Trials@uspto.gov
`Tel: 571-272-7822
`
` Paper 11
`
`Entered:September 22, 2016
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________
`
`PRAXAIR DISTRIBUTION, INC. and NOxBOX LIMITED,
`Petitioner,
`v.
`
`MALLINCKRODT HOSPITAL PRODUCTS,
`Patent Owner.
`_______________
`
`Case IPR2016-00777 (8,282,966 B2)
`Case IPR2016-00778 (8,431,163 B2)
`Case IPR2016-00779 (8,293,284 B2)
`Case IPR2016-00780 (8,795,741 B2)1
`_______________
`
`Before LORA M. GREEN, TINA E. HULSE, and ROBERT A. POLLOCK,
`Administrative Patent Judges.
`
`HULSE, Administrative Patent Judge.
`
`DECISION
`Denying Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`1 This Decision addresses issues that are common to each of the above-referenced
`cases. We, therefore, issue a single Decision that has been entered in each case.
`
`

`

`IPR2016-00777 (8,282,966 B2); IPR2016-00778 (8,431,163 B2);
`IPR2016-00779 (8,293,284 B2); IPR2016-00780 (8,795,741 B2)
`
`
` INTRODUCTION
`
`Praxair Distribution, Inc. (“Praxair”) and NOxBOX Limited (“NOxBOX”)
`(collectively, “Petitioner”) filed Petitions requesting an inter partes review of:
`(1) claims 1–29 of U.S. Patent No. 8,282,966 B2 ( “the ’966 patent”) (Ex. 1001,
`IPR2016-00777); (2) claims 1–25 of U.S. Patent No. 8,431,163 B2 (“the ’163
`patent”) (Ex. 1001, IPR2016-00778); (3) claims 1–30 of U.S. Patent No.
`8,293,284 B2 (“the ’284 patent”) (Ex. 1001, IPR2016-00779); and (4) claims 1–44
`of U.S. Patent No. 8,795,741 B2 (“the ’741 patent”) (Ex. 1001, IPR2016-00780).
`Paper 4 (IPR2016-00777) (“Pet.”).2, 3 Mallinckrodt Hospital Products IP Ltd.
`(“Patent Owner”) filed a Preliminary Response to each Petition. Paper 8 (“Prelim.
`Resp.”).
`Institution of an inter partes review is authorized by statute when “the
`information presented in the petition . . . and any response . . . 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.” 35 U.S.C. § 314(a); see 37 C.F.R. § 42.108.
`Upon considering the Petitions and Preliminary Responses, we exercise our
`discretion and deny each Petition under 35 U.S.C. §§ 314(a) and 325(d).
`Related Proceedings
`A.
`The parties state that Patent Owner has asserted the ’966 patent against
`Petitioner in a case pending in the U.S. District Court for the District of Delaware,
`
`
`2 The parties make similar arguments in their papers and cite similar evidence in
`each of the cases. Accordingly, citations to papers and exhibits in this Decision
`refer to those filed in IPR2016-00777, unless stated otherwise.
`3 Petitioner filed Petitions as Paper 4 in each of the other proceedings. We refer to
`those Petitions as “-778 Pet.,” “-779 Pet.,” and “-780 Pet.”
`
` 2
`
`
`
`
`
`

`

`IPR2016-00777 (8,282,966 B2); IPR2016-00778 (8,431,163 B2);
`IPR2016-00779 (8,293,284 B2); IPR2016-00780 (8,795,741 B2)
`
`INO Therapeutics LLC v. Praxair Distribution, Inc., No. 1:15-cv-00170 (GMS).
`Pet. 10; Paper 7, 1.
`Praxair previously filed petitions requesting inter partes review of the claims
`of each of the involved patents. Case IPR2015-00522, Paper 1 (the ’966 patent);
`Case IPR2015-00524, Paper 1 (the ’284 patent); Case IPR2015-00525, Paper 1
`(the ’163 patent); Case IPR2015-00526, Paper 1 (the ’741 patent). We denied each
`of those petitions because Petitioner failed to establish a reasonable likelihood that
`it would prevail in its assertion that any of the claims of the involved patents are
`unpatentable. Cases IPR2015-00522, IPR2015-00524, IPR20150-00525,
`IPR2015-00526, Paper 12 (“-522 Dec. Inst.”).
`The Involved Patents
`B.
`The involved patents are all related and share substantially the same
`Specification. The Specification discloses methods of reducing the risk of an
`adverse event, such as pulmonary edema, associated with treating a patient with
`inhaled nitric oxide gas (“iNO”). Ex. 1001, Abstract. Nitric oxide is a lung-
`specific vasodilator that significantly improves blood oxygenation and reduces the
`need for extracorporeal oxygenation. Id. at 3:33–42. INOmax—nitric oxide for
`inhalation—is an FDA-approved drug for treatment of term and near term (>34
`weeks gestation) neonates who have hypoxic respiratory failure associated with
`evidence of pulmonary hypertension, known as persistent pulmonary hypertension
`in the newborn (“PPHN”). Id. at 1:18–22, 6:23–29.
`The Specification also describes the INOT22 Study, which was conducted,
`in part, to assess the safety and effectiveness of INOmax in patients four weeks to
`eighteen years of age undergoing assessment of pulmonary hypertension. Id. at
`9:20–30, 43–44. Initially, the study protocol did not include a baseline pulmonary
`
` 3
`
`
`
`
`
`

`

`IPR2016-00777 (8,282,966 B2); IPR2016-00778 (8,431,163 B2);
`IPR2016-00779 (8,293,284 B2); IPR2016-00780 (8,795,741 B2)
`
`capillary wedge pressure (“PCWP”) value as an exclusion criterion.4 Id. at 12:25–
`26. During the study, at least two patients developed signs of pulmonary edema.
`Id. at 13:2–3. The Specification states “[t]his is of interest because pulmonary
`edema has previously been reported with the use of iNO in patients with LVD [left
`ventricular dysfunction], and may be related to decreasing PVR [pulmonary
`vascular resistance] and overfilling of the left atrium.” Id. at 13:3–6. The
`Specification further states that “after the surprising and unexpected identification
`of SAEs [serious adverse events] in the early tested patients, it was determined that
`patients with pre-existing LVD had an increased risk of experiencing an AE or
`SAE [such as pulmonary edema] upon administration.” Id. at 12:26–30, 13:62–64.
`The study protocol was amended to exclude patients with a baseline PCWP greater
`than 20 mmHg, which was selected to avoid enrolling children with LVD who
`“would be most likely at-risk for these SAEs.” See id. at 12:32–38.
`Illustrative Claim
`C.
`Petitioner challenges: (1) claims 1–29 the ’966 patent (IPR2016-00777);
`(2) claims 1–25 of the ’163 patent (IPR2016-00778); (3) claims 1–30 of the ’284
`patent (IPR2016-00779); and (4) claims 1–44 of the ’741 patent (IPR2016-00780).
`The challenged claims are all similar. Claim 1 of the ’966 patent is illustrative and
`is reproduced below:
`1. A method of reducing the risk of occurrence of pulmonary
`edema associated with a medical treatment comprising inhalation of
`20 ppm nitric oxide gas, said method comprising:
`
`
`4 PCWP provides an estimate of left atrial pressure, which may be used to diagnose
`the severity of left ventricular dysfunction and to measure pulmonary hypertension.
`Ex. 1001, 5:9–18.
`
` 4
`
`
`
`
`
`

`

`IPR2016-00777 (8,282,966 B2); IPR2016-00778 (8,431,163 B2);
`IPR2016-00779 (8,293,284 B2); IPR2016-00780 (8,795,741 B2)
`
`
`(a) performing echocardiography to identify a child in need of 20
`ppm inhaled nitric oxide treatment for pulmonary hypertension,
`wherein the child is not dependent on right-to-left shunting of
`blood;
`(b) determining that the child identified in (a) has a pulmonary
`capillary wedge pressure greater than or equal to 20 mm Hg and
`thus has left ventricular dysfunction, so is at particular risk of
`pulmonary edema upon treatment with inhaled nitric oxide; and
`(c) excluding the child from inhaled nitric oxide treatment, based
`on the determination that the child has left ventricular
`dysfunction and so is at particular risk of pulmonary edema
`upon treatment with inhaled nitric oxide.
`Common among almost all the independent claims of all the involved
`patents is a limitation like step (c) of the ’966 patent claim 1 above, which
`excludes a child from treatment with inhaled nitric oxide based on a determination
`that the patient has left ventricular dysfunction and so is at particular risk of
`pulmonary edema upon treatment with inhaled nitric oxide. See claims 1(c),5 6(c),
`13(e), and 22(e) of the ’966 patent (Ex. 1001, IPR2016-00777); claims 1(c) and
`6(e) of the ’163 patent (Ex. 1001, IPR2016-00778); claims 1(c), 6(c), 13(e), and
`23(e) of the ’284 patent (Ex. 1001, IPR2016-00779); claims 1(e) and 34(e) of the
`’741 patent (Ex. 1001, IPR2016-00780).
`However, not all of the independent claims recite the exact language as
`claim 1(c) above. Certain claims recite excluding a patient from treatment with
`inhaled nitric oxide or, despite the patient’s ongoing need for treatment for hypoxic
`respiratory failure, discontinuing treatment with inhaled nitric oxide after it has
`begun, where the exclusion or discontinuation is based on a determination that the
`
`
`5 For ease of reference, we refer to particular steps of particular claims, e.g.,
`step (c) of claim 1, as “claim 1(c).”
`
` 5
`
`
`
`
`
`

`

`IPR2016-00777 (8,282,966 B2); IPR2016-00778 (8,431,163 B2);
`IPR2016-00779 (8,293,284 B2); IPR2016-00780 (8,795,741 B2)
`
`patient has left ventricular dysfunction and so is at particular risk of pulmonary
`edema upon treatment with inhaled nitric oxide. See claims 12(c) and 20(e) of the
`’163 patent (Ex. 1001, IPR2016-00778); claims 9(e) and 37(e) of the ’741 patent
`(Ex. 1001, IPR2016-00780). Additionally, claim 24 of the ’741 patent recites
`“(d) determining that a second patient . . . has pre-existing left ventricular
`dysfunction, so is at particular risk of increased PCWP leading to pulmonary
`edema upon treatment with inhaled nitric oxide” and then “(e) administering a
`second treatment regimen to the second patient [determined to have LVD],
`wherein the second treatment regimen does not comprise either (i) administration
`of inhaled nitric oxide for 14 days or (ii) administration of inhaled nitric oxide until
`the second patient’s hypoxia has resolved.” Ex. 1001, claim 24 (IPR2016-00780).
`Despite the differences in claim language, we interpret the above “exclusion
`limitations” to require excluding a patient from inhaled nitric oxide treatment—
`either by never treating the patient or discontinuing treatment—after determining
`that the patient has left ventricular dysfunction and so is at particular risk of
`pulmonary edema upon treatment with inhaled nitric oxide.
`
` 6
`
`
`
`
`
`

`

`IPR2016-00777 (8,282,966 B2); IPR2016-00778 (8,431,163 B2);
`IPR2016-00779 (8,293,284 B2); IPR2016-00780 (8,795,741 B2)
`
`
`D.
`
`The Asserted Grounds of Unpatentability
`
`In IPR2016-00777, Petitioner challenges the patentability of claims 1–29 of
`the ’966 patent on the following grounds (-777 Pet. 25–51):
`References
`Basis
`Claims Challenged
`Greenough6 and Jaypee7
`§ 103
`1–3, 5–9, 11, 13–17, 20,
`22–25, and 28
`4, 10, 12, 18, 19, 21, 26,
`27, and 29
`
`Greenough, Jaypee, and
`Widlitz8
`
`§ 103
`
`In IPR2016-00778, Petitioner challenges the patentability of claims
`1–25 of the ’163 patent on the following grounds (-778 Pet. 25–51):
`References
`Basis
`Claims Challenged
`Greenough and Jaypee
`§ 103
`1, 2, 4, 6, 7, 9, 11–13,
`15, 18, 20, 21, 23, and
`25
`3, 5, 8, 10, 14, 16, 17,
`19, 22, and 24
`
`Greenough, Jaypee, and
`Widlitz
`
`§ 103
`
`In IPR2016-00779, Petitioner challenges the patentability of claims
`1–30 of the ’284 patent on the following grounds (-779 Pet. 25–53):
`References
`Basis
`Claims Challenged
`Greenough and Jaypee
`§ 103
`1–3, 5–9, 11, 13, 14, 16–
`18, 21, 23–27, and 29
`
`
`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.
`8 Widlitz et al., Pulmonary Arterial Hypertension in Children, EUROPEAN
`RESPIRATORY JOURNAL (published Jan. 2003) (“Widlitz”). Ex. 1008.
`
` 7
`
`
`
`
`
`

`

`IPR2016-00777 (8,282,966 B2); IPR2016-00778 (8,431,163 B2);
`IPR2016-00779 (8,293,284 B2); IPR2016-00780 (8,795,741 B2)
`
`
`Claims Challenged
`4, 10, 12, 15, 19, 20, 22,
`28, and 30
`
`References
`Greenough, Jaypee, and
`Widlitz
`
`Basis
`§ 103
`
`In IPR2016-00780, Petitioner challenges the patentability of claims
`1–44 of the ’741 patent on the following grounds (-780 Pet. 25–54):
`References
`Basis
`Claims Challenged
`Greenough and Jaypee
`§ 103
`1, 2, 4, 6–14, 17–27, 29–
`35, 37–40, and 42–44
`3, 5, 15, 16, 28, 36, and
`41
`
`Greenough, Jaypee, and
`Widlitz
`
`§ 103
`
`Petitioner also relies on the declaration of Dr. Edward Lawson. Ex. 1002.
`ANALYSIS
`
`Under 35 U.S.C. § 314(a), the Board has discretion to decline to institute an
`inter partes review. Moreover, under 35 U.S.C. § 325(d), the Board may decline
`to institute an inter partes review where “the same or substantially the same prior
`art or arguments previously were presented to the Office.” We determine whether
`to exercise our discretion on a case-by-case basis. In light of the totality of the
`circumstances in these proceedings, we determine that exercising our discretion to
`decline institution is appropriate.
`A. Failure to Address Evidence of Secondary Considerations
`Patent Owner asserts that the INOT22 clinical study was designed by
`leading experts in the field, but did not initially exclude patients with pre-existing
`LVD. Prelim. Resp. 3–9, 35–36. After observing unexpected significant adverse
`effects, the inventors recognized the risks of administering iNO to those patients,
`and the study protocol was amended to exclude patients with pre-existing non-
`RTL-dependent LVD. Id. at 9–12. Accordingly, Patent Owner argues that
`
` 8
`
`
`
`
`
`

`

`IPR2016-00777 (8,282,966 B2); IPR2016-00778 (8,431,163 B2);
`IPR2016-00779 (8,293,284 B2); IPR2016-00780 (8,795,741 B2)
`
`Petitioner’s assertion that the claims are obvious “is belied by the overwhelming
`evidence that [persons of ordinary skill in the art] did not expect the results of the
`INOT22 study at the time of the inventions.” Id. at 35.
`In response to similar arguments in the prior proceedings, we found that
`“[t]he INOT22 study also provides compelling evidence that the claims are not
`obvious.” -522 Dec. Inst. 16. We stated that “[w]e find persuasive Patent Owner’s
`argument and evidence that, if it were obvious to a person of ordinary skill in the
`art to exclude children with LVD from treatment with iNO, the experts in the field
`who designed the study . . . would have excluded those children from the original
`protocol.” Id. We also noted that during prosecution of the involved patents, the
`applicants argued that the fact that children with LVD were not excluded from the
`original protocol of the INOT22 study is evidence of nonobviousness. Id. Because
`Petitioner did not address any of these arguments in the petitions, “we agree[d]
`with Patent Owner that Petitioner and its declarant should have addressed these
`arguments in the Petitions to show a reasonable likelihood of success on the
`merits.” Id. at 16–17.
`In its current Petitions, Petitioner again does not address the compelling
`evidence of secondary considerations set forth during prosecution and in the
`Preliminary Responses in the earlier proceedings. At best, Petitioner responds in a
`footnote, stating “this Petition explicitly shows that Patent Owner’s statements
`regarding the INOT22 study are incorrect: at least Greenough and Jaypee teach
`that children and neonates with LVD should be excluded from treatment.” Pet. 6
`n.4. But even if it were true that Greenough and Jaypee teach that children and
`neonates with LVD should be excluded from treatment with iNO, that argument is
`still insufficient to address the strong evidence of secondary considerations. In
`
` 9
`
`
`
`
`
`

`

`IPR2016-00777 (8,282,966 B2); IPR2016-00778 (8,431,163 B2);
`IPR2016-00779 (8,293,284 B2); IPR2016-00780 (8,795,741 B2)
`
`other words, athough the argument may address the combination of references, it
`does not explain why the many experts in the field would have designed a study
`that did not exclude patients with pre-existing LVD if it were obvious to do so.
`Despite our admonition for failing to address the evidence of secondary
`considerations in the prior proceedings, the current Petitions suffer from that same
`fatal flaw. Thus, notwithstanding Petitioner’s assertion that its current arguments
`are substantially different in light of the new citations to Greenough and Jaypee
`(Pet. 13–17), we determine that Petitioner’s argument is substantially the same as
`before under 35 U.S.C. § 325(d) in that it is equally deficient.
`B. The Prior Art Should Have Been Known
`In determining whether to exercise our discretion to decline review, we have
`also considered whether the new prior art references asserted in the later-filed
`petitions were unknown or unavailable. See, e.g., Conopco, Inc. v. Procter &
`Gamble Co., IPR2014-00628, slip op. at 11 (PTAB Oct. 20, 2014) (Paper 21).
`Petitioner describes Greenough as “a textbook on neonatal respiratory disorders,
`including indications and contraindications for iNO treatment and an entire chapter
`dedicated to the treatment of persistent pulmonary hypertension of the newborn
`(‘PPHN’).” Pet. 26. Petitioner similarly describes Jaypee as “a textbook on
`pediatric and neonatal mechanical ventilation that reviews pediatric conditions,
`including pulmonary hypertension and PPHN,” and includes “an entire chapter on
`iNO.” Id. at 27.
`Notwithstanding their relevance to the subject matter of the involved patents,
`Petitioner contends that “[d]espite conducting diligent searches, [Petitioner] did not
`find the Greenough or Jaypee references prior to filing the first set of IPRs.” Id.
`at 18. Petitioner’s contention, however, is inconsistent with the testimony of its
`
`
`
`10
`
`
`
`

`

`IPR2016-00777 (8,282,966 B2); IPR2016-00778 (8,431,163 B2);
`IPR2016-00779 (8,293,284 B2); IPR2016-00780 (8,795,741 B2)
`
`own declarant, Dr. Lawson, who states that “Greenough is a formative work in the
`area of neonatology” and that Dr. Anne Greenough is “a thought leader in this
`area.” Ex. 1002 ¶¶ 40, 41. This testimony suggests that Greenough is not an
`obscure text that would be difficult to find upon a reasonably diligent search of the
`relevant prior art.
`Consistent with Dr. Lawson’s testimony, Petitioner acknowledges that
`“other articles by the author of Greenough were cited during prosecution.” Pet. 28
`n.15. Patent Owner also provides evidence that Greenough is catalogued and
`shelved “at dozens of major libraries in the United States, including the Library of
`Congress, the National Library of Medicine, the Harvard University Library, and at
`least two libraries in Chicago, home of Petitioner’s counsel.” Prelim. Resp. 17–18
`(citing Exs. 2010–2013, 2047, 2048). Patent Owner also notes that both textbooks
`are readily identified by searching Google Books using keywords from the ’966
`patent specification. Id. at 17 (citing Exs. 2003, 2008, 2009).
`Finally, Petitioner admits that it was only after being sued that its efforts to
`search for prior art “intensified” and that it was through these “additional efforts”
`that Petitioner was able to find the new references. Pet. 19. We are not persuaded
`that litigation justifies the failure to find references that appear to have been readily
`available.
`Having considered the arguments and evidence, we determine that, at a
`minimum, Petitioner should have known of the Greenough and Jaypee references
`at the time it filed its earlier petitions. Accordingly, we determine that this factor
`weighs in favor of exercising our discretion to decline to institute an inter partes
`review of the challenged claims.
`
`
`
`11
`
`
`
`

`

`IPR2016-00777 (8,282,966 B2); IPR2016-00778 (8,431,163 B2);
`IPR2016-00779 (8,293,284 B2); IPR2016-00780 (8,795,741 B2)
`
`
`C. NOxBOX Does Not Preclude Exercising Our Discretion
`Finally, Petitioner argues that we should not exercise our discretion to deny
`the Petitions “solely using [our] discretion under 35 U.S.C. § 325(d) because doing
`so would deprive NOxBOX Limited, a separate operating entity from Praxair
`Distribution, Inc., of any opportunity to avail itself of the opportunity to challenge
`the claims of the [involved patents] before the Board.” Pet. 19–20. We are not
`persuaded. As Patent Owner notes, Praxair Inc. is a real party-in-interest in both
`sets of proceedings and recently acquired NOxBOX. Prelim. Resp. 28. As such,
`we find persuasive Patent Owner’s argument that Praxair “should not be allowed to
`‘purchase’ a second bite at the apple at this late date.” Id. Regardless, we are not
`exercising out discretion “solely” under § 325(d). We exercise our discretion
`under both § 314(a) and § 325(d).
`
`CONCLUSION
`
`Because Petitioner—by failing to address the compelling evidence of
`secondary considerations—asserts substantially the same arguments previously
`presented to the Board, and because we find Petitioner should have known of the
`prior art asserted in these proceedings at the time it filed its earlier petitions, we
`exercise our discretion under 35 U.S.C. §§ 314(a) and 325(d) and decline to
`institute an inter partes review of any of the challenged claims of any of the
`involved patents.
`
`ORDER
`
`In consideration of the foregoing, it is hereby:
`ORDERED that Petitioner’s requests for an inter partes review of
`(1) claims 1–29 the ’966 patent (IPR2016-00777); (2) claims 1–25 of the ’163
`
`
`
`12
`
`
`
`

`

`IPR2016-00777 (8,282,966 B2); IPR2016-00778 (8,431,163 B2);
`IPR2016-00779 (8,293,284 B2); IPR2016-00780 (8,795,741 B2)
`
`patent (IPR2016-00778); (3) claims 1–30 of the ’284 patent (IPR2016-00779); and
`(4) claims 1–44 of the ’741 patent (IPR2016-00780) are denied.
`
`PETITIONER:
`
`Benjamin Weed
`Margaux Nair
`K&L GATES LLP
`
`Sanjay Murthy
`Maria Doukas
`MORGAN, LEWIS & BOCKIUS LLP
`
`benjamin.weed.PTAB@klgates.com
`margaux.nair.PTAB@klgates.com
`sanjay.murthy@morganlewis.com
`maria.doukas@morganlewis.com
`
`PATENT OWNER:
`
`Robert Steinberg
`Daniel G. Brown
`LATHAM & WATKINS LLP
`
`bob.steinberg@lw.com
`daniel.brown@lw.com
`
`
`
`
`13
`
`
`
`