`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`WATSON LABORATORIES, INC.
`Petitioner
`
`V.
`
`UNITED THERAPEUTICS, INC.
`
`Patent Owner
`
`Trial N0. IPR2017—01621
`
`Patent No. 9,358,240
`
`DECLARATION OF MS. PILAR WYMAN
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`WATSON LABORATORIES v. UNITED THERAPEUTICS, |PR2017-01621
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`UNITED THERAPEUTTCS, EX. 2093
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`Page 1 of 13
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`IPR2017-01621
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`I, Pilar Wyman, hereby declare:
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`INTRODUCTION
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`1.
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`I am a paid consultant for United Therapeutics Corporation in
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`connection with two patent proceedings, IPR2017-01621 and IPR20l7-01622. My
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`compensation does not depend on the content of this declaration, the substance of
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`any other testimony that I may offer in connection with this proceeding, or the
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`disposition of this proceeding.
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`2.
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`I am a professional freelance medical indexer and indexing consultant.
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`My Curriculum Vitae describing my background and experience is provided as Ex.
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`2094.
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`I have personal knowledge of the facts and opinions set forth in this
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`declaration, which I believe to be true, and if called upon to do so, I would testify
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`competently to them.
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`In particular, as shown in my Curriculum Vitae, I have been
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`involved in indexing medical publications for many years, as well as employed as
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`a librarian.
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`I was also lead consultant for the American Medical Association’s
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`AMA Manual ofStyle, 10'}l edition chapter 13, “Medical Indexes.”
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`3.
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`I am informed by counsel that a reference is considered “prior art” in
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`these proceedings if it is publicly accessible and can be located prior to a certain
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`date using reasonable diligence by a hypothetical person referred to as the person
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`of ordinary skill in the “art” (which I will often refer to as a “POSA”) or field to
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`UNITED THERAPEUTICS, EX. 2093
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`Page 2 of 13
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`IPR2017-01621
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`which the patent pertains.
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`I am further informed that, for these proceedings, the
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`patties have offered two alternative definitions for a POSA:
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`(a) a POSA at the time of invention would have been a person with a post-
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`graduate degree in medicine or drug development (such as the
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`pharmaceutical sciences) with at least two years of experience in the
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`investigation or treatment of pulmonary hypertension. A POSA may also
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`have had additional experience in the study, development, or use of
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`dosage forms that had been used to treat pulmonary hypertension, such as
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`solid oral dosage forms (e.g., tablets and capsules), injectables, and
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`inhaled therapies. A POSA may have had a lower level of formal
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`education if such a person had more years of experience in the
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`investigation or treatment of pulmonary hypertension; and
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`(b) according to Dr- Bennett (Ex. 1013,1H] 12-13), a POSA holds a Ph.D.
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`degree in pharmaceutical science or a related discipline like chemistry or
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`medicinal chemistry, as well as at least two years of practical experience
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`in the development of potential drug candidates, specifically in the
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`delivery of drug by inhalation.
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`I understand that this person according to
`
`his definition could have had a lower level of formal education than a
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`PhD- degree if such a person had more years of experience in the
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`Page 3 of 13
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`development of inhalable drugs. Also, according to Dr. Bennett’s
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`definition, this person would regularly review literature about
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`pharmaceutical sciences and drug delivery and would know how to carry
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`out library research using library resources to find out more information
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`about areas being researched. In addition, this POSA would know how to
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`evaluate potential drugs for their in vitro and in vivo activity and toxicity
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`using tests disclosed in the relevant literature. Furthermore, because drug
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`development involves a multidisciplinary approach, I understand that a
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`POSA according to Dr. Bennett may interface or consult with individuals
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`having specialized expertise, for example, a pharmacologist and/or
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`physician with experience in the administration, dosing and efficacy of
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`drugs for the treatment of a particular disease state.
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`These definitions of a POSA are interchangeable for purposes of my analysis.
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`4.
`
`I have reviewed the Declaration of Scott Bennett along with all of its
`
`attachments (Ex. 1013).
`
`1 have also conducted some searches of PubMed (NLM)
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`and American Heart Association Scientific Sessions in connection with preparing
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`this Declaration and reviewed certain other exhibits identified below.
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`UNITED THERAPEUTICS, EX. 2093
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`Page 4 of 13
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`lPR2017-0162l
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`Document 1. Robert Voswinckel, et al. "Inhaled trepostinil sodium for the
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`treatment of pulmonary hypertension" Abstract #1414, Circulation, 110, 17,
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`Supplement (October 2004): 111-295.
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`5.
`
`The first reference discussed in the Bennett Declaration is
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`Voswinckel, an abstract that is contained in a 1102—page supplement to the journal
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`Circulation in 2004 — specifically to vol. 1 10, issue 17 (Ex. 1013, 27-32). The
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`Supplement, dated October 26, 2004, contains 1 102 pages (Ex. 1013, 29), with the
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`Voswinckel abstract appearing on page 295 (Ex. 1013, 32). According to Ex-
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`1013, the abstract was also presented at a meeting of the American Heart
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`Association in New Orleans in Nov. 2004 (Ex. 1013, 27).
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`6.
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`The Bennett Declaration asserts that this abstract would have been
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`available by December 2004. Ex. 1013, 13-14.
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`I do not agree with this conclusion
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`for the following reasons. What is shown in the Bennett Declaration is an online
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`entry from the British Library (Ex. 1013, 33):
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`Page 5 of 13
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`IPR2017-0162l
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`o This is a catalogue record for the entire 1102-page Supplement. This record
`
`provides no meaningfill way to find or search for individual abstracts
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`published in it (it does not list individual authors, titles, or specific key
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`words).
`
`0
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`It does not indicate any date when the catalogue record was created, nor is
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`there any reason provided by Dr. Bennett to believe it existed by December
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`2004.
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`UNITED THERAPEUTICS, EX. 2093
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`Page 6 of 13
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`- The catalogue record reveals in the “subjects” field that the entire 1102—page
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`Supplement was catalogued broadly, under the general terms: “Medicine,”
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`“Biotechnology,” and “Pharmaceutical Chemistry.”
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`7.
`
`In addition, the cover of the Supplement in which the Voswinckel
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`abstract appears contains a “LOAN BAN” sticker, indicating that its circulation
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`was restricted until May 22, 2005. See Ex. 1013, 27. In my experience as a
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`librarian, this indicates that this bound issue was not available for review outside of
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`the premises of the British Library during this time period. Not only that, per an
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`email response dated April 20, 2018 from the British Library provided to me by
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`counsel (Ex. 2092), visitors must request individual items in the collection to be
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`brought to them for review in the Reading Room. Thus, the Supplement
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`containing Voswinckel would not have been simply sitting out for anyone to view,
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`and a member of the public would have had to know it existed in order to request
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`it. As noted above, there is no indication of when the Supplement was catalogued.
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`8.
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`It is also worth mentioning that even today this Supplement is difficult
`
`to access, whereas other articles from the same period have since been digitized or
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`uploaded. This Supplement’s contents are not indexed in PubMed (a common
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`database for clinical research and POSAs), nor is this Supplement listed in the
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`online listing of ('ircuiation Supplements from the American Heart Association
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`Page 7 of 13
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`and the Scientific Sessions. Indeed, I could not locate the Voswinckel abstract by
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`searching for it in PubMed; whereas other articles published by Circulation such as
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`Nagaya et al., “Plasma Brain Natriuretic peptide as a prognostic indicator in
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`patients with primary pulmonary hypertension”, (2000) Circulation, 102(8): pp-
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`865-870 (Endnote 71 of the Sulica and Poon reference in the Bennett Declaration
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`at Ex. 1013, 47) can easily be located in PubMed.
`
`9.
`
`Even if it had been shown that the Supplement was catalogued by a
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`library by a certain date that is relevant to these proceedings, a POSA exercising
`
`reasonable diligence still would not have been able to find the Voswinckel abstract
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`because the Supplement lacks a meaningful table of contents and key word index
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`for finding it.
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`10.
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`First, the table of contents for the Supplement provided by Dr.
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`Bennett’s excerpts gives a single heading of “Abstracts From Scientific Sessions
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`2004” which identifies pages “Ill-1 — 111-1 102”, the entire 1 102-page section
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`containing the Voswinckel abstract (Ex. 1013, 29). This would not allow a POSA
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`exercising reasonable diligence to locate it because it would require reviewing the
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`thousands of abstracts contained within the 1102 pages.
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`11.
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`Second, the 262—page author and subject index obtained from the
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`British Library for this Supplement, a copy of which was provided to me by
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`WATSON LABORATORIES v- UNITED THERAPEUTICS, IPR2017-01621
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`Page 8 of 13
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`counsel (Ex. 2096,59—262), would not allow a POSA exercising reasonable
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`diligence to locate the Voswinckel abstract. While the Voswinckel abstract is
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`listed in the author portion of the index (Ex. 2096, 54), it is only listed twice in the
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`subject index under the categories “Prostaglandins” (Ex. 2096, 219) and
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`“Pulmonary Circulation” (Ex. 2096, 221). However, it is not listed under the more
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`descriptive categories “Hypertension” (Ex. 2096, 165—166), “Hypertension,
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`Pulmonary” (Ex. 2096, 166—167), “Prostacyclin” (Ex. 2096, 218), “Pulmonary
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`Heart Disease” (Ex. 2096, 221) or “Vasodilation” (Ex. 2096, 255).
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`In particular,
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`each of the categories “Hypertension, Pulmonary”, “Prostacyclin”, and
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`“Pulmonary Heart Disease” cite to abstracts with the term “pulmonary
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`hypertension” in the title.
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`In my opinion, a POSA would be more likely to search
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`for a pulmonary hypertension abstract like the Voswinckel abstract in one of these
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`more descriptive categories than in the two general ones where it is cited.
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`Document 2. R. Sulica and M. Poon, “Medical therapeutics for pulmonary
`
`arterial hypertension: from basic science and clinical trial design to evidence-
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`based medicine,” Expert Review of Cardiovascular Therapy, 3, 3 (March
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`2005): 347-360
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`12.
`
`The second reference in the Bennett Declaration discussed in par. 33
`
`is an article by Sulica and Poon, provided as Ex. 1047, that cites the Voswinckel
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`Page 9 of 13
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`abstract. The Bennett Declaration also provides a Scopus record for the Sulica and
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`Poon publication (Ex. 1013, 39-48). The Bennett Declaration uses the Sulica and
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`Poon reference to assert that the Voswinckel abstract was able to be located by
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`these authors at least by March 2005 when they published their own article citing
`
`to it. However, it is possible that these authors learned about the Voswinckel
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`abstract through methods other than searching at a library that would not be
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`available to a POSA exercising reasonable diligence to find it.
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`13.
`
`First, the Scopus record provided by the Bennett Declaration shows
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`that the Voswinckel abstract has not been cited by any other medical publications
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`as of the 2017 date of the Scopus record. Ex. 1013, 39-48. Endnote 1 of the
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`Scopus record (Ex. 1013, 40), for example, shows a reference by Simmoneau et al-
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`that was cited by other authors and researchers 1321 times:
`
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`By contrast, the Voswinckel abstract, in endnote 51 (Ex. 1013, 45), lists no
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`citations by anyone else:
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`14.
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`In view of the fact that the Voswinckel abstract has never been cited
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`by others besides Drs. Sulica and Poon according to the Scopus record, it is
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`possible that they learned about the Voswinckel abstract while attending the New
`
`Orleans meeting in 2004 for which the Supplement was published. As seen in
`
`endnote 70 (Ex. 1013, 47), Dr. Sulica did in fact present on pulmonary
`
`hypertension at the very same meeting and published an abstract in the same
`
`supplement:
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`Thus, Dr. Sulica might have obtained a copy of the Meeting Abstracts by virtue of
`
`her participation at the meeting, or herself being an author of an abstract in the
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`same Supplement. However, learning about it these ways would not indicate that it
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`could be located by a POSA exercising reasonable diligence attempting to find it
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`through indexing records who had no advance knowledge of its existence.
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`15.
`
`Second, I have been informed by counsel that Dr. Sulica (the lead
`
`author) was one of the clinical principal investigators working on the subject
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`matter underlying the Voswinckel abstract around the time she published her
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`article with Dr. Poon. Ex. 2095. The documents do not show exactly when Dr.
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`Sulica’s work began on the clinical trial, but it is possible that Dr. Sulica learned
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`Page 11 of 13
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`about the Voswinckel abstract fiom interactions with the other investigators in this
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`study.
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`16.
`
`Third, as mentioned above regarding the Supplement, the Voswinckel
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`abstract is one of thousands of abstracts in a bound llO2—page supplement, which
`
`was not widely available nor carried by many libraries, and which, when it was
`
`carried, was catalogued only generally in the one instance identified in the Bennett
`
`Declaration. And while other libraries do also carry the parent journal Circulation,
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`it is not clear that their cataloguing for supplements would be any more detailed
`
`than that of the British Library. Dr. Bennett has provided no records indicating
`
`that the particular supplement containing the Voswinckel abstract has been
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`catalogued at any other library and, if so, when it was catalogued.
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`17.
`
`If a POSA or other researcher did not already know about the abstract
`
`from the AHA Scientific Sessions meeting or otherwise, the abstract could have
`
`been found only by searching the Subject Index in the hard copy of the Supplement
`
`or by flipping through it page by page. For this reason and the reasons cited above,
`
`I do not believe that a POSA exercising reasonable diligence could have easily
`
`accessed the Voswinckel abstract based on the materials identified in the Bennett
`
`Declaration.
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`Page 12 of 13
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`18.
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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.
`
`Date:
`
`April 25: 2018
`
`‘
`J5 /
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`/
`. £0 hflE-a’Z—a.
`
`Pilar Wyman
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`Page 13 of 13
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