`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________
`
`
`WATSON LABORATORIES, INC.
`Petitioner
`
`v.
`
`UNITED THERAPEUTICS, INC.
`Patent Owner
`
`
`
`Patent No. 9,339,507
`Issue Date: July 13, 2017
`Title: TREPROSTINIL ADMINISTRATION BY INHALATION
`_______________
`
`Inter Partes Review No. 2017-01622
`____________________________________________________________
`
`PATENT OWNER PRELIMINARY RESPONSE
`
`
`
`
`
`4812-5158-1520.1
`
`

`

`IPR2017-01622
`
`Patent Owner Preliminary Response
`
`
`
`
`
`TABLE OF CONTENTS
`
`
`
`I. 
`
`II. 
`
`INTRODUCTION ........................................................................................... 1 
`
`SUMMARY OF ARGUMENT ....................................................................... 1 
`
`III.  BACKGROUND ............................................................................................. 2 
`
`IV.  CLAIM CONSTRUCTION ............................................................................ 6 
`
`A. 
`
`B. 
`
`Person of Ordinary Skill in the Art (“POSA”) ...................................... 7 
`
`Claim Terms .......................................................................................... 9 
`
`1. 
`
`2. 
`
`3. 
`
`“pulsed” ....................................................................................... 9 
`
`“opto-acoustical trigger” ........................................................... 10 
`
`“single event dose”.................................................................... 12 
`
`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 
`
`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. 
`
`Petitioner has not demonstrated public accessibility of the
`Opti-Neb Manual. ..................................................................... 24 
`i
`
`4812-5158-1520.1
`
`

`

`IPR2017-01622
`
`
`
`Patent Owner Preliminary Response
`
`2. 
`
`Petitioner has not demonstrated public accessibility for
`the EU Community Register. .................................................... 29 
`
`C. 
`
`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. .............. 33 
`
`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. ..................................................................................... 34 
`
`Dr. Donovan selects specific portions in the EU
`Community Register regarding Vent-Neb while ignoring
`other portions inconsistent with her conclusions. ..................... 36 
`
`The Donovan Declaration has a number of other
`instances of conclusory or unsupported assertions. .................. 39 
`
`Conclusion ................................................................................ 40 
`
`B. 
`
`None of the Grounds 1-3 present a prima facie case of
`obviousness ......................................................................................... 40 
`
`1. 
`
`2. 
`
`3. 
`
`Ground 1 – Voswinckel in view of Chaudry, Patton, and
`Ghofrani .................................................................................... 45 
`
`Ground 2 – Voswinckel in view of Chaudry, Patton, and
`the Opti-Neb Manual ................................................................ 47 
`
`Ground 3 –Voswinckel in view of Chaudry, Ghofrani,
`and the EU Community Register .............................................. 50 
`
`C. 
`
`Conclusion ........................................................................................... 52 
`
`VIII.  CONCLUSION .............................................................................................. 52 
`
`
`
`
`4812-5158-1520.1
`
`
`
`ii
`
`

`

`IPR2017-01622
`
`
`
`Patent Owner Preliminary Response
`
`TABLE OF AUTHORITIES
`
`CASES 
`
`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
`
`Advanced Cardiovascular Sys. v. Medtronic, Inc., 265 F.3d 1294 (Fed.Cir.2001) 10
`
`Blue Calypso, LLC v. Groupon, Inc., 815 F.3d 1331 (Fed. Cir. 2016) ............ 24, 26
`
`Cuozzo Speed Technologies, LLC v. Lee, 136 S. Ct. 2131(2016) ............................. 6
`
`In re Antonie, 559 F.2d 618 (CCPA 1977) .............................................................. 39
`
`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) ........................................... 11
`
`KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (2007) ................................................ 40
`
`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
`
`Motorola Mobility LLC v. Arnouse, IPR2013-00010 (PTAB Jan. 30, 2013) ......... 18
`
`Murphy Bros. v. Michetti Pipe Stringing, 526 U.S. 344 (1999) .............................. 19
`
`Mylan Labs. Ltd. v. Aventis Pharma S.A., IPR2016-00627 (PTAB Aug. 23, 2016)
` ............................................................................................................................. 34
`
`Phillips v. AWH Corp., 415 F.3d 1303 (Fed. Cir. 2005) .......................................6, 9
`
`Riverwood Int’l Corp. v. R.A. Jones &Co., Inc., 324 F.3d 1346 (Fed. Cir. 2003) .. 21
`
`4812-5158-1520.1
`
`iii
`
`

`

`IPR2017-01622
`
`
`
`Patent Owner Preliminary Response
`
`ServiceNow, Inc., v. Hewlett-Packard Co., IPR2015-00716 (PTAB Aug. 26, 2015)
` ............................................................................................................................. 21
`
`Straight Path IP Group Inc. v. Sipnet EU S.R.O., 806 F.3d 1356 (Fed. Cir. 2015) . 9,
`10
`
`Synopsys, Inc. v. Mentor Graphics Corp., 814 F.3d 1309 (Fed. Cir. 2016) ............ 33
`
`Trs. of Columbia Univ. v. Illumina, Inc., 620 F. App'x 916 (Fed. Cir. 2015) ......... 34
`
`TRW Automotive US LLC v. Magna Electronics, Inc., IPR2014-00293 (PTAB June
`27, 2014) .......................................................................................... 15, 18, 19, 20
`
`Zetec, Inc. v. Westinghouse Elec. Co., IPR2014-00384 (PTAB July 23, 2014)48, 50
`
`STATUTES 
`
`21 U.S.C. § 355(b) ................................................................................................... 19
`
`35 U.S.C. § 102(a) ................................................................................................... 24
`
`35 U.S.C. § 271(e)(2)(A) ......................................................................................... 18
`
`35 U.S.C. § 286 ........................................................................................................ 20
`
`35 U.S.C. § 311(b) ................................................................................................... 24
`
`35 U.S.C. § 313 .......................................................................................................... 1
`
`35 U.S.C. § 315(a) ................................................................................................... 20
`
`35 U.S.C. § 315(b) ............................................................................................ 13, 14
`
`37 C.F.R. § 42.100(b) ................................................................................................ 6
`
`37 C.F.R. § 42.107 ..................................................................................................... 1
`
`37 C.F.R. § 42.108 ................................................................................................... 33
`
`37 C.F.R. § 42.108(c) ............................................................................................... 34
`
`RULES 
`
`Fed. R. Civ. P. 5.1(b)(2)(E) ..................................................................................... 14
`iv
`
`4812-5158-1520.1
`
`

`

`IPR2017-01622
`IPR2017-01622
`
`
`
`Patent Owner Preliminary Response
`Patent Owner Preliminary Response
`
`NJ L.Civ.R. 5.1(a) .................................................................................................... 14
`NJ L.CiV.R. 5.1(a) .................................................................................................... 14
`
`
`
`
`
`4812-5158-1520.1
`4812-5158-1520.1
`
`
`
`v
`
`

`

`IPR2017-01622
`
`
`
`Patent Owner Preliminary Response
`
`Exhibit No.
`2001
`2002
`
`2003
`
`2004
`
`2005
`
`2006
`
`2007
`
`2008
`
`2009
`
`2010
`
`2011
`2012
`2013
`
`2014
`2015
`2016
`
`2017
`
`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
`
`4812-5158-1520.1
`
`vi
`
`

`

`IPR2017-01622
`
`
`
`Patent Owner Preliminary Response
`
`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
`
`2018
`
`2019
`2020
`2021
`2022
`2023
`2024
`
`2025
`2026
`2027
`2028
`2029
`
`2030
`
`
`
`
`
`4812-5158-1520.1
`
`vii
`
`

`

`IPR2017-01622
`
`
`
`Patent Owner Preliminary Response
`
`I.
`
`INTRODUCTION
`
`
`
`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
`
`Preliminary Response to the Petition of Watson Laboratories, Inc. (“Petitioner” or
`
`“Watson”) challenging claims1-9 of U.S. Patent No. 9,339,507 (“the ’507 patent”).
`
`This preliminary response is timely filed within three months of the Board’s
`
`notice, mailed July 13, 2017, according the Petition a filing date. The three-month
`
`nominal due date falls on October 13, 2017.
`
`II.
`
`SUMMARY OF ARGUMENT
`
`Patent Owner urges denial of the Petition on all grounds because (i) the
`
`Petition was not timely filed, (ii) three of the five references relied upon for
`
`Grounds 1-3 do not qualify as prior art, and (iii) Petitioner has failed to
`
`demonstrate a likelihood of success on Grounds 1-3.
`
`
`1 The caption incorrectly identifies Patent Owner as “United Therapeutics, Inc.,”
`
`whereas the face of the patent identifies Patent Owner as “United Therapeutics
`
`Corporation.” Ex. 1001, 1(73). Accordingly, appropriate correction of this caption
`
`is suggested.
`
`4812-5158-1520.1
`
`1
`
`

`

`IPR2017-01622
`
`
`
`Patent Owner Preliminary Response
`
`III. BACKGROUND
`The ’507 patent relates to the treatment of pulmonary hypertension and is
`
`listed in the Orange Book for the product Tyvaso (treprostinil) Inhalation Solution,
`
`a drug-device combination for delivery of treprostinil by inhalation. Ex. 1001, col.
`
`18:12; Ex. 2012. At the time of the invention, as today, pulmonary hypertension
`
`was a poorly understood, often fatal, disease with limited treatment options. The
`
`first approved treatment for pulmonary hypertension—and sole approved treatment
`
`for over five years—was epoprostenol, which has significant burdens and
`
`challenges to patients. For example, epoprostenol can only be administered
`
`intravenously. Ex. 2004. Accordingly, the need for a permanent transcutaneous
`
`intravenous catheter posed risks of infection, occlusion, and sepsis. Id. These
`
`problems and even a short interruption in infusion risked hemodynamic collapse
`
`and even death because of the delivery complications and several minute half-life
`
`of the drug. Id. Moreover, epoprostenol requires daily mixing and refrigeration,
`
`thus requiring the patient to carry a cold pack to avoid degradation at room
`
`temperature and an infusion pump in order to safely administer the drug. Id.
`
`Later-approved intravenous and subcutaneous administration of treprostinil also
`
`had limitations, such as intolerable site pain in some instances. Ex. 1136, 1.
`
`Inhaled delivery of treprostinil, as in Tyvaso®, has several benefits over
`
`subcutaneous and intravenous administration of epoprostenol and treprostinil. It is
`2
`
`4812-5158-1520.1
`
`

`

`IPR2017-01622
`
`
`
`Patent Owner Preliminary Response
`
`less intrusive and complicated, and it removes the requirements of subcutaneous
`
`and intravenous administration that present significant problems. In addition,
`
`treprostinil is stable at room temperature, with a half-life of several hours rather
`
`than several minutes, thus freeing patients of the burden of carrying ice packs to
`
`ensure the safety and efficacy of the drug.
`
`As of May 15, 2006, the priority date of the ’507 patent, the only FDA-
`
`approved prostacyclin-type drug that could be given in an inhalable form was
`
`iloprost, marketed as Ventavis®. At that time, the results of an Aerosolized
`
`Iloprost Randomized (AIR) Study documenting the effects of inhaled iloprost had
`
`been public about three and a half years, and Ventavis® had been on the market for
`
`about one and a half years. Ex. 1162, 21; Ex. 2005, 1-28. Clinicians were largely
`
`still of the opinion, however, that intravenous administration of a prostacyclin
`
`analog was preferable to inhaled delivery. Ex. 1162, 21. Thus, there was concern
`
`that the adoption of Ventavis® could be happening too rapidly without a full
`
`understanding of the side effects. Id.
`
`Further, adoption of Ventavis® posed a number of issues. For instance,
`
`Ventavis® has a half-life between 20-25 min. Ex. 1162, 21, 23-24. As a result,
`
`Ventavis® needs to be used 6-9 times a day, as frequently as every 2 hours, which
`
`was considered challenging for patients to implement. Id. Moreover, the fact that
`
`4812-5158-1520.1
`
`3
`
`

`

`IPR2017-01622
`
`
`
`Patent Owner Preliminary Response
`
`Ventavis® has a short half-life results in periods where patients may be off-
`
`medication while asleep unless they wake up to take a dose of the drug. Id.
`
`Nocturnal hypoxemia is a common symptom of patients with pulmonary
`
`hypertension; thus, periods where a patient is off-medication and asleep are risky.
`
`Id. There were also concerns about how to address the interaction between the
`
`patient and the nebulizer. Id.
`
`In contrast, because of the pharmacodynamic differences between iloprost
`
`and treprostinil, Tyvaso® (inhaled treprostinil) does not need to be administered as
`
`frequently as Ventavis®, leading to higher patient compliance and less risk of
`
`rebound hypertension. Tyvaso® (inhaled treprostinil) has a much longer half-life
`
`than Ventavis® when inhaled by human subjects suffering from pulmonary
`
`hypertension. This allows Tyvaso® to be administered markedly less frequently
`
`— about 1 to 4 times a day. Patients are more likely to comply with a regimen that
`
`requires less frequent administrations. Furthermore, because Tyvaso® has a longer
`
`half-life than Ventavis®, there is less risk when the patient is asleep or otherwise
`
`unable to take the medication.
`
`When viewed purely as a number, 2-5 fewer events per day may not seem
`
`important. However, in the context of a pulmonary hypertension patient’s life, it
`
`can have a substantial impact on quality of life. Studies have shown a statistically
`
`4812-5158-1520.1
`
`4
`
`

`

`IPR2017-01622
`
`
`
`Patent Owner Preliminary Response
`
`significant improvement in quality of life reported by pulmonary hypertension
`
`patients who switched from inhaled iloprost to inhaled treprostinil, using FDA
`
`approved levels of iloprost and treprostinil. One question used in the quality of life
`
`questionnaire was “how easy or difficult is it to plan when you will use the
`
`medication each time?” to which each patient in the study responded with a grade
`
`of 1 (extremely difficult), 2 (very difficult), 3 (difficult), 4 (somewhat easy), 5
`
`(easy), 6 (very easy), and 7 (extremely easy). Ex. 1058, 17. The 71 subjects who
`
`answered this question both while taking inhaled iloprost and then again after
`
`switching to inhaled treprostinil responded with an average score of 3.6 (between
`
`difficult and somewhat easy) for inhaled iloprost and 6.0 (very easy) for inhaled
`
`treprostinil. Id.
`
`Another study reported that “the transition from inhaled iloprost to inhaled
`
`treprostinil resulted in a time saving of approximately 1.4 h per day.” Ex. 2021, 5.
`
`Patients transferring from inhaled iloprost to inhaled treprostinil also had improved
`
`six-minute walk distances (a common metric to assess pulmonary hypertension),
`
`improved patient satisfaction, and improved quality of life. Id. at 5-6
`
`Tyvaso® is a commercially successful product, which is becoming more
`
`successful each year. Tyvaso’s® commercial success is particularly evident when
`
`compared to Ventavis®. Once Tyvaso® entered the market, it was clinically
`
`4812-5158-1520.1
`
`5
`
`

`

`IPR2017-01622
`
`
`
`Patent Owner Preliminary Response
`
`preferred to Ventavis®, and Tyvaso® rapidly increased its market share, while the
`
`share held by Ventavis® rapidly decreased. See, e.g., Ex. 1059, 8; Ex. 1162, 9; Ex.
`
`1163, 16. Despite Ventavis’® long presence in the U.S. market before the launch
`
`of Tyvaso®, Tyvaso® took away the majority of the U.S. market for inhaled
`
`prostacyclins from Ventavis® in a single year. Id. From September 2009 to
`
`September 2010, when the majority of this rapid sales growth occurred for
`
`Tyvaso®, UTC had an average 25.0% share of sales representative contacts in the
`
`pulmonary hypertension market compared to 30.7% share of sales representative
`
`contacts for Actelion, who markets Ventavis®. Ex. 1059, 8. Thus, Tyvaso®
`
`enjoyed tremendous commercial success during this period despite being marketed
`
`with a substantially lower share of pulmonary hypertension sales representatives.
`
`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 a person of ordinary
`
`skill in the art. 37 C.F.R. § 42.100(b); see Cuozzo Speed Technologies, LLC v.
`
`Lee, 579 U.S. __, 136 S. Ct. 2131(2016); see also Phillips v. AWH Corp., 415 F.3d
`
`1303, 1316 (Fed. Cir. 2005). Consistent with the law, Patent Owner presents
`
`arguments for claim construction in the context of the specification, prosecution
`
`history, and understanding in the art.
`
`Independent claim 1 recites:
`
`6
`
`4812-5158-1520.1
`
`

`

`IPR2017-01622
`
`
`
`Patent Owner Preliminary Response
`
`A kit for treating pulmonary hypertension comprising:
`
`
`
`a formulation comprising 200 to 1000 μg/ml of treprostinil or a
`
`pharmaceutically acceptable salt thereof;
`
`
`
`a pulsed ultrasonic nebulizer comprising an opto-acoustical
`
`trigger configured to (a) aerosolize a fixed amount of treprostinil per
`
`pulse, and (b) deliver by inhalation a therapeutically effective single
`
`event dose of said formulation,
`
`
`
`said single event dose comprising from 15 μg to 90 μg of
`
`treprostinil or a pharmaceutically acceptable salt thereof delivered in 1
`
`to 18 breaths; and
`
`
`
`instructions for using the pulsed ultrasonic nebulizer with the
`
`formulation to treat a patient with pulmonary hypertension by
`
`delivering 15 μg to 90 μg treprostinil or a pharmaceutically acceptable
`
`salt thereof in 1 to 18 breaths to the patient in the single event dose.
`
`Ex. 1001, col.18:12-28.
`
`Person of Ordinary Skill in the Art (“POSA”)
`
`A.
`The claims of the ’507 patent are directed to methods for “treating
`
`pulmonary hypertension” with a specific pulsed ultrasonic nebulized. Several of
`
`the inventors listed on the ’507 patent have post-graduate degrees in the field of
`
`medicine or drug development and all had at least several years of research,
`7
`
`4812-5158-1520.1
`
`

`

`IPR2017-01622
`
`
`
`Patent Owner Preliminary Response
`
`executive, and/or clinical experience in the investigation and treatment of
`
`pulmonary hypertension and in developing pharmaceutical products for the
`
`treatment of pulmonary hypertension. Ex. 2020, ¶1, 7; Ex. 1028, 1; Ex. 1029, 1;
`
`Ex. 2023; Ex. 2024; Ex. 2025.
`
`Consistent with the experience of the named inventors, a POSA at the time
`
`of invention would have been a person with a post-graduate degree in medicine or
`
`drug development (such as the pharmaceutical sciences) with at least two years of
`
`experience in the investigation or treatment of pulmonary hypertension. A POSA
`
`may also have had additional experience in the study, development, or use of
`
`dosage forms that had been used to treat pulmonary hypertension, such as solid
`
`oral dosage forms (e.g., tablets and capsules), injectables, and inhaled therapies. A
`
`POSA may have had a lower level of formal education if such a person had more
`
`years of experience in the investigation or treatment of pulmonary hypertension.
`
`To the extent that this conflicts with Petitioner’s definition of a POSA, it
`
`does not affect the analysis provided in the Declaration of Dr. Richard Dalby (“the
`
`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
`
`art. Ex. 2001, ¶10; Ex. 2022.
`
`4812-5158-1520.1
`
`8
`
`

`

`IPR2017-01622
`
`
`
`Patent Owner Preliminary Response
`
`B. Claim Terms
`Patent Owner offers claim construction for the terms “pulsed,” “opto-
`
`acoustical trigger,” and “single event dose.”
`
`1.
`“pulsed”
`Analysis of the claims begin with the plain meaning. See, e.g., Straight Path
`
`IP Group Inc. v. Sipnet EU S.R.O., 806 F.3d 1356, 1360-1361 (Fed. Cir. 2015); see
`
`also Ex. 2001, ¶12. The term “pulsed” is an adjective form of the word “pulse,”
`
`which the Oxford Dictionary of English defines as “[a] single vibration or short
`
`burst of sound, electric current, light, or other wave.” Ex. 2002, 3.
`
`In this case, the specification informs on the wave to which the “pulse”
`
`refers. See Phillips, 415 F.3d at 1316. The specification uses the term “pulse” to
`
`refer to intermittent delivery of aerosol for a fixed duration, followed by pauses of
`
`a fixed duration. See, e.g., Ex. 1001, col.14:38-39.
`
`The term “pulsed” also appears in the claims of U.S. Patent No. 9,358,240
`
`(“the ’240 patent”), of which the ’507 patent is a continuation. Ex. 1001, 1(60). In
`
`the prosecution of the ’240 patent, a Response dated February 2, 2016 indicates
`
`that a “pulsed” ultrasonic nebulizer produces “a ‘pulse’ of aerosol production
`
`followed by a pause” and that the generated pulses are “spaced apart in time that
`
`correspond to each breath inhaled by a human.” Ex. 1163, 12-13. This
`
`interpretation in the ’240 patent’s prosecution history is consistent with the use of
`9
`
`4812-5158-1520.1
`
`

`

`IPR2017-01622
`
`
`
`Patent Owner Preliminary Response
`
`the term “pulse” in the specification. See Advanced Cardiovascular Sys. v.
`
`Medtronic, Inc., 265 F.3d 1294, 1306 (Fed.Cir.2001) (“The prosecution history of
`
`a related patent can be relevant if, for example, it addresses a limitation in common
`
`with the patent in suit”).
`
`A POSA would, thus, understand that the claimed “pulsed ultrasonic
`
`nebulizer” generates aerosol at regular intervals, meaning that the pulse would
`
`occur with a specified periodicity, i.e., as a wave form with consistent time
`
`intervals between each pulse. Ex. 2001, ¶14. Accordingly, the term “pulse” refers
`
`to a period of aerosol generation, and the term “pulsed” refers to the generation of
`
`such pulses with a specified periodicity. Ex. 2001, ¶15.
`
`“opto-acoustical trigger”
`
`2.
`United Therapeutics and Watson reached an agreement in Civil Action No:
`
`3:15-cv-05723 PGS-LHG in the U.S. District Court for the District of New Jersey
`
`(“the civil action”) that the phrase “an opto-acoustical trigger” in claim 1 means “a
`
`trigger with an optical element (e.g., light) and an acoustical element (e.g.,
`
`sound).” Pet. 7; Dkt. No. 66. Although the stipulation provides examples of the
`
`optical and acoustical elements of the “opto-acoustical trigger,” the term “trigger”
`
`is not given a particular construction. Thus, the term “trigger” should be given its
`
`plain and ordinary meaning. Ex. 2001, ¶17; see also Straight Path, 806 F.3d at
`
`1360-1361.
`
`4812-5158-1520.1
`
`10
`
`

`

`IPR2017-01622
`
`
`
`Patent Owner Preliminary Response
`
`The Oxford Dictionary of English defines “trigger” as “an event that is the
`
`cause of a particular action, process, or situation.” Ex. 2002, 4. In view of this
`
`definition, an “opto-acoustical trigger” would be understood to require an optical
`
`element (e.g., light) and an acoustical element (e.g., sound) that is designed to
`
`cause a particular action, process, or situation. Ex. 2001, ¶17.
`
`The “opto-acoustical trigger” is taught by the specification to synchronize
`
`breath and pulse to provide exact dosage. Ex. 1001, col.14:39-412; Ex. 2001, ¶19
`
`see also In re Smith, No. 2016-2303 (Fed. Cir. Sept. 26, 2017) (Explaining that the
`
`broadest reasonable interpretation applied by the Board should be consistent with
`
`the specification’s use of the term as it would be understood by a POSA).
`
`
`2 The Petitioner asserts is that the specification refers to the “prior art OPTINEB®
`
`device” is taught in the specification as having an opto-acoustical trigger. Pet. 7.
`
`However, the assertion that this device was in the prior art is not supported by (i)
`
`paragraph 70 of the Donovan Declaration (Ex. 1002) which relates generally to the
`
`topics regarding which Dr. Donovan was asked to opine, or (ii) the specification,
`
`which notes that “a modified OPTINEB® inhalation device” was used in “Study
`
`iii).” Id.; Ex. 1001, col. 16:21-23.
`
`4812-5158-1520.1
`
`11
`
`

`

`IPR2017-01622
`
`
`
`Patent Owner Preliminary Response
`
` As Dr. Dalby explains, in order to provide the exact dosage, the timing of
`
`inhalation must be synchronized with the pulse to avoid sedimentation. Ex. 2001,
`
`¶19; see also Ex. 2007. If the breath is not synchronized with the pulse, an exact
`
`dosage would be impossible to deliver due to the sedimentary loss during the time
`
`elapsed between pulse and inhalation. Id. Therefore, a POSA would understand
`
`the term “opto-acoustical trigger” to refer to an optical element (e.g., light) and an
`
`acoustical element (e.g., sound that is designed to cause a human to immediately
`
`inhale each aerosol pulse from the pulsed ultrasonic nebulizer. Ex. 2001, ¶17-19.
`
`“single event dose”
`
`3.
`The claims also recite the term “single event dose.” Claim 1 requires that 15
`
`to 90 micrograms of treprostinil or its salt be delivered in 1 to 18 breaths to the
`
`pulmonary hypertension patient in a “single event dose.” The specification
`
`provides further teachings relating to the single event at issue, e.g.:
`
`Administering of treprostinil in a single event can be carried out in a
`
`limited number of breaths by a patient….
`
`The total time of a single administering event can be less than 5
`
`minutes, or less than 1 minute, or less than 30 seconds.
`
`Treprostinil can be administered a single time per day or several times
`
`per day.
`
`4812-5158-1520.1
`
`12
`
`

`

`IPR2017-01622
`
`
`
`Patent Owner Preliminary Response
`
`Ex. 1001, col. 7:54-62. The working examples in the specification conclude that
`
`an inhaled dose of 15 micrograms “induced pulmonary vasodilation for longer than
`
`3 hours compared to placebo inhalation.” Ex. 1001, col. 17:39-44. Claims 3 and 9
`
`further indicate that the single event dose can be separated in time, instructing “not
`
`to repeat the single event dose for a period of at least 3 hours.” Based on this
`
`usage, a POSA would understand it to mean the total time during which the
`
`pulmonary hypertension patient inhales a necessary dose of treprostinil in one
`
`sitting, which may be spaced apart from the next single event dose by several
`
`hours, and there may be more than one pulse and more than one breath
`
`corresponding to each pulse within a single event dose. Ex. 2001, ¶21.
`
`V. THE PETITION SHOULD BE DENIED ON ALL GROUNDS
`BECAUSE IT WAS NOT TIMELY FILED.
`
`Under 35 U.S.C. § 315(b), “[a]n inter partes review may not be instituted if
`
`the petition requesting the proceeding is filed more than 1 year after the date on
`
`which the petitioner, real party in interest, or privy of the petitioner was served
`
`with a complaint alleging infringement of the patent.” In the instant case, a
`
`complete Petition was not filed within this 1-year time period, and, thus, the
`
`Petition should be denied.
`
`4812-5158-1520.1
`
`13
`
`

`

`IPR2017-01622
`
`
`
`Patent Owner Preliminary Response
`
`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
`
`timeframe for filing an inter partes review begins upon service of a complaint
`
`alleging infringement of the patent.
`
`The complaint at issue – an Amended Complaint– was filed in the Civil
`
`Action. See Pet. 4. Under the local rules in the District of New Jersey, service is
`
`governed by Rule 5(b)