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`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________
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`WATSON LABORATORIES, INC.
`Petitioner
`
`v.
`
`UNITED THERAPEUTICS, INC.
`Patent Owner
`
`
`
`Patent No. 9,358,240
`Issue Date: June 7, 2016
`Title: TREPROSTINIL ADMINISTRATION BY INHALATION
`_______________
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`Inter Partes Review No. 2017-01621
`____________________________________________________________
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`PATENT OWNER PRELIMINARY RESPONSE
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`4827-7573-9470.2
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`TABLE OF CONTENTS
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`
`
`I.
`
`II.
`
`INTRODUCTION ........................................................................................... 1
`
`SUMMARY OF ARGUMENT ....................................................................... 1
`
`III. BACKGROUND ............................................................................................. 2
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`IV. CLAIM CONSTRUCTION ............................................................................ 6
`
`A.
`
`B.
`
`Person of Ordinary Skill in the Art (“POSA”) ...................................... 7
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`Claim Terms .......................................................................................... 9
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`1.
`
`2.
`
`3.
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`“pulsed” and “pulse” ................................................................... 9
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`“opto-acoustical trigger” ........................................................... 10
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`“single event dose”.................................................................... 12
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`V.
`
`THE PETITION SHOULD BE DENIED ON ALL GROUNDS
`BECAUSE IT WAS NOT TIMELY FILED................................................. 13
`
`A.
`
`B.
`
`The Amended Complaint was served on June 17, 2016. .................... 14
`
`The holding in TRW should not be applied to these facts. .................. 15
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`VI. GROUNDS 1, 2, AND 3 SHOULD BE DENIED BECAUSE NONE
`OF GHOFRANI, THE OPTI-NEB MANUAL, OR THE EU
`COMMUNITY REGISTER HAVE BEEN QUALIFIED AS PRIOR
`ART. .............................................................................................................. 21
`
`A. Ghofrani is not prior art “by another.” ................................................ 21
`
`B.
`
`Petitioner has not demonstrated that the Opti-Neb Manual and
`the EU Community Register were publically accessible. ................... 24
`
`1.
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`Petitioner has not demonstrated public accessibility of the
`Opti-Neb Manual. ..................................................................... 24
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`2.
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`Petitioner has not demonstrated public accessibility for
`the EU Community Register. .................................................... 29
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`C.
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`Conclusion ........................................................................................... 33
`
`VII. THE PETITION SHOULD BE DENIED BECAUSE IT FAILS TO
`DEMONSTRATE A REASONABLE LIKELIHOOD OF SUCCESS
`ON GROUNDS 1, 2, AND 3. ....................................................................... 33
`
`A.
`
`The testimony of Dr. Donovan reflects improper hindsight. .............. 34
`
`1.
`
`2.
`
`3.
`
`4.
`
`Dr. Donovan cherry-picks a breathing rate and inhalation
`times to arrive at the claimed doses using the Opti-Neb
`Manual. ..................................................................................... 35
`
`Dr. Donovan selects specific portions in the EU
`Community Register regarding Vent-Neb while ignoring
`other portions inconsistent with her conclusions. ..................... 37
`
`The Donovan Declaration has a number of other
`instances of conclusory or unsupported assertions. .................. 40
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`Conclusion ................................................................................ 40
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`B.
`
`None of the Grounds 1-3 presents a prima facie case of
`obviousness ......................................................................................... 40
`
`1.
`
`2.
`
`3.
`
`Ground 1 – Voswinckel in view of Patton and Ghofrani ......... 45
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`Ground 2 – Voswinckel in view of Patton and the Opti-
`Neb Manual ............................................................................... 48
`
`Ground 3 –Voswinckel in view of Ghofrani and the EU
`Community Register ................................................................. 51
`
`C.
`
`Petitioner has not addressed objective indicia of non-
`obviousness presented during prosecution. ......................................... 53
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`D.
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`Conclusion ........................................................................................... 54
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`VIII. CONCLUSION .............................................................................................. 55
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`TABLE OF AUTHORITIES
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`CASES
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`Actavis, Inc. v. Research Corp. Techs., Inc., IPR2014-01126 (PTAB Jan. 9, 2015)
` ............................................................................................................................. 29
`
`Activision Blizzard, Inc. v. Acceleration Bay, LLC, IPR 2015-01964 (PTAB Mar.
`29, 2017) ............................................................................................................. 24
`
`Blue Calypso, LLC v. Groupon, Inc., 815 F.3d 1331 (Fed. Cir. 2016) ............ 24, 26
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`Cisco Systems, Inc. v. C-Cation Techs., LLC, IPR2014-00454 (PTAB Aug. 29,
`2014) ................................................................................................................... 54
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`Cuozzo Speed Technologies, LLC v. Lee, 136 S. Ct. 2131(2016) ............................. 6
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`DeSilva v. Dileonardi, 181 F.3d 865 (7th Cir. 1999) .............................................. 54
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`In re Antonie, 559 F.2d 618 (CCPA 1977) .............................................................. 40
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`In re Cronyn, 890 F.2d 1158 (Fed. Cir. 1989) ......................................................... 26
`
`In re Hall, 781 F.2d 897 (Fed. Cir. 1986) ................................................................ 24
`
`In re Katz, 687 F.2d 450 (CCPA 1982) ................................................................... 21
`
`In re Smith, No. 2016-2303 (Fed. Cir. Sept. 26, 2017) ........................................... 12
`
`KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (2007) ................................................ 40
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`Kyocera Wireless Corp. v. Int’l Trade Comm’n, 545 F.3d 1340 (Fed. Cir. 2008) .. 24
`
`Lacks Industries, Inc. v. McKechnie Vehicle Components USA, Inc., 322 F.3d 1335
`(Fed. Cir. 2003) ................................................................................................... 21
`
`Merial Ltd. v. Virbac, IPR2014-01279 (PTAB 2015) ............................................. 34
`
`Motorola Mobility LLC v. Arnouse, IPR2013-00010 (PTAB Jan. 30, 2013) .. 18, 19
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`Murphy Bros. v. Michetti Pipe Stringing, 526 U.S. 344 (1999) .............................. 19
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`Mylan Labs. Ltd. v. Aventis Pharma S.A., IPR2016-00627 (PTAB Aug. 23, 2016)
` ............................................................................................................................. 34
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`Phillips v. AWH Corp., 415 F.3d 1303 (Fed. Cir. 2005) .......................................6, 9
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`Riverwood Int’l Corp. v. R.A. Jones &Co., Inc., 324 F.3d 1346 (Fed. Cir. 2003) .. 21
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`ServiceNow, Inc., v. Hewlett-Packard Co., IPR2015-00716 (PTAB Aug. 26, 2015)
` ............................................................................................................................. 21
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`Straight Path IP Group Inc. v. Sipnet EU S.R.O., 806 F.3d 1356 (Fed. Cir. 2015) . 9,
`10
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`Synopsys, Inc. v. Mentor Graphics Corp., 814 F.3d 1309 (Fed. Cir. 2016) ............ 34
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`Trs. of Columbia Univ. v. Illumina, Inc., 620 F. App'x 916 (Fed. Cir. 2015) ......... 34
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`TRW Automotive US LLC v. Magna Electronics, Inc., IPR2014-00293 (PTAB June
`27, 2014) .......................................................................................... 15, 18, 19, 20
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`Zetec, Inc. v. Westinghouse Elec. Co., IPR2014-00384 (PTAB July 23, 2014)49, 51
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`STATUTES
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`21 U.S.C. § 355(b) ................................................................................................... 19
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`35 U.S.C. § 102(a) ................................................................................................... 24
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`35 U.S.C. § 271(e)(2)(A) ......................................................................................... 18
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`35 U.S.C. § 286 ........................................................................................................ 20
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`35 U.S.C. § 311(b) ................................................................................................... 24
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`35 U.S.C. § 313 .......................................................................................................... 1
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`35 U.S.C. § 315(a) ................................................................................................... 20
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`35 U.S.C. § 315(b) ............................................................................................ 13, 14
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`37 C.F.R. § 42.100(b) ................................................................................................ 6
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`37 C.F.R. § 42.107 ..................................................................................................... 1
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`37 C.F.R. § 42.108 ................................................................................................... 33
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`37 C.F.R. § 42.108(c) ............................................................................................... 34
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`RULES
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`Fed. R. Civ. P. 5.1(b)(2)(E) ..................................................................................... 14
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`NJ L.Civ.R. 5.1(a) .................................................................................................... 14
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`Exhibit No.
`2001
`2002
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`2003
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`2004
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`2005
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`2006
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`2007
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`2008
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`2009
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`2010
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`2011
`2012
`2013
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`2014
`2015
`2016
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`2017
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`EXHIBITS
`
`Description
`Declaration of Dr. Richard Dalby
`Oxford Dictionary of English. 2nd ed. Revised. Oxford University
`Press, 2005 (excerpt).
`Newman, Stephen P. Respiratory drug delivery: essential theory and
`practice. Respiratory Drug Delivery Online, 2009 (excerpt).
`Hill, N., Therapeutic Options for the Treatment of Pulmonary
`Hypertension, Medscape Pulmonary Medicine 9(2) (2005).
`Exhibits Accompanying First Declaration of Dr. Roham Zamanian
`and Amendment and Reply filed in 12/591,200 (Nov. 9, 2015) (Ex.
`1162)
`Declaration of Dr. Edmund Elder and Exhibits Accompanying
`Second Declaration of Dr. Roham Zamanian Amendment and Reply
`filed in 12/591,200 (Feb. 2, 2016) (Ex. 1163)
`Finlay, Warren H. The Mechanics of Inhaled Pharmaceutical
`Aerosols: an Introduction. Academic Press, 2002 (excerpt).
`“Mechanical Ventilation.” American Journal of Respiratory and
`Critical Care Medicine 196(2):P3-4 (2017).
`Motion for Leave to File An Amended Complaint and Exhibits Filed
`in Civil Action No: 3:15-cv-05723 PGS-LHG
`Email Correspondence to Watson’s Counsel Serving Motion for
`Leave to File An Amended Complaint and attached Exhibits (Ex.
`2009).
`Consent Order Entering Motion for Leave to File An Amended
`Complaint in Civil Action No: 3:15-cv-05723 PGS-LHG
`Orange Book Listing for Tyvaso® (Accessed October 3, 2017)
`First Notice Letter Sent June 12, 2015 by Watson Regarding Orange
`Book Listed Tyvaso® Patents
`Issue Notifications for US Patent No. 9,399,507 and US Patent No.
`9,358,240
`FDA Form 3542, Listing US Patent No. 9,399,507 in Orange Book
`FDA Form 3542, Listing US Patent No. 9,358,240 in Orange Book
`Email Correspondence between United Therapeutics and Watson
`Regarding Proposed Schedule for Civil Action No: 3:15-cv-05723
`PGS-LHG in view of US Patent No. 9,399,507 and US Patent No.
`9,358,240
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`Second Notice Letter Sent June 29, 2016 by Watson Regarding
`Orange Book Listed Tyvaso® Patents
`Docket Navigator Summary Statistics on Unopposed Motions for
`Magistrate Judge Lois H. Goodman
`Declaration of Dr. Werner Seeger
`Bourge et al., Cardiovascular Therapeutics 31:38-44 (2013)
`Curriculum vitae of Dr. Richard Dalby
`Curriculum vitae of Dr. Lewis Rubin
`2002 Press Release Regarding Promotion of Robert Roscingo
`(accessed October 10, 2017)
`Shield Therapeutics Biography for Carl Sterritt (accessed October
`10, 2017)
`Declaration of Dr. Hossein A. Ghofrani
`Declaration of Dr. Frank Reichenberger
`Declaration of Dr. Freidrich Grimminger
`Excerpts from Deposition of Dr. Maureen Donovan in Civil Action
`No: 3:15-cv-05723 PGS-LHG
`Email Correspondence with Orange Book Staff Confirming Date of
`Listing for US Patent No. 9,399,507 and US Patent No. 9,358,240
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`2018
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`2019
`2020
`2021
`2022
`2023
`2024
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`2025
`2026
`2027
`2028
`2029
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`2030
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`I.
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`INTRODUCTION
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`
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`Pursuant to 35 U.S.C. § 313 and 37 C.F.R. § 42.107, Patent Owner United
`
`Therapeutics Corporation (“Patent Owner” or “United Therapeutics”)1 files this
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`Preliminary Response to the Petition of Watson Laboratories, Inc. (“Petitioner” or
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`“Watson”) challenging claims 1-9 of U.S. Patent No. 9,358,240 (“the ’240
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`patent”).
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`This preliminary response is timely filed within three months of the Board’s
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`notice, mailed July 13, 2017, according the Petition a filing date. The three-month
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`nominal due date falls on October 13, 2017.
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`II.
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`SUMMARY OF ARGUMENT
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`Patent Owner urges denial of the Petition on all grounds because (i) the
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`Petition was not timely filed, (ii) three of the four references relied upon for
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`Grounds 1-3 do not qualify as prior art, and (iii) Petitioner has failed to
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`demonstrate a likelihood of success on Grounds 1-3.
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`1 The caption incorrectly identifies Patent Owner as “United Therapeutics, Inc.,”
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`whereas the face of the patent identifies Patent Owner as “United Therapeutics
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`Corporation.” Ex. 1001, 1(73). Accordingly, appropriate correction of this caption
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`is suggested.
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`III. BACKGROUND
`The ’240 patent relates to the treatment of pulmonary hypertension and is
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`listed in the Orange Book for the product Tyvaso® (treprostinil) Inhalation
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`Solution, a drug-device combination for delivery of treprostinil by inhalation. Ex.
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`1001, col. 18:2-3; Ex. 2012. At the time of the invention, as today, pulmonary
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`hypertension was a poorly understood, often fatal, disease with limited treatment
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`options. The first approved treatment for pulmonary hypertension —and sole
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`approved treatment for over five years—was epoprostenol, which has significant
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`burdens and challenges to patients. For example, epoprostenol can only be
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`administered intravenously. Ex. 2004. Accordingly, the need for a permanent
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`transcutaneous intravenous catheter posed risks of infection, occlusion, and sepsis.
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`Id. These problems and even a short interruption in infusion risked hemodynamic
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`collapse and even death because of the delivery complications and several minute
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`half-life of the drug. Id. Moreover, epoprostenol requires daily mixing and
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`refrigeration, thus requiring the patient to carry a cold pack to avoid degradation at
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`room temperature and an infusion pump in order to safely administer the drug. Id.
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`Later-approved intravenous and subcutaneous administration of treprostinil also
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`had limitations, such as intolerable site pain in some instances. Ex. 1136, 1.
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`Inhaled delivery of treprostinil, as in Tyvaso®, has several benefits over
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`subcutaneous and intravenous administration of epoprostenol and treprostinil. It is
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`less intrusive and complicated, and it removes the requirements of subcutaneous
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`and intravenous administration that present significant problems. In addition,
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`treprostinil is stable at room temperature, with a half-life of several hours rather
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`than several minutes, thus freeing patients of the burden of carrying ice packs to
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`ensure the safety and efficacy of the drug.
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`As of May 15, 2006, the priority date of the ’240 patent, the only FDA-
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`approved prostacyclin-type drug that could be given in an inhalable form was
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`iloprost, marketed as Ventavis®. At that time, the results of an Aerosolized
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`Iloprost Randomized (AIR) Study documenting the effects of inhaled iloprost had
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`been public about three and a half years, and Ventavis® had been on the market for
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`about one and a half years. Ex. 1162, 21; Ex. 2005, 1-28. Clinicians were largely
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`still of the opinion, however, that intravenous administration of a prostacyclin
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`analog was preferable to inhaled delivery. Ex. 1162, 21. Thus, there was concern
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`that the adoption of Ventavis® could be happening too rapidly without a full
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`understanding of the side effects. Id.
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`Further, adoption of Ventavis® posed a number of issues. For instance,
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`Ventavis® has a half-life between 20-25 min. Ex. 1162, 21, 23-24. As a result,
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`Ventavis® needs to be used 6-9 times a day, as frequently as every 2 hours, which
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`was considered challenging for patients to implement. Id. Moreover, the fact that
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`Ventavis® has a short half-life results in periods where patients may be off-
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`medication while asleep unless they wake up to take a dose of the drug. Id.
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`Nocturnal hypoxemia is a common symptom of patients with pulmonary
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`hypertension; thus, periods where a patient is off-medication and asleep are risky.
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`Id. There were also concerns about how to address the interaction between the
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`patient and the nebulizer. Id.
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`In contrast, because of the pharmacodynamic differences between iloprost
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`and treprostinil, Tyvaso® (inhaled treprostinil) does not need to be administered as
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`frequently as Ventavis®, leading to higher patient compliance and less risk of
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`rebound hypertension. Tyvaso® (inhaled treprostinil) has a much longer half-life
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`than Ventavis® when inhaled by human subjects suffering from pulmonary
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`hypertension. This allows Tyvaso® to be administered markedly less frequently
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`— about 1 to 4 times a day. Patients are more likely to comply with a regimen that
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`requires less frequent administrations. Furthermore, because Tyvaso® has a longer
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`half-life than Ventavis®, there is less risk when the patient is asleep or otherwise
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`unable to take the medication.
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`When viewed purely as a number, 2-5 fewer events per day may not seem
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`important. However, in the context of a pulmonary hypertension patient’s life, it
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`can have a substantial impact on quality of life. Studies have shown a statistically
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`significant improvement in quality of life reported by pulmonary hypertension
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`patients who switched from inhaled iloprost to inhaled treprostinil, using FDA
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`approved levels of iloprost and treprostinil. One question used in the quality of life
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`questionnaire was “how easy or difficult is it to plan when you will use the
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`medication each time?” to which each patient in the study responded with a grade
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`of 1 (extremely difficult), 2 (very difficult), 3 (difficult), 4 (somewhat easy), 5
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`(easy), 6 (very easy), and 7 (extremely easy). Ex. 1058, 17. The 71 subjects who
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`answered this question both while taking inhaled iloprost and then again after
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`switching to inhaled treprostinil responded with an average score of 3.6 (between
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`difficult and somewhat easy) for inhaled iloprost and 6.0 (very easy) for inhaled
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`treprostinil. Id.
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`Another study reported that “the transition from inhaled iloprost to inhaled
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`treprostinil resulted in a time saving of approximately 1.4 h per day.” Ex. 2021, 5.
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`Patients transferring from inhaled iloprost to inhaled treprostinil also had improved
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`six-minute walk distances (a common metric to assess pulmonary hypertension),
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`improved patient satisfaction, and improved quality of life. Id. at 5-6
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`Tyvaso® is a commercially successful product, which is becoming more
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`successful each year. Tyvaso’s® commercial success is particularly evident when
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`compared to Ventavis®. Once Tyvaso® entered the market, it was clinically
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`preferred to Ventavis®, and Tyvaso® rapidly increased its market share, while the
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`share held by Ventavis® rapidly decreased. See, e.g., Ex. 1059, 8; Ex. 1162, 9; Ex.
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`1163, 16. Despite Ventavis’® long presence in the U.S. market before the launch
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`of Tyvaso®, Tyvaso® took away the majority of the U.S. market for inhaled
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`prostacyclins from Ventavis® in a single year. Id. From September 2009 to
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`September 2010, when the majority of this rapid sales growth occurred for
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`Tyvaso®, UTC had an average 25.0% share of sales representative contacts in the
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`pulmonary hypertension market compared to 30.7% share of sales representative
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`contacts for Actelion, who markets Ventavis®. Ex. 1059, 8. Thus, Tyvaso®
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`enjoyed tremendous commercial success during this period despite being marketed
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`with a substantially lower share of pulmonary hypertension sales representatives.
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`IV. CLAIM CONSTRUCTION
`The claims of a patent must be given their broadest reasonable interpretation
`
`consistent with the specification as it would be interpreted by one of ordinary skill
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`in the art. 37 C.F.R. § 42.100(b); see Cuozzo Speed Technologies, LLC v. Lee, 579
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`U.S. __, 136 S. Ct. 2131(2016); see also Phillips v. AWH Corp., 415 F.3d 1303,
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`1316 (Fed. Cir. 2005). Consistent with the law, Patent Owner presents arguments
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`for claim construction in the context of the specification, prosecution history, and
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`understanding in the art.
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`Independent claim 1 recites:
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`A method of treating pulmonary hypertension comprising:
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`
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`administering by inhalation to a human suffering from
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`pulmonary hypertension a therapeutically effective single event dose
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`of a formulation comprising from 200 to 1000 μg/ml of treprostinil or
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`a pharmaceutically acceptable salt thereof
`
`
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`with a pulsed ultrasonic nebulizer that aerosolizes a fixed
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`amount of treprostinil or a pharmaceutically acceptable salt thereof
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`per pulse,
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`
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`said pulsed ultrasonic nebulizer comprising an opto-acoustical
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`trigger which allows said human to synchronize each breath to each
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`pulse,
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`
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`said therapeutically effective single event dose comprising from
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`15 μg to 90 μg of treprostinil or a pharmaceutically acceptable salt
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`thereof delivered in 1 to 18 breaths.
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`Ex. 1001, col.18:1-38.
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`Person of Ordinary Skill in the Art (“POSA”)
`
`A.
`The claims of the ’240 patent are directed to methods for “treating
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`pulmonary hypertension” with a specific “pulsed ultrasonic nebulizer.” Several of
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`the inventors listed on the ’240 patent have post-graduate degrees in the field of
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`medicine or drug development and all had at least several years of research,
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`executive, and/or clinical experience in the investigation and treatment of
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`pulmonary hypertension and in developing pharmaceutical products for the
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`treatment of pulmonary hypertension. Ex. 2020, ¶1, 7; Ex. 1028, 1; Ex. 1029, 1;
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`Ex. 2023; Ex. 2024; Ex. 2025.
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`Consistent with the experience of the named inventors, a POSA at the time
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`of invention would have been a person with a post-graduate degree in medicine or
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`drug development (such as the pharmaceutical sciences) with at least two years of
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`experience in the investigation or treatment of pulmonary hypertension. A POSA
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`may also have had additional experience in the study, development, or use of
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`dosage forms that had been used to treat pulmonary hypertension, such as solid
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`oral dosage forms (e.g., tablets and capsules), injectables, and inhaled therapies. A
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`POSA may have had a lower level of formal education if such a person had more
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`years of experience in the investigation or treatment of pulmonary hypertension.
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`To the extent that this conflicts with Petitioner’s definition of a POSA, it
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`does not affect the analysis provided in the Declaration of Dr. Richard Dalby (“the
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`Dalby Declaration”), in which the Dalby Declaration applies Petitioner’s definition
`
`of POSA to analyze the conclusions drawn by Petitioner and Dr. Donovan on the
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`art. Ex. 2001, ¶10; Ex. 2022.
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`B. Claim Terms
`Patent Owner offers claim construction for the terms “pulsed,” “opto-
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`acoustical trigger,” and “single event dose.”
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`1.
`“pulsed” and “pulse”
`Analysis of the claims begins with the plain meaning. See, e.g., Straight
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`Path IP Group Inc. v. Sipnet EU S.R.O., 806 F.3d 1356, 1360-1361 (Fed. Cir.
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`2015); see also Ex. 2001, ¶12. In the present case, both terms “pulse” and
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`“pulsed” appear in the claims. Ex. 1001, col.18:1-38. The term “pulsed” is an
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`adjective form of the word “pulse,” which the Oxford Dictionary of English
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`defines as “[a] single vibration or short burst of sound, electric current, light, or
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`other wave.” Ex. 2002, 3.
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`In this case, both the specification and prosecution history inform on the
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`wave to which the “pulse” refers. See Phillips, 415 F.3d at 1316. The
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`specification uses the term “pulse” to refer to intermittent delivery of aerosol for a
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`fixed duration, followed by pauses of a fixed duration. See, e.g., Ex. 1001,
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`col.13:59-60. This interpretation is confirmed by the prosecution history. For
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`example, citing the as-filed specification, the Response dated February 2, 2016
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`indicates that a “pulsed” ultrasonic nebulizer produces “a ‘pulse’ of aerosol
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`production followed by a pause” and that the generated pulses are “spaced apart in
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`time that correspond to each breath inhaled by a human.” Ex. 1163, 12-13.
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`A POSA would, thus, understand that the claimed “pulsed ultrasonic
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`nebulizer” generates aerosol at regular intervals, meaning that the pulse would
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`occur with a specified periodicity, i.e., as a wave form with consistent time
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`intervals between each pulse. Ex. 2001, ¶14. Accordingly, the term “pulse” as it
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`appears in the claims refers to a period of aerosol generation, and the term “pulsed”
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`refers to the generation of such pulses with a specified periodicity. Ex. 2001, ¶15.
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`“opto-acoustical trigger”
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`2.
`United Therapeutics and Watson reached an agreement in Civil Action No:
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`3:15-cv-05723 PGS-LHG in the U.S. District Court for the District of New Jersey
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`(“the Civil Action”) that the phrase “an opto-acoustical trigger” in claim 1 means
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`“a trigger with an optical element (e.g. light) and an acoustical element (e.g.
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`sound).” Pet. 7; Dkt. No. 66. Although the stipulation provides examples of the
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`optical and acoustical elements of the “opto-acoustical trigger,” the term “trigger”
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`is not given a particular construction. Thus, the term “trigger” should be given its
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`plain and ordinary meaning. Ex. 2001, ¶17; see also Straight Path, 806 F.3d at
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`1360-1361.
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`The Oxford Dictionary of English defines “trigger” as “an event that is the
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`cause of a particular action, process, or situation.” Ex. 2002, 4. In view of this
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`definition, an “opto-acoustical trigger” would be understood to require an optical
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`element (e.g., light) and an acoustical element (e.g., sound) that is designed to
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`cause a particular action, process, or situation. Ex. 2001, ¶17.
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`The “opto-acoustical trigger” is required by claim 1 to “allow[] said human
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`to synchronize each breath to each pulse.” Read in context of the language of
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`claim 1, a POSA would understand the optical element (e.g., light) and the
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`acoustical element (e.g., sound) are designed to “cause the particular action,
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`process, or situation” of the synchronization of the patient’s inhalation with each
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`pulse. Ex. 2001, ¶18.
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`This interpretation is consistent with the specification, which further teaches
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`that synchronization between breath and pulse with the opto-acoustical trigger is
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`used to provide exact dosage. Ex. 1001, col.13:60-632; Ex. 2001, ¶19; see also In
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`2 The Petitioner asserts that the “prior art OPTINEB® device” is taught in the
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`specification as having an opto-acoustical trigger. Pet. 7. However, the assertion
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`that this device was in the prior art is not supported by (i) paragraph 70 of the
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`Donovan Declaration (Ex. 1002), which relates generally to the topics regarding
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`which Dr. Donovan was asked to opine, or (ii) the specification, which notes that
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`“a modified OPTINEB® inhalation device” was used in “Study iii).” Id.; Ex.
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`1001, col. 15:60-62.
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`re Smith, No. 2016-2303 (Fed. Cir. September 26, 2017) (Explaining that the
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`broadest reasonable interpretation applied by the Board should be consistent with
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`the specification’s use of the term as it would be understood by a POSA).
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`As Dr. Dalby explains, in order to provide the exact dosage, the timing of
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`inhalation must be synchronized with the pulse to avoid sedimentation. Ex. 2001,
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`¶19; see also Ex. 2007. If the breath is not synchronized with the pulse, an exact
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`dosage would be impossible to deliver due to the sedimentary loss during the time
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`elapsed between pulse and inhalation. Id. Therefore, a POSA would understand
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`the term “opto-acoustical trigger” to refer to an optical element (e.g., light) and an
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`acoustical element (e.g., sound) that is designed to cause a human to immediately
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`inhale each aerosol pulse from the pulsed ultrasonic nebulizer. Ex. 2001, ¶17-19.
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`“single event dose”
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`3.
`The claims also recite the term “single event dose.” Claim 1 requires that 15
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`to 90 micrograms of treprostinil or its salt be delivered in 1 to 18 breaths to the
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`pulmonary hypertension patient in a “single event dose.” The specification
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`provides further teachings relating to the single event at issue, e.g.:
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`Administering of treprostinil in a single event can be carried out in a
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`limited number of breaths by a patient….
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`The total time of a single administering event can be less than 5
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`minutes, or less than 1 minute, or less than 30 seconds.
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`Treprostinil can be administered a single time per day or several times
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`per day.
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`Ex. 1001, col. 7:54-62. The working examples in the specification conclude that
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`an inhaled dose of 15 micrograms “induced pulmonary vasodilation for longer than
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`3 hours compared to placebo inhalation.” Ex. 1001, col. 17:14-19. Claims 3 and 9
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`further indicate that the single event dose can be separated in time, instructing “not
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`to repeat the single event dose for a period of at least 3 hours.” Based on this
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`usage, a POSA would understand it to mean the total time during which the
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`pulmonary hypertension patient inhales a necessary dose of treprostinil in one
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`sitting, which may be spaced apart from the next single event dose by several
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`hours, and there may be more than one pulse and more than one breath
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`corresponding to each pulse within a single event dose. Ex. 2001, ¶21.
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`V. THE PETITION SHOULD BE DENIED ON ALL GROUNDS
`BECAUSE IT WAS NOT TIMELY FILED.
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`Under 35 U.S.C. § 315(b), “[a]n inter partes review may not be instituted if
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`the petition requesting the proceeding is filed more than 1 year after the date on
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`which the petitioner, real party in interest, or privy of the petitioner was served
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`with a complaint alleging infringement of the patent.” In the instant case, a
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`complete Petition was not filed within this 1-year time period, and, thus, the
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`Petition should be denied.
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`A. The Amended Complaint was served on June 17, 2016.
`The plain statutory language of 35 U.S.C. § 315(b) indicates that the 1-year
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`t