`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`WATSON LABORATORIES, INC.
`Petitioner
`
`V.
`
`UNITED THERAPEUTICS, INC.
`Patent Owner
`
`Patent No. 9,358,240
`Issue Date: June 7, 2016
`Title: TREPROSTINIL ADMINISTRATION BY INHALATION
`
`Inter Partes Review No. 20 1 7-0 I 62 1
`
`DECLARATION OF DR. FRIEDRICH GRIMJVIINGER
`
`4812—?351—36T0
`
`UNITED THERAPEUTICS. EX. 2028
`WATSON LABORATORIES V. UNITED THERAPEUTICS, |PR201?-01621
`Page 1 of5
`
`
`
`IPR2017-0162l
`
`Declaration of Dr. Friedrich Grimminger
`
`I, Dr. Friedrich Grinuninger, hereby declare as follows:
`
`1.
`
`I am a member of University of Giessen and Marburg Lung Center
`
`(“UGMLC”), a research center at the University Hospital Giessen studying
`
`pulmonary hypertension.
`
`2.
`
`I am not a paid consultant for United Therapeutics Corporation, which
`
`I understand is the assignee of US. Patent No. 9,358,240, in connection with
`
`IPR2017-01621.
`
`3.
`
`I am a co-author of the German language article: Hossein Ardeschir
`
`Ghofi‘ani er a1. “Neue TherapieOptionen in der Behandlung der pulmonalarteriellen
`
`Hypertenie,”1 Herz, 30, 4 (June 2005): 296-302 (“the Ghofrani article”).
`
`I
`
`understand that Watson Laboratories, Inc. (“Watson”) submitted an English
`
`language translation of this article in this proceeding as Exhibit 1005, which I have
`
`reviewed.
`
`4.
`
`Dr. Frank Reichenberger and I both have experience in the use of
`
`selective endothelin A receptor agonists for treatment pulmonary hypertension.
`
`Therefore, we were asked by Dr. Werner Seeger to draft and, indeed, drafted the
`
`section of the Ghofrani article relating to selective endothelin A receptor agonists.
`
`In Exhibit 1005, this section is on page 3. In line with the normal practice in the
`
`1 The title is translated as “New therapies in the treatment of pulmonary
`
`hypertension” in Exhibit 1005.
`
`4812—?351—88?G
`
`UNITED THERAPEUTICS. EX. 2025
`WATSON LABORATORIES V. UNITED THERAPEUTICS, |PR201?-01621
`Page 2 of 5
`
`
`
`IPR2017-01621
`
`Declaration of Dr. Friedrich Grimminger
`
`UGMLC research center, both Dr. Reichenberger and I were listed as authors on
`
`the Ghofrani article for this contribution.
`
`5.
`
`I did not make material contributions to any other section of the
`
`Ghofrani article, and I specifically did not contribute to the following excerpt:
`
`Initial trials in Giessen have shown proof of efficacy of inhaled
`
`treprostinil for the effective reduction of the pulmonary vascular
`
`resistance (PVR) [6]. In this first study, 17 patients with severe pre-
`
`capillary pulmonary hypertension were administered inhaled
`
`treprostinil (15 mcg/inhalation). This led to a major reduction in
`
`pulmonary selective pressure and resistance with an overall duration
`
`of action of > 130 min. In direct comparison with inhaled iloprost,
`
`inhaled treprostinil showed a stronger pulmonary selectivity, so that it
`
`is possible to increase the dosage to up to 90 mcg (absolute inhaled
`
`dose per inhalation exercise) without adverse effects occurring [6].
`
`Due to these unique properties (pronounced pulmonary selectivity and
`
`long duration of action after an individual inhalation), it is possible to
`
`reduce the number inhalations necessary to up to four per day; the
`
`inhalation period can be reduced to < 1 min. by selecting a suitable
`
`device. Additionally, the initial data shows that it is technically
`
`feasible for there to be only one to two breaths in an application.
`
`The information in this excerpt was compiled and composed by Dr. Robert
`
`Voswinckel and Dr. Werner Seeger, and the idea to perform the underlying work
`
`originated with them.
`
`4312-?351-3670
`
`UNITED THERAPEUTICS. EX. 2025
`WATSON LABORATORIES V. UNITED THERAPEUTICS, |PR201?-01621
`Page 3 of 5
`
`
`
`IPR2017-0162l
`
`Declaration of Dr. Friedrich Grimminger
`
`6.
`
`Dr. Hossein A. Ghofiani — the first listed author —drafled the section
`
`of the Ghofrani article relating to phosphodiesterase inhibitors, and the remaining
`
`sections on vasoactive therapy, inhaled iloprost, combination therapies, and
`
`treatment of early forms of treatment of pulmonary hypertension, as well as the
`
`introduction were drafied by Dr. Hossein A. Ghofrani and Dr. Werner Seeger.
`
`[The remainder ofthis page is intentionafly left blank]
`
`4812-?351-SSYD
`
`UNITED THERAPEUTICS. EX. 2025
`WATSON LABORATORIES V. UNITED THERAPEUTICS, |PR201?-01621
`Page 4 of 5
`
`
`
`iPR2017-0162]
`
`Declaration of Dr. Friedrich Grimminger
`
`7.
`
`I hereby declare that all statements made herein of my knowledge are
`
`true and that all statements made on information and belief are believed to be true;
`
`and fimher that these statements were made with the knowledge that willful false
`
`statements and the like so made are punishable by fine or imprisonment, or both
`
`under Section 1001 of Title 18 of the United States Code.
`
`Date:
`
`{jg/5’15!"/ fl?
`
`,2017
`
`Dr. Friedrich Grimminger
`
`4812-1151—8670
`
`UNITED THERAPEUTICS. EX. 2025
`WATSON LABORATORIES V. UNITED THERAPEUTICS, |PR201?-01621
`Page 5 of 5
`
`