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,
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`v.
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`UNITED THERAPEUTICS, INC.,
`Patent Owner.
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`Case No. IPR2017-01621
`Patent No. 9,358,240
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`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 9,358,240
`
`
`
`Mail Stop PATENT BOARD
`Patent Trial and Appeal Board
`United States Patent and Trademark Office
`PO Box 1450
`Alexandria, Virginia 22313-1450
`Submitted Electronically via the Patent Review Processing System
`
`

`

`TABLE OF CONTENTS
`
`
`INTRODUCTION ............................................................................................... 1
`I.
`II. MANDATORY NOTICES – 37 C.F.R. § 42.8 .................................................. 3
`A. Real Party-In-Interest Under 37 C.F.R. § 42.8(b)(1) ...................................... 3
`B. Related Matters Under 37 C.F.R. § 42.8(b)(2) ................................................ 4
`C. Lead and Back-Up Counsel Under 37 C.F.R. § 42.8(b)(3) ............................. 4
`D. Service Information Under 37 C.F.R. § 42.8(b)(4) ......................................... 5
`III. REQUIREMENTS FOR IPR – 37 C.F.R. § 42.104 ........................................ 5
`A. Grounds for Standing Under 37 C.F.R. § 42.104(a) ....................................... 5
`B. Identification of the Challenge Under 37 C.F.R. § 42.104(b) and Relief
`Requested ................................................................................................................ 5
`C. Claim Construction Under 37 C.F.R. §§ 42.100(b), 42.104(b)(3) .................. 6
`D. How the Construed Claims are Unpatentable Under 37 C.F.R. §
`42.104(b)(4) ............................................................................................................ 7
`E. Supporting Evidence Under 37 C.F.R. § 42.104(b)(5) ................................... 7
`IV. THE CHALLENGED CLAIMS ..................................................................... 7
`V. LEVEL OF ORDINARY SKILL IN THE ART ................................................ 8
`VI. DETAILED EXPLANATION UNDER 37 C.F.R. § 42.104(B) .................... 9
`A. All References Relied Upon as Grounds for Trial Are Prior Art to the ‘240
`Patent ...................................................................................................................... 9
`1. Applicable Legal Standards ......................................................................... 9
`2. Based On The Record of Proceedings Before the PTO, The Date of
`Invention is No Earlier than May 15, 2006 ............................................... 10
`a. For Purposes of this Petition, Petitioner Assumes That Each Claim is
`Supported by the Provisional Application. .................................................... 10
`b. The Efforts to Antedate Prior Art Found In the File History Do Not
`Show a Date of Invention for the ’240 Patent Claims Before May 15, 2006
`
`11
`The Prior Art References Relied Upon Are Printed Publications ............. 12
`a. Voswinckel Is a Prior Art Printed Publication ....................................... 12
`b. Ghofrani Is a Prior Art Printed Publication ............................................ 14
`
`3.
`
`i
`
`

`

`i. Ghofrani Was Publicly Accessible More Than 1 Year Before the
`Earliest Possible Filing Date ...................................................................... 14
`ii. Ghofrani Is “By Another” ................................................................... 15
`c. Patton Is a Prior Art Printed Publication ................................................ 16
`d. The OptiNeb® User Manual Is a Printed Publication ............................ 16
`e. EU Community Register Is a Printed Publication .................................. 18
`B. Ground 1: Claims 1-9 are Invalid as Obvious Under § 103(a) Over
`Voswinckel in view of Patton and Ghofrani ........................................................ 21
`1. Claim 1 Would Have Been Obvious Over Voswinckel in View of Patton
`and Ghofrani .............................................................................................. 22
`a. Preamble: “A method of treating pulmonary hypertension” .................. 22
`i. Limitation [A]: “administering by inhalation to a human suffering
`from pulmonary hypertension a therapeutically effective single event dose
`of a formulation comprising from 200 to 1000 µg/ml of treprostinil or a
`pharmaceutically acceptable salt thereof” .................................................. 23
`ii. Limitation [B]: “with a pulsed ultrasonic nebulizer [B1] that
`aerosolizes a fixed amount of treprostinil or a pharmaceutically acceptable
`salt thereof per pulse,” ................................................................................ 24
`iii.
`Limitation [C]: “said pulsed ultrasonic nebulizer comprising an
`opto-acoustical trigger which allows said human to synchronize each
`breath to each pulse” .................................................................................. 26
`iv. Limitation [D]: “said therapeutically effective single event dose
`comprising from 15 µg to 90 µg of treprostinil or a pharmaceutically
`acceptable salt thereof delivered in 1 to 18 breaths.” ................................ 28
`2. Claim 2 Would Have Been Obvious Over Voswinckel in view of Patton
`and Ghofrani .............................................................................................. 30
`3. Claim 3 Would Have Been Obvious Over Voswinckel in view of Patton
`and Ghofrani .............................................................................................. 31
`4. Claim 4 Would Have Been Obvious Over Voswinckel in view of Patton,
`and Ghofrani .............................................................................................. 32
`5. Claim 5 Would Have Been Obvious Over Voswinckel in view of Patton
`and Ghofrani .............................................................................................. 33
`6. Claim 6 Would Have Been Obvious Over Voswinckel in view of Patton
`and Ghofrani .............................................................................................. 34
`
`ii
`
`

`

`7. Claim 7 Would Have Been Obvious Over Voswinckel in view of Patton
`and Ghofrani .............................................................................................. 34
`8. Claim 8 Would Have Been Obvious Over Voswinckel in view of Patton,
`and Ghofrani .............................................................................................. 34
`9. Claim 9 Would Have Been Obvious Over Voswinckel in view of Patton
`and Ghofrani .............................................................................................. 35
`C. Ground 2: Claims 1-9 are Invalid as Obvious Under § 103(a) Over
`Voswinckel in view of Patton and the OptiNeb® User Manual .......................... 35
`1. Claim 1 Would Have Been Obvious Over Voswinckel in view of Patton
`and the OptiNeb® User Manual ................................................................ 36
`i. Limitation [D]: “said therapeutically effective single event dose
`comprising from 15 µg to 90 µg of treprostinil or a pharmaceutically
`acceptable salt thereof delivered in 1 to 18 breaths.” ................................ 36
`2. Claims 2, 3, 7, and 8 Would Have Been Obvious Over Voswinckel in
`view of Patton, and the OptiNeb® User Manual. ...................................... 39
`3. Claim 4 Would Have Been Obvious Over Voswinckel in view of Patton
`and the OptiNeb® User Manual ................................................................ 39
`4. Claim 5 Would Have Been Obvious Over Voswinckel in view of Patton,
`and the OptiNeb® User Manual. ............................................................... 40
`5. Claim 6 Would Have Been Obvious Over Voswinckel in view of Patton,
`and the OptiNeb® User Manual ................................................................ 41
`D. Ground 3: Claims 1-9 are Invalid as Obvious Under § 103(a) Over
`Voswinckel in view of Ghofrani and the EU Community Register. .................... 42
`1. Claim 1 Would Have Been Obvious Over Voswinckel in view of
`Ghofrani and the EU Community Register ............................................... 42
`i. Limitation [B]: “with a pulsed ultrasonic nebulizer [B1] that
`aerosolizes a fixed amount of treprostinil or a pharmaceutically acceptable
`salt thereof per pulse,” ................................................................................ 43
`ii. Limitation [C]: “said pulsed ultrasonic nebulizer comprising an opto-
`acoustical trigger which allows said human to synchronize each breath to
`each pulse” ................................................................................................. 45
`2. Claims 2-9 Would Have Been Obvious Over Voswinckel in view of
`Ghofrani and the EU Community Register. .............................................. 47
`
`iii
`
`

`

`a. Alleged Evidence Regarding Secondary Considerations Does Not
`Render the Claimed Subject Matter Non-Obvious ........................................ 47
`VII. CONCLUSION .............................................................................................. 50
`
`
`
`
`
`
`iv
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`

`

`PETITIONER’S EXHIBIT LIST
`
`
`1003
`
`1004
`
`1005
`
`Exhibit Description
`1001
`U.S. Patent No. 9,358,240
`1002
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`Inter Partes Review of U.S. Patent No. 9,358,240
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`Declaration of Scott Bennett, Ph.D.
`Affidavit of Christopher Butler, June 15, 2017
`Affidavit of Christopher Butler, June 16, 2017
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`1024
`
`v
`
`

`

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`Revatio, FDA Label, 4/2015
`St. Louis Federal Reserve, Consumer Price Index,
`https://fred.stlouisfed.org/series/CPIAUCSL (accessed 5/17/2017)
`Tracleer, FDA Label, 10/2016
`Tyvaso, FDA Label, 06/2016
`Uptravi, FDA Label, 12/2015
`UTC, “Q2 2010 United Therapeutics Earnings Conference Call,”
`7/28/2010
`
`xi
`
`

`

`UTC, Form 10‐K, 2000
`UTC, Form 10‐K, 2002
`UTC, Form 10‐K, 2003
`UTC, Form 10‐K, 2004
`UTC, Form 10‐K, 2005
`UTC, Form 10‐K, 2006
`UTC, Form 10‐K, 2007
`UTC, Form 10‐K, 2008
`UTC, Form 10‐K, 2009
`UTC, Form 10‐K, 2010
`UTC, Form 10‐K, 2011
`UTC, Form 10‐K, 2012
`UTC, Form 10‐K, 2013
`UTC, Form 10‐K, 2014
`UTC, Form 10‐K, 2015
`UTC, Form 10‐K, 2016
`
`Veletri, FDA Label, 6/2012
`Ventavis, FDA Label, 11/2013
`Request for Review filed in 12/591,200 (Mar. 9, 2015)
`Substantive Submission filed in 12/591,200 (Nov. 9, 2015) (with
`accompanying Declaration of Dr. Roham T. Zamanian)
`Amendment and Reply filed in 12/591,200 (Feb. 2, 2016) (with
`accompanying Second Declaration of Dr. Roham T. Zamanian)
`Final Rejection of 12/591,200 (Oct. 10, 2014)
`
`1143
`1144
`1145
`1146
`1147
`1148
`1149
`1150
`1151
`1152
`1153
`1154
`1155
`1156
`1157
`1158
`1159
`1160
`1161
`1162
`
`1163
`
`1164
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`
`
`
`
`xii
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`

`

`I.
`
`INTRODUCTION
`This Petition seeks inter partes review—and ultimately the cancellation of—
`
`claims 1-9 of U.S. Patent No. 9,358,240, which relates to a method of treating
`
`pulmonary hypertension using a pulsed ultrasonic nebulizer and a formulation of a
`
`drug called treprostinil. As we show below, the ’240 patent claims are invalid and
`
`should be cancelled.
`
`On November 10, 2004, a group of researchers—including some of the named
`
`inventors on the ’240 patent—presented the findings of a study that involved the
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`aerosolized delivery of treprostinil with a pulsed ultrasonic nebulizer for the
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`treatment of patients with pulmonary hypertension at a widely-attended American
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`Heart Association conference in Louisiana. Abstracts of the presentations were
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`published before the conference in a supplement to the widely-distributed periodical
`
`Circulation. This abstract, which we will call “Voswinckel,” put the public in
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`possession of everything needed to arrive at the claimed subject matter. Instead of
`
`promptly seeking a patent, those identifying themselves as inventors of the ’240
`
`patent waited. They waited roughly nineteen months before filing the provisional
`
`application to which the ’240 patent claims priority. Under the law, they waited too
`
`long.
`
`Allowing the ’240 patent claims to stand in light of knowledge that was placed
`
`in the public domain in November 2004 is at odds with some of the most
`
`1
`
`

`

`fundamental concepts in United States patent law. As has long been the law, §
`
`102(b) “presents a sort of statute of limitations, formerly two years, now one year,
`
`within which an inventor, even though he has made a patentable invention, must act
`
`on penalty of loss of his right to a patent.” Application of Foster, 343 F.2d 980, 987-
`
`88 (CCPA 1965). The clock starts running when the public is placed in possession
`
`of the claimed subject matter “through the categories of the disclosure enumerated
`
`in 102(b), which include a ‘printed publication’ anywhere describing the invention.”
`
`Id. at 988. Although the patent laws do not allow inventors to recapture that which
`
`they placed in the public domain more than a year before their earliest filings by
`
`making minor, obvious variations upon their public disclosures, id., that’s precisely
`
`what has happened here.
`
`While Voswinckel does not expressly disclose some of the minor details of
`
`the claims, those details would have been blatantly obvious to those skilled in the
`
`art. For example,
`
` Using pulsed ultrasonic nebulizers having audible and visual indicators
`
`instructing the user when to breathe was well-known in the art; and
`
` The dosing specified by the claims was also not only specifically
`
`described by a separate printed publication discussing inhalable
`
`treprostinil, but it was readily derivable from the manual for the
`
`2
`
`

`

`OptiNeb® nebulizer described by Voswinckel based on the skill and
`
`knowledge of an ordinarily skilled artisan.
`
`As we show below, none of the claims contribute significantly to the
`
`disclosure of Voswinckel. They recite only minor, known differences. Accordingly,
`
`they should each be cancelled as unpatentable under 35 U.S.C. § 103(a).
`
`II. MANDATORY NOTICES – 37 C.F.R. § 42.8
`A. Real Party-In-Interest Under 37 C.F.R. § 42.8(b)(1)
`Watson Laboratories, Inc. is the real party-in-interest for the purposes of this
`
`proceeding.
`
` Out of an abundance of caution, Petitioner identifies Teva
`
`Pharmaceuticals USA, Inc., Teva Parenteral Medicines, Inc., Pliva Hrvatska D.O.O.,
`
`and Barr Laboratories, Inc.1 as real parties-in-interest for the IPR requested by this
`
`Petition solely to the extent that Patent Owner contends that these separate legal
`
`entities should be named a real party-in-interest in the requested IPR, and the
`
`
`1 The following entities are parent corporations and/or publicly-held companies
`
`that own 10 percent or more of the stock of the Teva real parties-in-interest: Sicor
`
`Inc.; Teva Pharmaceuticals Holdings Cooperatieve, U.A.; IVAX LLC; Orvet UK;
`
`Teva Pharmaceuticals Europe B.V.; Teva Pharmaceuticals Industries Ltd.; Barr
`
`Pharmaceuticals, LLC; Ivax International B.V.; IVAX International GmbH; Ivax
`
`International (Luxembourg) S.a.r.l.;and IVAX Holdings GmbH.
`
`3
`
`

`

`Petitioner does so to avoid the potential expenditure of resources to resolve such a
`
`challenge. Watson Laboratories, Inc. is an indirectly-owned, wholly owned
`
`subsidiary of Teva Pharmaceuticals USA, Inc. No unnamed entity is funding,
`
`controlling, or otherwise has an opportunity to control or direct this Petition or the
`
`Petitioner’s participation in any resulting IPR.
`
`B. Related Matters Under 37 C.F.R. § 42.8(b)(2)
`Patent Owner has asserted the ’240 patent in the United States District Court
`
`for the District of New Jersey in case No. 3:15-cv-5723. Petitioner is the defendant
`
`in that action. Petitioner is also filing petition IPR2017-01622 related to U.S. Pat.
`
`No. 9,339,507. The ’240 patent and the ’507 patent share a common parent and
`
`provisional application.
`
`C. Lead and Back-Up Counsel Under 37 C.F.R. § 42.8(b)(3)
`Lead: Michael K. Nutter (Reg. No. 44,979, WINSTON & STRAWN LLP,
`
`35 W. Wacker Dr., Chicago, IL 60601, P: 312-558-5600 / F: 312-558-5700,
`
`mnutter@winston.com). Backup: Andrew R. Sommer (Reg. No. 53,932,
`
`WINSTON & STRAWN LLP, 1700 K Street, N.W., Washington, D.C. 20006-3817,
`
`P: 202-282-5896 / F: 202-282-5100, asommer@winston.com); Kurt A. Mathas (pro
`
`hac vice motion to be filed, WINSTON & STRAWN LLP, 35 W. Wacker Dr.,
`
`Chicago, IL 60601, P: 312-558-5600 / F: 312-558-5700, kmathas@winston.com).
`
`4
`
`

`

`Service Information Under 37 C.F.R. § 42.8(b)(4)
`
`D.
`Service via hand-delivery may be made at the postal mailing address of lead
`
`and back-up counsel. Petitioner consents to service by e-mail at the following email
`
`address: IPR2017-01621@winston.com.
`
`III. REQUIREMENTS FOR IPR – 37 C.F.R. § 42.104
`A. Grounds for Standing Under 37 C.F.R. § 42.104(a)
`Petitioner certifies that the ’240 patent is available for inter partes review
`
`(“IPR”). Petitioner is not barred or estopped from requesting this IPR. Petitioner is
`
`filing this petition within one year of being served with a complaint alleging
`
`infringement of the ’240 patent. Patent Owner filed an amended complaint asserting
`
`the ’240 patent on June 21, 2016, which was the date Watson is deemed served with
`
`the amended complaint under the Federal Rules. Dkt No. 49; Fed. R. Civ. P.
`
`15(a)(2), (3).
`
`B.
`
`Identification of the Challenge Under 37 C.F.R. § 42.104(b) and
`Relief Requested
`
`Petitioner requests cancellation of claims 1-9 of the ’240 patent in view of the
`
`following prior art references: (1) Robert Voswinckel, et al. “Inhaled treprostinil
`
`sodium for the treatment of pulmonary hypertension” Abstract #1414, Circulation,
`
`110, 17, Supplement (October 2004): III-295 (“Voswinckel”); (2) Hossein Ardeschi
`
`Ghofrani, Robert Voswinckel, et al., “Neue Therapieoptionen in der Behandlung der
`
`pulmonalarteriellen Hypertonie,” Hertz, 30,4 (June 2005): 296-302 (“Ghofrani”);
`
`5
`
`

`

`(3) WO 93/00951 to Patton (“Patton”); (4) OptiNeb®-ir Operating Instructions
`
`(“OptiNeb® User Manual”); and (5) Annexes
`
`to Commission Decision
`
`C(2005)3436 of 05 September 2005, (Annex III – Ventavis® Labelling and Package
`
`Leaflet) (“EU Community Register”). Each of these references is a prior art printed
`
`publication or patent under 35 U.S.C. § 102 (pre-AIA).
`
`Petitioner presents the following grounds for trial:
`
`Ground: Claims
`
`Reference(s):
`
`Ground 1
`
`1-9
`
`Ground 2
`
`1-9
`
`Ground 3
`
`1-9
`
`Obvious over Voswinckel in view of Patton and
`
`Ghofrani
`
`Obvious over Voswinckel in view of Patton and the
`
`OptiNeb® User Manual
`
`Obvious over Voswinckel in view of Ghofrani and the
`
`EU Community Register.
`
`
`
`C. Claim Construction Under 37 C.F.R. §§ 42.100(b), 42.104(b)(3)
`Under 37 C.F.R. § 41.100(b), a claim of an unexpired patent is given its
`
`broadest reasonable interpretation in light of its specification. See Cuozzo Speed
`
`Techs., LLC v. Lee, 136 S.Ct. 2131 (2016). For the purposes of this proceeding, all
`
`terms should have their broadest reasonable interpretation when the claims are read
`
`6
`
`

`

`in light of the ’240 patent’s specification, as would have been understood by a
`
`POSA.
`
`Consistent with an agreement reached in the district court litigation between
`
`the parties under the more restrictive Phillips standard for claim construction, the
`
`district court has ordered that the phrase “an opto-acoustical trigger” found in claim
`
`1 means “a trigger with an optical element (e.g., light) and an acoustical element
`
`(e.g., sound).” Dkt. No. 66. Thus, the broadest reasonable interpretation of this term
`
`in light of the ’240 patent