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`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________
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`STEADYMED LTD.
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`Petitioner
`
`v.
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`UNITED THERAPEUTICS CORPORATION
`
`Patent Owner
`
`
`U.S. Patent No. 8,497,393
`Issue Date: Jul. 30, 2013
`Title: PROCESS TO PREPARE TREPROSTINIL, THE ACTIVE
`INGREDIENT IN REMODULIN®
`_______________
`
`Case IPR2016-00006
`_______________
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`JOINT WRITTEN STATEMENT
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`Mail Stop “PATENT BOARD”
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
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`WEST\269177408.1
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`Pursuant to the Board’s Order in Paper No. 14, United Therapeutics
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`Corporation (“Patent Owner”) and SteadyMed Ltd. (“Petitioner”) hereby
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`submit this Joint Written Statement identifying those parts of the Decision to
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`Institute that should remain under seal, accompanied by a redacted copy of the
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`Decision to Institute. Further, a joint motion to seal is filed concurrently herewith.
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`The portions of the Decision to Institute that are redacted and should remain
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`under seal are as follows (the precise words being redacted are shown in the
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`attached redacted copy of the Decision to Institute):
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`On page 17, lines 21-23;
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`On page 18, line 24;
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`On page 19, lines 1-4, 16-18, and 20-22;
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`On page 20, lines 1-17 and footnote 7; and
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`On page 21, lines 1-3 and 6-9.
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`Patent Owner and Petitioner conferred on April 18, 2016 concerning the
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`specific scope of redactions presented in the attached redacted version of the
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`Decision to Institute. After reviewing and discussing the proposed redactions,
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`Petitioner has indicated that it does not object to the scope of proposed redactions
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`sought by Patent Owner in this filing.
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`Patent Owner therefore respectfully requests that the redacted portions of the
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`Decision to Institute identified in this Joint Written Statement and accompanying
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`redacted version of the Decision to Institute remain under seal.
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`Date: April 21, 2016
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`Respectfully submitted,
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`/s/ Stuart E. Pollack /
`Stuart E. Pollack
`Reg. No. 43,862
`Lisa A. Haile
`Reg. No. 38,347
`Counsel for Petitioner
`
`/s/ Stephen B. Maebius
`Stephen B. Maebius
`Reg. No. 35,264
`Counsel for Patent Owner
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`CERTIFICATE OF SERVICE
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`The undersigned certifies that a copy of the attached Joint Written Statement
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`was served via electronic mail to the following:
`
`Stephen B. Maebius
`George Quillin
`FOLEY & LARDNER LLP
`UT393-IPR@foley.com
`
`Shaun R. Snader
`UNITED THERAPEUTICS CORP.
`ssnader@unither.com
`
`Douglas Carsten
`Richard Torczon
`Robert Delafield
`WILSON, SONSINI, GOODRICH & ROSATI
`dcarsten@wsgr.com
`rtorczon@wsgr.com
`bdelafield@wsgr.com
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`
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`Date: April 21, 2016
`
`
`/s Stuart E. Pollack /
`Stuart E. Pollack, J.D., Ph.D.
`Reg. No. 43,862
`DLA Piper LLP (US)
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`Respectfully submitted,
`
`
`/s Lisa A. Haile /
`Lisa A. Haile, J.D., Ph.D.
`Reg. No. 38,347
`DLA Piper LLP (US)
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
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`STEADYMED LTD.,
`Petitioner,
`
`v.
`
`UNITED THERAPEUTICS CORPORATION,
`Patent Owner.
`____________
`
`Case IPR2016-00006
`Patent 8,497,393 B2
`____________
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`
`
`Before LORA M. GREEN, JONI Y. CHANG, and
`JACQUELINE T. HARLOW, Administrative Patent Judges.
`
`HARLOW, Administrative Patent Judge.
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
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`I.
`INTRODUCTION
`Petitioner, SteadyMed LTD (“SteadyMed”), filed a Petition
`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 101 (“Prelim. Resp.”). We have
`jurisdiction under 35 U.S.C. § 314, 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.”
`For the reasons set forth below, we institute an inter partes review of
`claims 1–22 of the ’393 patent.
`
`A. Related Matters
`The ’393 patent is asserted in: United Therapeutics Corp. v. Sandoz,
`Inc., No. 14-cv-05499 (D.N.J.); United Therapeutics Corp. v. Teva
`Pharmaceuticals U.S.A., Inc., No. 14-cv-05498 (D.N.J.); and United
`Therapeutics Corp. v. Watson Laboratories, Inc., No. 15-cv-05723 (D.N.J).
`Pet. 1. SteadyMed is not party to the above identified litigations. Id.
`
`
`1 Paper 10 is the Unredacted Preliminary Response. Paper 8, filed
`concurrently with Paper 10, is a redacted version of the Preliminary
`Response.
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`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
`’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.2 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 (“purification by column chromatography is eliminated . . . .
`[T]he salt formation is a much easier operation than column
`chromatography.”).
`
`
`2 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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`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.
`
`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
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`a) alkylating a compound of structure II with an alkylating
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`agent to produce a compound of formula III,
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`wherein [recitation of Markush groups for the specified
`structures],
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`b) hydrolyzing the product of formula III of step (a) with
`a base,
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`c) contacting the product of step (h)3 with a base B to form
`a salt of formula Is.
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`and
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`d) optionally reacting the salt formed in step (c) with an
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`acid to form the compound of formula I.
`
`
`3 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.
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`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
`SteadyMed relies upon the following prior art references (Pet. 4–6):
`
`Phares
`WO 2005/007081 A2
`Jan. 27, 2005
`(Ex. 1005)
`Kawakami
`JP 56-122328A
`Sept. 25, 1981
`(Ex. 10064)
`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)
`(“Moriarty”) (Ex. 1004); and
`Seyhan N. Eğe, ORGANIC CHEMISTRY 543–547 (2d ed. 1989) (“Eğe”)
`(Ex. 1008).
`
`E. Asserted Grounds of Unpatentability
`SteadyMed asserts the following grounds of unpatentability (Pet. 3–
`
`4):
`
`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
`
`Basis
`
`Reference(s)
`
`§ 102(b) Phares
`§ 103(a) Moriarty and
`Phares or Kawakami
`§ 103(a) Moriarty, Phares, Kawakami, and Eğe
`
`
`4 SteadyMed submitted a certified English translation of Kawakami as
`Ex. 1007. As discussed in Part II.F below, UTC argues the admissibility of
`this translation.
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`II. ANALYSIS
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`A. 35 U.S.C. § 325(d)
`UTC urges the exercise of our discretion under 35 U.S.C. § 325(d) to
`deny some or all of the grounds of unpatentability presented by SteadyMed
`because the same, or substantially similar issues were addressed during
`prosecution. Prelim. Resp. 25–26. UTC states that the Patent Office
`considered Moriarty alone, and in combination with Phares, during
`prosecution of the ’393 patent. Id. at 8–10, 26. UTC also reports that Phares
`was considered alone, and in combination with Moriarty, during prosecution
`of U.S. Patent Application No. 13/910,583 (“the ’583 application”)
`(Ex. 2010) filed June 5, 2013, which is a continuation of the
`’446 application. Id. at 11–14.
`Regarding the patentability of claims 6, 15, 21, and 22, in particular,
`UTC asserts that Eğe “is nothing more than a first-year organic chemistry
`textbook,” and that SteadyMed “relies on nothing more than conclusory
`statements in three paragraphs of the [Declaration of Jeffery D. Winkler]” to
`support its unpatentability arguments. Id. at 26. UTC therefore contends
`that SteadyMed “has provided no evidence of probative value that is any
`different than what was already before the Patent Office during
`prosecution.” Id. at 26–27.
`Although it is within our discretion to “reject the petition or request
`because, the same or substantially the same prior art or arguments previously
`were presented to the Office” pursuant to 35 U.S.C. § 325(d), we decline to
`do so here.
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`We note that during prosecution of the ’446 application, which issued
`as the ’393 patent, the Examiner rejected the claims as anticipated by
`Moriarty, but subsequently withdrew that rejection, without elaboration, in
`response to a declaration filed by David A. Walsh (“Walsh Declaration”)
`(Ex. 1002, 346–350), one of the named inventors of the ’393 patent, and the
`Executive Vice President of Chemical Research and Development at UTC.
`Ex. 1002, 344, 346–360. Although Phares is listed as a cited reference on
`the face of the ’393 patent (Ex. 1001, [56]), we observe that the Examiner
`neither relied on, nor otherwise discussed Phares during prosecution of the
`’446 application (Ex. 1002, 295–296, 327–330, 359). In addition, neither
`Eğe nor Kawakami was considered during prosecution of the
`’446 application. Id. at 235–359. The grounds of unpatentability asserted in
`the instant Petition likewise differ from the rejections entered by the
`Examiner during prosecution of the ’731 application, the parent to the ’446
`application. See Ex. 1002, 122–124.
`Moreover, as discussed in detail in Part II.B below, the Declaration of
`Jeffrey D. Winkler (“Winkler Declaration”) (Ex. 1009), submitted in support
`of SteadyMed’s Petition, calls into question Dr. Walsh’s conclusion that
`treprostinil prepared according to the process claimed in the ’393 patent is
`“physically different from treprostinil prepared according to the process of
`‘Moriarty’” (Ex. 1002, 347 (¶ 6)). Ex. 1009 ¶¶ 63–71. In addition, as set
`forth in Part II.F, we disagree with UTC’s characterization of Dr. Winkler’s
`testimony as conclusory. See, e.g., Ex. 1009 ¶¶ 80–90.
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`We, therefore, decline to exercise our discretion to deny the Petition
`pursuant to 35 U.S.C. § 325(d). See Nestle USA, Inc. v. Steuben Foods, Inc.,
`Case IPR2014-01235, slip op. at 7 (PTAB Dec. 22, 2014) (Paper 12) (“[W]e
`conclude that Petitioner’s arguments regarding the unpatentability of claims
`18–20, which include arguments relating to Biewendt and a combination of
`references previously not considered and supported by a declaration
`previously not considered, are persuasive. . .”); Merial Ltd., v. Virbac, Case
`IPR2014-01279, slip op. at 9 (PTAB Jan. 22, 2015) (Paper 13) (noting the
`different burdens of proof and evidentiary standards applicable to ex parte
`examination and inter partes review proceedings).
`
`B. 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); see also In re Cuozzo
`Speed Techs., LLC, 793 F.3d 1268, 1278–79 (Fed. Cir. 2015) (“Congress
`implicitly approved the broadest reasonable interpretation standard in
`enacting the AIA,” and “the standard was properly adopted by PTO
`regulation.”), cert. granted sub nom. Cuozzo Speed Techs., LLC v. Lee, 136
`S. Ct. 890 (2016) (mem.). 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 specification with
`reasonable clarity, deliberateness, and precision. In re Paulsen, 30 F.3d
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`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).
`
`“Product” / “A product comprising a compound [of/having] formula [I/IV]
`. . . or a pharmaceutically acceptable salt thereof”
`Independent claims 1 and 9 recite the phrase “[a] product comprising
`a compound [of/having] formula [I/IV] . . . or a pharmaceutically acceptable
`salt thereof . . . .” Ex. 1001, 19:48–20:46. In addition, each challenged
`dependent claim recites the term “product.” Id. at 17:51–21:16. Because the
`parties advance similar arguments pertaining to the construction of these
`terms, we address these terms together.
`SteadyMed asserts that the phrase “[a] product comprising a
`compound [of/having] formula [I/IV] . . . or a pharmaceutically acceptable
`salt thereof” should be interpreted to mean “a chemical composition that
`includes, but is not limited to, a compound of Formula I, or a
`pharmaceutically acceptable salt thereof, and that may also include other
`non-mentioned substances (including impurities), additives, or carriers,
`without limitation as to the types or relative amounts thereof.” Pet. 11.
`SteadyMed contends that because independent claims 1 and 9 recite “[a]
`product comprising,” the claim term “product” should be construed to
`include “the treprostinil compound along with other substances (including
`impurities),” i.e., a “chemical composition.” Id. at 11.
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`UTC counters that “[a] product comprising a compound [of/having]
`formula [I/IV] . . . or a pharmaceutically acceptable salt thereof” should be
`interpreted as “a substance resulting from a chemical reaction constituted
`primarily of formula I/IV or a pharmaceutically acceptable salt thereof.”
`Prelim. Resp. 21. As an initial matter, UTC notes that SteadyMed’s
`proposed construction refers only to Formula I, and asserts that SteadyMed
`“inexplicably read[s] Formula IV out of the term entirely.” Id. at 22.
`UTC further argues that the claims and Specification of the ’393
`patent use “product” to refer to a substance resulting from a chemical
`reaction. Id. at 17. UTC also contends that the prosecution history for the
`’393 patent supports its proposed construction because “during prosecution,
`the Patent Owner and Examiner explicitly discussed the ‘product’ of the
`claims as a real world substance that results from employing a specific
`chemical process, as differentiated from the substance obtained from
`employing a different chemical process.” Id. at 18–19. UTC points to
`chemistry textbooks as buttressing its position that a skilled artisan would
`understand the claim term “product” as referring to “a substance resulting
`from a chemical reaction.” Id. at 19. UTC further reasons that “the
`‘product’ claimed in a product-by-process claim is necessarily a substance
`that results from the process specified in that claim” (id.), and that
`SteadyMed’s proposed construction “contradicts this inherent limitation of
`the claims” (id. at 22).
`On this record, and for purposes of this decision, we interpret the
`phrase “[a] product comprising a compound [of/having] formula [I/IV] or a
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`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.”
`The claim term “product,” as it is used in the ’393 patent, does not
`require construction because the claimed “product” is defined by the
`limitations recited in the challenged claims. This is evidenced by
`independent claims 1 and 9, which recite “[a] product comprising . . . ,” and
`go on to define the essential elements of the claimed product. The
`transitional term “‘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.” Genentech,
`Inc. v. Chiron Corp., 112 F.3d 495, 501 (Fed. Cir. 1997); see also Ex. 1001,
`4:23–25 (defining “comprising” as “including, but not limited to”). Thus,
`the open-ended structure of the challenged claims forecloses limitation of
`the term “product” beyond that achieved by the recited claim elements.
`Indeed, neither UTC nor SteadyMed identifies any disclosure in the
`’393 patent or its prosecution history that necessitates a contrary
`understanding of the term “product.” For example, the portions of the
`Specification to which UTC points comport with an understanding of
`“product” as being defined only by the recited claim elements. See
`Ex. 1001, 5:45–46, 7:16–20, 17:37–40. Furthermore, far from disavowing
`or otherwise limiting claim scope, the portions of the prosecution history
`identified by UTC are consistent with an understanding that the claimed
`“product” is defined solely by the recited claim elements. See Ex. 1002,
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`315, 328–329, 346–350. We similarly are unpersuaded that the chemistry
`textbook glossaries to which UTC points (Exs. 2011, 2012, 2014) provide a
`basis for narrowly interpreting “product” to require that the product result
`from a chemical reaction.
`Regarding the larger claim phrase “[a] product comprising a
`compound [of/having] formula [I/IV] . . . or a pharmaceutically acceptable
`salt thereof,” as explained above, we determine that the embedded claim
`term “comprising” means “including, but not limited to.” See Genentech,
`112 F.3d at 501; see also Ex. 1001, 4:23–25. Accordingly, we reject UTC’s
`proposal that claims 1 and 9 be read to require a product “constituted
`primarily of formula I/IV or a pharmaceutically acceptable salt thereof.”
`Prelim. Resp. 21 (emphasis added).
`
`“[A/the] process comprising”
`SteadyMed argues that the claim phrase “[a/the] process comprising,”
`which appears in independent claims 1 and 9, should be interpreted as “a
`process that includes, but is not limited to, the recited process steps, and may
`include, without limitation, any other non-recited steps.” Pet. 12. UTC
`counters that this claim phrase should be construed to mean “a/the process
`including but not limited to.” Prelim. Resp. 23–24. For the reasons set forth
`above, we agree with UTC that these claim phases should be interpreted to
`mean “a/the process including, but not limited to.”
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`Product-by-Process Claims
`Each of the challenged claims is a product-by-process claim.
`Ex. 1001, 17:51–21:16; Pet. 5; Prelim. Resp. 3. The general rule when
`determining patentability of a product-by-process claim is to “focus . . . on
`the product and not on the process of making it.” Amgen, Inc. v. Hoffman-
`La Roche Ltd., 580 F.3d 1340, 1369 (Fed. Cir. 2009). This general rule
`embodies the long-standing principle that “an old product is not patentable
`even if it is made by a new process.” Id. at 1370. An exception applies
`when process steps recited in the claim impart “structural and functional
`differences” to the claimed product. Greenliant Sys., Inc. v. Xicor LLC,
`692 F.3d 1261, 1267–1268 (Fed. Cir. 2012). If the exception applies, the
`structural and functional differences conveyed by the recited process steps
`“‘are relevant as evidence of no anticipation’ although they ‘are not
`explicitly part of the claim.’” Id. at 1268 (citing Amgen, 580 F.3d at 1370).
`SteadyMed contends that the challenged claims do not yield a
`treprostinil product having structural or functional differences as compared
`to treprostinil products produced by prior art methods. Pet. 19–22.
`Specifically, SteadyMed asserts that the Walsh Declaration, relied on by
`UTC during prosecution as evidencing differences in the treprostinil
`products of the ’393 patent and Moriarty, fails to demonstrate any functional
`or structural differences between the instantly claimed and prior art
`treprostinil products. Id. SteadyMed relies on the Winkler Declaration
`(Ex. 1009) to support its position. Id.
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`UTC acknowledges that “at the time of the ’393 patent, there existed
`at least three prior art methods” for making treprostinil. Prelim. Resp. 33.
`Relying on the Walsh Declaration, UTC asserts that the process steps recited
`in independent claims 1 and 9 are entitled to patentable weight because they
`yield a “physically different and improved final product with significantly
`reduced overall impurities and a distinct and unexpected impurity profile” as
`compared to treprostinil produced using prior art methods. Id. at 3.
`The Walsh Declaration compares the impurity profile of treprostinil
`free acid “prepared according to the process of ‘Moriarty’” to the impurity
`profiles of treprostinil free acid and treprostinil diethanolamine “prepared
`according to the process specified in claim 1 or [9]” of the ’393 patent.5
`Ex. 1002, 347–348 (¶ 6). Dr. Walsh concludes that the treprostinil free acid
`and treprostinil diethanolamine prepared according to the process of
`claims 1 and 9 is physically different from the treprostinil diethanolamine
`prepared according to the process of Moriarty “at least because neither of
`[the ’393 patent products] contains a detectable amount of any of benzindene
`triol, treprostinil methyl ester, 1AU90 treprostinil stereoisomer and 2AU90
`treprostinil stereoisomer, each of which were present in detectable amounts
`in treprostinil produced according to the process of ‘Moriarty’.” Id. at 349
`(¶ 8). In addition, Dr. Walsh provides “data obtained from representative
`Certificates of Analysis” indicating that treprostinil free acid “prepared
`
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`5 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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`according to ‘Moriarty’” is 99.4% pure, while the treprostinil free acid and
`treprostinil diethanolamine “prepared according to the process specified in
`claim 1 or [9]” are 99.8% pure and 99.9% pure, respectively. Id. at 347–348
`(¶ 6).
`
`SteadyMed disputes Dr. Walsh’s contention that there are physical
`differences between the treprostinil products of the ’393 patent and prior art.
`Pet. 19–22; see also Ex. 1009 ¶¶ 63–71. As an initial matter, SteadyMed
`points out that the 99.7% treprostinil purity reported by Moriarty (Ex. 1004,
`13) is higher than the 99.5% purity recited in claims 2 and 10 of the
`’393 patent, the only challenged claims that recite a purity level. Pet. 20; see
`also Ex. 1009 ¶ 65. In addition, Dr. Winkler testifies that the limited sample
`set, consisting of “only two specific batches of treprostinil” (Ex. 1009 ¶ 66),
`and absence of any disclosure concerning the reaction conditions, reagents,
`and solvents used in carrying out the process of claims 1 and 9 of the
`’393 patent (id. ¶ 67), undermine the veracity of Dr. Walsh’s conclusion
`regarding the purity of these products. Id. ¶¶ 66–67. SteadyMed also
`observes that the statement in the Specification of the ’393 patent that in one
`embodiment the purity of treprostinil is “at least 90.0%, 95.0%, 99.0%,
`99.5%” (Ex. 1001, 8:66–67), supports the conclusion that the 99.8% purity
`purportedly achieved by Dr. Walsh “is based on a particular set of process
`steps that are not claimed and which must have been found after the filing
`date.” Pet. 20.
`Dr. Winkler additionally testifies that the alleged differences in purity
`between the treprostinil batches described by Dr. Walsh are attributable to
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`experimental error. Id. ¶¶ 68–70. Dr. Winkler testifies that “the literature
`on [High Performance Liquid Chromatography’s (“HPLC’s”)] precision
`indicates that the ‘RSD’ or ‘relative standard deviation’ for a typical
`instrument is about 1%. (Ex. 1017.).” Id. ¶ 70. Dr. Winkler further
`observes that “[i]n the present case, we can estimate the precision of the
`equipment the inventors actually used, since the inventors found that
`Example 4’s Batch 1 had an HPLC Assay of 100.4%, which is obviously
`greater than the 100% value theoretically achievable. (Ex. 1001, col. 13,
`lines 50-65).” Id. Dr. Winkler, thus, concludes that “[t]his deviation
`between experimental and theoretical shows that the instrument can have
`variations of at least 0.4%, which is greater than the differences in purity that
`the inventors offered to support their contention regarding greater purity
`over the prior art.” Id. On this record, we credit Dr. Winkler’s testimony, as
`it is consistent with the disclosures of the prior art and the disclosure of the
`’393 patent itself.
`UTC does not challenge SteadyMed’s arguments concerning the
`shortcomings of the Walsh Declaration. Rather, UTC points to
`correspondence with, and reports submitted to, the Food and Drug
`Administration (“FDA”) relating to the acceptance of a supplemental new
`drug application for treprostinil. Prelim. Resp. 36–38. UTC contends that
`these reports show that “
`
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` Prelim.
`
`Resp. 38; see also Ex. 2006, 3–4.
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`17
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`On the record before us, and for purposes of this decision, we
`conclude that the process steps recited in the challenged claims do not
`impart structural or functional differences to the claimed product.
`As an initial matter, we observe that the challenged product-by-
`process claims are drawn to “[a] product comprising a compound” of either
`formula I or formula IV, or a pharmaceutically acceptable salt of the recited
`formula. Ex. 1001, 17:51–19:29, 19:48–20:46). “‘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.” Genentech, 112 F.3d at 501. Thus, a product
`comprising a particular compound must contain that compound, but may
`additionally include other substances, such as impurities. On this record,
`therefore, it is unclear how claims 1, 3–9, and 11–22, which claim a product
`comprising a particular compound, but do not recite limitations concerning
`the purity profile of that product, could be restricted to a product including
`the claimed compound, but also having a particular purity profile. In
`addition, although claims 2 and 10 require a purity of at least 99.5%
`(Ex. 1001, 19:29–30, 20:47–48), these claims similarly are drawn to a
`product comprising a compound, and do not specify the type of impurities
`that may be present in the compound or restrict the amount of any particular
`impurity that may be present, so long as the product remains at least 99.5%
`pure.
`
`Furthermore, the evidence presently before us, including UTC’s own
`testing results, suggests that
`,
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` We observe that UTC offers no explanation for the variation between
`the 99.7% purity reported by Moriarty, and the 99.4% purity Dr. Walsh
`obtained for treprostinil purportedly prepared according to the process
`described by Moriarty. Neither does UTC offer reasoning for crediting
`Dr. Walsh’s results over those reported by Moriarty himself. Similarly,
`UTC neglects Dr. Winker’s assessment of the experimental error present,
`but unaccounted for, in the impurity measurements reported in the Walsh
`Declaration, and fails to account for the absence of any disclosure regarding
`the experimental protocols followed by Dr. Walsh, such as the reaction
`conditions, or the solvents or reagents used, in synthesizing treprostinil
`according to Moriarty or the ’393 patent.
`Moreover, the Process Optimization Report (Ex. 2005) proffered by
`UTC supports the conclusion that
`
`
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`
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`The Process Optimization Report discloses the impurity analyses for
`five batches of treprostinil identified by UTC
`. Ex. 2005, 4–6; see also Prelim.
`
`
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`Resp. 36 (“
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` Notably, UTC’s
`specification for treprostinil produced according to the ’393 patent permits
`
`
`6 We note that UTC likely intended to reference independent claim 9 of the
`’393 patent, rather than dependent claim 10; however our analysis is equally
`applicable to claim 9 or claim 10.
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`each of the following impurities:
`
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`
`. Ex. 2006, 6. The
`analysis of treprostinil purportedly prepared according to the process of
`Moriarty, set forth in the Walsh Declaration, reveals that each of the
`impurities detected in Moriarty treprostinil was present in an amount
`
`
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` Compare
`
`Ex.1002, 347, with Ex. 2006, 6.
`Accordingly, on the record before us, and for purposes of this
`decision, we conclude that the process steps recited in the challenged claims
`of ’393 patent do not impart structural or functional differences to the
`claimed product as compared to prior art processes, and therefore, that these
`process steps do not patentably limit the claimed product. We note,
`however, that the factual dispute between the parties concerning the
`existence of any stru
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