Trials@uspto.gov
`Tel: 571-272-7822
`
`
`Paper 10
`Entered: August 25, 2016
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________
`
`PRAXAIR DISTRIBUTION, INC. and NOxBOX LIMITED,
`Petitioner,
`v.
`INO THERAPEUTICS LLC,
`Patent Owner.
`_______________
`
`Case IPR2016-00781
`Patent 8,846,112 B2
`_______________
`
`
`Before LORA M. GREEN, TINA E. HULSE, and
`ROBERT A. POLLOCK, Administrative Patent Judges.
`
`POLLOCK, Administrative Patent Judge.
`
`
`
`DECISION
`Denying Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`

`

`IPR2016-00781
`Patent 8,846,112 B2
`
` INTRODUCTION
`Petitioner, Praxair Distribution, Inc. (“Praxair”) and NOxBOX Limited
`(“NOxBOX”), filed a Petition (Paper 4; “Pet.”) to institute an inter partes review
`of claims 1–19 of U.S. Patent No. 8,846,112 B2 (Ex. 1001; “the ’112 patent”).1
`Patent Owner, Mallinckrodt Hospital Products IP Ltd.,2 filed a Patent Owner
`Preliminary Response arguing, inter alia, that Petitioner is estopped from
`requesting or maintaining this IPR under 35 U.S.C. § 315(e)(1), and that the Board
`should exercise its discretion to deny this Petition under 35 U.S.C. § 325(d). Paper
`8 (“Prelim. Resp.”), 15–37.
`We have jurisdiction under 35 U.S.C. § 314. For the reasons provided
`below, we deny the Petition for an inter partes review under 35 U.S.C.
`§§ 315(e)(1) and 325(d).
`
` BACKGROUND
`
` The ’112 Patent
`The ’112 patent issued on September 30, 2014, from a series of continuation
`and divisional applications beginning with application No. 12/494,598 filed on
`June 30, 2009. Ex. 1001. The ’112 patent is broadly directed to “methods of
`distributing a pharmaceutical product comprising nitric oxide gas” (id. Abstract)
`and discloses that nitric oxide is a lung-specific vasodilator that significantly
`improves blood oxygenation and reduces the need for extracorporeal oxygenation.
`Id. at 3:36–45, 7:1–29.
`
`
`1 Praxair further identifies Praxair, Inc. as a real party-in-interest. Pet. 8.
`2 Patent Owner further identifies “INO Therapeutics LLC, Mallinckrodt Hospital
`Products, Inc., and Mallinckrodt PLC, affiliates of Mallinckrodt Hospital Products
`IP Ltd.” as real parties-in-interest. Paper 6, 1.
`
` 2
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`IPR2016-00781
`Patent 8,846,112 B2
`
`INOmax® is an FDA-approved blend of nitric oxide and nitrogen, which
`may be administered in conjunction with ventilary support for iNO (inhaled nitric
`oxide) therapy. Id. at 1:20–25, 3:34–36, 3:57–62. The product is approved “for
`treatment of . . . term and near-term (>34 weeks gestation) neonates having
`hypoxic respiratory failure associated with clinical or echocardiographic evidence
`of pulmonary hypertension, a condition also known as persistent pulmonary
`hypertension in the newborn (PPHN).” Id. at 6:34–40. iNO has also been used for
`a variety of other conditions, where it generally “acts by preventing or treating
`reversible pulmonary vasoconstriction, reducing pulmonary arterial pressure and
`improving pulmonary gas exchange.” Id. at 6:40–52.
`Example 1 of the Specification discusses the conduct and results of the
`INOT22 Study, in which children undergoing cardiac catheterization were
`administered oxygen, oxygen in conjunction with iNO, or iNO alone. Id. at 9:35–
`10:27. The Specification states that “[i]dentifying patients with pre-existing LVD
`[left ventricular dysfunction] is known to those skilled in the medicinal arts, and
`such techniques for example may include assessment of clinical signs and
`symptoms of heart failure, or echocardiography diagnostic screening.” Id. at 5:15–
`19. During the INOT22 study, patients with pre-existing LVD experienced an
`increased rate of serious adverse events (SAEs) including pulmonary edema. See,
`e.g., id. at 9:47–51, 14:17–25. In an effort to minimize the risk of adverse events,
`the INOT22 protocol was amended to exclude patients with an elevated pulmonary
`capillary wedge pressure (PCWP). See id. at 14:17–25. PCWP is a measure of left
`atrial pressure that may be used to diagnose LVD. Id. at 5:20–28. The
`Specification states, for example:
`The upper limit of normal PCWP in children is 10-12 mm Hg
`and 15 mm Hg in adults. In INOT22, a baseline PCWP value was not
`
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`IPR2016-00781
`Patent 8,846,112 B2
`
`included as exclusion criteria. However, after the surprising and
`unexpected identification of SAEs in the early tested patients, it was
`determined that patients with pre-existing LVD had an increased risk
`of experiencing an AE or SAE upon administration (e.g., worsening of
`left ventricular function due to the increased flow of blood through the
`lungs). Accordingly, the protocol for INOT22 was thereafter amended
`to exclude patients with a baseline PCWP greater than 20 mm Hg after
`one patient experienced acute circulatory collapse and died during the
`study. The value “20 mm Hg” was selected to avoid enrollment of a
`pediatric population with LVD such that they would be most likely at-
`risk for these SAEs.
`Id. at 12:47–61. In light of the above results indicating that iNO therapy may be
`detrimental to patients with pre-existing LVD, the Specification proposes
`amending the INOmax® prescribing information to include a precaution for
`patients with LVD. Id. at 9:51–53.
` Prior Adjudication of All Claims
`Praxair previously requested inter partes review of claims 1–19 of the ’112
`patent in IPR2015-00529. In our Final Written Decision in that proceeding, we
`determined that Praxiar had demonstrated by a preponderance of the evidence that
`claims 1–8 and 10–19 of the ’112 patent were unpatentable, but determined that
`Praxair had not proven by a preponderance of the evidence that claim 9 was
`unpatentable. Praxair Distribution, Inc. v. Mallinckrodt Hospital Prods. IP Ltd.,
`Case IPR2015-00529, slip op. at 39–42, 46 (July 7, 2016) (Paper 53) (“Praxair
`I”).3
`
`
`3 Praxair also requested, and the Board denied, institution of inter partes review of
`four related patents that share the same specification as the ’112 patent. Praxair
`Distribution, Inc. v. Mallinckrodt Hospital Prods. IP Ltd., Case IPR2015-00522,
`-0524, -00525, -00526, slip op. at 25 (July 29, 2015) (Paper 53).
`
`
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`IPR2016-00781
`Patent 8,846,112 B2
` Illustrative Claim and “Providing . . . Information” Step
`The independent claims at issue, claims 1, 7, 12, and 14 of the ’112 patent,
`involve “supplying [a] cylinder containing compressed nitric oxide gas to a
`medical provider” in conjunction with a “providing . . . information” step,
`generally related to the finding that in patients with pre-existing left ventricular
`dysfunction, inhaled nitric oxide may increase pulmonary capillary wedge pressure
`(PCWP) leading to pulmonary edema, such that iNO is contraindicated in this
`patient subpopulation. The “providing . . . information” step of illustrative claim
`1 (formatted for clarity), is set forth below in italics:
`1. A method of providing pharmaceutically acceptable nitric oxide gas,
`the method comprising:
`obtaining a cylinder containing compressed nitric oxide gas in the form
`of a gaseous blend of nitric oxide and nitrogen:
`supplying the cylinder containing compressed nitric oxide gas to a
`medical provider responsible for treating neonates who have
`hypoxic respiratory failure, including some who do not have left
`ventricular dysfunction;
`providing to the medical provider
`(i) information that a recommended dose of inhaled nitric oxide
`gas for treatment of neonates with hypoxic respiratory failure
`is 20 ppm nitric oxide and
`(ii) information that, in patients with pre-existing left ventricular
`dysfunction, inhaled nitric oxide may increase pulmonary
`capillary wedge pressure (PCWP), leading to pulmonary
`edema,
`the information of (ii) being sufficient to cause a medical
`provider considering inhaled nitric oxide treatment for a
`plurality of neonatal patients who (a) are suffering from a
`condition for which inhaled nitric oxide is indicated, and
`(b) have pre-existing left ventricular dysfunction, to elect to
`avoid treating one or more of the plurality of patients with
`inhaled nitric oxide in order to avoid putting the one or more
`patients at risk of pulmonary edema.
`
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`IPR2016-00781
`Patent 8,846,112 B2
`
`In construing the claims of the ’112 patent in IPR2015-00529, we
`determined that the “information” provided in this, and similarly-worded claim
`steps in other claims, constituted printed matter and, therefore, accorded the term
`no patentable weight with respect to claims 1–8 and 10–19. See Praxair I, 15–21.4
`In the matter before us, Petitioner states that “the instant Petition is crafted under
`the assumption that all of the claim elements in the ’112 patent should be given
`patentable weight” (Pet. 9), but that “[i]f [Praxair I] does not give the ‘providing
`information’ limitations patentable weight, then . . . the Board need not consider
`the present petition except in the eventuality of Federal Circuit reversal” (id. at 12;
`see id. at 1, n.1). Consistent with this focus on the “providing . . . information”
`limitation, Petitioner asserts that the challenged claims are unpatentable in light of
`INOmax label5 (the primary reference asserted in IPR2015-00529) and two
`“recently discovered” references, Greenough6 and Jaypee,7 which allegedly
`disclose the provided “information.” See e.g., Pet. 13–14, 15, 22–25, 33–34.
`
`
`4 We likewise determined that the similar language of independent claim 7, cast as
`“providing . . . a recommendation,” was also entitled to no patentable weight. Id.
`at 21–22; see id. at 21, n.11. For the purpose of this Decision, we consider
`collectively the “providing” limitations of claims 1–8 and 10–19.
`5 Center for Drug Evaluation and Research, Application Number: NDA 20845,
`INOmaxTM, Final Printed Labeling, available at http://www.accessdata.fda.gov
`/drugsatfda_docs/nda/99/20845_INOmax_prntlbl.pdf (August 9, 2000).
`(“INOmax label”). Ex. 1010.
`6 NEONATAL RESPIRATORY DISORDERS, 149, 183–87, 392 (Anne Greenough &
`Anthony D. Milner eds., 2nd ed. 2003) (“Greenough”). Ex. 1006.
`7 Praveen Khilnani, PEDIATRIC & NEONATAL MECHANICAL VENTILATION 148–58
`(Jaypee Brothers Medical Publishers, Ltd., New Dehli, 2006) (“Jaypee”).
`Ex. 1007.
`
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`

`IPR2016-00781
`Patent 8,846,112 B2
`
`We consider below whether Petitioner is estopped from requesting this IPR
`under 35 U.S.C. § 315(e)(1) and, separately, whether the Board should exercise its
`discretion to deny this Petition under 35 U.S.C. § 325(d).
`
` ANALYSIS – 35 U.S.C. § 315(e)(1)
`Once a Petitioner has obtained a final written decision, that Petitioner may
`not request or maintain subsequent proceedings on a ground that it “reasonably
`could have raised” during the prior proceeding. See Dell Inc. v. Elecs. and
`Telecomms. Research Inst., IPR2015-00549, slip. op. 4–6 (PTAB Mar. 26, 2015)
`(Paper 10) (representative). Specifically, section 315(e)(1) of the Patent Statute
`provides:
`
`(e) Estoppel. —
`(1) Proceedings before the office.—The petitioner in an inter
`partes review of a claim in a patent under this chapter that results in a
`final written decision under section 318(a), or the real party in interest
`or privy of the petitioner, may not request or maintain a proceeding
`before the Office with respect to that claim on any ground that the
`petitioner raised or reasonably could have raised during that inter partes
`review.
`35 U.S.C. § 315(e)(1); see 37 C.F.R. § 42.73(d).
`As in this proceeding, Praxair challenged claims 1–19 of the ’112 patent in
`IPR2015-00529. On July 7, 2016, that earlier proceeding resulted in a final written
`decision, pursuant to 35 U.S.C. § 318(a).
`The legislative history of the America Invents Act broadly describes grounds
`that “reasonably could have been raised” as encompassing “prior art which a
`skilled searcher conducting a diligent search reasonably could have been expected
`to discover.” 157 Cong. Rec. S1375 (daily ed. Mar. 8, 2011) (statement of Sen.
`Kyl); see id. at S1376 (statement of Sen. Kyl) (“This [estoppel] effectively bars
`
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`IPR2016-00781
`Patent 8,846,112 B2
`
`such a party or his real parties in interest or privies from later using inter partes
`review . . . against the same patent, since the only issues that can be raised in an
`inter partes review . . . are those that could have been raised in [an] earlier post-
`grant or inter partes review.”); 157 Cong. Rec. S952 (daily ed. Feb. 28, 2011)
`(statement of Sen. Grassley) (“It also would include a strengthened estoppel
`standard to prevent petitioners from raising in a subsequent challenge the same
`patent issues that were raised or reasonably could have been raised in a prior
`challenge.”).
` Whether Praxair Reasonably Could Have Raised Greenough and
`Jaypee During the Earlier Proceeding and Is, Therefore, Estopped
`Under 35 U.S.C. § 315(e)
`Petitioner describes Greenough as “a textbook on neonatal respiratory
`disorders, including indications and contraindications for iNO treatment,”
`including “an entire chapter dedicated to the treatment of persistent pulmonary
`hypertension of the newborn (“PPHN”).” Pet. 22–23. Petitioner similarly
`describes Jaypee as “a textbook on pediatric and neonatal mechanical ventilation
`that reviews pediatric conditions, including pulmonary hypertension and PPHN,”
`and encompasses “an entire chapter on iNO.” Id. at 23–24. Despite their evident
`relevance to the subject matter of the ’112 patent, Petitioner contends that
`“[d]espite conducting diligent searches, Praxair did not find the Greenough or
`Jaypee references prior to filing the first set of IPRs,” including IPR2015-00529.
`Id. at 15. We infer that these references came to Petitioner’s attention some time
`after they were cited by the Examiner during the prosecution of one or more
`applications related to the ’112 patent. See Pet. 15; Prelim. Resp. 18, 35; Ex. 2014,
`3, 5, 21–23 (April 29, 2015, Office Action, Notice of References Cited, and
`
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`IPR2016-00781
`Patent 8,846,112 B2
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`Examiner’s Search Report for Application No. 14/454,373, each citing Greenough
`and Jaypee).
`As evidence of diligence in searching the prior art, Petitioner submits
`Exhibit 1009, an “Exemplary List of Search Results from Cardinal Intellectual
`Property, Inc.” Pet. 15. But, as Patent Owner points out, Petitioner’s assertion that
`it did not find Greenough or Jaypee “[d]espite conducting diligent searches” is
`predicated on a single search report by an unidentified searcher of indeterminate
`skill and experience listing a mere fifteen “exemplary” search results. See Prelim.
`Resp. 18–19; Pet. 15; Ex. 1009. Petitioner does not, as Patent Owner points out,
`“identify the actual searcher, his or her skill level and experience in the field, []
`why he or she searched using certain keywords and keyword combinations,” or
`explain whether either Greenough or Jaypee were encompassed by the initial
`search results but not selected for the exemplary list. Prelim. Resp. 19. On the
`record before us, we, therefore, find scant evidence that Praxair engaged “a skilled
`searcher conducting a diligent search” as contemplated in the legislative history.
`See 157 Cong. Rec. S1375.
`Also at odds with Petitioner’s assertion of diligence is Petitioner’s
`contention that “a person of skill in the art would have been seeking out
`[Greenough and Jaypee] when trying to ascertain the collective academic thinking
`regarding iNO therapy as of the [earliest priority date]” of the ’112 patent. Pet. 26.
`In addition, the testimony of Petitioner’s technical expert, Dr. Lawson, evidences
`that the newly-asserted references are not obscure texts unlikely to be discovered
`upon a reasonably diligent search of the relevant prior art. In particular,
`Dr. Lawson states that:
`A person of skill in the art interested in iNO treatment would have
`referred to the INOmax Label, Greenough and Jaypee as they are all
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`IPR2016-00781
`Patent 8,846,112 B2
`
`part of a collected literature regarding treatment of patients with iNO.
`Anne Greenough, the author of Greenough, is a thought leader in this
`area. Moreover, the authors of Greenough and Jaypee are familiar with
`each other’s works; for example, Jaypee cites other articles authored by
`Anne Greenough.
`Ex. 1002 ¶ 51. Consistent with Dr. Lawson’s testimony, Petitioner admits that
`“other articles by the author of Greenough were cited during prosecution” (Pet. 24,
`n.11), whereas Patent Owner provides evidence that Greenough is catalogued and
`accessible “at dozens of major libraries in the United States, including the Library
`of Congress, the National Library of Medicine, and the Harvard University
`Library,” and that both textbooks are readily identified by searching Google Books
`using keywords from the ’112 Patent specification. Prelim. Resp. 17–18 (citing
`Exs. 2003, 2008-2013).
`On the record before us, we are not persuaded that Petitioner has
`demonstrated that a skilled searcher conducting a diligent search would not have
`expected to discover Greenough and Jaypee. Accordingly, we determine that
`Petitioner Praxair reasonably could have raised the grounds asserted here in
`IPR2015-00529. And, because Praxair previously challenged claims 1–19 of the
`’112 Patent in IPR2015-00529, which resulted in a final decision under § 318(a), it
`is now estopped under 35 U.S.C. § 315(e)(1) from requesting or maintaining the
`current proceeding before the Office with respect to those claims. See Westlake
`Servs., LLC v. Credit Acceptance Corp., No. CBM2014-00176, slip. op. 3–5
`(PTAB May 14, 2015) (precedential) (applying estoppel provision to all claims
`subject to a final written decision).
`
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`IPR2016-00781
`Patent 8,846,112 B2
` Whether Praxair’s Foreign Subsidiary, NOxBOX, is Estopped
`Under 35 U.S.C. § 315(e)
`As noted above, the estoppel provision of 35 U.S.C. § 315(e) expressly
`applies not only to a named petitioner, but to “a real party in interest or privy of the
`petitioner.” Our rules similarly provide that:
`A petitioner, or the real party in interest or privy of the petitioner, is
`estopped in the Office from requesting or maintaining a proceeding
`with respect to a claim for which it has obtained a final written decision
`on patentability in an inter partes review . . . on any ground that the
`petitioner raised or reasonably could have raised during the trial.
`37 C.F.R. § 42.73(d)(1) (emphasis added).
`“[A]t a general level, the ‘real party-in-interest’ is the party that desires
`review of the patent” whereas, “[t]he notion of ‘privity’ is more expansive,
`encompassing parties that do not necessarily need to be identified in the petition as
`a ‘real party-in-interest.’” Office Patent Trial Practice Guide, 77 Fed. Reg. 48,756,
`48,759 (Aug. 14, 2012). “Privity is essentially a shorthand statement that collateral
`estoppel is to be applied in a given case . . . . The concept refers to a relationship
`between the party to be estopped and the unsuccessful party in the prior litigation
`which is sufficiently close so as to justify application of the doctrine of collateral
`estoppel.” Id. (quoting 154 Cong. Rec. S9987 (daily ed. Sept. 27, 2008) (statement
`of Sen. Kyl)). In determining whether privity exists, “[t]he emphasis is not on the
`concept of identity of parties, but on the practical situation.” Id.
`Petitioner discloses that NOxBOX, a UK company, “is an iNO delivery
`device manufacturer and was recently acquired by Praxair, Inc., to complement
`Praxair Distribution, Inc. which is the manufacture of iNO drug to be marketed
`under the brand NoxiventTM.” Pet. 8, 17.
`
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`IPR2016-00781
`Patent 8,846,112 B2
`
`We agree with Patent Owner. NOxBox is a privy of Praxair, Inc., a real
`party-in-interest in IPR2015-00529 (as well as in the instant case). See Pet. 8;
`IPR2015-00529, Paper 1 at 6. Under the facts before us, we determine that
`NOxBOX is estopped under § 315(e) from participating in this proceeding and,
`accordingly, deny the instant Petition for an inter partes review.
`
` ANALYSIS – 35 U.S.C. § 325(d)
`
`Patent Owner argues that the Board should exercise its discretion under
`35 U.S.C. § 325(d) to deny the instant Petition because Praxair “advances
`substantially the same arguments it presented in the prior -00529 proceeding,”
`“was, or should have been, aware of the newly asserted Greenough and Jaypee
`references when it filed its first petition,” and “is unfairly using the previous IPR
`proceeding as a roadmap to remedy the deficiencies in its first petition.” Prelim.
`Resp. 2, 21–37. Petitioner, in contrast, contends that “the Board should institute
`trial in light of the discretion permitted by 35 U.S.C. § 325(d)” because the instant
`Petition “is directed to entirely new art and arguments, including specific
`recitations of information” recited in the claimed “providing” steps. Pet. 1; see id.
`at 12–14.
`We do not find Petitioner’s arguments persuasive. Although Petitioner now
`relies on Greenough and Jaypee, its underlying argument—that the prior art taught
`or suggested the exclusion of neonates with LVD from iNO treatment—is
`essentially the same as that raised in IPR2015-00529. Whereas Petitioner
`characterizes its present art and arguments as “explicitly contraindicat[ing] patients
`with LVD from iNO treatment” and “substantially different from those previously
`considered by the Office because all of the references unquestionably relate to
`neonates” (Pet. 13–14), the earlier Petition asserted that “Bernasconi discloses that
`
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`iNO can lead to pulmonary edema in neonates with LVD,” such that one of
`ordinary skill in the art would “look to Bernasconi . . . to understand the additional
`contraindications and potential adverse reactions, beyond those approved by the
`FDA, relating to iNO therapy.” Praxair Distribution, Inc. v. Mallinckrodt Hospital
`Prods. IP Ltd., Case IPR2015-00529, Paper 1 at 11, 19 (July 5, 2015).
`Petitioner’s “entirely new” argument, thus, appears to be that Greenough and
`Jaypee expressly state that which one of ordinary skill in the art would have
`understood from the art cited in IPR2015-00529. Further, given that Petitioner
`raises Greenough and Jaypee as allegedly disclosing the same “information” that
`we previously accorded no patentable weight in the “providing” limitations of
`claims 1–8 and 10–19, Petitioner’s argument with respect to these claims is
`effectively unchanged as compared to the prior IPR proceeding. See section II(B)
`and (C), supra.
`Accordingly, because, Petitioner now advances the same or substantially the
`same arguments it presented in IPR2015-00529 and because, as discussed above, it
`should have been aware of the newly-cited Greenough and Jaypee references when
`it filed the earlier Petition, we exercise our discretion under § 325(d) to deny the
`instant Petition with respect to all challenged claims.
`
` ORDER
`
`For the reasons given, it is
`ORDERED that Praxair Distribution Inc., and NOxBOX Limited are
`estopped under § 315(e) from participating in this proceeding and, accordingly, the
`Petition for an inter partes review is denied; and
`FURTHER ORDERED that the Petition is denied under § 325(d) with
`respect to all claims.
`
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`IPR2016-00781
`Patent 8,846,112 B2
`
`
`PETITIONER:
`
`Benjamin Weed
`benjamin.weed.PTAB@klgates.com
`
`Sanjay K. Murthy
`sanjay.murthy@klgates.com
`
`Sara Kerrane
`Sara.kerrane@klgates.com
`
`Margaux Nair
`margaux.nair@klgates.com
`
`Maria Doukas
`maria.doukas@klgates.com
`
`
`
`
`PATENT OWNER:
`
`Bob Steinberg
`bob.steinberg@lw.com
`
`Daniel Brown
`daniel.brown@lw.com
`
`
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