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`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. 8,795,741
`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
`
`
`
`
`

`

`Petition for Inter Partes Review of U.S. Patent No. 8,795,741
`
`Table of Contents
`
`Page
`
`INTRODUCTION ........................................................................................... 1
`I.
`SUMMARY OF THE PROSECUTION HISTORY ....................................... 1
`II.
`III. BACKGROUND ON PULMONARY HYPERTENSION, HYPOXIC
`RESPIRATORY FAILURE, AND DIAGNOSTIC STEPS USED IN
`TREATMENT ................................................................................................. 3
`IV. GROUNDS FOR STANDING (37 C.F.R. § 42.104(a)) ................................. 5
`V.
`PAYMENT OF FEES (37 C.F.R. § 42.103) ................................................... 5
`VI. MANDATORY NOTICES (37 C.F.R. § 42.8) ............................................... 6
`A.
`Real-Parties-In-Interest ......................................................................... 6
`B.
`Related Matters ...................................................................................... 6
`C.
`Lead and Backup Counsel (37 C.F.R. § 42.8(b)(3)) and Service
`Information (37 C.F.R. § 42.8(b)(4)) .................................................... 6
`VII. PERSON OF SKILL IN THE ART AND STATE OF THE ART ................. 7
`VIII. CLAIM CONSTRUCTION ............................................................................ 7
`A.
`Broadest Reasonable Interpretation Standard ....................................... 7
`IX. STATEMENTS OF THE PRECISE RELIEF REQUESTED AND THE
`REASONS THEREFORE (37 C.F.R. §§ 42.22(a) and 42.104(b)) ................ 9
`A. Ground 1: Claims 1-2, 4, 6-14, 17-23, 31, 32, 34-35, 37-40, and
`42-44 Are Unpatentable Under 35 U.S.C. § 103(a) as Obvious
`Over Bernasconi, Loh and Goyal ....................................................... 13
`1.
`Overview of Prior Art Applied in Ground 1 ............................. 14
`2. Motivation to Combine Art Applied in Ground 1 .................... 15
`3.
`Independent Claims 1 and 9 ...................................................... 18
`(a)
`Part (a) of Independent Claims 1 and 9 .......................... 19
`(b)
`Part (b) of Independent Claims 1 and 9 .......................... 19
`(c)
`Part (c) of Independent Claims 1 and 9 .......................... 20
`(d)
`Part (d) of Independent Claims 1 and 9 .......................... 21
`(e)
`Part (e) of Independent Claims 1 and 9 .......................... 22
`
`i
`
`

`

`Petition for Inter Partes Review of U.S. Patent No. 8,795,741
`
`4.
`
`5.
`
`Independent Claims 34 and 37 .................................................. 23
`(a)
`Part (a) of Independent Claims 34 and 37 ...................... 23
`(b)
`Part (b) of Independent Claims 34 and 37 ...................... 24
`(c)
`Part (c) of Independent Claims 34 and 37 ...................... 24
`(d)
`Part (d) of Independent Claims 34 and 37 ...................... 24
`(e)
`Part (e) of Independent Claims 34 and 37 ...................... 25
`Claims 2, 4, 6-8, 10-14, 17-23, 31, 32, 35, 38-40, and 42-44 .. 26
`(a) Dependent Claims 2 and 14 ............................................ 26
`(b) Dependent Claims 4, 17, 35, and 42 ............................... 26
`(c) Dependent Claims 10-12, 18-21, 38-40, 43, and 44 ....... 27
`(d) Dependent Claims 6, 7, 22, 23, 31, and 32 ..................... 28
`(e) Dependent Claims 8 and 13 ............................................ 29
`Ground 2: Claims 24-27, 29-30, and 33 Are Unpatentable Under
`35 U.S.C. § 103(a) as Obvious Over Bernasconi, Loh, INOMAX
`label, Juliana and Goyal ..................................................................... 30
`1.
`Overview of Prior Art Applied in Ground 2 ............................. 30
`2.
`Independent Claim 24 ............................................................... 32
`(a)
`Part (a) of Independent Claim 24 ................................... 32
`(b)
`Part (b) of Independent Claim 24 ................................... 32
`(c)
`Part (c) of Independent Claim 24 ................................... 33
`(d)
`Part (d) of Independent Claim 24 ................................... 34
`(e)
`Part (e) of Independent Claim 24 ................................... 34
`Dependent Claims 25-27, 29-30, and 33 .................................. 35
`(a) Dependent Claims 27, 29, 30, and 33 ............................. 35
`(b) Dependent Claims 25 and 26 .......................................... 35
`Ground 3: Claims 3, 5, 15, 16, 36, and 41 are Unpatentable Under
`35 U.S.C. § 103(a) as Obvious Over Bernasconi, Loh, Macrae and
`Goyal ................................................................................................... 36
`
`B.
`
`C.
`
`3.
`
`ii
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`

`

`Petition for Inter Partes Review of U.S. Patent No. 8,795,741
`
`E.
`
`D. Ground 4: Claim 28 Is Unpatentable Under 35 U.S.C. § 103(a) as
`Obvious Over Bernasconi, Loh, INOMAX label, Juliana, Macrae
`and Goyal ............................................................................................ 38
`Ground 5: Claims 1-23, 31, 32, 34-44 Are Unpatentable Under 35
`U.S.C. § 103(a) as Obvious Over Ichinose, Neonatal Group,
`Macrae, Loh, Germann and Goyal ..................................................... 39
`1.
`Overview of Prior Art Applied in Ground 5 ............................. 39
`2.
`Independent Claims 1 and 9 ...................................................... 42
`(a)
`Part (a) of Independent Claims 1 and 9 .......................... 42
`(b)
`Part (b) of Independent Claims 1 and 9 .......................... 43
`(c)
`Part (c) of Independent Claims 1 and 9 .......................... 44
`(d)
`Part (d) of Independent Claims 1 and 9 .......................... 45
`(e)
`Part (e) of Independent Claims 1 and 9 .......................... 46
`Independent Claims 34 and 37 .................................................. 47
`(a)
`Part (a) of Independent Claims 34 and 37 ...................... 47
`(b)
`Part (b) of Independent Claims 34 and 37 ...................... 48
`(c)
`Part (c) of Independent Claims 34 and 37 ...................... 48
`(d)
`Part (d) of Independent Claims 34 and 37 ...................... 49
`(e)
`Part (e) of Independent Claims 34 and 37 ...................... 49
`Dependent Claims 2-8, 10-23, 25-33, 35-36, and 38-44 .......... 50
`(a) Dependent Claims 2 and 14 ............................................ 50
`(b) Dependent Claims 4, 17, 35, and 42 ............................... 50
`(c) Dependent Claims 10-12, 18-21, 38-40, 43, and 44 ....... 51
`(d) Dependent Claims 6, 7, 22, 23, 31 and 32 ...................... 53
`(e) Dependent Claims 8 and 13 ............................................ 54
`(f) Dependent Claims 3, 5, 15, 16, 36, and 41 ..................... 54
`Ground 6: Claims 24-30 and 33 Are Unpatentable Under 35 U.S.C.
`§ 103(a) as Obvious Over Ichinose, Neonatal Group, Macrae, Loh,
`INOMAX label, Germann and Goyal .................................................. 54
`1.
`Overview of Prior Art Applied in Ground 6 ............................. 55
`
`3.
`
`4.
`
`F.
`
`iii
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`

`

`Petition for Inter Partes Review of U.S. Patent No. 8,795,741
`
`2.
`
`Independent Claim 24 ............................................................... 55
`(a)
`Part (a) of Independent Claim 24 ................................... 55
`(b)
`Part (b) of Independent Claim 24 ................................... 56
`(c)
`Part (c) of Independent Claim 24 ................................... 57
`(d)
`Part (d) of Independent Claim 24 ................................... 58
`(e)
`Part (e) of Independent Claim 24 ................................... 58
`Dependent Claims 25-30 and 33 ............................................... 59
`(a) Dependent Claims 25 and 26 .......................................... 59
`(b) Dependent Claims 27, 29, 30, and 33 ............................. 60
`(c) Dependent Claim 28 ....................................................... 60
`CONCLUSION .............................................................................................. 60
`
`3.
`
`X.
`
`
`iv
`
`

`

`Petition for Inter Partes Review of U.S. Patent No. 8,795,741
`
`List of Exhibits
`
`Ex. 1001: U.S. Patent No. 8,795,741 to Baldassarre (“ʼ741 Patent), filed
`
`November 21, 2012, issued August 5, 2014.
`
`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
`
`with Left Ventricular Dysfunction, 90 Circulation, 2780-2785 (1994).
`
`(“Loh”).
`
`Ex. 1007: P. Goyal, et al., Efficacy of Nitroglycerin Inhalation in Reducing
`
`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
`
`v
`
`

`

`Petition for Inter Partes Review of U.S. Patent No. 8,795,741
`
`Children: Reaching a European Consensus, 30 Intensive Care
`
`Medicine, 372-380 (2004). (“Macrae”).
`
`Ex. 1009:
`
`Ichinose, et al., Inhaled Nitric Oxide: A Selective Pulmonary
`
`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
`
`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
`
`vi
`
`

`

`Petition for Inter Partes Review of U.S. Patent No. 8,795,741
`
`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,
`
`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”).
`
`vii
`
`

`

`Petition for Inter Partes Review of U.S. Patent No. 8,795,741
`
`Ex. 1021: Chemla,
`
`et al., Haemodynamic Evaluation of Pulmonary
`
`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
`
`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
`
`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: Reserved.
`
`viii
`
`

`

`Petition for Inter Partes Review of U.S. Patent No. 8,795,741
`
`Ex. 1030: Henrichsen, et al., Inhaled Nitric Oxide can Cause Severe Systemic
`
`Hypotension, 129 The
`
`Journal of Pediatrics, 183
`
`(1996).
`
`(“Henrichsen”).
`
`Ex. 1031: Reserved.
`
`Ex. 1032: Juliana, et al., Severe Persistent Pulmonary Hypertension of the
`
`Newborn in a Setting Where Limited Resources Exclude the use of
`
`Inhaled Nitric Oxide: Successful Treatment with Sildenafil, 164 Eur. J.
`
`Pediatr. 626-629 (2005). (“Juliana”).
`
`Ex. 1033: Reserved.
`
`Ex. 1034: Reserved.
`
`Ex. 1035: Reserved.
`
`Ex. 1036: Reserved.
`
`Ex. 1037: Reserved.
`
`Ex. 1038: Reserved.
`
`Ex. 1039: Reserved.
`
`Ex. 1040: Reserved.
`
`Ex. 1041: Reserved.
`
`Ex. 1042: Claim Chart for Claims 1, 2, 4, 6-14, 17-23, 31-32, 34-35, 37-40, and
`
`42-44.
`
`Ex. 1043: Claim Chart for Claims 3, 5, 15, 16, 36 and 41.
`
`ix
`
`

`

`Petition for Inter Partes Review of U.S. Patent No. 8,795,741
`
`Ex. 1044: Claim Chart for Claims 1–23, 31-32, and 34-44.
`
`Ex. 1045: Claim Chart for Claims 24-27, 29-30 and 33.
`
`Ex. 1046: Claim Chart for Claim 28.
`
`Ex. 1047: Claim Chart for Claims 24-30 and 33.
`
`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.
`
`Ex. 1053: Prosecution History for U.S. Patent No. 8,293,284.
`
`Ex. 1054: Reserved.
`
`Ex. 1055: Prosecution History for U.S. Patent No. 8,795,741.
`
`
`
`x
`
`

`

`Petition for Inter Partes Review of U.S. Patent No. 8,795,741
`
`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
`
`1 to 44 of U.S. Patent No. 8,795,741 (“the ʼ741 Patent”). (Ex. 1001.)
`
`Nitric oxide (“NO”) is a gaseous chemical compound used to treat patients
`
`with severe breathing problems. The ʼ741 Patent discloses a series of well-known
`
`diagnostic steps to determine whether a patient would be at risk of a Serious
`
`Adverse Event, such as pulmonary edema, if treated with iNO and, if so, excluding
`
`such patients from treatment.1 As detailed below, the medical literature addressing
`
`iNO described these methods long before June 30, 2009, the earliest possible
`
`priority date (“EPD”) of the ʼ741 Patent.
`
`II.
`
`SUMMARY OF THE PROSECUTION HISTORY
`
`The application leading to the ’741 Patent was filed on November 21, 2012.
`
`(Ex. 1055.) On January 11, 2013, the Examiner issued a double patenting rejection
`
`over (i) U.S. Patent No. 8,282,966; (ii) U.S. Patent No. 8,293,284; and (iii) co-
`
`pending U.S. Serial No. 13/651,660 (now U.S. Patent No. 8,431,163).2 (Ex. 1055
`
`
`1 “Serious Adverse Event” is a statutorily defined term of art. (See 21 C.F.R. §
`
`312.32; Ex. 1002 ¶ 37; Ex. 1013.)
`
`2 Petitioner has concurrently filed petitions for inter partes review of each of
`
`these three patents, as well as U.S. Patent No. 8,846,112, all commonly owned.
`
`
`
`1
`
`

`

`Petition for Inter Partes Review of U.S. Patent No. 8,795,741
`
`
`at 216.) The Examiner did not reject any of the claims over the prior art because,
`
`as discussed below, they already included elements (namely, 20 parts per million
`
`(“ppm”) iNO) that he (incorrectly) believed distinguished the claims over the prior
`
`art, as he had found in prosecutions for (i) U.S. Patent No. 8,282,966 (see Ex. 1052
`
`at 986) and (ii) U.S. Patent No. 8,293,284 (see Ex. 1053 at 965). Applicants filed
`
`terminal disclaimers to overcome the double patenting rejections. On March 1,
`
`2013, the Examiner issued a notice of allowance stating:
`
`Applicant’s amendments have overcome the rejections of record. The
`instantly claimed subject matter is free of the art. See US Patents 8282966
`and 8293284 for a complete rationale. (Ex. 1055 at 313, emphasis added; see
`also Ex. 1052 and Ex. 1053.)
`
`On March 8, 2013, Applicants indicated they did not concede that the rationale
`
`from the prosecutions of U.S. Patent Nos. 8,282,966 and 8,293,284 applied to the
`
`present case. (Ex. 1055 at 341.) Applicants then withdrew the application from
`
`issuance, filed an IDS, and amended the claims. (Id. at 350-414.) On June 23,
`
`2014, the Examiner issued a notice of allowance stating:
`
`The closest prior art of Rosales et al. (Pediatric Cardiology, 1999, 20:224-
`226) teaches administration of inhaled nitric oxide at 80 ppm to a 1 month
`old newborn and Rosales et al. speculated that NO induced pulmonary
`hypertensive crisis by increasing pulmonary load on a noncompliant left
`ventricle which could develop pulmonary edema (pages Abstract; Case
`report 224-225 and 226). However, 80 ppm [NO] is not sufficiently specific
`
`
`
`2
`
`

`

`Petition for Inter Partes Review of U.S. Patent No. 8,795,741
`
`
`
`to the instantly claimed 20 ppm of NO and there is no guidance or
`motivation to decrease the treatment dosage of 80 ppm 4 fold to 20 ppm.
`The Examiner also notes in Preston et al. (Chest 2002; 121:656-659) that an
`adult patient receiving 20 ppm inhaled NO developed pulmonary edema but
`had no signs of left heart disease (page 657 and Table 1) and concluded that
`iNO should be administered at low (≤ 10 ppm) during careful monitoring
`(Page 658). Thus, the artisan is directed to administering less than 10 ppm
`NO for treatment which is less than the instantly claimed 20 ppm NO. See
`also the reasons provided in US Patent No’s: 8282966 and 8293284. (Ex.
`1055 at 644-45, emphasis added; see also Ex. 1052 and Ex. 1053.)
`
`On June 27, 2014, Applicants again indicated they did not concede that “the
`
`Examiner’s stated reasons for allowance are the only reasons for which the claims
`
`are allowable.” (Ex. 1055 at 674.)
`
`III. BACKGROUND ON PULMONARY HYPERTENSION, HYPOXIC
`RESPIRATORY FAILURE, AND DIAGNOSTIC STEPS USED IN
`TREATMENT
`
`In 2000, the Food and Drug Administration (“FDA”) approved 20 ppm 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; Ex. 1004 at 8.) iNO may be used
`
`to treat pulmonary hypertension. (Ex. 1002 ¶ 17; Ex. 1004 at 8, 12.) It was well
`
`known before the EPD that when a patient exhibited symptoms of pulmonary
`
`
`
`3
`
`

`

`Petition for Inter Partes Review of U.S. Patent No. 8,795,741
`
`
`hypertension or hypoxic respiratory failure a pediatric cardiologist had to
`
`determine the best and safest method of treatment. (Ex. 1002 ¶ 17, FN 6; Ex. 1004
`
`at 8.) Specifically, pediatric cardiologists had to examine patients before
`
`administering iNO to determine: (1) whether the treatment would likely benefit the
`
`patient; and (2) whether the patient would be at risk of reacting negatively to the
`
`treatment. (Ex. 1002 ¶ 17; Ex. 1004 at 8.)
`
`It was also known before the EPD that patients with either systolic or
`
`diastolic left ventricular dysfunction (“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
`
`often ordered various known diagnostic tests, such as echocardiography, to
`
`determine whether the patient had LVD, or any other condition contraindicating
`
`use of iNO. (Ex. 1002 ¶¶ 15, 19-21, 24; 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.4 (Ex. 1002 ¶¶ 15, 22; Ex.
`
`3 Pulmonary edema is a buildup of fluid in the lungs. (Ex. 1002 ¶ 14, FN 3.)
`
`4 “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
`
`
`
`4
`
`

`

`Petition for Inter Partes Review of U.S. Patent No. 8,795,741
`
`
`1006 at 2781, 2782, Table 1.) A high wedge pressure, 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.)
`
`IV. GROUNDS FOR STANDING (37 C.F.R. § 42.104(a))
`Petitioner certifies that (1) the ʼ741 Patent, issued on August 5, 2014, 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 ʼ741 Patent. This Petition is filed in accordance with 37
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`C.F.R. § 42.106(a). Concurrently filed herewith is a Power of Attorney and an
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`Exhibit List per 37 C.F.R. § 42.10(b) and § 42.63(e), respectively.
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`V.
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`PAYMENT OF FEES (37 C.F.R. § 42.103)
`
`In accordance with 37 C.F.R. § 42.15 and § 42.103, Petitioner authorizes the
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`USPTO to charge the required fees for IPR of 44 claims, and any additional fees,
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`to Deposit Account 02-1818.
`
`____________________
`cardiac catheterization or by echocardiography. (Ex. 1002 ¶¶ 22-23; Ex. 1006
`
`at 2781; Ex. 1007 at 209; Ex. 1012 at 75-79.)
`
`
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`5
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`Petition for Inter Partes Review of U.S. Patent No. 8,795,741
`
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`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
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`McCandless Ave., Pittsburgh, PA 15201 (“Praxair” or “Petitioner”), and Praxair,
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`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 ʼ741 Patent.
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`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
`
`
`
`6
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`Petition for Inter Partes Review of U.S. Patent No. 8,795,741
`
`
`
`Please address all correspondence and service to counsel listed above.
`
`Petitioner consents to service by email.
`
`VII. PERSON OF SKILL IN THE ART AND STATE OF THE ART
`A person of ordinary skill in the art (“POSA”) is a hypothetical person
`
`presumed to know the relevant prior art. (See IPR2013-00116, Final Written
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`Decision, Paper 68 at 9.) A POSA is of ordinary creativity, not merely an
`
`automaton, and is capable of combining teachings of the prior art. (Id. (citing KSR
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`Int’l Co. v. Teleflex Inc., 550 U.S. 398, 420-21 (2007).) Petitioner submits that a
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`POSA with regard to the ’741 Patent is a pediatric cardiologist with experience
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`prescribing iNO. (Ex. 1002 ¶¶ 54-55.) 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
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`ʼ741 Patent. (See 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).
`
`
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`7
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`Petition for Inter Partes Review of U.S. Patent No. 8,795,741
`
`
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`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 then it must be described in the specification “with reasonable clarity,
`
`deliberateness, and precision.” In re Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994).
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`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.
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`1993). Petitioner submits that the claim terms of the ʼ741 Patent are not limited to
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`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
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`construction only to the extent the Board determines that a specific construction is
`
`necessary to clarify the broadest reasonable interpretation of the term “children.”
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`B. Claim Construction of the Term “Children”
`Claims 34 and 37 recite “children.” (Ex. 1001 at 17:26; 18:1.) Before the
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`EPD, Merriam Webster (Ex. 1051) defined a “child” (“children”) 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 specification, a POSA
`
`would have understood “children” to mean an unborn or recently born human
`
`
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`8
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`Petition for Inter Partes Review of U.S. Patent No. 8,795,741
`
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`being. The specification states that “the term ‘children’ (and variations thereof)
`
`includes those being around 4 weeks to 18 years of age. (Ex. 1001 at 4:22-23
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`(emphasis added).) As the word “includes” demonstrates, this disclosure is not
`
`limiting. Instead, it specifies one subset of ages included under the commonly
`
`understood definition of “children.”
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`IX. STATEMENTS 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 1-44 on the
`
`grounds listed in the table below.
`
`Ground
`
`35 U.S.C.
`
`Index of References
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`§ 103
`
`Bernasconi, Loh and Goyal.
`
`§ 103
`
`§ 103
`
`§ 103
`
`§ 103
`
`§ 103
`
`and
`
`Bernasconi, Loh, INOMAX label,
`Juliana and Goyal.
`Bernasconi, Loh, Macrae
`Goyal.
`Bernasconi, Loh, INOMAX label,
`Juliana, Macrae and Goyal.
`Ichinose, Neonatal Group, Macrae,
`Loh, Germann and Goyal.
`Ichinose, Neonatal Group, Macrae,
`Loh, INOMAX label, Germann and
`Goyal.
`
`ʼ741 Patent
`Claims
`1, 2, 4, 6-14, 17-
`23, 31, 32, 34-35,
`37-40, and 42-44
`24-27, 29, 30, and
`33
`3, 5, 15, 16, 36,
`and 41
`28
`
`1-23, 31, 32, and
`34-44
`24-30 and 33
`
`
`
`9
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`Petition for Inter Partes Review of U.S. Patent No. 8,795,741
`
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`Per 37 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.)5
`
`Claims 1, 9, 24, 34, and 37 are the five independent claims. Claim 1 recites:
`
`A method of treating patients who are candidates for [iNO]6 treatment,
`which method reduces the risk that inhalation of nitric oxide gas will induce
`an increase in [wedge pressure]7 leading to pulmonary edema in neonatal
`patients with hypoxic respiratory failure, the method comprising:
`(a) identifying a plurality of term or near-term neonatal patients who have
`hypoxic respiratory failure and are candidates for 20 ppm [iNO] treatment;
`(b) determining that a first patient of the plurality does not have [LVD]8;
`
`
`5 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.)
`
`6 “Inhaled nitric oxide” abbreviated as “iNO.”
`
`7 “Pulmonary capillary wedge pressure (PCWP)” abbreviated as “wedge
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`pressure.” See FN 4.
`
`8 “Left ventricular dysfunction” abbreviated as “LVD.”
`
`
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`10
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`Petition for Inter Partes Review of U.S. Patent No. 8,795,741
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`
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`(c) determining that a second patient of the plurality has [LVD], so is at
`particular risk of increased [wedge pressure] leading to pulmonary edema
`upon treatment with [iNO];
`(d) administering 20 ppm [iNO] treatment to the first patient; and
`(e) excluding the second patient from treatment with [iNO], based on the
`determination that the second patient has [LVD], so is at particular risk of
`increased [wedge pressure] leading to pulmonary edema upon treatment with
`[iNO].
`
`(Ex. 1001 at 14:28-49.) Independent claim 9 includes almost all of the same
`
`elements as claim 1 except part (e) recites:
`
`excluding the second patient from treatment with [iNO] based on the
`determination in (c), or, despite the second patient’s ongoing need for [iNO]
`treatment for hypoxic respiratory failure, discontinuing the second patient’s
`treatment with [iNO] after it was begun, the discontinuation being in view of
`the determination in (c).
`
`(Ex. 1001 at 15:29-35.) Independent claim 24 includes almost all of the same
`
`method steps as claim 1, except part (c) recites:
`
`administering a first treatment regimen to the first patient, wherein the first
`treatment regimen comprises administration of 20 ppm [iNO] for 14 days or
`until the first patient’s hypoxia has resolved.
`
`(Ex. 1001 at 16:41-44.) Additionally, part (e) recites:
`
`administering a second treatment regimen to the second patient, wherein the
`second treatment regimen does not comprise either (i) administration of
`
`
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`11
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`Petition for Inter Partes Review of U.S. Patent No. 8,795,741
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`
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`[iNO] for 14 days or (ii) administration of [iNO] until the second patient's
`hypoxia has resolved.
`
`(Ex. 1001 at 16:49-53.) Independent claim 34 recites:
`
`A method of treating patients who are candidates for [iNO] treatment, which
`method reduces the risk that inhalation of nitric oxide gas will induce an
`increase in [wedge pressure] leading to pulmonary edema, the method
`comprising:
`(a) identifying a plurality of patients who are children with a condition that
`makes them candidates for 20 ppm [iNO] treatment;
`(b) determining that a first patient of the plurality does not have [LVD];
`(c) determining that a second patient of the plurality has [LVD], so is at
`particular risk of increased [wedge pressure] leading to pulmonary edema
`upon treatment with [iNO];
`(d) administering 20 ppm [iNO] treatment to the first patient; and
`(e) excluding the second patient from treatment with [iNO], based on the
`determination that the second patient has [LVD], so is at particular risk of
`increased [wedge pressure] lead