UNITED STATES PATENT AND TRADEMARK OFFICE
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`LIQUIDIA TECHNOLOGIES, INC.
`Petitioner
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`V.
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`UNITED THERAPEUTICS CORPORATION
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`Patent Owner
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`Patent No. 10,716,793 B2
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`Issue Date: July 21 , 2020
`Title: TREPROSTINIL ADMINISTRATION BY INHALATION
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`Inter Parres Review No. IPR2021-00406
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`DECLARATION OF DR. FRANK REICHENBERGER
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`IPR2021—00406
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`Declaration of Dr. Frank Reichenberger
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`I, Dr. Frank Reichenberger, hereby declare as follows:
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`1.
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`I was 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 US. Patent No. 10,716,793.
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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 al. “Neue Therapieoptionen in der Behandlung der pulmonalaiteriellen
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`Hypertonie,”I Herz, 30, 4 (June 2005): 296-302 (“the Ghofrani article”). I
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`understand that Liquidia Technologies, Inc. (“Liquidia”) submitted this publication
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`along with an English language translation of the article in this proceeding as
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`Exhibit 1010, which I have reviewed.
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`4.
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`Dr. Friedrich Grirnminger and I both have experience in the use of
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`selective endothelin A receptor agonists for treatment pulmonary hypertension.
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`Therefore, we were asked by Dr. Werner Seeger to draft the section of the
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`Ghofrani article relating to selective endothelin A receptor agonists. And indeed,
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`we did draft this section. In Exhibit 1010, this section is in English on page 11. In
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`
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`1 The title is translated as “Pulmonary hypertension e new aspects of therapy” in
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`Exhibit 1010.
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`IPR2021—00406
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`Declaration of Dr. Frank Reichenberger
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`line with the normal practice in the UGMLC research center, both Dr. Grimminger
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`and l were listed as authors on 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 reduction of the pulmonary vascular
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`resistance (PVR) [6]. In this first study, 17 patients with severe pre—
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`c-apillary pulmonary hypertension were administered inhaled
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`treprostinil (15 meg/inhalation). 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 after 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 < l 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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`(Ex. 1010, p. 11). The information in this excerpt was compiled and composed by
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`Dr. Robert Voswinckel and Dr. Werner Seeger, and the idea to perform the
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`underlying work originated with at least them.
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`IPR2021-00406
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`Declaration of Dr. Frank Reichenberger
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`6.
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`Dr. Hossein A. Ghofraniwthe first listed authorflafied the section
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`of the Ghofrani 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 ofpulmonary 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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`7.
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`I am also listed as a co-author on two abstracts: Voswinckel, R., et 01].,
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`Abstract 218: “Inhaled treprostinil is a potent pulmonary vasodilator in severe
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`pulmonary hypertension,” European Heart Journal 25:22 (2004) (“Voswinckel
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`JESC”) and Robert Voswinckel, et at, Abstract 1414: “Inhaled Treprostinil
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`Sodium (TRE) For the Treatment of Pulmonary Hypertension,” Abstracts from the
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`2004 Scientific Sessions of the American Heart Association, Circulation, 110(17
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`Suppl.):lII—295 (October 26, 2004) (“Voswinckel JAHA”), which I understand
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`Liquidia submitted in this proceeding as Exhibit 1007 and Exhibit 1008,
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`respectively.
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`8.
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`In each of Voswinckel JESC and Voswinckel JAHA, I am listed as a
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`co-author on that abstract because it was and is the practice of our group to include
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`as authors of abstracts and summary review articles the members of our group who
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`contribute to or oversee any part in the trials, clinical routine management, or
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`related parallel studies, not just members who were directly responsible for
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`conceiving, analyzing, and designing a particular study.
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`Declaration of Dr. Frank Reichenberger
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`9.
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`In the case of any studies of inhaled treprostinil described in these
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`documents (Voswinckel JESC and Voswinckel JAHA), I was listed as a co-author
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`because I assisted with the clinical responsibilities of overseeing patients and was
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`performing work related to the treatment of pulmonary hypertension. I was not
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`designing studies or methods of treatment involving inhaled treprostinil.
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`10.
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`These articles do not report on primary data - one is a review article
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`(Ghofrani article) and two are abstracts (Voswinckel JESC and Voswinckel
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`JAHA). My involvement in any study by our group into inhaled treprostinil was
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`limited to support and administrative tasks such as collecting data or checking on
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`patients. 1 was not involved in the conception, design or intent of the study such as
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`selecting treprostinil for inhaled administration, the dosages or timing of
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`administration, the protocols or devices used, or the selection of study parameters.
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