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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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`Patent No. 9,339,507
`Issue Date: July 13, 2017
`Title: TREPROSTINIL ADMINISTRATION BY INHALATION
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`Inter Partes Review No. 20 1 7-0 I 622
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`DECLARATION OF DR. FRIEDRICH GRINIMJNGER
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`4822—81 10-0331
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`UNITED THERAPEUTICS. EX. 2028
`WATSON LABORATORIES V. UNITED THERAPEUTICS, IPR201?-01622
`Page 1 of5
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`IPR2017—01622
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`Declaration of Dr. Friedrich Grimminger
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`I, Dr. Friedrich Grimminger, hereby declare as follows:
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`1.
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`I am a member of University of Giessen and Marburg Lung Center
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`(“UGMLC”), a research center at the University Hospital Giessen studying
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`pulmonary hypertension.
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`2.
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`I am not a paid consultant for United Therapeutics Corporation, which
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`I understand is the assignee of U.S. Patent No. 9,339,507, in connection with
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`IPR2017-01622.
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`3.
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`I am a co-author of the German language article: Hossein Ardeschir
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`Ghofrani er a3. “Neue Therapieopticnen in der Behandlung der pulmonalarteriellen
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`Hypertonie,”I Herz, 30, 4 (June 2005): 296-302 (“the Ghofrani article”). I
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`understand that Watson Laboratories, Inc. (“Watson”) submitted an English
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`language translation of this article in this proceeding as Exhibit 1005, which I have
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`reviewed.
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`4.
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`Dr. Frank Reichenberger and I both have experience in the use of
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`selective endothelin A receptor agonists for treatment pulmouary hypertension.
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`Therefore, we were asked by Dr. Werner Seeger to draft and, indeed, drafted the
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`section of the thfrani article relating to selective endothelin A receptor agonists.
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`In Exhibit 1005, this section is on page 3. In line with the normal practice in the
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`‘ The title is translated as “New therapies in the treatment of pulmonary
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`hypertension” in Exhibit 1005.
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`4322-81 1 0-0881
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`UNITED THERAPEUTICS. EX. 2025
`WATSON LABORATORIES V. UNITED THERAPEUTICS, |PR201 Y-01622
`Page 2 of 5
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`IPR2017-0l622
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`Declaration of Dr. Friedrich Grimminger
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`UGMLC research center, both Dr. Reichenberger and I were listed as authors on
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`the Ghofrani article for this contribution.
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`5.
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`I did not make material contributions to any other section of the
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`Ghofrani article, and I specifically did not contribute to the following excerpt:
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`Initial trials in Giessen have shown proof of efficacy of inhaled
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`treprostinil for the effective reductic'm of the pulmonary vascular
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`resistance (PVR) [6]. In this first study, 17 patients with severe pre-
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`capillary pulmonary hypertension were administered inhaled
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`treprostinil (15 mog/inhalatiou). This led to a major reduction in
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`pulmonary selective pressure and resistance with an overall duration
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`of action of > 180 min. In direct comparison with inhaled iloprost,
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`inhaled treprostinil showed a stronger pulmonary selectivity, so that it
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`is possible to increase the dosage to up to 90 mcg (absolute inhaled
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`dose per inhalation exercise) without adverse effects occurring [6].
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`Due to these unique properties (pronounced pulmonary selectivity and
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`long duration of action afier an individual inhalation), it is possible to
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`reduce the number inhalations necessary to up to four per day; the
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`inhalation period can be reduced to < 1 min. by selecting a suitable
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`device. Additionally, the initial data shows that it is technically
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`feasible for there to be only one to two breaths in an application.
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`The information in this excerpt was compiled and composed by Dr. Robert
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`Voswinckel and Dr. Werner Seeger, and the idea to perform the underlying work
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`originated with them.
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`4822-3110-0831
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`UNITED THERAPEUTICS. EX. 2025
`WATSON LABORATORIES V. UNITED THERAPEUTICS, |PR201 Y-01622
`Page 3 of 5
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`IPR2017-01622
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`Declaration of Dr. Friedrich Grimminger
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`6.
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`Dr. Hossein A. Ghofi‘ani — the first listed author —drafted the section
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`of the Ghofi'ani article relating to phosphodiesterase inhibitors, and the remaining
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`sections on vasoactive therapy, inhaled iloProst, combination therapies, and
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`treatment of early forms of treatment of pulmonary hypertension, as well as the
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`introduction were drafted by Dr. Hossein A. Ghofrani and Dr. Werner Seeger.
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`[The remainder ofthfs page is intentionally left blank]
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`4322-31 1 0-0831
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`UNITED THERAPEUTICS. EX. 2025
`WATSON LABORATORIES V. UNITED THERAPEUTICS, |PR201?-01622
`Page-4 of5
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`IPR2017-01622
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`Declaration of Dr. Friedrich Grimminger
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`7.
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`I hereby declare that all statements made herein of my knowledge are
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`true and that all statements made on information and belief are believed to be true;
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`and further that these statements were made with the knowledge that willful false
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`statements and the like so made are punishable by fine or imprisonment, or both
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`under Section 1001 of Title 18 of the United States Code.
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`Date: @fldflffi’ fl
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`,2017
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`
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`Dr. Friedrich Grinuninger
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`4822-81 1 0-0881
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`UNITED THERAPEUTICS. EX. 2025
`WATSON LABORATORIES V. UNITED THERAPEUTICS, |PR201?-01622
`Page 5 of 5
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