Case 1:20-cv-00755-RGA-JLH Document 75 Filed 04/30/21 Page 1 of 79 PageID #: 2675
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`UNITED THERAPEUTICS
`CORPORATION,
`
`Plaintiff,
`
`v.
`
`LIQUIDIA TECHNOLOGIES, INC.,
`
`Defendant.
`
`)
`)
`)
`)
`)
`)
`)
`)
`)
`)
`
`C.A. No. 20-755 (RGA)
`
`JOINT CLAIM CONSTRUCTION BRIEF
`
`MORRIS, NICHOLS, ARSHT & TUNNELL LLP
`Jack B. Blumenfeld (#1014)
`Michael J. Flynn (#5333)
`1201 North Market Street
`P.O. Box 1347
`Wilmington, DE 19899
`(302) 658-9200
`jblumenfeld@morrisnichols.com
`mflynn@morrisnichols.com
`
`Attorneys for Plaintiff United Therapeutics
`Corporation
`
`OF COUNSEL:
`
`Art Dykhuis
`WILSON SONSINI GOODRICH & ROSATI
`12235 El Camino Real
`San Diego, CA 92130
`(858) 305-2300
`
`Adam W. Burrowbridge
`WILSON SONSINI GOODRICH & ROSATI
`1700 K Street NW, Fifth Floor
`Washington, DC 20006
`(202) 973-8800
`
`William C. Jackson
`BOIES SCHILLER FLEXNER LLP
`1401 New York Avenue NW
`
`SHAW KELLER LLP
`Karen E. Keller (#4489)
`Jeff Castellano (#4837)
`Nathan R. Hoeschen (#6232)
`I.M. Pei Building
`1105 North Market Street, 12th Floor
`Wilmington, DE 19801
`(302)298-0700
`kkeller@shawkeller.com
`jcastellano@shawkeller.com
`nhoeschen@shawkeller.com
`
`Attorneys for Defendant Liquidia
`Technologies, Inc.
`
`OF COUNSEL:
`
`Sanya Sukduang
`Jonathan Davies
`Douglas W. Cheek
`COOLEY LLP
`1299 Pennsylvania Avenue, NW, Suite 700
`Washington, DC 20004-2400
`(202)842-7800
`
`Ivor Elrifi
`COOLEY LLP
`55 Hudson Yards
`New York, NY 10001-2157
`(212)479-6000
`
`IPR2021-00406
`United Therapeutics EX2024
`Page 1 of 79
`
`

`

`Case 1:20-cv-00755-RGA-JLH Document 75 Filed 04/30/21 Page 2 of 79 PageID #: 2676
`
`
`
`
`
`Washington, DC 20005
`(202) 237-2727
`
`Bill Ward
`BOIES SCHILLER FLEXNER LLP
`725 S Figueroa Street, 31st Floor
`Los Angeles, CA 90017
`(213) 995-5745
`
`Douglas Carsten
`MCDERMOTT WILL & EMERY LLP
`18565 Jamboree Road, Suite 250
`Irvine, CA 92615
`(949) 851-0633
`
`April 30, 2021
`
`
`
`
`Deepa Kannappan
`Lauren Krickl
`COOLEY LLP
`3175 Hanover Street
`Palo Alto, CA 94304-1130
`(650)843-5000
`
`Erik Milch
`COOLEY LLP
`11951 Freedom Drive, 14th Floor
`Reston, VA 20190-5640
`(703)546-8000
`
`
`
`
`
`2
`
`IPR2021-00406
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`Page 2 of 79
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`

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`Case 1:20-cv-00755-RGA-JLH Document 75 Filed 04/30/21 Page 3 of 79 PageID #: 2677
`
`
`
`TABLE OF CONTENTS
`
`Page
`
`I. 
`
`NATURE AND STAGE OF PROCEEDINGS .................................................................. 1 
`
`A. 
`
`Plaintiff’s Opening Position .................................................................................... 1 
`
`II. 
`
`INTRODUCTION .............................................................................................................. 1 
`
`A. 
`
`B. 
`
`Plaintiff’s Opening Position .................................................................................... 1 
`
`Defendant’s Answering Position ............................................................................ 2 
`
`III. 
`
`BACKGROUND OF TECHNOLOGY .............................................................................. 3 
`
`A. 
`
`B. 
`
`Plaintiff’s Opening Position .................................................................................... 3 
`
`Defendant’s Answering Position ............................................................................ 4 
`
`IV. 
`
`PERSON OF ORDINARY SKILL IN THE ART .............................................................. 6 
`
`A. 
`
`B. 
`
`Plaintiff’s Opening Position .................................................................................... 6 
`
`Defendant’s Answering Position ............................................................................ 6 
`
`V. 
`
`DISPUTED CLAIM TERMS ............................................................................................. 7 
`
`A. 
`
`Term 1: “a process” ................................................................................................ 7 
`
`Representative claim – ’066 patent, claim 1 ........................................................... 7 
`
`i. 
`
`Plaintiff’s Opening Position ........................................................................ 8 
`
`1. 
`
`2. 
`
`“a process” should be given its plain ordinary meaning ................. 8 
`
`Liquidia’s construction improperly imports limitations ................. 8 
`
`Defendant’s Answering Position .............................................................. 11 
`
`Plaintiff’s Reply Position .......................................................................... 16 
`
`Defendant’s Sur-Reply Position ............................................................... 21 
`
`ii. 
`
`iii. 
`
`iv. 
`
`B. 
`
`Term 2: “ambient temperature” ............................................................................ 24 
`
`Representative claim – ’066 patent, claim 8 ......................................................... 24 
`
`i. 
`
`Plaintiff’s Opening Position ...................................................................... 24 
`
`
`
`iii
`
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`

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`Case 1:20-cv-00755-RGA-JLH Document 75 Filed 04/30/21 Page 4 of 79 PageID #: 2678
`
`
`
`
`
`1. 
`
`“ambient temperature” should be given its plain and
`ordinary meaning .......................................................................... 24 
`
`ii. 
`
`iii. 
`
`iv. 
`
`Defendant’s Answering Position .............................................................. 25 
`
`Plaintiff’s Reply Position .......................................................................... 30 
`
`Defendant’s Sur-Reply Position ............................................................... 32 
`
`C. 
`
`Term 3: “stored” / “storing” / “storage” ............................................................... 33 
`
`Representative claim – ’066 patent, claim 8 ......................................................... 34 
`
`i. 
`
`Plaintiff’s Opening Position ...................................................................... 34 
`
`1. 
`
`UTC’s construction of “stored” / “storing” / “storage” is
`supported by the intrinsic evidence ............................................... 34 
`
`Defendant’s Answering Position .............................................................. 36 
`
`Plaintiff’s Reply Position .......................................................................... 40 
`
`Defendant’s Sur-Reply Position ............................................................... 42 
`
`ii. 
`
`iii. 
`
`iv. 
`
`D. 
`
`Term 4: “pharmaceutical batch” ........................................................................... 44 
`
`Representative claim – ’901 patent, claim 1 ......................................................... 44 
`
`i. 
`
`Plaintiff’s Opening Position ...................................................................... 44 
`
`1. 
`
`UTC’s construction for “pharmaceutical batch” should be
`adopted by the Court ..................................................................... 44 
`
`Defendant’s Answering Position .............................................................. 47 
`
`Plaintiff’s Reply Position .......................................................................... 51 
`
`Defendant’s Sur-Reply Position ............................................................... 54 
`
`ii. 
`
`iii. 
`
`iv. 
`
`E. 
`
`Term 5: “contacting the solution comprising treprostinil from step (b) with
`a base to form a salt of treprostinil” ...................................................................... 56 
`
`Representative claim – ’901 patent, claim 1 ......................................................... 56 
`
`i. 
`
`Plaintiff’s Opening Position ...................................................................... 56 
`
`1. 
`
`Plain and ordinary meaning is appropriate ................................... 56 
`
`ii. 
`
`Defendant’s Answering Position .............................................................. 57 
`
`iv
`
`IPR2021-00406
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`
`
`
`
`
`
`
`iii. 
`
`iv. 
`
`Plaintiff’s Reply Position .......................................................................... 61 
`
`Defendant’s Sur-Reply Position ............................................................... 64 
`
`
`
`
`v
`
`IPR2021-00406
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`Case 1:20-cv-00755-RGA-JLH Document 75 Filed 04/30/21 Page 6 of 79 PageID #: 2680
`
`
`
`Cases
`
`TABLE OF AUTHORITIES
`
`
`Page(s)
`
`Acceleration Bay LLC v. Activision Blizzard, Inc.,
`No. 16-453-RGA, 2017 WL 6508715 (D. Del. Dec. 20, 2017)...............................................58
`
`ActiveVideo Networks, Inc. v. Verizon Commc’ns,
`694 F.3d 1312 (Fed. Cir. 2012)................................................................................................11
`
`Aylus Networks, Inc. v. Apple Inc.
`856 F.3d 1353 (Fed. Cir. 2017)........................................................................................ passim
`
`Am. Med. Sys., Inc. v. Biolitec, Inc.,
`618 F.3d 1354 (Fed. Cir. 2010)................................................................................................21
`
`Biagro W. Sales, Inc. v. Grow More, Inc.,
`423 F.3d 1296 (Fed. Cir. 2005)..................................................................................................8
`
`Biogen Idec, Inc. v. GlaxoSmithKline LLC,
`713 F.3d 1090 (Fed. Cir. 2013)................................................................................................63
`
`Biovail Corp. Int’l v. Andrx Pharms., Inc.,
`239 F.3d 1297 (Fed. Cir. 2001)..........................................................................................28, 37
`
`Cont’l Circuits LLC v. Intel Corp.,
`915 F.3d 788 (Fed. Cir. 2019)............................................................................................21, 63
`
`E.I. du Pont de Nemours & Co. v. Phillips Petroleum Co.,
`849 F.2d 1430 (Fed. Cir. 1988)................................................................................................10
`
`E.I. du Pont de Nemours & Co. v. Unifrax I LLC,
`No. 14-1250-RGA, 2016 WL 158031 (D. Del. Jan. 13, 2016), aff’d, 921 F.3d
`1060 (Fed. Cir. 2019) ...............................................................................................................28
`
`Ekchian v. Home Depot, Inc.,
`104 F.3d 1299 (Fed. Cir. 1997)................................................................................................60
`
`Finjan, Inc. v. Secure Computing Corp.,
`626 F.3d 1197 (Fed. Cir. 2010)................................................................................................11
`
`GE Lighting Sols., LLC v. AgiLight, Inc.,
`750 F.3d 1304 (Fed. Cir. 2014)................................................................................................19
`
`Infinity Comput. Prods., Inc. v. Oki Data Ams., Inc.,
`987 F.3d 1053, 2021 WL 476067 (Fed. Cir. Feb. 10, 2021) .............................................28, 37
`
`
`
`vi
`
`IPR2021-00406
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`

`

`Case 1:20-cv-00755-RGA-JLH Document 75 Filed 04/30/21 Page 7 of 79 PageID #: 2681
`
`
`
`Infinity Comput. Prods., Inc. v. Oki Data Ams., Inc.,
`No. 18-463-LPS, 2019 WL 2422597 (D. Del. June 10, 2019), aff’d, 2021 WL
`476067 (Fed. Cir. Feb. 10, 2021) .............................................................................................38
`
`Input/Output, Inc. v. Sercel, Inc.,
`No. 5:06-CV-236, 2008 WL 5427982 (E.D. Tex. Apr. 28, 2008) ...........................................25
`
`Intel Corp. v. VIA Techs., Inc.,
`319 F.3d 1357 (Fed. Cir. 2003)................................................................................................35
`
`Jazz Pharms., Inc. v. Roxane Labs., Inc.,
`No. 10-6108 (ES), 2012 WL 4103880 (D.N.J. Sept. 14, 2012) ...............................................10
`
`Moleculon Research Corp. v. CBS, Inc.,
`793 F.2d 1261 (Fed. Cir. 1986)................................................................................................52
`
`Nautilus, Inc. v. Biosig Instruments, Inc.,
`572 U.S. 898 (2014) ...........................................................................................................35, 37
`
`Norian Corp. v. Stryker Corp.,
`363 F.3d 1321 (Fed. Cir. 2004)..........................................................................................52, 56
`
`Omega Eng’g, Inc. v. Raytek Corp.,
`334 F.3d 1314 (Fed. Cir. 2003)..........................................................................................15, 23
`
`Orthopaedic Hosp. v. DJO Global, Inc.,
`No. 19-CV-970 JLS (WVG), 2020 WL 3498167 (S.D. Cal. June 29, 2020) ....................57, 64
`
`OSRAM GmbH v. Int’l Trade Comm’n,
`505 F.3d 1351 (Fed. Cir. 2007)................................................................................................51
`
`Personalized Media Commc’ns, LLC v. Apple Inc.,
`952 F.3d 1336 (Fed. Cir. 2020)................................................................................................22
`
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005)........................................................................................ passim
`
`Rosco, Inc. v. Velvac Inc.,
`No. 11-117-LPS, 2012 WL 6028239 (D. Del. Dec. 4, 2012) ..................................................25
`
`Sanofi-Aventis U.S. LLC. v. Sandoz, Inc.,
`No. 07–2762 (JAP), 2010 WL 1049877 (D.N.J. Mar. 18, 2010) ................................11, 16, 46
`
`Schering Corp. v. Mylan Pharms., Inc.,
`No. 09–6383 (JLL), 2011 WL 2446563 (D.N.J. June 15, 2011) .............................................10
`
`SciMed Life Sys. v. Advanced Cardiovascular Sys.,
`242 F.3d 1337 (Fed. Cir. 2001)..................................................................................................2
`
`
`
`vii
`
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`

`Case 1:20-cv-00755-RGA-JLH Document 75 Filed 04/30/21 Page 8 of 79 PageID #: 2682
`
`
`
`Shire Dev., LLC v. Watson Pharm., Inc.,
`787 F.3d 1359 (Fed. Cir. 2015)................................................................................................22
`
`Simpson Strong-Tie Co., Inc. v. Oz-Post Int’l., LLC,
`No. 3:18-cv-01188-WHO, 2020 WL 3187950 (N.D. Cal. June 15, 2020) ................................9
`
`SIPCO, LLC V. Abb, Inc.,
`No. 6:11–CV–0048 LED–JDL, 2012 WL 3112302 (E.D. Tex. July 30, 2012) ................10, 46
`
`Smith & Nephew, Inc. v. Ethicon, Inc.,
`276 F.3d 1304 (Fed. Cir. 2001)................................................................................................52
`
`Southwall Techs., Inc. v. Cardinal IG Co.,
`54 F.3d 1570 (Fed. Cir. 1995)..................................................................................................22
`
`SRI Int’l v. Matsushita Elec. Corp. of Am.,
`775 F.2d 1107 (Fed. Cir. 1985) (en banc) ................................................................................39
`
`Sunovion Pharms., Inc. v. Teva Pharms. USA, Inc.,
`731 F.3d 1271 (Fed. Cir. 2013)..........................................................................................22, 38
`
`Therasense, Inc. v. Dickinson & Co.,
`593 F.3d 1325 (Fed. Cir. 2010)................................................................................................66
`
`Thorner v. Sony Comput. Entm’t Am., LLC,
`669 F.3d 1362 (Fed. Cir. 2012)..........................................................................................16, 30
`
`United Therapeutics Corp. v. SteadyMed Ltd.,
`702 F. App’x 990 (Fed. Cir. 2017) ......................................................................................5, 50
`
`Verizon Servs. Corp. v. Vonage Holdings Corp.,
`503 F.3d 1295 (Fed. Cir. 2007)................................................................................................23
`
`Vitronics Corp. v. Conceptronic, Inc.,
`90 F.3d 1576 (Fed. Cir. 1996)....................................................................................................9
`
`Vivid Techs., Inc. v. Am. Sci. & Eng’g., Inc.,
`200 F.3d 795 (Fed. Cir. 1999)..............................................................................................9, 52
`
`Rules and Statutes
`
`21 C.F.R. 210.3(b)(2) .....................................................................................................................45
`
`21 C.F.R. § 210.3 .....................................................................................................................49, 55
`
`§ 505(b)(2) of the Federal Food, Drug and Cosmetic Act ...............................................................1
`
`
`
`
`
`
`
`viii
`
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`Case 1:20-cv-00755-RGA-JLH Document 75 Filed 04/30/21 Page 9 of 79 PageID #: 2683
`
`
`
`TABLES OF EXHIBITS
`All Exhibits are attached to the Joint Appendix, filed concurrently.
`
`Joint Exhibits
`
`Description
`U.S. Patent No. 9,593,066 (UTC_LIQ00000001-12)
`U.S. Patent No. 9,604,901 (UTC_LIQ00003447-58)
`
`Plaintiff’s Exhibits
`
`Liquidia Technologies, Inc. v United Therapeutics Corp., IPR2020-00769,
`Paper No. 1 (UTC_LIQ00049402-49480)
`Liquidia Technologies, Inc. v United Therapeutics Corp., IPR2020-00770,
`Paper No. 1 (UTC_LIQ00059721-59802)
`Liquidia Technologies, Inc. v United Therapeutics Corp., IPR2020-00769,
`Paper No. 7 (UTC_LIQ00049380-49396)
`Declaration of Robert R. Ruffolo, Ph.D. (“Ruffolo Decl.”)
`Supplemental Declaration of Robert R. Ruffolo, Ph.D. (“Supp. Ruffolo”)
`Declaration of Jeffrey D. Winkler, Ph.D. In Support of Petition for Inter
`Partes Review of U.S. Patent No. 9,604,901 (UTC_LIQ00049708 –
`UTC_LIQ00049791)
`
`Defendant’s Exhibits
`
`Description
`U.S. Patent No. 9,156,786 (UTC_LIQ00083983-93)
`U.S. Patent No. 4,306,075 (UTC_LIQ00083611-64)
`U.S. Patent No. 6,809,223 (LIQ00084714-23)
`Liquidia Technologies, Inc. v United Therapeutics Corp., IPR2020-00769,
`Paper No. 6 (LIQ00083807-83).
`Liquidia Technologies, Inc. v United Therapeutics Corp., IPR2020-00770,
`Paper No. 6 (LIQ00083725-806).
`Liquidia Technologies, Inc. v United Therapeutics Corp., IPR2020-00770,
`Paper No. 9 (LIQ00083884-99)
`Liquidia Technologies, Inc. v United Therapeutics Corp., IPR2020-00770,
`Paper No. 12 (LIQ00084488-571).
`
`Ex.
`1
`2
`
`P1
`
`P2
`
`P3
`
`P4
`P5
`
`P6
`
`Ex.
`D1
`D2
`D3
`
`D4
`
`D5
`
`D6
`
`D7
`
`
`
`ix
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`Case 1:20-cv-00755-RGA-JLH Document 75 Filed 04/30/21 Page 10 of 79 PageID #: 2684
`
`D8
`
`D9
`
`D10
`
`D11
`
`D12
`
`D13
`
`D14
`
`D15
`
`D16
`
`D17
`
`D18
`
`D19
`
`D20
`
`D21
`
`D22
`
`D23
`
`D24
`
`
`
`
`
`Declaration of Rodolfo Pinal, Ph.D. In Support of Patent Owner’s Response
`(Paper No. 12) in Inter Partes Review of U.S. Patent No. 9,604,901
`(LIQ00084572-713)
`Deposition Testimony of Rodolfo Pinal, Ph.D. in Inter Partes Review of
`U.S. Patent No. 9,604,901 (LIQ00084724-90).
`SteadyMed Ltd. v. United Therapeutics Corp., IPR2016-00006,
`Paper No. 32 (UTC_LIQ00001170-226)
`SteadyMed Ltd. v. United Therapeutics Corp., IPR2016-00006,
`Paper No. 82 (UTC_LIQ00040890-980)
`August 24, 2016 Amendment and Request for Reconsideration for U.S.
`Patent Application No. 14/849,981 (UTC_LIQ00003127-33)
`November 30, 2016 Final Office Action for U.S. Patent Application No.
`14/849,981 (UTC_LIQ00003141-47)
`January 26, 2015 Reply Under 37 C.F.R. § 1.111 for U.S. Patent Application
`No. 13/933,623 (LIQ00084196-203)
`March 19, 2015 Final Office Action for U.S. Patent Application No.
`13/933,623 (LIQ00084170-77)
`August 11, 2015 Reply Under 37 C.F.R. § 1.116 for U.S. Patent Application
`No. 13/933,623 (LIQ00084187-95)
`August 4, 2015 Declaration Under 37 C.F.R. § 1.132 of Dr. Liang Guo for
`U.S. Patent Application No. 13/933,623 (LIQ00083900-34).
`August 11, 2016 Amendment & Request for Reconsideration for U.S. Patent
`Application No. 14/754,932 (LIQ00006759-65)
`October 19, 2016 Final Office Action for U.S. Patent Application No.
`14/754,932 (UTC_LIQ0006774-79)
`Robert Moriarty et al., The Intramolecular Asymmetric Pauson-Khand
`Cyclization as a Novel and General Stereoselective Route to Benzindene
`Prostacyclins: Synthesis of UT-15 (Treprostinil), 69 J. ORG. CHEM. 1890
`(2004) (UTC_LIQ00041294-306)
`PCT International Publication No. WO 2005/007081, which was filed May
`24, 2004 (LIQ00083489-610)
`Storage, HAWLEY’S CONDENSED CHEMICAL DICTIONARY (15th ed. 2007)
`(LIQ00084791-93)
`Organic Chemistry, AMERICAN CHEMICAL SOCIETY (last visited Feb. 25,
`2021), available at https://www.acs.org/content/acs/en/careers/college-to-
`career/areas-of-chemistry/organic-chemistry.html (LIQ00084794-800)
`Liquidia Submits New Drug Application for LIQ861 (treprostinil) inhalation
`powder to U.S. Food and Drug Administratoin for the Treatment of
`Pulmonary Arterial Hypertension (PAH), LIQUIDIA CORPORATION (Jan. 27,
`
`x
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`Case 1:20-cv-00755-RGA-JLH Document 75 Filed 04/30/21 Page 11 of 79 PageID #: 2685
`
`D25
`
`D26
`
`D27
`
`D28
`
`D29
`
`D30
`
`D31
`
`D32
`
`D33
`
`
`
`
`
`
`
`
`
`202) (last visited Mar. 2, 2021), available at
`https://investors.liquidia.com/news-releases/news-release-details/liquidia-
`submits-new-drug-application-liq861-treprostinil (LIQ00084801-03)
`Preservation, Packaging, Storage, and Labeling, U.S. PHARMACOPEIA
`(2006) (LIQ00084804-18)
`Liquidia Technologies, Inc. v United Therapeutics Corp., IPR2020-00770,
`Paper No. 14 (LIQ00084819-28)
`U.S. Patent No. 8,497,393 (LIQ00084829-44)
`Hernander, Regulatory Definitions for “Ambient”, “Room Temperature”
`and “Cold Chain”, PHARMA PATHWAY (Apr. 7, 2017) (Mar. 5, 2021),
`available at https://pharmapathway.com/regulatory-definitions-ambient-
`room-temperature-cold-chain/ (LIQ00084845-47)
`United Therapeutics Corp. v. Liquidia Technologies, Inc., C.A. No. 20-755-
`RGA, Plaintiff’s Objections and Responses to Defendant’s First Set of
`Interrogatories (Nos. 1-7) (D. Del. Dec. 17, 2020)
`United Therapeutics Corp. v. Liquidia Technologies, Inc., C.A. No. 20-755-
`RGA, Transcript from the April 15, 2021 Deposition of Robert R. Ruffolo,
`Ph.D.
`Declaration of Rodolfo Pinal, Ph.D. in support of Patent Owner’s
`Preliminary Response (Paper No. 6) in Inter Partes Review of U.S. Patent
`No. 9,593,066 (LIQ00084204-345)
`Ruffolo R.R., Kurz K., and Paget C.J., “Evaluation of a Novel
`Antihypertensive Agent, LY127210, in Anesthetized and Conscious
`Spontaneously Hypertensive Rats,” 232 J. Pharmacology and Experimental
`Therapeutics, 134, 135 (1985)
`Liquidia Technologies, Inc. v United Therapeutics Corp., IPR2020-00770,
`Paper No. 25 (IPR2020-00770)
`
`xi
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`Case 1:20-cv-00755-RGA-JLH Document 75 Filed 04/30/21 Page 12 of 79 PageID #: 2686
`
`
`
`I.
`
`NATURE AND STAGE OF PROCEEDINGS
`
`A.
`
`Plaintiff’s Opening Position
`
`This action arises out of Liquidia Therapeutics Corporation’s (“Defendant” or
`
`“Liquidia”) submission of New Drug Application No. 213005 under § 505(b)(2) of the Federal
`
`Food, Drug and Cosmetic Act to the United States Food and Drug Administration (“FDA”)
`
`seeking approval, prior to the expiration of U.S. Patent No. 9,593,066 (“the ’066 patent”) and
`
`U.S. Patent No. 9,604,901 (“the ’901 patent”), to manufacture, market, and sell a version of
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`UTC’s TYVASO® (treprostinil) Inhalation Solution that is approved by FDA for treatment of
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`pulmonary arterial hypertension.
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`II.
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`INTRODUCTION
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`A.
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`Plaintiff’s Opening Position
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`United Therapeutics Corporation’s (“Plaintiff” or “UTC”) proposed claim constructions
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`align with the claims, patent specifications, and prosecution histories as would be understood by
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`a person of ordinary skill in the art (“POSA”) as of the filing date. Specifically, UTC’s proposed
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`construction of the “stored” / “storing” / “storage” terms reflect a POSA’s understanding that
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`these terms require stability of the material being stored. The Patent Trial Appeal Board has
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`adopted this construction in a pending inter partes review initiated by Liquidia. UTC’s proposed
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`construction of the “pharmaceutical batch” term accounts for how a POSA would have
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`recognized that the commercial manufacturing process described and claimed in the ’901 patent
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`significantly differed from the drug development process described in the prior art as described
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`in the ’901 patent. The other terms at issue, which are proposed for construction by Liquidia,
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`would have been understood by a POSA to have their plain and ordinary meaning.
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`Liquidia’s proposed claim constructions are naked attempts to manufacture non-
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`infringement defenses where the plain language of the claims offers no such defense. Liquidia
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`1
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`repeatedly asks this Court to commit the “cardinal sin[]” of claim construction by importing
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`additional limitations into the claims. Phillips v. AWH Corp., 415 F.3d 1303, 1320 (Fed. Cir.
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`2005) (quoting SciMed Life Sys. v. Advanced Cardiovascular Sys., 242 F.3d 1337, 1340 (Fed.
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`Cir. 2001)). For example, Liquidia asks this Court to construe “a process” to expressly exclude
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`certain specific steps despite Liquidia offering in the parallel IPR a construction—one that
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`Liquidia argued was the “the same construction[] that would be appropriate in district court
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`litigation”—that includes these same steps. Likewise, Liquidia proposes an unnecessary,
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`limiting construction for the term “ambient temperature,” which is contrary to the plain and
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`ordinary meaning of this term. The Court should decline Liquidia’s invitation to read limitations
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`into the claims and should adopt UTC’s constructions.
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`B.
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`Defendant’s Answering Position
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`Liquidia filed an NDA seeking FDA approval to market LIQ861, its novel powder
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`formulation of treprostinil for the treatment of pulmonary arterial hypertension. Ex. D24.
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`Although UTC asserted three patents, only two, the ’066 and ’901 patents, form the basis of the
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`30-month stay. Liquidia provided UTC with documentary evidence establishing non-
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`infringement of the asserted claims of the ’066 and ’901 patents. To justify maintaining its
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`infringement allegations, UTC now seeks to broaden constructions of the disputed phrases
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`despite expressly limiting the scope of these same phrases during prosecution and before the
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`PTAB.1 To do this, UTC is forced to rely on extrinsic evidence, including its declaration from
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`Dr. Ruffolo, because it lacks intrinsic evidence support. In contrast, Liquidia’s proposed
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`1 Liquidia pursued IPR proceedings for both the ’066 and ’901 patents—the “’066 IPR” and
`“’901 IPR,” respectively.
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`2
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`constructions are fully supported by the intrinsic evidence and in-line with UTC’s
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`contemporaneous statements regarding the scope of the asserted claims.
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`III. BACKGROUND OF TECHNOLOGY
`A.
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`Plaintiff’s Opening Position
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`The ’066 and ’901 patents are related to the large-scale, commercial manufacturing of
`pharmaceutical compositions and pharmaceutical products of a compound known as
`treprostinil, with specific limitations regarding stability, storage, and purity. The ’066 and ’901
`patents share the same specification and priority date – December 17, 2007. Treprostinil is a
`prostacyclin derivative, which is part of a class of “useful pharmaceutical compounds
`possessing activities such as platelet aggregation inhibition, gastric secretion reduction, lesion
`inhibition, and bronchodilation.” Ex. 1 (’066 patent) at col. 1:23-26 (D.I. 52-2 at 5). “Because
`Treprostinil, and other prostacyclin derivatives are of great importance from a medicinal point
`of view, a need exists for an efficient process to synthesize these compounds on a large scale
`suitable for commercial production.” Id. at 1:66-2:3.
`The ’066 and ’901 patents improve upon the existing processes for synthesizing
`treprostinil, describing for the first time a large-scale, commercial manufacturing process that
`produces batches of treprostinil or salts thereof with improved synthetic and manufacturing
`efficiencies, and at higher multikilogram levels of production to satisfy increasing commercial
`and medical demands for the drug, with a higher level of purity. See, e.g., id. at 5:57-6:3, 17:27-
`29, Example 6 (D.I. 52-2 at 7, 12-13). In addition to being “more economical, safer, faster,
`greener, easier to operate, and provid[ing] higher purity,” the inventions allow the “crude
`treprostinil salts [to] be stored as raw material at ambient temperature,” which thereafter may be
`converted to a final treprostinil API through acidification with dilute hydrochloric acid. Id. at
`6:1-3, 17:29-40 (D.I. 52-2 at 7, 13).
`The next-generation manufacturing process described in the ’066 and ’901 patents is able
`to increase production efficiencies while delivering larger multikilogram quantities of an ultra-
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`3
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`pure treprostinil active pharmaceutical ingredient (“API”). The prior processes for producing
`treprostinil API were not suitable for large scale-manufacturing of medical-grade quantities of
`the drug and had a significantly higher level of impurities when compared to the processes
`described in the ’066 and ’901 patents. E.g., id. at col. 15, Example 6 (D.I. 52-2 at 12). Thus,
`the resulting treprostinil API is not only a manufacturing process improvement, but also provides
`treprostinil in much larger quantities and with a higher level of purity than the prior art
`processes, and which results in large, multikilogram batch production of treprostinil for use as an
`active ingredient in a pharmaceutical composition or pharmaceutical product. Id. at 5:57-6:3,
`17:27-40 (D.I. 52-2 at 7, 13).
`B.
`Defendant’s Answering Position
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`The claims of the ’066 and ’901 patents, which share a specification, “relate[] to a
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`process for producing prostacyclin derivatives and novel intermediate compounds useful in the
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`process.” See, e.g., Ex. 2 at 1:20-22. UTC and its expert, Dr. Ruffolo, attempt to artificially
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`restrict the claims of the patents-in-suit to “large-scale, commercial manufacturing process[es].”
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`See, e.g., supra § III.A, at 3-4; Ex. P4, ¶¶33, 41. For example, Dr. Ruffolo devotes pages of his
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`declaration to characterizing the alleged inventions as a “streamlined, next generation
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`manufacturing process” that “provides treprostinil in much larger quantities and with higher
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`levels of purity than previously reported in the art at the level of laboratory benchtop synthesis,
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`as reported in Moriarty ….” 2 Ex. P4, ¶35. However, the ’066 and ’901 patents do not claim the
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`“commercial,” “multikilogram” batch limitations that UTC seeks to import. UTC’s ’901 IPR
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`expert, Dr. Rudolfo Pinal, testified that none of the claims of the ’901 patent included the terms
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`“commercial,” “high-scale,” “industrial scale,” or “large-scale manufacturing.” Ex. D9 at
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`2 Moriarty et al., The Intramolecular Asymmetric Pauson-Khand Cyclization as a Novel and
`General Stereoselective Route to Benzindene Prostacyclins: Synthesis of UT-15 (Treprostinil), J.
`Org. Chem. 69:1890-1902 (2004) (Ex. D20), is a prior art reference relied upon by Liquidia in
`this Action and before the PTAB.
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`4
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`105:21-106:21. Dr. Pinal also acknowledged that the term “pharmaceutical product,” as recited
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`in claim 6 of the ʼ901 patent, does not limit “pharmaceutical” products to only those
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`commercialized, but instead includes, for example, “pharmaceutical products” administered in a
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`clinical trial. Id. at 112:12-115:20. Finally, while Dr. Ruffolo opines that “benchtop” solvents
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`and reagents are different from those used in “manufacturing plants” (Ex. P4, ¶¶39, 45), Dr.
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`Pinal admitted that the claims of the ’901 patent, except claim 7, do not require any particular
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`solvent or reagent. Ex. D9 at 52:22-54:7. Although Dr. Pinal’s statements were made in relation
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`to the ʼ901 patent, the claims of the ʼ066 patent also lack such limitations. See Ex. 1 at claims.
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`Dr. Ruffolo also attempts to distinguish the claimed inventions from the alleged
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`“benchtop” scale of the prior art process of Moriarty. Ex. P4, ¶35. The ʼ066 patent claims do
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`not require any particular quantity of treprostinil and claim 1 of the ʼ901 patent only requires at
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`least 2.9 grams, which clearly is not a “multikilogram” quantity. Ex. 1 at