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,
`Patent Owner.
`
`_____________________________
`
`Case No. IPR2020-00769 - Patent No. 9,593,066
`Case No. IPR2020-00770 - Patent No. 9,604,901
`_____________________________
`
`DECLARATION OF RODOLFO PINAL, PH.D.
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`IPR2020-00769
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`TABLE OF CONTENTS
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` Page
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`I. 
`II. 
`III. 
`IV. 
`V. 
`
`QUALIFICATIONS ............................................................................................ 1 
`SCOPE OF WORK ............................................................................................. 5 
`SUMMARY OF OPINIONS .................................................................................. 6 
`LEGAL PRINCIPLES........................................................................................ 11 
`OVERVIEW OF THE CHALLENGED PATENTS .................................................. 15 
`Claims of the ’066 Patent ................................................................ 15 
` 
`Claims of the ’901 Patent ................................................................ 20 
` 
`Prosecution Histories ...................................................................... 21 
` 
`1.  The Examiner Already Considered All of Liquidia’s Prior Art
`During Prosecution .......................................................................... 21 
`2.  Examiner Valenrod Considered the Full Record of the ’393
`IPR During Prosecution .................................................................. 29 
`3.  The ’393 IPR Final Written Decision is Not Material to the
`Patentability of the Challenged Patent Claims ................................ 31 
`THE LEVEL OF ORDINARY SKILL IN THE ART ............................................... 41 
`VI. 
`VII.  CLAIM TERMS ............................................................................................... 49 
`Terms Construed by Liquidia ......................................................... 49 
` 
`1. 
`“‘Product’ or ‘Pharmaceutical Product’”................................. 50 
`2. 
`“Pharmaceutical composition comprising treprostinil” ........... 52 
`3. 
`“A process comprising” and “the process comprising” .......... 53 
`Additional Terms............................................................................. 54 
`1.  Starting Batch and Pharmaceutical Batch ............................... 54 
`2.  Stored, Storing, Storage ........................................................... 57 
`3.  A Salt Treprostinil ................................................................... 58 
`VIII.  DR. WINKLER’S GROUNDS LACK CREDIBLE BASES, IGNORE CLAIM
`LIMITATIONS, AND MISCONSTRUE THE ASSERTED ART ............................................ 59 
`  Misguided Focus on General Syntheses of Treprostinil ................. 59 
`Lack of Support for Conclusions .................................................... 65 
` 
`1.  Phares Does Not Render Obvious Claims 1-7 of the ’066
`Patent. .............................................................................................. 67 
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`2.  Phares Fails to Teach All Aspects of Claims 8-10 of the ’066
`Patent. ............................................................................................109 
`3.  Moriarty and Phares Do Not Render Obvious Claims 1-10 of
`the ’066 Patent. ..............................................................................112 
`4.  Phares Does Not Render Obvious Claims 1-9 of the ’901
`Patent. ............................................................................................117 
`5.  Moriarty and Phares Do Not Render Obvious Claims 1-9 of the
`’901 Patent. ....................................................................................127 
`OBJECTIVE INDICIA OF NON-OBVIOUSNESS ................................................ 136 
`CONCLUDING STATEMENTS ........................................................................ 137 
`APPENDIX – LIST OF EXHIBITS ................................................................... 138 
`
`IX. 
`X. 
`XI. 
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`I, Rodolfo Pinal, declare as follows:
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`I. QUALIFICATIONS
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`
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`I am currently Associate Professor in the Department of Industrial and
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`Physical Pharmacy at Purdue University, in West Lafayette, Indiana, where I have
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`been teaching since 2003. I also serve as Director of the NSF-I/UCRC Purdue
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`Dane O. Kildsig Center for Pharmaceutical Processing Research (CPPR), a
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`position I have held since 2005. Since 2016, I have served as Director of Graduate
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`Studies in the Department of Industrial and Physical Pharmacy at Purdue. I am also
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`a member of the Faculty Senate at Purdue.
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`
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`I received my Ph.D. from the University of Arizona in Pharmaceutical
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`Sciences with a concentration in Physical Chemistry.
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`I have over 30 years of experience studying formulation science,
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`specifically on aspects pertaining to formulations for pharmaceutical composition
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`and pharmaceutical product development. My professional experience includes
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`over thirteen years working in the pharmaceutical industry.
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`
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`At Purdue, I teach at both the graduate and undergraduate levels,
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`including courses in pharmaceutical sciences, pharmaceutical formulation,
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`pharmaceutical excipients, pharmaceutical processing and manufacturing, as well
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`as performance testing and methods of analysis in pharmaceutical systems.
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` My research at Purdue focuses on three main areas. One has to do
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`with the characterization of pharmaceutical solids, including crystal polymorphs,
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`solvates, hydrates, and amorphous systems. A second area consists of utilizing the
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`findings from this first area to elucidate the effect of solid-state properties on the
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`performance attributes of pharmaceutical dosage forms. The third area combines
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`the findings from the other two areas with the focus of developing novel
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`technologies and processes for the production of dosage forms. My research on
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`practical applications applies the findings from the theoretical part of my research,
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`in order to develop formulation approaches and processing/manufacturing methods
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`for drugs deemed problematic due to their solid-state, as well as
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`solution/dissolution properties.
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`
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`Prior to joining academia, I gained over thirteen years of industry
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`experience in pharmaceutical research and development as a scientist with
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`Hoffman-La Roche. From 1990-1993, I served as a Research Associate and then as
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`a Senior Scientist in the pre-formulation group. During this time, my work focused
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`on the physiochemical characterization of new chemical entities (i.e., drug
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`candidates), including developing stability-indicating methods, stability screening
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`of drug candidates, photodegradation and drug-excipient compatibility studies, and
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`solubility/solubilization and partitioning studies.
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`From 1993-1997, I served as a Principal Scientist in the Sterile
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`Dosage Forms group at Roche. In this role, I developed injectable formulations for
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`new and investigational drug products. I was responsible for developing
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`formulations for use in clinical trials, development of HPLC methods for assaying
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`potency and stability of the active compound as well as pharmaceutical
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`compositions intended for injection. I was also responsible for writing the
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`directions for manufacturing clinical batches in the cGMP suite and for supervising
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`the sterile suite operators during the manufacture of the resulting pharmaceutical
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`products.
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`From 1997-2003, I served as Principal Scientist and then a Research
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`Leader in the Solid-State Pharmaceutics group at Roche, which was part of the oral
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`dosage forms development group. In this role, I was responsible for identifying and
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`devising methods for the measurement and monitoring of physical
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`properties/parameters critical for the development of a given specific
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`pharmaceutical product or process. I also worked extensively with process
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`chemists from the Chemical Synthesis Department “Kilo Lab” at the company’s
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`site in New Jersey, as well as with process chemists from the industrial production
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`site located in South Carolina.
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`I have authored or co-authored over 60 research papers and book
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`chapters. I also regularly serve as a reviewer for a variety of academic journals,
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`including Pharmaceutical Research, Journal of Pharmaceutical Sciences, Crystal
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`Growth and Design, and International Journal of Pharmaceutics and Molecular
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`Pharmaceutics, among others.
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`I am a member of several professional and honors organizations,
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`including the American Chemical Society (ACS), the American Association of
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`Pharmaceutical Scientists (AAPS), and the Rho Chi Honor Society. In 2016-2017,
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`I served as Chair of the Patient-Centric Drug Development, Product Design and
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`Manufacturing Focus Group (PCFG) of the APPS.
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`I have first-hand industrial experience in the scale-up process for
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`making APIs (active pharmaceutical ingredients). The laboratory under my
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`supervision was responsible for the solid-state characterization of every batch of
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`API generated at the New Jersey facility during the scale up of the synthesis. This
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`responsibility extended to API batches produced at other sites but utilized during
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`research and development at the New Jersey plant. The solid-state characterization
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`work performed in my laboratory included crystal form and polymorphism,
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`covering thermodynamic vs. kinetic stability, hygroscopicity, crystal morphology,
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`particle size, solvates, hydrates, etc. A quick description of part of my
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`responsibilities is as follows. As process (Kilo Lab) chemists began to work on
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`replacing the synthetic process of APIs originally used by (drug discovery)
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`medicinal chemists, toward one suitable for large scale production, they sent
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`samples of their produced batches to me. My laboratory performed the solid-state
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`characterization work required and convey the information to the Kilo Lab.
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`Through an iterative process, the two groups would find the different polymorphs
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`of the API, establish the stability relationship among them, and also establish the
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`specifications for crystal morphology, particle size among the relevant attributes
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`necessary for downstream processing. I was responsible for writing the sections
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`pertaining to crystal polymorphism and particle morphology included in NDA and
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`IND submissions to the FDA.
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` For a more detailed listing of my credentials and publications, please
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`see my curriculum vitae. EX2003.
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`II. SCOPE OF WORK
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`
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`I understand a petition has been filed with the United States Patent
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`and Trademark Office for Inter Partes Review of each of U.S. Patent Nos.
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`9,593,066 (IPR2020-00769) and 9,604,901 (IPR2020-00770) (together, “the
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`challenged patents”). I understand these petitions were filed on behalf of Liquidia
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`Technologies, Inc. (“Liquidia”). I understand the challenged patents are currently
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`assigned to United Therapeutics Corporation (“UT”).
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` UT retained me as a technical expert in both proceedings to provide
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`various opinions regarding the challenged patents. I have not previously served as
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`an expert witness for UT and I do not have any current or past affiliation with
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`Liquidia.
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`I have been specifically asked to provide my expert opinions on the
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`validity of claims 1-10 of the ’066 patent and claims 1-9 of the ’901 patent
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`(together, “the challenged claims”). In connection with my analysis, I have
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`reviewed both petitions, as well as the declaration submitted by Dr. Winkler in
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`each case (EX1002) and the documents he cites. I have also reviewed and
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`considered various other documents in arriving at my opinions and may cite to
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`them in this declaration. For convenience, I list additional documents considered in
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`arriving at my opinions in Section XI.
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`
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`I understand this declaration will be submitted in both IPR
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`proceedings. In citing EX1001, EX1002, and EX1006, which are different across
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`the two cases, I have noted which case includes the material I am citing (e.g.,
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`EX1002 (’066), ¶137). If a citation is the same across the two cases, I have not
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`added a case-specific designation (e.g., EX1005, 1).
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` UT is compensating me $480 per hour for my services. No part of my
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`compensation depends opinions or on the outcome of this proceeding.
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`III. SUMMARY OF OPINIONS
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` Both of Dr. Winkler’s declarations assert that the disclosures of
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`Phares (EX1008) and Moriarty (EX1009), either alone or in combination, render
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`the challenged claims unpatentable. I understand both claim sets already underwent
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`examination in view of Moriarty and Phares during prosecution. See Section V.C,
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`below. I agree with the Patent Office that the challenged claims recite inventive
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`subject matter that is patentably distinct from these references’ disclosures.
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` Dr. Winkler asserts “three strong reasons” that purportedly support a
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`finding of unpatentability. See Declaration of Dr. Jeffery D. Winkler (“Winkler,”
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`EX1002), ¶36. Each of these reasons lacks merit. In my opinion, neither Dr.
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`Winkler’s testimony nor his references demonstrates a reasonable likelihood that
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`any of the challenged claims is anticipated by Phares, is rendered obvious by
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`Phares alone, or is rendered obvious by Moriarty in view of Phares.
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` Dr. Winkler’s first theory is that general synthetic routes to
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`treprostinil and its salts appeared in publications prior to the challenged patents’
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`December 17, 2007 priority date. While the challenged claims require access to
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`treprostinil, they do not simply recite the synthesis of treprostinil or its salt. Rather,
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`they are drawn to a pharmaceutical batch, a pharmaceutical composition, and a
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`pharmaceutical product, each with specific limitations regarding, e.g., purity,
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`stability, and storage of a treprostinil API.
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` Dr. Winkler’s second and third theories appear to be legal conclusions
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`about product-by-process claims and the relevance of an IPR of a different
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`patent—U.S. Patent No. 8,497,393 (“the ’393 patent,” EX1004). Each of these
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`rationales lacks credible bases, ignores claim limitations, and overlooks or
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`misconstrues the asserted art.
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`In each of his declarations, Dr. Winkler ignores the material
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`difference between merely synthesizing treprostinil and aspects such as
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`manufacturing a pharmaceutical batch, pharmaceutical composition, or
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`pharmaceutical product that comprises treprostinil.
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` Dr. Winkler also misconstrues disclosures of general benchtop
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`chemistry techniques as evidence of ease of implementation or expectations of
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`success. In science-based endeavors, including chemistry, there is always a gap
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`between theory and practice. When translating between disciplines like organic or
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`medicinal chemistry at micro-scale on the benchtop and process chemistry or
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`engineering at the industrial production level, the gap is even greater. In fact, areas
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`of specialization such as process chemistry exist in the pharmaceutical industry
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`precisely to fill such technological gaps. As discussed in more detail below, what
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`works at the benchtop does not automatically provide a reasonable expectation of
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`success for the process chemist manufacturing pharmaceuticals at industrial batch-
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`scale.
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` Other process concerns, like crystal morphology, yields, and the
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`identity of undesired impurities, are also ignored by Dr. Winkler. These
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`considerations are critical to the development of a pharmaceutical process. For
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`instance, Stahl notes an example of pharmaceutical product development whereby
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`process chemists attempted to use a salt formation step “to avoid a large scale
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`chromatographic separation,” while still “enabl[ing] development quantities to be
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`made.” Stahl, P. H., & Wermuth, C. G. (Eds.) (2002). Handbook of
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`Pharmaceutical Salts (1st ed.) Weinheim, Germany: Wiley-VCH (“Stahl,”
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`EX2008), 218-19. This approach “was, however, unsuitable for large-scale use due
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`to the potentially explosive nature of nitropyrazoles and the toxicity and
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`availability of the reagents used.” Id. And even after “an alternative route was
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`developed for large-scale manufacture,” which relied upon “salt formation at
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`various points to enable hundreds of kilograms to be made,” the updated synthesis
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`resulted in a mixture of isomers, with attempts to remove the undesired isomer
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`leading to unacceptably substantial losses in product yield. Id. (noting, eventually,
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`a different synthetic route was developed, which improved intermediate purity,
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`which made it “no longer necessary to use the maleate salt as an intermediate
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`purification step”).
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` Thus, mere general knowledge of techniques, like salt formation, even
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`with a modified synthesis operable at a large scale, does not guarantee success in
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`the preparation of a pharmaceutical batch, pharmaceutical composition, or
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`pharmaceutical product.
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` Dr. Winkler also conflates what could be done and what would be
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`done. See Section VIII. Even assuming that the person of ordinary skill in the art
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`(“POSA”) could have cobbled together the disparate teachings of the prior art, Dr.
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`Winkler does not explain why the POSA would have done so, much less why the
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`POSA would have had a reasonable expectation of success without hindsight.
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`In his analysis, Dr. Winkler takes highly-specific steps or procedures
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`from the disclosures in the claimed invention, and by limiting himself to the
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`underlying chemical principle, which is typically discussed in general chemistry
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`books, argues that the step/procedure has been previously disclosed. Dr. Winkler
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`repeatedly and mistakenly represents general chemistry principles, of which every
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`chemist is aware, as being one and the same as the innumerable possibilities to
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`practice, some of which would work and many of which would not, for a specific
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`chemical system in the context of its process.
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` Many assertions also lack citations to a supporting disclosure in the
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`prior art. Where citations are provided, many do not support the assertion, or are
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`the product of picking, choosing, and combining various disclosures that are not
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`directly related to each other in the cited reference, or to the challenged claims.
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` Thus, in my opinion, Dr. Winkler’s analyses do not accurately address
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`the scope and content of the prior art (see Section VIII), fail to consider the
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`differences between the claimed inventions and the asserted references (see
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`Sections V, VII, & VIII), incorrectly resolve the level of ordinary skill in the
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`pertinent art (see Section VI), and ignore known evidence of secondary
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`considerations (see Section IX).
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`IV. LEGAL PRINCIPLES
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`I have been advised that the burden is on Liquidia to demonstrate the
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`unpatentability of the challenged claims.
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`I have been advised that anticipation is about prior invention and
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`therefore, a single prior art reference must be found to disclose all elements of the
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`claimed invention, arranged as in the challenged claim. I have been further advised
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`that it is not enough that the prior art reference includes multiple, distinct teachings
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`that may somehow be combined to achieve the claimed invention. Rather, it is my
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`understanding that the reference must clearly and unequivocally disclose the
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`claimed invention or direct the POSA to the claimed invention without any need
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`for picking, choosing, and combining various disclosures that are not directly
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`related to each other in the reference.
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`I have been further advised that anticipation does not require all
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`elements to be expressly disclosed in a single prior art reference. A single prior art
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`reference would still anticipate a claimed invention if the claim elements are
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`disclosed inherently rather than expressly. In addition, I have been advised that the
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`POSA need not recognize the inherent characteristics or functioning of the prior art
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`in order for a prior art reference to render a claimed invention anticipated as
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`inherent.
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`I have also been advised that anticipation under an inherency theory
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`requires an inherent element to necessarily flow from the teachings of a prior art
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`reference. That is, I understand that an inherent element is not proven by
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`probabilities or possibilities. Rather, the element must necessarily be present. I
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`understand that the fact that a certain thing may result from a given set of
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`circumstances is not sufficient to show inherent anticipation.
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`I also understand that if there are structural or functional differences
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`in the product of the product-by-process claims of the invention from the product
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`of the prior art that arise from the process from which it was made, those
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`differences may be evidence of no anticipation even if those differences are not
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`explicitly claimed.
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`I have also been advised that a claimed invention is not patentable
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`under an obviousness theory if it would have been obvious to the POSA at the time
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`the claimed invention was made. As I understand it, that means that even if all of
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`the requirements of the claimed invention cannot be found in a single, anticipatory
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`prior art reference, the claim may be held unpatentable as obvious over one or
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`more prior art references if the POSA would still have come up with the claimed
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`invention in view of the prior art disclosures.
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`I have further been advised that the ultimate conclusion of whether a
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`claim is obvious should be based upon several factual determinations. That is, a
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`determination of obviousness requires inquiries into: (i) the level of ordinary skill
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`in the field; (ii) the scope and content of the prior art; (iii) what difference, if any,
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`existed between the claimed invention and the prior art; and (iv) any secondary
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`evidence bearing on obviousness.
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`I have also been advised that, in order to be considered as prior art, a
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`reference must be reasonably related to the claimed invention of the patent. I
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`understand that a reference is reasonably related if it is in the same field as the
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`claimed invention or is from another field to which the POSA would look to solve
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`a known problem.
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`I have been advised that a claimed invention composed of several
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`elements is not proved obvious merely by demonstrating that each element was
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`independently known in the prior art. In evaluating whether such a claimed
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`invention would have been obvious, motivations that would have prompted the
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`POSA to combine elements or concepts from the prior art in the same way as they
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`appear in the claimed invention (or the lack of such motivations) must be
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`considered.
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`I have also been advised, however, that an obviousness analysis must
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`not use or rest upon the benefit of hindsight; many true inventions might seem
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`obvious after the fact. Thus, an obviousness analysis should be conducted from the
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`perspective of the POSA at the time the claimed invention was made and should
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`not rely upon what is known today or what is taught by the patent at issue.
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` Finally, I have been advised that any obviousness rationale for
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`modifying or combining prior art must include a showing that the POSA would
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`have had a reasonable expectation of success.
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`I also understand that, like anticipation, if there are structural or
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`functional differences between a product recited in product-by-process claims of
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`the invention and a product disclosed in the prior art that arise from the process
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`from which each product was made, those differences may be evidence of non-
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`obviousness even if those differences are not explicitly claimed.
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` With regard to objective indicia of non-obviousness, I have been
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`advised that any objective evidence may be considered as an indication that the
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`claimed invention would not have been obvious at the time the claimed invention
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`was made. I understand that the purpose of these secondary considerations is to
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`prevent a hindsight analysis of the obviousness of the claimed invention.
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`I have been advised that there are several factors that may be
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`considered as secondary considerations. These factors include the commercial
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`success of the invention, industry praise for the invention, skepticism of the
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`invention, licensing of the invention, copying of the invention, any long-felt need
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`that the invention solved, failure of others, and unexpected results of the invention.
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`I have been further advised that in order for evidence of secondary
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`considerations to be significant, there must be a sufficient nexus between the
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`claimed invention and the evidence of secondary considerations. I understand that
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`this nexus serves to provide a link between the merits of the claimed invention and
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`the evidence of secondary considerations provided.
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`V. OVERVIEW OF THE CHALLENGED PATENTS
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` Both of the challenged patents are entitled “Process to Prepare
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`Treprostinil, the Active Ingredient in Remodulin®.” EX1001, Title. I understand
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`the challenged patents also share a priority date of December 17, 2007. Id., [60].
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` Claims of the ’066 Patent
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` The ’066 patent has 10 claims. Claim 1 and claim 8 are independent.
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`Claim 1 recites:
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`1. A pharmaceutical composition comprising treprostinil or a
`pharmaceutically acceptable salt thereof, said composition prepared
`by a process comprising
`providing a starting batch of treprostinil having one or more
`impurities resulting from prior alkylation and hydrolysis
`steps,
`forming a salt of treprostinil by combining the starting batch
`and a base,
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`isolating the treprostinil salt, and
`preparing a pharmaceutical composition comprising treprostinil
`or a pharmaceutically acceptable salt thereof from the
`isolated treprostinil salt,
`whereby a level of one or more impurities found in the starting
`batch of treprostinil is lower in the pharmaceutical
`composition, and
`wherein said alkylation is alkylation of benzindene triol.
`EX1001 (’066), 17:51-63.
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` Claims 2-7 depend directly or indirectly from claim 1, and recite
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`additional limitations associated with this batch-based pharmaceutical
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`composition. Id., 17:64-18:37.
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` Dr. Winkler asserts independent claim 8 “is drawn to a process of
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`preparing the same product from claim 1.” EX1002 (’066), ¶¶26-27. It is not.
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`Rather, independent claim 8 recites:
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`8. A process of preparing a pharmaceutical product comprising
`treprostinil or a pharmaceutically acceptable salt thereof, comprising
`
`alkylating a triol intermediate of the formula:
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`hydrolyzing the resulting compound to form treprostinil,
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`forming a salt of treprostinil stable at ambient temperature,
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`storing the treprostinil salt at ambient temperature, and
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`preparing a pharmaceutical product from the treprostinil salt after
`storage,
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`wherein the pharmaceutical product comprises treprostinil or a
`pharmaceutically acceptable salt thereof.
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`EX1001 (’066), 18:38-61.
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` Below I provide a comparison of independent claims 1 and 8. See
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`EX1001 (’066), 17:51-63, 18:38-61.
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`CLAIM 8
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`8. A process of preparing a
`pharmaceutical product
`comprising treprostinil or a
`pharmaceutically acceptable salt
`thereof,
`
`
`
`CLAIM 1
`1. A pharmaceutical
`composition comprising
`treprostinil or a
`pharmaceutically acceptable
`salt thereof, said
`composition prepared by a
`process comprising
`providing a starting batch
`of treprostinil having one or
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`LIMITATION
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`I
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`II
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`LIMITATION
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`III
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`IV
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`V
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`VI
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`CLAIM 1
`more impurities resulting
`from prior alkylation and
`hydrolysis steps,
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`See Limitation XI
`(“wherein said alkylation is
`alkylation of benzindene
`triol”).
`
`See Limitation II,
`mentioning, in a non-
`identical limitation,
`impurities within a starting
`batch of treprostinil
`resulting from prior
`hydrolysis steps.
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`CLAIM 8
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`comprising alkylating a triol
`intermediate of the formula:
`
`
`
`hydrolyzing the resulting
`compound to form treprostinil,
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`forming a salt of treprostinil forming a salt of treprostinil
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`by combining the starting
`batch and a base,
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`
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`VII
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`
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`[wherein the salt is] stable at
`ambient temperature,
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`isolating the treprostinil
`salt
`and preparing a
`pharmaceutical
`composition comprising
`treprostinil or a
`pharmaceutically acceptable
`salt thereof from the
`isolated treprostinil salt,
`whereby a level of one or
`more impurities found in
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`VIII
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`IX
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`X
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`LIMITATION
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`XII
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`XIII
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`XIV
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`XV
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`CLAIM 1
`the starting batch of
`treprostinil is lower in the
`pharmaceutical
`composition,
`and wherein said alkylation
`is alkylation of benzindene
`triol.
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`CLAIM 8
`
`See Limitation III (reciting a
`process step of alkylating a triol
`intermediate that is benzindene
`triol).
`storing the treprostinil salt at
`ambient temperature, and
`preparing a pharmaceutical
`product from the treprostinil salt
`
`after storage
`
`wherein the pharmaceutical
`product comprises treprostinil or a
`pharmaceutically acceptable salt
`thereof.
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` While both independent claims recite limitations relating to
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`treprostinil or a pharmaceutically acceptable salt of treprostinil, and make
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`reference to reactions like alkylation, hydrolysis, and salt formation, they differ in
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`almost every other respect.
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` Claim 1 recites unique limitations relating to a pharmaceutical
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`composition formed by a specified process, including:
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` A starting batch;
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` Impurities resulting from prior alkylation and hydrolysis steps;
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` Forming a treprostinil salt by combining the starting batch and a base;
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` Isolating the treprostinil salt;
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` Preparing a pharmaceutical composition (from the isolated treprostinil
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`salt); and
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` Expressly requiring that a level of one or more impurities found in the
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`starting batch of treprostinil is lower in the pharmaceutical composition.
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` Claim 8 recites unique limitations relating to a process for preparing a
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`pharmaceutical product, including:
`
` Forming of a treprostinil salt that is stable at ambient temperature;
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` Storing the treprostinil salt at ambient temperature; and
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` Preparing a pharmaceutical product after storage of the treprostinil salt.
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` Claims 9 and 10 depend directly from claim 8, reciting the
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`pharmaceutical product resulting from the claim 8 process and adding further
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`limitations to the process, respectively. EX1001 (’066), 18:62-65.
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` Claims of the ’901 Patent
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` The ’901 patent has 9 claims. Claim 1, the only independent claim,
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`recites:
`
`1. A pharmaceutical batch consisting of treprostinil or a salt thereof
`and impurities resulting from
`(a) alkylating a benzindene triol,
`(b) hydrolyzing the product of step (a) to form a solution
`comprising treprostinil,
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`(c) contacting the solution comprising treprostinil from step (b)
`with a base to form a salt of treprostinil, (d) isolating the
`salt of treprostinil, and (e) optionally reacting the salt of
`treprostinil with an acid to form treprostinil, and
`wherein the pharmaceutical batch contains at least 2.9 g of
`treprostinil or its salt.
`EX1001 (’901), 17:24-18:2; see also EX2007 (Complete ’901 Prosecution History
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`(“’901 PH”)), 3-6 (correcting claim 1, which issued reciting “(c) containing the,”
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`to “(c) contacting the”).
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