`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________
`
`STEADYMED LTD.
`Petitioner
`
`v.
`
`UNITED THERAPEUTICS CORPORATION
`Patent Owner
`
`U.S. Patent No. 8,497,393
`Issue Date: Jul. 30, 2013
`Title: PROCESS TO PREPARE TREPROSTINIL, THE ACTIVE
`INGREDIENT IN REMODULIN®
`_______________
`
`Case IPR2016-00006
`_______________
`
`
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`
`
`Updated Patent Owner’s Exhibit List
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`
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`Mail Stop “PATENT BOARD”
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`4843-0144-6709.1
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`
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`IPR2016-00006
`U.S. Patent No. 8,497,393
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`Exhibit List
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`Ex #
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`2001
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`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
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`2012
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`2013
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`2014
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`2015
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`Exhibit Description
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`November 19, 2015 Conference Call Before the Panel
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`Remodulin® Label
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`FDA Approval Letter
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`Process Validation Report: (Protocol No.: “VAL 00131”)
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`Process Optimization Report
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`UTC Letter of January 2009 to FDA
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`U.S. Patent No. 8,242,305; the ’305 patent;
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`U.S. Provisional Patent Application No. 61/014,232
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`U.S. Patent No. 8,748,657; the ’657 patent
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`The ’657 patent prosecution history
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`Zumdahl, Chemistry, pp. A25, A36 (1986)
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`Brown, et al., Chemistry: The Central Science, pp. G-2, G-10 (9th ed.
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`2003)
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`Trial testimony of Dr. Williams and Dr. Aristoff
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`Suchocki, et al., Conceptual Chemistry, p. G-6 (2001)
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`U.S. Patent No. 4,668,814; the ’814 patent
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`4843-0144-6709.1
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`2
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`IPR2016-00006
`U.S. Patent No. 8,497,393
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`Exhibit List
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`2016
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`2017
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`2018
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`2019
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`2020
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`2021
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`2022
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`2023
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`2024
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`2025
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`2026
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`UTC Form 10K 2014 Annual Report
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`Declaration of Liang Gou, Ph.D., dated May 9, 2016 (not filed)
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`Declaration of Rex Mauthe, dated May 10, 2016 (not filed)
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`May 10, 2016 Conference Call Before the Panel
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`Declaration of Robert M. Williams, Ph.D
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`Curriculum Vitae of Robert M. Williams, Ph.D
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`Declaration of Robert R. Ruffolo, Jr., Ph.D
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`Curriculum Vitae of Robert R. Ruffolo, Jr., Ph.D
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`The Scotts Co., LLC v. Encap, LLC, IPR2013-00110, Paper 79 (PTAB
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`June 24, 2014)
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`Prosecution History of U.S. Patent No. 6,209,259
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`Williams, et.al., Asymmetric, Stereocontrolled Total Synthesis of
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`Paraherquamide A, J. Am. Chem. Soc. 2003, 125, 12172-12178.
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`2027
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`Williams, et.al., Stereocontrolled Total Synthesis of (+)-
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`Paraherquamide B, J. Am. Chem. Soc. 1996, 118, 557-579.
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`2028
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`Williams, et.al., Synthetic Studies on Et-743. Assembly of the
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`Pentacyclic Core and a Formal Total Synthesis, J. Org. Chem. 2008,
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`73, 9594-9600.
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`4843-0144-6709.1
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`3
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`IPR2016-00006
`U.S. Patent No. 8,497,393
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`Exhibit List
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`2029
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`Winkler, J., et.al., A Pauson-Khand Approach to the Synthesis of
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`Ingenol, Org. Lett., 2005, 8, 1489-1491.
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`2030
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`R. Adhiyaman, et.al., Crystal modification of dipyridamole using
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`different solvents and crystallization conditions, Int’l J. Pharm. 2006,
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`321, 27-34.
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`2031
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`Marti, E., Purity determination by differential scanning calorimetry,
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`2032
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`2033
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`2034
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`2035
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`2036
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`Thermochimica Acta, 1972, 5, 173-220.
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`U.S. Patent No. 4,306,075
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`U.S. Patent Nos. 5,153,222
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`ICH Guidance For Industry: Q7A Good Manufacturing Practice
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`Guidance for Active Pharmaceutical Ingredients (2001).
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`Reviewer Guidance: Validation of Chromatographic Methods (1994).
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`Certificate of Analysis data for 56 samples of treprostinil product as
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`produced by the prior art process according to Moriarty through 2004
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`2037
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`Certificate of Analysis data for 157 samples of treprostinil product as
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`produced by the ’393 patent processes
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`2038
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`ICH Harmonised Tripartite Guideline: Impurities in New Drug
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`Substances Q3A(R2) (2006)
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`4843-0144-6709.1
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`4
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`IPR2016-00006
`U.S. Patent No. 8,497,393
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`Exhibit List
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`2039
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`ICH Guidance for Industry: M7 Assessment and Control of DNA
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`Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential
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`Carcinogenic Risk (2015)
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`2040
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`Olsen, Bernard A., What’s New with Impurities in Pharmaceuticals?,
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`Southern California Pharmaceutical Discussion Group, January 15,
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`2015
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`2041
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`“Janet Woodcock,” available at
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`http://www.fiercebiotech.com/special-report/janet-woodcock-fda
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`(accessed July 6, 2016)
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`2042
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`Carpenter, The Political Economy of FDA Drug Review: Processing,
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`Politics and Lessons for Policy (2004)
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`2043
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`ICH Draft Consensus Guideline: Guideline for Elemental Impurities
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`Q3D (2013)
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`2044
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`ICH Guidance For Industry: Q7A Good Manufacturing Practice
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`Guidance for Active Pharmaceutical Ingredients (2001)
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`2045
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`Schrager et al., Diethylstilbestrol Exposure, American Family
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`Physician, 2004, 10, 2395-2400.
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`2046
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`NTP Report on Carcinogens Background Document for Saccharin
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`4843-0144-6709.1
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`5
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`
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`IPR2016-00006
`U.S. Patent No. 8,497,393
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`(1999)
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`
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`Exhibit List
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`2047
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`FDA Guidance for Industry: Non-Penicillin Beta-Lactam Drugs: A
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`CGMP Framework for Preventing Cross-Contamination (2013)
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`2048
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`Heinemann and Richter, Clinical Pharmacology of Human Insulin,
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`Diabetes Care, 1993, 3, 90-100.
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`2049
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`“FDA: Drug Shortages,” available at
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`http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ (accessed July
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`5, 2016)
`
`2050
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`FDA Guidance for Industry: Changes to an Approved NDA or ANDA,
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`(2004)
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`2051
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`2052
`
`Transcript of June 14, 2016 Deposition of Dr. Jeffrey D. Winkler
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`UT-15 Injection Drug Substance Volume 1.2 Chemistry,
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`Manufacturing and Controls, NDA 21-272
`
`2053
`
`United Therapeutics NDA Annual Report, Remodulin® (treprostinil
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`sodium) Injection
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`2054
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`United Therapeutics Silver Spring Process Optimization Report for the
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`Conversion of UT-15C Intermediate to UT-15 API (Treprostinil)
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`2055
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`Declaration of Robert A. Delafield II, dated July 25, 2016 (not filed)
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`4843-0144-6709.1
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`6
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`IPR2016-00006
`U.S. Patent No. 8,497,393
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`Exhibit List
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`Declaration of Thomas Higgs, dated July 27, 2016 (not filed)
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`Declaration of Rex Mauthe, dated July 27, 2016 (not filed)
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`Deposition transcript of Dr. Robert R. Ruffolo, Jr., Ph.D
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`Deposition transcript of Dr. Robert M. Williams, Ph.D
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`2056
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`2057
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`2058
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`2059
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`Date: Sept. 22, 2016
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`Respectfully submitted,
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`
`
`/Stephen B. Maebius/
`Stephen B. Maebius
`Registration No. 35,264
`Counsel for Patent Owner
`
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`4843-0144-6709.1
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`7
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`IPR2016-00006
`Patent 8,497,393
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`CERTIFICATE OF SERVICE
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`The undersigned hereby certifies that a copy of the Updated Exhibit List and
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`Exhibits 2058 and 2059 were served on Sept. 22, 2016 via email to the counsel of
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`record for the Petitioner at the following address: Steadymed-IPR@dlapiper.com.
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`Date: Sept. 22, 2016
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`/Stephen B. Maebius/
`Stephen B. Maebius
`Registration No. 35,264
`Counsel for Patent Owner
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`4843-0144-6709.1