UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`ARGENTUM PHARMACEUTICALS LLC
`Petitioner
`
`v.
`
`MERCK PATENTGESELLSCHAFT
`Patent Owner
`
`Patent No. 8,673,921
`Issue Date: March 18, 2014
`Title: POLYMORPHIC FORMS OF
`1-[4-(5-CYANOINDOL-3-YL)BUTYL]-4-
`(2-CARBAMOYLBENZOFURAN-5-YL)
`PIPERAZINE HYDROCHLORIDE
`
`Inter Partes Review No.: Unassigned
`
`DECLARATION OF DR. ROBIN D. ROGERS, PH.D.
`
`Argentum EX1002
`
`

`

`Patent No. 8,673,921
`Declaration in Support of Inter Partes Review
`
`I.
`
`TABLE OF CONTENTS
`
`Legal Principles ............................................................................................. 8
`
`Introduction ................................................................................................... 1
`A. Anticipation ......................................................................................... 8
`B.
`Obviousness ......................................................................................... 9
`Summary of Opinions .................................................................................. 10
`A. What is a crystal? ............................................................................... 19
`B.
`Characterizing crystals ....................................................................... 25
`C.
`Identifying Crystals............................................................................ 28
`D.
`Crystallization Techniques ................................................................. 33
`State of the Prior Art .................................................................................... 35
`A. U.S. Patent No. 5,532,241 (’241 Patent) (Ex. 1004) ........................... 35
`B.
`Bartoszyk (Ex. 1005) ......................................................................... 37
`C.
`Brittain (Ex. 1010) ............................................................................. 39
`D.
`Byrn, 2nd Edition (Ex. 1012) .............................................................. 43
`E.
`Gould (Ex. 1011) ............................................................................... 44
`F.
`Lieberman (Ex. 1013) ........................................................................ 45
`G. Vippagunta (Ex. 1027) ....................................................................... 46
`H. Hancock (Ex. 1028) ........................................................................... 49
`I.
`Beckmann (Ex. 1029) ........................................................................ 50
`J.
`Zinnes (Ex. 1030) .............................................................................. 51
`K. Armarego (Ex. 1031) ......................................................................... 51
`L.
`Pavia (Ex. 1032) ................................................................................ 52
`
`II. My Background and Qualifications ................................................................ 1
`
`III. Materials Reviewed ....................................................................................... 8
`
`IV.
`
`V.
`
`VI.
`
`Person of Ordinary Skill in the Art ............................................................... 11
`
`VII. The ’921 Patent ............................................................................................ 12
`
`VIII. Claim Construction ...................................................................................... 17
`
`Technical Background ................................................................................. 19
`
`IX.
`
`X.
`
`-ii-
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`Patent No. 8,673,921
`Declaration in Support of Inter Partes Review
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`XI. Ground 1: Claims 1, 14, and 15 Are Anticipated by the ’241 Patent As
`
`XII. Ground 2: Claims 1, 14, and 15 are Obvious over the ’241 Patent as
`
`Characterized by Patent Owner Admissions................................................. 52
`A.
`Claim 1 .............................................................................................. 52
`B.
`Claim 14 ............................................................................................ 57
`C.
`Claim 15 ............................................................................................ 59
`Characterized by Patent Owner Admission and Bartoszyk ........................... 59
`A.
`Claim 1 .............................................................................................. 60
`B.
`Claim 14 ............................................................................................ 64
`C.
`Claim 15 ............................................................................................ 68
`by Patent Owner Admissions, Byrn, and Pavia ............................................ 70
`A. Why the Test or Data is Being Used .................................................. 70
`B.
`patent and the Patent Owner Admissions of the ‘921 patent ............... 71
`C.
`How the Tests Were Performed and the Data Was Generated ............ 74
`
`XIII. Ground 3: Claims 1 and 11 are Obvious over the ’241 Patent as Characterized
`
`Comparing the Designed Experiments with Example 4 of the ‘241
`
`1.
`
`2.
`
`First Experiment ...................................................................... 74
`
`Second Experiment .................................................................. 77
`
`3.
`
`4.
`
`5.
`
`D. How the Data was Used to Determine a Value ................................... 82
`
`Third Experiment ..................................................................... 80
`
`Fourth Experiment ................................................................... 80
`
`Fifth Experiment ...................................................................... 81
`
`E.
`
`1.
`
`2.
`
`3.
`
`Data Generated from the First Experiment ............................... 86
`
`Data Generated from the Second Experiment .......................... 92
`
`Data Generated from the Third Experiment ........................... 103
`
`4.
`
`5.
`
`Data Generated from the Fourth Experiment.......................... 105
`
`Data Generated from the Fifth Experiment ............................ 107
`
`by Patent Owner Admissions, Byrn, and Pavia ................................ 110
`
`Claims 1 and 11 are Obvious in view of the 241 Patent as characterized
`
`1.
`
`2.
`
`Claim 11 ................................................................................ 110
`
`Claim 1 .................................................................................. 130
`
`-iii-
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`Patent No. 8,673,921
`Declaration in Support of Inter Partes Review
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`XIV. Ground 4: Claims 1, 12 14, and 15 are Obvious over the ’241 Patent as
`Characterized by Patent Owner Admissions, Bartoszyk, Byrn, and Pavia .. 132
`
`1.
`
`2.
`
`3.
`
`4.
`
`Claim 12 ................................................................................ 132
`
`Claim 1 .................................................................................. 135
`
`Claim 14 ................................................................................ 137
`
`Claim 15 ................................................................................ 141
`
`XV. No Objective Evidence Supporting Non-Obviousness ............................... 144
`
`XVI. Conclusion ................................................................................................. 145
`
`-iv-
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`

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`Patent No. 8,673,921
`Declaration in Support of Inter Partes Review
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`I, Robin Rogers, do declare as follows:
`
`I.
`
`Introduction
`
`1.
`
`I am over the age of eighteen (18) and otherwise competent to make this
`
`declaration.
`
`2.
`
`I have been retained as an expert witness on behalf of Argentum
`
`Pharmaceuticals LLC for an inter partes review (“IPR”) for U.S. Patent No.
`
`8,673,921 (“’921 patent”) (Ex. 1001). I am being compensated for my time in
`
`connection with this IPR at my standard consulting rate, which is $700 per hour. I
`
`understand that my declaration accompanies a petition for inter partes review
`
`involving the above-mentioned U.S. Patent.
`
`II. My Background and Qualifications
`
`1.
`
`I am currently a Research Professor at The University of Alabama,
`
`Tuscaloosa, AL USA and an Adjunct Professor at McGill University, Montreal,
`
`Quebec, Canada. Formerly, I was Canadian Excellence Research Chair in Green
`
`Chemistry and Green Chemicals at McGill University (2015-2017) and
`
`Distinguished Research Professor, Robert Ramsay Chair of Chemistry, and the
`
`Director of the Center for Green Manufacturing at the University of Alabama (1996-
`
`2015). I am also Honorary Professor in the Institute for Process Engineering at The
`
`Chinese Academy of Sciences in Beijing, China. In addition to my academic
`
`1
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`

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`Patent No. 8,673,921
`Declaration in Support of Inter Partes Review
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`positions, I am also President, Owner, and Founder of 525 Solutions, Inc., in
`
`Tuscaloosa, Alabama, USA, a research and development (“R&D”) company that
`
`focuses on developing proprietary, broad-based ionic liquid technologies applicable
`
`in medicinal, pharmaceutical, and materials fields.
`
`2.
`
`I received a B.S. in Chemistry (summa cum laude) in 1978 and a Ph.D.
`
`in chemistry in 1982 from The University of Alabama. During the period 1982-1996,
`
`I was successively an assistant, associate, full, and Presidential Research Professor at
`
`Northern Illinois University. During the period of 1991-1998, I also held a faculty
`
`appointment at the Argonne National Research Laboratory, Argonne, Illinois. In
`
`1996, I became a Professor of Chemistry at The University of Alabama and, in 1998
`
`I was named Director of The University of Alabama’s Center for Green
`
`Manufacturing. I was awarded the titles Distinguished Research Professor in 2004
`
`and Robert Ramsay Chair of Chemistry in 2005. From 2007 to 2009, I held a joint
`
`appointment as Chair in Green Chemistry in the School of Chemistry & Chemical
`
`Engineering and Director of the Queen’s University Ionic Liquid Laboratory
`
`(“QUILL”) at The Queen’s University of Belfast, Belfast, Northern Ireland, UK.
`
`3.
`
`I am a member of various professional societies, including the
`
`American Association for the Advancement of Science (Fellow), American
`
`Chemical Society (Fellow), American Crystallographic Association, American
`
`2
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`Patent No. 8,673,921
`Declaration in Support of Inter Partes Review
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`Institute of Chemical Engineers, Materials Research Society, American Association
`
`of Crystal Growth, and Royal Society of Chemistry (Fellow).
`
`4.
`
`In 1989, I joined the Editorial Board of the Journal of Chemical
`
`Crystallography (then named Journal of Crystallographic and Spectroscopic
`
`Research). I became Associate Editor of the journal in 1993 and was the Editor from
`
`1996-2000. In 1998, I founded the journal Crystal Engineering and served as Editor
`
`until 1999. In 2000, I was asked by the American Chemical Society (“ACS”) to
`
`found a new journal called Crystal Growth & Design, for which I currently serve as
`
`Founding Editor-in-Chief. I also have served or currently serve as editor or on the
`
`editorial board of the following journals:
`
`• Separation Science and Technology: Associate Editor, 1996-1999;
`
`Editorial Board, 1999-;
`
`• Industrial & Engineering Chemistry Research: Editorial Board, 1999-
`
`2001;
`
`• Journal of Chromatography, B, Guest Editor, Volume 743 (1 + 2),
`
`2000;
`
`• Solvent Extraction and Ion Exchange, Editorial Board, 2002-;
`
`• Green Chemistry, International Advisory Board, 2002-;
`
`• Chemical Communications, Editorial Advisory Board, 2005-;
`
`3
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`

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`Patent No. 8,673,921
`Declaration in Support of Inter Partes Review
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`
`
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`• Accounts of Chemical Research, Guest Editor (with G. A. Voth),
`
`Special Issue on Ionic Liquids, Volume 40(11), 2007;
`
`• ChemSusChem, International Advisory Board, 2008-;
`
`• Chemistry Letters, Advisory Board, 2010-;
`
`• Australian Journal of Chemistry, Guest Editor, Research Front on
`
`Crystal Engineering, Volume 63(4), 2010;
`
`• Separation Science & Technology, Guest Editor (with H. Rodriguez and
`
`J. Chen), Special Issue on Ionic Liquids (2012);
`
`• Chemical Communications Guest Editor (with D. MacFarlane and S.
`
`Zhang), Special Issue on Ionic Liquids (2012);
`
`• Science China – Chemistry Guest Editor (with S. Zhang), Special Issue
`
`on Ionic Liquids (2012);
`
`• Catalysis Today Guest Editor (with S. Zhang), Special Issue on Ionic
`
`Liquids (2012). Green Chemistry and Sustainable Technology,
`
`Springer, Heidelberg, Germany, Book Series Editor (with L.-N. He, D.
`
`Su, P. Tundo, and Z. C. Zhang);
`
`• Chimica Oggi/Chemistry Today, Scientific Advisory Board, 2014-; and
`
`• Green Energy & Environment, 2016-
`
`5.
`
`In 2002, the ACS asked me to organize and chair a specialty meeting
`
`
`
`4
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`Patent No. 8,673,921
`Declaration in Support of Inter Partes Review
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`devoted to the topic of polymorphism (Polymorphism in Crystals: Fundamentals,
`
`
`
`Prediction, and Industrial Practice, Tampa, FL, February 23-27, 2003). I was asked
`
`to organize and chair follow-up meetings in 2004 (Polymorphism in Crystals,
`
`Tampa, FL, February 8-11, 2004), in 2006 (Process Crystallization in the
`
`Pharmaceutical and Chemical Industries, Philadelphia, PA, April 25–27, 2006), and
`
`in 2007 (Crystallization Process Development: Case Studies and Research, Boston,
`
`MA, February 26-27, 2007).
`
`6.
`
`In 2010, I was co-founder, co-organizer, and Vice Chair of the first
`
`Gordon Research Conference devoted to the topic of Crystal Engineering
`
`(Waterville Valley Resort, NH, June 6-11, 2010). I was the organizer and Chair of
`
`the second Gordon Research Conference on Crystal Engineering, which was held in
`
`June of 2012.
`
`7.
`
`I have published more than 810 articles in refereed journals, edited 14
`
`books, and have been named as an inventor on 60 domestic and foreign patents. I
`
`have also given over 1,000 presentations before regional, national and international
`
`meetings, and over 240 seminars worldwide. In both 2014 and 2015, I have been
`
`named to the Thomson Reuters Highly Cited Researchers List, ranking among the
`
`top 1% most cited in chemistry.
`
`8.
`
`Since 1996, I have had a leadership role in the development of the field
`
`
`
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`Patent No. 8,673,921
`Declaration in Support of Inter Partes Review
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`of ionic liquids (pure salts liquid at low temperature); probing their fundamental
`
`
`
`nature while advancing their technological relevance in areas which include
`
`crystallization and novel pharmaceutical forms. These efforts have been recognized
`
`with several awards including the 2005 Presidential Green Chemistry Challenge
`
`Award, the 2011 American Chemical Society Award in Separations Science and
`
`Technology, and in recently being elected as a Fellow of the American Association
`
`for the Advancement of Science.
`
`9.
`
`I use and have used over the past 40 years X-ray diffraction techniques,
`
`including single crystal X-ray diffraction and powder X-ray diffraction and other
`
`techniques including Differential Scanning Calorimetry and Thermogravimetric
`
`Analysis, among other techniques, in my research efforts. I have also used other
`
`spectroscopic techniques to analyze crystalline and amorphous forms, including
`
`Infra-red and Raman spectroscopy.
`
`10.
`
`I am also familiar with and use spectroscopic techniques in my research
`
`efforts. I am familiar with and use crystallization techniques to create and isolate
`
`solid-state forms of compounds in my research efforts.
`
`11.
`
`I have collaborated with organic chemists in industry and in academia
`
`as part of a team in the discovery and characterization of novel drug compounds. I
`
`have also acted as a consultant in industry in the development of pharmaceutical
`
`
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`Patent No. 8,673,921
`Declaration in Support of Inter Partes Review
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`drug compounds. I have also trained students in organic synthesis and supervised
`
`
`
`their Ph.D. research. Within my research group, I regularly hire and supervise Ph.D.
`
`organic chemists and direct their research in the synthesis and characterization of
`
`novel forms of active pharmaceutical ingredients.
`
`12.
`
`In my position as Founding Editor-in-Chief of the American Chemical
`
`Society journal Crystal Growth & Design, I regularly evaluate and judge suitability
`
`for publication of numerous manuscripts which utilize and study crystal engineering,
`
`polymorphism, and crystal growth and the characterization of solid-state materials.
`
`Accordingly, I am quite familiar with the academic and scientific standards for
`
`experimental work in this field.
`
`13.
`
`In 2004, 2005, and 2008, I organized three special issues of Crystal
`
`Growth & Design dedicated to the phenomenon of polymorphism, and in 2009, I
`
`organized a special issue dedicated to pharmaceutical co-crystals. Many of these
`
`papers addressed pharmaceutical compounds, hydration, salt selection, and the use of
`
`single-crystal X-Ray diffraction and powder X-Ray diffraction techniques.
`
`14. Based on my experience and qualifications, I consider myself an expert
`
`in the field of solid-state chemistry including crystal engineering, crystallization,
`
`hydration, solvate formation, and polymorphism, including the isolation and
`
`characterization of solvates and hydrates of organic compounds and their
`
`
`
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`Patent No. 8,673,921
`Declaration in Support of Inter Partes Review
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`applications in pharmaceutical products. Accordingly, I believe that I am more than
`
`
`
`competent to express the opinions set forth below.
`
`15. Additional details of my education and experience, and a complete list
`
`of my publications are set forth in my curriculum vitae, a copy of which is attached
`
`as Ex. 1023.
`
`III. Materials Reviewed
`
`
`
`
`
`16.
`
`In forming my opinions, I have reviewed, among other things, U.S.
`
`Patent No. 8,673,921 (“the ‘921 patent”), and papers filed in the Patent Office in
`
`connection with the prosecution of this patent, which I understand to constitute the
`
`prosecution history of the patent. A full list of materials I have considered can be
`
`found in Appendix A.
`
`
`
`
`
`IV. Legal Principles
`
`A. Anticipation
`
`17.
`
`I understand from counsel that a patent claim is “anticipated” if all
`
`elements of the claim are disclosed in a single prior art reference in the same way the
`
`elements are arranged in the claim. I further understand that where a reference
`
`provides broad disclosure of a larger group of, e.g., combinations, as well as specific
`
`preferences for the combinations, the reference still anticipates so long as all claim
`
`elements are disclosed as arranged in the claim. I am also told that the prior art
`
`
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`Patent No. 8,673,921
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`reference must be enabling (i.e., allowing a Person of Ordinary Skill in the Art
`
`
`
`(“POSA”) to make and use the claimed invention without undue experimentation) in
`
`order to anticipate the claim.
`
`B. Obviousness
`
`18.
`
`I understand that an obviousness analysis involves comparing a claim to
`
`the prior art to determine whether the claimed invention would have been obvious to
`
`a POSA in view of the prior art, and in light of the general knowledge in the art. I
`
`also understand that when a POSA would have reached the claimed invention
`
`through routine experimentation, the invention may be deemed obvious. I understand
`
`that a finding of obviousness for a specific range or ratio in a patent can be overcome
`
`if the claimed range or ratio is proven to be critical to the performance or use of the
`
`claimed invention.
`
`19.
`
`I also understand that obviousness can be established by combining or
`
`modifying the teachings of the prior art to achieve the claimed invention. It is also
`
`my understanding that where this is a reason to modify or combine the prior art to
`
`achieve the claimed invention, there must also be a reasonable expectation of success
`
`in so doing. I understand that the reason to combine prior art references can come
`
`from a variety of sources, not just the prior art itself or the specific problem the
`
`patentee was trying to solve. And I understand that the references themselves need
`
`not provide a specific hint or suggestion of the alteration needed to arrive at the
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`Patent No. 8,673,921
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`claimed invention; the analysis may include recourse to logic, judgment, and
`
`
`
`common sense available to a person of ordinary skill that does not necessarily
`
`require explication in any reference.
`
`20.
`
`I understand that when considering the obviousness of an invention, one
`
`should also consider whether there are any secondary considerations that support the
`
`nonobviousness of the invention. I understand that secondary considerations of
`
`nonobviousness include failure of others, copying, unexpectedly superior results,
`
`perception in the industry, commercial success, and long-felt but unmet need.
`
`V.
`
`Summary of Opinions
`
`21. Based on my investigation and analysis and for the reasons set forth
`
`below, it is my opinion that claims 1, 14, and 15 of the ’921 patent would have been
`
`anticipated by U.S. Patent No. 5,532,241 (“’241 patent”) as characterized by Patent
`
`Owner’s Admissions in the ’921 patent.
`
`22.
`
`In addition, it is my opinion that claims 1, 14, and 15 would have been
`
`obvious to one of ordinary skill in the art at the time of the alleged invention in view
`
`of the combined teachings of the ’241 patent as characterized by Patent Owner’s
`
`Admissions in the ’921 patent and Bartoszyk.
`
`23.
`
`It is my opinion that claims 1 and 11 would have been obvious to one of
`
`ordinary skill in the art in view of the combined teachings of the ’241 patent as
`
`characterized by Patent Owner’s Admissions in the ’921 patent, Pavia, and Byrn.
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`Patent No. 8,673,921
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`
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`24.
`
`It is my opinion that claims 1, 12, 14, and 15 would have been obvious
`
`to one of ordinary skill in the art in view of the combined teachings of the ’241
`
`patent as characterized by Patent Owner’s Admissions in the ’921 patent, Bartoszyk,
`
`Pavia, and Byrn.
`
`VI. Person of Ordinary Skill in the Art
`
`25.
`
`I understand that a hypothetical POSA would “be aware all the pertinent
`
`prior art” at the time of the alleged invention, June 19, 2001. A hypothetical POSA
`
`would be part of a multidisciplinary team including a solid-state chemist and a
`
`clinician/scientist.
`
`26. After reviewing the ’921 patent, its prosecution history, and considering
`
`the relevant literature and state of the art as of June 19, 2001, it is my opinion that
`
`the ‘921 Patent is directed to a competent person with expertise and experience in
`
`synthesis, crystallization, and characterization of salts and polymorphic forms. The
`
`POSA would have an understanding of the importance, use, and characterization of
`
`pharmaceutical salts and polymorphs thereof, and several years of experience in
`
`crystallization and solid-state chemistry, including X-ray diffraction for determining
`
`crystalline forms. Such person would typically be a researcher or team of researchers
`
`involved in the research and development of pharmaceutical products. To the extent
`
`necessary, a person skilled in the art would understand that the process of developing
`
`pharmaceutical compositions requires a multi-disciplinary approach, and would draw
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`upon not only his or her own skills, but would also take advantage of certain
`
`
`
`specialized skills of others, to solve any given problem.
`
`27. A POSA would have (1) a Ph.D. in chemistry, pharmaceutical sciences,
`
`or a related discipline, and at least one year experience working in pharmaceutical
`
`solid product development and/or solid-state chemistry; (2) a similar M.Sc. degree
`
`and at least two to three years’ experience, or (3) at least a similar bachelor’s degree
`
`in chemistry, pharmaceutical sciences, or a related discipline, along with several
`
`years of experience working in pharmaceutical solid product development and/or
`
`solid-state chemistry. A solid-state chemist would have extensive experience in the
`
`synthesis and screening of crystallized compounds. A person of ordinary skill in the
`
`art would collaborate with others having expertise in methods of treating mood
`
`disorders, including depression. A POSA with such expertise would have an M.D.
`
`with extensive experience in the study and treatment of mood disorders. A person of
`
`ordinary skill in the art would understand the references referred to herein and have
`
`the capability to draw inferences from them. These descriptions are approximate, and
`
`a higher level of education or specific skill might make up for less experience, and
`
`vice-versa.
`
`VII. The ’921 Patent
`
`28.
`
`I understand that the ’921 patent (Ex. 1001) is listed in the FDA’s
`
`Orange Book as covering the Viibryd® product. The Orange Book states that the
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`Patent No. 8,673,921
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`’921 patent will expire on June 5, 2022.
`
`
`
`29. The ’921 patent issued from U.S. Patent Application No. 14/032,183
`
`(“’183 Application”), filed September 19, 2013, which purports to claim priority to a
`
`series of continuation and divisional applications.
`
`30. The ’183 Application claims priority to a series of continuation and
`
`divisional applications, of which European Patent No. 01113674, filed on June 19,
`
`2001, is the earliest possible priority date for the ’921 patent.
`
`31. The ’921 patent is directed to crystalline modifications of the
`
`hydrochloride salt of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-
`
`yl)-piperazine (“vilazodone”), amorphous vilazodone hydrochloride, and a
`
`crystalline modification of the dihydrochloride of vilazodone. Ex. 1001 at Abstract.
`
`32. The ‘921 patent also states that the ‘241 patent discloses vilazodone and
`
`its physiologically acceptable salts. Ex. 1001 at 1:35-37. The ‘921 patent also states
`
`that the ‘241 patent discloses a process by which vilazodone and its physiologically
`
`acceptable salts can be prepared. Ex. 1001 at 1:37-41. Further, the ‘921 patent states
`
`that the use of vilazodone and its physiologically acceptable salts in treating certain
`
`medical disorders was well known. Id.
`
`33.
`
`In more detail, the ’921 patent states that Example 4 of the ’241 patent
`
`teaches a process for preparing vilazodone free base and vilazodone hydrochloride.
`
`
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`Patent No. 8,673,921
`Declaration in Support of Inter Partes Review
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`Ex. 1001 at 1:35-39. Specifically, the ‘921 patent states that Example 4 yielded the
`
`
`
`active ingredient vilazodone as a mixture of crystalline vilazodone hydrochloride,
`
`amorphous vilazodone hydrochloride, and vilazodone free base. Ex. 1001 at 1:65-
`
`2:5.
`
`34. The Background section further states:
`
`Certain crystalline, i.e. morphological forms of pharmaceutical
`
`compounds may be of interest to those involved in the development
`
`of a suitable dosage form because if the morphological form is not
`
`held constant during clinical and stability studies, the exact dosage
`
`used or measured may not be comparable from one lot to the next.
`
`Once a pharmaceutical compound is produced for use, it is important
`
`to recognize the morphological form delivered in each dosage form
`
`to assure that the production process use the same form and that the
`
`same amount of drug is included in each dosage. Therefore, it is
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`imperative to assure that either a single morphological form or some
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`known combination of morphological forms is present. In addition,
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`certain morphological forms may exhibit enhanced
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`thermodynamic stability and may be more suitable than other
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`morphological forms for inclusion in pharmaceutical
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`formulations.
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`Ex. 1001 at 2:6-21 (emphases added).
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`35. The ’921 patent discloses that the vilazodone crystalline modifications
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`are suitable to treat or prevent a wide-range of disorders, including depressive
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`disorders, anxiety disorders, bipolar disorders, mania, dementia, substance-related
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`disorders, sexual dysfunctions, eating disorders, obesity, fibromyalgia, sleeping
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`disorders, psychiatric disorders, cerebral infract, tension, and provide therapy for the
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`side effects of hypertension, cerebral disorders, chronic pain, acromegaly,
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`hypogonadism, secondary amenorrhea, premenstrual syndrome and undesired
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`puerperal lactation. Ex. 1001 at Abstract.
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`36.
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`Independent claim 1 of the ’921 patent recites:
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`A compound which is 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-
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`carbamoyl-benzofuran-5-yl)-piperazine hydrochloride in its
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`crystalline modification, wherein the compound is an anhydrate,
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`hydrate, solvate or dihydrochloride.
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`37.
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`Independent claim 11 of the ’921 patent recites:
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`A pharmaceutical composition comprising a compound which is 1-
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`[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-
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`piperazine hydrochloride anhydrate in its crystalline modification
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`IV, and one or more conventional auxiliary substances and/or
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`carriers.
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`38. Dependent claim 12 recites a method of treating the same list of
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`disorders listed in the Abstract using the composition disclosed in claim 11. Claim
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`12 recites:
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`Patent No. 8,673,921
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`A method of treating a patient suffering from a depressive disorder,
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`an anxiety disorder, a bipolar disorder, mania, dementia, a
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`substance-related disorder, a sexual dysfunction, an eating disorder,
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`obesity, fibromyalgia, a sleeping disorder, a psychiatric disorder,
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`cerebral infarct, tension, side-effects in the treatment of
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`hypertension, a cerebral disorder, chronic pain, acromegaly,
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`hypogonadism, secondary amenorrhea, premenstrual syndrome and
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`undesired puerperal lactation, or combinations thereof, comprising
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`administering to the patient in need thereof the pharmaceutical
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`composition of claim 11.
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`39. Dependent claim 14 recites a method of treating a patient with disorders
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`listed in the Abstract of the ’921 patent using the compound disclosed in claim 1.
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`Claim 14 recites:
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`A method of treating a patient suffering from a depressive disorder,
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`an anxiety disorder, a bipolar disorder, mania, dementia, a
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`substance-related disorder, a sexual dysfunction, an eating disorder,
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`obesity, fibromyalgia, a sleeping disorder, a psychiatric disorder,
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`cerebral infarct, tension, side-effects in the treatment of
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`hypertension, a cerebral disorder, chronic pain, acromegaly,
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`hypogonadism, secondary amenorrhea, premenstrual syndrome and
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`undesired puerperal lactation, or combinations thereof, comprising
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`administering to the patient in need thereof an effective amount of a
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`compound of claim 1.
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`40. Dependent claim 15 additionally recites “[a] pharmaceutical
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`composition comprising a compound according to claim 1, and one or more
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`
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`conventional auxiliary substances and/or carriers.”
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`41. The ‘921 patent states that throughout the specification, the use of the
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`term “Form” is synonymous with “modification” or “crystalline modification.” Ex.
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`1001 at 2:41-43.
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`42. The ’921 patent does not provide any in vitro or in vivo data, on humans
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`or animals, regarding the efficacy and activity of vilazodone hydrochloride in
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`treating the disorders that are claimed in the patent.
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`43. The ’921 patent also discloses that Form IV “has superior properties
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`over other crystalline forms and is more suitable for inclusion in pharmaceutical
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`formulations.” Ex. 1001 at 12:38-41. However, the ’921 patent does not say how
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`Form IV is more suitable for pharmaceutical formulations, nor does it provide any
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`data to support this assertion.
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`VIII. Claim Construction
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`44.
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`I have been advised that, in the present proceeding, the ’921 patent
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`claims are to be given their broadest reasonable interpretation (“BRI”) in view of the
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`specification as understood by a POSA. I understand that claim language is read in
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`light of the whole patent, including the other claims, the specification, and the
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`prosecution history as it would be interpreted by a POSA. I also understand that,
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`absent some reason to the contrary, claim terms are typically given their ordinary
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`and customary meaning, as they would have been understood by a POSA. I have
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`followed these principles in my analysis described throughout this declaration.
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`45. The ’921 patent provides definitions for certain claim terms, but other
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`claim terms are not defined in the patent. I discuss a few terms below and what I
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`under