Trials@uspto.gov
`571-272-7822
`
` Paper No. 82
` Entered: March 31, 2017
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`STEADYMED LTD.,
`Petitioner,
`
`v.
`
`UNITED THERAPEUTICS CORPORATION,
`Patent Owner.
`____________
`
`Case IPR2016-00006
`Patent 8,497,393 B2
`____________
`
`Before LORA M. GREEN, JONI Y. CHANG, and
`JACQUELINE T. HARLOW, Administrative Patent Judges.
`
`HARLOW, Administrative Patent Judge.
`
`FINAL WRITTEN DECISION
`35 U.S.C. § 318(a) and 37 C.F.R. § 42.73
`
`Liquidia - Exhibit 1005 - Page 1
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`
`571-272-7822
`
` Paper No. 82
` Entered: March 31, 2017
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`STEADYMED LTD.,
`Petitioner,
`
`v.
`
`UNITED THERAPEUTICS CORPORATION,
`Patent Owner.
`____________
`
`Case IPR2016-00006
`Patent 8,497,393 B2
`____________
`
`Before LORA M. GREEN, JONI Y. CHANG, and
`JACQUELINE T. HARLOW, Administrative Patent Judges.
`
`HARLOW, Administrative Patent Judge.
`
`FINAL WRITTEN DECISION
`35 U.S.C. § 318(a) and 37 C.F.R. § 42.73
`
`Liquidia - Exhibit 1005 - Page 1
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`INTRODUCTION
`I.
`Petitioner, SteadyMed LTD (“SteadyMed”), filed a Petition on
`October 2, 2015, requesting an inter partes review of claims 1–22 of
`U.S. Patent No. 8,497,393 B2 (Ex. 1001, “the ’393 patent”). Paper 1
`(“Pet.”). Patent Owner, United Therapeutics Corporation (“UTC”), filed a
`Preliminary Response on January 14, 2016. Paper 10 (“Prelim. Resp.”).1
`We determined that the information presented in the Petition demonstrated
`that there was a reasonable likelihood that SteadyMed would prevail with
`respect to at least one challenged claim. Pursuant to 35 U.S.C. § 314, we
`instituted trial on April 8, 2016, as to claims 1–22 of the ’393 patent.
`Paper 12 (“Dec.”).2
`After institution, UTC filed a Patent Owner Response. Paper 31
`(“PO Resp.”).3 SteadyMed filed a Reply to the Patent Owner Response.
`Paper 51 (“Pet. Reply”).4
`In addition, SteadyMed filed a Motion to Exclude Evidence (Paper 63,
`“Pet. Mot. Exclude”).5 UTC filed an Opposition (Paper 66, “PO Opp.
`Exclude”), and SteadyMed filed a Reply (Paper 72, “Pet. Reply Exclude”).
`UTC likewise filed a Motion to Exclude Evidence (Paper 65, “PO Mot.
`
`1 Paper 8 is a redacted version of the Patent Owner Preliminary Response.
`2 Paper 78 is a redacted version of the Decision on Institution.
`3 Paper 76 is a redacted version of the Patent Owner Response to Petition.
`4 Paper 52 is a redacted version of the Reply to Patent Owner’s Response.
`5 Paper 62 is a redacted version of Petitioner’s Motion to Exclude Evidence.
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`Exclude”). SteadyMed filed an Opposition (Paper 68, “Pet. Opp.
`Exclude”),6 and UTC filed a Reply (Paper 71, “PO Reply Exclude”).
`Oral hearing was held November 29, 2016.
`This final written decision is entered pursuant to 35 U.S.C. § 318(a).
`We have jurisdiction under 35 U.S.C. § 6.
`We hold that SteadyMed has demonstrated by a preponderance of the
`evidence that claims 1–22 are unpatentable under 35 U.S.C. § 102(b) and
`35 U.S.C. § 103(a). SteadyMed’s Motion to Exclude is dismissed. UTC’s
`Motion to Exclude is denied.
`
`A. Related Matters
`
`The ’393 patent is asserted in several cases in the District of New
`Jersey. Pet. 1; Paper 4; Paper 15; Paper 21.
`
`B. The ’393 Patent
`
`The ’393 patent, titled “Process to Prepare Treprostinil, the Active
`Ingredient in Remodulin®,” issued July 30, 2013, from U.S. Patent
`Application No. 13/548,446 (“the ’446 application”) (Ex. 1002), filed
`July 13, 2012. Ex. 1001, [54], [45], [21], [22]. The ’446 application is a
`continuation of U.S. Patent Application No. 12/334,731 (“the
`’731 application”) (Ex. 1002), filed on December 15, 2008, now issued as
`U.S. Patent No. 8,242,305 (“the ’305 patent”). Ex. 1001, [63]. The
`
`6 Paper 67 is a redacted version of Petitioner’s Opposition to Patent Owner’s
`Motion to Exclude Evidence.
`
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`’393 patent claims priority to U.S. Provisional Patent Application
`No. 61/014,232 (Ex. 2008), filed December 17, 2007. Ex. 1001, [60].
`The ’393 patent recites 22 product-by-process claims for prostacyclin
`derivatives, including treprostinil.7 Id. at 17:51–21:16; Pet. 5; Prelim.
`Resp. 3. The process disclosed by the ’393 patent takes advantage of carbon
`treatment and salt formation steps to remove impurities, eliminating the need
`for purification by column chromatography. Id. at 17:29–32; see also id.
`at 5:41–45 (“[P]urification by column chromatography is eliminated . . . .
`[T]he salt formation is a much easier operation than column
`chromatography.”).
`The process for forming prostacyclin derivatives described in the
`’393 patent includes four steps: (a) alkylating a prostacyclin derivative to
`form an alkylated prostacyclin derivative; (b) hydrolyzing the alkylated
`prostacyclin derivative with a base to form a prostacyclin acid;
`(c) contacting the prostacyclin acid with a base to form a prostacyclin
`carboxylate salt; and (d) optionally reacting the prostacyclin carboxylate salt
`formed in (c) with an acid to form the desired compound, or
`pharmaceutically acceptable salt thereof. Id. at 1:65–3:19.
`
`
`7 The ’305 patent, which issued from the parent to the application for the
`’393 patent, recites claims to a process for the preparation of prostacyclin
`derivatives comprising steps similar to those set forth in the product-by-
`process claims of the ’393 patent. Compare Ex. 1001, 17:51–21:16, with
`Ex. 2007, 17:39–24:3.
`
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`C.
`
`Illustrative Claim
`
`Each of the challenged claims is a product-by-process claim. Of the
`challenged claims, claims 1 and 9 are independent. Claim 1, reproduced
`below, is illustrative of the claimed subject matter.
`1.
`A product comprising a compound of formula I
`
`or a pharmaceutically acceptable salt thereof, wherein said
`product is prepared by a process comprising
`a) alkylating a compound of structure II with an alkylating
`agent to produce a compound of formula III,
`
`wherein [recitation of Markush groups for the specified
`structures],
`b) hydrolyzing the product of formula III of step (a) with
`a base,
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`c) contacting the product of step (h)8 with a base B to form
`a salt of formula Is.
`
`and
`
`d) optionally reacting the salt formed in step (c) with an
`acid to form the compound of formula I.
`
`Ex. 1001, 17:51–19:29. Claim 9 is drawn to a product comprising a specific
`treprostinil compound within the genus set forth in claim 1, and made by the
`process recited in claim 1. Id. at 19:48–20:46.
`
`D. Prior Art Relied Upon
`
`In its Petition, SteadyMed relies upon the following prior art
`references (Pet. 4–6):
`Phares
`WO 2005/007081 A2
`Kawakami
`JP 56-122328A
`
`Jan. 27, 2005
`Sept. 25, 1981
`
`(Ex. 1005)
`(Ex. 1006)9
`
`Moriarty et al., The Intramolecular Asymmetric Pauson-Khand Cyclization
`as a Novel and General Stereoselective Route to Benzindene Prostacyclins:
`
`8 We note that the reference to “step (h),” rather than “step (b),” in claim 1 is
`an apparent typographical error. See Ex. 1001, 3:66–67 (“(c) contacting the
`product of step (b) with a base B to for a salt of formula IVs”); see also
`Pet. 25; Ex. 1009 ¶ 51.
`9 SteadyMed submitted a certified English translation of Kawakami as
`Ex. 1007. Exhibits 1011, 1019, and 1020 are translator declarations attesting
`to the accuracy of that translation.
`
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`Synthesis of UT-15 (Treprostinil), 69 J. Org. Chem. 1890–1902 (2004)
`(“Moriarty”) (Ex. 1004); and
`
`Seyhan N. Eğe, ORGANIC CHEMISTRY 543–547 (2d ed. 1989) (“Eğe”)
`(Ex. 1008).
`
`E. Instituted Grounds of Unpatentability
`We instituted the instant trial based on the following grounds of
`unpatentability:
`
`Claims
`1–5, 7–9, 11–14, and 16–20
`1–5, 7–9, 11–14, and 16–20
`6, 10, 15, 21, and 22
`
`Reference(s)
`
`Basis
`§ 102(b) Phares
`§ 103(a) Moriarty and Phares
`§ 103(a) Moriarty, Phares, Kawakami,
`and Eğe
`
`II. ANALYSIS
`A. Claim Construction
`In an inter partes review, claim terms in an unexpired patent are given
`their broadest reasonable interpretation in light of the specification of the
`patent in which they appear. 37 C.F.R. § 42.100(b). Under the broadest
`reasonable interpretation standard, 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. In re Translogic Tech.,
`Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007). Under this standard, we may
`take into account definitions or other explanations provided in the written
`description of the specification. In re Morris, 127 F.3d 1048, 1054 (Fed.
`Cir. 1997). Any special definition for a claim term must be set forth in the
`
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`specification with reasonable clarity, deliberateness, and precision. In re
`Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994).
`Only those terms that are in controversy need be construed, and only
`to the extent necessary to resolve the controversy. Vivid Techs., Inc. v. Am.
`Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999).
`
`1. “A product comprising a compound [of/having] formula [I/IV] . . .
`or a pharmaceutically acceptable salt thereof” / “product”
`Independent claims 1 and 9 recite the phrase “[a] product comprising
`a compound [of/having] formula [I/IV] . . . or a pharmaceutically acceptable
`salt thereof . . . .” In addition, each challenged dependent claim recites the
`term “product.” In the Decision on Institution, we construed “[a] product
`comprising a compound [of/having] formula [I/IV] . . . or a pharmaceutically
`acceptable salt thereof” to mean “a product including, but not limited to, a
`compound [of/having] formula [I/IV] or a pharmaceutically acceptable salt
`thereof.” We additionally determined that the claim term “product,” as it is
`used in the ’393 patent, does not require interpretation because the claimed
`“product” is defined by the limitations recited in the challenged claims.
`In its Patent Owner Response, UTC contends that our constructions of
`the above terms, as set forth in the Decision on Institution, are unreasonably
`broad. PO Resp. 13. In particular, UTC argues that we erred in interpreting
`the subsidiary term “comprising,” as recited in the larger phrase “[a] product
`comprising a compound [of/having] formula [I/IV] . . . or a pharmaceutically
`acceptable salt thereof” to mean “including, but not limited to.” Id. at 13–
`16. UTC also asserts that we erred in declining to construe “product” as “a
`
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`substance resulting from a chemical reaction,” and having the impurity
`profile conferred by the recited process steps. Id. at 16–18.
`
`a. “Comprising”
`UTC contends that the intrinsic evidence overrides the presumption
`that the transition phrase “comprising,” as recited in the challenged claims,
`is an “open” phrase. Id. at 13. Although UTC does not identify which
`portions of the prosecution history or specification of the ’393 patent support
`deviating from the well-established meaning of “comprising” in patent law,
`UTC nevertheless urges that review of the intrinsic record demonstrates
`disclaimer or disavowal of an open-ended interpretation of “comprising.”
`Id. at 13–16.
`SteadyMed agrees with the construction of “comprising” set forth in
`the Decision on Institution, and contends that “comprising” is a term of art
`in patent law, and not susceptible to the narrow construction proffered by
`UTC. Pet. Reply 21. SteadyMed also observes (id.) that UTC argued in its
`Preliminary Response for broadly construing that term to mean “including
`but not limited to” (Prelim. Resp. 23). SteadyMed further asserts that UTC
`fails to identify any statements in the prosecution history regarding the
`meaning of “comprising,” and improperly conflates the examiner’s
`allowance of the challenged claims with a disavowal of claim scope.
`Pet. Reply 21.
`SteadyMed additionally argues that the interpretation of “comprising”
`proffered by UTC cannot effect UTC’s desired result of limiting the
`challenged claims to require a particular impurity profile. SteadyMed
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`asserts that the record is devoid of support for the conclusion that the
`claimed products and recited processes have unique impurity profiles. Id. at
`22. In this regard, SteadyMed contends that the observed impurity profiles
`are not unique to the challenged claims, but rather, depend on unclaimed
`elements like what solvents were used, whether intermediate products were
`purified, and what bases, acids, or other reactants were used (id. at 23).
`“In the patent claim context the term ‘comprising’ is well understood
`to mean ‘including but not limited to.’” CIAS, Inc. v. Alliance Gaming
`Corp., 504 F.3d 1356, 1360 (Fed. Cir. 2007); see also Genentech, Inc. v.
`Chiron Corp., 112 F.3d 495, 501 (Fed. Cir. 1997) (“‘Comprising’ is a term
`of art used in claim language which means that the named elements are
`essential, but other elements may be added and still form a construct within
`the scope of the claim.”). Moreover, the specification of the ’393 patent
`itself adopts this art-established definition of “comprising,” stating “[t]he
`expression ‘comprising’ means ‘including but not limited to.’ Thus, other
`non-mentioned substances, additives, carriers, or steps may be present.”
`Ex. 1001, 4:23–25.
`Indeed, in its Preliminary Response, UTC noted both that
`“comprising” is a term of art in patent law, and that the specification of the
`’393 patent defines “comprising” consistently with its well-understood
`meaning in arguing that the claim term “[a/the] process comprising” should
`be construed to mean “a/the process including but not limited to.” Prelim.
`Resp. 23–24. In contrast, UTC does not identify, and we do not discern
`support in either the specification or the prosecution history for the
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`proposition that the Applicant disclaimed or disavowed the full scope of
`“comprising.”
`Accordingly, upon review of the parties’ arguments and the evidence
`before us, including the claims, specification, and prosecution history of the
`’393 patent, we conclude that the broadest reasonable interpretation of the
`term “comprising,” as it is used in the ’393 patent, is “including, but not
`limited to.”
`
`b. “Product”
`UTC asserts that both the specification and prosecution history of the
`’393 patent demonstrate that the product of the challenged claims must have
`the particular impurity profile that is conferred by the recited process steps
`(PO Resp. 17), and, thus, the challenged claims exclude products made using
`different processes, such as the process taught by Moriarty (id. at 16). UTC
`further argues that “product” should be construed as “a substance resulting
`from a chemical reaction.” Id. at 17.
`SteadyMed agrees with our determination in the Decision on
`Institution that the term “product,” as it is used in the ’393 patent, does not
`require interpretation because the claimed “product” is defined by the
`limitations recited in the challenged claims. Pet. Reply 21. In this regard,
`SteadyMed points out that UTC’s expert, Dr. Williams, contemplates four
`different meanings for that term, only one of which conforms to the narrow
`interpretation advanced by UTC. Id. at 21–22.
`SteadyMed additionally asserts that UTC’s proffered interpretation of
`“product” cannot effect the desired result of limiting the challenged claims
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`to require a particular impurity profile. SteadyMed argues that the record is
`devoid of support for the conclusion that that claimed processes and their
`products have unique impurity profiles. Id. at 22. In this regard, SteadyMed
`contends that the observed impurity profiles are not unique to the challenged
`claims, but rather, depend on unclaimed elements like what solvents were
`used, whether intermediate products were purified, and what bases, acids, or
`other reactants were used. Id. at 23.
`In patent parlance, “product” claims relate to structural entities, i.e.,
`compositions of matter, machines, and manufactures. 1 DONALD S. CHISUM,
`CHISUM ON PATENTS, § 1.02 (Matthew Bender, 2017) (“Three of the four
`classes of statutory subject matter of utility patents (machines, manufactures,
`and compositions of matter) relate to structural entities and can be grouped
`as ‘product’ claims in order to contrast them with process claims.”); see also
`MPEP § 2103 (9th ed., Rev. 07.2015, November 2015) (“Product claims are
`claims that are directed to either machines, manufactures or compositions of
`matter.”). Accordingly, “[f]or products, the claim limitations will define
`discrete physical structures or materials.” MPEP § 2103.
`That a product is claimed in product-by-process format does not
`support deviation from this rule. Indeed, to subsume evaluation of whether
`the process steps recited in the challenged claims distinguish the claimed
`product from the prior art into the claim construction analysis, as UTC
`suggests, would be to improperly conflate the claim construction
`determination and patentability analysis, and would require importing
`unrecited limitations into the claims. As our reviewing court has explained:
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`“In determining validity of a product-by-process claim, the focus
`is on the product and not the process of making it.” Amgen Inc.
`v. F. Hoffman–La Roche Ltd., 580 F.3d 1340, 1369
`(Fed.Cir.2009). . . . However, there is an exception to this
`general rule that the process by which the product is made is
`irrelevant. As we recognized in Amgen, if the process by which
`a product is made imparts “structural and functional differences”
`distinguishing the claimed product from the prior art, then those
`differences “are relevant as evidence of no anticipation” although
`they “are not explicitly part of the claim.”
`Greenliant Sys., Inc. v. Xicor LLC, 692 F.3d 1261, 1268 (Fed. Cir. 2012).
`Even setting aside the art-established meaning of “product,” UTC’s
`proposed construction of that term as “a substance resulting from a chemical
`reaction,” having the impurity profile conferred by performance of the
`recited process steps is unsupported by either the intrinsic or extrinsic
`evidence of record. Neither the specification nor the prosecution history of
`the ’393 patent defines the term “product.” In addition, the portions of the
`specification to which UTC points comport with an understanding of
`“product” as being defined only by the recited claim elements. For example,
`the bulk of the specification excerpts identified by UTC in its Patent Owner
`Response (PO Resp. 17) as supporting an interpretation of “product” as “a
`substance resulting from a chemical reaction” simply mirror the language of
`the process steps recited in the challenged claims, and do not further
`characterize the claim term “product.” Ex. 1001, 3:3–4, 3:65–66, 6:65–66.
`Reference in the ’393 patent specification to preparing the compound of
`formula II “from a compound of formula XI, which is a cyclization product
`of a compound of formula X” (id. at 7:17) likewise does not support UTC’s
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`proposed construction (PO Resp. 17). Indeed, if any conclusion can be
`drawn from the specification excerpts highlighted by UTC, it is that the
`claim term “product” is defined solely by the recited claim limitations. See
`Ex. 1001, 5:45–46 (referring to the purportedly improved impurity of the
`“product of the process according to the present invention.”).
`Moreover, as UTC’s expert, Dr. Williams explains, “chemists use the
`word ‘product’ in two different contexts, routinely.” Ex. 2059, 248:4–5.
`“[T]here’s the molecular structural context, and then there’s the real-world
`substance context of the word ‘product.’” Id. at 248:19–21. Indeed,
`Dr. Williams’ own writings indicate that the term “product” does not
`necessarily refer to the result of a chemical reaction. Ex. 2020 ¶ 63 (“The
`scarcity of the natural product from marine sources renders Et-743 an
`important target for synthesis.”). Accordingly, we do not agree with UTC
`that the broadest reasonable interpretation of “product” as used in the
`’393 patent includes a requirement that the claimed “product” be “a
`substance resulting from a chemical reaction.”
`Nor do we agree with UTC (PO Resp. 17) that the specification or
`prosecution history of the ’393 patent disclaims or disavows from the scope
`of the term “product” substances having a different overall purity, or
`different impurity profile than is purportedly conferred by the recited
`process steps. “While a court may look to the specification and prosecution
`history to interpret what a patentee meant by a word or phrase in a claim,
`extraneous limitations cannot be read into the claims from the specification
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`or prosecution history.” Bayer AG. v. Biovail Corp., 279 F.3d 1340, 1348
`(Fed. Cir. 2002).
`During prosecution of the ’393 patent, relying on the Declaration of
`Dr. David Walsh (“Walsh Declaration”), the applicants argued that “the
`product of present claims is physically differen[t] than treprostinil produced
`according to the process of Moriarty,” and, therefore, “Moriarty cannot
`anticipate the present claims.” Ex. 1002, 344. In his declaration, Dr. Walsh
`presented a comparison of three certificates of analysis, one for each of
`treprostinil free acid prepared according to Moriarty, treprostinil
`diethanolamine prepared according to challenged claims 1 or 9, and
`treprostinil free acid prepared according to challenged claims 1 or 9.10 Id. at
`347–349. Dr. Walsh went on to testify that the treprostinil of Moriarty was
`physically different from treprostinil prepared according to challenged
`claims 1 or 9 because the former included detectable amounts of certain
`impurities not observed in the latter. Id. at 349. The examiner subsequently
`issued a Notice of Allowance. Id. at 354–360.
`The applicants’ arguments during prosecution concerning the alleged
`physical differences between treprostinil prepared according to Moriarty and
`treprostinil prepared according to the process steps recited in the challenged
`claims are not tantamount to a clear disclaimer or disavowal of the full scope
`of the claim term “product.” As an initial matter, the applicants did not
`
`10 Issued claim 9 of the ’393 patent is identified as claim 10 in the Walsh
`Declaration, and other documents in the prosecution history in the
`’393 patent.
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`identify a specific impurity profile associated with treprostinil produced
`according to the recited process steps that could serve as a definite limitation
`on claim scope; rather, the applicants simply asserted that the Moriarty
`treprostinil was physically different from that made according to the
`’393 patent (Ex. 1002, 344). Moreover, the certificates of analysis for
`treprostinil diethanolamine and treprostinil free acid presented in the Walsh
`Declaration indicate that treprostinil compounds produced according to the
`challenged claims can have different impurity profiles and purity levels,
`suggesting that an attempt to define such parameters would prove elusive.
`Ex. 1002, 348. Indeed, as discussed in greater detail in Parts II.C.2.b,
`II.D.2.e, and II.E.3.d., below, the evidence of record establishes that the
`variability in the impurity profile and overall purity level between individual
`batches of treprostinil produced according to the process steps recited in the
`challenged claims renders the claimed treprostinil structurally and
`functionally the same as treprostinil produced according to Moriarty. In
`addition, even assuming Dr. Walsh’s analysis of the impurity profiles for
`treprostinil produced according to Moriarty and the ’393 patent is correct,
`the prosecution history is devoid of evidence to support the conclusion that
`those differences are due to the recited process steps themselves, and not the
`use of unclaimed reagents and reaction conditions, or that any differences in
`impurity profile extend to the thousands of additional compounds covered
`by the challenged claims.
`The specification of the ’393 patent likewise does not disclaim or
`disavow the full scope of the term “product.” Akin to its arguments
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`concerning the prosecution history of the ’393 patent, UTC does not
`specifically identify the contours of the subject matter purportedly
`disavowed or disclaimed by the specification. In addition, although UTC
`points to Example 6 of the ’393 patent specification, and the related
`discussion, as supporting the conclusion that “the claimed ‘product’ must
`have an impurity profile conferred by its process steps” (PO Resp. 17), UTC
`does not identify, and we do not discern discussion in the specification of the
`impurity profile for treprostinil prepared either by the recited process, or as
`described by Moriarty.
`Example 6 of the specification presents a comparison of processes for
`preparing treprostinil according to Moriarty and a working example of the
`process disclosed in the ’393 patent. Ex. 1001, 15:1–17:26. Example 6
`reports an overall purity of ~99.0% for Moriarty treprostinil, and one of
`99.9% for treprostinil prepared in accordance with the claimed invention.
`Example 6 does not disclose the impurity profile for treprostinil made by
`either process.
`In describing Example 6, the specification states:
`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
`
`17
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`IPR2016-00006
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`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 17:27–40.
`Neither the purported difference in overall purity of treprostinil
`produced according to Moriarty versus that produced according to the
`process of the ’393 patent, nor stated advantages of the ’393 patent process
`as compared to the Moriarty process constitutes a disavowal or disclaimer of
`the full scope of the term “product.” Example 6 includes numerous process
`steps in addition to those recited in the challenged claims, and it is not
`apparent from the specification that the reported purity improvement over
`Moriarty treprostinil is due to the recited process steps, rather than the
`unclaimed steps. Furthermore, as Dr. Williams testifies, “there is the
`possibility for significant batch-to-batch variations in the impurity profile of
`each batch of treprostinil.” Ex. 2020 ¶ 93 (internal quotation omitted). In
`addition, as discussed in greater detail in Parts II.C.2.b., II.D.2.e., and
`II.E.3.d., below, the overall purity for Moriarty treprostinil set forth in the
`’393 patent specification is inconsistent with that reported by Moriarty
`(99.7%) (Ex. 1004, 13), as well as the average purity of 46 commercial
`Moriarty batches (99.7%) (Ex. 1021; Ex. 2059, 218:3–219:20). Lastly, we
`observe that the challenged claims contain no limitations relating to the
`impurity profile of the recited product, “and it is the claims ultimately that
`define the invention.” Purdue Pharma L.P. v. Endo Pharm. Inc., 438 F.3d
`1123, 1136 (Fed. Cir. 2006).
`
`18
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`Accordingly, upon review of the parties’ arguments and the evidence
`before us, including the claims, specification, and prosecution history of the
`’393 patent, we conclude that the term “product,” as it is used in that patent,
`does not require construction because the claimed “product” is defined by
`the limitations recited in the challenged claims. We additionally conclude
`that the broadest reasonable construction of the larger phrase “[a] product
`comprising a compound [of/having] formula [I/IV] . . . or a pharmaceutically
`acceptable salt thereof” is “a product including, but not limited to, a
`compound [of/having] formula [I/IV] or a pharmaceutically acceptable salt
`thereof.”
`
`2. “[A/the] process comprising”
`Claims 1 and 9 recite “[a/the] process comprising.” In the Decision
`on Institution, we construed this term to mean “a/the process including, but
`not limited to.” Dec. 13. Neither SteadyMed nor UTC challenges the
`interpretation set forth in the Decision on Institution. See PO Resp. 13–18;
`Pet. Reply 21–23. Accordingly, for the reasons set forth in the Decision on
`Institution (Dec. 13), we broadly, but reasonably, construe “[a/the] process
`comprising” to mean “a/the process including, but not limited to.”
`
`B. Principles of Law
`
`To establish anticipation, each and every element in a claim, arranged
`as recited in the claim, must be found in a single prior art reference. Net
`MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359, 1369 (Fed. Cir. 2008).
`“A reference anticipates a claim if it discloses the claimed invention ‘such
`
`19
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`that a skilled artisan could take its teachings in combination with his own
`knowledge of the particular art and be in possession of the invention.’”
`In re Graves, 69 F.3d 1147, 1152 (Fed. Cir. 1995) (emphasis omitted)
`(quoting In re LeGrice, 301 F.2d 929, 936 (CCPA 1962)).
`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;
`(3) the level of ordinary skill in the art; and (4) objective evidence of
`nonobviousness. Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966).
`When a work is available in one field of endeavor, design
`incentives and other market forces can prompt variations of it,
`either in the same field or a different one. If a person of ordinary
`skill can implement a predictable variation, § 103 likely bars its
`patentability. For the same reason, if a technique has been used
`to improve one device, and a person of ordinary skill in the art
`would recognize that it would improve similar devices in the
`same way, using the technique is obvious unless its actual
`application is beyond his or her skill. Sakraida [v. Ag Pro, Inc.,
`425 U.S. 273 (1976)] and Anderson’s–Black Rock [v. Pavement
`Salvage Co., 396 U.S. 57 (1969)] are illustrative—a court must
`ask whether the improvement is more than the predictable use of
`prior art elements according to their established functions.
`KSR, 550 U.S. at 417.
`
`20
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`The level of ordinary skill in the art may be reflected by the prior art
`of record. See Okajima v. Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001);
`In re GPAC Inc., 57 F.3d 1573, 1579 (Fed. Cir. 1995); In re Oelrich,
`579 F.2d 86, 91 (CCPA 1978).
`“The objective indicia of non-obviousness play an important role as a
`guard against the statutorily proscribed hindsight reasoning in the
`obviousness analysis.” WBIP, LLC v. Kohler Co., 829 F.3d 1317, 1328
`(Fed. Cir. 2016). Indeed, “evidence of secondary considerations may often
`be the most probative and cogent evidence [of nonobviousness] in the
`record.” Stratoflex, Inc. v. Aeroquip Corp., 713 F.2d 1530, 1538 (Fed. Cir.
`1983).
`
`C. Anticip
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