patent Owner’s construction of
`“pharmaceutical batch” “pulls language directly from FDA regulations” and
`18
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`IPR2020-00770
`Patent 9,604,901 B2
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`“creates more ambiguity than clarity by introducing terms that themselves
`would require construction.” Reply 4 (internal quotation marks omitted).
`According to Petitioner, “a POSA would understand ‘pharmaceutical batch’
`to mean one ‘made according to the process recited in steps (a)–(d) and
`optionally (e), wherein no purification steps appear between alkylation and
`salt formation.’” Id. at 5. Petitioner further argues that “under either
`construction, Moriarty discloses a ‘pharmaceutical batch’ of 500g.” Id. at 6.
`As discussed below, we agree with Petitioner that the challenged
`claims exclude any isolation6 between the alkylation and salt formation
`steps. See infra, Section II.C.3. That interpretation, however, flows from the
`language “contacting the solution comprising treprostinil from step (b) with
`a base to form a salt of treprostinil,” and not “pharmaceutical batch.” Id. As
`a result, we decline to adopt Petitioner’s proposed construction of
`“pharmaceutical batch.”
`Claim terms need only be construed to the extent necessary to resolve
`the controversy. Wellman, Inc. v. Eastman Chem. Co., 642 F.3d 1355, 1361
`(Fed. Cir. 2011). Here, we do not need to define the outer bounds of the term
`“pharmaceutical batch” because the parties’ dispute over this term centers on
`the issue of storage stability.7 Patent Owner argues “the correct construction
`
`
`6 The parties use the terms “purification” and “isolation” interchangeably in
`the papers. We use the term “isolation” in this Decision.
`7 The parties agree on the “pharmaceutical” aspect of the term. We note
`the ’901 patent defines “pharmaceutically acceptable” as “being useful in
`preparing a pharmaceutical composition that is generally safe, non-toxic and
`neither biologically nor otherwise undesirable and includes being useful for
`veterinary use as well as human pharmaceutical use.” Ex. 1001, 5:27–31.
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`IPR2020-00770
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`
`of ‘pharmaceutical batch’ requires storage stability such that the batch could
`be stored stably for a period of time customary in pharmaceutical
`manufacturing.” PO Resp. 43 (citing Ex. 2025 ¶ 78)). Petitioner contends
`otherwise. Reply 6 (arguing Patent Owner’s construction “imports storage
`limitations into ‘pharmaceutical batch’ (POR9), but the Board’s construction
`did not (Dec. at 15-16)”). We agree with Petitioner.
`Patent Owner supports its argument, relying on the testimony of
`Dr. Pinal, who in turn relies on the definitions of “batch,” “in-process
`material,” and “lot” in the FDA regulations. Ex. 2025 ¶ 78 (citing Ex. 2004,
`133–34). Even if we consider the FDA regulations, none of the cited
`definitions mentions, let alone requires, storage. Thus, we reiterate that the
`term “pharmaceutical batch” in claim 1 does not require storage stability.
`See Paper 14, 6. This determination as to the scope of “pharmaceutical
`batch” is sufficient for purposes of this Decision, and we need not further
`address the term.
`
`2. “Storing”/“Storage”
`Claim 6 recites “storing a pharmaceutical batch of a salt of treprostinil
`as claimed in claim 1 at ambient temperature, and preparing a
`pharmaceutical product from the pharmaceutical batch after storage.” In our
`Decision to Institute, we agreed with Patent Owner that the terms
`“storing”/“storage” “require that the stored material possesses stability
`sufficient to allow manufacture and which maintains integrity for a sufficient
`period of time to be useful for the preparation of a pharmaceutical product.”
`Dec. 17 (quoting Prelim. Resp. 11).
`
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`
`In its Response, Patent Owner maintains its proposed claim
`construction. PO Resp. 11. Together with its Response, Patent Owner
`submitted the Prosecution History of Application No. 13/933,623
`(“the ’623 application) (Ex. 2028). The ’623 application, issued as Patent
`No. 9,156,786 (the ’786 patent), is the parent of the application that issued as
`the challenged ’901 patent. See Ex. 1001, code (63); Ex. 2028, 264.
`Petitioner asserts that Patent Owner’s proposed construction is
`“inconsistent with its construction of this same term during prosecution of
`the ʼ901 Patent’s parent, the ʼ786 Patent.” Reply 7. We agree.
`During the prosecution of the ’623 application, the applicant amended
`pending claim 1 as following:
`for preparing a
`1.
`(Currently Amended) A process
`pharmaceutical product comprising treprostinil or a treprostinil
`salt, comprising:
`combining treprostinil and a base in solution to form a base
`addition salt;
`allowing crystallization of the base addition salt of treprostinil;
`[[and]]
`collecting the base addition salt of treprostinil, storing the
`collected base addition salt, and preparing a pharmaceutical
`product comprising treprostinil or a treprostinil salt from the base
`addition salt after storage.
`Ex. 2028, 159. The examiner rejected this claim as obvious over Phares and
`another prior art reference. Id. at 172. The examiner specifically addressed
`the limitation directed to storing the treprostinil salt. Id. at 173–74.
`According to the examiner,
`The step of storing the treprostinil diethanolamine salt is
`inherently met by Phares. Examiner is interpreting the term
`
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`“storing” to mean a time period between preparation of
`treprostinil salt and its use in preparation of a pharmaceutical
`product. Said limitation is inherently met by Phares. Phares
`teaches
`preparation
`of
`pharmaceutical
`products
`and
`administration
`of
`said
`compounds
`to
`a
`subject
`(paragraphs [0049], [0071], [0072], [0074]). It is inherent that
`some time elapses between preparation of a compound and its
`use in preparation of a pharmaceutical formulation. Phares
`describes obtaining an X-ray diffraction spectrum of treprostinil
`diethanolamine. It is inherent that while obtaining the X-ray
`diffraction spectrum the compound is being stored.
`
`Id.
`
`In response, the applicant further amended the relevant part of the
`claim to “storing the collected base addition salt at ambient temperature, and
`preparing a pharmaceutical product comprising treprostinil or a treprostinil
`salt from the base addition salt after the storage.” Id. at 189. Relying on a
`Rule 132 Declaration of Dr. Liang Guo, the applicant argued:
`[T]he PTO’s interpretation of the term “storing” is too broad
`even under the broadest reasonable interpretation standard. Even
`under the broadest reasonable interpretation standard, the PTO
`may not erase the meaning of a step in a method claim that is tied
`to the preamble. The claim is directed to “preparing a
`pharmaceutical product.” In the accompanying Guo Declaration,
`Dr. Liang Guo explains that a person of ordinary skill in the art
`would recognize that the term “stored” in the expression “crude
`treprostinil salts can be stored as raw material at ambient
`temperature” in paragraph 0046 of the specification as filed
`means stored for a period of at least three months. Guo
`Declaration at ¶ 6. Thus, “storing” in the context of “preparing a
`pharmaceutical product” would be understood by one of ordinary
`skill in the art to mean a period of at least three months. Based
`on this understanding of “storing,” Phares clearly does not meet
`the storing element of claim 1.
`
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`Id. at 193; see also id. at 198 (Guo Declaration ¶ 6 stating the same). The
`examiner, apparently finding
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