IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`PRAXAIR DISTRIBUTION, INC.
`Petitioner
`v.
`INO THERAPEUTICS, INC. d/b/a IKARIA, INC.
`Patent Owner
`
`
`
`PETITION FOR INTER PARTES REVIEW OF U.S. PATENT NO. 8,282,966
`PURSUANT TO §§ 35 U.S.C. 311-319 AND 37 C.F.R. § 42
`
`
`
`Mail Stop PATENT BOARD
`Patent Trial and Appeal Board
`United States Patent and Trademark Office
`PO Box 1450
`Alexandria, Virginia 22313–1450
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`Ex. 2016-0001
`
`

`
`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
`
`Table of Contents
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`Page
`
`I.
`II.
`
`INTRODUCTION ........................................................................................... 1
`OVERVIEW .................................................................................................... 1
`A.
`Summary of the ’966 Patent .................................................................. 1
`B.
`Summary of the Prosecution History of the ’966 Patent ...................... 3
`III. BACKGROUND ON PULMONARY HYPERTENSION, HYPOXIC
`RESPIRATORY FAILURE, AND DIAGNOSTIC STEPS USED IN
`TREATMENT ................................................................................................. 4
`IV. GROUNDS FOR STANDING (37 C.F.R. § 42.104(a)) ................................. 6
`V.
`PAYMENT OF FEES (37 C.F.R. § 42.103) ................................................... 6
`VI. MANDATORY NOTICES (37 C.F.R. § 42.8) ............................................... 7
`A.
`Real-Parties-in-Interest .......................................................................... 7
`B.
`Related Matters ...................................................................................... 7
`C.
`Lead and Backup Counsel (37 C.F.R. § 42.8(b)(3)) and Service
`Information (37 C.F.R. § 42.8(b)(4)) .................................................... 7
`VII. PERSON OF ORDINARY SKILL IN THE ART .......................................... 8
`VIII. CLAIM CONSTRUCTION ............................................................................ 8
`A.
`Broadest Reasonable Interpretation Standard ....................................... 8
`B.
`Claim Construction of the Term “Child” and “Children” .................. 10
`IX. STATEMENT OF THE PRECISE RELIEF REQUESTED AND THE
`REASONS THEREFORE (37 C.F.R. §§ 42.22(a) and 42.104(b)) .............. 11
`A. Ground 1: Independent Claims 1, 6, 13, and 22 and Dependent
`Claims 2-3, 5, 7-9, 11, 14-17, 20, 23-25, and 28 are Unpatentable
`Under 35 U.S.C. § 103(a) as Obvious Over Bernasconi in View of
`INOMAX label, Loh and Goyal ........................................................... 14
`1.
`Overview of Prior Art Applied in Ground 1 ............................. 15
`2. Motivation to Combine Art Applied in Ground 1 .................... 17
`3.
`Independent Claims 1 and 6 ...................................................... 21
`(a)
`Part (a) of Independent Claims 1 and 6 .......................... 22
`(b)
`Part (b) of Independent Claims 1 and 6 .......................... 25
`
`i
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`Ex. 2016-0002
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`

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`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
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`4.
`
`(c)
`Part (c) of Independent Claims 1 and 6 .......................... 27
`Independent Claims 13 and 22 .................................................. 28
`(a)
`Part (a) of Independent Claims 13 and 22 ...................... 28
`(b)
`Part (b) of Independent Claims 13 and 22 ...................... 29
`(c)
`Part (c) of Independent Claims 13 and 22 ...................... 30
`(d)
`Part (d) of Independent Claims 13 and 22 ...................... 31
`(e)
`Part (e) of Independent Claims 13 and 22 ...................... 31
`Dependent Claims 2-3, 5, 7-9, 11, 14-17, 20, 23-25, and 28 ... 32
`(a) Dependent Claims 2 and 8 .............................................. 32
`(b) Dependent Claims 3, 9, and 16 ....................................... 33
`(c) Dependent Claims 5, 11, 20, and 28 ............................... 33
`(d) Dependent Claims 14 and 24 .......................................... 34
`(e) Dependent Claims 15 and 25 .......................................... 35
`(f) Dependent Claims 7, 17, and 23 ..................................... 35
`Ground 2: Dependent Claims 4, 10, 12, 18, 19, 21, 26, 27, and 29
`are Unpatentable Under 35 U.S.C. § 103(a) as Obvious Over
`Bernasconi, the INOMAX label, Loh, Goyal and Macrae .................. 37
`Ground 3: Independent Claims 1, 6, 13, and 22 and Dependent
`Claims 2-5, 7-12, 14-21, and 23-29 are Unpatentable Under 35
`U.S.C. § 103(a) as Obvious Over Ichinose, Neonatal Group,
`Macrae, Loh, Goyal, and Germann .................................................... 39
`1.
`Overview of Prior Art in Ground 3 ........................................... 40
`2. Motivation to Combine Art Applied in Ground 3 .................... 41
`3.
`Independent Claims 1 and 6 ...................................................... 43
`(a)
`Part (a) of Independent Claims 1 and 6 .......................... 43
`(b)
`Part (b) of Independent Claims 1 and 6. ......................... 47
`(c)
`Part (c) of Independent Claims 1 and 6 .......................... 48
`Independent Claims 13 and 22 .................................................. 49
`(a)
`Part (a) of Independent Claims 13 and 22 ...................... 49
`(b)
`Part (b) of Independent Claims 13 and 22 ...................... 50
`
`5.
`
`4.
`
`B.
`
`C.
`
`ii
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`Ex. 2016-0003
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`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
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`5.
`
`(c)
`Part (c) of Independent Claims 13 and 22 ...................... 51
`Part (d) of Independent Claims 13 and 22 ...................... 52
`(d)
`Part (e) of Independent Claims 13 and 22 ...................... 53
`(e)
`Dependent Claims 2-5, 7-12, 14-21, and 23-29 ........................ 54
`(a) Dependent Claims 2 and 8 .............................................. 54
`(b) Dependent Claims 3, 9, and 16 ....................................... 54
`(c) Dependent Claims 5, 11, 20, and 28. .............................. 55
`(d) Dependent Claims 14 and 24 .......................................... 56
`(e) Dependent Claims 15 and 25 .......................................... 56
`(f) Dependent Claims 7, 17, and 23 ..................................... 57
`(g) Dependent Claims 4, 10, 12, 18, 19, 21, 26, 27, 29 ....... 58
`CONCLUSION .............................................................................................. 58
`
`
`
`X.
`
`
`
`iii
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`Ex. 2016-0004
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`

`
`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
`
`List of Exhibits
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`Ex. 1001: U.S. Patent No. 8,282,966 to Baldassarre et al. (“ʼ966 Patent), filed
`
`June 22, 2010, issued October 9, 2012.
`
`Ex. 1002: Declaration of Dr. Maurice Beghetti.
`
`Ex. 1003: Curriculum vitae of Dr. Maurice Beghetti.
`
`Ex. 1004: Bernasconi et al., Inhaled Nitric Oxide Applications in Paediatric
`
`Practice, 4
`
`Images
`
`in Paediatric Cardiology, 4-29
`
`(2002).
`
`(“Bernasconi”).
`
`Ex. 1005: Davidson, et al., Inhaled Nitric Oxide for the Early Treatment of
`
`Persistent Pulmonary Hypertension of
`
`the Term Newborn: A
`
`Randomized, Double-Masked, Placebo-Controlled, Dose-Response,
`
`Multicenter Study, 101 Pediatrics, 325-334 (1998). (“Davidson”).
`
`Ex. 1006: Loh, et al., Cardiovascular Effects of Inhaled Nitric Oxide in Patients
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`with Left Ventricular Dysfunction, 90 Circulation, 2780-2785 (1994).
`
`(“Loh”).
`
`Ex. 1007: P. Goyal, et al., Efficacy of Nitroglycerin Inhalation in Reducing
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`Pulmonary Arterial Hypertension in Children with Congenital Heart
`
`Disease, 97 British Journal of Anaesthesia, 208-214 (2006).
`
`(“Goyal”).
`
`Ex. 1008: Macrae, et al., Inhaled Nitric Oxide Therapy in Neonates and
`
`iv
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`Ex. 2016-0005
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`

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`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
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`Children: Reaching a European Consensus, 30 Intensive Care
`
`Medicine, 372-380 (2004). (“Macrae”).
`
`Ex. 1009:
`
`Ichinose, et al., Inhaled Nitric Oxide: A Selective Pulmonary
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`Vasodilator: Current Uses and Therapeutic Potential, 109
`
`Circulation, 3106-3111 (2004). (“Ichinose”).
`
`Ex. 1010: Germann, et al., Inhaled Nitric Oxide Therapy in Adults: European
`
`Expert Recommendations, 31 Intensive Care Med, 1029-1041 (2005).
`
`(“Germann”).
`
`Ex. 1011: The Neonatal Inhaled Nitric Oxide Study Group, Inhaled Nitric Oxide
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`in Full-Term and Nearly Full-Term Infants with Hypoxic Respiratory
`
`Failure, 336 The New England Journal of Medicine, 597-604 (1997).
`
`(“Neonatal Group”).
`
`Ex. 1012: Pozzoli, et al., Non-Invasive Estimation of Left Ventricular Filling
`
`Pressures by Doppler Echocardiography, 3 Eur J Echocardiogr.,
`
`75-79 (2002). (“Pozzoli”).
`
`Ex. 1013:
`
`“What
`
`is
`
`a
`
`Serious Adverse
`
`Event?”
`
`available
`
`at
`
`http://web.archive.org/web/20090611022009/http://www.fda.gov/Safe
`
`ty/MedWatch/HowToReport/ucm053087.htm
`
`(June
`
`11,
`
`2009).
`
`(“FDA Safety Information”).
`
`Ex. 1014: Center for Drug Evaluation and Research, Application Number: NDA
`
`v
`
`Ex. 2016-0006
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`

`
`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
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`20845,
`
`INOMAX, Final Printed Labeling,
`
`available
`
`at
`
`http://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20845_inoma
`
`x_prntlbl.pdf (August 9, 2000). (“INOMAX label”).
`
`Ex. 1015:
`
` Richard E. Klabunde, Pulmonary Capillary Wedge Pressure,
`
`Cardiovascular Physiology Concepts, 4/11/2007 available at
`
`http://www.cvphysiology.com/Heart%20Failure/HF008.htm
`
`(“Klabunde”).
`
`Ex. 1016: Hoehn, Therapy of Pulmonary Hypertension in Neonates and Infants,
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`Pharmacology & Therapeutics 2007 114:318-326. (“Hoehn”).
`
`Ex. 1017:
`
`Ivy et al., Pediatric Pulmonary Hypertension, J Am Coll Cardiol.
`
`62(25_S) (2013). (“Ivy”).
`
`Ex. 1018: Simonneau, et al., Clinical Classification of Pulmonary Hypertension,
`
`J. Am. Coll. Cardiol. 43(12 Suppl S):5S-12S (2004). (“Simonneau
`
`2004”).
`
`Ex. 1019: Simonneau, et al., Updated Clinical Classification of Pulmonary
`
`Hypertension, J Am. Coll. Cardiol. 54(1 Suppl):S43-54 (2009).
`
`(“Simonneau 2009”).
`
`Ex. 1020: Simonneau, et al., Updated Clinical Classification of Pulmonary
`
`Hypertension, J. Am. Coll. Cardiol. 62(25 Suppl):D34-41 (2013).
`
`(“Simonneau 2013”).
`
`vi
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`Ex. 2016-0007
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`

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`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
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`Ex. 1021: Chemla,
`
`et al., Haemodynamic Evaluation of Pulmonary
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`Hypertension, 20 Eur Respir J., 1314-1331 (2002). (“Chemla”).
`
`Ex. 1022: Griffiths, et al. “Inhaled Nitric Oxide Therapy in Adults.” 353 New
`
`England Journal of Medicine, 2683-2695 (2005). (“Griffiths”).
`
`Ex. 1023: Royster, et al., Differences in Pulmonary Artery Wedge Pressures
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`Obtained by Balloon Inflation Versus Impaction Techniques, 61
`
`Anesthesiology, (1984). (“Royster”).
`
`Ex. 1024:
`
`Ignarro, L.J., ed. Nitric Oxide Biology and Pathobiology, Academic
`
`Press, (2000). (“Ignarro”).
`
`Ex. 1025: M. Hoeper, et al., Definitions and Diagnosis of Pulmonary
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`Hypertension 62:25 J. of the American College of Cardiology (2013).
`
`(“Hoeper”).
`
`Ex. 1026: Kaldijian, L., et al., A Clinician’s Approach to Clinical Ethical
`
`Reasoning, J Gen Intern Med. 20(3): 306–311 (Mar. 2005).
`
`(“Kaldijian”).
`
`Ex. 1027:
`
`Jonsen, A. et al., Clinical Ethics: A Practical Approach to Ethical
`
`Decisions in Clinical Medicine 4th ed. (1998). (“Jonsen”).
`
`Ex. 1028: Ware, L., Inhaled Nitric Oxide in Infants and Children, Crit Care
`
`Nurs Clin North Am. Mar;14(1):1-6 (2002). (“Ware”).
`
`Ex. 1029: Wessel, D.L., Commentary: Simple Gases and Complex Single
`
`vii
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`Ex. 2016-0008
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`

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`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
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`Ventricles, J. of Thoracic and Cardiovascular Surgery, 112:3 655–57
`
`(Sept. 1996). (“Wessel”).
`
`Ex. 1030: Henrichsen, et al., Inhaled Nitric Oxide can Cause Severe Systemic
`
`Hypotension, 129 The
`
`Journal of Pediatrics, 183
`
`(1996).
`
`(“Henrichsen”).
`
`Ex. 1031: Waldmann, et al., Oxford Desk Reference Critical Care, Oxford
`
`University Press (2008). (“Waldmann”).
`
`Ex. 1032: Reserved
`
`Ex. 1033: Claim Chart for Claims 1–3, 5–9, 11, 13–17, 20, 22–25, and 28.
`
`Ex. 1034: Claim Chart for Claims 4, 10, 12, 18, 19, 21, 26, 27, and 29.
`
`Ex. 1035: Claim Chart for Claims 1–29.
`
`Ex. 1036: Reserved
`
`Ex. 1037: Reserved
`
`Ex. 1038: Reserved
`
`Ex. 1039: Reserved
`
`Ex. 1040: Reserved
`
`Ex. 1041: Reserved
`
`Ex. 1042: Reserved.
`
`Ex. 1043: Reserved.
`
`Ex. 1044: Reserved.
`
`viii
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`Ex. 2016-0009
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`

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`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
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`Ex. 1045: Reserved.
`
`Ex. 1046: Reserved.
`
`Ex. 1047: Reserved.
`
`Ex. 1048: Reserved.
`
`Ex. 1049: Reserved.
`
`Ex. 1050: Reserved.
`
`Ex. 1051: Webster’s Third New International Dictionary of the English
`
`Language Unabridged 388 (2002). (“Webster”).
`
`Ex. 1052: Prosecution History for U.S. Patent No. 8,282,966.
`
`ix
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`Ex. 2016-0010
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`

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`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
`
`I.
`
`INTRODUCTION
`Praxair Distribution, Inc. (“Petitioner” or “Praxair”) petitions for Inter
`
`Partes Review (“IPR”) under 35 U.S.C. §§ 311–319 and 37 C.F.R. § 42 of Claims
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`1 to 29 of U.S. Patent No. 8,282,966 (“the ʼ966 Patent”). (Ex. 1001.)
`
`II. OVERVIEW
`A.
`Summary of the ’966 Patent
`Nitric oxide (“NO”) is a gaseous chemical compound used to treat patients
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`with severe breathing problems. In 2000, the U.S. Food and Drug Administration
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`(“FDA”) approved inhaled nitric oxide (“iNO”) to treat term and near-term infants
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`(born after the 33rd week of pregnancy) with respiratory failure. Patent Owner
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`iNO Therapeutics, Inc. d/b/a Ikaria, Inc. (“Patent Owner” or “Ikaria”) is the
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`exclusive supplier in the U.S. for iNO, which it sells under the brand INOMAX®.
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`Ikaria’s original patents covering this drug expired in 2013. Like many
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`pharmaceutical companies facing the loss of patent protection, Ikaria has used later
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`acquired patents like the ʼ966 Patent to impermissibly extend its patent protection
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`for INOMAX®.1
`
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`1 By adding the ʼ966 Patent to the FDA’s Orange Book, Ikaria is seeking to
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`extend its potential monopoly on INOMAX® until 2029—33 years after the
`
`original patents covering the drug product and method of use issued.
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`1
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`Ex. 2016-0011
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`

`
`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
`
`Indeed, Ikaria filed the application leading to the ʼ966 Patent nine years after
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`INOMAX® was approved. Yet the ʼ966 Patent does not relate to any inventive
`
`method of treating a patient with iNO or using iNO. To the contrary, it discloses a
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`series of well-known diagnostic steps and analyses to determine whether the
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`patient is at risk of a Serious Adverse Event, such as pulmonary edema, if treated
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`with iNO and excluding such patients from treatment based on the assessed risk.2
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`(Ex. 1001 at Abstract, 1:46-60; Ex. 1002 ¶ 14.) Methods for evaluating and
`
`excluding patients from treatment with iNO were known long before June 30,
`
`2009, the earliest possible priority date (“EPD”) of the ʼ966 Patent.
`
`The claims of the ʼ966 Patent merely combine well-known methods and
`
`techniques (e.g., echocardiography, measuring wedge pressure, measuring blood
`
`oxygen, etc.) for determining who can or cannot be safely treated with iNO. (See,
`
`e.g., Ex. 1016 at 322; Ex. 1004 at 8; Ex. 1006 at 2781; Ex. 1014 at 2-3; Ex. 1011 at
`
`598.) These conventional practices are disclosed in the prior art references relied
`
`on in this Petition. Indeed, these references are not only from the same field, they
`
`all relate to risks associated with using iNO. Accordingly, this Petition should be
`
`granted and trial instituted on all of the challenged claims.
`
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`2 “Serious Adverse Event” is a statutorily defined term of art. (See 21 C.F.R.
`
`§ 312.32; Ex. 1002 ¶ 37; Ex. 1013.)
`
`2
`
`Ex. 2016-0012
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`

`
`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
`
`Summary of the Prosecution History of the ’966 Patent
`
`B.
`The application leading to the ’966 Patent was filed on June 22, 2010. (Ex.
`
`1001.) After extensive prosecution including four rejections, on August 15, 2012,
`
`Applicants amended all four independent claims to specify that the dosage of iNO
`
`should be 20 parts per million (“ppm”), and that a child identified as needing
`
`treatment has a pulmonary capillary wedge pressure greater than or equal to 20 mm
`
`Hg and thus has left ventricular dysfunction (“LVD”). (Ex. 1052 at 883, additions
`
`via amendment underlined.) Representative application Claim 31 (which issued as
`
`Claim 1) reproduced below illustrates this August 15, 2012 Amendment:
`
`
`On August 31, 2012, the Examiner issued a notice of allowance including
`
`the following reasons for allowance:
`
`the cited art of record does not teach or suggest, alone or in combination, the
`patient population of a child in need of the administration of 20 ppm iNO
`and determining the [pulmonary capillary wedge pressure] as greater than or
`
`3
`
`Ex. 2016-0013
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`

`
`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
`
`equal to 20 mm Hg in the method as instantly claimed to reduce the risk of
`occurrence of pulmonary edema. (Ex. 1052 at 986, emphasis added.)
`The same day, Applicants filed comments asserting that “the Examiner’s
`
`statement of reasons for allowance . . . are just some of many reasons that the
`
`present claims are allowable over the cited art of record.” (Ex. 1052 at 1001.)
`
`III. BACKGROUND ON PULMONARY HYPERTENSION, HYPOXIC
`RESPIRATORY FAILURE, AND DIAGNOSTIC STEPS USED IN
`TREATMENT
`
`In 2000 (nine years before the EPD), the FDA approved 20 ppm of iNO to
`
`treat neonatal hypoxic respiratory failure, which is often associated with
`
`pulmonary hypertension. (Ex. 1004 at 3; Ex. 1014 at 6.) Pulmonary hypertension
`
`is characterized by an increased pulmonary artery pressure and increased
`
`pulmonary vascular resistance. (Ex. 1002 ¶ 16; See Ex. 1004 at 8.) iNO may be
`
`used to treat pulmonary hypertension. (Ex. 1002 ¶ 17; Ex. 1004 at 8, 12.) iNO is a
`
`selective pulmonary vasodilator that relaxes pulmonary vessels, decreasing
`
`pulmonary arterial pressure, pulmonary vascular resistance, and right ventricular
`
`afterload. (Ex. 1002 ¶ 16; Ex. 1004 at 1, 2.)
`
`It was well known before the EPD that when a patient exhibited symptoms
`
`of pulmonary hypertension or hypoxic respiratory failure, a pediatric cardiologist
`
`had to perform diagnostic tests to determine the best and safest method of
`
`treatment. (Ex. 1002 ¶¶ 17, 19; Ex. 1004 at 8.) Specifically, it was well known
`
`that pediatric cardiologists had
`
`to examine and evaluate patients before
`
`4
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`Ex. 2016-0014
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`

`
`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
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`administering iNO to determine: (1) whether the treatment would likely benefit the
`
`patient; and (2) whether the patient would be at risk of having a negative reaction
`
`to the treatment. (Ex. 1002 ¶ 17; Ex. 1004 at 8.)
`
`It was also known before the EPD that patients with either systolic or
`
`diastolic LVD should not be treated with iNO because they could have an
`
`increased risk of suffering a Serious Adverse Event, such as pulmonary edema.3
`
`(Ex. 1002 ¶ 18; Ex. 1004 at 8; Ex. 1013; Ex. 1009 at 3109; Ex. 1010 at 1033.)
`
`Thus, before prescribing iNO, pediatric cardiologists could have ordered various
`
`known diagnostic processes and tests, such as echocardiography4, to determine
`
`whether the patient had LVD, or any other condition contraindicating the use of
`
`iNO. (Ex. 1002 ¶¶ 15, 19-21, 55; Ex. 1004 at 8; Ex. 1008 at 373-374.)
`
`Before the EPD, pediatric cardiologists also used wedge pressure to confirm
`
`whether the patient could be safely treated with iNO.5 (Ex. 1002 ¶¶ 15, 22; Ex.
`
`3 Pulmonary edema is a buildup of fluid in the lungs. (Ex. 1002 ¶14, FN 3.)
`
`4 Echocardiography is the use of ultrasound waves to image and investigate the
`
`heart. (See Ex. 1002 ¶ 15, FN 4.)
`
`5 “Wedge pressure” is also sometimes referred to as pulmonary capillary wedge
`
`pressure (“PCWP”), pulmonary arterial wedge pressure (“PAWP”), or merely
`
`“wedge.” (Ex. 1002 ¶ 22, FN 9.) Wedge pressure may be determined via
`
`measurement through cardiac catheterization or by extrapolation through
`
`5
`
`Ex. 2016-0015
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`

`
`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
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`1006 at 2781, 2782, Table 1.) As detailed in the literature, a high wedge pressure
`
`of, for example over 20 mm Hg, often indicated LVD, and the pediatric
`
`cardiologist thus knew not to treat the patient with iNO. (Ex. 1002 ¶ 22; Ex. 1004
`
`at 8; Ex. 1006 at 2781, 2782, Table 1; Ex. 1015 at 1.) Indeed, pediatric
`
`cardiologists safely and effectively used iNO for at least nine years before the
`
`EPD. (Ex. 1002 ¶¶ 17, 24; Ex. 1004 at 3.)
`
`IV. GROUNDS FOR STANDING (37 C.F.R. § 42.104(a))
`Petitioner certifies that (1) the ʼ966 Patent, issued on October 9, 2012, is
`
`available for IPR; (2) Petitioner is not barred or estopped from requesting an IPR
`
`on the grounds identified in this Petition; and (3) Petitioner has not filed any
`
`complaint relating to the ʼ966 Patent. This Petition is filed in accordance with 37
`
`C.F.R. § 42.106(a). Concurrently filed herewith is a Power of Attorney and an
`
`Exhibit List per 37 C.F.R. § 42.10(b) and § 42.63(e), respectively.
`
`V.
`
`PAYMENT OF FEES (37 C.F.R. § 42.103)
`
`In accordance with 37 C.F.R. § 42.15 and § 42.103, Petitioner authorizes the
`
`USPTO to charge the required fees for an IPR of 29 claims, and any additional
`
`fees, to Deposit Account 02–1818.
`
`____________________
`echocardiography. (Ex. 1002 ¶¶ 22-23; Ex. 1006 at 2781; Ex. 1007 at 209; Ex.
`
`1012 at 75-79.)
`
`6
`
`Ex. 2016-0016
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`

`
`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
`
`VI. MANDATORY NOTICES (37 C.F.R. § 42.8)
`A. Real-Parties-in-Interest
`Petitioner certifies that Praxair Distribution, Inc., with its head office at 28
`
`McCandless Ave, Pittsburgh, PA 15201 (“Praxair” or “Petitioner”), and Praxair,
`
`Inc., with its worldwide headquarters at 39 Old Ridgebury Rd., Danbury, CT
`
`06810, are the real-parties-in-interest.
`
`B. Related Matters
`Petitioner is not aware of any current litigation involving the ʼ966 Patent.
`
`C. Lead and Backup Counsel (37 C.F.R. § 42.8(b)(3)) and Service
`Information (37 C.F.R. § 42.8(b)(4))
`
`Lead Counsel
`
`Backup Counsel
`
`Sanjay K. Murthy
`Reg. No. 45,976
`K&L GATES LLP
`70 W. Madison Street, Suite 3100
`Chicago, IL 60602
`sanjay.murthy@klgates.com
`T: (312) 807-4416
`F: (312) 827-8138
`
`Sara Kerrane
`Reg. No. 62,801
`K&L GATES LLP
`1 Park Plaza
`Twelfth Floor
`Irvine, CA 92614
`sara.kerrane@klgates.com
`T: (949) 623-3547
`F: (949) 623-4470
`
`Michael J. Abernathy
`Pro hac vice Authorization
`Requested
`K&L GATES LLP
`70 W. Madison Street, Suite 3100
`Chicago, IL 60602
`michael.abernathy@klgates.com
`T: (312) 807-4257
`F: (312) 827-8032
`
`7
`
`
`
`Ex. 2016-0017
`
`

`
`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
`
`Please address all correspondence and service to counsel listed above.
`
`Petitioner consents to service by email.
`
`VII. PERSON OF ORDINARY SKILL IN THE ART
`A person of ordinary skill in the art (“POSA”) is a hypothetical person who
`
`is presumed to know the relevant prior art. (See IPR2013-00116 at 9, 37). A
`
`POSA has ordinary creativity, is not an automaton, and is capable of combining
`
`teachings of the prior art. (Id. (citing KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398,
`
`420-421 (2007)).) With respect to the ʼ966 Patent, Petitioner submits that a POSA
`
`is a pediatric cardiologist with experience prescribing iNO before the EPD. (Ex.
`
`1002 ¶¶ 26, 27.) Such a POSA would have had knowledge of diagnostic
`
`techniques and scientific literature related to pediatric cardiology, and would have
`
`understood how to search the literature for relevant publications. (Id.)
`
`VIII. CLAIM CONSTRUCTION
`A. Broadest Reasonable Interpretation Standard
`In accordance with 37 C.F.R. § 42.100(b), the challenged claims must be
`
`given their broadest reasonable interpretation in light of the specification of the
`
`’966 Patent. (Ex. 1002 ¶ 25.) The Patent Trial and Appeal Board (“Board”)
`
`interprets claims using the “broadest reasonable construction in light of the
`
`specification of the patent in which [they] appear[].” (37 C.F.R. § 42.100(b);
`
`Office Patent Trial Practice Guide, 77 Fed. Reg. 48756, 48766 (Aug. 14, 2012).)
`
`8
`
`Ex. 2016-0018
`
`

`
`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
`
`Under this broadest reasonable interpretation standard, claim terms are
`
`generally given their ordinary and customary meaning, as would be understood by
`
`a POSA in the context of the entire disclosure. (In re Translogic Tech., Inc. 504
`
`F.3d 1249, 1257 (Fed. Cir. 2007).) If a special definition for a claim term is
`
`proffered, it must be described in the specification “with reasonable clarity,
`
`deliberateness, and precision.” (In re Paulsen, 30 F.3d 1475, 1480 (Fed. Cir.
`
`1994).) Absent such a special definition, limitations are not to be read from the
`
`specification into the claims. (See In re Van Genus, 988 F.2d 1181, 1184 (Fed.
`
`Cir. 1993).)
`
`Therefore, where not specified, a POSA would have understood all the terms
`
`of each of the claims of the ʼ966 Patent to have their ordinary and customary
`
`meaning.6 Petitioner submits that the claim terms of the ʼ966 Patent are not limited
`
`to special definitions in the specification and therefore under the broadest
`
`reasonable interpretation standard, the terms should be construed to have their
`
`broadest ordinary and customary meanings. Petitioner provides the following
`
`specific construction only to the extent the Board determines that a specific
`
`6 Any contention that terms should be construed to have a special meaning
`
`should be disregarded unless the Patent Owner amends the claims in
`
`compliance with 35 U.S.C. § 112 to make them expressly correspond to that
`
`meaning. See 77 Fed. Reg. 48764 at II.B.6 (August 14, 2012).
`
`9
`
`Ex. 2016-0019
`
`

`
`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
`
`construction is necessary to clarify the broadest reasonable interpretation of the
`
`term “children.”
`
`B. Claim Construction of the Term “Child” and “Children”
`As discussed, the Federal Circuit has instructed that a special definition for a
`
`claim term must be described in the specification “with reasonable clarity,
`
`deliberateness, and precision.” (In re Paulsen, supra.) Claims 1, 6, 13, and 22
`
`recite a “child” and claims 13 and 22 recite “children.” (Ex. 1001 at 14:10-22, 36-
`
`54; 15:5-24; 16:4-24.) The specification states that “the term ‘children’ (and
`
`variations thereof) includes those being around 4 weeks to 18 years of age.” (Ex.
`
`1001 at 4:13-14 (emphasis added).) As the word “includes” demonstrates, this
`
`disclosure does not precisely and clearly limit the term “children” (“child”) to only
`
`that age range. Instead, it merely specifies one subset of ages included under the
`
`commonly understood definition of “children
`
`(and variations
`
`thereof).”
`
`Additionally, dependent claims 2 and 8 of the ’966 Patent, which specify that “the
`
`child is a neonate,” confirm that specification’s age range for children (and
`
`variations thereof) is not limiting.
`
`Merriam Webster (Ex. 1051) defined a “child” (“children”) at the EPD as
`
`“an unborn or recently born human being.” (Ex. 1051 at 388.) Accordingly, as
`
`claims must be given their broadest reasonable interpretation in light of the
`
`10
`
`Ex. 2016-0020
`
`

`
`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
`
`specification of the ’966 Patent, a POSA would have understood the term
`
`“children” (“child”) to mean an unborn or recently born human being.
`
`IX. STATEMENT OF THE PRECISE RELIEF REQUESTED AND THE
`REASONS THEREFORE (37 C.F.R. §§ 42.22(a) and 42.104(b))
`Petitioner requests inter partes review and cancellation of claims 1-29 on the
`
`grounds listed in the table below.
`
`Ground
`
`35 U.S.C.
`
`Index of References
`
`1
`
`2
`
`3
`
`§ 103
`
`§ 103
`
`§ 103
`
`Bernasconi in view of INOMAX
`label, Loh, and Goyal.
`Bernasconi in view of INOMAX
`label, Loh, Goyal, and Macrae.
`Ichinose in view of Neonatal Group,
`Macrae, Loh, Goyal, and Germann .
`
`ʼ966 Patent
`Claims
`1-3, 5-9, 11, 13-17,
`20, 22-25, and 28
`4, 10, 12, 18, 19,
`21, 26, 27, and 29
`1-29
`
`Per C.F.R. § 42.6(c), copies of the references are filed herewith.
`
`Additionally, Petitioner provides the declaration of Dr. Maurice Beghetti in
`
`support of the grounds for challenging the claims. (Ex. 1002.)7
`
`Claims 1, 6, 13, and 22 are the four independent claims of the ʼ966 Patent.
`
`Independent claim 1 recites:
`
`7 Dr. Beghetti is the Head of Paediatric Cardiology at the University Hospital of
`
`Geneva in Geneva, Switzerland and is the lead author of the Bernasconi
`
`reference discussed below. He is a highly qualified expert in the field with
`
`specific experience in pediatric cardiology and iNO. (Ex. 1002 ¶¶ 1-13, 28-32;
`
`Ex. 1003.)
`
`11
`
`Ex. 2016-0021
`
`

`
`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
`
`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:
`(a) performing echocardiography to identify a child in need of 20 ppm
`[iNO]8 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 [wedge pressure]9
`greater than or equal to 20 mm Hg and thus has [LVD]10, so is at particular
`risk of pulmonary edema upon treatment with [iNO]; and
`(c) excluding the child from [iNO] treatment based on the determination that
`the child has [LVD] and so is at particular risk of pulmonary edema upon
`treatment with [iNO].
`
`(Ex. 1001 at 14:6-22.)
`
`Independent claim 6 includes almost all of the same method steps as claim 1,
`
`except part (a) recites “carrying out a diagnostic process comprising measuring
`
`blood oxygen level, to identify a child as being in need of 20 ppm [iNO] treatment
`
`for hypoxic respiratory failure, wherein the child is not dependent on right-to-left
`
`shunting of blood.” (Ex. 1001 at 14:40-44.)
`
`
`8 “Inhaled nitric oxide” is abbreviated as “iNO.”
`
`9 “Pulmonary capillary wedge pressure (PCWP)” abbreviated as “wedge
`
`pressure.” See FN 5.
`
`10 “Left ventricular dysfunction” is abbreviated as “LVD.”
`
`12
`
`Ex. 2016-0022
`
`

`
`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
`
`Independent claim 13 recites:
`
`A method of treatment comprising:
`(a) performing echocardiography to identify a plurality of children who are
`in need of 20 ppm [iNO] treatment for pulmonary hypertension, wherein the
`children are not dependent on right-to-left shunting of blood;
`(b) determining that a first child of the plurality has a [wedge pressure]
`greater than or equal to 20 mm Hg and thus has [LVD], so is at particular
`risk of pulmonary edema upon treatment with [iNO];
`(c) determining that a second child of the plurality does not have [LVD];
`(d) administering the 20 ppm [iNO] treatment to the second child; and
`(e) excluding the first child from treatment with [iNO], based on the
`determination that the first child has [LVD], so is at particular risk of
`pulmonary edema upon treatment with [iNO].
`
`(Ex. 1001 at 15:5-24.) Independent claim 22 recites:
`
`A method of treatment comprising:
`(a) identifying a plurality of children who are in need of 20 ppm [iNO]
`treatment, wherein the children are not dependent on right-to-left shunting of
`blood;
`(b) in the first child of the plurality, measuring [wedge pressure] to
`determine that the first child of the plurality has a [wedge pressure] greater
`than or equal to 20 mm Hg and thus has [LVD], so is at particular risk of
`pulmonary edema upon treatment with [iNO];
`(c) in the second child of the plurality, performing echocardiography and/or
`measurement of [wedge pressure] to determine that the second child of the
`plurality does not have [LVD];
`(d) administering the 20 ppm [iNO] treatment to the second child; and
`
`13
`
`Ex. 2016-0023
`
`

`
`Petition for Inter Partes Review of U.S. Patent No. 8,282,966
`
`(e) excluding the first child from treatment with [iNO], based on the
`determination that the first child has [LVD], so is at particular risk of
`pulmonary edema upon treatment with [iNO].
`
`(Ex. 1001 at 16:4-24.)
`
`A. Ground 1: Independent Claims 1, 6, 13, and 22 and Dependent
`Claims 2-3, 5, 7-9, 11, 14-17, 20, 23-25, and 28 are Unpatentable
`Under 35 U.S.C. § 103(